CN107837276A - The pharmaceutical composition being locally administered - Google Patents

Abstract

The present invention provides the Etimicin for preparing effective dose or its pharmaceutically-acceptable salts and has the dexamethasone of anti-inflammatory effective dose or the composition of its pharmaceutically acceptable derivates, application of the said composition in preparation prevention or the topical ophthalmic such as conjunctivitis, angular blepharitis, keratitis, sclerotitis, trachoma, scheroma, otitis externa, tympanitis, epifolliculitis, furuncle, impetigo for the treatment of people or mammal use or ear use or nose use or external preparation for skin medicine.Medicine of the present invention has more preferable security and validity than Etimicin.

Description

The pharmaceutical composition being locally administered

Technical field

The present invention relates to pharmaceutical technology field, is specifically to provide prevention or treatment conjunctivitis, angular blepharitis, sand Eye, keratitis, dry eye syndrome, otitis externa, tympanitis, epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection or mouth Etimicin or the dexamethasone of its pharmaceutical salts and effective dose of a kind of effective dose of chamber ulcer treatment etc. or derivatives thereof Topical ophthalmic use or ear use nose use or external preparation for skin or oral cavity medicine compositions and purposes.

Background technology

Etimicin is the aminoglycoside medicaments of domestic-developed, and it is semi-synthetic water-soluble to be classified as forth generation in the world at present Property aminoglycoside antibiotics (document：Chaudhary M1,Kesava Naidu G,Kumar S,Payasi A.Comparative antibacterial activity of a novel semisynthetic antibiotic: etimicin sulphate and other aminoglycosides.World J Microbiol Biotechnol.2012Dec；28(12):3365-71.), its mechanism of action is to suppress the normal protein synthesis of sensitive bacteria, its Ear renal toxicity is low.Other national research institutions do not find obvious toxicity to the sub-acute toxicity test of Etimicin yet.At present Drip-feed Etimicin treats some infectious diseases, recommended dose of being grown up：For normal renal function urinary infection or complete The patient of the sexy dye of body, a 0.l~0.15g, 2 times a day, or a 0.2~0.3g, 1 times a day, it is diluted in 0.9% chlorination Sodium injection or 5% glucose injection l00ml or 250ml iv drip, instil 1 hour every time, the course for the treatment of is 5~10. Clinical studies show this product to below infected with it is preferable the effect of：Respiratory tract infection：Such as acute bronchitis, chronic bronchitis Acute attack, community's pulmonary infection etc.；Kidney and urogenital infections：Such as acute pyelonephritis, cystitis, chronic renal plevis Ephritis or chronic cystitis acute attack etc.；Skin soft tissue and other infection：Such as skin and soft tissue infection, wound, wound Infection and the infection of other sensitive bacterias with operation postpartum.

Etimicin is Formulations for systemic administration at present, and to be easily caused whole body flora unbalance or be also easy to produce drug-fast bacteria for Formulations for systemic administration. It is worth noting that, germ also constantly changes to the drug resistance of aminoglycoside antibiotics, document also constantly reports such The drug resistance of medicine.163 plants of enterococcus that the detection such as Dan Zhiying is isolated from the sample of inpatient are to gentamicin and chain The height antibody-resistant bacterium (MICs >=2000mg/L) of mycin.As a result find, anti-109 plants of gentamicin height antibody-resistant bacterium (66.9%), anti-streptomycin height antibody-resistant bacterium 114 plants (69.9%).Total Test bacterial strain is to vancomycin sensitive.Prompting is faced Bed should use antibiotic with caution, select sensitive medicaments to be treated (document：Dan Zhiying, Wang Haiyi, Wu Hongfan, etc.；163 plants of intestines balls Bacterium is to high concentration aminoglycoside antibiotics resistance condition survey, Tianjin medicine, Tianjing Medical Journal, 1997,25(10)611-613；), Zheng is that gentle Shi Wei peaks agar dilution detects gentamicin, amikacin, to block that mould 6 kinds of element, TOB, Netilmicin and neomycin medicines are to the minimum inhibitory concentrations of 37 plants of ESBL-producing E.colis, to ammonia The resistant characterization and expression of drug resistance genes of base glucoside medicine are studied, and are detected 5 kinds of aminoglycoside drugs with PCR methods and are modified Enzyme gene, and being confirmed using DNA sequencing, as a result find gentamicin, amikacin, kanamycins, TOB and how 256mg/L is all higher than to 37 plants of EHECs MIC50, MIC90 for meter Xing, its resistant rate is respectively 78.4%, 45.9%, 72.9%th, 83.8% and 64.9%, and neomycin still has higher antibacterial activity (document：Zheng Weiping, Shi Weifeng；Production is super wide Compose beta-lactamase EHEC to study aminoglycoside drug drug resistance and drug resistant gene, international laboratory medicine magazine, International Journal of Laboratory Medicine,2009,3:220-222)。

Infected keratitis is still global common diseases causing blindness so far, it is estimated that annual 5000000 people in the whole world occurs each The infected keratitis of type, about 20% blind person is blinded because of ocular infection.China is used as developing country, particularly exists Many rural areas, because people life environment is poor and the backwardness of health care consciousness, the incidence of disease of infectious keratonosus It is higher.China's luscitas caused by disease of cornea and the blind patient of eyes, occupy the 2nd of ophthalmology blinding disease by about 2,000,000 Position.Therefore, it is not only in the case where the drug-fast bacteria of Formulations for systemic administration constantly increases, develops new local anti-infective medicine reply and constantly increase Drug-fast bacteria or the control or treatment of disease be highly desirable and be worth.

Ophthalmic infection disease also includes many, and harm is not shallow, for example, conjunctivitis be conjunctival tissue extraneous and body from The effect of body factor and the general designation of inflammatory reaction occurred.Although conjunctivitis is not serious to eyesight influence in itself, work as it When inflammation involves cornea or causes complication, the infringement of eyesight can be caused.Conjunctivitis has foreign body sensation, burn feeling, itched, photophobia, stream Tear.Important sign has conjunctival congestion, oedema, exudate, nipple hyperplasia, folliculus, pseudomembrane, true film, granuloma, lymphoglandulae auriculares anteriores Enlargement etc..Trachoma and complication account for the 3% of the inpairment of vision cause of disease.Lacrimal Passage Block is the common disease and frequently-occurring disease of ophthalmology, Obstruction of lacrimal passage often results in excessive tear, can develop into acute and chronic dacryocystitis, and excessive tear is hindered beauty to the dipping of face with tear in itself, given Patient causes body and psychological discomfort, and dacryocystitis can spread into eyeball and socket of the eye as the focus of infection of eye, cause bad Consequence, and [Liu Shuan, Tao Hai, Wang Wei, the epidemiological study of Lacrimal Passage Block are entered frequently as the contraindication of intraocular surgery Exhibition, international ophthalmology magazine, 2,008 8 (1):140-143].

Xerophthalmia is a kind of tear and ocular one kind disease caused by many factors, including ocular malaise symptoms, eyesight become Change and tear film is unstable and (or) the damage of ocular, and have potential ocular surface injury and visual disorder, with tear osmotic pressure Rise and ocular inflammatory reaction.The common sympton of xerophthalmia mainly has：Eyes are dry and astringent, foreign body sensation, pain burning heat sensation, tired, eye are itched, Sticky secretion, photophobia, severe patient affect one's power of vision, and are made troubles to work and life.And current document report polyethylene glycol, Trehalose, hyaluronic acid, chitosan, dexamethasone etc. have certain therapeutic action to xerophthalmia.

In recent years, with the aging of population, the increasingly exacerbation and a large amount of uses of various display screens of environmental pollution, do The quantity of eye patient is in obvious increase trend.Dry eyes are as a kind of common disease at present, it has also become global pandemic disease, both at home and abroad Epidemiological investigation shows that the incidence of disease of dry eyes is up to 7.8%~22.1%~33.7%, women illness rate apparently higher than Male, and its illness rate is in rising trend with the growth at age.According to statistics, there are dry eye patients in the U.S. more than 50,000,000, merely from Population calculates, thus it is speculated that Chinese dry eye patients are more than 300,000,000.The common sympton of xerophthalmia mainly has：Eyes are dry and astringent, foreign body sensation, pain Burning heat sensation, tired, eye are itched, sticky secretion, photophobia, severe patient affect one's power of vision, and are made troubles to work and life.Majority is dry Eye patient goes to a doctor repeatedly, and mood is urgent, and complaint dry eyes shape influences its quality of life；Half patient feels that dry eye disorders make its vision Quality is decreased obviously, and produces pessimistic idea, it is believed that can do by myself blinded because of dry eyes some day.The diagnosis and treatment work of xerophthalmia is more next More be taken seriously [document 1：Du Xianghong, Liang Qingfeng, Du Xianghong, Liang Qingfeng；Dry eye patients mental handicape Progress, Chinese Journal of Ophthalmology, Chinese Journal of Ophthalmology, 2,016 52 (3):226-228；Text Offer 2：Yang Yongming, Ma Linkun, the Advance of Epidemiological Research of dry eyes, international ophthalmology magazine, 2,010 10 (10):1944- 1946；].

Gram or positive sensitive bacteria cause the impetigo of skin, scabies, epifolliculitis, eczema concurrent infection, trauma infection contamination, Tinea disease concurrent infection and other suppurative skin infections etc..

Tympanitis (OM) is North America and whole world baby, the common disease of children.Many researchers reported children in the world There are the incidence of disease and popularity of symptom and asymptomatic tympanitis.In these research work, the OM long-term incidence of disease is estimated as 4 ~62%, prevalence rate be 2~52% [Tian Jingfa, tympanitis epidemiology, foreign medical science Otolaryngology fascicle, 1992,3: 65-166]。

Tang Zhihui etc. is to investigate the Hong-Kong children with otitis media with effusion incidence of disease, and the further research knot with west Fruit is compared, and primary school, kindergarten (4~5 years old) and kindergarten are randomly selected within 1995~1998 years in Hong Kong (2~3 years old), 6872 2~7 years old children are checked, receive the otoscopy implemented by hals,Nasen und Ohrenheilkunde expert in the school And the Tympanometry performed by audiologist, in order to make the comparison of standardization with abroad studies result, according to their institutes The diagnostic criteria of use recalculates, and as a result finds, in the research object of 2~3 years old, 4~5 years old and 6~7 years old is divided into, if Standard is made with otoscope clinical diagnosis, incidence of otitis media with effusion rate is 5.2%~21.6%；If diagnosis mark is made with tympanogram Standard, the incidence of disease are 7.3%~30.7%.Either with which kind of method, as a result all with the incidence of disease difference of west research of the same age without Conspicuousness, and the incidence of disease increases and declined with the age.2~3 years old, 4~5 years old, conclusion Hong Kong, and point of 6~7 years old Children in China The secreting property tympanitis incidence of disease does not have significant difference [Tang Zhihui, Yu Weixiang, inscription of looking after one's family, etc. Hong-Kong with west reported literature With the comparison of Western Children incidence of otitis media with effusion rate, Comparison of prevalence rates of secretory otitis media in Hong Kong Chinese children with western Populations, Chinese hals,Nasen und Ohrenheilkunde magazine, CHINESE J.OTORHINOLARYNGOLOGY, 2004,39 (7):429- 432；].

Document report, heating children's complicated with acute tympanitis account for certain proportion in the children that generate heat, may be in clinic by mistake Examine, misdiagnosis [Zhou Jianye, Zhou Weidong, Zou Feng；Children's complicated with acute tympanitis of generating heat incidence investigation, Chinese Medicine guide, 12 phases in 2010:2029-2030；].Document also reports that the tinnitus incidence related to tympanitis is 19.75% [Chen Chuli, Liu It is fluffy, Chen Lihua, etc.；Tinnitus incidence and tinnitus the feature investigation of tympanitis patient, audiology and speech disease magazine, Journal of Audiology and Speech Pathology,2015,23(1):72-74；], clinical treatment is anxious at present Property the auristilla such as otitis media suppurative conventional chloramphenicol, neomycin, gentamicin, polymyxins there is interior ototoxicity, Long-term use can cause patient phonosensitive nerve deafness occur, be subject to certain restrictions otology local application.

RAU there is no specific treatment method at present, easily recurrence, closely related with bacterium infection etc., have celebrating big at present Mycin or dexamethasone are used for the treatment of the disease, but variety of problems or deficiency all be present.

One medicine may show different effects and toxic reaction after different way of administration or medicine-feeding part administration, It is effective with a kind of method of administration, but another method of administration is invalid or poor effect, or different pharmaceutical is in different way of administration Toxicity be different, this is very common in materia medica, and at present, the gatifloxacin of oral or intravenous administration and Moses are husky Magnitude can be clearly used for ophthalmology disease treatment [document 1, Chen Zuji, gatifloxacin ophthalmology application study be in progress, eye Optometry magazine, Chinese Journal of Optometry＆Ophthalmology, 2006,8 (6):400-402；Document 2nd, Chen Zuji；The new fluoroquinolone antibacterial agent MOXIFLOXACIN of broad-spectrum high efficacy and its application in ophthalmology, ophthalmology research, Chinese Ophthalmic Research, 06 phase in 2005:656-659；], however, cefalexin, cefadroxil can only Orally can not drug administration by injection or poor effect, Ceftriaxone Sodium, cefminox sodium etc. can only drug administration by injection can not be administered orally or Oral nearly unavailable, the topical treatment such as sodium cromoglycate eye-drop or spray conjunctivitis or allergy or asthma etc. are effective, are World's situation of selling well common medicine, but oral tablet easy to carry or capsule are valueless；More typically but to be generally known Example perhaps also has：The intravenous injection toxicity of the spectinomycin hydrochloride of aminoglycoside is far above toxicity during its intramuscular injection, Cause the medicine can not therapeutic dose upper vein be administered and can only intramuscular injection.However, any open source literature there is no to report at present The administering drug combinations such as Etimicin and dexamethasone are used for treatment or clinical efficacy or toxicity for being locally administered of ophthalmology disease etc., It is unknown its different dose profiles the effect of or the toxicity such as adverse reaction or retina or cornea or excitant etc., medicine is to eye Toxic action there is diversity and complexity.Eyes are the windows of people's soul, also one of most important organ of animal, eyes Cornea etc. is very sensitive to medicine, once the exposure to chemical substance is uncomfortable or causes serious adverse reaction, some fine differences The result of production likely results in serious adverse reaction or blindness etc., and in recent years, ophthalmically acceptable perfluoropropane gas is examining qualified feelings Still there is the serious blinding adverse reaction of unknown cause in condition, cause tens of people to blind.Therefore, it is reduction adverse reaction and raising Curative effect, tackle growing drug-fast bacteria, it is necessary to study composition of Etimicin and dexamethasone etc..

The content of the invention

The present invention relates to pharmaceutical technology field, and in particular to the topical ophthalmic of people and mammal is used or ear is used or nose is used or skin Skin external application or oral cavity medicine compositions, the Etimicin Sulfate containing effective dose or Etimicin or its medicine in said composition It is any one or more of in acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound on, wherein The composition also dexamethasone of the effective dose containing anti-inflammatory or the derivative of pharmaceutically acceptable dexamethasone or its Any one or more of in pharmaceutically-acceptable salts or its inclusion compound, remaining is pharmaceutically acceptable carrier；

Or per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose is used or preparation for external application to skin or oral cavity system Etimicin Sulfate containing effective dose or Etimicin or its pharmaceutically acceptable salt or different crystal forms or without fixed in agent It is any one or more of in type thing or its solvate or its inclusion compound etc., wherein the composition also effective agent containing anti-inflammatory The derivative or its pharmaceutically-acceptable salts or its isomers of the dexamethasone of amount or pharmaceutically acceptable dexamethasone or its It is any one or more of in inclusion compound；Remaining is pharmaceutically acceptable carrier；

Wherein, the derivative or its pharmaceutically-acceptable salts of dexamethasone or pharmaceutically acceptable dexamethasone or its is different Structure body or its inclusion compound are selected from：Dexamethasone, dexamethasone acetate, dexamethasone -21- phosphate, dexamethasone -21- sulfuric acid Salt, the 21- benzyl oxides derivative of the 21- ether derivants of dexamethasone or dexamethasone or its pharmaceutically acceptable salt or its difference It is any one or more of in crystal formation or amorphous article or its solvate or its inclusion compound.

Aforementioned pharmaceutical compositions can be used for preparing prevention or the conjunctivitis for the treatment of people and mammal, angular blepharitis, sand Eye, keratitis, severe conjunctival scorching (vernal keratoconjunctivitis), sclerotitis, episcleritis, retinal vasculitis, sensitive bacterial sense The eye medicinal of eye disease, xerophthalmia or the scheroma of dye or dry eye syndrome etc., the illness of otitis externa and tympanitis, ear or Skin soft-tissue infection's property disease caused by the ear of nasa surgery operation patient or the topical drug of nose, sensitive bacterial, such as Epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence burn, scald, the topical skin medicaments on the pernio surface of a wound, Or canker sore or recurrent oral ulceration medicine.

The wherein described composition also local anaesthetics containing effective dose, including be singly not limited to tetracaine hydrochloride, procaine, Chloroprocanine, lidocaine, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzene assistant card Cause, Ropivacaine or its pharmaceutical salts or its inclusion compound etc., its weight of material or weight are than that can be the 5~50% of whole weight of formulation (w/w)；Remaining is pharmaceutically acceptable carrier.

The pharmaceutical composition of the present invention can be eye drops, gel for eye use, ophthalmic ointment, ophthalmically acceptable film on pharmaceutical preparation Agent, ophthalmically acceptable dripping pill, external-use gel, ointment, emulsifiable paste, plastics, film, auristilla, oral cavity adhesion tablet, buccal tablets etc..

Contained steroid or antibacterials or the concentration of anti-dry eye drugs will be according to selected examinations in the present composition Agent and the inflammatory type treated and change.Its concentration should be to described in eye, ear or nose or the application of skin histology or oral cavity partial It will be enough to mitigate the inflammation in these tissues after composition.This amount herein is referred to as " anti-inflammatory effective dose " or " had Imitate dosage ".

The Etimicin or Etimicin Sulfate of the present invention or its pharmaceutically acceptable salt or its solvate or its bag Any one or more of application in manufacture local skin external used medicine or pharmaceutical composition in compound etc., contains Etimicin It is or any or more in its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound Kind, and its pharmaceutically acceptable carrier, wherein the Etimicin concentration that the composition contains is 0.05~5.0wt%；Or It can be expressed as：Per 1000ml or 1000g or 1000cm²Preparation for external application to skin or oral preparations in contain Etimicin or sulphur In sour Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. It is any one or more of, 0.5~50g is calculated as or in terms of the potency of Etimicin or Etimicin Sulfate by the weight of Etimicin For the unit of 500,000 units~50,000,000, wherein dexamethasone or dexamethasone of the composition also containing anti-inflammatory effective dose Pharmaceutically acceptable derivates or its inclusion compound；Remaining is pharmaceutically acceptable carrier.

The Etimicin or Etimicin Sulfate of the present invention or its pharmaceutically acceptable salt or its solvate or its bag It is any one or more of in compound etc. to manufacture through topical ophthalmic use or ear use or nose use or external preparation for skin medicine or oral cavity medicine thing Or the application in pharmaceutical composition, containing Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its It is any one or more of in solvate or its inclusion compound, and its pharmaceutically acceptable carrier, wherein the composition contains Etimicin weight or ratio of weight and number be 0.010-1.0wt%；Or it can be expressed as：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or preparation for external application to skin or oral preparations in containing Etimicin or sulfuric acid according to for rice It is any in star or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. Or it is a variety of, 0.1~10g is calculated as with the weight of Etimicin or 100,000 lists are calculated as with the potency of Etimicin or Etimicin Sulfate Position~10,000,000 units, wherein dexamethasone or dexamethasone of the composition also containing anti-inflammatory effective dose pharmaceutically may be used The derivative of receiving or its inclusion compound；Remaining is pharmaceutically acceptable carrier.

The topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, wherein the anti-inflammatory Agent includes dexamethasone or dexamethasone acetate or its different crystal forms or amorphous article or its solvate or its inclusion compound.Ground plug The inclusion compound of rice pine or dexamethasone acetate etc. has many documents to record, for example, the inclusion compound (document of dexamethasone：Zhang Yue, Korea Spro It is quiet, Zhang Duoting, Yang Jing, etc.；Embedding characteristic research of the hydroxypropyl-β-cyclodextrin of medium substitution value to dexamethasone, pharmacy are real Trample magazine, Journal of Pharmaceutical Practice, 03 phase in 2010).

The topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, wherein the anti-inflammatory Agent includes dexamethasone sodium phosphate or its different crystal forms or amorphous article or its solvate or its inclusion compound.

In the ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations of the present invention, pharmaceutically acceptable carrier can Including water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically acceptable preservative or bacteriostatic agent, antioxygen Agent, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, diluent, NMF etc. or any one in them It is or a variety of.

Its pharmaceutically acceptable salt of Etimicin or different crystal forms or amorphous article or its solvate or its inclusion compound Played in eye drops or gel for eye use or topical ophthalmic with Etimicin Sulfate or Etimicin same treatment with it is pre- Anti- effect.

It is antixerophthalmic polyethylene glycol containing effective dose in the medical composite for eye of the present invention, trehalose, transparent Matter acid, Sodium Hyaluronate, chitosan, dexamethasone or dexamethasone acetate or dexamethasone sodium phosphate or its inclusion compound, overstate ground Phosphorus Suo Si sodium, lifitegrast, polysaccharide, glucan, chondroitin sulfate, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, Appointing in methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, cellulose derivative etc. One or more, wherein the weight for the anti-dry eyes agent that the composition contains is 0.0010-6.0wt%.

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：A kind of topical ophthalmic is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, containing Etimicin Sulfate or Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound, wherein institute The derivative of dexamethasone or pharmaceutically acceptable dexamethasone of the composition also containing anti-inflammatory effective dose is stated, remaining is medicine Acceptable carrier on, wherein the Etimicin concentration that the composition contains is 0.10-0.8wt%；Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in containing Etimicin or sulfuric acid according to For any in rice star or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. One or more, 1.0~10.0g is calculated as with the weight of Etimicin or 1,000,000 unit~1000 are calculated as with Etimicin potency Ten thousand units, wherein dexamethasone or dexamethasone pharmaceutically acceptable of the composition also containing anti-inflammatory effective dose spread out Biology；Remaining is pharmaceutically acceptable carrier；Pharmaceutically acceptable carrier include water, pharmaceutically acceptable thickener, PH adjusting agent and or pharmaceutically acceptable preservative or bacteriostatic agent, antioxidant, stabilizer, isotonic regulator, absorption enhancement Agent, solubilizer, excipient, diluent, NMF or they in it is any one or more of.

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to For rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its It is any one or more of in inclusion compound etc., 1.0~8g is calculated as with the weight of Etimicin or is calculated as 1,000,000 with Etimicin potency The unit of unit~8,000,000, wherein dexamethasone or dexamethasone of the composition also containing anti-inflammatory effective dose are pharmaceutically Acceptable derivates；Remaining is pharmaceutically acceptable carrier；

Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically may be used The preservative or bacteriostatic agent of receiving, antioxidant, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, dilution Agent, NMF or they in it is any one or more of.

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or Etimicin Sulfate or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. received, with Etimicin Weight be calculated as 1.0~6g or the unit of 1,000,000 units~6,000,000 be calculated as with Etimicin potency, wherein the composition also contains There are the dexamethasone or the pharmaceutically acceptable derivates of dexamethasone or its inclusion compound of anti-inflammatory effective dose；Remaining is pharmacy Upper acceptable carrier；

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or Etimicin Sulfate or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. received, with Etimicin Weight be calculated as 2.0~6.0g or the unit of 2,000,000 units~6,000,000 be calculated as with Etimicin potency, wherein the composition is also Dexamethasone or the pharmaceutically acceptable derivates of dexamethasone or its inclusion compound containing anti-inflammatory effective dose；Remaining is medicine Acceptable carrier on；

Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically may be used The preservative or bacteriostatic agent of receiving, antioxidant, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, dilution Agent, NMF, attenuation agent or they in it is any one or more of.Generally, in addition to water, these compounds are used in eye drops Weight range typically can be 0.0001~30.0%.

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 1.0g is calculated as with the weight of Etimicin or 1,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 1.5g is calculated as with the weight of Etimicin or 1,500,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 2.0g is calculated as with the weight of Etimicin or 2,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 2.5g is calculated as with the weight of Etimicin or 2,500,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 3.0g is calculated as with the weight of Etimicin or 3,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 3.5g is calculated as with the weight of Etimicin or 3,500,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 4.0g is calculated as with the weight of Etimicin or 4,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention is used or ear is used or nose is used or the pharmaceutical composition of external preparation for skin, can be included：Often 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain Etimicin Or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound It is any one or more of in, 4.5g is calculated as with the weight of Etimicin or 4,500,000 units are calculated as with Etimicin potency, wherein Dexamethasone or the pharmaceutically acceptable derivates of dexamethasone or its bag of the composition also containing anti-inflammatory effective dose Compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 5.0g is calculated as with the weight of Etimicin or 5,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 6.0g is calculated as with the weight of Etimicin or 6,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 7.0g is calculated as with the weight of Etimicin or 7,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 8.0g is calculated as with the weight of Etimicin or 8,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 9.0g is calculated as with the weight of Etimicin or 9,000,000 units are calculated as with Etimicin potency, The pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the wherein described composition also containing anti-inflammatory effective dose or Its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 10.0g is calculated as with the weight of Etimicin or 10,000,000 lists are calculated as with Etimicin potency Position, wherein the pharmaceutically acceptable derivates of dexamethasone or dexamethasone of the composition also containing anti-inflammatory effective dose Or its inclusion compound；Remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, in terms of the weight or parts by weight of Etimicin For 1.0~10g, the weight or parts by weight of the derivative or its inclusion compound of dexamethasone or pharmaceutically acceptable dexamethasone 0.01~10g is calculated as, remaining is pharmaceutically acceptable carrier；Wherein, the weight of Etimicin can in terms of Etimicin potency For 1,000,000-1,000 ten thousand units；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, be calculated as 1.5 with the weight of Etimicin~ 8.0g, or 1,500,000-1,000 ten thousand units are calculated as with Etimicin potency, dexamethasone or pharmaceutically acceptable dexamethasone 0.25~8.0g of derivative or its inclusion compound, remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or with Etimicin potency is calculated as 3,000,000 units, dexamethasone or dexamethasone acetate or its inclusion compound 0.5g, and remaining is pharmaceutically may be used The carrier of receiving；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or with Etimicin potency is calculated as 3,000,000 units, dexamethasone or dexamethasone acetate or its inclusion compound 1.0g, and remaining is pharmaceutically may be used The carrier of receiving；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 5.0g or with Etimicin potency is calculated as 5,000,000 units, dexamethasone or dexamethasone acetate or its inclusion compound 1.0g, and remaining is pharmaceutically may be used The carrier of receiving；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or with Etimicin potency is calculated as 3,000,000 units, and dexamethasone sodium phosphate 1.0g, remaining is pharmaceutically acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Preparation for external application to skin in containing Etimicin or its pharmaceutically acceptable different crystallization or its can pharmaceutically connect The solvate received or its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or any one or more in them Kind, 3.0g, dexamethasone or dexamethasone acetate or its inclusion compound 5.0g are calculated as with the weight of Etimicin, remaining is pharmaceutically Acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 0.5~50g is calculated as with the weight of Etimicin or 20,000,000 units, dexamethasone sodium phosphate 0.01 are calculated as with Etimicin potency ~5g, remaining is pharmaceutically acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 0.50~50g is calculated as with the weight of Etimicin or 20,000,000 units, dexamethasone or its inclusion are calculated as with Etimicin potency 0.01~10g of thing, remaining is pharmaceutically acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 10.0~50g is calculated as with the weight of Etimicin or 20,000,000 units are calculated as with Etimicin potency, dexamethasone acetate or its 0.01~10g of inclusion compound, remaining is pharmaceutically acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 10.0~30g is calculated as with the weight of Etimicin or 20,000,000 units are calculated as with Etimicin potency, dexamethasone sodium phosphate or Dexamethasone or dexamethasone acetate or 0.1~3g of its inclusion compound, remaining is pharmaceutically acceptable carrier；

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 0.5~3g is calculated as with the weight of Etimicin or 20,000,000 units, dexamethasone sodium phosphate or ground are calculated as with Etimicin potency Sai meter Song or dexamethasone acetate or 0.01~1g of its inclusion compound, remaining is pharmaceutically acceptable carrier；

Pharmaceutically acceptable carrier or sorbefacient or NMF etc. are selected from but are not limited only to：Water, chirality or racemization Or D- or L- or the amino acid of racemization or its salt, such as D- or L- or DL-Lys, Lysine Acetate, cysteine, egg ammonia Acid, arginine or acetic arginine or L-aminobutanedioic acid or Monosodium L-aspartate, glutamic acid, glycine, taurine, alanine, figured silk fabrics ammonia Acid, leucine, isoleucine, serine, threonine, cysteine, cystine, methionine, asparagine, glutamine, 5- Oxylysine, histidine, phenylalanine, tyrosine, tryptophan, 3- hydroxy-prolines, 4- hydroxy-prolines, proline, height Cysteine, homocystine, homoserine, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4- ammonia Base butyric acid, 2- amino-2-methyls propionic acid, 2- methyl -3- alanines, 2,6- diaminopimelic acids, 2- amino -3- phenyl fourths Acid, phenylglycine, canavanine, canaline, 4- hydroxyarginines, 4- hydroxyls ornithine, homoarginine, 4- hydroxyls are high Arginine, beta-lysine, 2,4-diamino-butanoic, 2,3- diaminopropionic acids, 2- methyl serines etc. or unit or polybasic carboxylic acid Or its pharmaceutical salts, gallic acid, propylgallate, progallin A, gallate, malic acid, butanedioic acid, Vitamin C Acid, L-AA, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, nicotinic acid, niacinamide, pantothenic acid, sodium pantothenate, pantothenic acid Calcium, vitamin B1, vitamin B2, vitamin E, beta carotene, Pyridoxamine Hydrochloride, glutathione, allantoin, citric acid or lemon Lemon acid sodium or lactic acid, sodium lactate, lactobionic acid, sodium lactonic, gluconic acid, sodium gluconate or trehalose, urea, thiocarbamide, Or maltitol, sorbierite, mannitol, lactitol, xylitol, antierythrite, Hyaluronic Acid or sodium hyaluronate or its hydrate or One or more in their pharmaceutically acceptable salt or their isomers etc., sorbierite include D- D-sorbites, anhydrous One or more in sorbierite or the water thing of sorbierite half or 1 water sorbierite or sorbitol instant etc., it is above-mentioned to include its isomery Body；Generally, concentration range can be 0.000~5.0% used in these compounds.The group in the present invention such as above-mentioned wetting agent Contribute to reduce adverse reaction of the medicine to part in compound.

Pharmaceutically acceptable carrier can include pharmaceutically acceptable antioxidant and stabilizer, and they are selected from but not only It is limited to sulfurous acid and its salt, bisulfites, pyrosulfite, dithionite, TGA and its pharmaceutical salts, thio breast Acid and its pharmaceutical salts, thio-2 acid and salt, monohydroxy or multi-hydroxy carboxy acid and pharmaceutical salts, tartaric acid, sorbic acid or its is medicinal Salt, nitrate, acetic acid pharmaceutical salts, citrate, EDTA and edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate calcium or the hydrate of sodium ethylene diamine tetracetate calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), N- bis- (2- ethoxys) glycine, maltitol, xylitol, sorbierite, mannitol, vitamin E, beta carotene, Pyridoxamine Hydrochloride, One or several kinds in taurine, amino acid or their pharmaceutically acceptable salt etc..

Pharmaceutically acceptable carrier can be selected from comprising pharmaceutically acceptable chelating agent but be not limited only to EDTA and Edta salt including EDETATE SODIUM, the sodium of EDTA tetra- or its hydrate, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate calcium or second The hydrate of sodium ethylene diamine tetracetate calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), one in N- bis- (2- ethoxys) glycine etc. Kind is several.

It is thickener or stabilizer that the preparation of the present invention, which can include one or more pharmaceutically acceptable water soluble adjuvants, It may be selected from the composition being made up of water-soluble polymer and penetration enhancer and their mixture.The present invention eye drops or The water-soluble polymer that can be used in ophthalmically acceptable or skin use or oral preparations includes but is not limited to natural and synthesis gather Compound, polysaccharide, poly- aminoglycoside, cellulose derivative, guar gum, xanthans, glucan, carboxyl vinyl polymer, poly- third It is olefin(e) acid sodium, hyaluronidase, hyaluronic acid, Sodium Hyaluronate, chondroitin sulfate, locust bean gum, poloxamer, polyvinyl alcohol, poly- Vinylpyrrolidone, polyethylene glycol, gellan gum, alginic acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl are fine Dimension element, sodium carboxymethylcellulose or derivative of dextrin and dextrin etc. and their mixture.It is dense used in these compounds Spending scope can be 0.00~15.0%.Above-mentioned water-soluble thickener in the present composition can coordinate controlling for xerophthalmia Treat or prevent.

Using viscosity enahncers the viscosity of the composition of the present invention can also be made to be more than the viscous of simple aqueous as needed Degree, so as to improve the eye absorption of reactive compound by the target tissue or increase the retention time in eye.These are viscous Spending reinforcing agent is included for example, polysaccharide, glucan, hyaluronic acid, poloxamer, polyvinyl alcohol, chondroitin sulfate, polyvinyl pyrrole Pyrrolidone, methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, sea Algae is sugared or other reagents well known by persons skilled in the art.These reagents typically can be made with 0.01%-5wt% concentration With.

Thickener more preferably poloxamer, chondroitin sulfate, methylcellulose, hydroxypropyl methyl cellulose, exocellular polysaccharide Glue, hydroxyethyl cellulose, polyvinylpyrrolidone, polyethylene glycol, hyaluronic acid or Sodium Hyaluronate, trehalose etc., eye drops In the more excellent concentration with 0.02%-1wt% use.

In gel, the auxiliary gel matrix material for forming gel can be included, is selected from but is not limited only to poloxamer, Portugal Grape sugar phosphate, glucose phosphate ester derivant, xanthans, carboxyl vinyl polymer, Sodium Polyacrylate, cellulose derive Thing, polysaccharide, chondroitin sulfate, hyaluronic acid or Sodium Hyaluronate, guar gum, polyvinyl alcohol, alginic acid etc..

The excipient of hydrogel is also selected from but is not limited only to chitosan, poly- (hydroxyethyl meth acrylate), poly- (N- ethene Base pyrrolidones), polyvinyl alcohol, the polymer of acrylic acid, the one or more therein, wherein carbomer system such as carbomer series Row may include that carbomer 934, carbomer940, Acritamer 940, Carbopol 941, CARBOPOL 974P etc. are therein a kind of or more Kind, generally, concentration range can be in 0.001-25.0% used in these compounds.

Hyaluronic acid or Sodium Hyaluronate include but is not limited to macromolecular hyaluronic acid (molecular weight ranges 1,800,000~ 2200,000), middle molecular weight hyaluronic acid (molecular weight ranges 1,000,000~1,800,000), micromolecule hyaluronic acid (molecule Measure scope 200,000~1,000,000), more preferably in, micromolecule hyaluronic acid.

Also including solubilizer (including may include surfactant), solubilizer is selected from but not only pharmaceutically acceptable auxiliary material Be limited to polyethylene glycol oxide list oleic acid sorbitan ester, Tween-80, VE succinic acid macrogol ester (vitamin E TPGS), Glycerine-polyethylene glycol epoxide stearate, PEG-32 glyceryl palmitostearates, lauryl sodium sulfate, mono laurate mountain Pears alcohol acid anhydride ester, polyethylene glycol, polyethylene glycol 100-20000 (polyethylene glycol 200, polyethylene glycol 400, Macrogol 600, poly- second Glycol 4000, Macrogol 6000, PEG 8000 etc.), HS15, polyvinylpyrrolidine Ketone, polyvinyl alcohol, amino acid or its pharmaceutical salts, pharmaceutically acceptable alcohols, pharmaceutically acceptable polyalcohol, poloxamer, pool Luo Shamu 407, azone, laurocapram, cyclodextrin or cyclodextrin pharmaceutically acceptable derivates, amide-type or urea and spread out Biology, inorganic acid or inorganic acid salt, pharmaceutically acceptable organic acid or acylate, pharmaceutically acceptable carbohydrate or sugar lime, One or more in pharmaceutically acceptable amine etc. or their chiral isomer etc. or their pharmaceutically acceptable salt； Cyclodextrin includes alpha-cyclodextrin, beta-schardinger dextrin, gamma-cyclodextrin, hydroxypropyl-β-cyclodextrin etc..

The preparation of the pharmaceutical composition of the present invention with multiple dose form when being provided for preventing the preservative of contamination of products Or bacteriostatic agent, be selected from but be not limited only to pharmaceutically acceptable preservative or bacteriostatic agent, as organic acid bacteriostatic agent, benzoic acid, Sorbic acid or its pharmaceutical salts, dehydroactic acid sodium, the esters of oxybenzene esters compound or nipalgin, methyl hydroxybenzoate, para hydroxybenzene (Domiphen bromide, benzalkonium chloride, benzene are pricked for propyl formate, phenmethylol, benzyl carbinol, phenoxetol, anesin, quaternary ammonium derivative Bromine ammonium, hexadecyl ammonium methyl, cetylpyridinium chloride, Benzethonium etc.), polyquaternium (polyquaternium -1, PQ-1, Polidronium Chloride), organic Mercury derivatives (thiomersalate, thimerosal, phenylmercuric acetate and phenylmercuric nitrate etc.), pharmaceutically In acceptable phenol compound, o-phenyl phenol, chloreresol, chlorohexidene etc. or their pharmaceutically acceptable salt etc. It is one or more of.Generally, concentration range used in these compounds can be 0.0005-5.0%, and this depends on selected Preservative or bacteriostatic agent；More preferably use esters, sorbic acid or its pharmaceutical salts of nipalgin, thimerosal, the conduct of polyquaternium -1 Anti-microbial preservative；These preservatives are typically used with 0.001%-1.0wt% concentration；

The pharmaceutically acceptable isotonic regulator that uses can be included but not in the preparation of the pharmaceutical composition of the present invention It is limited to：Sodium chloride, potassium chloride, calcium chloride, sodium bromide, sodium phosphate, sodium sulphate, sodium nitrate, glucose, boric acid, borax, glycerine, It is propane diols, polyethylene glycol, PEG-400, PEG300, PEG-200, glucose, fructose, maltitol, xylitol, sorbierite, sweet Reveal the one or more in alcohol, inverted sugar, dextran, sodium lactate or sodium lactonic, gluconic acid or sodium gluconate etc.； Physiological saline (being usually the solution of sodium chloride)；Or isotonic regulation is carried out with cushioning liquid, cushioning liquid can include Sharpe phosphorus Phthalate buffer (is made up of, Acidic Liquid two kinds of storing solutions：8.4g/l containing AMSP, alkalies：Phosphoric acid disodium hydrogen 9.4g/l, in use, be obtained by mixing according to different proportion, if necessary plus appropriate sodium chloride is into isotonic), Palitzsch's buffer solution (it is made up of two kinds of storing solutions, Acidic Liquid：Boronic acid containing 12.4g/l, alkalies：Borax 19.1g/l, in use, according to not year-on-year Example is obtained by mixing, and if necessary plus appropriate sodium chloride is into isotonic), lucky Fei Shi buffer solutions, [buffer solution etc. is in medicament for borate buffer etc. It is described on：Tu Xide, the Zhang Jun longevity, Zhu Jiabi, pharmacy (third edition), 2002, Beijing, People's Health Publisher].

Eye, ear, the nose of the present invention is used, skin composition contains in medicinal acceptable carrier and resisted with one or more Scorching medicine.The pH that the composition will typically have 5.5-8.0.The ophthalmic composition must also be configured to have with eye and The consistent osmotic value of aqueous humor in ocular tissue.These osmotic values are typically about 200- about 400 milliosmols/kg water (" mOsm/kg "), it is preferred that about 300mOsm/kg.

The composition and recipe quantity of the pharmaceutically acceptable pH adjusting agent used in the preparation of the pharmaceutical composition of the present invention It is this area conventional selection, is selected from but is not limited only to pharmaceutically acceptable inorganic acid or organic acid or its pharmaceutical salts, inorganic Alkali or organic base or its pharmaceutical salts, the lewis acid or alkali of broad sense can also be included, one or several kinds can be contained, it includes But it is not limited to hydrochloric acid, sulfuric acid or its pharmaceutical salts, boric acid or its pharmaceutical salts, borax, phosphoric acid or its pharmaceutical salts, acetic acid or its is medicinal Salt, such as sodium acetate, lactic acid and lactic acid pharmaceutical salts, citric acid or its pharmaceutical salts, tartaric acid or citric acid or its pharmaceutical salts, phosphoric acid Disodium hydrogen, sodium dihydrogen phosphate, potassium dihydrogen phosphate, ascorbic acid, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, hydrogen-oxygen Change sodium, potassium hydroxide, sodium carbonate, sodium acid carbonate, trihydroxy aminomethane, diethanol amine, monoethanolamine, diisopropanolamine (DIPA), 2- ammonia Base -2- (methylol) 1,3-PDs amine, N- methyl glucoses amine and their salt, multi-hydroxy carboxy acid and pharmaceutical salts, such as grape Uronic acid, gluconic acid, lactobionic acid, malic acid, threonic acid, glucoheptonic acid, amino acid or their pharmaceutically acceptable salt Or the one or several kinds in its hydrate etc..

The preparation of the topical ocular administration of the preparation of the present invention includes eye drops, situ-gel eye drops, heat-sensitive gel drop Ocular fluid, gel for eye use, eye ointment etc.；Eye drops can unit dose package or multiple-unit container.Wherein, situ-gel eye drops or temperature-sensitive Gel eyedrop, the pharmaceutically acceptable auxiliary material of gel for eye use may include thickener, surfactant, antioxidant, chelating Agent or metal ion couplant, preservative or bacteriostatic agent, pH adjusting agent, osmotic pressure regulator etc..

Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its is molten Any one or more of thermosensitive type situ-gel eye drops in agent compound or its inclusion compound, its pharmaceutically acceptable auxiliary material can Including thickener, surfactant, antioxidant, chelating agent, preservative, pH adjusting agent, osmotic pressure regulator etc..

The thermosensitive type situ-gel eye drops or temperature-sensitive of a kind of Etimicin Sulfate or its pharmaceutically acceptable salt etc. coagulate The preparation method of glue eye drops, it may include following steps：(1) partial purification water is heated to 50 DEG C~60 DEG C, pharmaceutically will may be used The auxiliary material of receiving is dissolved in purified water, and room temperature is cooled to after dissolving；(2) Etimicin Sulfate is added to institute in step (1) Solution in, stirring is to being completely dissolved；(3) by thermosensitive type gel rubber material dispersing and dissolving in the partial purification water that water temperature is room temperature In；(4) solution of step (2) and (3) is mixed, solution ph is adjusted to 6.2~7.8, be settled to required volume, crossed and filter out Bacterium, it is aseptic subpackaged in eye drop bottle, produce.

The prescription of gel for eye use can include as follows：

The Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms of effective dose or without fixed Type thing or its solvate or its inclusion compound, there is the dexamethasone of the effective dose of anti-inflammatory or pharmaceutically acceptable dexamethasone Derivative or its pharmaceutically-acceptable salts or its isomers or its inclusion compound in any one or more of, gel-type vehicle (card ripple Nurse series, carbomer 934, carbomer940, Acritamer 940, Carbopol 941, CARBOPOL 974P etc., polyvinyl alcohol, chitosan, Poloxamer, methylcellulose, hydroxyethyl cellulose etc.), pharmaceutically acceptable thickener, stabilizer (antioxidant or stably Agent), preservative or bacteriostatic agent, osmotic pressure regulator, pH adjusting agent etc., and pure water adds to 1000g.

Wherein, gel-type vehicle is usually 0.5~100.0g, more preferably 1~60.0g, more preferably 1~20.0g；

Stabilizer (antioxidant or stabilizer) is usually 0.05~200g, more preferably 1~150g, more preferably 1~120g；

Preservative or bacteriostatic agent are usually 0.005~20g, more preferably 0.01~2g；

Osmotic pressure regulator is usually 0.1~80.0g, more preferably 1~60.0g, more preferably 1~40.0g；

PH adjusting agent is usually 0.1~20.0g, more preferably 1~20.0g, more preferably 1~10.0g；

And supply 1000ml or 1000g with water.

Eye drops preparation method may include the following steps：

The preparation technology of eye drops：Etimicin Sulfate or Etimicin are dissolved in distilled water or pure water or water for injection Or in the pure water or water for injection of acidifying, there are the dexamethasone of the effective dose of anti-inflammatory or pharmaceutically acceptable dexamethasone In derivative or its pharmaceutically-acceptable salts or its isomers or its inclusion compound it is any one or more of be dissolved in water or DL in In water, auxiliary material is dissolved in distilled water or pure water or water for injection or the pure water or water for injection of acidifying, both are mixed, stirred Mixing is mixed, regulation solution ph (more preferably pH value is between 6.0-7.5) between 5.8-7.8, adjusts osmotic pressure, is added water to complete Amount or filtering, filling, sterilizing, packaging.

Eye drops goes thermal source and bacteria remover filter type to include adding the activity with liquid measure 0.005~1% in preparing Charcoal removes thermal source, 0.20~0.8 μm of filtering with microporous membrane, pressure sterilizing, can also use ultrafiltration.In hyperfiltration process, ultrafilter can From flat, rolling, tubular type, hollow fiber form or circle boxlike etc., more preferably rolling and hollow fiber form ultrafilter, using cutting After staying the membrane filtration that relative molecular mass is 30,000 to 300,000, or again using the super of retention relative molecular mass 4000~60000 The milipore filter of membrane filtration, preferably relative molecular mass 6000~30000.

The invention provides can be selected effective for the pharmaceutical preparation of topical treatment ocular infection disease and xerophthalmia The elementary sum symbol toxicity dosage range related to curative effect, these are not open before.

The preparation of the present invention prevent or treat the conjunctivitis of people or mammal, angular blepharitis, trachoma, keratitis, Severe conjunctival inflammation (vernal keratoconjunctivitis), sclerotitis, episcleritis, retinal vasculitis, the eye disease of sensitive bacterial infection When sick, xerophthalmia or scheroma or dry eye syndrome etc., the eye drops dosage of the method for the embodiment of the present invention 4 may generally be：One day 2-5 Secondary, each 1-3 drops, children can be with weight loss.The dosage of gel for eye use can suitably be adjusted according to the dosage of eye drops It is whole.

Auristilla preparation method may include the following steps：

The preparation technology of eye drops：Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms will be replaced Or amorphous article or its solvate or its inclusion compound are with there is the dexamethasone of the effective dose of anti-inflammatory or pharmaceutically acceptable The derivative of dexamethasone or its pharmaceutically-acceptable salts or its isomers or its inclusion compound are dissolved in water for injection or or glycerine Or in ethanol equal solvent, add appropriate auxiliary material, stir and evenly mix, regulation solution ph filters between 5.0-7.8, is filling, going out Bacterium, packaging.Auristilla dosage can typically include：One day 2-5 times, each 1-6 drops.

The preparation of ointment or emulsifiable paste

Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its is molten Agent compound or its inclusion compound and the dexamethasone of effective dose or the derivative of pharmaceutically acceptable dexamethasone for having anti-inflammatory Or its pharmaceutically-acceptable salts or its isomers or its inclusion compound, matrix and pharmaceutically acceptable infiltration with ointment or emulsifiable paste Agent, emulsifying agent or surfactant etc. are well mixed and obtain.The local skin outer used time can be according to size of skin infection etc. Dosage is determined, typically once or twice a day.

The derivative of wherein described dexamethasone or dexamethasone is selected from dexamethasone, dexamethasone acetate, dexamethasone Sodium phosphate, dexamethasone -21- phosphate, dexamethasone -21- sulfate, the 21- ether derivants or dexamethasone of dexamethasone 21- benzyl oxides derivative or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound It is any one or more.

The matrix and pharmaceutically acceptable bleeding agent of ointment or emulsifiable paste, emulsifying agent or surfactant etc. are selected from but not only limited In：Water, propane diols, glycerine, lanolin, vaseline, spermaceti, cera alba, paraffin, ceresine, vegetable oil, hydrogenated vegetable oil, axunge, Cholesterol, isopropyl myristate, hexadecanol, octadecyl alcolol, the fat of polyoxyethylene stearate 40, polyethylene glycol 100-20000, poly- second two It is alcohol -400, PEG-4000, PEG-4000, atoleine, sodium stearyl sulfate, glycerin monostearate, poly- Stearine, glycerin gelatine, sodium alginate, the series of polyethylene glycol, the series of poloxamer, polyvinyl alcohol, polyethylene Pyrrolidones, methylcellulose, carbomer, sodium carboxymethylcellulose, Tween-80, polyethylene glycol oxide list oleic acid sorbitan ester, VE succinic acid macrogol ester (vitamin E TPGS), glycerine-polyethylene glycol epoxide stearate, PEG-32 stearic acid Tripalmitin, lauryl sodium sulfate, Sorbitan monolaurate etc..

The purpose of the present invention also provides the pelliculae pro cavo oris of Etimicin dexamethasone, and pelliculae pro cavo oris can be by following component groups Into：Weight of material is than Etimicin or its pharmaceutically acceptable salt and dexamethasone or dexamethasone acetate or dexamethasone phosphorus Sour sodium etc. 10~50% (w/w), filmogen 40~90% (w/w), flavouring 0~6% (w/w), (w/ of colouring agent 0~5% w)；Local anaesthetics containing effective dose in the pelliculae pro cavo oris of the Etimicin dexamethasone of the present invention, including singly it is not limited to salt Sour totokaine, procaine hydrochloride, chloroprocanine, lidocaine hydrochloride, oxybuprocaine, phenmethylol, menthol, according to for card Cause, Bupivacaine, dyclonine, benzocainum, Ropivacaine or the pharmaceutical salts of its parent compound or its inclusion compound etc., its thing Expect that weight ratio can be 5~50% (w/w)；

The filmogen is selected from but is not limited only to polyvinyl alcohol, IR, hypromellose Element, hydroxypropylcellulose, gelatin, pulullan polysaccharide, modified starch, HPMC K4M, HPMC E5, hydroxyl One or more in third methylcellulose E50, HPMC K100, cellulose family or natural macromolecular material etc.； The flavouring is sweetener, acid or aromatic；The colouring agent is natural pigment or artificial color.

The pelliculae pro cavo oris of described Etimicin dexamethasone, preferred ingredient composition are as follows：

Weight of material fills in rice than Etimicin or its pharmaceutically acceptable salt and dexamethasone dexamethasone or acetic acid 15~40% (w/w) such as pine or dexamethasone sodium phosphate, filmogen 60~80% (w/w), flavouring 0.01~2% (w/w), Colouring agent 0.01~1% (w/w)；

Flavouring used it is optional but be not limited only to lactose, Sucralose, aspartame, stevioside, acesulfame potassium, sorbierite, One or more in mannitol, saccharin sodium；Colouring agent used is optional but is not limited only to titanium dioxide, iron oxide, β-carrot Element, beet red, lac are red, red pigment of cowberry, capsanthin, red rice are red, carmine, amaranth, famille rose, erythrosine, newly red, lemon One or more in Huang, sunset yellow, indigo, light blue.

The purpose of the present invention, which lies also in provide, a kind of is used for respiratory tract, skin and soft tissue infection caused by treating sensitive bacteria Compound Etimicin or with dexamethasone plastics and preparation method thereof.

The present invention is achieved through the following technical solutions：A kind of compound Etimicin or with dexamethasone azoles plastics, with 1000g weight or with 1000ml volumes represent, by effective dose Etimicin or with dexamethasone or dexamethasone acetate or Dexamethasone sodium phosphate etc., chitosan, polyvinyl alcohol, the series of carbopol, hyaluronic acid, gelatin, pulullan polysaccharide, ethyl are fine Tie up element, sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyethylene kind, PP type, cellulose family Or one or more 10~80g, propane diols or glycerine in the pharmaceutically acceptable filmogen such as natural macromolecular material In one or more 20~200g, pharmaceutically acceptable 0~30g of surfactant, pharmaceutically acceptable bacteriostatic agent 0~ 5g, 50~600g of purified water, ethanol are added to 1000g or 1000ml compositions.

Plastics made from the inventive method have that adhesive force is strong, stretchability is good, film forming is fast and it is difficult for drop-off, have it is certain Tearing toughness, it is heat-resisting, acid and alkali-resistance, easy cleaning the advantages that.

Embodiments of the invention into film test and cleaning

Embodiments of the invention coating liquid (embodiment 52) is dipped with banister brush and gently coats thin layer on a glass, is observed Film formation time is about within 3 minutes on a glass for film formation time result this plastics, while in back of people's hand of the present invention or pin One layer of this product of toe film, observation film formation time this plastics of result are about within 2 minutes in human body film formation time, and skin does not have red It is swollen to wait adverse reaction, illustrate that the film forming of this product is good.Rinsed with running water after ten minutes, washed away soon on glass plate Medicine film and human body trick on medicine film.

The purpose of the present invention also provides a kind of mouth paster of the treatment canker sore containing Etimicin dexamethasone, its In per single dose paster in its adhesion layer can contain effective dose Etimicin or with dexamethasone or dexamethasone acetate or ground Sai meter Song sodium phosphates etc.；Its adhesion layer can contain main ingredient Etimicin 0.1-5mg, more preferably content in wherein per single dose paster For 0.5-3mg, dexamethasone or dexamethasone acetate or dexamethasone sodium phosphate 0.01-2mg, preferred content 0.05-1mg, More preferably 0.1-0.6mg.

The Etimicin oral dexamethasone paster of the present invention can be single-layer sheet or double-layer tablets, and single-layer sheet here is general The tablet of logical single-layer sheet, the only adhesion layer of the dexamethasone of Etimicin containing main ingredient.

The preferred double-layer tablets of mouth paster described in the present invention, it is characterised in that including the dexamethasone of Etimicin containing main ingredient Adhesion layer and protective layer or support layer not soluble in water.It can contain in the oral mucosa paster of the Etimicin dexamethasone of the present invention There is the local anaesthetics of effective dose, including be singly not limited to tetracaine hydrochloride, procaine, chloroprocanine, lidocaine, Ao Buka Cause, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine or its pharmaceutical salts or its bag Compound etc., its weight of material than can be whole tablet weight 5~50% (w/w).

The Etimicin oral dexamethasone sticking tablet of the present invention can be a kind of double-layer tablets, can be by medicated layer and protective layer Or support layer composition.Medicine layer includes active component Etimicin and dexamethasone or dexamethasone acetate or dexamethasone phosphoric acid One or several kinds among sodium, and filler, sustained-release matrix material, adhesive matrix, wetting agent and lubricant；Protective layer or branch Holding layer includes the one or several kinds among filler, lubricant, wetting agent, adhesive, colouring agent.

Etimicin oral dexamethasone paster of the present invention, its adhesion material be selected from but be not limited only to it is following a kind of or Many kinds of substance：Hydroxypropyl methyl cellulose, the series of carbopol, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), hydroxyl Propyl methocel (HPC), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (CMC-Na), hydroxypropyl cellulose (HPC), hydroxyl One or several kinds among propyl methocel (HPMC), chitosan, gelatin, starch, dextrin etc.；In each paster, institute The gross weight for saying adhesion material can be 10-70mg.

Etimicin oral dexamethasone paster of the present invention, in addition to pharmaceutically acceptable filler, help Agent or lubricant are flowed, wherein, filler may be selected from but be not limited only to starch, amylum pregelatinisatum, dextrin, mannitol, xylitol, breast One or several kinds among sugar etc., preferable dextrin, lactose, the one or several kinds among microcrystalline cellulose；Glidant or lubrication Agent may be selected from but be not limited only to talcum powder, magnesium stearate, superfine silica gel powder, Compritol 888 ATO, lauryl sodium sulfate, dodecane One or several kinds among base sodium sulfonate, VE succinic acid macrogol ester.Wetting agent may be selected from but be not limited only to ethanol, Water.

Etimicin oral dexamethasone paster of the present invention, described protective layer not soluble in water is mainly with propylene Sour resin or ethyl cellulose are that film forming agent is equipped with appropriate pharmaceutical plasticizers (if necessary) and the solution spraying of filler formation exists The fish tail and waterproof layer that one surface of drug containing adhesion layer is formed.Described plasticizer may be selected from but be not limited only to the fourth of phthalic acid two One in ester, diethyl phthalate, dioctyl phthalate, castor oil, epoxidized soybean oil, citric acid ester plasticizer Kind is several, and the citric acid ester plasticizer can be enumerated but be not limited to citric acid tri-n-hexyl ester (THC), acetyl tributyl citrate three Just own ester (ATHC), trioctyl lemon acid (TOC), ATOC (ATOC), ATBC (TBC), acetyl ATBC (ATBC), THC (THC), the own ester of acetyl tributyl citrate (ATHC), BTHC (BTHC), plasticizer optimization citric acid tributyl and/or tributyl 2-acetylcitrate.The plasticizer consumption can be protective layer weight The 5% to 30% of amount (dry weight), more preferably 8%~25%.

Appropriate flavouring or and colouring agent can be added as needed.Flavouring used is optional but is not limited only to lactose, three One or more in chlorine sucrose, aspartame, stevioside, acesulfame potassium, sorbierite, mannitol, saccharin sodium；Colouring agent used can Select but be not limited only to titanium dioxide, iron oxide, beta carotene, beet red, lac are red, red pigment of cowberry, capsanthin, red rice are red, kermes One or more in red, amaranth, famille rose, erythrosine, newly red, lemon yellow, sunset yellow, indigo, light blue.

Stickup tablet (above-mentioned individual layer, double layer adhesive sheet) of the present invention is prepared via a method which：By active component Dissolving, through granulation, whole grain after being mixed with filler, add tabletting after adhering to sustained release agent and magnesium stearate mixing and produce individual layer stickup Piece, then the solution spraying containing acrylic resin, plasticizer and pigment is made i.e. by protective layer in coat tablets by Membrane jetter Obtain double layer adhesive sheet.

The method of what the present invention narrated prepare Etimicin oral dexamethasone sticking tablet also may be selected as follows：

1) can be micronized by Etimicin or with dexamethasone or dexamethasone acetate or dexamethasone sodium phosphate, its Remaining auxiliary material cross that 80~100 mesh sieves are standby or all solids to cross 80~100 mesh sieves standby.

2) medicated layer is pelletized：The Etimicin dexamethasone for weighing medicated layer recipe quantity is passed with recipe quantity filler with equivalent The method added is mixed, then addition sustained-release matrix material is well mixed, with ethanol softwood, 20~40 mesh sieve whole grains；Will be made Particle be put into baking oven with 45 DEG C~60 DEG C drying, 20~40 mesh sieve whole grains, and add recipe quantity adhesive matrix, lubricant mixes Close uniformly, it is standby.

3) support layer is pelletized：The preparation of adhesive：It is added to by the flavouring of recipe quantity or with colouring agent containing adhesive Adhesive is used as in the aqueous solution.The filler of recipe quantity is weighed, is placed in wet granulator, addition adhesive softwood, 20~ 40 mesh are pelletized, and are dried in 45 DEG C~60 DEG C of baking oven, 20~40 mesh sieve whole grains, it is equal to be eventually adding recipe quantity mix lubricant It is even, it is standby.

4) detection of intermediate：Two kinds of particles is taken out and does determination of moisture, and does the assay of medicated layer.

5) tabletting：The piece weight of medicated layer is first regulated, then adjusts the piece weight of full wafer, double-layer tablets are pressed into bi-layer tablet press.

The usage of Etimicin oral dexamethasone sticking tablet or pelliculae pro cavo oris：General daily medication 1-3 times, affected part is each 1.

Study whether the medicine of the present invention can be used for topical treatment by following experiment

First, the excitant evaluation experimental of drug combination preparation of the invention to rabbit eyes

1st, test objective

The power reacted after dosing eyes of pharmaceutical composition of the observation present invention, with investigate Etimicin Sulfate or according to for The pharmaceutical composition of rice star and different groups whether rabbit eyes occurs adverse reaction and its degree, bibliography (document： Qian Chen, Sun Baohai, Chen Zaixin, etc.；The Eye irritation effect of besifloxacin hydrochloride, West China pharmaceutical journal, 2013,28 (3):326- 327)。

2nd, test method：Every group takes body weight 2.5-3kg healthy rabbits 4 (male and female half and half, random packet), preselects animal flesh Eye observation：For cornea without muddy, conjunctiva without congested, oedema and secretion, pupil is circular, and both sides etc. are big, light is reflected good.

Ophthalmic slit lamp inspection：Corneal transparency, no cloudiness, spot screen, iris texture is clear, no congestion and edema.

Fluorescent staining：L0% fluorescence rope sodium injections, face the used time with 5 times of normal saline dilution, fixed rabbit, per lagophthalmos Clean with normal saline flushing after dripping, observation cornea uncolored person is that cornea is normal, pre- select anophthalmia disease through above-mentioned and is good for Health rabbit is used for this experiment.

3rd, single-dose Eye irritation is tested

Eye drops and the eye drops of dosage treatment control group 1 that in the present invention prepared by each embodiment method are instilled into every rabbit The eye conjunctiva of right eye is intracapsular, passively closes 10s, and physiological saline is added dropwise as blank control, after administration, lagophthalmos eyelid to left eye with method Passive closure about 10 seconds, 1,2,4,24,48,72 hour, 7 days eye local reaction situations after record administration.With reference to《Chemicals Excitant, anaphylaxis and hemolytic investigative technique guideline》Middle Eye irritation reaction standards of grading corneal, iris and conjunctiva point Do not scored (table 1), judges whether eye drops has excitant.

4th, multiple dosing Eye irritation is tested

First dyed before daily 1st dropwise addition eye drops with 2% Fluress and (use the l0% of 5 times of normal saline dilution Fluorescence rope sodium injection), then judge whether cornea is undermined degree of injury with ophthalmic slit lamp inspection, then use physiological saline After gently rinsing, eye drops and the eye drops of dosage treatment control group 1 prepared by each embodiment method instill every rabbit right eye Eye conjunctiva it is intracapsular, passively close 10s, give left eye that physiological saline is added dropwise as control with method, during the daily morning about 9 from every about 3h drops medicine 1 time, drip 3 times altogether, successive administration 7 days, reference《Chemical induced irritation, anaphylaxis and hemolytic investigative technique instruct Principle》Middle Eye irritation reaction standards of grading corneal, iris and conjunctiva are scored respectively, judge to give drop from its mean scores Whether ocular fluid has excitant.Corneal injury is checked with fluorescein sodium during observation, and with slit lamp examination corneal transparence and rainbow Film texture changes.

5th, experimental result (table 2) single-dose Eye irritation is tested：Standards of grading, the eye drip of embodiment are reacted according to Eye irritation Liquid stimulate the reaction synthesis mean scores are 0~3.

Multiple dosing Eye irritation is tested：The Etimicin eye drops successive administration of the present invention 7 days, except embodiment 11 and implement Outside the eye drops of example 12, it was observed that rabbit cornea it is transparent, without muddiness, iris is without congested, swelling, clean mark, compared with left eye Compared with without significant difference；Iris or conjunctiva mild hyperaemia after the only single or multiple administrations of the rabbit of embodiment 11 and embodiment 12 or Slight oedema, but comprehensive mean scores are still within 3.Show that each composition eye drops of the present invention is non-stimulated to lagophthalmos Property.In addition, the tissue pathological slice HE dyeing detections of experimental animal eyeball (including cornea, iris, conjunctiva), do not find obvious Difference.

Table 1, eye irritation laboratory strength standards of grading

Rank	Mean scores	Evaluation
			1	0~3	It is nonirritant
2	4~8	Slight stimulation
			3	9~12	Moderate excitant
4	13~16	Intensity excitant

Table 2, each embodiment single-dose, the irritant experiment result of multiple dosing

Sample	Single-dose mean scores	Multiple dosing overall average score value	As a result
				Embodiment 1	0	0	It is nonirritant
Embodiment 2	0	0	It is nonirritant
				Embodiment 3	0	0	It is nonirritant
Embodiment 5	0	0	It is nonirritant
				Embodiment 9	0	0	It is nonirritant
Embodiment 10	0	0	It is nonirritant
				Embodiment 11	0.25	0.5	It is nonirritant
Embodiment 12	0.25	1.25	It is nonirritant
				Embodiment 17	0	0	It is nonirritant
Embodiment 18	0	0	It is nonirritant

2nd, the treatment evaluation experimental of drug combination preparation of the invention to Bacteritic Keratitis in Rabbits

1st, in vivo studies rabbit eye injury type bacterial keratitis animal model

EHEC, staphylococcus aureus, Pseudomonas aeruginosa and the blood that will be inoculated on plain agar culture medium flat plate The micrococcus scarlatinae of agar plate is scraped with oese, and 2 × 10 are made into respectively with physiological saline⁹(photoelectricity is than turbid by CFU/ml Instrument determines concentration), reference literature method modeling type and progress pharmacodynamic experiment (document：Xiao Yi, Li Chen, Mei Qi Ping, etc.；Rabbit The foundation of eye injury type bacterial keratitis animal model, Shaanxi medical journal, 2003；32(2):187-188；Document 2：Grandson Boat, Yang Shuqun, Zhou Yuan great, etc., the pharmacodynamic study of levofloxacin eyedrops, Chongqing Medical, Chongqing Medical Journal,2004,33(7):1069-1071；), with 1.0g/kg urethane auricular vein injecting anesthetics rabbit (healthy rabbits, Body weight about 2.5-3kg, male and female half and half), rabbit cornea damage (eyes) is caused with corneal trephine, lagophthalmos palpebra inferior is pulled open, makes rabbit It is continuous to instill 2 days per four kinds of bacterium 0.1ml of ocular infections, eye discharge is taken with Sterile Saline cotton swab after 2d, it is sterile to be put into 4ml In normal saline bottle, Bacteria Culture is done to its liquid with agar plate method.

After modeling, there is obvious inflammatory reaction in lagophthalmos, and conjunctival hyperemia is serious, and corneal edema, superficial ulcer is formed, ulcer There is more secretion in face, and rabbit activity is reduced, and appetite reduces, and when checking lagophthalmos, scream is uneasy.

2nd, packet is set, and is grouped at random (in addition to Normal group and positive controls, every group of 5 rabbit)：

The method group of embodiment 5 (eye drops prepared by the method for bacterial infection+embodiment 5)；

The method group of embodiment 17 (eye drops of the method for bacterial infection+embodiment 17)；

The method group of embodiment 23 (eye drops of the method for bacterial infection+embodiment 23)；

Treat control group (eye drops of bacterial infection+Etimicin control group)；

Positive controls (bacterial infection+drop physiological saline), 3；

Normal group (normal rabbits, be uninfected by bacterium, only drip physiological saline) 3.

Different eye drops 0.2ml/d (eyes) in the treatment group drop present invention, Etimicin control group drop Etimicin Eye drops, positive controls and Normal group drop physiological saline 0.2ml/d (eyes), every 0.2ml, 4 times/d, continuity point medicine 7 days (d).Once scored every 24h eyes, Continuous Observation 7d, appraisal result, which takes statistics, learns t inspections processing.And in administration Preceding 1d, 7d takes discharge of eye to carry out Bacteria Culture with Sterile Saline cotton swab after administration, is placed in 37 DEG C of incubators and sentences after culture 48h Disconnected yin and yang attribute result.

Wherein, the preparation of Etimicin control group eye drops：

Etimicin Sulfate (in terms of Etimicin) 2g of recipe quantity is dissolved in 0.9% physiological saline 970ml, stirring is molten Solution, solution pH value is adjusted to 6.8 with 0.5M sodium hydroxide solutions and 0.5M hydrochloric acid solutions, adds 0.9% physiological saline extremely 1000ml, filling by 5ml/ bottles through 0.22 μm of filtering with microporous membrane, sealing, 100 DEG C sterilize 30 minutes, let cool, and examine, packaging.

3rd, result is shown (table 3)：

Rabbit discharge of eye bacteria cultivation results：After continuity point medicine 7 days, Normal group Bacteria Culture is feminine gender, positive Control group Bacteria Culture is the positive, and 17 groups of 5 groups of embodiment, embodiment Bacteria Cultures are feminine gender, and treat control group, embodiment 23 The Bacteria Culture part of method group is the positive；Compared with positive controls, the eye drops of each treatment group is to EHEC, golden yellow Positive eye number after staphylococcus, Pseudomonas aeruginosa, the administration of S. pyogenes infection group has notable difference (P after 7d is treated< 0.01).The method group of embodiment 5, the method group of embodiment 17 have the therapeutic effect of highly significant；Rabbit eyes are entered according to standards of grading Row inflammatory score is 0 grade：Eyelid is without redness, and conjunctiva is without hyperemia, and corneal transparency, iris texture is clear, and eye is bright without secretion, category In healing or basic healing.

The method group of embodiment 23 also has significant therapeutic effect, and compared with treating control group, positive for bacteria quantity always detects Strain number drop by half more than, have obvious difference；It is 0 grade that the method group of embodiment 23 carries out inflammatory score to be 4 to rabbit eyes： Eyelid is without redness, and conjunctiva is without hyperemia, and corneal transparency, iris texture is clear, and eye is bright without secretion, belongs to healing or controls substantially More；1 is 0.5 grade to 1 grade.

Treat control group and rabbit eyes are carried out with inflammatory score, 3 are 0 grade, and 2 are 0.5 grade to 1 grade：Conjunctiva slightly fills Blood, eye is slightly red and swollen, and secretion covering is less than 6mm；Obviously the eye drops for the treatment of control group is also effective, but relative embodiment 23 method groups, the method group of embodiment 5, the method group of embodiment 17 are less better.

The result of lagophthalmos secretion Bacteria Culture after table 3, eye drops in treatment

3rd, the experiment of composition attenuation

Bibliography method [document：Shi Ninghua, Miao Yian, Zhang Zhijian, etc., Etimicin ototoxicity test III, according to for The comparison that meter Xing Yu gentamicins, amikacin influence on vestibular function, Chinese antibiotic magazine, CHINESE J OF ANTIBIOTICS,1999,24(6):445-448；], the ototoxicity that can observation dexamethasone caused by antagonism Etimicin.Side Method：Health, hearing and the normal cavy of equilibrium function 80 are taken, 260~350g of body weight, male and female half and half, is randomly divided into 5 groups: 0.9% saline control group (16)；Etimicin Sulfate A groups 40mg/kg, 1ml solution Etimicin containing 40mg, 0.9% Physiological saline solution Etimicin Sulfate；Etimicin Sulfate B groups 10mg/kg, 1ml solution Etimicin containing 10mg, 0.9% life Manage salt solution dissolving Etimicin Sulfate；According to alternately rice A groups (Etimicin Sulfate+dexamethasone sodium phosphate, 40mg/2.5mg/kg, 1ml liquid Etimicin containing 40mg and dexamethasone sodium phosphate 2.5mg, 0.9% two kinds of physiological saline solution medicine), according to alternately Rice B groups (Etimicin Sulfate+dexamethasone, 10mg/0.25mg/kg, the method sample of Example 24), each group Etimicin Sulfate With Etimicin weight calculation amount；Daily intramuscular injection once, common 28d, a vestibular is checked during administration weekly and after the completion of administration Function, 0.9% physiological saline group daily administration volume are consistent with Etimicin Sulfate group.

Vestibular function is tested：Animal respectively before administration, administration 4 weeks after check vestibular function and nystagmus inhibiting rate change. Animal is placed in circulator, with 1 turn per second of the circle of rotating speed rotation 20, the nystagmus duration is observed immediately, calculates administration Nystagmus inhibiting rate (nystagmus inhibiting rate is the difference and the percentage of nystagmus time before administration of nystagmus time before and after administration) afterwards, nystagmus suppression The size of rate processed represents the impaired degree of vestibular function.

As a result it is as shown in table 4：Etimicin is compared with physiological saline group；It is aobvious compared to having according to alternately meter Zu Yu Etimicins group Write sex differernce, Etimicin A groups and the difference of the nystagmus inhibiting rate according to alternately rice A groups have a conspicuousness, Etimicin B groups and according to Alternately rice B component does not also have conspicuousness in the difference of the poor absolute value of the nystagmus inhibiting rate of physiological saline group, it is seen that ground plug rice Pine has significant protective effect to the ototoxicity caused by Etimicin.

The each group animal of table 4 nystagmus inhibiting rate (%, n=16)

Group	Number of animals (n)	Nystagmus inhibiting rate
			Physiological saline group	16	9.03±6.14
Etimicin A groups	16	17.67±7.05
			Etimicin B groups	16	12.46±4.28
According to alternately rice A groups	16	13.22±4.86
			According to alternately rice B groups	16	11.34±4.53

4th, animal local application irritation test X

Body weight 2.5-3kg healthy rabbits 15 are taken, are divided into 3 groups, i.e. 40 groups of embodiment, 43 groups of embodiment and normal control Group, every group 5.40 groups of embodiment, 43 groups of embodiment drip left and right ear with auristilla respectively, each 1-2 drops, 5 times a day, continuously 7d；Normal group does not drip any decoction.Observe and record animal whether there is restlessness, loses the appetite, grabs nose phenomenon.In last When 24h is administered hyperemia, oedema, red and swollen phenomenon are whether there is with the reflective spectroscopy White Rabbit ear-drum of ophthalmology, duct, the basal part of the ear (snail).As a result 3 Phenomena such as group animal is showed no ear-drum, duct, basal part of the ear hyperemia, oedema, redness, show to have no that embodiment group drips ear through multiple dosing Liquid has local irritation reaction.

5th, skin hypersensitivity is tested

Healthy guinea pig 48,250~350g of body weight is taken, male and female half and half, is randomly divided into 6 groups, bibliography method：(document： Zhang Meisong, He Xinjun, Chen Yu, the experimental study etc., purplish or white patches on the skin of dispelling secondary color ointment to animal skin allergic reaction, the Zhejiang traditional Chinese medical science are miscellaneous Will, 2013,48 (6):410-411；)

24h takes off 48 guinea pig back diamond wools before experiment, depilation scope about 3cm × 3am per side, after depilation Cavy is randomly divided into DNFB positive controls, saline control group and the method group of embodiments of the invention 25, reality The method group of example 28, the method group of embodiment 35, the method group of embodiment 37, the method group of embodiment 52 are applied, every group 8, DNFB is used Acetone sesame oil is made into 1% sensitization concentration and 0.1% and excites the concentration standby.

Sensitization contact：In each group cavy left dorsal portion, depilation skin embrocates 1%2,4- dinitrofluorobenzene, physiology salt respectively Water, the method group of embodiment 25, the method group of embodiment 28, the method group of embodiment 35, the method group of embodiment 37, the method group preparation of embodiment 52, every 0.5ml, then covered with 1 layer of oilpaper and 2 layers of gauze, piece adhesive plaster removes tested material with after determining 6h.7th day and the 14th day with same The method of sample is repeated 1 times.

Excite contact：The 14d after last coating, by 0.1%2,4- dinitrofluorobenzene, physiological saline and the method for embodiment 25 Group, the method group of embodiment 28, the method group of embodiment 35, the method group of embodiment 37, the substances of the method group of embodiment 52 are applied to cavy respectively Hair removal section on the right side of back, tested material is removed after 6h, observes at once, then observes skin whether there is erythema, water again in 24,48 and 72h It is swollen to wait allergic reaction.Erythema and oedema press following scale：Divide without erythema 0, slight erythema 1 is divided, and moderate erythema 2 is divided, once again Erythema 3 is divided, and edematous erythema 4 divides；Divide without oedema 0, Mild edema 1 is divided, and intermediate edema 2 is divided, and severe edema 3 divides；Also see simultaneously Examine cavy and the severe allergic reactions such as asthma, astasia or shock and changes of weight whether occur, sensitization rate=skin occur is red The cavy number of spot, oedema or systemic anaphylaxis/tested cavy sum.

The tested area of DNFB positive controls guinea pig skin excites rear 6h to start have slight erythema and oedema Occur, 24~48h erythema and oedema are obvious, have mitigated during 72h, and allergic reaction incidence is 100%, but without asthma, stand The systemic allergy such as shakiness；And saline control group and the method group of embodiment 25, the method group of embodiment 28, the method for embodiment 35 Group, the tested area of guinea pig skin of the method group of embodiment 52 have no that the cutaneous anaphylaxises such as erythema, oedema and asthma, astasia etc. are tight Allergic reaction again, sensitization rate are 0, the difference for having highly significant with positive controls.The method group part guinea pig skin of embodiment 37 goes out The local reactions such as existing erythema, oedema, its allergy incidence are 12.0%.

The skin hypersensitivity evaluation criterion of table 5

Allergic reaction incidence %	Classification	Allergic reaction intensity
			0~10	Ⅰ	Without sensitization
11~30	Ⅱ	Slight sensitization
			31~60	Ⅲ	Moderate sensitization
61~80	Ⅳ	Height sensitization
			81~100	V	Extreme sensitization

The pharmaceutical composition for demonstrating the present invention of skin irritation or the skin hypersensitivity experiment of embodiments of the invention Administering drug combinations safe foundation is provided.

6th, the irritant experiment of mucous membrane of mouth

Bibliography method observes the stimulation of Etimicin dexamethasone sticking tablet and film to Golden Hamster mucous membrane of mouth Property [document：Li Liang, Zheng Guoan, Guo Sheng, etc., Cydiodine buccal tablet mucous membrane of mouth irritation test, Inner Mongol traditional Chinese medicine, 2,009 28 (23):62-63；].

Method：The male golden yellow gopher 24 of health is taken, body weight about 100-140g, is randomly divided into 4 groups, respectively embodiment 50 method groups and the method group intact mucosa group of embodiment 54, the method breakage mucous membrane group of embodiment 50, the method breakage mucous membrane group of embodiment 53, every group 6, compareed using itself left and right sides mucous membrane, left side administration, right side is as blank control；The sterile pins of 24h scratch before administration Buccal mucous membrane at left and right sides of damaged mucous membrane group Golden Hamster.

Medication：Dorsal position is taken to fix Golden Hamster, the method group of embodiment 50 accurately takes about 0.25 × 0.1cm diaphragm It is put on the left of its chamber in cheek pouch, what medicine right side cheek pouch does not let alone；The method group of embodiment 53 weighs ten/a piece of dose and put Enter on the left of its chamber in cheek pouch, what medicine right side cheek pouch does not let alone, is administered daily 3 times, continuous 7d.Gross examination of skeletal muscle is evaluated：Every time 1h before administration and after administration, 1 after last dose, 24,48,72h, observe and record with the mucous membrane of medicament contact whether there is erythema, gruel Situations such as rotten and oedema, and scored by literature method；If any other reactions, observe and record.

As a result show：Make gross examination of skeletal muscle evaluation and Histological evaluation after direct oral cavity mucosal drug delivery 7d, gross examination of skeletal muscle display is real Apply the method group of example 50 and the method group of embodiment 53 is nonirritant to the oral cavity intact mucosa of Golden Hamster and damaged mucous membrane；Pathological tissue Learn and check that the display method group of embodiment 50 and the method group of embodiment 53 do not produce the pathology such as inflammation to intact mucosa and damaged mucous membrane Change；Histopathology scoring shows that the method group of embodiment 50 and the method group of embodiment 53 are non-stimulated to intact mucosa and damaged mucous membrane Property, conclusion：The method group of embodiment 50 and the method group of embodiment 53 are nonirritant to the mucous membrane of mouth of Golden Hamster.

The purposes of the present invention：Composition of the present invention be used to preparing the otitis externa that treats or prevents people or mammal and Illness, ear or the nasa surgery of tympanitis operate the application in the ear of patient or the topical drug of nose；The composition is used In the conjunctivitis for preparing treatment or prevention people or mammal, angular blepharitis, keratitis, dacryocystitis, sty, trachoma, eye The application on local eye medicinal in sterileization treatment, scheroma or the xerophthalmia or dry eye syndrome of section's peri-operation period；Institute State composition be used for prepare treatment or prevention people or mammal sensitive bacterial caused by skin soft-tissue infection's property disease, such as Epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence burn, scald, the topical skin medicaments on the pernio surface of a wound Or the application on Aphthasol thing.

Embodiment

Except in embodiment and when indicated otherwise, all numerical value used should be by specification and claims It is interpreted as being modified with term " about " in all examples, therefore, unless the contrary indication, this specification and appended The numerical parameter gone out given in claims is approximation, the required property that it can be according to sought by by present disclosure Matter and change, at least, and not be intended to limit the application of doctrine of equivalents right, each numerical parameter takes an examination The number and routine for considering effective digital round up method to explain.

Although the number range and parameter that set the wide scope of disclosure are approximations.But institute in a particular embodiment The numerical value provided is reported as precisely as possible, and any number is substantially comprising some by finding in their own test The error that standard deviation is necessarily led to.

It is pointed out that unless in text clearly in addition explanation, used in this specification and the appended claims Singulative "one", " one kind " and "the" include the plural form of referring to thing, so, such as.If refer to containing " one Mixture including two or more compounds during the composition of kind compound ", it is further noted that unless herein clearly Ground illustrates that term "or" generally includes "and/or" in addition.

This " solvate " referred to herein as also include penetrating into crystal structure the molecule of solvent molecule, atom and/ Or the crystal formation of ion, the solvent molecule of solvate can be at regularly arranged and/or disorderly arranged, including hydrate.

Different crystal forms or polymorphic referred to herein as with identical chemical composition but formed the molecule of crystal, atom and/ Or the different crystal of space arrangement of ion.

Pharmaceutical composition

" pharmaceutical composition " used herein refers to the composition of medicine, and described pharmaceutical composition can contain at least one Pharmaceutically acceptable carrier.

" pharmaceutically acceptable excipient " used herein refers to the medicine that the compound for being applied to occasionally provide herein is administered With carrier or solvent, it includes, and well known to a person skilled in the art any examples of such carriers suitable for specific administration mode.

In the preparation technology of various embodiments of the present invention, the situation of the title of each component has been limited in the prescription of embodiment Under, for simplicity for each component in prescription, can carry out simplifying appellation or the property omitted address.

The concentration unit used in description of the invention has molar concentration (M) or (mol/L) or equivalent concentration (N), or hundred Divide specific concentration etc., chronomere can use second (s), minute (min), hour (h) etc., and volume unit, which can be used, rises (l or L), milli (ml), microlitre (μ l) are risen, mass unit can use gram (g), milligram (mg) etc..

" appropriate water for injection ", " appropriate sodium chloride ", appropriate each mean in " ethanol in proper amount " etc. can be by raw material or system Agent etc. is handled to the suitable less dosage or minimum dosage of required state or optimal dosage or preferable dosage.

In order to further appreciate that the present invention, the preferred embodiment of the invention is described with reference to embodiment, still It should be appreciated that these descriptions are simply further explanation the features and advantages of the present invention, rather than to the claims in the present invention Limitation.

Illustrate the effect of the present invention with specific embodiment below, but protection scope of the present invention is not limited by following examples System.

Specific embodiment

The preparation of the sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 1

Prescription：Etimicin Sulfate (in terms of Etimicin) 1g, dexamethasone sodium phosphate 1g, Sodium Hyaluronate 0.5g, boron Sour sodium 1g, sorbic acid 1g, taurine 5g, appropriate sodium chloride, 2M L MALIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, note Penetrate and add to 1000ml with water

Preparation technology：Take the Sodium Hyaluronate of recipe quantity to be added in 900ml waters for injection to let cool after heating for dissolving, successively Etimicin Sulfate, dexamethasone sodium phosphate, Boratex, sorbic acid, the taurine of recipe quantity are added, is stirred to dissolve, is stirred, PH value is adjusted to 6.5 with L MALIC ACID solution and sodium hydroxide solution, and the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 300mOsmol/k, full dose is added water to, filling by 5ml/ bottles after measure is qualified through 0.45 μm of miillpore filter pressure filtration, sealing, 121 DEG C of sterilizings, let cool, and examine, packaging.

The preparation of the sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 2

Prescription：Etimicin Sulfate (in terms of Etimicin) 2g, dexamethasone sodium phosphate 1g, Sodium Hyaluronate 1g, boric acid 0.5g, Boratex 2g, thimerosal 0.05g, taurine 5g, appropriate sodium chloride, 2M malic acid solutions are appropriate, 1M sodium hydroxide solutions In right amount, water for injection adds to 1000ml

Preparation technology：Take the Sodium Hyaluronate of recipe quantity to be added in 900ml waters for injection to let cool after heating for dissolving, successively Etimicin Sulfate, dexamethasone sodium phosphate, boric acid, Boratex, thimerosal, the taurine of recipe quantity are added, is stirred to dissolve, Stirring, pH value is adjusted to 6.5 with malic acid solution and sodium hydroxide solution, the osmotic pressure of solution is adjusted about with appropriate sodium chloride For 298mOsmol/k, full dose is added water to, it is filling by 5ml/ bottles after measure is qualified through 0.45 μm of miillpore filter pressure filtration, it is close Envelope, 121 DEG C of sterilizings, lets cool, and examines, packaging.

The sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 3

Preparation technology：1) sodium dihydrogen phosphate and disodium hydrogen phosphate for weighing recipe quantity are put into stainless steel cask, and thereto 1000ml water for injection is added, is stirred to dissolve.Gained homogeneous solution is placed at room temperature；2) in 1000ml waters for injection In, trehalose, Etimicin Sulfate, dexamethasone sodium phosphate, polyquaternium -1, the sodium chloride of recipe quantity are sequentially added, is stirred It is allowed to dissolve；3) two kinds of solution are well mixed, are 6.5 with 1mol/L citric acid and NaOH solution regulation pH, add injection With water to full dose；4) resulting solution of filtration step 3, filtrate is filled into 5ml plastics eye droppings bottles, and seals, examines, labeling.

The sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 4

Prescription：Etimicin Sulfate 3g, dexamethasone sodium phosphate 1g, sodium dihydrogen phosphate (anhydrous) 1.5g, disodium hydrogen phosphate (anhydrous) 8g, PVP K30 12g, sodium chloride 5g, polyquaternium -1 0.01g, 1M citric acid or molten with NaOH Appropriate liquid, water for injection add to 1000ml

Preparation technology：1) sodium dihydrogen phosphate and disodium hydrogen phosphate for weighing recipe quantity are put into stainless steel cask, and thereto 1000ml water for injection is added, is stirred to dissolve.Gained homogeneous solution is placed at room temperature；2) in 1000ml waters for injection In, sequentially add the PVP K30 of recipe quantity, Etimicin Sulfate, dexamethasone sodium phosphate, polyquaternium -1, Sodium chloride, stirring are allowed to dissolve；3) two kinds of solution are well mixed, are 6.5 with 1M citric acid and NaOH solution regulation pH, mend Add to the full amount of water for injection；4) resulting solution of filtration step 3, filtrate is filled into 5ml plastics eye droppings bottles, and seal, examine, Labeling.

The preparation of the sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 5

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, trehalose 5g, Boratex 2g, Boric acid 0.2g, Cys 1g, acetic acid 1B 4g, sodium pantothenate 3g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, Boratex, boric acid, cysteine, acetic acid 1B, sodium pantothenate, polyquaternium- 1, it is stirred to dissolve, stirs, pH value is adjusted to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, with appropriate sodium chloride The osmotic pressure for adjusting solution is about 295mOsmol/k, adds water to full dose, qualified through 0.45 μm of miillpore filter pressure filtration, measure Afterwards, it is filling by 8ml/ bottles, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

Take 10 bottles of above-mentioned sample lucifuges to be placed in 25 DEG C or so of room temperature, 6 are placed in the environment of relative humidity 75% ± 5% Month, solution keeps clear and bright, and the pH value for determining solution is 6.7.

The preparation of the sulfated compound Etimicin dexamethasone sodium phosphate eye drops of embodiment 6

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 2g, trehalose 10g, Boratex 2g, boric acid 0.2g, Cys 1g, niacinamide 4g, L-ASPARTIC ACID 3g, Polyquaternium-10 .009g, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, Boratex, boric acid, cysteine, niacinamide, L-ASPARTIC ACID, polyquaternium -1, It is stirred to dissolve, stirs, adjusts pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, adjusted with appropriate sodium chloride The osmotic pressure for saving solution is about 295mOsmol/k, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, It is filling by 8ml/ bottles, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

Take 10 bottles of above-mentioned sample lucifuges to be placed in 25 DEG C or so of room temperature, 6 are placed in the environment of relative humidity 75% ± 5% Month, solution keeps clear and bright, and the pH value for determining solution is 6.7.

The preparation of the sulfated compound Etimicin dexamethasone sodium phosphate unit dose package eye drops of embodiment 7

Prescription：Etimicin Sulfate (in terms of Etimicin) 5.0g, dexamethasone sodium phosphate 1g, trehalose 3.78g, phosphoric acid Sodium dihydrogen 2.4g, disodium hydrogen phosphate 6.6g, taurine 10g, appropriate sodium chloride, water for injection are settled to 1000ml.

Preparation technology：Etimicin Sulfate, dexamethasone sodium phosphate, trehalose, the biphosphate of recipe quantity are weighed respectively Sodium, disodium hydrogen phosphate, taurine add 900mL waters for injection to dissolve, and after stirring, oozing for solution is adjusted with appropriate sodium chloride Pressure is about 300mOsmol/k thoroughly, is settled to 1000mL with water for injection, obtains decoction；By above-mentioned decoction through 0.45 μm of miillpore filter Filtering 1 time, then through 0.22 μm of filtering with microporous membrane；Decoction after the assay was approved, the filling above-mentioned decoctions of 0.25ml to 1ml single dose bags Fill in plastic containers, sealing, produce.

The preparation of the Etimicin Dexamethasone Eye Drops of embodiment 8

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 3g, trehalose 10g, Boratex 2g, boric acid 0.2g, L MALIC ACID 1g, DL-Lys 4g, sodium pantothenate 1g, the 0.006g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, Boratex, boric acid, L MALIC ACID, DL-Lys, sodium pantothenate, polyquaternium -1, are stirred Mixing makes dissolving, stirring, adjusts pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, is adjusted with appropriate sodium chloride The osmotic pressure of solution is about 295mOsmol/k, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, is pressed 8ml/ bottles are filling, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

Take 10 bottles of above-mentioned sample lucifuges to be placed in 25 DEG C or so of room temperature, 6 are placed in the environment of relative humidity 75% ± 5% Month, solution keeps clear and bright, and the pH value for determining solution is 6.7.

The preparation of the Etimicin Dexamethasone Eye Drops of embodiment 9

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone sodium phosphate 1g, trehalose 5g, Boratex 2g, Boric acid 0.2g, Cys 1g, vitamin C 2g, taurine 3g, the 0.008g of polyquaternium -1, appropriate sodium chloride, 1M L- L-aminobutanedioic acid solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, Boratex, boric acid, cysteine, vitamin C, taurine, polyquaternium -1, stirring Make dissolving, stir, pH value is adjusted to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, it is molten with appropriate sodium chloride regulation The osmotic pressure of liquid is about 295mOsmol/k, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, is pressed 8ml/ bottles are filling, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

Take 10 bottles of above-mentioned sample lucifuges to be placed in 25 DEG C or so of room temperature, 6 are placed in the environment of relative humidity 75% ± 5% Month, solution keeps clear and bright, and the pH value for determining solution is 6.7.

The preparation of the Etimicin Sulfate dexamethasone sodium phosphate eye drops of embodiment 10

Prescription：Etimicin Sulfate (in terms of Etimicin) 6g, dexamethasone sodium phosphate 2g, trehalose 10g, Boratex 2g, boric acid 0.2g, Cys 1g, L-arginine 2g, taurine 5g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, Boratex, boric acid, cysteine, L-arginine, taurine, polyquaternium -1, are stirred Mixing makes dissolving, stirring, adjusts pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, is adjusted with appropriate sodium chloride The osmotic pressure of solution is about 295mOsmol/k, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, is pressed 8ml/ bottles are filling, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The preparation of the Etimicin dexamethasone sodium phosphate unit dose package eye drops of embodiment 11

Prescription：Etimicin (in terms of Etimicin) 8g, dexamethasone sodium phosphate 0.5g, trehalose 6g, boric acid 0.8g, boron Sand 1.2g, taurine 10g, niacinamide 3g, 2M citric acid solution and appropriate sodium citrate solution, water for injection 400ml, pH6.81 Sharpe phosphate buffer be settled to 1000ml.

Preparation technology：The Etimicin Sulfate of recipe quantity, dexamethasone sodium phosphate, taurine, niacinamide, sea are weighed respectively Algae sugar, boric acid, borax add 400ml waters for injection to dissolve, and solution is adjusted in right amount with 2M citric acid solutions and sodium citrate solution PH value is that about 6.8, Jia Shashi phosphate buffers are settled to 1000ml, obtains decoction；By above-mentioned decoction through 0.45 μm of miillpore filter Filtering, then through 0.22 μm of filtering with microporous membrane；After the assay was approved, under hundred grades of environment, the filling above-mentioned decoctions of 0.3ml are extremely for decoction In 1ml unit dose package plastic containers, sealing, produce.

The preparation of the Etimicin dexamethasone sodium phosphate unit dose package eye drops of embodiment 12

Prescription：Etimicin (in terms of Etimicin) 10g, dexamethasone sodium phosphate 0.25g, trehalose 8g, boric acid 0.8g, Borax 1.2g, taurine 10g, vitamin B₂The hydrate 2g of sodium phosphate 2, appropriate sodium chloride, 2M citric acid solutions and sodium citrate Appropriate solution, water for injection are settled to 1000ml.

Preparation technology：The Etimicin for weighing recipe quantity is placed in the beaker of 200ml waters for injection, adds appropriate citric acid Solution makes dissolving, takes the taurine, dexamethasone sodium phosphate, vitamin B of recipe quantity respectively₂Sodium phosphate, trehalose, boric acid, boron Sand adds 700ml waters for injection to dissolve, and two solution are mixed, solution is adjusted in right amount with 2M citric acid solutions and sodium citrate solution PH value is about 6.8, and the osmotic pressure of appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, obtain decoction；By above-mentioned decoction through 0.45 μm of filtering with microporous membrane, then through 0.22 μm of filtering with microporous membrane；Decoction is examined After qualified, under hundred grades of environment, the filling above-mentioned decoctions of 0.4ml sealing, are got product into 1ml unit dose package plastic containers.

The preparation of the Etimicin dexamethasone sodium phosphate unit dose package eye drops of embodiment 13

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, dexamethasone sodium phosphate 1g, Sodium Hyaluronate 1g, boron Sour 0.8g, borax 2.0g, methionine 1g, taurine 5g, trehalose 3g, appropriate sodium chloride, 2M citric acid solutions and citric acid Appropriate sodium solution, water for injection are settled to 1000ml.

Preparation technology：The Etimicin for weighing recipe quantity is placed in the beaker of 100ml waters for injection, adds appropriate citric acid Solution makes dissolving, adds taurine, methionine, dexamethasone sodium phosphate, trehalose, boric acid, the boron of recipe quantity successively wherein Sand, it is stirred to dissolve, takes the Sodium Hyaluronate of recipe quantity to be added to heating for dissolving in 800ml waters for injection and let cool, then by two The mixing of kind of solution, then it is about 6.8 to adjust the pH value of solution in right amount with 2M citric acid solutions and sodium citrate solution, appropriate chlorination The osmotic pressure of sodium regulation solution is about 305mOsmol/k, adds water for injection to be settled to 1000ml, obtains decoction；Above-mentioned decoction is passed through 0.45 μm of filtering with microporous membrane, then through 0.22 μm of filtering with microporous membrane；After the assay was approved, the filling above-mentioned decoctions of 0.25ml are extremely for decoction In 1ml unit dose package plastic containers, sealing, produce.

The Etimicin Sulfate dexamethasone DL eye drops of embodiment 14

Prescription：Etimicin Sulfate 3g, dexamethasone 0.01g, hydroxypropyl methylcellulose 3g, the poly- second two of VE succinic acid Alcohol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or and NaOH solution In right amount, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1 of recipe quantity are weighed, is dissolved in 200ml Water for injection, stir, 0.22 μm of filtering with microporous membrane；Weigh the hydroxypropyl methylcellulose of recipe quantity, VE succinic acid gathers Glycol ester is dissolved in 520ml waters for injection, and two kinds of solution are mixed, 0.45 μm of filtering with microporous membrane, mixed with above-mentioned solution, It is standby；2) dexamethasone of the micronizing of recipe quantity is weighed, is suspended in 200ml waters for injection, adding citric acid solution regulation pH value To 6.2, high-shearing dispersion emulsifying machine shears 15min (1200r/min), is prepared into dexamethasone suspension, standby；3) by 2) liquid 1) liquid is transferred to, stirs 10min, adds dilute citric acid solution and NaOH solution to adjust pH value to 6.5, adds appropriate sodium chloride to adjust molten The osmotic pressure of liquid is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, will Mixed rotary liquid is filled and is distributed into 5ml plastics eye droppings bottles, and is sealed, examines, produced.

The Etimicin Sulfate dexamethasone DL eye drops of embodiment 15

Prescription：Etimicin Sulfate 3g, dexamethasone 0.25g, hydroxypropyl methylcellulose 4g, Tween-80 0.3g, sodium chloride In right amount, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or appropriate, the water for injection with NaOH solution Add to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1 of recipe quantity are weighed, is dissolved in 200ml Water for injection, stir, 0.22 μm of filtering with microporous membrane；Weigh the hydroxypropyl methylcellulose of recipe quantity, Tween-80 is dissolved in 520ml waters for injection, two kinds of solution are mixed, 0.45 μm of filtering with microporous membrane, mixed with above-mentioned solution, it is standby；2) place is weighed The dexamethasone for the micronizing just measured, 200ml waters for injection are suspended in, adding citric acid solution adjusts pH value to 6.2, and high shear divides Mulser shearing 15min (1000r/min) is dissipated, is prepared into dexamethasone suspension, it is standby；3) 2) liquid is transferred to 1) liquid, stirred 10min, add dilute citric acid solution and NaOH solution to adjust pH value to 6.3, add appropriate sodium chloride to adjust the osmotic pressure of solution about For 300mOsmol/k, add water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, mixed rotary liquid is filled and dispensed Enter in 5ml plastics eye droppings bottles, and seal, examine, produce.

The sulfated compound Etimicin Dexamethasone Eye Drops of embodiment 16

Prescription：Etimicin Sulfate 3g, dexamethasone 0.5g, Macrogol 4000 5g, the poly- second two of VE succinic acid Alcohol ester 2g, appropriate sodium chloride, trehalose 4g, xylitol 1g, the 0.01g of polyquaternium -1, natrium adetate 0.1g, 1M lemon Acid is appropriate with NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, trehalose, natrium adetate, xylitol, the polyquaternary amine of recipe quantity are weighed Salt -1, Macrogol 4000, VE succinic acid macrogol ester are dissolved in 750ml waters for injection, stir, through 0.65 μ M filtering with microporous membrane, it is standby；2) dexamethasone of the micronizing of recipe quantity is weighed, 200ml waters for injection is suspended in, adds lemon Acid solution adjusts pH value to 6.2, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), is prepared into dexamethasone suspension Liquid, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, added dilute citric acid solution and NaOH solution adjusts pH value to 6.6, with suitable The osmotic pressure of the sodium chloride regulation solution of amount is about 308mOsmol/k, adds water to full dose, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and sealed, examine, produce.

The Etimicin Sulfate Dexamethasone Eye Drops of embodiment 17

Prescription：Etimicin Sulfate 3g, dexamethasone 1g, Macrogol 6000 2g, tocopheryl succinate acid polyethylene glycol Ester 5g, Taurine 5g, trehalose 30g, appropriate sodium chloride, the 0.005g of polyquaternium -1, natrium adetate 0.1g, 1M lemon Acid is appropriate with NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, Taurine, trehalose, natrium adetate, the polyquaternary amine of recipe quantity are weighed Salt -1, VE succinic acid macrogol ester, are dissolved in 200ml waters for injection, stir, 0.65 μm of filtering with microporous membrane； The Macrogol 6000 for weighing recipe quantity is dissolved in 520ml waters for injection, two kinds of solution is mixed, 0.45 μm of miillpore filter mistake Filter, is mixed with above-mentioned solution, standby；2) dexamethasone of the micronizing of recipe quantity is weighed, 200ml waters for injection is suspended in, adds Citric acid solution adjusts pH value to 6.2, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), is prepared into dexamethasone and mixes Suspension, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, added dilute citric acid solution and NaOH solution to adjust pH value to 6.5, use The osmotic pressure of appropriate sodium chloride regulation solution is about 308mOsmol/k, adds water to full dose, high-shearing dispersion emulsifying machine shearing 15min, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and sealed, examine, produce.

The Etimicin Sulfate Dexamethasone Eye Drops of embodiment 18

Prescription：Etimicin Sulfate 3g, dexamethasone acetate 1g, Macrogol 6000 3g, the poly- second of VE succinic acid Diol ester 5g, glycine 10g, trehalose 8g, sodium chloride：Potassium chloride (9:1) in right amount, the 0.005g of polyquaternium -1, ethylenediamine tetraacetic Sodium acetate 0.1g, 1M citric acid are appropriate with NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, glycine, trehalose, natrium adetate, the polyquaternary amine of recipe quantity are weighed Salt -1, VE succinic acid macrogol ester, are dissolved in 200ml waters for injection, stir, 0.65 μm of filtering with microporous membrane； The Macrogol 6000 for weighing recipe quantity is dissolved in 520ml waters for injection, two kinds of solution is mixed, 0.45 μm of miillpore filter mistake Filter, is mixed with above-mentioned solution, standby；2) dexamethasone acetate of the micronizing of recipe quantity is weighed, is suspended in 200ml injections Water, adding citric acid solution adjust pH value to 6.2, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), are prepared into acetic acid Dexamethasone suspension, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, add dilute citric acid solution and NaOH solution to adjust pH Value is to 6.5, with appropriate sodium chloride：(weight is than 9 for potassium chloride:1) osmotic pressure for adjusting solution is about 308mOsmol/k, adds water To full dose, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, i.e. .

The sulfated compound Etimicin Dexamethasone Eye Drops of embodiment 19

Prescription：Etimicin Sulfate 3g, dexamethasone 2g, hydroxypropyl methylcellulose 6g, VE succinic acid macrogol ester 3g, sodium chloride 5g, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or appropriate with NaOH solution, note Penetrate and add to 1000ml with water

Preparation technology：1) Etimicin Sulfate of recipe quantity, sodium chloride, natrium adetate, polyquaternium -1, dissolving are weighed In 200ml waters for injection, stir, 0.65 μm of filtering with microporous membrane；Weigh hydroxypropyl methylcellulose, the vitamin E of recipe quantity Butanedioic acid macrogol ester is dissolved in 520ml waters for injection, two kinds of solution is mixed, 0.45 μm of filtering with microporous membrane, and above-mentioned Solution mixes, standby；2) dexamethasone of the micronizing of recipe quantity is weighed, is suspended in 200ml waters for injection, adding citric acid solution PH value is adjusted to 6.2, high-shearing dispersion emulsifying machine shears 10min (1200r/min), is prepared into dexamethasone suspension, standby； 3) 2) liquid is transferred to 1) liquid, stirs 10min, added dilute citric acid solution and NaOH solution adjusts pH value to 6.4, add water to full dose, High-shearing dispersion emulsifying machine shears 10min, and liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The Etimicin Sulfate Dexamethasone Eye Drops of embodiment 20

Prescription：Etimicin Sulfate 5g, dexamethasone acetate 1g, hydroxypropyl methylcellulose 4g, the poly- second two of VE succinic acid Alcohol ester 0.5g, trehalose 5g, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or Appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, trehalose, natrium adetate, polyquaternium -1, dissolving are weighed In 200ml waters for injection, stir, 0.45 μm of filtering with microporous membrane；Weigh hydroxypropyl methylcellulose, the vitamin E of recipe quantity Butanedioic acid macrogol ester is dissolved in 520ml waters for injection, two kinds of solution is mixed, 0.65 μm of filtering with microporous membrane, and above-mentioned Solution mixes, standby；

2) dexamethasone acetate of the micronizing of recipe quantity is weighed, is suspended in 200ml waters for injection, adding citric acid solution is adjusted PH value is saved to 6.3, high-shearing dispersion emulsifying machine shears 10min (1200r/min), is prepared into dexamethasone acetate suspension, standby With；3) 2) liquid is transferred to 1) liquid, stirs 10min, added dilute citric acid solution and NaOH solution adjusts pH value to 6.5, with appropriate The osmotic pressure of sodium chloride regulation solution is about 300mOsmol/k, adds water to full dose, high-shearing dispersion emulsifying machine shearing 10min will Liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and is sealed, examines, produced.

The preparation of the Etimicin dexamethasone gel eye drops of embodiment 21

Prescription：It is Etimicin Sulfate (in terms of Etimicin) 3.0g, dexamethasone sodium phosphate 1g, Acritamer 940 3g, poly- Vinyl alcohol 1g, trehalose 3g, taurine 10g, vitamin B₁1g, benzalkonium bromide 0.02g, natrium adetate 0.3g, Tween-80 1g, appropriate triethanolamine or 2M citric acid solutions regulation pH value 6.9, water for injection is settled to 1000g.

Preparation technology：Take the Acritamer 940 of recipe quantity and polyvinyl alcohol to add water about 860ml, stand, make its swelling, with suitable The triethanolamine and/or 2M citric acid solutions of amount adjust pH value to obtain matrix to about 6.9, take recipe quantity Etimicin Sulfate, Sai meter Song sodium phosphates, trehalose, taurine, vitamin B₁, benzalkonium bromide, Tween-80 be added to stirring in 100ml water make it is molten, slowly Slowly add into above-mentioned matrix, stir, then adjust pH value to be added water to about 6.9 with triethanolamine and/or 2M citric acid solutions 1000g, vacuum outgas, it is sub-packed in 10g flexible pipes, 100 DEG C of 30min sterilizings, produces.

The preparation of the Etimicin dexamethasone gel eye drops of embodiment 22

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, dexamethasone sodium phosphate 1g, poloxamer188 25g, PLURONICS F87 2g, trehalose 3g, sodium dihydrogen phosphate 3.0g, disodium hydrogen phosphate 4.2g, taurine 10g, natrium adetate 0.3g, Phenoxyethanol 2.0g, 2M citric acid solution and appropriate sodium hydroxide solution, water for injection are settled to 1000ml.

Preparation technology：Weigh the poloxamer188 of recipe quantity, PLURONICS F87 is placed in the beakers of 900ml waters for injection In, it is stirred to dissolve, then take Etimicin Sulfate, dexamethasone sodium phosphate, taurine, trehalose, the phosphoric acid of recipe quantity respectively Sodium dihydrogen, disodium hydrogen phosphate, natrium adetate, Phenoxyethanol be added in above-mentioned solution stirring make it is molten, with 2M citric acid solutions and The pH value that sodium hydroxide solution adjusts solution in right amount is about 6.6, adds water for injection to be settled to 1000ml, by above-mentioned decoction through 0.45 μm filtering with microporous membrane, filling by 5ml/ bottles after measure is qualified, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The sulfated compound Etimicin Dexamethasone Eye Drops of embodiment 23

Prescription：Etimicin Sulfate (in terms of Etimicin) 2g, dexamethasone hydroxypropyl-beta-cyclodextrin inclusion (with Dexamethasone meter) 1g, hydroxypropyl methylcellulose 6g, VE succinic acid macrogol ester 1g, taurine 10g, trehalose 3g, gather The 0.01g of quaternary ammonium salt -1, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, injection 1000ml is added to water

Preparation technology：1) weigh the Etimicin Sulfate of recipe quantity, dexamethasone hydroxypropyl-beta-cyclodextrin inclusion, Taurine, trehalose, natrium adetate, polyquaternium -1,100ml waters for injection are dissolved in, are stirred, 1 μm of miillpore filter Filtering；Weigh the hydroxypropyl methylcellulose of recipe quantity, VE succinic acid macrogol ester is dissolved in 620ml waters for injection, by two The mixing of kind of solution, 1 μm of filtering with microporous membrane, mix with above-mentioned solution, add dilute citric acid solution and NaOH solution regulation pH value to 6.4, the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 308mOsmol/k, adds water to full dose, and liquid is filled and is distributed into In 5ml plastics eye droppings bottles, and seal, examine, produce.

The sulfated compound Etimicin Dexamethasone Eye Drops of embodiment 24

Prescription：Etimicin Sulfate (in terms of Etimicin) 10g, dexamethasone 0.25g, hydroxypropyl methylcellulose 1g, dimension life Plain E butanedioic acids macrogol ester 3g, taurine 8g, vitamin B₂Sodium phosphate 2g., trehalose 3g, the 0.01g of polyquaternium -1, second Sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, taurine, vitamin B of recipe quantity are weighed₂Sodium phosphate, trehalose, according to ground Acid disodium, polyquaternium -1,100ml waters for injection are dissolved in, are stirred, 0.45 μm of filtering with microporous membrane；Weigh recipe quantity Hydroxypropyl methylcellulose, VE succinic acid macrogol ester be dissolved in 620ml waters for injection, two kinds of solution are mixed, 0.65 μm filtering with microporous membrane, is mixed with above-mentioned solution, standby；2) dexamethasone of the micronizing of recipe quantity is weighed, is suspended in 200ml Water for injection, adding citric acid solution adjust pH value to 6.7, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), prepared Dexamethasone suspension is obtained, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, add dilute citric acid solution and NaOH solution to adjust For pH value to 6.7, the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 308mOsmol/k, adds water to full dose, high shear dispersion Mulser shears 10min, and liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The preparation of the Etimicin Sulfate dexamethasone sodium phosphate cream of embodiment 25

Preparation technology：1) stearic acid and octadecyl alcolol for weighing recipe quantity mix in beaker, and heating makes fusing, standby；2) Etimicin Sulfate (in terms of Etimicin) 3g, potassium sorbate, dexamethasone sodium phosphate of recipe quantity is taken to add 650ml's respectively Water for injection, it is stirred to dissolve, adds glycerine and Tween 80, stirring, be with 1mol/L citric acid and NaOH solution regulation pH 6.5；3) be stirred continuously it is lower will 1) be added in solution 2), benefit adds to the full amount of water for injection, emulsification, crosses 200 mesh nylon mesh, cold But, dispense, produce.

The preparation of the Etimicin Sulfate dexamethasone sodium phosphate cream of embodiment 26

Preparation technology：1) stearic acid and octadecyl alcolol for weighing recipe quantity mix in beaker, and heating makes fusing, standby；2) Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone sodium phosphate, Polidronium Chloride of recipe quantity is taken to add 650ml's respectively In the beaker of water for injection, it is stirred to dissolve, adds glycerine and Tween 80, stirring, with 1mol/L citric acid and NaOH solution It is 6.5 to adjust pH；3) be stirred continuously it is lower will 1) be added in solution 2), benefit adds to the full amount of water for injection, and emulsification, crosses 200 mesh Buddhist nuns Dragon sieve, is cooled down, and packing, is produced.

The preparation of the Etimicin Sulfate dexamethasone sodium phosphate cream of embodiment 27

Preparation technology：1) stearic acid and octadecyl alcolol for weighing recipe quantity mix in beaker, and heating makes fusing, standby；2) Etimicin Sulfate (in terms of Etimicin) 5g of recipe quantity, dexamethasone sodium phosphate is taken to add 650ml water for injection respectively, It is stirred to dissolve, adds glycerine and vitamin E TPGS, stirring, be 6.5 with 1mol/L citric acid and NaOH solution regulation pH； 3) be stirred continuously it is lower will 1) be added in solution 2), benefit adds to the full amount of water for injection, and emulsifies, and cools down, and packing, produces.

The preparation of the Etimicin Sulfate Dexamethasone ointment of embodiment 28

Prescription：It is Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone 3g, albolene 860g, beeswax 50g, sweet Oily 50g, lanolin 30g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline, honeybee Wax, glycerine, lanolin add the Etimicin Sulfate of sieving, dexamethasone is sufficiently stirred and mixed to cold in 65~70 DEG C of meltings But, packing.

The preparation of the Etimicin Sulfate Dexamethasone ointment of embodiment 29

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone 1g, albolene 832g, the poly- hydrocarbon of stearic acid The fat 60g of oxygen 40, glycerine 60g, lanolin 40g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, cross 120 mesh sieves, separately by vaseline, hard The poly- fat of hydrocarbon oxygen 40 of resin acid, glycerine, lanolin are abundant in 60~70 DEG C of meltings, Etimicin Sulfate, the dexamethasone for adding sieving Stir and evenly mix to cooling, packing.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 30

Prescription：It is Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 1g, spermaceti 50g, stearyl alcohol 30g, sweet Oily 50g, lanolin 30g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone acetate finely ground, 120 mesh sieves are crossed, separately by vaseline 820g, spermaceti, stearyl alcohol, glycerine, lanolin add the Etimicin Sulfate of sieving, dexamethasone stirs in 65~70 DEG C of meltings Mixing is mixed, then adds albolene to cooling down, to stir and evenly mix to full dose, by the specification packing of 10g/ branch, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 31

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone 5g, the fat 50g of polyoxyethylene stearate 40, poly- second The 60g of glycol -4000, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin added in 60~70 DEG C of meltings Etimicin Sulfate, the dexamethasone of sieve stir and evenly mix, then add albolene, to cooling down, to be stirred and evenly mixed, by 20g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 32

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 5g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin added in 60~70 DEG C of meltings Etimicin Sulfate, the dexamethasone of sieve stir and evenly mix, then add albolene, to cooling down, to be stirred and evenly mixed, by 20g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 33

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone 5g, the fat 50g of polyoxyethylene stearate 40, poly- second The 60g of glycol -4000, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin added in 60~70 DEG C of meltings Etimicin Sulfate, the dexamethasone of sieve stir and evenly mix, then add albolene, to cooling down, to be stirred and evenly mixed, by 10g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 34

Prescription：Etimicin Sulfate 8g, dexamethasone 3g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, Spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin added in 60~70 DEG C of meltings Etimicin Sulfate, the dexamethasone of sieve stir and evenly mix, then add albolene, to cooling down, to be stirred and evenly mixed, by 20g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 35

Prescription：Etimicin Sulfate 10g, dexamethasone acetate 0.5g, the fat 50g of polyoxyethylene stearate 40, polyethylene glycol- 4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone finely ground, 120 mesh sieves are crossed, separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin added in 60~70 DEG C of meltings Etimicin Sulfate, the dexamethasone acetate of sieve stir and evenly mix, then add albolene, to cooling down, to stir and evenly mix, press to full dose The specification packing of 20g/ branch, is sealed, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 36

Prescription：Etimicin Sulfate 20g, dexamethasone acetate 0.5g, glycine 20g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone acetate, glycine finely ground, cross 120 mesh sieves, separately Vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin is molten in 60~70 DEG C Solution, adds the Etimicin Sulfate of sieving, dexamethasone acetate stirs and evenly mixs, then adds albolene to full dose, to cooling down, stirring Mix, dispense, seal by the specification of 20g/ branch, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 37

Prescription：Etimicin Sulfate 30g, dexamethasone 1g, glycine 20g, taurine 20g, the fat of polyoxyethylene stearate 40 50g, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone, glycine, taurine finely ground, cross 120 mesh sieves, Separately by vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin in 60~70 DEG C Melt, add the Etimicin Sulfate of sieving, dexamethasone stirs and evenly mixs, then add albolene, to cooling down, stirring is mixed to full dose It is even, dispense, seal by the specification of 10g/ branch, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Dexamethasone ointment of embodiment 38

Prescription：Etimicin Sulfate 40g, dexamethasone acetate 0.5g, glycine 20g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Take that to state formula ratio Etimicin Sulfate, dexamethasone acetate, glycine finely ground, cross 120 mesh sieves, separately Vaseline 700g, the fat of polyoxyethylene stearate 40, PEG-4000, spermaceti, atoleine, lanolin is molten in 60~70 DEG C Solution, adds the Etimicin Sulfate of sieving, dexamethasone acetate stirs and evenly mixs, then adds albolene to full dose, 200 mesh sieve mistakes Filter, to cooling down, stir and evenly mix, dispense, seal by the specification of 20g/ branch, packaging.

The preparation of the sulfated compound Etimicin auristilla of embodiment 39

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 0.25g, natrium adetate 0.2g, 95% ethanol 500ml, glycerine 350ml, water add to 1000ml.

Preparation technology：Take dexamethasone acetate to be dissolved in 95%300ml ethanol, add glycerine and stir evenly to obtain A liquid；Take sulfuric acid according to It is placed in for rice star and natrium adetate in about 80ml water, low-grade fever makes to dissolve to obtain B liquid in water-bath；B liquid is poured into A liquid, with less Amount purified water drip wash holds the utensil of B liquid, and washing lotion is poured into A liquid, stirred evenly, after being cooled to room temperature, full dose is added water to, stirs evenly, and 200 Mesh screen, it is filling by 15ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 40

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 0.5g, natrium adetate 0.2g, 95% ethanol 500ml, taurine 6g, glycerine 350ml, water add to 1000ml.

Preparation technology：Take dexamethasone acetate to be dissolved in 95%300ml ethanol, add glycerine and stir evenly to obtain A liquid；Take sulfuric acid according to It is placed in for meter Xing, taurine and natrium adetate in about 80ml water, low-grade fever makes to dissolve to obtain B liquid in water-bath；B liquid is poured into A liquid In, the utensil of B liquid is held with a small amount of purified water drip wash, washing lotion is poured into A liquid, stirred evenly, after being cooled to room temperature, adds water to full dose, Stir evenly, 200 mesh screens are filling by 8ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 41

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 1g, natrium adetate 0.2g, 95% Ethanol 500ml, taurine 5g, glycine 3g, glycerine 350ml, water add to 1000ml.

Preparation technology：Take dexamethasone acetate to be dissolved in 95%300ml ethanol, add glycerine and stir evenly to obtain A liquid；Take sulfuric acid according to It is placed in for meter Xing, taurine, glycine and natrium adetate in about 80ml water, low-grade fever makes to dissolve to obtain B liquid in water-bath；By B liquid Pour into A liquid, the utensil of B liquid is held with a small amount of purified water drip wash, washing lotion is poured into A liquid, stirred evenly, after being cooled to room temperature, adds water To full dose, stir evenly, 200 mesh screens, dispense, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 42

Prescription：Etimicin Sulfate (in terms of Etimicin) 2g, dexamethasone 1g, Tween-80 1g, natrium adetate 0.2g, ethanol 450ml, glycerine 400ml, 1000ml is added to water.

Preparation technology：Tween-80, dexamethasone is taken to be dissolved in ethanol, glycerine stirs evenly to obtain A liquid；Take Etimicin Sulfate and Natrium adetate is placed in about 100ml purified waters, and low-grade fever makes to dissolve to obtain B liquid in water-bath；B liquid is poured into A liquid, with a small amount of pure Change the utensil that water drip wash holds B liquid, washing lotion is poured into A liquid, stirred evenly, after being cooled to room temperature, full dose is added water to, stirs evenly, 200 mesh sieves Filtering, packing, is produced.

The preparation of the sulfated compound Etimicin auristilla of embodiment 43

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone 1g, natrium adetate 0.2g, 95% ethanol 400ml, taurine 5g, glycine 5g, glycerine 450ml, water add to 1000ml.

Preparation technology：Take dexamethasone to be dissolved in 95%300ml ethanol, add glycerine and stir evenly to obtain A liquid；Sulfuric acid is taken according to for rice Star, taurine, glycine and natrium adetate are placed in about 80ml water, and low-grade fever makes to dissolve to obtain B liquid in water-bath；B liquid is poured into A In liquid, the utensil of B liquid is held with a small amount of purified water drip wash, washing lotion is poured into A liquid, stirred evenly, after being cooled to room temperature, added water to complete Amount, is stirred evenly, and 200 mesh screens are filling by 10ml/ bottles, sealing, is produced.

The preparation of the sulfated compound Etimicin auristilla of embodiment 44

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 0.3g, natrium adetate 0.2g, Propane diols 50ml, glycerine 500ml, water 200ml, 70% ethanol add to 1000ml.

Preparation technology：Take Etimicin Sulfate, dexamethasone sodium phosphate, natrium adetate to be dissolved in 200ml water respectively, add Enter propane diols, glycerine stirs evenly, and after being cooled to room temperature, adds 70% ethanol to stir evenly to scale, through 0.8 μm of filtering with microporous membrane, measure is closed It is filling by 8ml/ bottles after lattice, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 45

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, natrium adetate 0.2g, third Glycol 50ml, glycerine 500ml, taurine 5g, water 200ml, 70% ethanol add to 1000ml.

Preparation technology：Take Etimicin Sulfate, dexamethasone sodium phosphate, natrium adetate to be dissolved in 200ml water respectively, add Enter propane diols, glycerine stirs evenly, and after being cooled to room temperature, adds 70% ethanol to stir evenly to scale, through 0.8 μm of filtering with microporous membrane, measure is closed It is filling by 8ml/ bottles after lattice, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 46

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, dexamethasone sodium phosphate 0.5g, natrium adetate 0.2g, Propane diols 50ml, glycerine 500ml, water 200ml, 70% ethanol add to 1000ml.

Preparation technology：Take Etimicin Sulfate, dexamethasone sodium phosphate, natrium adetate to be dissolved in 200ml water respectively, add Enter propane diols, glycerine stirs evenly, and after being cooled to room temperature, adds 70% ethanol to stir evenly to scale, qualified through 1 μm of filtering with microporous membrane, measure Afterwards, it is filling by 5ml/ bottles, sealing, produce.

The preparation (specification 5g/ branch) of the sulfated compound Etimicin eye ointment of embodiment 47

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone 1g, atoleine 20ml, lanolin 80g, Yellow petroleum jelly adds to 1000g；

Preparation method：By aseptic manipulation and recipe quantity, Etimicin Sulfate, dexamethasone are taken, puts in sterilizing mortar, adds A small amount of atoleine, fine and smooth pasty state is ground into, it is standby.Separately take the stearyl alcohol, lanolin, yellow petroleum jelly of sterilizing to put suitable having and cover to hold In device, heating fusing, mix, as eye pasting substrate.When eye pasting substrate temperature is down to 70-80 DEG C or so, by fine and smooth pasty state Hydrochloric acid An Tuosha stars under fast stirring, are added in eye pasting substrate, and wash mortar into eye pasting substrate with a small amount of white oil, side Edged stirs, and finally stirring makes into 1000g, and assay is aseptic subpackaged, produces.

The preparation (specification 5g/ branch) of the sulfated compound Etimicin eye ointment of embodiment 48

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, water for injection 40ml, it is stearic Alcohol 30g, lanolin 30g, yellow petroleum jelly add to 1000g；

Preparation method：By aseptic manipulation and recipe quantity, Etimicin Sulfate, dexamethasone sodium phosphate are taken, puts sterile milk In alms bowl, sterilized water for injection is added thereto grinding, until be completely dissolved, it is standby.Separately take stearyl alcohol, lanolin, yellow petroleum jelly Put in suitable container with lid, heating fusing, add sterilizing paraffin hydrocarbons to mix, as eye pasting substrate.When eye pasting substrate temperature drops During to 70-80 DEG C or so, add eye ointment base by the Etimicin Sulfate dissolved, dexamethasone sodium phosphate under fast stirring In matter, and mortar is washed into eye pasting substrate with a small amount of injection, it is stirring while adding.Finally stirring makes into 1000g, Assay, it is aseptic subpackaged, produce.

The preparation (prescription 1000) of the sulfated compound Etimicin oral cavity film of embodiment 48

Prescription：Etimicin Sulfate (in terms of Etimicin) 0.5g, dexamethasone acetate cyclodextrin inclusion compound is (with acetic acid Sai meter Song is counted) 60mg, tetracaine hydrochloride 2g, polyvinyl alcohol (17-88) 3g, sodium carboxymethylcellulose 1.5g, glycerine 2.5g, saccharin Sodium 0.05g, water for injection adds to 100g.

Preparation method：First polyvinyl alcohol, sodium carboxymethylcellulose are soaked with appropriate purified water respectively, fully water after expansion Bath is allowed to be completely dissolved, and mixes the two, standby, takes Etimicin Sulfate, tetracaine hydrochloride, dexamethasone acetate cyclodextrin encapsulated Thing is dissolved in the hot waters for injection of 30ml, adds saccharin sodium, glycerine stirring and dissolving, then by this decoction and above-mentioned standby polyethylene Alcohol, the mixing of sodium carboxymethylcellulose rubber cement liquid, appropriate water for injection is added to be mixed to ormal weight.Stand, applied after bubble eliminates Film, 50 DEG C of dryings, demoulding, the diaphragm (every containing about Etimicin 0.5mg) of required size is divided into, is irradiated under uviol lamp 15min sterilizes, and packs.

The preparation (prescription 1000) of the sulfated compound Etimicin ocular inserts of embodiment 49

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, PVA (0588) 12g, glycerine 2.0g, 1M citric acid solution and appropriate sodium citrate solution, water for injection add to 50ml；

Preparation method：First by PVA (0588), the appropriate water for injection of glycerine, fully water-bath is allowed to be completely dissolved after expansion, 200 mesh screens, successively plus Etimicin Sulfate, dexamethasone sodium phosphate 1, stirring and dissolving, with appropriate 1M citric acid solutions and Sodium citrate solution adjusts pH value to 6.8, adds appropriate water for injection to be mixed to ormal weight.Stand, the film after bubble eliminates, 50 DEG C of dryings, demoulding, 0.5 × 1.0cm diaphragm (every containing about Etimicin 3mg) is divided into, irradiates 15min under uviol lamp Sterilizing, is packed.

The preparation (prescription 1000) of the sulfated compound Etimicin film of embodiment 50

Prescription：Etimicin Sulfate (in terms of Etimicin) 1g, dexamethasone sodium phosphate 120mg, tetracaine hydrochloride 4g, gather Vinyl alcohol (17-88) 4g, sodium carboxymethylcellulose 2.0g, glycerine 2.5g, Sucralose 0.05g, with 1M citric acid solutions and lemon Lemon acid sodium solution is appropriate, and water for injection adds to 100g.

Preparation method：First polyvinyl alcohol, sodium carboxymethylcellulose are soaked with appropriate water for injection respectively, fully after expansion Water-bath is allowed to be completely dissolved, and mixes the two, standby；Take Etimicin Sulfate, tetracaine hydrochloride, dexamethasone acetate sodium phosphate molten In 30ml waters for injection, Sucralose, glycerine stirring and dissolving are added, then by this decoction and above-mentioned standby polyvinyl alcohol, carboxylic Sodium carboxymethylcellulose pyce rubber cement liquid is well mixed, and is adjusted pH value to 6.8 with appropriate 1M citric acid solutions and sodium citrate solution, is added suitable Water for injection is measured to ormal weight, is mixed.Stand, the film after bubble eliminates, 50 DEG C of dryings, demoulding, be divided into 0.5 × 1.0cm Diaphragm (every containing about Etimicin 1mg), under uviol lamp irradiate 15min sterilizing, pack.

Preparation (the prescription of the Etimicin dexamethasone sticking tablet of embodiment 51：1000)

Preparation technology：

The Etimicin Sulfate for weighing recipe quantity is dissolved with 6ml waters for injection, and dexamethasone acetate 6ml ethanol dissolves Afterwards, two solution were sequentially added into the dextrin of recipe quantity of 100 mesh sieves, pelletized after fully mixing through 40 mesh sieves, 50 After~55 DEG C of drying 2h, through 40 mesh sieve whole grains, carbopol 934, the magnesium stearate for adding the mesh sieve of mistake 100 of recipe quantity fully mix Afterwards, with diameter 6mm flat punch tablettings, pressure about 6-8kg；Acrylic acid II resins alcohol 95 ml is dissolved, adds O-phthalic Dioctyl phthalate, titanium dioxide, uranidin grinding are uniform, with Membrane jetter even application in plain piece surface, after drying, form tablet Protective layer.

Preparation (the prescription of the Etimicin dexamethasone plastics of embodiment 52：1000ml)

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone acetate 1g, pulullan polysaccharide 20g, polypropylene Alcohol 15g, ethylene glycol 80g, glycerine 20g, azone 5g, water for injection 400g, ethanol add to 1000ml.

Preparation technology：The pulullan polysaccharide and POLYPROPYLENE GLYCOL for weighing recipe quantity respectively are added in water for injection, are soaked and are added Heat, it is set fully to dissolve；The dexamethasone acetate of recipe quantity is taken to be dissolved in the ethylene glycol of recipe quantity, glycerine, azone and 100ml respectively In ethanol, two solution are well mixed, then, add ethanol to dispense in 30ml medicinal bottles to full dose, seal and produce.

Preparation (the prescription of the Etimicin dexamethasone sticking tablet of embodiment 53：1000)

Medicated layer particle：

Protective layer particle：

Preparation process：

Medicated layer particle recipe：By in the Etimicin Sulfate 4ml waters for injection of recipe quantity, the dexamethasone of recipe quantity is molten In 10% polyvinylpyrrolidone ethanol solution；After hydroxypropyl methyl cellulose, Acritamer 940 separately are crossed into 80 mesh sieves, with The dextrin mixing of 80 mesh is crossed, adds the above-mentioned polyvinylpyrrolidonesolution solution system dissolved with Etimicin Sulfate solution and dexamethasone Softwood, stir, wet grain is made after crossing 40 mesh sieves, by wet grain in about 50 DEG C of dry dry granulars, separately added the tristearin of 80 mesh Sour magnesium is standby after mixing.

Protective layer pellet preparation method：Ethyl cellulose is dissolved in ethanol, 3% solution for standby is made.Ethyl cellulose, kermes It is red mixed with titanium dioxide after, add above-mentioned ethyl cellulose solution softwood processed in right amount, softwood is crossed into 40 mesh sieves is made wet grain, will It is wet 50-60 DEG C drying after, add magnesium stearate mix after it is standby；With diameter 6mm flat punch tablettings, pressure about 6-8kg will be upper State two kinds of pellets and be pressed into double-layer tablets on a bi-layer tablet press, produce.

The sulfated compound Etimicin dexamethasone of embodiment 54 overstates the preparation of ground phosphorus Suo Si sodium eye drops

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, overstate ground phosphorus Suo Si sodium 30g, sea Algae sugar 3g, boric acid 0.5g, Cys 1g, 1B 3g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L- door winters Propylhomoserin solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the sulphur of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, overstate ground phosphorus Suo Si sodium, boric acid, cysteine, 1B, polyquaternium -1, stirring Make dissolving, adjust pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, oozing for solution is adjusted with appropriate sodium chloride Pressure is about 320mOsmol/k thoroughly, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, is filled by 8ml/ bottles Dress, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The compound Etimicin dexamethasone of embodiment 55 overstates the preparation of ground phosphorus Suo Si sodium eye drops

Prescription：Etimicin Hydrochloride (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, overstate ground phosphorus Suo Si sodium 10g, sea Algae sugar 3g, boric acid 0.5g, Cys 1g, 1B 3g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L- door winters Propylhomoserin solution is appropriate, and 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the salt of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, overstate ground phosphorus Suo Si sodium, boric acid, cysteine, 1B, polyquaternium -1, stirring Make dissolving, adjust pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, oozing for solution is adjusted with appropriate sodium chloride Pressure is about 300mOsmol/k thoroughly, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, after measure is qualified, is filled by 8ml/ bottles Dress, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The preparation of the compound Etimicin dexamethasone lifitegrast eye drops of embodiment 56

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, dexamethasone sodium phosphate 1g, lifitegrast 25g, sea Algae sugar 3g, Cys 1g, 1B 3g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M citric acid solutions are appropriate, 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：Take the trehalose of recipe quantity to be added in 900ml waters for injection to dissolve, sequentially add the salt of recipe quantity Sour Etimicin, dexamethasone sodium phosphate, lifitegrast, cysteine, 1B, polyquaternium -1, stirring make molten Solution, pH value is adjusted to 6.8 with lemon propylhomoserin solution and sodium hydroxide solution, the osmotic pressure of solution is adjusted about with appropriate sodium chloride For 310mOsmol/k, full dose is added water to, it is filling by 8ml/ bottles after measure is qualified through 0.45 μm of miillpore filter pressure filtration, it is close Envelope, 121 DEG C of sterilizings, lets cool, and examines, packaging.

The Etimicin Sulfate dexamethasone of embodiment 57 overstates ground phosphorus Suo Si sodium eye drops

Prescription：Etimicin Sulfate 3g, dexamethasone 1g, overstate ground phosphorus Suo Si sodium 30g, Macrogol 6000 2g, vitamin E butanedioic acids macrogol ester 2g, trehalose 5g, appropriate sodium chloride, the 0.005g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid is appropriate with NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity is weighed, ground phosphorus Suo Si sodium is overstated, is trehalose, natrium adetate, poly- Quaternary ammonium salt -1, VE succinic acid macrogol ester, are dissolved in 200ml waters for injection, stir, 0.45 μm of miillpore filter Filtering；The Macrogol 6000 for weighing recipe quantity is dissolved in 520ml waters for injection, and two kinds of solution are mixed, 0.45 μm of micropore filter Membrane filtration, mixed with above-mentioned solution, it is standby；2) dexamethasone of the micronizing of recipe quantity is weighed, is suspended in 200ml injections Water, adding citric acid solution adjust pH value to 6.5, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), filled in being prepared into The loose suspension of rice, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, add dilute citric acid solution and NaOH solution adjust pH value to 6.5, the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 308mOsmol/k, adds water to full dose, high-shearing dispersion emulsifying machine 15min is sheared, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

Industrial applicibility etc. and its explanation etc.：

The present invention is described in detail above by embodiment and embodiment, it will nevertheless be understood that these are said Bright that any restrictions are not formed to the scope of the present invention, person skilled substantially can be in the spirit without departing from the present invention and guarantor In the case of protecting scope, technical solutions and their implementation methods of the present invention can be carried out with a variety of modifications, improvement and replacement and group Close, to realize the technology of the present invention, these are because falling within the scope of protection of the present invention.In particular, it will be understood that The change of many details is possible, and all similar replacements and change are apparent for a person skilled in the art , they are considered as being included in the spirit, scope and content of the present invention, and the present invention is not limited to above-described embodiment.

Claims (16)

1. a kind of topical ophthalmic is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, the sulfuric acid containing effective dose Etimicin or Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound, wherein the composition also dexamethasone of the effective dose containing anti-inflammatory or can pharmaceutically connect Any one or more of in the derivative for the dexamethasone received or its pharmaceutically-acceptable salts or its inclusion compound, remaining is pharmaceutically Acceptable carrier；The derivative of wherein described dexamethasone or dexamethasone be selected from dexamethasone, dexamethasone acetate, fill in The loose sodium phosphate of rice, dexamethasone -21- phosphate, dexamethasone -21- sulfate, the 21- ether derivants or ground plug of dexamethasone Meter Song 21- benzyl oxides derivative or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag Any of compound is a variety of.

2. the topical ophthalmic of claim 1 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, it is characterised in that： Per 1000ml or 1000g or 1000cm²Eye-drops preparations or ear use nose use or oral preparations in the sulphur containing effective dose Sour Etimicin or Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its It is any one or more of in inclusion compound etc., wherein the composition also dexamethasone of the effective dose containing anti-inflammatory or pharmaceutically It is any one or more of in the derivative of acceptable dexamethasone or its pharmaceutically-acceptable salts or its inclusion compound；Remaining is medicine Acceptable carrier on；The pharmaceutical composition of the present invention can be eye drops on pharmaceutical preparation, gel for eye use, ophthalmically acceptable soft Cream, ocular inserts, ophthalmically acceptable dripping pill, external-use gel, ointment, emulsifiable paste, plastics, film, auristilla, oral cavity adhesion tablet, oral cavity contain Piece.

3. the topical ophthalmic of claim 1 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, it is characterised in that： Per 1000ml or 1000g or 1000cm²Eye-drops preparations or ear nose section medicine or external preparation for skin or oral preparations in contain sulphur Sour Etimicin or Etimicin or its pharmaceutically acceptable salt or its different crystallization or amorphous article or its solvate Its inclusion compound or they in it is any one or more of, the weight or ratio of weight and number counted using Etimicin is 0.010- The derivative of 1.0wt% or 0.01~10g, the dexamethasone containing anti-inflammatory effective dose or pharmaceutically acceptable dexamethasone Weight or ratio of weight and number be calculated as 0.01-1.0wt%；Remaining is pharmaceutically acceptable carrier.

4. the topical ophthalmic according to claim 1-2 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, It is characterized in that：A kind of topical ophthalmic is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, containing sulfuric acid according to for Rice star or Etimicin or its pharmaceutically acceptable salt or its different crystallization or amorphous article or its solvate or its bag Compound or they in it is any one or more of, wherein dexamethasone of the composition also containing anti-inflammatory effective dose or pharmaceutically The derivative of acceptable dexamethasone, remaining is pharmaceutically acceptable carrier, wherein the composition contain according to for rice Star concentration is 0.10-0.8wt%；Or per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically Acceptable salt or its different crystallization or its solvate or its inclusion compound or they in it is any one or more of, with according to for rice The weight of star is calculated as 1.0~8.0g or is calculated as the unit of 1,000,000 units~8,000,000 with Etimicin potency, wherein the composition Dexamethasone also containing anti-inflammatory effective dose or or pharmaceutically acceptable dexamethasone derivative；Remaining is pharmaceutically may be used The carrier of receiving.

Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically acceptable Preservative or bacteriostatic agent, antioxidant, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, diluent, guarantor Humectant or they in it is any one or more of.

5. the topical ophthalmic according to claim 1-4 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, It is characterized in that：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or Its different crystallization or its solvate or its inclusion compound or they in it is any one or more of, be calculated as with the weight of Etimicin 1.0~10g, or be calculated as 1,000,000-1,000 ten thousand units with Etimicin potency, dexamethasone or pharmaceutically acceptable fills in rice 0.1~10g of derivative of pine, remaining is pharmaceutically acceptable carrier.

6. topical ophthalmic according to claims 1 to 5 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, It is characterized in that：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or Its different crystallization or its solvate or its inclusion compound or they in it is any one or more of, be calculated as with the weight of Etimicin 3.0g or with Etimicin potency be calculated as 3,000,000 units, dexamethasone or dexamethasone acetate or dexamethasone sodium phosphate or its Inclusion compound 1.0g, remaining is pharmaceutically acceptable carrier.

7. topical ophthalmic according to claims 1 to 5 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, It is characterized in that：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or Its different crystallization or its solvate or its inclusion compound or they in it is any one or more of, be calculated as with the weight of Etimicin 5.0g or with Etimicin potency be calculated as 5,000,000 units, dexamethasone or dexamethasone acetate or dexamethasone sodium phosphate or its Inclusion compound 1.0g, remaining is pharmaceutically acceptable carrier.

8. the topical ophthalmic of claim 1 is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, it is characterised in that： Per 1000ml or 1000g or 1000cm²Eye-drops preparations or ear use nose use or oral preparations in the sulphur containing effective dose Sour Etimicin or Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its It is any one or more of in inclusion compound etc., wherein the composition also dexamethasone of the effective dose containing anti-inflammatory or pharmaceutically It is any one or more of in the derivative of acceptable dexamethasone or its pharmaceutically-acceptable salts or its inclusion compound；It is wherein described The composition also local anaesthetics containing effective dose, including but not limited to tetracaine hydrochloride, procaine, chloroprocanine, benefit Cacaine, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine or its Pharmaceutical salts or its inclusion compound etc., its weight of material than can be whole weight of formulation 5~50% (w/w)；Remaining is pharmaceutically may be used The carrier of receiving.

9. local skin externally-applied medicinal composition according to claim 1, it is characterised in that：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or its different crystallization or its solvate or its Inclusion compound or they in it is any one or more of, 0.5~50g, dexamethasone sodium phosphate or ground are calculated as with the weight of Etimicin 0.010~5g of Sai meter Song or dexamethasone acetate, remaining is pharmaceutically acceptable carrier.

10. local skin external application according to claims 1 to 2 or oral cavity are used or oral cavity medicine compositions, its feature exist In：Per 1000ml or 1000g or 1000cm²External preparation for skin or oral preparations in contain Etimicin Sulfate or Etimicin Its pharmaceutically acceptable salt or its different crystallization or amorphous article or its solvate or its inclusion compound or they in appoint What is one or more, is calculated as 0.25~10g with the weight or parts by weight of Etimicin, the ground plug rice containing anti-inflammatory effective dose The weight or parts by weight of the derivative of loose or pharmaceutically acceptable dexamethasone are calculated as 0.01-1.0wt%；Wherein described group The compound also local anaesthetics containing effective dose, including but not limited to tetracaine hydrochloride, procaine, chloroprocanine, benefit card Cause, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine or its medicine With salt or its inclusion compound etc., its weight is than that can be 5~50% (w/w) that whole weight of formulation or parts by weight are calculated as；Remaining is Pharmaceutically acceptable carrier.

11. topical ophthalmic according to claims 1 to 10 is used or ear is used or nose is used or external preparation for skin or the combination of oral cavity medicine thing Thing, it is characterised in that：

In its pharmaceutically acceptable carrier, it is selected from but is not limited only to water, glycerine, D- or L- or the amino acid of racemization or its salt, Such as D- or L- or DL-Lys, Lysine Acetate, cysteine, methionine, arginine or acetic arginine or L-aminobutanedioic acid Or Monosodium L-aspartate, glutamic acid, glycine, taurine, alanine, valine, leucine, isoleucine, serine, Soviet Union's ammonia Acid, cysteine, cystine, methionine, asparagine, glutamine, 5- oxylysines, histidine, phenylalanine, junket ammonia Acid, tryptophan, 3- hydroxy-prolines, 4- hydroxy-prolines, proline, homocysteine, homocystine, homoserine, bird ammonia Acid, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- amino-2-methyls propionic acid, 2- first Base -3- alanines, 2,6- diaminopimelic acids, 2- amino-3-phenyl butyrics, phenylglycine, canavanine, secondary sword bean ammonia Acid, 4- hydroxyarginines, 4- hydroxyls ornithine, homoarginine, 4- hydroxyhomoarginines, beta-lysine, 2,4-diamino-butanoic, 2,3- diaminopropionic acids, 2- methyl serines etc. or unit or polybasic carboxylic acid or its pharmaceutical salts, gallic acid, gallic acid third It is ester, progallin A, gallate, malic acid, butanedioic acid, ascorbic acid, L-AA, sodium ascorbate, different anti- Bad hematic acid, sodium isoascorbate, nicotinic acid, niacinamide, pantothenic acid, sodium pantothenate, calcium pantothenate, vitamin B1, vitamin B2, vitamin E, Beta carotene, Pyridoxamine Hydrochloride, glutathione, allantoin, citric acid or sodium citrate or lactic acid, sodium lactate, lactobionic acid, Sodium lactonic, gluconic acid, sodium gluconate or trehalose, urea, thiocarbamide or maltitol, sorbierite, mannitol, lactose Alcohol, xylitol, antierythrite, Hyaluronic Acid or sodium hyaluronate or its hydrate or their pharmaceutically acceptable salt or theirs is different One or more in structure body etc., sorbierite include D- D-sorbites, anhydrous sorbierite or the water thing of sorbierite half or 1 water sorbierite Or the one or more in sorbitol instant etc., it is above-mentioned to include its isomers；Concentration range used in these compounds can With 0.000~5.0%；

Pharmaceutically acceptable pH adjusting agent is selected from but is not limited only to pharmaceutically acceptable inorganic acid or organic acid or its is medicinal The lewis acid or alkali of salt, inorganic base or organic base or its pharmaceutical salts or broad sense, can be hydrochloric acid, sulfuric acid or its medicine With salt, boric acid or its pharmaceutical salts, borax, phosphoric acid or its pharmaceutical salts, acetic acid or its pharmaceutical salts, such as sodium acetate, lactic acid and lactic acid Pharmaceutical salts, citric acid or its pharmaceutical salts, tartaric acid or citric acid or its pharmaceutical salts, disodium hydrogen phosphate, sodium dihydrogen phosphate, di(2-ethylhexyl)phosphate Hydrogen potassium, ascorbic acid, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, sodium hydroxide, potassium hydroxide, sodium carbonate, carbon Sour hydrogen sodium, trihydroxy aminomethane, diethanol amine, monoethanolamine, diisopropanolamine (DIPA), 2- amino -2- (methylol) 1,3-PD Amine, N- methyl glucoses amine and their salt, multi-hydroxy carboxy acid and pharmaceutical salts, as glucuronic acid, gluconic acid, lactobionic acid, In malic acid, threonic acid, glucoheptonic acid, amino acid or their pharmaceutically acceptable salt or its hydrate or its isomers It is one or several kinds of；

Pharmaceutically acceptable antioxidant and stabilizer are selected from but are not limited only to sulfurous acid and its salt, bisulfites, burnt sulfurous Hydrochlorate, dithionite, TGA and its pharmaceutical salts, thiolactic acid and its pharmaceutical salts, thio-2 acid and salt, monohydroxy Or multi-hydroxy carboxy acid and pharmaceutical salts, tartaric acid, sorbic acid or its pharmaceutical salts, nitrate, acetic acid pharmaceutical salts, citrate, EDTA And edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate calcium or ethylenediamine tetrem The sour hydrate of sodium calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), N- bis- (2- ethoxys) glycine, maltitol, xylose Alcohol, sorbierite, mannitol, vitamin E, beta carotene, Pyridoxamine Hydrochloride, taurine, amino acid or they pharmaceutically can connect One or several kinds in its hydrate of the salt received or its isomers etc.；

Pharmaceutically acceptable chelating agent be selected from but be not limited only to EDTA and edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, according to ground Sour calcium disodium (including sodium ethylene diamine tetracetate calcium or the hydrate of sodium ethylene diamine tetracetate calcium 2, sodium ethylene diamine tetracetate calcium 4 are hydrated Thing), one in (2- ethoxys) glycine of N- bis- or its hydrate of their pharmaceutically acceptable salt or its isomers etc. Kind is several；

Pharmaceutically acceptable preservative or bacteriostatic agent, selected from organic acid bacteriostatic agent, oxybenzene esters compound or nipalgin Esters, methyl hydroxybenzoate, propylparaben, phenmethylol, benzyl carbinol, phenoxetol, anesin, quaternary ammonium derive Thing, Domiphen bromide, benzalkonium chloride, benzalkonium bromide, hexadecyl ammonium methyl, cetylpyridinium chloride, Benzethonium, polyquaternary amine Salt, polyquaternium -1, organic Mercury derivatives, thiomersalate, thimerosal, phenylmercuric acetate and phenylmercuric nitrate, pharmacy In upper acceptable phenol compound, o-phenyl phenol, chloreresol, chlorohexidene etc. or their pharmaceutically acceptable salt etc. One or more.Generally, concentration range used in these compounds is 0.0005-5.0%, and this prevents depending on selected Rotten agent or bacteriostatic agent；Polyquaternium -1 is more preferably used to be used as anti-microbial preservative；Typically with 0.001%-1.0wt%'s Concentration uses these preservatives；

Pharmaceutically acceptable isotonic regulator, pharmaceutically acceptable isotonic regulator are selected from but are not limited only to sodium chloride, chlorine Change potassium, calcium chloride, sodium bromide, sodium phosphate, sodium sulphate, sodium nitrate, glucose, boric acid, borax, glycerine, propane diols, poly- second two Alcohol, PEG-400, PEG300, PEG-200, glucose, fructose, maltitol, xylitol, sorbierite, mannitol, inverted sugar, Its hydrate of dextran, sodium lactate or sodium lactonic, gluconic acid or sodium gluconate or one kind or several in its isomers Kind；

Pharmaceutically acceptable carrier also includes solubilizer, and solubilizer is selected from but is not limited only to polyethylene glycol oxide list oleic acid sorbierite Acid anhydride ester, Tween-80, VE succinic acid macrogol ester (vitamin E TPGS), glycerine-polyethylene glycol epoxide stearate, PEG-32 glyceryl palmitostearates, lauryl sodium sulfate, Sorbitan monolaurate, polyethylene glycol, polyethylene glycol 400-6000, HS15, polyvinylpyrrolidone, polyvinyl alcohol, amino acid or its pharmaceutical salts, medicine Learn acceptable alcohols, pharmaceutically acceptable polyalcohol, poloxamer, poloxamer188, azone, laurocapram, cyclodextrin It is or cyclodextrin pharmaceutically acceptable derivates, amide-type or urea and derivative, inorganic acid or inorganic acid salt, pharmaceutically acceptable Organic acid or acylate, pharmaceutically acceptable carbohydrate or sugar lime, pharmaceutically acceptable amine etc. or theirs is chiral different One or more in structure body etc. or their pharmaceutically acceptable salt；

Pharmaceutically acceptable carrier --- thickener or stabilizer or matrix, it is selected from but is not limited only to water-soluble polymer and oozes Saturating accelerator and the composition of their mixture composition；The water-soluble polymeric that can be used in the pharmaceutical composition of the present invention Thing includes but is not limited to natural and synthesis polymer, polysaccharide, poly- aminoglycoside, cellulose derivative, guar gum, xanthan Glue, glucan, carboxyl vinyl polymer, Sodium Polyacrylate, hyaluronidase, hyaluronic acid, Sodium Hyaluronate, chondroitin sulfate Element, locust bean gum, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, gellan gum, Pulan polysaccharide, marine alga It is acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, poly- Derivative of vinyl alcohol or dextrin and dextrin etc. and their mixture；Thickener more preferably poloxamer, chondroitin sulfate, first Base cellulose, hydroxypropyl methyl cellulose, gellan gum, hydroxyethyl cellulose, polyvinylpyrrolidone, polyethylene glycol, thoroughly Bright matter acid or Sodium Hyaluronate, trehalose etc., the more excellent concentration with 0.02%-1wt% uses in eye drops；

The excipient of pharmaceutically acceptable carrier --- gel or the filler of the matrix of film or adhesion tablet are selected from but not only It is limited to the polymerization of chitosan, poly- (hydroxyethyl meth acrylate), poly- (NVP), polyvinyl alcohol, acrylic acid Thing, carbomer, polyvinyl alcohol, IR, hydroxypropyl methylcellulose, hydroxypropylcellulose, gelatin, Propiram Polysaccharide, modified starch, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), carboxymethyl cellulose One or more in plain sodium (CMC-Na), chitosan, gelatin, starch, dextrin, wherein carbomer series include carbomer 934, One or more in carbomer940, Acritamer 940, Carbopol 941, CARBOPOL 974P.

12. claim 1-8 local medical composite for eye, it is characterised in that：Contain effective agent in medical composite for eye Fill in rice antixerophthalmic polyethylene glycol, trehalose, hyaluronic acid, Sodium Hyaluronate, chitosan, dexamethasone or the acetic acid of amount Pine or dexamethasone sodium phosphate or its inclusion compound, overstate ground phosphorus Suo Si sodium, lifitegrast, polysaccharide, glucan, chondroitin sulfate, Poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxylic One or more in sodium carboxymethylcellulose pyce, cellulose derivative.

13. the purposes of claim 1~8, wherein the composition is used to prepare the external ear for treating or preventing people or mammal Application in the topical drug of scorching and tympanitis illness, the ear of ear or nasa surgery operation patient or nose.

14. the purposes of claim 1~8, wherein the composition is used to prepare the conjunctiva for treating or preventing people or mammal Inflammation, angular blepharitis, keratitis, dacryocystitis, sty, trachoma, sterileization treatment, scheroma or the dry eyes of ophthalmology peri-operation period The application on local eye medicinal on disease or dry eye syndrome.

15. the purposes of claim 1~10, wherein the composition is used to prepare the sensitivity for treating or preventing people or mammal Skin soft-tissue infection's property disease caused by bacterium, such as epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence is burnt Wound, scald, the topical skin medicaments application on the pernio surface of a wound.

16. the purposes of claim 1~10, wherein the composition is used to prepare the sensitivity for treating or preventing people or mammal Application on the medicine of canker sore caused by bacterium.