CN105434346A

CN105434346A - Preparation composition and preparation method and use thereof

Info

Publication number: CN105434346A
Application number: CN201410391082.7A
Authority: CN
Inventors: 于莉; 詹姆斯·格瑞·弗格森
Original assignee: Shanghai Hightide Biopharmaceutical Ltd; Shenzhen Jun Shengtai Bioisystech Co Ltd
Current assignee: Shanghai Hightide Biopharmaceutical Ltd; Shenzhen Jun Shengtai Bioisystech Co Ltd; Shenzhen Hightide Biopharmaceutical Ltd
Priority date: 2014-08-08
Filing date: 2014-08-08
Publication date: 2016-03-30

Abstract

The present invention provides a preparation composition comprising a solvent, a drug component and a surfactant, the preparation composition is emulsion, surfactant-containing liquid droplets are distributed in the solvent, the volume average particle diameter of the liquid droplet is 100mum or less, the drug component comprises one drug or more drugs for treatment of otitis media, otitis externa, rhinitis, nasosinusitis, lower respiratory tract inflammation, xerostomia, xerophthalmia and dry noses, the surface tension of the preparation composition is less than 60mN / m, and the absolute value of the zeta potential is more than 15mV. The present invention also discloses a preparation method and use of the preparation composition. The preparation composition can relieve the otitis media, the otitis externa, the rhinitis, the nasosinusitis, the lower respiratory tract inflammation, the xerostomia, the xerophthalmia, the dry noses and other symptoms, can be used in the form of sprays or liquid droplets, can be applied to an effective site without use of a propellant or an atomization device, is easy to operate, and can effectively avoid stimulation and injury caused by the propellant and use inconvenience of the atomization device.

Description

A kind of preparation compositions and preparation method thereof, purposes

Technical field

The present invention relates to a kind of preparation compositions and preparation method thereof, and the purposes of said preparation compositions.

Background technology

Otitis media, otitis externa, rhinitis and sinusitis are all common otorhinolaryngology diseases.Wherein, otitis media (Otitismedia) is the inflammatory lesion of involving middle ear (comprising pharyngotympanic tube, tympanum, tympanic antrum and mastoid air cell) all or part of structure, is apt to occur in child.Apyetous and suppurative two large classes can be divided into.Apyetous person comprises secretory otitis media, barotraumatic otits media (because the change of takeoff and landing pressure, the increase of diving hydraulic pressure etc. cause); Suppurative person has acute and chronic dividing.External otitis (Otitisexterna) is the inflammation of infection of external auditory meatus, often because digging wound, ear is scratched or sewage enters caused by after external auditory meatus.External otitis can cause the swelling of external auditory meatus local skin and be attended by pain or tenderness sense, external ear is scratched where it itches, outer ear discharge increases.There are diffusivity and limitation two kinds.Rhinitis is that the symptom produced by nasal mucosa irriate or inflammation is referred to as, and can be divided into allergic rhinitis, sinusitis, acute rhinitis etc.The symptom of rhinitis comprises nasal obstruction, many tears, itches, sneeze, seriously can cause headache, dizzy and olfactory sensation decline.Pathogenic factor and the symptom of above disease are summarized as follows:

Otitis media normally causes due to salpingian periodicity open function generation obstacle.Pharyngotympanic tube is unique passage of MEV drain.Major function guides nasopharynx part gas to enter tympanum, to maintain tympanum pressure at both sides balance, thus ensures the normal vibration of tympanum.Pharyngotympanic tube mucosa continues mutually with nasopharynx part mucosa of tympanic cavity, is made up of pseudostratified ciliated columnar epithelium cell, has considerable secretory cell.The wash (mucus) of these emiocytosises, pharyngotympanic tube both not exclusively openings can be made, but can in suitable chance, opening once in a while during as dehisced, swallow, yawn or chewing, regulate bulging room pressure with this, thus keep the balance of tympanum external and internal pressure.When eustachian tube function generation obstacle, tympanum pressure at both sides disequilibrium on the one hand, tract hydrops cannot be discharged in time on the other hand, and then brings angor to patient.Wherein otalgia is its early clinic symptom, deafness, tinnitus, the symptom such as dizzy all cover by otalgia time, easily out in the cold.General Symptoms is different because of the virulence of patient's resistance and bacterial infection, often has the uncomfortable and inappetence of fear of cold, heating, body etc.Headache feature shows as the violent otalgia of their early stage formerly, then to the temporo top occipitalia radiation of suffering from ear homonymy, causes insufferable half side headache.If pharyngotympanic tube obturation also can cause tympanum pressure to reduce, ambient pressure increases relatively, thus makes otopiesis and affect audition.

Domestic and international research report, in the sample of patients with secretory otitis media, represent the content of phospholipid minimizing more obvious than Normal group of surfactant, its difference has statistical significance (p<0.01), confirm that the surfactant of patients with secretory otitis media reduces and be mainly manifested in nasopharynx, middle ear and pharyngotympanic tube local, force that salpingian opening pressure increases, compliance becomes possibility, thus cause tympanum hydrops, hydrops stores, and secretory otitis media occurs.[research of nasopharynx part surfactant and secretory otitis media relation. West China medical university journal .1999; 30 (3): 310-311] content of phospholipid reduces also has report in patients with rhinitis.[ JLaryngolOtol.2000Apr；114(4):254-9.Studyofsurfactantlevelincasesofprimaryatrophicrhinitis.SayedRH1,Abou-ElhamdKE,Abdel-KaderM,SaleemTH.； AnnOtol RhinolLaryngolSuppl.2006Sep；196:40-4.Surfactantanditsroleinchronicsinusitis.SchlosserRJ.]

Cause the reason of external otitis to have multiple, wherein great majority are bacteriological infection, and minority is fungal infection, and noninfective dermatosis causes.When suffering from external otitis, the chief complaint of patient is to itch in external ear Dodge, swelling, pain and stiff, white or yellow transudate.If transudate blocks auditory meatus, then there will be part hearing disability.

Under normal physiological conditions, the mucus that bronchia mucosal produces, can stick as dust, pollen, dust and the material such as microorganism as antibacterial and virus.Mucus can flow out from nose front portion or throat rear portion flows down.When nasal mucosa irriate or inflammation, it is excessive that mucus produces, and cannot remove in time and cause nasal obstruction, many tears, itch, sneeze.

Normal paranasal sinus (Paranasalsinuses) is the gassiness cavity in craniofacial bone around nasal cavity, and totally four is right: maxillary sinus, sinus frontalis, sieve hole and sphenoid sinus, their inwall is all lined with mucosa, and they respectively have certain position, shape and outlet.When suffering from sinusitis, the mucosa of patient is congested, swelling, and nasal cavity has a large amount of glutinous pus or purulence nasal mucus, causes serious nasal obstruction, pus tears, headache, giddy and olfactory sensation to decline.

Lower respiratory tract inflammation mainly comprises: bronchitis, chronic bronchitis, pneumonia, bronchiectasis etc., and cardinal symptom is cough, expectoration, asthma, chest pain, heating etc.Current clinical treatment mostly is antibiotic, cough-relieving and phlegm-eliminating medicine.

Dryness in the nasal cavity disease take dry nasal cavity as the nose illness of main manifestations.Doctor trained in Western medicine is called rhinitis sicca, is with the nasal cavity Chronic inflammatory conditions that nasal mucosa is dry, nasal discharge is reduced to main manifestations.Symptom is that intranasal is dry, and nasal secretion reduces, and intranasal has prodding and itching feeling or foreign body sensation, often causes sneeze, burning sensation, often lures that patient digs nose into, and cause epistaxis in a small amount, olfactory sensation is not generally gone down.Before nasal septum, inferior segment mucosa is often rotten to the corn, and can have the thin crust attachment of small pieces, that goes is often hemorrhage.The cause of disease is still unclear, thinks relevant with working environment and outside climatic more, and vitamin deficiency, anemia, a large amount of smoking, drinking can cause nasal mucosa and change, and causes primary disease.The treatment of primary disease, local can be dripped with lubrication medicinal liquid by intranasal, and whole body vitimin supplement A, vitamin B2, vitamin C, vitamin E etc. can strengthen nutrition.

Xerophthalmia refers to that the tear matter that any reason causes or amount exception or kinetics are abnormal, causes tear film stability to decline, and the general name of various diseases with ophthalmic uncomfortable and (or) eye table organization characteristics of lesion.Also known as angle conjunctival xerosis.Common symptom comprise eyes dry and astringent, easily tired, ophthalmic pruritus, have that foreign body sensation, pain burning sensation, secretions are sticky, aversion to wind, photophobia, to external world stimulate very sensitive; Sometimes eyes are too dry, basic oligodacrya, stimulate reflexive lacrimal secretion on the contrary, and cause and usually shed tears; More severe case eyes can redness, hyperemia, keratinization, corneal epithelium broken skin and have filament to stick, this damage with the passing of time then can cause angle conjunctive disorder, and can affect one's power of vision.

Tear film is primarily of phospholipid, protein, mucoprotein, electrolyte and water composition.The composition of lipid layer is mainly derived from tarsal glands, twinkle (nictation) time, lipid is gathered on the water liquid layer of inferior cornea by eyelid compression, distribute in horizontal band-like, twinkle at the end of (nictation), lipid is laid in rapidly water liquid layer with the speed opened faster than eyelid disease, water liquid layer is not directly exposed in air, decreases the evaporation of tear.Current bibliographical information causes the most common cause of xerophthalmia to be meibomian gland dysfunction (MeibomianGlandDysfunction, MGD), and MGD can affect the function of tear film, causes xerophthalmia.[ survOphthalmol.2007Jul-Aug (4): 369-74.TheCorrelationBetweentheTearFilmLipidLayerandDryE yeDisease, FoulksGN; chinese Journal of Ophthalmology.the abnormal clinical progress with xerophthalmia of tear lipid layer March 48 (3): 282-5. in 2012, Xiao Xinye, Liu Zuguo .]

The treatment means of current xerophthalmia mainly comprises artificial tears, inflammation-inhibiting, promotion lacrimal secretion etc., and wherein artificial tears is the most frequently used, the most acceptable therapeutic modality of patient.Commercially available artificial tears has liposic (Bausch-Lomb company of the U.S.) main component to be 1% medium chain triglyceride, 0.2% Carbopol, sorbitol, sodium hydroxide etc., and antiseptic is 0.01% cetrimonium bromide; RefreshDryEyeTherapy (predecessor RefreshEndura, Allergan company of the U.S.) main component is 1% polyoxyethylene sorbitan monoleate, 1% glycerol, carbomer, Oleum Ricini, mannitol, sodium hydroxide etc.

Xerostomia is a kind of symptom in oral cavity caused by aptyalism.The generation of saliva and secretion by whole body, locally, the impact of extraneous and self each factor.Because salivation reduces, patient feels xerostomia, has foreign body sensation, burn feeling, at laboratory rodent chow, during particularly drier food, can not form food group and impact is swallowed.Salivation amount is few, also little to the souring of tooth and oral mucosa, and oral cavity self-cleaning action is deteriorated.Thus, the caries prevalence rate of xerostomia patient is higher.The sense of taste of most xerostomia patient is also affected, and effectively can not stimulate appetite, and can affect the function of whole digestive system.

The treatment of current xerostomia comprises etiological treatment and symptomatic treatment.Etiological treatment is the most effective when the clear and definite cause of disease, as Drug xerostomia, by adjustment medicine and dosage thereof, can alleviate xerostomia.Saliva being consumed and increases and the xerostomia of generation, solving by eliminating the reasons such as mouth breathing.If the xerostomia caused by salivary gland parenchymal destruction, as after head-neck malignant tumor radiotherapy, Sjogren syndrome, alleviate xerostomia mainly through symptomatic treatment at present, reduce complication.

By above description, we can see: the common feature of these diseases is that tract (ear or nose) is owing to infecting or inflammatory reaction, the liquid secreted by cavity mucous membrane is caused to increase, cannot discharge in time, and cause tract to block, and then produce the malaise symptoms such as earplug, nasal obstruction, pain, cough.Or to be reduced by the secretions (nasal discharge, tear film, saliva) of corresponding site or stability declines that the eye that causes is done, xerostomia and the malaise symptoms such as dryness in the nasal cavity, asthma.

At present, in clinical treatment, use antibiotic, steroid hormone and operative treatment more.But in these Therapeutic Method, except operation, all can not within the short time (minute-hour), the malaise symptoms such as the earplug of rapid reduction of patient, nasal obstruction, pain, cough, asthma, eye are dry, xerostomia and dryness in the nasal cavity.Therefore, need badly at present a kind of can at short notice effectively the earplug of reduction of patient, nasal obstruction, pain, cough, asthma, eye do, the product of the malaise symptoms such as xerostomia and dryness in the nasal cavity.

Summary of the invention

Technical problem to be solved by this invention be to provide a kind of can at short notice effectively the earplug of reduction of patient, nasal obstruction, pain, cough, asthma, eye do, the preparation compositions of the product of the malaise symptoms such as lower respiratory tract inflammation, xerostomia and dryness in the nasal cavity.

It is as follows that the present invention solves the problems of the technologies described above adopted technical scheme:

A kind of preparation compositions is provided, comprises solvent, ingredient and surfactant; Described preparation compositions is emulsion, is distributed with the drop containing surfactant in described solvent; The volume average particle size of described drop is less than 100 μm; Described ingredient comprise treatment rhinitis, sinusitis, otitis media, external otitis, lower respiratory tract inflammation, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more; The surface tension of preparation compositions is less than 60mN/m, and the absolute value of zeta current potential is more than 15mV.

In the past between the more than ten years, people once attempted to utilize surfactant to solve the problem such as otitis media, rhinitis, but there is various problem in technology and application aspect, such as, utilize the nasal wash product that artificially synthesised surfactant prepares for component, although patient can be helped to remove nasal cavity mucus, reduce nasal obstruction symptom, but contained by product, the toxic and side effects of component causes the anosmia of patient, and consequence is serious; The research such as Jang reports the effect of Curosurf at Cavia porcellus otitis media model of atomization, [Efficacyoftransnasalnebulizedsurfactantonexperimentaloti tismediawitheffusioninguineapig. intJ pediatrOtorhinolaryngol.2010Jan; , but atomising device is complicated, uses inconvenience 74 (1): 71-4].Chandrasekhar etc. report surfactant aerosol for treating otitis media zoopery [Otitismedia:treatmentwithintranasalaerosolizedsurfactant. laryngoscope.2004Mar; 114 (3): 472-85.], but this preparation not only needs to use propellant, and active component exists in solid form, for reaching curative effect, must first in the moistening attachment of target site, therefore increase onset time, propellant may cause the nasal cavity having local inflammation to react simultaneously stimulates and injury.In addition, the aerosol products described in literary composition needs the canned production equipment of particular pressure, and production cost is expensive, uses inconvenience.

When preparation compositions provided by the invention is applied to tubal mucosa place, surfactant and middle ear effusion surface contact.Because the surface tension (being less than 60mN/m) of preparation compositions is lower, the surface tension of tubal mucosa place transudate can be reduced fast, pharyngotympanic tube is more easily opened, simultaneously, preparation compositions is paid on cavity mucous membrane, and produce lubrication, therefore middle ear effusion is able to smooth outflow.The elimination of hydrops, can reduce ear pressure, eliminates tinnitus, headache syndromes; Reduce simultaneously and infect probability, promote that inflammation is eliminated, promote recovery from illness.For external auditory meatus pus, preparation compositions by reducing the surface tension of pus, is attached on external auditory meatus mucosa on the one hand on the other hand, produces lubrication, impels pus to flow out smoothly, alleviate earplug, bulge of the ear symptom.Based on same purpose mechanism, preparation compositions can be attached to nasal mucosal surface, promotes that nasal cavity mucus is removed, alleviates nasal obstruction symptom.

As everyone knows, salpingian one end enters tympanum by antetheca, and the other end then enters nasopharynx part, and its position is very hidden, is unfavorable for treatment.Preparation compositions provided by the invention is used in the form of a spray by aerosol apparatus, make preparation can effectively arrive the target sites such as pharyngotympanic tube, nasal cavity, paranasal sinus thus play curative effect, also can be applied to external auditory meatus and nasal cavity with the form of [Dan and nasal drop.

The present invention be used for lower respiratory tract inflammation treatment mainly surfactant can reach trachea by aerosol form, moistening trachea, reduce disease to the stimulation of tunica mucosa tracheae, dilution sputum, is beneficial to sputum expectoration, reduces pulmonary surface tension, alleviate asthma, adopt the preparation of Natural Surfactant-Lecithin both can moistening trachea, reduce pulmonary surface tension, damaged mucosa can be repaired again.

The present invention be used for dryness in the nasal cavity disease (or rhinitis sicca) treatment mainly surfactant effectively can reach nasal cavity by aerosol apparatus or nasal drop form, reduce the surface tension of nasal cavity and mucus, supplement the liquid of disappearance, adopt the preparation prepared of Natural Surfactant-Lecithin both can moistening nasal cavity, damaged mucosa can be repaired again.

The present invention is used for the treatment of xerophthalmia, mainly utilizes surfactant to reduce capillary character, increases the thickness of tear lipid layer, is conducive to keeping tear film stability, extends breakup time of tear film, reduce tear evaporation, keeps eye table tear content.The preparation adopting Natural Surfactant-Lecithin to prepare can supplement the disappearance of lecithin in tear lipid layer.

Have result of study to show, the saliva of buccal cavity surface tension of xerostomia patient apparently higher than normal person [ sleep, Vol.31, No.3,2008.UpperAirwaySurfaceTensionbutnotUpperAirwayCollapsib ilityisElevatedinPrimary syndrome.CassieJ.Hilditch, R.DougMcEvoy, etc.].Surfactant in the present invention can reduce the surface tension of xerostomia patient saliva of buccal cavity, and the present invention simultaneously can supplement saliva fluid, alleviates xerostomia symptom.

Compare with nebulization therapy with aerosol, spray, without using the atomising device of propellant and complexity, makes preparation produce droplet by means of only nasal spray device by the power that compressed air produces, and a kind of water type spray of ejection.Its advantage is that the droplet of ejection is comparatively thin, is evenly distributed, not easily runs off, adhesion speed is fast, onset is rapid at nasal cavity; And aerosol apparatus service condition is simple, and cost is low.But when adopting spray pattern to treat, the stability of preparation has considerable influence to spray agent, and when especially there is the phenomenons such as sedimentation when preparation, the normal use for preparation is very unfavorable.

Explore through great many of experiments, preparation compositions entirety provided by the invention is emulsion, and comprise liquid flux and be distributed in the drop in solvent, drop contains the surfactant with excellent surface activity.Further, the absolute value of the zeta current potential of preparation compositions is more than 15mV, and the volume average particle size of drop is less than 100 μm.Have above-mentioned feature drop can in solvent Stable distritation, avoid the sedimentation phenomenon that solid powder surfactant easily occurs.

This preparation compositions is the colloidal dispersion system that surfactant is formed in a solvent, and zeta current potential is an important indicator characterizing dispersion stability.The volume average particle size at drop of preparation compositions provided by the invention is under the prerequisite of less than 100 μm, and the absolute value of the zeta current potential of preparation compositions is more than 15mV.The dispersion with above-mentioned feature can keep comparatively steady statue, not easily occurs condensation, coacervation.

Meanwhile, when using with spray pattern, the drop containing surfactant sprays from aerosol apparatus with droplet form together with solvent.After arriving the target areas such as such as pharyngotympanic tube, nasal cavity, paranasal sinus, liquid surfactant is directly scattered in middle ear effusion and nasal cavity mucus, reduce the surface tension of middle ear effusion and nasal cavity mucus, simultaneously, be attached on mucous membrane surface and play lubrication, work along both lines, middle ear effusion and nasal cavity mucus are removed smoothly, the malaise symptoms of rapid recovery patient.

In addition, preparation compositions provided by the invention has good stability, active component is all can eat general non-toxic components by medicine, surfactant is present in solvent in liquid form, when using with spray pattern, requiring low to service conditions such as atomisation pressures, adopting conventional aerosol apparatus, without the need to adopting propellant and special atomizing device.Further, the preparation existed in liquid form, without the need to through the necessary course of dissolution of solid state surface activating agent, shortens the responding time of preparation; Simultaneously also without the need to accelerating its dissolving at target site by other materials.

And, in preparation compositions provided by the invention, be added with simultaneously treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more, rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease can be treated targetedly.

Therefore preparation compositions provided by the invention has novelty and can practicality concurrently.

Meanwhile, present invention also offers the preparation method of above-mentioned preparation compositions, comprising:

S1, by the ultrasonic middle dispersion 1-3min of the surfactant of liquid state at 40-60KHZ;

S2, at rotating speed be more than 3000rpm stirring condition under, the surfactant of liquid state, ingredient are mixed homogeneously with solvent, form the preparation compositions being dispersed with the drop containing surfactant in solvent, and the absolute value that described preparation compositions surface tension is less than 60mN/m, zeta current potential is more than 15mV;

Described ingredient comprise treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more.

In addition, the invention discloses the purposes that above-mentioned preparation compositions is used for the treatment of otitis media, external otitis, rhinitis, sinusitis, dryness in the nasal cavity disease targetedly.

According to the difference of purposes, use auxiliary treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, dryness in the nasal cavity disease by nasal cavity, the xerostomia using auxiliary treatment a variety of causes to cause by oral cavity, uses auxiliary treatment xerophthalmia by eyes.

Detailed description of the invention

In order to make technical problem solved by the invention, technical scheme and beneficial effect clearly understand, below in conjunction with embodiment, the present invention is further elaborated.Should be appreciated that specific embodiment described herein only in order to explain the present invention, be not intended to limit the present invention.

Preparation compositions provided by the invention comprises solvent, ingredient and surfactant; Described preparation compositions is emulsion, is distributed with the drop containing surfactant in described solvent; The volume average particle size of described drop is less than 100 μm; Described ingredient comprise treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more; The surface tension of preparation compositions is less than 60mN/m, and the absolute value of zeta current potential is more than 15mV.

In above-mentioned preparation compositions, solvent, ingredient and to be distributed in solvent and drop containing surfactant is the main body of preparation compositions.

For whole formulation compositions objects system, its surface tension should be less than 60mN/m.As previously mentioned, when the surface tension of preparation compositions is less than 60mN/m, the surface tension of tubal mucosa place transudate can be reduced, middle ear effusion is flowed out smoothly, reduce ear pressure, eliminate tinnitus, headache syndromes; Reduce simultaneously and infect probability, promote that inflammation is eliminated, promote recovery from illness.

According to the present invention, for faster and better plays therapeutic effect, under preferable case, the surface tension of described preparation compositions is less than 40mN/m, more preferably the surface tension of described preparation compositions is less than 30mN/m, and the surface tension most preferably being described preparation compositions is less than 27mN/m.The surface tension of preparation compositions is less, is more beneficial to the surface tension reducing tubal mucosa place transudate, is more conducive to the outflow of middle ear effusion.

But found by great many of experiments, preparation compositions surface tension is less, and preparation compositions is more unstable, and the surfactant in solvent more easily assembles even layering and sedimentation, poor stability, cannot effectively use with spraying or drop-wise.

Therefore, for ensureing that preparation compositions provided by the invention has enough stability, spraying or drop-wise can be adopted to use, and the volume average particle size of described drop to be less than 100 μm, the volume average particle size being more preferably described drop is less than 10 μm, even less than 6 μm.

According to the present invention, for making preparation compositions more stable, under preferable case, the volume average particle size of described drop is 1-100 μm, and the volume average particle size being more preferably described drop is 1-10 μm, even 1-6 μm.

Above-mentioned volume average particle size is defined as: refer to identical with the grain shape of this particle swarm, cumulative volume is identical, and granule number is identical, but the particle diameter of an even-grained imaginary particle swarm.

When the particle diameter of the drop in solvent meets above-mentioned condition, the dispersion in a solvent that drop can be more stable.

In the present invention, under preferable case, the volume average particle size of described drop is 50-500nm, and the volume average particle size being more preferably described drop is 100-500nm, even 200-400nm.Now, described drop stability is in a solvent better.

For ensureing that preparation compositions provided by the invention has enough stability, under technique ensures that particle diameter meets the prerequisite of above-mentioned condition, other materials that surfactant in preparation compositions and the relative amount of solvent and selectivity add will affect the size of zeta current potential, find after deliberation, during zeta current potential more than the absolute value 15mV of preparation compositions provided by the invention, preparation compositions has good stability.

As known in the art, zeta current potential (Zetapotential) is again electrokinetic potential or eletrokinetic potential (Zeta-potential or ζ-electromotive force), refers to the current potential of shear surface (ShearPlane).More preferably, in situation, the zeta current potential absolute value of described preparation compositions is more than 20mV, even more than 40mV.Now, preparation compositions has more excellent stability.

According to preparation compositions provided by the invention, in order to improve the stability of said preparation compositions, reduce the stimulation to user, under preferable case, the pH value of above-mentioned preparation compositions is 5.0-7.4, is more preferably 6.0-7.4 simultaneously.

Can ensure that preparation compositions has the effect improving the symptoms such as rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease by above-mentioned condition, there is good system stability simultaneously.

Meanwhile, in preparation compositions provided by the invention also containing treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more.Can be treated rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease targetedly by the ingredient of above-mentioned interpolation, make preparation compositions have good combined therapy effect.

In the present invention, the various materials that the surfactant adopted can select the field such as medicine, food known, safe, such as, described surfactant is selected from, but be not limited to that natural phospholipid, sterol, Curosurf, stearic acid, oleic acid, lauric acid, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, fatty acid Pyrusussuriensis are smooth, one or more in Polysorbate, Myrj 45, polyoxyethylene aliphatic alcohol ether, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol.For ensureing the safety in utilization of preparation compositions provided by the invention, therefore, above-mentioned surfactant preferably adopts high, the active excellent material of safety, such as above-mentioned surfactant is selected from, but is not limited to one or more in lecithin, sterol, Curosurf, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol.

When adopting above-mentioned various material (such as phospholipid) as surfactant, on the basis realizing the object of the invention, the composition (such as phospholipid) of otitis media and patients with rhinitis's nasopharynx part disappearance can also be supplemented.

For preparation compositions provided by the invention, especially when surfactant is above-mentioned various material, excessive or too small pH value will cause surfactant to be hydrolyzed, and the stability of preparation compositions will reduce greatly.

Above-mentioned various material is all by commercially available.

For the solvent in preparation compositions provided by the invention, being not particularly limited, can be one or more in water, ethanol, glycerol, Medical silicone oil, edible vegetable oil.Such as described solvent is water.

Above-mentioned treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, in the medicine of dryness in the nasal cavity disease, one or more are known in the field, such as, treatment rhinitis, the medicine of lower respiratory tract inflammation comprises, but be not limited to cortisone, hydrocortisone, beclometasone, triamcinolone acetonide, mometasone, dexamethasone, fluocinolone acetonide, budesonide, the glucocorticoidss such as fluticasone, ephedrine hydrochloride, the vasoconstrictors such as xylometazoline hydrochloride, hydrochloric acid levocabastine, the antihistaminics such as A-5610, and etc. Fructus Xanthii, dandelion, Radix Scutellariae, Fructus Lagenariae gourdae, Herba Ephedrae, Flos Magnoliae, Herba Asari, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Catechu, dragon well green tea, one or more in the Chinese medicines such as Cortex Phellodendri and extract thereof.

More than treat rhinitis, sinusitis, lower respiratory tract anti-inflammatory drugs consumption for being no more than its conventional effective dose.

Similar, treatment external otitis, otitis media, the medicine of lower respiratory tract inflammation comprises, but be not limited to ofloxacin, levofloxacin, norfloxacin, lomefloxacin, tosufloxacin, Sparfloxacin, Roxithromycin, chloromycetin, penicillin, clindamycin, nitrofural, amoxicillin, ampicillin, clavulanate potassium, cefaclor, cefixime, cefdinir, cefradine, cefalexin, Cefpodoxime Proxetil, CEFUROXIME AXETIL, cefprozil, azithromycin, minocycline, Acetylmidecamycin, the antibioticses such as acetylspiramycin, the antiviral classes such as metronidazole, cortisone, the glucocorticoidss such as triamcinolone acetonide, Moschus moschiferous is fragrant, dried Alumen, Calamina, sheet brain, dry kermes, Cacumen Platycladi, Echinacea root, counterfeit indigo root, Deng one or more in Chinese medicine and extract thereof.

More than treat external otitis, otitis media, lower respiratory tract anti-inflammatory drugs consumption for being no more than its conventional effective dose.

Similar, can also medicine containing conventional treatment external otitis, lower respiratory tract inflammation, dryness in the nasal cavity disease, xerostomia and xerophthalmia in preparation compositions in the present invention, these medicines include, but are not limited in D-panthenol, glycerol, hyaluronic acid, butanediol, Polyethylene Glycol, propylene glycol, hexanediol, xylitol, Sorbitol one or more.

More than treat external otitis, lower respiratory tract inflammation, dryness in the nasal cavity disease, xerostomia and xerophthalmia the consumption of medicine for being no more than its usual amounts.

According to the present invention, in above-mentioned preparation compositions, the relative amount of solvent, ingredient and surfactant can change in a big way, as is known in the art, solvent, ingredient are different with the relative amount of surfactant, and surface tension and the zeta current potential of preparation compositions are also different.In the present invention, the surface tension of preparation compositions and zeta current potential only need be made to meet described requirement above, those skilled in the art, when preparing said preparation compositions, make the surface tension of preparation compositions and zeta current potential fall into described scope above by the relative amount adjusting solvent, ingredient and surfactant.Usually, for corresponding disease, after determining the material composition needed for preparation compositions, by constantly changing the addition of each material composition, making the final preparation compositions obtained meet condition of the present invention, now, the addition of each raw material components can be recorded.During the preparation compositions of follow-up preparation same composition, only directly need prepare according to the addition of known each raw material components.

Under preferable case, in described preparation compositions, surface-active contents is 0.1-25.0wt%, and solvent is 70.0-99.899wt%, and the content of described ingredient is 0.001-5.0wt%.When aforesaid surfactant adopt many kinds of substance with the use of time, the relative amount of various material does not limit, and only needs the surface tension of preparation compositions entirety to meet described condition above.

In the present invention, for better ensureing the stability of preparation compositions, preventing the generation of sedimentation, extending its memory time, under preferable case, in preparation compositions provided by the invention, also comprise stabilizing agent.The edible stabilizing agent that the stabilizing agent applied is known in the field such as lecithin, poloxamer, saponarin, tannin, fatty acid glyceride, sucrose fatty acid ester, methyl glycol fatty acid ester, cholesterol, cholesteryl ester, Polyethylene Glycol, cellulose and derivant, dextrin, arabic gum, Tragacanth class, pecto-cellulose cheese, gelatin, alginic acid.

In above-mentioned adoptable stabilizing agent, the material that moieties and surfactant adopt is identical, such as lecithin, poloxamer, cholesterol, cholesteryl ester.In the present invention, above-mentioned each material has good stability in preparation compositions provided by the invention, and himself can simultaneously as surfactant and stabilizing agent.

The addition of aforementioned stable agent can change in a big way, only need ensure that the surface tension of preparation compositions is in described scope above.Under preferable case, stabiliser content is 0.01-5.0wt%.

In order to improve the compliance of product, also comprise aromatic in preparation compositions provided by the invention, such as, but not limited to Mentholum, Borneolum Syntheticum, Fructus Citri Limoniae oil, patchouli oil, Oleum Cinnamomi, red date tincture, vanillin, Oleum menthae, geranium absolute, eucalyptus oil, Oleum Menthae Rotundifoliae, eugenol, citral, concrete of jasmine, Hang Zhou chrysanthemum flower extract, osmanthus concrete, benzyl alcohol, phenethanol, terpineol, methyl cyclopentenyl ketone, jasminal, butanoic acid, caproic acid, isoamyl acetate, benzyl acetate, linalyl acetate, ethyl propionate, ethyl n-butyrate., isoamyl butyrate, benzyl butyrate, iso-amyl iso-valeriate, ethyl hexanoate, cognac oil, ethyl lactate, allyl hexanoate, nonyl lactone, ethyl maltol, allyl cyclohexyl propionate, maltol, gamma-undecalactone (peach aldehyde), raspberry ketone (4-(4-hydroxyphenyl)-2-butanone), benzyl propionate, butyl butyrate, ethyl isovalerate, Ethyl formate, benzyl benzoate, methylpyrazine, 2,3-dimethyl pyrazine, trimethylpyrazine, 2-acetyl group pyrazine, 4-methyl-5-(beta-hydroxyethyl) thiazole, 2-acetylthiazole, 2，3，5，6-tetramethylpyrazine, hexadecanoyl (strawberry aldehyde, strawberry aldehyde), ethyl vanillin, hydroxycitronellal, and the correctives known in field, one or more in essence.

The addition of above-mentioned aromatic can change in a big way, only need ensure that the surface tension of preparation compositions is in described scope above.Under preferable case, fragrance level is 0.01-5.0wt%.

For improving the memory time of preparation compositions, avoid breed bacteria, under preferable case, also antibacterial is comprised in preparation compositions provided by the invention, such as, but be not limited to parabens and salt, benzoic acid and salt, benzyl alcohol, phenethanol, phenylacetic acid, phenoxyethanol, glycerol monolaurate, chlorobutanol, sorbic acid and salt, calcium propionate, sodium propionate, dehydroactic acid and salt, sodium diacetate, lauric monoglyceride fat, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, chlorhexidine acetate, propylene glycol, carbon dioxide, nisin, natamycin, Charantin, thimerosal, one or more in Mercury pernitrate..

The addition of above-mentioned antibacterial can change in a big way, only need ensure that the surface tension of preparation compositions is in described scope above.Under preferable case, antibacterial content is 0.01-2.0wt%.

Antioxidant can also be comprised in preparation compositions provided by the invention.Described antioxidant is selected from, but is not limited to one or more in butylhydroxy anisole, dibenzylatiooluene, tert-butyl hydroquinone, propyl gallate, ascorbyl palmitate, thiodipropionic acid dilauryl cinnamic acid ester, 4-hexyl resorcin, tocopherol (vitamin E), L-AA, sodium D-isoascorbate, tea polyphenols, Herba Rosmarini Officinalis extract, Rhizoma Zingiberis Recens extract, sugar alcohols saccharide, aminoacid and dipeptide aminoacid.

The addition of above-mentioned antioxidant can change in a big way, only need ensure that the surface tension of preparation compositions is in described scope above.Under preferable case, antioxidant content is 0.001-5.0wt%.

In the present invention, when preparation compositions contains above-mentioned antibacterial, aromatic, stabilizing agent, during antioxidant, in preparation compositions, each constituent content can change in a big way, such as, for preparation compositions generally speaking, surface-active contents can be 0.1-25.0wt%, solvent can be 53.0-99.868wt%, antibacterial content can be 0.01-2.0wt%, fragrance level can be 0.01-5.0wt%, stabiliser content can be 0.01-5.0wt%, antioxidant content can be 0.001-5.0wt%, the content of described ingredient is 0.001-5.0wt%.

In above-mentioned preparation method, for surfactant, concrete adoptable material as previously mentioned, can be one or more in lecithin, sterol, Curosurf, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol.The above-mentioned various surfactant met the demands can directly be commercially available.

Above-mentioned solvent can be one or more in water, ethanol, glycerol, Medical silicone oil, edible vegetable oil.Preferred employing water, can reduce the stimulation to user.

Above-mentioned treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, one or more in the medicine of dryness in the nasal cavity disease are known in the field, such as, treatment rhinitis, the medicine of lower respiratory tract inflammation comprises, but be not limited to cortisone, hydrocortisone, beclometasone, triamcinolone acetonide, mometasone, dexamethasone, fluocinolone acetonide, budesonide, the glucocorticoidss such as fluticasone, ephedrine hydrochloride, the vasoconstrictors such as xylometazoline hydrochloride, hydrochloric acid levocabastine, the antihistaminics such as A-5610, and etc. Fructus Xanthii, dandelion, Radix Scutellariae, Fructus Lagenariae gourdae, Herba Ephedrae, Flos Magnoliae, Herba Asari, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Catechu, dragon well green tea, one or more in the Chinese medicines such as Cortex Phellodendri and extract thereof.

Similar, can also medicine containing conventional treatment external otitis, lower respiratory tract inflammation, dryness in the nasal cavity disease, xerostomia and xerophthalmia in preparation compositions in the present invention, described medicine include, but are not limited in D-panthenol, glycerol, hyaluronic acid, butanediol, Polyethylene Glycol, propylene glycol, hexanediol, xylitol, Sorbitol one or more.

According to the present invention, in described step S1, when being liquid under the surfactant base room temperature state adopted, can directly by the ultrasonic middle dispersion 1-3min of surfactant at 40-60KHZ.Now, only the surface tension of preparation compositions and zeta current potential need be made to fall into described scope above by the relative amount of adjustment solvent and surfactant.Under preferable case, in described preparation compositions, surface-active contents is 0.1-25.0wt%, and solvent is 70.0-99.899wt%, and the content of described ingredient is 0.001-5.0wt%.

When being solid-state under the surfactant base room temperature adopted, needing is first liquid by solid state surface activating agent Feedstock treating.Then by the ultrasonic middle dispersion 1-3min of the surfactant of liquid state at 40-60KHZ.

Above-mentioned is that liquid method can adopt method conventional in prior art by solid state surface activating agent Feedstock treating, such as, mixed by the material of this solid state surface activating agent raw material of solid state surface activating agent raw material and solubilized, dissolved.Understandable, for different solid active materials, the material of above-mentioned solubilized solid state surface activating agent raw material may be different, and in the present invention, those skilled in the art can know, and only need to dissolve above-mentioned solid state surface activating agent raw material.

According to the present invention, in described step S2, be preferably under the stirring condition of more than 3000rpm at rotating speed, surfactant is mixed homogeneously with solvent.Now, the drop containing surfactant that volume average particle size is less than 100 μm can be formed in a solvent.Such as can form the drop that volume average particle size is 1-100 μm.Above-mentioned drop can stable existence in a solvent, and preparation compositions entirety exists with emulsion form.For different liquid surfactants, when formation volume average particle size is the drop of 1-100 μm in a solvent, required rotating speed is different, and those skilled in the art can adjust according to practical situation.As known to those skilled in the art, along with the raising of speed of agitator and the prolongation of time, the volume average particle size of the drop that can be formed is less.

Concrete, solvent is mixed with surfactant, such as, surfactant is added in solvent.During mixing, detect surface tension and the zeta current potential of solvent/surfactant mixture, when surface tension is less than 60mN/m (or the target surface tension value preset) and the absolute value of zeta current potential is more than 15mV, stops mixing, preparation compositions disclosed by the invention can be obtained.The surface tension of preparation compositions obtains by automatic surface tension measuring device (USKino, A601) test.The zeta current potential of preparation compositions obtains by zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) test.In above-mentioned preparation method, the concrete material that surfactant and solvent adopt and its relative amount are as mentioned before.

Under preferable case, after described step S2, also comprise ultrasonication or high pressure homogenization step.Concrete, the method for above-mentioned ultrasonication or high-pressure homogenization is conventional in prior art, is not particularly limited in the present invention.

Can, by further for drop homogenize, make drop less by ultrasonication or high-pressure homogenization, forming volume average particle size be the drop of 50-500nm.Wherein, what drop can be more stable is scattered in solvent.The volume average particle size of above-mentioned drop can directly be obtained by existing various particle diameter testing equipment (such as laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain)) test.

Understandable, the drop in preparation compositions may be the drop formed by surfactant, also may be the drop jointly formed by other materials (such as ingredient) in surfactant and preparation compositions.And what obtained by the test of above-mentioned testing equipment is the volume average particle size of drop in whole preparation compositions, comprise the common drop formed of other materials (such as ingredient) in the drop and surfactant and preparation compositions formed by surfactant.

According to the present invention, the pH value by adjusting preparation compositions improves the stability of preparation compositions further within the scope of 6.0-7.4.Understandable, when preparing preparation compositions, the pH value comprising the original mixture of each material composition adopting different raw materials to obtain can be different, if when the pH value of original mixture is in above-mentioned scope, and can without the need to adjusting pH value again.If not in above-mentioned scope, under preferable case, adjust by the pH value of existing method to preparation compositions.Such as, the mode by adding buffer solution adjusts.In the present invention, alternative buffer system is citric acid-Fructus Citri Limoniae sodium buffer, Acetic acid-sodium acetate buffer, phosphate buffer, HEPES and Tris-citrate buffer solution, and preferred buffer system is HEPES and the Tris-citrate buffer solution of pH6.0-7.4.

The addition of above-mentioned various buffer solution meets above-mentioned condition to make the pH value of preparation compositions.

According to the present invention, when preparing above-mentioned preparation compositions, also can according to actual user demand, add in antibacterial, aromatic, stabilizing agent, antioxidant one or more.

The concrete material of the employing of above-mentioned antibacterial, aromatic, stabilizing agent, antioxidant as mentioned before, does not repeat them here.

The addition of above-mentioned antibacterial, aromatic, stabilizing agent, antioxidant also can be as mentioned before, the addition of such as described surfactant is 0.1-25.0wt%, the addition of solvent is 53.0-99.868wt%, the addition of antibacterial is 0.01-2.0wt%, the addition of aromatic is 0.01-5.0wt%, the addition of stabilizing agent is 0.01-5.0wt%, and the addition of antioxidant is 0.001-5.0wt%, and the content of described ingredient is 0.001-5.0wt%.

According to the present invention.When preparing preparation compositions, also add in the medicine of conventional treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease one or more, make preparation compositions have better combined therapy effect.Concrete, the concrete material that ingredient adopts as mentioned before, does not repeat them here.

Concrete, the step of adding ingredient is not particularly limited, such as, said medicine composition and surfactant etc. can be mixed together and be prepared.

The consumption of said medicine composition is no more than its conventional effective dose.

The above-mentioned various materials added for improving preparation compositions combination property may exist with various form in a solvent, comprise drops.Because the addition of above-mentioned various material belongs to trace relative to surfactant and solvent, the volume average particle size impact of various materials on drop in preparation compositions of above-mentioned interpolation is less, in the present invention, ignores on above-mentioned impact.

In concrete commercial production, after preparing preparation compositions by said method, preparation compositions is poured into jetmizer or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), sedimentation volume ratio, microbial limit after testing, outer package after meeting the requirements, to obtain final product.

Above-mentioned outer package can adopt existing conventional packaging, comprises charge cask, pump (or valve) and toucher.

Preparation compositions provided by the invention can fill in aerosol apparatus, use in the form of a spray.

Preparation compositions provided by the invention also can adopt nasal drop or ear drop to use, and the packaging of nasal drop or ear drop adopts the conventional packaging of nasal drop or ear drop, comprises charge cask, dropper.

More than packaging knows in field.

The object of this invention is to provide a kind of stable, spraying and drop-wise can be adopted to carry out preparation compositions used and preparation method thereof.Said preparation compositions has that treatment otitis media, external otitis, rhinitis, sinusitis, xerostomia, eyes are dry and astringent, the purposes of dry nasal cavity.

Preparation compositions action principle provided by the invention for providing lower surface tension in site of administration, thus plays the object of relief of symptoms.Only be described to be applied to otitis media in description of the present invention.Those skilled in the art are knowing after in the present invention, can know and adopt preparation compositions provided by the invention to other beyond otitis media because mucilage secretion is too much, cause tract to block and the disease (such as external otitis, rhinitis, sinusitis etc.) that causes is effective equally.

By the following examples the present invention is further detailed.

Embodiment 1

The present embodiment is for illustration of preparation compositions disclosed by the invention (when not yet adding ingredient) and preparation method thereof.

Take hydrogenated phospholipid 2.38g, sterol 0.12g, methyl hydroxybenzoate 0.4g, ethyl hydroxybenzoate 0.2g and Mentholum 0.1g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, and under high-speed stirred (6000rpm) state, mix homogeneously, continues to add water to final volume 100ml, mix homogeneously, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 48.851mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 2.342 μm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-28.5mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.2.

Mixed liquor is through 3750rpm after centrifugal 5 hours, and obvious sediment does not appear in bottom.

Embodiment 2

Take soybean phospholipid 2.35g, poloxamer 0.15g, vitamin E 0.08g and phenethanol 0.5g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, even in high-speed stirred (6000rpm), continues to add water to final volume 100ml, mix homogeneously, pours into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 16.252mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 5.712 μm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-25.8mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.1.

Embodiment 3

Take soybean phospholipid 3.75g and vitamin E 0.64g is positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, above-mentioned alcoholic solution is joined in the Tris-citrate buffer solution of the pH6.0-7.4 of 0.05g glycerol monolaurate and 99ml, more evenly ultrasonic in Ultrasonic Cell Disruptor.Pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 26.225mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure particle size distribution, result is volume average particle size 223nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-32.2mV.The pH value of mixed liquor through adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.5.

Through 3750rpm after centrifugal 5 hours, there is not obvious sediment in bottom.

Embodiment 4

Take soybean phospholipid 3.75g, vitamin E 0.013g, Mentholum 0.1g is positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, above-mentioned alcoholic solution is joined in 99ml water, mix homogeneously, adopt high pressure homogenizer homogenate 10min, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 28.253mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure particle size distribution, result is volume average particle size 252nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-21.2mV.The pH value of mixed liquor through adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.0.

Embodiment 5

Take soybean phospholipid 2.5g, vitamin E 0.01g, methyl hydroxybenzoate 0.4g, ethyl hydroxybenzoate 0.2g, phenethanol 0.5g and Mentholum 0.1g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, and mix homogeneously; Poloxamer 0.12g is dissolved in 5ml water, the aqueous solution containing poloxamer is mixed with above-mentioned alcoholic solution under high velocity agitation, and continue to add water to final volume 100ml, mix homogeneously, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 20.185mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 4.422 μm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-19.8mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.1.

Embodiment 6

Take soybean phospholipid 3.75g and vitamin E 0.64g, phenethanol 0.5g is positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, and under high-speed stirred (6000rpm) state, is added by above-mentioned alcoholic solution and is dissolved with in the 99ml water of poloxamer 0.15g, more evenly ultrasonic in Ultrasonic Cell Disruptor.Pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 16.425mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure particle size distribution, result is volume average particle size 275nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-17.8mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 5.9.

Embodiment 7

Take hydrogenated phospholipid 1.38g, soybean phospholipid 1.0g, sterol 0.12g, methyl hydroxybenzoate 0.4g, ethyl hydroxybenzoate 0.2g and Mentholum 0.1g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, mix homogeneously, continues to add water to final volume 100ml, mix homogeneously, adopt high pressure homogenizer homogenate 10min, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 28.518mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 356nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-35.8mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 6.2.

Embodiment 8

The present embodiment is for illustration of preparation compositions disclosed by the invention (ingredient containing treatment rhinitis, sinusitis)

And preparation method thereof.

Take soybean phospholipid 1.0g, sterol 0.12g, triamcinolone acetonide 4mg, methyl hydroxybenzoate 0.4g, ethyl hydroxybenzoate 0.2g and Mentholum 0.1g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, mix homogeneously, continues to add water to final volume 100ml, mix homogeneously, adopt high pressure homogenizer homogenate 10min, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 24.518mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 305nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-25.8mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 5.7.

Embodiment 9

The present embodiment is for illustration of preparation compositions disclosed by the invention (ingredient containing treatment otitis media) and preparation method thereof.

Take soybean phospholipid 1.0g, sterol 0.12g, methyl hydroxybenzoate 0.4g, ethyl hydroxybenzoate 0.2g and Mentholum 0.1g to be positioned in container.Add dehydrated alcohol 1ml, ultrasonic (40KHZ) dissolves, under high-speed stirred (6000rpm) state, mix homogeneously, continue to add aqueous solution containing 0.3wt% levofloxacin hydrochloride (by levofloxacin) to final volume 100ml, mix homogeneously, adopts high pressure homogenizer homogenate 10min, pour into aerosol apparatus or liquid-drop machine, sealing.The mass parameter such as appearance character, loading amount, main constituent content, often discharge rate (or often dripping amount), microbial limit after testing, outer package after meeting the requirements, to obtain final product.

The surface tension of finished product is 27.184mN/m through adopting automatic surface tension measuring device (USKino, A601) to detect its surface tension.Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 235nm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-43.9mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 5.8.

Comparative example 1

This comparative example is used for comparative illustration preparation compositions disclosed by the invention (when not yet adding ingredient) and preparation method thereof.

Take hydrogenated phospholipid 2.5g to be positioned in container.Add water to final volume 100ml, ultrasonic (40KHZ) dissolves, and under magnetic agitation state, stirs 30min.

Through the particle size distribution adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure product, result is volume average particle size 525.234 μm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-2.5mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 5.7.

Mixed liquor is through 3750rpm after centrifugal 5 hours, and obvious sediment appears in bottom.

Comparative example 2

Take soybean phospholipid 5.0g, vitamin e1 .0g, phenethanol 0.5g is positioned in container, under hand operated mixing state, add 100ml water, mix homogeneously.

Through adopting laser particle analyzer Mastersizer2000 (MalvernInstrumentsLtd, Britain) to measure particle size distribution, result is volume average particle size 785.347 μm.Through the zeta current potential adopting zeta potential measurement instrument NANOTRACWAVE (MicroTrac, the U.S.) to measure product, result is-2.2mV.Through the pH value adopting pH meter (Shanghai thunder magnetic, PHSJ3F) to measure product, result is 5.7.

Performance test

Following performance test is carried out to the above-mentioned preparation compositions (when not yet adding ingredient) prepared: 1, otitis media Function detection

Intramuscular injection ketamine 70mg/kg and subcutaneous injection pentobarbital 30mg/kg general anesthesia, adopt the hemophilus influenza Injection in Tympanic Cavity of deactivation, set up Secretory Otitis Media model.Laboratory animal is variegated Cavia porcellus, random packet, and intact animal organizes 10, and modeling success animal 30, is divided into each 10 of non-processor group, normal saline group, treatment group at random.The preparation compositions spray nose adopting embodiment 2 to prepare is used, every Cavia porcellus, and each spray nose 2.5mg, bilateral nasal cavity 5mg, sprays 2 every day, continuous 7 days.Record acoustic immitance tympanogram and auditory brainstem response (ABR) threshold value, statistical analysis adopts one factor analysis of variance.

Table 1 is group tympanum pressure (daPa) respectively

Group	Quantity	Meansigma methods	SD
				Intact animal's group	20	33.06	18.75
Animal pattern group	20	140.6	26.00
				Normal saline group	20	129.0	21.94
Treatment group	20	28.21	16.78

Table 2 is group tympanum pressure multiple comparisons LSD respectively

Group	Comparable group	Equal value difference	P value
				Treatment group	Animal pattern group	112.4*	0.000
Treatment group	Normal saline group	100.8*	0.000
				Animal pattern group	Intact animal's group	107.6*	0.000
Animal pattern group	Normal saline group	11.62	0.252

Note: * difference has statistical significance (P<0.05)

Table 3ABR threshold value (dB)

Group	Quantity	Meansigma methods	SD
				Intact animal's group	10	14.9	3.0
Animal pattern group	10	53.0	4.3
				Normal saline group	10	52.6	4.9
Treatment group	10	24.6	3.6

Table 4 each group reaction threshold value multiple comparisons LSD

Group	Comparable group	Equal value difference	P value
				Treatment group	Animal pattern group	28.4*	0.000

Treatment group	Normal saline group	28.0*	0.000
				Treatment group	Intact animal's group	9.73*	0.000
Animal pattern group	Normal saline group	0.400	0.513

Note: * difference has statistical significance (P<0.05)

Result shows, and intact animal organizes ABR threshold value for (14.9 ± 3.0) dBHL.

Animal pattern non-processor group ABR threshold value is increased to (53.0 ± 4.3) dBHL, has statistical significance with intact animal's group.

Normal saline group ABR threshold value is (52.6 ± 4.9) dBHL, compares no difference of science of statistics with animal pattern non-processor group.

After inhalation treats 7 days, treatment group ABR threshold value is down to (24.6 ± 3.6) dBHL, and with animal pattern non-processor group, normal saline group compares statistical significance.

Therefore, adopt preparation compositions provided by the invention to treat Negative middle ear pressure and the ABR threshold value that significantly can reduce secretory otitis media Cavia porcellus, the improvement conversion of these indexs had both been the rapid alleviation of previously described otitis media symptom clinically.

Based on similar principles, preparation compositions provided by the invention (when not yet adding ingredient) plays effect equally for external otitis, rhinitis and sinusitis remission.

It will be appreciated by those skilled in the art that, the preparation compositions containing ingredient, on the basis with above-mentioned effect, due to the effect of ingredient, also can have the effect for the treatment of corresponding symptom.

2, sedimentation stability detects

Each 2 of the finished product of Example 2, embodiment 4 and comparative example 2,0.5ml/ props up, through 3750rpm centrifugal 5 hours, detects sedimentation stability.By the naked eye, do not find that obvious sediment occurs in embodiment 2 and embodiment 4, in comparative example 2, find that there is obvious sediment.

In above-mentioned test, under 3750rpm is similar to normal condition for centrifugal 5 hours, preserve the effect of a year.As can be seen from embodiment 1-9, preparation compositions provided by the invention has excellent stability.Wherein, embodiment 1-7 sufficient proof is before interpolation ingredient, and system has excellent stability and improves effect of corresponding symptom; After adding ingredient, whole preparation compositions has excellent stability, and preparation compositions can be made to have good therapeutic efficiency by the effect of ingredient.

The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.

Claims

1. a preparation compositions, is characterized in that, comprises solvent, ingredient and surfactant; Described preparation compositions is emulsion, is distributed with the drop containing surfactant in described solvent; The volume average particle size of described drop is less than 100 μm;

Described ingredient comprise treatment rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, external otitis, xerostomia, xerophthalmia, dryness in the nasal cavity disease medicine in one or more;

The surface tension of described preparation compositions is less than 60mN/m, and the absolute value of the zeta current potential of described preparation compositions is more than 15mV.

2. preparation compositions according to claim 1, is characterized in that, the absolute value of the zeta current potential of described preparation compositions is more than 20mV.

3. preparation compositions according to claim 1, is characterized in that, the absolute value of the zeta current potential of described preparation compositions is more than 40mV.

4. preparation compositions according to claim 1, is characterized in that, the volume average particle size of described drop is 1-100 μm.

5. preparation compositions according to claim 1, is characterized in that, the volume average particle size of described drop is 50-500nm.

6. according to the preparation compositions in claim 1-5 described in any one, it is characterized in that, the pH value of described preparation compositions is 5.0-7.4.

7. preparation compositions according to claim 6, is characterized in that, the pH value of described preparation compositions is 6.0-7.4.

8. according to the preparation compositions in claim 1-5,7 described in any one, it is characterized in that, the surface tension of described preparation compositions is less than 40mN/m.

9. according to the preparation compositions in claim 1-5,7 described in any one, it is characterized in that, the surface tension of described preparation compositions is less than 30mN/m.

10. according to the preparation compositions in claim 1-5,7 described in any one, it is characterized in that, the surface tension of described preparation compositions is less than 27mN/m.

11., according to the preparation compositions in claim 1-5,7 described in any one, is characterized in that, described surfactant be selected from natural or synthetic surfactant one or more.

12. preparation compositions according to claim 11, it is characterized in that, described surfactant comprises that natural phospholipid, sterol, Curosurf, stearic acid, oleic acid, lauric acid, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, fatty acid Pyrusussuriensis are smooth, one or more in Polysorbate, Myrj 45, polyoxyethylene aliphatic alcohol ether, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol.

13. preparation compositions according to claim 11, it is characterized in that, described surfactant comprise in lecithin, sterol, Curosurf, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol one or more.

14. preparation compositions according to claim 12, is characterized in that, described solvent is one or more in water, ethanol, glycerol, Medical silicone oil, edible vegetable oil.

15. according to claim 1-5, 7, 12, 13, preparation compositions in 14 described in any one, is characterized in that, described ingredient cortisone, hydrocortisone, beclometasone, triamcinolone acetonide, mometasone, dexamethasone, fluocinolone acetonide, budesonide, fluticasone, ephedrine hydrochloride, xylometazoline hydrochloride, hydrochloric acid levocabastine, A-5610, Fructus Xanthii, dandelion, Radix Scutellariae, Fructus Lagenariae gourdae, Herba Ephedrae, Flos Magnoliae, Herba Asari, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Catechu, dragon well green tea, Cortex Phellodendri, ofloxacin, levofloxacin, norfloxacin, lomefloxacin, tosufloxacin, Sparfloxacin, Roxithromycin, chloromycetin, penicillin, clindamycin, nitrofural, amoxicillin, ampicillin, clavulanate potassium, cefaclor, cefixime, cefdinir, cefradine, cefalexin, Cefpodoxime Proxetil, CEFUROXIME AXETIL, cefprozil, azithromycin, minocycline, Acetylmidecamycin, acetylspiramycin, metronidazole, cortisone, triamcinolone acetonide, Moschus moschiferous is fragrant, dried Alumen, Calamina, sheet brain, dry kermes, Cacumen Platycladi, Echinacea root, counterfeit indigo root, D-panthenol, glycerol, hyaluronic acid, butanediol, Polyethylene Glycol, propylene glycol, hexanediol, xylitol, one or more in Sorbitol.

16. preparation compositions according to claim 15, is characterized in that, in described preparation compositions, surface-active contents is 0.1-25.0wt%, and solvent is 70.0-99.899wt%, and the content of described ingredient is 0.001-5.0wt%.

17., according to the preparation compositions in claim 1-5,7,12,13,14 described in any one, is characterized in that, also containing one or more in antibacterial, aromatic, stabilizing agent, antioxidant in described preparation compositions.

18. preparation compositions according to claim 17, it is characterized in that, described antibacterial comprise in parabens and salt, benzoic acid and salt, benzyl alcohol, phenethanol, phenylacetic acid, phenoxyethanol, glycerol monolaurate, chlorobutanol, sorbic acid and salt, calcium propionate, sodium propionate, dehydroactic acid and salt, sodium diacetate, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, chlorhexidine acetate, propylene glycol, carbon dioxide, nisin, natamycin, Charantin, thimerosal, Mercury pernitrate. one or more;

Described aromatic comprises Mentholum, Borneolum Syntheticum, Fructus Citri Limoniae oil, patchouli oil, Oleum Cinnamomi, red date tincture, vanillin, Oleum menthae, geranium absolute, eucalyptus oil, Oleum Menthae Rotundifoliae, eugenol, citral, concrete of jasmine, Hang Zhou chrysanthemum flower extract, osmanthus concrete, benzyl alcohol, phenethanol, terpineol, methyl cyclopentenyl ketone, jasminal, butanoic acid, caproic acid, isoamyl acetate, benzyl acetate, linalyl acetate, ethyl propionate, ethyl n-butyrate., isoamyl butyrate, benzyl butyrate, iso-amyl iso-valeriate, ethyl hexanoate, cognac oil, ethyl lactate, allyl hexanoate, nonyl lactone, ethyl maltol, allyl cyclohexyl propionate, maltol, gamma-undecalactone, raspberry ketone, benzyl propionate, butyl butyrate, ethyl isovalerate, Ethyl formate, benzyl benzoate, methylpyrazine, 2,3-dimethyl pyrazine, trimethylpyrazine, 2-acetyl group pyrazine, 4-methyl-5-(beta-hydroxyethyl) thiazole, 2-acetylthiazole, 2，3，5，6-tetramethylpyrazine, hexadecanoyl, ethyl vanillin, one or more in hydroxycitronellal,

Described stabilizing agent comprise in lecithin, poloxamer, saponarin, tannin, fatty acid glyceride, sucrose fatty acid ester, methyl glycol fatty acid ester, cholesterol, cholesteryl ester, Polyethylene Glycol, cellulose and derivant, dextrin, arabic gum, Tragacanth class, pecto-cellulose cheese, gelatin, alginic acid one or more;

Described antioxidant comprise in butylhydroxy anisole, dibenzylatiooluene, tert-butyl hydroquinone, propyl gallate, ascorbyl palmitate, thiodipropionic acid dilauryl cinnamic acid ester, 4-hexyl resorcin, tocopherol, L-AA, sodium D-isoascorbate, tea polyphenols, Herba Rosmarini Officinalis extract, Rhizoma Zingiberis Recens extract, sugar alcohols saccharide, aminoacid one or more.

19. preparation compositions according to claim 18, it is characterized in that, in described preparation compositions, surface-active contents is 0.1-25.0wt%, and solvent is 53.0-99.868wt%, and antibacterial content is 0.01-2.0wt%, fragrance level is 0.01-5.0wt%, stabiliser content is 0.01-5.0wt%, and antioxidant content is 0.001-5.0wt%, and the content of described ingredient is 0.001-5.0wt%.

The preparation method of 20. preparation compositions as claimed in claim 1, is characterized in that, comprising:

21. preparation methoies according to claim 20, is characterized in that, after described step S2, also comprise ultrasonication or high pressure homogenization step, and forming volume average particle size is in a solvent the drop of 50-500nm.

22. preparation methoies according to claim 20 or 21, it is characterized in that, the addition of described surfactant is 0.1-25.0wt%, and the addition of solvent is 70.0-99.899wt%, and the content of described ingredient is 0.001-5.0wt%.

23. preparation methoies according to claim 20 or 21, is characterized in that, also comprise and be scattered in solvent by one or more in antibacterial, aromatic, stabilizing agent, antioxidant;

The addition of described surfactant is 0.1-25.0wt%, the addition of solvent is 53.0-99.868wt%, the addition of antibacterial is 0.01-2.0wt%, the addition of aromatic is 0.01-5.0wt%, the addition of stabilizing agent is 0.01-5.0wt%, the addition of antioxidant is 0.001-5.0wt%, and the content of described ingredient is 0.001-5.0wt%.

24. preparation methoies according to claim 23, it is characterized in that, described antibacterial comprise in parabens and salt, benzoic acid and salt, benzyl alcohol, phenethanol, phenylacetic acid, phenoxyethanol, glycerol monolaurate, chlorobutanol, sorbic acid and salt, calcium propionate, sodium propionate, dehydroactic acid and salt, sodium diacetate, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, chlorhexidine acetate, propylene glycol, carbon dioxide, nisin, natamycin, Charantin, thimerosal, Mercury pernitrate. one or more;

Described antioxidant comprise in butylhydroxy anisole, dibenzylatiooluene, tert-butyl hydroquinone, propyl gallate, ascorbyl palmitate, thiodipropionic acid dilauryl cinnamic acid ester, 4-hexyl resorcin, tocopherol (vitamin E), L-AA, sodium D-isoascorbate, tea polyphenols, Herba Rosmarini Officinalis extract, Rhizoma Zingiberis Recens extract, sugar alcohols saccharide, aminoacid one or more.

25. according to the preparation method in claim 20,21,24 described in any one, it is characterized in that, described surfactant comprises that natural phospholipid, sterol, Curosurf, stearic acid, oleic acid, lauric acid, benzalkonium chloride, benzalkonium bromide, cetrimonium bromide, fatty acid Pyrusussuriensis are smooth, one or more in Polysorbate, Myrj 45, polyoxyethylene aliphatic alcohol ether, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol.

26. preparation methoies according to claim 25, it is characterized in that, described surfactant comprise in lecithin, sterol, Curosurf, poloxamer, dipalmitoyl phosphatidyl choline, cholesterol, cholesteryl ester, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl glycerol, Polyethylene Glycol one or more;

Described solvent is one or more in water, ethanol, glycerol, Medical silicone oil, edible vegetable oil;

Described ingredient comprises cortisone, hydrocortisone, beclometasone, triamcinolone acetonide, mometasone, dexamethasone, fluocinolone acetonide, budesonide, fluticasone, ephedrine hydrochloride, xylometazoline hydrochloride, hydrochloric acid levocabastine, A-5610, Fructus Xanthii, dandelion, Radix Scutellariae, Fructus Lagenariae gourdae, Herba Ephedrae, Flos Magnoliae, Herba Asari, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Catechu, dragon well green tea, Cortex Phellodendri, ofloxacin, levofloxacin, norfloxacin, lomefloxacin, tosufloxacin, Sparfloxacin, Roxithromycin, chloromycetin, penicillin, clindamycin, nitrofural, amoxicillin, ampicillin, clavulanate potassium, cefaclor, cefixime, cefdinir, cefradine, cefalexin, Cefpodoxime Proxetil, CEFUROXIME AXETIL, cefprozil, azithromycin, minocycline, Acetylmidecamycin, acetylspiramycin, metronidazole, cortisone, triamcinolone acetonide, Moschus moschiferous is fragrant, dried Alumen, Calamina, sheet brain, dry kermes, Cacumen Platycladi, Echinacea root, counterfeit indigo root, D-panthenol, glycerol, hyaluronic acid, butanediol, Polyethylene Glycol, propylene glycol, hexanediol, xylitol, one or more in Sorbitol.

In 27. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of otitis media, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of otitis media.

In 28. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of external otitis, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of external otitis.

In 29. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of rhinitis, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of rhinitis.

In 30. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of sinusitis, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of sinusitis.

In 31. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of xerostomia, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of xerostomia.

In 32. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of xerophthalmia, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of xerophthalmia.

In 33. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of dryness in the nasal cavity disease, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of dryness in the nasal cavity disease.

In 34. preparation compositions as described in claim 1-19, described ingredient is the medicine for the treatment of lower respiratory tract inflammation, and it is characterized in that, described preparation compositions is used for the treatment of the purposes of lower respiratory tract inflammation.