CN108969511A - Bromhexine and its derivative are treating and preventing the application on eye surface diseases - Google Patents
Bromhexine and its derivative are treating and preventing the application on eye surface diseases Download PDFInfo
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- CN108969511A CN108969511A CN201810764764.6A CN201810764764A CN108969511A CN 108969511 A CN108969511 A CN 108969511A CN 201810764764 A CN201810764764 A CN 201810764764A CN 108969511 A CN108969511 A CN 108969511A
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- bromhexine
- derivative
- application
- eye surface
- surface diseases
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- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 229960003870 bromhexine Drugs 0.000 title claims abstract description 29
- 201000010099 disease Diseases 0.000 title claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 15
- 208000005494 xerophthalmia Diseases 0.000 claims abstract description 14
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 210000000795 conjunctiva Anatomy 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 8
- 239000002552 dosage form Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000003292 glue Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 238000013268 sustained release Methods 0.000 claims description 5
- 239000012730 sustained-release form Substances 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007943 implant Substances 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 3
- 239000004530 micro-emulsion Substances 0.000 claims description 3
- 210000004400 mucous membrane Anatomy 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 239000006072 paste Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 230000002459 sustained effect Effects 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 210000003195 fascia Anatomy 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 101000972282 Homo sapiens Mucin-5AC Proteins 0.000 abstract description 12
- 102100022496 Mucin-5AC Human genes 0.000 abstract description 9
- 108010093825 Mucoproteins Proteins 0.000 abstract description 5
- 102000001621 Mucoproteins Human genes 0.000 abstract description 5
- 210000000981 epithelium Anatomy 0.000 abstract description 4
- 230000036541 health Effects 0.000 abstract description 4
- 206010061218 Inflammation Diseases 0.000 abstract description 3
- 230000036592 analgesia Effects 0.000 abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 239000004615 ingredient Substances 0.000 abstract description 3
- 230000003248 secreting effect Effects 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 230000000202 analgesic effect Effects 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 230000005284 excitation Effects 0.000 abstract 1
- 102000004392 Aquaporin 5 Human genes 0.000 description 5
- 108090000976 Aquaporin 5 Proteins 0.000 description 5
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 5
- 206010013774 Dry eye Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 4
- 239000003889 eye drop Substances 0.000 description 4
- 229940012356 eye drops Drugs 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- 102000010637 Aquaporins Human genes 0.000 description 3
- 108010063290 Aquaporins Proteins 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 101150071538 AQP gene Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- YUWPMEXLKGOSBF-GACAOOTBSA-N Anecortave acetate Chemical compound O=C1CC[C@]2(C)C3=CC[C@]4(C)[C@](C(=O)COC(=O)C)(O)CC[C@H]4[C@@H]3CCC2=C1 YUWPMEXLKGOSBF-GACAOOTBSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 208000013521 Visual disease Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000607 artificial tear Substances 0.000 description 1
- UCDKONUHZNTQPY-UHFFFAOYSA-N bromhexine hydrochloride Chemical compound Cl.C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N UCDKONUHZNTQPY-UHFFFAOYSA-N 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Preparation (AREA)
Abstract
Bromhexine and its derivative are treating and preventing the application on eye surface diseases, the purpose of the present invention is to provide a kind of new purposes, technical solution provided by the invention is as follows: the solution of the present invention is: providing a kind of bromhexine and its derivative is treating and preventing the application on xerophthalmia and other eye surface diseases.Beneficial effects of the present invention and excitation are, bromhexine and its derivative can stimulate conjunctival epithelium secreting liquid (water in ocular, electrolytic salt) and mucoprotein (MUC5AC) ingredient, and then safeguard and promote the balance of ocular tear microenvironment and health and achieve the purpose that treating eye surface diseases includes xerophthalmia.Furthermore, the clinical practice applied outside eye over the years proves that bromhexine and its derivative may also have the function of analgesic analgesia and anti-inflammatory, it includes xerophthalmia bring ophthalmic uncomfortable and corresponding ocular inflammation that these function poles, which can further decrease eye surface diseases, and then more improve, safeguard and promote the balance and health of ocular tear microenvironment.
Description
Technical field
The present invention relates to a kind of new applications of drug, and in particular to be bromhexine and its derivative treat and prevent it is dry
Application on eye disease and other eye surface diseases.
Background technique
Xerophthalmia can lead to ophthalmic uncomfortable, visual disorders even visual loss because of the damage to ocular.It is estimated that in the U.S.
In crowd more than 50 years old, there are about 5,000,000 men and women to suffer from xerophthalmia, the case where other countries of the world should the minimum and U.S. differ
It is very few.Expenditure related with dry eyes is about 38.4 hundred million dollars to American Medical Systems every year, whole society related with dry eyes of the U.S.
Then there are about as many as 55,400,000,000 dollars for the annual conversion of burden.In mobile phone, computer essential present age for people's lives, xerophthalmia meeting
Influence each age interval crowd with getting worse, have been identified as at present epochmaking social public health problem it
One.
Mainly include at present following several means to the treatment of dry eyes, protects ocular lubricant (including the artificial tear of mucous membrane
Liquid), Punctal plug, anti-ocular inflammation medicine and water mucoprotein stimulant.Even so, the illness of many xerophthalmia can not obtain
Adequately alleviate.The frequency put drops in one's eyes is excessively high not only to be will increase expense but also is also not easily achieved for many patients.
Currently, the most common purposes of bromhexine is as expectoration dissolving phlegm medicine, for the respiratory disease excessive with mucus
In, such as the important activity ingredient in cough syrup, bromhexine is also possible to local analgesia, anti-inflammatory effects, there is no about
It may be used as treating and preventing the application on xerophthalmia and other eye surface diseases.
Summary of the invention
The purpose of the present invention is to provide a kind of new purposes, technical solution provided by the invention is as follows:
The solution of the present invention is: providing a kind of bromhexine and its derivative and is treating and preventing xerophthalmia and other oculars
Application in disease.
The molecular structure of bromhexine is shown in as follows:
The derivative of bromhexine includes the molecule being derived from its main molecules framework, such as the chloride of bromhexine
The derivative that (Bromhexine Chloride) further includes following essential molecular structure and is generated by it:
One of its application is: the bromhexine and its derivative is as treatment xerophthalmia and the medicine of other eye surface diseases
The active constituent of object.
Above-mentioned pharmaceutical dosage form can be solution (solutions), glue (gel), dropping liquid (drop), cream (ointment),
Suspension (suspension), micro emulsion (microemulsion), nano particle (nanoparticle), liposome
(liposome), lotion (lotion) pastes (paste) or similar dosage form.It includes 0.01% to 20% (w/ using concentration range
W and/or w/v), usual range is 0.5% to 5% (w/w and/or w/v).
It two is using it: the application is degradable or can not to mix or being integrated into bromhexine and its derivative
Certain polymer (polymer) carrier of degradation reaches the mesh of permanent and/or controllable release so that certain sustained-release dosage type is made
's.The carrier of this sustained-release dosage type includes but is not limited to external pump, contact lens, Punctal plug, can be attached to ocular (cornea,
Conjunctiva) mucous membrane tablet (tablet), pill (pill, pellet), capsule (capsule), particle (particle), gypsum
Plate (plaster), joint strip (strips) or the like；It can be inserted into or be imbedded at conjunctiva, under conjunctiva, the implantation of fascia under conjunctiva
Body (inserts) or sustained release reservoir (depots) and other forms ophthalmically acceptable injection, implant (inserts) or
It is sustained reservoir (depots).The above-mentioned dosage form that can be administered through ocular, such as eyedrops, eye ointment, eye glue is a kind of, bromhexine and its
The dosage rate of derivative can be according to drug effect situation from once differing to every ten minutes once a day.It is degradable or can not when being integrated into
For when being sustained purpose, the application frequency of bromhexine and its derivative can then to be reduced, dosage rate in the polymeric carrier of degradation
Range is about from primary to even every half a year four times per day.
Polymer for making slow-released carrier need to have good biological compatible, they include but is not limited to following chemical combination
Object: more poly 2-hydroxyethyl methacrylate rouge glues (p-HEMA hydrogel), poly lactide-glycolide acid (PLGA),
Polycaprolactone (PCL), hydroxypropyl cellulose (Hydroxypropyl cellulose), NSC 24345 (AnA), gelatin
(gelatin) or collagen (collagen) etc..
The beneficial effects of the present invention are, bromhexines and its derivative can stimulate conjunctival epithelium secreting liquid in ocular
(water, electrolytic salt) and mucoprotein (MUC5AC) ingredient, so safeguard and promote ocular tear microenvironment balance and health and
Achieve the purpose that treating eye surface diseases includes xerophthalmia.In addition, the clinical practice applied outside eye over the years proves bromhexine
And its derivative may also have the function of analgesic analgesia and anti-inflammatory, it includes dry that these function poles, which can further decrease eye surface diseases,
Eye disease bring ophthalmic uncomfortable and corresponding ocular inflammation, and then more improve, safeguard and promote the flat of ocular tear microenvironment
Weighing apparatus and health.
Detailed description of the invention
Fig. 1 is the comparison diagram that bromhexine handles people's original conjunctival epithelial cell AQP5 and MUC5AC mRNA after 24 hours；
Fig. 2 is the comparison diagram of the expression of MUC5AC albumen after bromhexine handles people's original conjunctival epithelium carefully.
Specific embodiment
Embodiment 1
Healthy People fornical conjunctiva tissue is taken, (≤1mm) is shredded in PBS, clostridiopetidase A and dispersion is added after being centrifuged off PBS
Enzyme is digested, and acquisition is unicellular, and supernatant containing enzyme is removed in centrifugation, and the DMEM containing 10% fetal calf serum is utilized to carry out adherent training
It supports, takes 5 μM of bromhexine processing primary conjunctival epithelial cells of people in 37 DEG C of CO2Incubator culture 24 hours, control group was extracted respectively
The RNA of (not doing above-mentioned bromhexine processing) and bromhexine processing group cell, carries out fluorescence quantitative PCR detection aquaporin
The variation that AQP5 and mucoprotein MUC5AC are expressed in mRNA level in-site.
As a result as shown in Figure 1,5 μM of bromhexines are handled 24 hours, people primary conjunctival epithelial cell AQP5 and MUC5AC occur
Obvious up-regulation, and there is not the case where up-regulation in control group.
It is collected simultaneously the albumen of control cell Yu bromhexine processing group cell, Western blot is carried out and detects MUC5AC
The expression of albumen changes.As a result as shown in Figure 2, it will thus be seen that 5 μM of bromhexines are handled 24 hours, the primary conjunctival epithelial cell of people
Middle MUC5AC protein expression is obviously raised, and control group is raised not as good as bromhexine processing group.
There is stimulation AQP5 and MUC5AC really with the conjunctiva primary cultured cell experimental verification of people and mouse bromhexine
Mucoprotein expresses raised effect.
Conjunctiva can with secreting liquid, and secretion intensity be can be increased by stimulation, from conjunctiva source
Liquid is the important component of ocular tear.The research in applicant laboratory has a unique discovery in recent years, with osmotic pressure gradient
What it is for power is mainly to pass through aquaporin (Aquaporins, AQPs) progress through conjunctiva fluid transport, this through conjunctiva
Fluid transport to maintain ocular tear amount and normal tear osmotic pressure it is extremely important.Applicant research department current research data
Prove that the raising of AQP5 expression can drive the generation and secretion for increasing conjunctival epithelium MUC5AC mucoprotein simultaneously, and MUC5AC glues egg
White specially produced by cup cell is secreted, and epochmaking colloid mucoprotein in tear is belonged to.It therefore, can be by stimulating AQPs table
The compound reached reinforces the fluid transport through conjunctiva, safeguards the balance of ocular tear quality and quantity, while also can increase in glass cell
The production of MUC5AC mucoprotein is secreted, and becomes the good drug for the treatment of dry eyes.
Embodiment 2
A kind of eye drops, wherein the content of bromhexine is 0.35% (w/w), and the pH value of eye drops is 6.5, and osmotic pressure ratio is
1.0, osmotic pressure ratio when which refers to compared with physiological saline.
Object using above-mentioned eye drops is commonly using patients with dry eye caused by electronic product in use, every time to list
The eye drip amount of eye is dripped for 2, and one day 3-6 times.After continuous use 15 days, Schimer's test value be increased, and the disease of xerophthalmia
Shape is greatly improved.
Claims (7)
1. a kind of drug containing bromhexine and its derivative is treating and preventing the application on xerophthalmia and other eye surface diseases.
2. application according to claim 1, which is characterized in that the bromhexine and its derivative are as treatment xerophthalmia
And the active constituent of the drug of other eye surface diseases.
3. application according to claim 1, which is characterized in that the dosage form of the drug is solution, glue, dropping liquid, cream, hangs
Supernatant liquid, micro emulsion, nano particle, liposome, lotion, paste or similar dosage form.
4. application according to claim 1, which is characterized in that the concentration range of the application is 0.01% to 20%.
5. application according to claim 4, which is characterized in that the concentration range of the application is 0.5% to 5%.
6. application according to claim 1, which is characterized in that the application is by the bromhexine and its derivative
It mixes or is integrated into carrier with manufactured sustained-release dosage type.
7. application according to claim 6, which is characterized in that the carrier is external pump, contact lens, lacrimal point
Plug, or the tablet of ocular mucous membrane, pill, capsule, particle, plasterboard, joint strip can be attached to or the like, or can be inserted into or heeling-in
The implant of fascia or sustained release reservoir or the ophthalmically acceptable injections of other forms under conjunctiva, conjunctiva and under conjunctiva, implant or
It is sustained reservoir.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810764764.6A CN108969511A (en) | 2018-07-12 | 2018-07-12 | Bromhexine and its derivative are treating and preventing the application on eye surface diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810764764.6A CN108969511A (en) | 2018-07-12 | 2018-07-12 | Bromhexine and its derivative are treating and preventing the application on eye surface diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108969511A true CN108969511A (en) | 2018-12-11 |
Family
ID=64537915
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810764764.6A Pending CN108969511A (en) | 2018-07-12 | 2018-07-12 | Bromhexine and its derivative are treating and preventing the application on eye surface diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108969511A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018089797A1 (en) * | 2016-11-14 | 2018-05-17 | Mingwu Wang | Formulations for the treatment of ocular surface diseases and related methods |
-
2018
- 2018-07-12 CN CN201810764764.6A patent/CN108969511A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018089797A1 (en) * | 2016-11-14 | 2018-05-17 | Mingwu Wang | Formulations for the treatment of ocular surface diseases and related methods |
Non-Patent Citations (2)
| Title |
|---|
| 刘凤 等: "溴苄环己胺治疗干眼症的疗效评价", 《天津医药》 * |
| 张然 等: "使用盐酸溴己新片联合聚乙二醇滴眼液治疗干眼症的效果观察", 《当代医药论丛》 * |
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Application publication date: 20181211 |