CN109364020B - Ophthalmic preparation for preventing and treating cataract and preparation method thereof - Google Patents
Ophthalmic preparation for preventing and treating cataract and preparation method thereof Download PDFInfo
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- CN109364020B CN109364020B CN201811324475.0A CN201811324475A CN109364020B CN 109364020 B CN109364020 B CN 109364020B CN 201811324475 A CN201811324475 A CN 201811324475A CN 109364020 B CN109364020 B CN 109364020B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- 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
- A61P27/12—Ophthalmic agents for cataracts
Abstract
The invention relates to an ophthalmic preparation for preventing and treating cataract, which comprises the following components in percentage by weight: 0.1% -10% of lanoline alkane type tetracyclic triterpene compound; 0.1-10% of a substrate; 0.05% -25% of a surfactant; 0.00001 to 0.5 percent of preservative; 65% -99% of water. The ophthalmic preparation has stable quality, simple and convenient preparation process and pharmacodynamic evaluation.
Description
The invention relates to an ophthalmic preparation for preventing and treating cataract and a divisional application of an invention patent with application date of 2016/8/22 and application number of 2016106969925.
Technical Field
The invention relates to an ophthalmic preparation for preventing and treating cataract and a preparation method thereof.
Background
Can cause the metabolic disturbance of the crystalline lens, lead to the denaturation of the proteins of the crystalline lens and generate opacity, and is called cataract. Most cataracts are senile, but children are also born with the disease, and some develop cataracts after injury, inflammation or illness.
According to the incomplete statistics of the world health organization, about 1600-2100 million cataract blind people exist all over the world. Cataracts are generally slow in disease course, the highest incidence of ophthalmic diseases, the most dangerous, and easily cause damage to eyes and even blindness in case of untimely treatment or careless prevention.
The treatment of cataract includes two aspects, namely drug treatment and operation treatment. The early and middle stage cataract patients can be treated by medicines, but the possibility of complete cure is not available at present, the patients usually wait for the mature period, and the vision is recovered by removing the clouded crystalline lens by operation, but the self-adjusting ability of the lens is lost due to the structural damage of the postoperative crystalline lens, and various complications are possible, so that the search for the preventive and therapeutic medicines with definite curative effect is important.
(3 beta) -8, 24-lanostadien-3-ol, commonly known as lanosterol, is one of lanostane type tetracyclic triterpenoids, is known as lanosterol, has CAS number of 79-63-0 and has chemical name of 3 beta-Hydroxy-8, 24-Lanostadiene, and recently, it is found that the application of lanosterol-containing ophthalmic drug to dogs with cataract for 6 weeks can reduce the severity of cataract and improve the transparency of crystalline lens, which indicates that lanosterol or compounds with similar active molecules can provide another treatment means for treating cataract, but ophthalmic preparations related to lanosterol are not reported.
Disclosure of Invention
The invention aims to solve the technical problem of providing an ophthalmic preparation for effectively preventing and treating cataract and a preparation method thereof.
In order to solve the technical problems, the invention adopts the following technical scheme:
an ophthalmic preparation for preventing and treating cataract consists of 0.1 to 10 weight percent of lanoline alkane type tetracyclic triterpene compound and 90 to 99.9 weight percent of auxiliary material.
Preferably, the lanolin alkyl tetracyclic triterpene compound accounts for 0.1-5%, more preferably 0.1-2%.
Preferably, the lanoline alkane type tetracyclic triterpene compound is lanosterol.
Preferably, the auxiliary materials are one or more selected from the group consisting of surfactants, isotonic regulators, preservatives, antioxidants, matrixes, pH regulators, penetration enhancers, excipients, stabilizers, organic solvents and water.
Among them, the surfactant is also called solubilizer.
Further preferably, the surfactant is one or more of polyethylene glycol-7-stearate, diethylene glycol monoethyl ether, caprylic/capric polyethylene glycol glyceride, polyoxyl (40) stearate, polyoxyethylene (35) castor oil, polyethylene glycol 40 hydrogenated castor oil, lecithin, tween-80, ethanol, polyethylene glycol, carbomer, poloxamer and hydroxypropyl-beta-cyclodextrin.
In the present invention, the amount of the surfactant added is 0.05% to 25%, preferably 0.1% to 10%, and most preferably 0.1% to 5% of the total mass of the ophthalmic preparation.
Further preferably, the isotonic regulator is one or more selected from sodium chloride, potassium chloride, glucose, mannitol, propylene glycol, glycerol, boric acid and borax.
In the invention, the addition amount of the isotonic regulator accounts for 0.05-25%, preferably 1-15%, and most preferably 5-12% of the total mass of the ophthalmic preparation.
Further preferably, the preservative is one or a combination of more selected from triethanolamine, boric acid, borax, sodium citrate, methyl paraben, ethyl paraben, propyl paraben, ethylparaben, phenylmercuric nitrate, benzalkonium chloride solution, ethylparaben, benzalkonium chloride, benzalkonium bromide, chlorhexidine acetate, polyquaternium, chlorobutanol, phenethyl alcohol and thimerosal.
In the invention, the addition amount of the preservative accounts for 0.0001-1%, preferably 0.0001-0.1%, and most preferably 0.0001-0.02% of the total mass of the ophthalmic preparation.
Further preferably, the antioxidant is one or more of sodium thiosulfate, sodium metabisulfite, sodium bisulfite, sodium sulfite, disodium edetate, butylated hydroxyanisole, butylated hydroxytoluene, alpha-tocopherol, sodium cyclohexanediamine tetraacetate, N-hydroxyethylenediamine triacetic acid, diethyltriaminehexaacetic acid, dimercaptoethylglycine, ethylenediamine tetraacetic acid, isoascorbic acid and sodium salt thereof, and thiourea.
In the present invention, the amount of the antioxidant added is 0.0001% to 1%, preferably 0.001% to 0.1%, and most preferably 0.01% to 0.02% of the total mass of the ophthalmic preparation.
Further preferably, the matrix is one or more of yellow vaseline, white vaseline, lanolin, liquid paraffin, sodium hyaluronate, polyvinyl alcohol, carbomer, xanthan gum, chitosan, xylan, polyacrylic acid, sodium alginate, methylcellulose, hypromellose and povidone.
In the invention, the addition amount of the matrix accounts for 0.5-90%, preferably 1-85% of the total mass of the ophthalmic preparation.
Further preferably, the pH regulator is one or a combination of several selected from sodium hydroxide, hydrochloric acid, sodium acetate, sodium carbonate, sodium bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, boric acid, citric acid, and sodium citrate.
In the invention, the addition amount of the pH regulator accounts for 0-15% of the total mass of the ophthalmic preparation.
Further preferably, the penetration enhancer is one or more of lecithin, sodium hyaluronate, sodium dodecyl sulfate, N-methyl pyrrolidone, sodium deoxycholate, hydroxypropyl-cyclodextrin, laurocapram, disodium edetate, tween-80 and propylene glycol.
In the invention, the addition amount of the penetration enhancer accounts for 0-20% of the total mass of the ophthalmic preparation, preferably 0.05-20%, and most preferably 0.1-0.5%.
Preferably, the stabilizer is one or a combination of more of cholesterol, soybean phospholipid, lecithin, glyceryl monooleate, stearin, polyvinyl alcohol, polyethylene glycol, hydroxypropyl methylcellulose, polyvinylpyrrolidone and poloxamer.
In the present invention, the amount of the stabilizer added is 0% to 90%, preferably 0.05% to 10%, and most preferably 1% to 5% of the total mass of the ophthalmic preparation.
Preferably, the excipient is one or more of mannitol, dextran, lactose, galactose, chitosan, arginine, meglumine, cyclodextrin, gelatin, glucose, inositol, sucrose, trehalose, sorbitol, xylitol, albumin, peptone, soluble starch, dextrin, acacia, hydroxymethyl cellulose and syrup.
In the present invention, the amount of the excipient added is 0% to 95%, preferably 0.1% to 20%, and most preferably 1% to 10% of the total mass of the ophthalmic preparation.
Preferably, the organic solvent is one or a combination of more of chloroform, ethanol, acetone, dimethyl sulfoxide and ethyl acrylate.
Preferably, the water is water for injection.
Preferably, the ophthalmic preparation is eye drops, eye ointment, ophthalmic gel, ophthalmic freeze-dried instant tablets or ophthalmic nano-liposomes.
Preferably, the ophthalmic preparation comprises the following components in percentage by weight:
further preferably, the ophthalmic preparation comprises the following components in percentage by weight:
in the invention, when the ophthalmic preparation is eye drops, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
in the invention, when the ophthalmic preparation is an eye ointment, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
further preferably, the ophthalmic preparation comprises the following components in percentage by weight:
in the invention, when the ophthalmic preparation is ophthalmic gel, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
further preferably, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
in the invention, when the ophthalmic preparation is an ophthalmic freeze-dried instant tablet, the ophthalmic preparation comprises lanoline alkane type tetracyclic triterpenoid and an excipient, wherein the mass ratio of the lanoline type tetracyclic triterpenoid to the excipient is 1: 9-30, preferably 1: 9-20, most preferably 1: 10 to 15.
The ophthalmic preparation comprises the following components in percentage by weight:
in the invention, when the ophthalmic preparation is the ophthalmic nano liposome, the ophthalmic preparation comprises the following components in percentage by weight:
preferably, the ophthalmic preparation comprises the following components in percentage by weight:
further preferably, the ophthalmic preparation comprises the following components in percentage by weight:
the invention also aims to provide a preparation method of the ophthalmic preparation for preventing and treating cataract, which is to uniformly mix the lanoline alkane type tetracyclic triterpenoid compound and the auxiliary materials to obtain the ophthalmic preparation.
In the invention, when the ophthalmic preparation is eye drops, the preparation method comprises the following steps: mixing the lanoline alkane type tetracyclic triterpene compound and the surfactant to form a first mixture, mixing the preservative and the water to form a second mixture, stirring and dissolving the first mixture and the second mixture, and performing hot-pressing sterilization to obtain the eye drops.
Preferably, the temperature of the hot-pressing sterilization is 100-130 ℃, and the time is 20-40 min.
In the invention, when the ophthalmic preparation is eye ointment, the preparation method comprises the following steps: heating and melting the lanoline alkane type tetracyclic triterpene compound, the matrix, the isotonic regulator and part of the antioxidant to form an oil phase, heating and dissolving the surfactant, the rest of the antioxidant, the preservative and part of the water to form a mixed solution, then adding the mixed solution into the oil phase, adding the rest of the water, and uniformly mixing to obtain the eye ointment.
Preferably, the heating and melting temperature is 70-80 ℃; the heating and dissolving temperature is 70-80 ℃.
In the invention, when the ophthalmic preparation is gel, the preparation method comprises the following steps: adding the water into the matrix for wetting and swelling, then adding the preservative, stirring and dissolving to form a first mixed solution, mixing the lanoline alkane type tetracyclic triterpenoid compound and the surfactant to form a second mixed solution, then adding the second mixed solution into the first mixed solution, and uniformly mixing to obtain the gel.
In the invention, when the ophthalmic preparation is a freeze-dried instant tablet, the preparation method comprises the following steps: dissolving the excipient in the water, adding the lanoline alkane type tetracyclic triterpene compound, uniformly dispersing, and freeze-drying to obtain the freeze-dried instant tablet.
In the invention, when the ophthalmic preparation is a nano liposome, the preparation method comprises the following steps: dispersing the lanoline alkane type tetracyclic triterpenoid compound and the stabilizer in the organic solvent to form a first mixed solution, dispersing the substrate and the penetration enhancer in part of the water to form a second mixed solution, dispersing the first mixed solution in the second mixed solution to form a third mixed solution, carrying out reduced pressure rotary evaporation on the third mixed solution to obtain a nano-crystalline suspension, adding the antioxidant, the preservative and the rest of the water into the nano-crystalline suspension, and uniformly mixing to obtain the nano-liposome.
Due to the adoption of the technical scheme, compared with the prior art, the invention has the following advantages:
the ophthalmic preparation has good curative effect on the prevention and treatment of cataract, and has stable quality and simple and convenient preparation.
Drawings
FIG. 1 is a schematic illustration of the grading of the degree of lenticular opacity (Hiraoka T, 1995).
Detailed Description
The technical solution of the present invention will be further described with reference to specific examples, but the present invention should not be limited to these examples.
Examples 1 to 5, comparative example 1: the raw material formula of the lanosterol eye drops is shown in table 1, and the preparation method comprises the following steps: weighing lanosterol, adding the lanosterol into a surfactant, and stirring to fully include the lanosterol. The preservative was weighed and dissolved in water for injection. Adding the aqueous solution of the preservative into the lanosterol mixture, and stirring to dissolve. Sterilizing under hot pressure at 115 deg.C for 30 min.
TABLE 1
Examples 6 to 10, comparative example 2: the raw material formula of the lanosterol eye ointment is shown in table 2, and the preparation method comprises the following steps: weighing lanosterol, matrix, isotonic regulator and part of antioxidant, melting in water bath, and heating to 75 deg.C. The surfactant, the rest antioxidant and the preservative are weighed and dissolved in part of the water for injection and heated to 75 ℃. Slowly adding into oil phase while stirring, adding the rest water for injection, and mixing.
TABLE 2
Examples 11 to 15, comparative example 3: the raw material formula of the lanosterol gel is shown in table 3, and the preparation method comprises the following steps: adding matrix into water for injection, wetting and swelling, adding antiseptic, and stirring for dissolving. Adding lanosterol into surfactant, stirring and dissolving. Then slowly adding the lanosterol solution into the matrix solution, and stirring and mixing uniformly.
TABLE 3
Examples 16 to 20, comparative example 4: the raw material formula of the lanosterol freeze-dried instant ophthalmic tablet is shown in table 4, and the preparation method comprises the following steps: adding excipient into water for injection, stirring to dissolve, adding lanosterol, dispersing, packaging in prepared bubble cap, and freeze drying.
Another 5ml eye drop bottle was filled with buffer. When in use, the big bottle cap of the eye drop bottle is unscrewed, the tablet is pressed out by the thumb and put into the bottle, and the bottle cap is screwed and shaken.
TABLE 4
Examples 21 to 25, comparative example 5: the raw material formula of the lanosterol nanoliposome is shown in table 5, and the preparation method comprises the following steps: the lanosterol, the stabilizing agent and the organic solvent are dispersed to obtain solution 1. Swelling and dispersing the matrix and the penetration enhancer in part of water for injection to obtain a solution 2. And dispersing the solution 1 in the solution 2 by high-speed shearing or ultrasonic to obtain a solution 3. And (3) carrying out reduced pressure rotary evaporation on the solution 3 to obtain a nano-crystalline suspension as a solution 4. Adding antioxidant, antiseptic and the rest water for injection into solution 4, and mixing.
TABLE 5
Study on therapeutic effects of ophthalmic formulations of examples 1 to 25 and comparative examples 1 to 5 on cataract
SD rat, injecting 2mmol/L sodium selenite solution subcutaneously into neck and back of young rat, and the injection dosage is 25 μmol/kg.
After 4 days of molding (D5), the degree of lenticular opacity was examined under a slit lamp and photographed, and the degree of lenticular opacity was graded by Hiraoka T grading method to give a total of 7 grades, as detailed in Table 6. The slit lamp photograph is a full-eye photograph under the eye normal position diffuse light and a lateral eye position slit light (40 degrees on the right side of the slit light, and the width of the slit light is 2mm) photograph, and is shown in detail in figure 1.
TABLE 6
Before animal modeling, 8 animals are randomly selected without any treatment to serve as a normal control group, D5 animals with the lenticular opacity degree of 1-3 grades are selected from the modeled animals to be grouped, and the animals are grouped according to the lenticular opacity degree, so that the lenticular opacity degree is ensured to have no obvious difference during grouping. Model control group, experimental group of examples 1 to 25, comparative group of comparative examples 1 to 5 and positive control group, respectively, 8 of each group.
Vehicle was administered to the model control group.
The eye drops of examples 1 to 25 and comparative examples 1 to 5 were administered in the form of eye drops to the experimental group and the comparative group, respectively, at a dose of 0.015 mg/eye.
In the positive control group, 0.00225 mg/eye of Facollin was administered in eye drops.
Each administration group was administered 4 times daily for 6 weeks (D5-D47).
Dose capacity: 15 μ l/eye/time, both eyes.
General clinical observations in the study (1) all animals were observed once a day during the study period, and observed for death, morbidity, respiration, secretions, feces, diet, drinking water, etc. No abnormality was observed in all animals after 47 days.
(2) Grading the degree of lenticular opacity respectively at D5, D7, D12, D19, D26, D33, D40 and D47, measuring the diameter of the lenticular opacity plaques, and recording the size of the diameter of the lenticular opacity plaques in the eyes of each animal. The cataract counts of each group of animals are summarized in Table 7, and the mean diameters of the lenticular opacity plaques are summarized in Table 8.
TABLE 7
TABLE 8
When the physiological and biochemical changes of the drug on the cataract crystalline lens are evaluated, the selenium cataract model is the most commonly used animal model, and the characteristics, the application and the relation between the selenium cataract model and the human cataract of the model are reviewed. The lanosterol ophthalmic preparation has certain delay effect on the development of the selenium cataract of the SD rats of grade 1 and grade 2, means that the development of the cataract can be controlled, and has certain rehabilitation and treatment effect on the cataract of grade 3. The lanosterol eye drops are compared with the commercially available phacolin eye drops in pharmacodynamics, and the test result shows that the lanosterol eye drops are obviously better than the phacolin eye drops in the treatment effect of early cataract.
Claims (2)
1. An ophthalmic formulation for the prevention and treatment of cataracts, characterized by:
the ophthalmic preparation is ophthalmic gel, and the ophthalmic preparation consists of the following components: 2.5g of lanosterol, 5g of matrix carbomer, 12.5g of surfactant polyoxyethylene (35) castor oil, 0.025g of preservative benzalkonium bromide and 500mL of water for injection;
or, the ophthalmic preparation consists of the following components: 2.5g of lanosterol, 5g of matrix lanolin, 12.5g of surfactant poloxamer, 0.025g of preservative triethanolamine and 500mL of water for injection;
or, the ophthalmic preparation consists of the following components: 2.5g of lanosterol, 5g of matrix sodium alginate, 12.5g of surfactant lecithin, 0.025g of preservative chlorhexidine acetate and 500mL of water for injection;
or, the ophthalmic preparation consists of the following components: 2.5g of lanosterol, 5g of matrix povidone, 8012.5 g of surfactant tween-sodium, 0.025g of preservative sodium citrate and 500mL of water for injection;
or, the ophthalmic preparation consists of the following components: 2.5g of lanosterol, 5g of matrix chitosan, 12.5g of surfactant hydroxypropyl-beta-cyclodextrin, 0.025g of preservative methyl paraben and 500mL of water for injection.
2. A method for preparing an ophthalmic preparation for preventing and treating cataract as claimed in claim 1, characterized in that: adding the matrix into the water for injection for wetting and swelling, then adding the preservative, stirring and dissolving to form a first mixed solution, mixing the lanosterol and the surfactant to form a second mixed solution, then adding the second mixed solution into the first mixed solution, and uniformly mixing to obtain the ophthalmic preparation.
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| CN106344587A (en) * | 2016-08-24 | 2017-01-25 | 上海毕傲图生物科技有限公司 | Lanosterol compound preparation for eyes |
| EP3536698B1 (en) * | 2017-01-25 | 2021-08-04 | Guangzhou Ocusun Ophthalmic Biotechnology Co., Ltd. | Lanosterol prodrug compound and use thereof |
| CN108524448B (en) * | 2017-03-02 | 2019-10-18 | 新疆维吾尔自治区药物研究所 | A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application |
| JP7056480B2 (en) * | 2017-09-08 | 2022-04-19 | ライオン株式会社 | Ophthalmic composition and tear oil layer stabilizer |
| CN109820825A (en) * | 2017-11-23 | 2019-05-31 | 河北嘉硕生物科技有限公司 | It is a kind of for treating the pharmaceutical composition of eye disease |
| CN109985052A (en) * | 2017-12-29 | 2019-07-09 | 上海蓝木化工有限公司 | The new application of triterpene compound |
| BR112021011653A2 (en) * | 2018-12-18 | 2021-09-08 | Santen Pharmaceutical Co., Ltd. | AGENT CONTAINING URSODEOXYCHOLIC ACID FOR THE TREATMENT OR PREVENTION OF PRESBYOPIA |
| WO2020177714A1 (en) * | 2019-03-04 | 2020-09-10 | 中山大学中山眼科中心 | Composition of lanosterol prodrug compound, preparation method therefor and use thereof |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
| CN112336870B (en) * | 2020-12-03 | 2022-09-20 | 温州医科大学 | Sustained-release system with synergistic effect of various vitamins in eyes and preparation method thereof |
| CN113413415B (en) * | 2021-06-30 | 2022-09-27 | 东莞博盛生物科技有限公司 | Lanosterol eye drops and preparation method thereof |
| CN115737654A (en) * | 2021-09-03 | 2023-03-07 | 成都瑞沐生物医药科技有限公司 | Eye preparation for preventing and/or treating cataract by eye drop administration |
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| CN109364019B (en) | 2021-12-28 |
| CN109481450B (en) | 2021-07-23 |
| CN106074568B (en) | 2021-05-14 |
| CN109481450A (en) | 2019-03-19 |
| CN109481392B (en) | 2021-12-24 |
| CN109364020A (en) | 2019-02-22 |
| CN109481392A (en) | 2019-03-19 |
| CN109364019A (en) | 2019-02-22 |
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Address after: 215123 units 101 and 102, C11 building, phase I project of biomedical industrial park, No. 218 Xinghu street, Suzhou Industrial Park, China (Jiangsu) pilot Free Trade Zone, Suzhou, Jiangsu Province Patentee after: Shengshi Taike Biopharmaceutical Technology (Suzhou) Co.,Ltd. Address before: 215125 Room 101, C11 floor, bio nano Park, 218 Xinghu street, Suzhou Industrial Park, Suzhou, Jiangsu Patentee before: CGENE TECH (SUZHOU, CHINA) Co.,Ltd. |