CN101077347A - Multifunctional membrane used for glaucoma post-operation and preparation method thereof - Google Patents
Multifunctional membrane used for glaucoma post-operation and preparation method thereof Download PDFInfo
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- CN101077347A CN101077347A CN 200610042894 CN200610042894A CN101077347A CN 101077347 A CN101077347 A CN 101077347A CN 200610042894 CN200610042894 CN 200610042894 CN 200610042894 A CN200610042894 A CN 200610042894A CN 101077347 A CN101077347 A CN 101077347A
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- chitosan
- film
- glaucoma
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- mitomycin
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- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000012528 membrane Substances 0.000 title claims description 6
- 229920001661 Chitosan Polymers 0.000 claims abstract description 54
- 239000003814 drug Substances 0.000 claims abstract description 12
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical group C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 19
- 239000012153 distilled water Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 229930192392 Mitomycin Natural products 0.000 claims description 10
- 229960004857 mitomycin Drugs 0.000 claims description 10
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 8
- 238000006480 benzoylation reaction Methods 0.000 claims description 6
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000006242 butyrylation Effects 0.000 claims description 4
- 238000010514 butyrylation reaction Methods 0.000 claims description 4
- 239000000470 constituent Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 239000001384 succinic acid Substances 0.000 claims description 4
- 241001597008 Nomeidae Species 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000012856 packing Methods 0.000 claims description 2
- 230000001954 sterilising effect Effects 0.000 claims description 2
- 238000004659 sterilization and disinfection Methods 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 239000007943 implant Substances 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000001035 drying Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000011010 flushing procedure Methods 0.000 description 5
- 238000007654 immersion Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 244000178870 Lavandula angustifolia Species 0.000 description 4
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000001742 aqueous humor Anatomy 0.000 description 4
- 239000001102 lavandula vera Substances 0.000 description 4
- 235000018219 lavender Nutrition 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229920002101 Chitin Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000031737 Tissue Adhesions Diseases 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 238000002647 laser therapy Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000035322 succinylation Effects 0.000 description 2
- 238000010613 succinylation reaction Methods 0.000 description 2
- 230000004382 visual function Effects 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 241000238421 Arthropoda Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000007950 Ocular Hypotension Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000000607 artificial tear Substances 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000000589 cicatrix Anatomy 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to medicine technology, and is especially one kind of eye implant with slowly released active component and post-operational adhesion preventing function. The eye implant consists of chitosan derivative and medicinal active component mainly, and is prepared into film implanted into eye tissue to slowly released active component and to avoid adhesion before degradation, needing no taking out. It is used mainly after glaucoma treating operation and has high medicine bioavailability.
Description
Technical field
The present invention relates to field of medicaments, concretely, but the present invention is a kind of slow-release and prevents ophthalmic implant of tissue adhesion and preparation method thereof.
Background technology
Glaucoma is a class serious threat visual function, the diseases causing blindness of irreversibility.According to EPDML investigation, 1,000 ten thousand glaucoma patients are arranged approximately, the annual newly-increased patient who also has an appointment more than 50,000 in China's 1,300,000,000 populations.Glaucomatous treatment has three kinds of Drug therapy, laser therapy and operative treatments, and wherein operative treatment is unsatisfactory curative effect or uncontrollable glaucomatous main means after medicine and the laser therapy.The purpose of operative treatment is: set up new eye external drainage passage, reduce intraocular pressure, remove the infringement of high intraocular pressure to retinal ganglial cells and fiber thereof, preserve visual function to avoid blinding.
Glaucoma filtration surgery is a kind of very special operation, on the one hand equally needs suitable wound healing process with most of surgical operations, with the many complication that prevent that the excessive outflow of aqueous humor from causing, as the ocular hypotension shallow of anterior chamber etc.It does not wish that again the wound that filters passage excessively heals on the other hand, to keep the suitable lasting drain of aqueous humor and to guarantee the success of filtering surgery.The cicatrix that conjunctiva reaches conjunctival surface down is the main reason of filtration surgery failure, so, how to reduce postoperative scar and form, be the key that improves success rate of operation.Use the success rate that antimetabolite such as ametycin (MMC) can improve filtering surgery, but because the using method of MMC some new complication have been caused.Therefore, both at home and abroad field of ophthalmology is all attempting to research and develop a kind of cicatrization that can effectively suppress filtration surgery, and newtype drug or the biomaterial that ocular tissue is had no side effect again is in the hope of improving success rate of operation.
Chitosan is a kind of new type natural biomaterial, it is the acetyl derivative that takes off of chitin, chitin is that occurring in nature output is only second to cellulosic natural polysaccharide, the natural growing amount of chitin can reach about 10,000,000,000 tons on the annual earth, it extensively is present in the wing and shell of arthropod class, also is present in the cell wall of fungus and algae.Chitosan is the natural macromolecular material that the unique a kind of surface of nature has polyvalent cation, its, characteristics were good biology, have natural, broad spectrum antibiotic activity is (as golden staphylococcus, bacillus subtilis etc.), hemostasis, regulate body's immunity and antitumor, the cholesterol regulating metabolism, bring high blood pressure down and blood sugar lowering promotion wound healing, suppress effects such as cicatrization, simultaneously, chitosan has excellent biological compatibility, biodegradability, nontoxic, no antigen, be widely used and study in field of biology, as utilize chitosan manufacture of intraocular skin, absorbable suture, hemostatic material, antiblocking agent, pharmaceutical carrier, repair cartilaginous tissue, artificial tears etc.But chitosan is used certain side effect in human body, thereby has limited its extensive use aspect medical.
Summary of the invention
But the purpose of this invention is to provide a kind of slow-release and prevent ophthalmic implant of tissue adhesion and preparation method thereof.
The present invention selects the basic framework of natural polymer chitosan as membrane material for use, overcome the deficiency of amino and protein interaction in the chitosan molecule by derivatization, not only extended the special performance of chitosan, give simultaneously certain medicament slow release performance again, thereby had the advantage of the different analogies of other material as the adherence preventing material behind the glaucoma operation.
A kind of multifunctional membrane used for glaucoma post-operation is characterized in that it is made up of chitosan derivatives and active constituents of medicine, and the weight ratio of chitosan derivatives and active constituents of medicine is 100: 0.1-1, active component is selected from mitomycin.
The used chitosan derivatives of biomembrane is selected from acetylated chitosan sugar, Butyrylation chitosan, hexanoyl chitosan, benzoylation chitosan or succinic acid chitosan.
Acetylated chitosan sugar, Butyrylation chitosan, hexanoyl chitosan, benzoylation chitosan and succinic acid chitosan; they can be the O positions, and the N position replaces, and also can be N, the simultaneously-substituted derivant in O position; molecular weight is between 10-200 ten thousand, and substitution value is between 0.1-3.
A kind of preparation method of multifunctional membrane used for glaucoma post-operation, it is characterized in that, chitosan derivatives is made film, put into anhydride and alcoholic acid mixed solution leaves standstill, be washed with distilled water to neutrality, film is put into saturated mitomycin solution leave standstill, vacuum drying under reduced pressure, section, sterilization, packing.
Zoopery shows; Biomembrane is being implanted in early days, and showing in the tissue slice around the embedded material has massive inflammatory cells infiltrated, postoperative during the 4th week inflammatory reaction be tending towards alleviating, embedded material begins to be degraded to the fragment that differs in size; Embedded material is degraded to clastic during 12 weeks.Illustrate that this biomembrane is to eye inner tissue's avirulence infringement.Use high performance liquid chromatograph and detect the release performance of its medicine in aqueous humor, find that experimental group is apparently higher than matched group (matched group is disposable use MMC in the art), the concentration that aqueous humor concentration behind the 15min is 130.30ng/ml ± 53.94 to the 2h is 22.51 ± 12.77, and matched group only 0.25h, 0.5h can detect MMC, other times all fail to detect MMC, and this illustrates the certain sustained release performance of this medicine film tool.
Anti of the present invention and slow releasing pharmaceutical biomembrane can effectively prevent the adhesion behind the glaucoma operation, have the function of slow release MMC simultaneously, characteristics such as it is long that it was had in the eye time of staying, and the curative effect effect is obvious.
The specific embodiment
Embodiment 1:
Certain amount of chitosan is dissolved in the 1wt% acetic acid solution, filters standing and defoaming, natural sialorrhea film forming on clean glass plate then, drying is put into film the sodium hydroxide solution of 1M again, takes out behind the 12h and uses distilled water immersion 8h, use distilled water flushing more repeatedly, drying gets chitosan film.Film is put into the mixed liquid of methanol and acetic anhydride again, taken out behind the 12h and use distilled water immersion 8h, use distilled water flushing repeatedly, drying gets acetylated chitosan sugar film.Get a certain size transparent modification of chitosan film, be immersed in and contain in a certain amount of mitomycin normal saline, soak certain hour and take out, drying, lavender acetylated chitosan sugar mitomycin film.
Embodiment 2:
The chitosan film preparation is as embodiment 1.Film is put into the mixed liquid of methanol and caproic anhydride again, taken out behind the 12h and use distilled water immersion 8h, use distilled water flushing repeatedly, drying gets the hexanoyl chitosan film.Get a certain size transparent modification of chitosan film, be immersed in and contain in a certain amount of mitomycin normal saline, soak certain hour and take out, drying, lavender hexanoyl chitosan mitomycin film.
Embodiment 3:
The chitosan film preparation is as embodiment 1.Film is put into the mixed liquid of methanol and benzoyl oxide again, taken out behind the 12h and use distilled water immersion 8h, use distilled water flushing repeatedly, drying gets the benzoylation chitosan film.Get a certain size transparent modification of chitosan film, be immersed in and contain in a certain amount of mitomycin normal saline, soak certain hour and take out, drying, lavender benzoylation chitosan mitomycin film.
Embodiment 4:
The chitosan film preparation is as embodiment 1.Film is put into the mixed liquid of methanol and succinic anhydrides again, taken out behind the 12h and use distilled water immersion 8h, use distilled water flushing repeatedly, drying gets the succinylation chitosan film.Get a certain size transparent modification of chitosan film, be immersed in and contain in a certain amount of mitomycin normal saline, soak certain hour and take out, drying, lavender succinylation chitosan mitomycin film.
Claims (4)
1, a kind of multifunctional membrane used for glaucoma post-operation is characterized in that it is made up of chitosan derivatives and active constituents of medicine, and the weight ratio of chitosan derivatives and active constituents of medicine is 100: 0.1-1, active component is selected from mitomycin.
As the said film of claim 1, it is characterized in that 2, chitosan derivatives is selected from acetylated chitosan sugar, Butyrylation chitosan, hexanoyl chitosan, benzoylation chitosan or succinic acid chitosan.
3, as claim 1 or 2 said films; it is characterized in that; acetylated chitosan sugar, Butyrylation chitosan, hexanoyl chitosan, benzoylation chitosan and succinic acid chitosan; they can be the O positions; the N position replaces; also can be N, the simultaneously-substituted derivant in O position, molecular weight be between 10-200 ten thousand, and substitution value is between 0.1-3.
4, as the said preparation method of claim 1, it is characterized in that, chitosan derivatives is made film, put into anhydride and alcoholic acid mixed solution leaves standstill, be washed with distilled water to neutrality, film is put into saturated mitomycin solution leave standstill, vacuum drying under reduced pressure, section, sterilization, packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610042894 CN101077347A (en) | 2006-05-26 | 2006-05-26 | Multifunctional membrane used for glaucoma post-operation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610042894 CN101077347A (en) | 2006-05-26 | 2006-05-26 | Multifunctional membrane used for glaucoma post-operation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101077347A true CN101077347A (en) | 2007-11-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610042894 Pending CN101077347A (en) | 2006-05-26 | 2006-05-26 | Multifunctional membrane used for glaucoma post-operation and preparation method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN101077347A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018686A (en) * | 2010-12-16 | 2011-04-20 | 浙江大学医学院附属邵逸夫医院 | Mitomycin-containing film agent and preparation method thereof |
| CN102451490A (en) * | 2011-12-26 | 2012-05-16 | 江苏省人民医院 | A mitomycin C cotton sheet for preventing scar adhesion and preparation method thereof |
| CN108743566A (en) * | 2018-05-23 | 2018-11-06 | 中南大学湘雅二医院 | A kind of preparation method and application of PHBV/rosiglitazone slow-release film |
| CN110314252A (en) * | 2019-05-22 | 2019-10-11 | 嘉兴市爵拓科技有限公司 | Collagen Implant is preparing the purposes in operation for glaucoma auxiliary reconstruction |
-
2006
- 2006-05-26 CN CN 200610042894 patent/CN101077347A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018686A (en) * | 2010-12-16 | 2011-04-20 | 浙江大学医学院附属邵逸夫医院 | Mitomycin-containing film agent and preparation method thereof |
| CN102451490A (en) * | 2011-12-26 | 2012-05-16 | 江苏省人民医院 | A mitomycin C cotton sheet for preventing scar adhesion and preparation method thereof |
| CN108743566A (en) * | 2018-05-23 | 2018-11-06 | 中南大学湘雅二医院 | A kind of preparation method and application of PHBV/rosiglitazone slow-release film |
| CN108743566B (en) * | 2018-05-23 | 2021-02-02 | 中南大学湘雅二医院 | Preparation method and application of PHBV/rosiglitazone sustained-release membrane |
| CN110314252A (en) * | 2019-05-22 | 2019-10-11 | 嘉兴市爵拓科技有限公司 | Collagen Implant is preparing the purposes in operation for glaucoma auxiliary reconstruction |
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