CN112076152A - Ophthalmic composition, preparation method and application thereof - Google Patents
Ophthalmic composition, preparation method and application thereof Download PDFInfo
- Publication number
- CN112076152A CN112076152A CN202011008276.6A CN202011008276A CN112076152A CN 112076152 A CN112076152 A CN 112076152A CN 202011008276 A CN202011008276 A CN 202011008276A CN 112076152 A CN112076152 A CN 112076152A
- Authority
- CN
- China
- Prior art keywords
- solution
- ophthalmic composition
- filter membrane
- preparation
- dissolving
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000000243 solution Substances 0.000 claims abstract description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 17
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 17
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 17
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 17
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 15
- 108010020346 Polyglutamic Acid Proteins 0.000 claims abstract description 14
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims abstract description 14
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 14
- 239000004359 castor oil Substances 0.000 claims abstract description 14
- 235000019438 castor oil Nutrition 0.000 claims abstract description 14
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 14
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 14
- 239000004310 lactic acid Substances 0.000 claims abstract description 14
- 229920002643 polyglutamic acid Polymers 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 239000008215 water for injection Substances 0.000 claims abstract description 12
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims abstract description 11
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 11
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims abstract description 11
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims abstract description 11
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 11
- 230000001954 sterilising effect Effects 0.000 claims abstract description 11
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 8
- 239000012467 final product Substances 0.000 claims abstract description 6
- 238000004806 packaging method and process Methods 0.000 claims abstract description 4
- 239000012528 membrane Substances 0.000 claims description 24
- 238000001914 filtration Methods 0.000 claims description 15
- 238000001816 cooling Methods 0.000 claims description 12
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 9
- 238000001356 surgical procedure Methods 0.000 claims description 9
- 239000003708 ampul Substances 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000004033 plastic Substances 0.000 claims description 6
- 229920003023 plastic Polymers 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 5
- 239000001110 calcium chloride Substances 0.000 claims description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 5
- 239000001103 potassium chloride Substances 0.000 claims description 5
- 235000011164 potassium chloride Nutrition 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000002919 epithelial cell Anatomy 0.000 abstract description 11
- 210000004087 cornea Anatomy 0.000 abstract description 10
- 238000001704 evaporation Methods 0.000 abstract description 7
- 230000008020 evaporation Effects 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 7
- 210000000795 conjunctiva Anatomy 0.000 abstract description 6
- 239000003223 protective agent Substances 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 44
- 230000000052 comparative effect Effects 0.000 description 17
- 150000002632 lipids Chemical class 0.000 description 7
- 230000006378 damage Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 238000002695 general anesthesia Methods 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000003020 moisturizing effect Effects 0.000 description 4
- 230000002980 postoperative effect Effects 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000002390 adhesive tape Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000002834 transmittance Methods 0.000 description 3
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003885 eye ointment Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000001050 lubricating effect Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 1
- 206010011033 Corneal oedema Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 102400000368 Surface protein Human genes 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 201000009310 astigmatism Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000001719 carbohydrate derivatives Chemical class 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 201000004778 corneal edema Diseases 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 229940020947 fluorescein sodium Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
Abstract
The present invention relates to an ophthalmic composition, a process for its preparation and its use. The ophthalmic composition comprises hydroxypropyl methylcellulose or carboxymethyl cellulose, polyglutamic acid, castor oil, trehalose, lactic acid, inorganic salt and water for injection. The preparation method comprises the following steps: dissolving castor oil in water for injection to obtain a first solution; dissolving hydroxypropyl methyl cellulose or carboxymethyl cellulose in part of the first solution to obtain a second solution; dissolving polyglutamic acid, trehalose, lactic acid and inorganic salt in the rest of the first solution to obtain a third solution; pouring the third solution into the second solution and stirring uniformly to obtain a fourth solution; packaging the fourth solution in a predetermined container, and performing wet heat sterilization to obtain the final product. The ophthalmic composition is used for preparing cornea or conjunctiva protective agent. The invention can provide better protection for corneal epithelial cells and simultaneously can slow down the evaporation of water in the preparation by simulating the main components of the three-layer structure in the natural tear film.
Description
Technical Field
The invention relates to an ophthalmic composition, a preparation method of the ophthalmic composition and a specific application of the ophthalmic composition, belonging to the field of biomedical materials.
Background
As far as the applicant is aware, in general anesthesia surgery, the patient cannot control his body due to the muscle relaxation, which may lead to an unintended opening of the eyes. The tear film is evaporated after the eyes are opened for a long time, the transient action of the patient cannot be automatically completed in the process, and if the patient is not protected, the cornea and the conjunctiva are damaged due to water evaporation, and the conditions of pain, astigmatism, corneal hyperplasia, keratitis and the like appear after the operation. Aiming at general anesthesia operation patients, a common method for clinically protecting eyes is to coat aureomycin eye ointment on the eyes and then attach medical paper adhesive tapes to upper and lower eyelids, so that the eyes of the patients are closed in the whole operation process. In recent years, novel hydrogel patches have been used clinically to maintain the moist state of the eye and prevent general anesthesia patients from drying during the surgery. The hydrogel eye patch generally comprises non-woven fabrics, hydrophilic polymer materials and purified water, and some of the hydrogel eye patches are supplemented with some of visible small molecule extracts. However, although the above method can achieve certain effects, it also has obvious disadvantages: the eye ointment has high viscosity and is not easy to be removed cleanly after the operation, and the eyes of a patient have sticky feeling; medical paper adhesive tapes are stuck to eyelids for a long time, and certain damage can be caused to the eyelids when the medical paper adhesive tapes are removed; in addition, the eye patch is in a non-flowable state, water molecules are firmly locked in the gel network, effective water supplement on the ocular surface cannot be carried out, the eye patch cannot be completely attached to the ocular surface of a patient due to fixed shape, and gaps are left to cause evaporation of water. Thus, the development of a low surface tension liquid protectant that acts directly on the ocular surface would be more beneficial in maintaining the microenvironment wettability and provide better protection to the cornea and conjunctiva.
For eye surgery, the patient needs to open his eyes all the time, and protection of the cornea and conjunctiva is also essential. The ophthalmology lavage liquid is commonly used for washing the ocular surface in the operation to maintain the moist state, but frequent washing can interrupt the damage of doctors, and is easy to cause corneal edema and corneal epithelium damage, and a plurality of patients can feel pain in the postoperative eyes. In the case of eye surgery, it is necessary to provide the surgeon with a clear surgical field while protecting the ocular surface, in which case the liquid protectant itself needs to be transparent and have a refractive index close to that of the human eye in addition to maintaining the ocular surface in a wet state for a long period of time.
The patent No. CN201280011250.4 and the invention patent No. CN103547257B disclose a viscoelastic liquid capable of enlarging lens and pupil, and can enlarge the operation visual field while protecting the cornea of the patient from being damaged by dryness; however, the formula only contains the polymer, inorganic salt, lactic acid and water for injection, and the formula still inevitably gradually evaporates on the ocular surface, so that the liquid viscosity is gradually increased to be unfavorable for postoperative removal, and even further damage is caused when the ocular surface is dried into a film.
The invention patent application of application No. CN201680003726.8, application publication No. CN106999424A discloses an improved intra-operative corneal protective preparation allegedly forming a protective layer on the corneal surface and having an optical amplification effect, compared to the above patent CN103547257B, the formulation of which is added with xanthan gum and carrageenan, the inventors allegedly that the applied formulation is maintained on the corneal surface for a longer time and the properties between product batches are more stable.
Patent No. CN201610184155.4, patent publication No. CN105749360B discloses another formulation of a cornea-protecting composition, which is composed of a solid moisturizing and lubricating component, a liquid moisturizing and lubricating component, inorganic salt and water; compared with the patent CN103547257B, the formula of the medicine contains more liquid moisturizing components such as polyethylene glycol, propylene glycol and the like, and in some embodiments, the medicine also contains medicines, and the file highlights that the medicine has stable component properties, and the number of bacterial colonies, the number of fine particles and the content of endotoxin are lower, so that the medicine is easy to meet the surgical requirements.
Patent No. CN201410296205.9, patent publication No. CN104083396B, discloses a cornea protective preparation consisting of drugs (tobramycin and/or dexamethasone), inorganic salts, sodium hyaluronate (or chondroitin sulfate, or chitosan), but the document does not mention a terminal sterilization mode.
The invention patent application No. CN201710858456.5, application publication No. CN107812243A discloses a corneal protective viscoelastic fluid, the formulation of which is similar to the above patent CN103547257B, except that chondroitin sulfate is introduced in some embodiments.
As represented by the above technical schemes, although there are many compositions for protecting the ocular surface, they are mainly water-soluble substances and lack proteins and lipids. Human tears are evenly distributed on the ocular surface to form a tear film, which is divided into a mucin layer, an aqueous layer and a lipid layer from inside to outside. The invention for protecting the cornea only contains hydrophilic substances, only imitates the aqueous layer of the natural tear film, is lack of protein and lipid, and has great space for improving both the protection of ocular surface cells and the maintenance of the stability of tears.
In addition, the inventors have found that the invention patent of application No. cn200480006830.x, publication No. 1761450B discloses a skin external preparation containing a saccharide derivative of α, α -trehalose, and although eye mucosa irritation test data is briefly mentioned therein, it is completely silent about the contents relating to corneal protection, and does not provide help or teaching for studies on corneal protection.
Disclosure of Invention
The invention aims to: aiming at the problems in the prior art, the ophthalmic composition is provided, and the tear is simulated to protect the ocular surface part of a patient in operation. In addition, a preparation method of the ophthalmic composition and a specific application of the ophthalmic composition are also provided.
The technical scheme for solving the technical problems of the invention is as follows:
an ophthalmic composition, characterized by comprising hydroxypropylmethyl cellulose or carboxymethyl cellulose, polyglutamic acid, castor oil, trehalose, lactic acid, inorganic salts, and water for injection.
The ophthalmic composition can remarkably prolong the single protection time and improve the survival rate of corneal epithelial cells and conjunctival epithelial cells by simulating the main components (protein analogues and lipid analogues) of the three-layer structure in the natural tear film.
The technical scheme of the invention is further perfected as follows:
preferably, the mass concentration of the hydroxypropyl methyl cellulose or the carboxymethyl cellulose is 0.1-2%, the mass concentration of the polyglutamic acid is 0.05-1%, the mass concentration of the castor oil is 0.01-0.1%, and the mass concentration of the trehalose is 2-10%.
More preferably, the mass concentration of the lactic acid is 0.1 to 0.3%, and the total mass concentration of the inorganic salts is 0.8 to 1.0%.
More preferably, the inorganic salt comprises sodium chloride, potassium chloride, calcium chloride.
More preferably, the ophthalmic composition has a pH of 6.5 to 7.6.
More preferably, the ocular composition has an osmolality of 265 to 330 mOsm/kg.
By adopting the preferable scheme, the specific details such as the dosage of each component, the pH value, the osmotic pressure and the like can be further optimized.
Preferably, the ophthalmic composition is a liquid corneal or conjunctival protectant for surgery.
In the ophthalmic composition of the present invention, the hydroxypropylmethyl cellulose or carboxymethyl cellulose acts as a physical barrier to prevent evaporation of ocular surface moisture; polyglutamic acid is a natural polypeptide, acts as mucin in the tear film, contacts with corneal epithelial cells or conjunctiva, has the functions of moisturizing and promoting epithelial cell proliferation, and is beneficial to the protection and repair of the corneal epithelial cells; the castor oil plays a role of lipid in a tear film, so that the stability of the ophthalmic composition is improved when the ophthalmic composition is used on the surface of eyes, the water evaporation is prevented, and the protection time is obviously prolonged; the trehalose can strongly bind water molecules, can form a unique protective film on the cell surface, replaces the function of cell membrane bound water, prevents the denaturation of membrane surface protein, and provides better protective performance for ocular surface tissues. In addition, lactic acid plays a role in adjusting pH, and inorganic salts play a role in adjusting osmotic pressure.
The present invention also provides:
a process for the preparation of an ophthalmic composition, characterized in that an ophthalmic composition as described above is used; the preparation method comprises the following steps:
firstly, dissolving a prescription amount of castor oil in a prescription amount of water for injection, and filtering the solution by a filter membrane to obtain a first solution; dividing the first solution into a first portion and a second portion;
secondly, adding hydroxypropyl methyl cellulose or carboxymethyl cellulose in a prescription amount into the first solution of the first part, heating, stirring, dissolving, cooling, and filtering by a filter membrane to obtain a second solution;
thirdly, dissolving the polyglutamic acid, the trehalose, the lactic acid and the inorganic salt in the formula amount into the first solution of the second part, uniformly stirring, and filtering by a filter membrane to obtain a third solution;
step four, pouring the third solution into the second solution and stirring uniformly to obtain a fourth solution; packaging the fourth solution in a predetermined container, and performing moist heat sterilization to obtain the final product of the ophthalmic composition.
The preparation method can effectively and smoothly prepare the target eye composition finished product, and the finished product can be directly applied to the cornea protection scene in the operation.
The technical scheme of the invention is further perfected as follows:
preferably, in the first step, a 0.22 μm filter membrane is adopted and the filtration process is carried out under a hundred-level laminar flow hood, and the volume ratio of the first part to the second part of the first solution is (1-5): 1; in the second step, the heating temperature is 70-80 ℃, ice bath cooling is adopted during cooling, and then the temperature is returned to the room temperature, wherein the room temperature refers to 25 +/-10 ℃, and a filter membrane of 8 mu m is adopted; in the third step, a filter membrane with the diameter of 8 mu m is adopted; in the fourth step, the temperature of the damp-heat sterilization is at least 121 ℃, the time is at least 20 minutes, and the predetermined container is a plastic ampoule bottle.
By adopting the preferred scheme, the specific process parameters of each step can be further optimized.
The present invention also provides:
use of the ophthalmic composition as described hereinbefore for the preparation of a corneal or conjunctival protectant.
The eye composition can be used as a cornea or conjunctiva protective agent and the like, can be used for protecting the ocular surface of general anesthesia patients and eye surgery patients, and can prevent postoperative injury, postoperative pain, corneal curvature change and other complications caused by dehydration and roughness of corneal and conjunctival tissues in the surgical process.
Compared with the prior art, the ophthalmic composition can provide better protection for corneal epithelial cells by simulating main components (protein analogues and lipid analogues) of a three-layer structure in a natural tear film, can slow down evaporation of water in a preparation, obviously prolongs single protection time, and improves survival rates of corneal epithelial cells and conjunctival epithelial cells.
Drawings
FIG. 1 is a graph showing the results of light transmittance in example 1 of the present invention.
FIG. 2 is a graph showing the results of the damage rate in example 2 of the present invention.
Detailed Description
The invention is described in further detail below with reference to embodiments and with reference to the drawings. The invention is not limited to the examples given.
Example 1
This embodiment is a method of preparing an ophthalmic composition comprising:
firstly, dissolving a prescription amount of castor oil in a prescription amount of water for injection, and filtering the solution by a filter membrane to obtain a first solution; the first solution is divided into a first portion and a second portion. Wherein, a 0.22 mu m filter membrane is adopted and the process of filtering by the filter membrane is carried out under a hundred-level laminar flow hood, and the volume ratio of the first part to the second part of the first solution is (1-5): 1.
And step two, adding hydroxypropyl methyl cellulose or carboxymethyl cellulose in the prescribed amount into the first solution of the first part, heating, stirring, dissolving, cooling, and filtering by a filter membrane to obtain a second solution. Wherein the heating temperature is 70-80 ℃, the ice bath is adopted for cooling during cooling, then the temperature is returned to the room temperature, the room temperature refers to 25 +/-10 ℃, and a filter membrane with the thickness of 8 mu m is adopted.
And step three, dissolving the formula amount of polyglutamic acid, trehalose, lactic acid and inorganic salt in the second part of the first solution, uniformly stirring, and filtering by a filter membrane to obtain a third solution. Wherein, 8 μm filter membrane was used.
Step four, pouring the third solution into the second solution and stirring uniformly to obtain a fourth solution; packaging the fourth solution in a predetermined container, and performing moist heat sterilization to obtain the final product of the ophthalmic composition. Wherein the temperature of the moist heat sterilization is at least 121 ℃, the time is at least 20 minutes, and the predetermined container is a plastic ampoule bottle.
In practice, the above operations are carried out in a GMP plant of ten thousand grades, and the equipment and instruments used are sterilized in advance.
In the finished product of the ophthalmic composition, the mass concentration of hydroxypropyl methylcellulose or carboxymethyl cellulose is 0.1-2%, the mass concentration of polyglutamic acid is 0.05-1%, the mass concentration of castor oil is 0.01-0.1%, the mass concentration of trehalose is 2-10%, the mass concentration of lactic acid is 0.1-0.3%, and the total mass concentration of inorganic salts is 0.8-1.0%. Wherein the inorganic salt comprises sodium chloride, potassium chloride, and calcium chloride.
The pH value of the ophthalmic composition is controlled to be 6.5-7.6, and the osmotic pressure is controlled to be 265-330 mOsm/kg.
The present embodiment contains a plurality of examples, and specific parameters of each example are shown in the following table:
for example: example 1 the specific preparation procedure for the finished product was:
the following operations were carried out in a GMP plant of a commercial scale, the equipment and instruments used having been sterilized in advance.
0.03g of castor oil was dissolved in 100mL of water for injection and passed through a 0.22 μm filter under a hundred-stage laminar flow hood to give solution A.
Taking 1.5g of hydroxypropyl methylcellulose, adding the hydroxypropyl methylcellulose into 80mL of solution A at 70-80 ℃, stirring and dissolving, transferring the solution A into an ice bath for cooling after 30 minutes, and filtering the solution A by using a filter membrane of 8 mu m after the solution A is returned to room temperature to remove insoluble impurities to obtain solution B.
0.5g of polyglutamic acid, 5g of trehalose, 0.24g of lactic acid, 0.5g of sodium chloride, 0.2g of potassium chloride and 0.13g of calcium chloride were dissolved in 20mL of the solution A, and the mixture was stirred uniformly, filtered through a 8 μm filter to remove insoluble impurities, thereby obtaining a solution C.
The solution C was poured into the solution B and stirred for 24 hours to obtain a solution D. And filling the solution D into a plastic ampoule bottle, and sterilizing at 121 ℃ for 20 minutes to obtain a final product.
The spectral transmittance of the finished ophthalmic composition of example 1 at 300-1100nm was measured by UV-visible spectrophotometry, and the results are shown in FIG. 1, which indicates that the finished ophthalmic composition has good transmittance.
The finished ophthalmic compositions of the other examples exhibited the same characteristics as those of example 1 when tested as described above.
Example 2
This example is an in vitro corneal protection effect experiment.
The test was carried out using 3 products, of which the 1 st product was a commercial ophthalmic perfusate (alkon, bi shi), the 2 nd product was the product of example 1, and the 3 rd product was the product of comparative example 1.
The specific procedure for the preparation of the product of comparative example 1 is as follows:
the following operations were carried out in a GMP plant of a commercial scale, the equipment and instruments used having been sterilized in advance.
Taking 1.5g of hydroxypropyl methylcellulose, adding 80mL of water for injection at 70-80 ℃, stirring and dissolving, transferring into an ice bath for cooling after 30 minutes, filtering by using a filter membrane of 8 mu m after returning to room temperature, and removing insoluble impurities to obtain a solution B.
0.24g of lactic acid, 0.5g of sodium chloride, 0.2g of potassium chloride and 0.13g of calcium chloride were dissolved in 20mL of water for injection, and the mixture was stirred uniformly and filtered through a 8 μm filter to remove insoluble impurities, thereby obtaining a solution C.
The solution C was poured into the solution B and stirred for 24 hours to obtain a solution D. And filling the solution D into a plastic ampoule bottle, and sterilizing at 121 ℃ for 20 minutes to obtain a final product.
The specific experimental procedure of this example is as follows:
in vitro corneal protection models were constructed with isolated rabbit eyes, and 3 groups were set. Group 1 isolated rabbit eyes were treated with product 1 (commercially available ophthalmic perfusate (alokang, applied) at a frequency of every 3 min/time) to keep the ocular surface moist; group 2 isolated rabbit eyes were coated with the product of example 1, keeping the ocular surface moist; group 3 isolated rabbit eyes were coated with the product of comparative example 1 to keep the ocular surface moist. After 1 hour, the cornea was removed, stained with 1% fluorescein sodium dropwise, and the rate of corneal epithelial cell damage per unit area was counted by a microscope.
The results are shown in FIG. 2 and indicate that the product of example 1 maintained moist corneal epithelial cell damage at a minimum. Therefore, the protective effect of the corneal epithelial cells can be further improved after the polyglutamic acid, the castor oil and the trehalose are added into the hydroxypropyl methylcellulose solution.
The finished ophthalmic compositions of the other examples of example 1 exhibited the same characteristics as those of example 1 when tested as described above.
Example 3
This example is a water loss experiment.
The test was performed using 3 products, wherein the 1 st product was the example 1 product of example 1, the 2 nd product was the comparative example 1 product, and the 3 rd product was the comparative example 2 product.
The specific procedure for the preparation of the product of comparative example 1 is described in example 2.
The specific procedure for the preparation of the product of comparative example 2 was as follows:
the following operations were carried out in a GMP plant of a commercial scale, the equipment and instruments used having been sterilized in advance.
Taking 1.5g of hydroxypropyl methylcellulose, adding 100mL of water for injection at 70-80 ℃, stirring and dissolving, and transferring into an ice bath for cooling after 30 minutes. And (3) after the temperature is restored to the room temperature, filtering the solution by using a filter membrane of 8 mu m to remove insoluble impurities, filling the filtered solution into a plastic ampoule bottle, and sterilizing the ampoule bottle at the temperature of 121 ℃ for 20 minutes to obtain the finished product.
The specific experimental procedure of this example is as follows:
3 products (mass m1) were weighed accurately and plated on slides (slide mass pre-weight record m 2). The mixture was left at 25. + -. 1 ℃ and 60. + -. 5% humidity for 30 minutes. The total weight of the slide and the product thereon was then measured (denoted m 3). The water loss rate of the product is (m1+ m2-m3)/m1) 100%, and the detailed results are shown as follows:
| product name | Product Mass/m 1 | Slide mass/m 2 | Total weight/m 3 after 30 minutes after standing | Water loss rate/%) |
| Example 1 product | 1.00 | 3.21 | 4.14 | 7％ |
| Example 1 product | 1.00 | 3.31 | 4.22 | 9％ |
| Example 1 product | 1.00 | 3.15 | 4.09 | 6％ |
| Example 1 product | 1.00 | 3.43 | 4.36 | 7％ |
| Comparative example 1 product | 1.00 | 3.28 | 4.07 | 21％ |
| Comparative example 1 product | 1.00 | 3.19 | 4.03 | 16％ |
| Comparative example 1 product | 1.00 | 3.37 | 4.14 | 23％ |
| Comparative example 1 product | 1.00 | 3.25 | 4.03 | 22％ |
| Comparative example 2 product | 1.00 | 3.36 | 4.14 | 22％ |
| Comparative example 2 product | 1.00 | 3.19 | 3.92 | 27％ |
| Comparative example 2 product | 1.00 | 3.45 | 4.23 | 22％ |
| Comparative example 2 product | 1.00 | 3.38 | 4.18 | 20％ |
From the above results, it is understood that the water loss of the product of example 1 is 7. + -. 1%, that of comparative example 1 is 21. + -. 3%, and that of comparative example 2 is 23. + -. 3%.
Therefore, the protein and lipid components in natural tears can be well simulated after the polyglutamic acid, the castor oil and the trehalose are added into the hydroxypropyl methyl cellulose solution, so that the evaporation of water in the natural tears is reduced, and better protection is provided for the eye surface.
The finished ophthalmic compositions of the other examples of example 1 exhibited the same characteristics as those of example 1 when tested as described above.
According to the embodiments of the present invention, the ophthalmic composition of the present invention can be applied to the range including corneal or conjunctival protective agents, etc., and can be used for protecting the ocular surface of general anesthesia patients and patients with eye surgery, and preventing postoperative injury, postoperative pain, corneal curvature change, etc. complications caused by dehydration, dryness and roughness of corneal and conjunctival tissues during the surgery.
In addition to the above embodiments, the present invention may have other embodiments. All technical solutions formed by adopting equivalent substitutions or equivalent transformations fall within the protection scope of the claims of the present invention.
Claims (10)
1. An ophthalmic composition, characterized by comprising hydroxypropylmethyl cellulose or carboxymethyl cellulose, polyglutamic acid, castor oil, trehalose, lactic acid, inorganic salts, and water for injection.
2. The ophthalmic composition according to claim 1, wherein the mass concentration of hydroxypropyl methylcellulose or carboxymethyl cellulose is 0.1-2%, the mass concentration of polyglutamic acid is 0.05-1%, the mass concentration of castor oil is 0.01-0.1%, and the mass concentration of trehalose is 2-10%.
3. The ophthalmic composition according to claim 2, wherein the lactic acid is contained in an amount of 0.1 to 0.3% by mass, and the inorganic salt is contained in an amount of 0.8 to 1.0% by mass in total.
4. The ophthalmic composition of claim 2, wherein the inorganic salt comprises sodium chloride, potassium chloride, calcium chloride.
5. The ophthalmic composition of claim 3, wherein the ophthalmic composition has a pH of 6.5 to 7.6.
6. The ophthalmic composition of claim 3, wherein the ophthalmic composition has an osmolality of 265 to 330 mOsm/kg.
7. An ophthalmic composition according to any one of claims 1 to 6, wherein the ophthalmic composition is a liquid corneal or conjunctival protectant for surgery.
8. A method for producing an ophthalmic composition, characterized by using the ophthalmic composition according to any one of claims 1 to 7; the preparation method comprises the following steps:
firstly, dissolving a prescription amount of castor oil in a prescription amount of water for injection, and filtering the solution by a filter membrane to obtain a first solution; dividing the first solution into a first portion and a second portion;
secondly, adding hydroxypropyl methyl cellulose or carboxymethyl cellulose in a prescription amount into the first solution of the first part, heating, stirring, dissolving, cooling, and filtering by a filter membrane to obtain a second solution;
thirdly, dissolving the polyglutamic acid, the trehalose, the lactic acid and the inorganic salt in the formula amount into the first solution of the second part, uniformly stirring, and filtering by a filter membrane to obtain a third solution;
step four, pouring the third solution into the second solution and stirring uniformly to obtain a fourth solution; packaging the fourth solution in a predetermined container, and performing moist heat sterilization to obtain the final product of the ophthalmic composition.
9. The method for preparing the ophthalmic composition as claimed in claim 8, wherein the first step is performed under a hundred-stage laminar flow hood by using a 0.22 μm filter membrane and filtering the solution with the filter membrane, and the volume ratio of the first part to the second part of the first solution is (1-5): 1; in the second step, the heating temperature is 70-80 ℃, ice bath cooling is adopted during cooling, and then the temperature is returned to the room temperature, wherein the room temperature refers to 25 +/-10 ℃, and a filter membrane of 8 mu m is adopted; in the third step, a filter membrane with the diameter of 8 mu m is adopted; in the fourth step, the temperature of the damp-heat sterilization is at least 121 ℃, the time is at least 20 minutes, and the predetermined container is a plastic ampoule bottle.
10. Use of the ophthalmic composition of any one of claims 1 to 7 for the preparation of a corneal or conjunctival protectant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011008276.6A CN112076152A (en) | 2020-09-23 | 2020-09-23 | Ophthalmic composition, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011008276.6A CN112076152A (en) | 2020-09-23 | 2020-09-23 | Ophthalmic composition, preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112076152A true CN112076152A (en) | 2020-12-15 |
Family
ID=73738582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011008276.6A Pending CN112076152A (en) | 2020-09-23 | 2020-09-23 | Ophthalmic composition, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112076152A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1373655A (en) * | 1999-07-20 | 2002-10-09 | 玫琳凯有限公司 | Treatment and composition for achieving skin anti-aging benefits by corneum protease activation |
| CN101181279A (en) * | 2007-10-16 | 2008-05-21 | 黑龙江海昌生物技术有限公司 | Arificial tears containing trehalose as well as preparation and application method thereof |
| CN101691478A (en) * | 2009-09-25 | 2010-04-07 | 海昌隐形眼镜有限公司 | Corneal contact lens nursing composition containing mycose and preparation method thereof |
| CN105749360A (en) * | 2016-03-28 | 2016-07-13 | 山东赛克赛斯药业科技有限公司 | Cornea protecting composition as well as preparation method and application thereof |
| CN106963770A (en) * | 2017-03-31 | 2017-07-21 | 牡丹江医学院 | It is a kind of to be used to prevent and treat eye drops of drying property angle/conjunctivitis and its production and use |
| CN109432393A (en) * | 2018-12-12 | 2019-03-08 | 广州无添加主义化妆品有限公司 | A kind of eye-care is spraying and preparation method thereof |
| CN110755465A (en) * | 2019-11-04 | 2020-02-07 | 海昌隐形眼镜有限公司 | Eye care solution and preparation method and application thereof |
-
2020
- 2020-09-23 CN CN202011008276.6A patent/CN112076152A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1373655A (en) * | 1999-07-20 | 2002-10-09 | 玫琳凯有限公司 | Treatment and composition for achieving skin anti-aging benefits by corneum protease activation |
| CN101181279A (en) * | 2007-10-16 | 2008-05-21 | 黑龙江海昌生物技术有限公司 | Arificial tears containing trehalose as well as preparation and application method thereof |
| CN101691478A (en) * | 2009-09-25 | 2010-04-07 | 海昌隐形眼镜有限公司 | Corneal contact lens nursing composition containing mycose and preparation method thereof |
| CN105749360A (en) * | 2016-03-28 | 2016-07-13 | 山东赛克赛斯药业科技有限公司 | Cornea protecting composition as well as preparation method and application thereof |
| CN106963770A (en) * | 2017-03-31 | 2017-07-21 | 牡丹江医学院 | It is a kind of to be used to prevent and treat eye drops of drying property angle/conjunctivitis and its production and use |
| CN109432393A (en) * | 2018-12-12 | 2019-03-08 | 广州无添加主义化妆品有限公司 | A kind of eye-care is spraying and preparation method thereof |
| CN110755465A (en) * | 2019-11-04 | 2020-02-07 | 海昌隐形眼镜有限公司 | Eye care solution and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105833344B (en) | A kind of injection aquagel is preparing the application in Ocular tamponades | |
| EP0138572A2 (en) | Hyaluronic acid fractions having pharmaceutical activity, methods for preparation thereof, and pharmaceutical compositions containing the same | |
| Noreen et al. | Terminalia arjuna gum/alginate in situ gel system with prolonged retention time for ophthalmic drug delivery | |
| US11878030B2 (en) | Ophthalmic formulations comprising cooperative complexes of low- and high-molecular-weight hyaluronic acid | |
| JPH0121133B2 (en) | ||
| BR122019023144B1 (en) | topical ophthalmic compositions for treating dry eye and their uses | |
| USRE42243E1 (en) | Synthetic viscoelastic material for ophthalmic applications | |
| US20230321145A1 (en) | Compositions and methods of treating dry eye syndrome and other traumatized non-keratinized epithelial surfaces | |
| CN110090294A (en) | Ophthalmic composition with improved dry-run protection and reservation | |
| CN108158983B (en) | A kind of sodium hyaluronate eye drops and preparation method thereof | |
| KR20160060227A (en) | Composition for preventing or treating eye disease | |
| CN101972224A (en) | Eye in-situ gel | |
| CN112076152A (en) | Ophthalmic composition, preparation method and application thereof | |
| EP1455750A1 (en) | Viscoelastic ophthalmic compositions comprising hyaluronic acid and chondroitin sulphate | |
| US20050215516A1 (en) | New free-radical scavenger containing viscoelastic composition, methods of use and package | |
| CN105749360B (en) | A kind of composition and the preparation method and application thereof for protecting cornea | |
| CN108578789A (en) | Ophthalmology viscoelastic agent | |
| CN108066282B (en) | A kind of Levofloxacin Eye drop and preparation method thereof | |
| Sharma et al. | Ocular Bioadhesive Drug Delivery Systems and Their Applications | |
| RU2286170C1 (en) | Ophthalmic film | |
| US20230201112A1 (en) | Dissolvable medical device and kit for corneal surface protection | |
| CN103142463B (en) | Medical composite for eye, its preparation method and application | |
| WO2019223748A1 (en) | Viscoelastic agent material | |
| Mundada | Update on Polymers for Ocular Drug Delivery | |
| CN104971344B (en) | Recombination human basic fibroblast growth factor instant gel preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210930 Address after: 215000 landlords of No.52 venture capital industrial square, loufengbei District, Suzhou Industrial Park, Jiangsu Province Applicant after: JIANGSU REGROWN MEDICAL TECHNOLOGY Co.,Ltd. Address before: 215122 East Building, No.52 Chuangtou industrial square, loufengbei District, Suzhou Industrial Park, Jiangsu Province Applicant before: JIANGSU DIYUN MEDICAL TECHNOLOGY Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20230406 Address after: 215000 East Building, Building 52, Chuangtou Industrial Building, Loufeng North District, Suzhou Industrial Park, Jiangsu Province Applicant after: JIANGSU DIYUN MEDICAL TECHNOLOGY Co.,Ltd. Address before: 215000 landlords of No.52 venture capital industrial square, loufengbei District, Suzhou Industrial Park, Jiangsu Province Applicant before: JIANGSU REGROWN MEDICAL TECHNOLOGY Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201215 |
|
| RJ01 | Rejection of invention patent application after publication |