CN116687661A - Aqueous humor drainage device and preparation method thereof - Google Patents
Aqueous humor drainage device and preparation method thereof Download PDFInfo
- Publication number
- CN116687661A CN116687661A CN202310654610.2A CN202310654610A CN116687661A CN 116687661 A CN116687661 A CN 116687661A CN 202310654610 A CN202310654610 A CN 202310654610A CN 116687661 A CN116687661 A CN 116687661A
- Authority
- CN
- China
- Prior art keywords
- aqueous humor
- drainage device
- humor drainage
- olefinic
- mitomycin
- 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
- 210000001742 aqueous humor Anatomy 0.000 title claims abstract description 138
- 238000002360 preparation method Methods 0.000 title abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 87
- 108010010803 Gelatin Proteins 0.000 claims abstract description 37
- 229920000159 gelatin Polymers 0.000 claims abstract description 37
- 235000019322 gelatine Nutrition 0.000 claims abstract description 37
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 37
- 239000008273 gelatin Substances 0.000 claims abstract description 35
- -1 maleic anhydride modified mitomycin Chemical class 0.000 claims abstract description 27
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 27
- 229920002554 vinyl polymer Polymers 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 23
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 claims abstract description 19
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims abstract description 15
- 238000000016 photochemical curing Methods 0.000 claims abstract description 11
- 150000003573 thiols Chemical class 0.000 claims abstract description 7
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound 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 30
- 229930192392 Mitomycin Natural products 0.000 claims description 24
- 229960004857 mitomycin Drugs 0.000 claims description 24
- 229920002307 Dextran Polymers 0.000 claims description 19
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 150000001336 alkenes Chemical class 0.000 claims description 9
- STMDPCBYJCIZOD-UHFFFAOYSA-N 2-(2,4-dinitroanilino)-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O STMDPCBYJCIZOD-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 7
- 230000001105 regulatory effect Effects 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 230000001678 irradiating effect Effects 0.000 claims description 6
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- KOMNUTZXSVSERR-UHFFFAOYSA-N 1,3,5-tris(prop-2-enyl)-1,3,5-triazinane-2,4,6-trione Chemical compound C=CCN1C(=O)N(CC=C)C(=O)N(CC=C)C1=O KOMNUTZXSVSERR-UHFFFAOYSA-N 0.000 claims description 3
- FYRWKWGEFZTOQI-UHFFFAOYSA-N 3-prop-2-enoxy-2,2-bis(prop-2-enoxymethyl)propan-1-ol Chemical compound C=CCOCC(CO)(COCC=C)COCC=C FYRWKWGEFZTOQI-UHFFFAOYSA-N 0.000 claims description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 3
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005336 allyloxy group Chemical group 0.000 claims description 3
- UOQACRNTVQWTFF-UHFFFAOYSA-N decane-1,10-dithiol Chemical compound SCCCCCCCCCCS UOQACRNTVQWTFF-UHFFFAOYSA-N 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 229910000077 silane Inorganic materials 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- LPSXSORODABQKT-UHFFFAOYSA-N tetrahydrodicyclopentadiene Chemical compound C1C2CCC1C1C2CCC1 LPSXSORODABQKT-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 abstract description 6
- 230000000052 comparative effect Effects 0.000 description 27
- 208000010412 Glaucoma Diseases 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 12
- 239000003999 initiator Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 9
- 230000021164 cell adhesion Effects 0.000 description 9
- 230000036573 scar formation Effects 0.000 description 8
- 210000002950 fibroblast Anatomy 0.000 description 7
- 238000000465 moulding Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000008901 benefit Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 210000000254 ciliated cell Anatomy 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000005671 trienes Chemical class 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000004410 intraocular pressure Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000002861 polymer material Substances 0.000 description 3
- 230000002980 postoperative effect Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000037390 scarring Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 2
- GUCYFKSBFREPBC-UHFFFAOYSA-N [phenyl-(2,4,6-trimethylbenzoyl)phosphoryl]-(2,4,6-trimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C(=O)C1=C(C)C=C(C)C=C1C GUCYFKSBFREPBC-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000012956 1-hydroxycyclohexylphenyl-ketone Substances 0.000 description 1
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical compound CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MQDJYUACMFCOFT-UHFFFAOYSA-N bis[2-(1-hydroxycyclohexyl)phenyl]methanone Chemical compound C=1C=CC=C(C(=O)C=2C(=CC=CC=2)C2(O)CCCCC2)C=1C1(O)CCCCC1 MQDJYUACMFCOFT-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 239000013039 cover film Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- VFHVQBAGLAREND-UHFFFAOYSA-N diphenylphosphoryl-(2,4,6-trimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C)=C1C(=O)P(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 VFHVQBAGLAREND-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/00736—Instruments for removal of intra-ocular material or intra-ocular injection, e.g. cataract instruments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/00781—Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/045—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Prostheses (AREA)
Abstract
The invention provides an aqueous humor drainage device and a preparation method thereof, and relates to the technical field of medical appliances; the aqueous humor drainage device is in a tubular structure; is prepared from thiol-ene material by a photo-curing method; the thiol material in the thiol-ene material is at least one selected from DT1, DT2, siTSH, TTTSH and dithiothreitol; the olefinic materials include a first olefinic material and a second olefinic material; the first olefinic material is maleic anhydride modified mitomycin; the second material is at least one selected from triene1, triene2, triene3, triene4 and vinyl gelatin. The aqueous humor drainage device provided by the invention is prepared from the thiol-ene material with good compatibility by a photocuring method, and the aqueous humor drainage device prepared from the material does not degrade in the use process while ensuring the biocompatibility because the material does not contain degradable groups, so that the stability of the aqueous humor drainage device structure is improved.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to an aqueous humor drainage device and a preparation method thereof.
Background
Glaucoma is the second leading blinding factor worldwide and the first irreversible blinding factor worldwide. In 2005, world-guard organization data showed that there were more than 7000 ten thousand glaucoma patients worldwide, with 8% blindness caused by glaucoma. In 2020, over 330 ten thousand people in the united states glaucoma patients, of which 270 ten thousand patients over 40 years old are afflicted with the most common open angle glaucoma, and the united states costs over 28.6 million dollars per year for glaucoma treatment as a whole, with over 420 ten thousand people in 2030 being expected for united states glaucoma patients and over 630 ten thousand people in 2050. In the Chinese glaucoma guide 2020, the estimated number of glaucoma patients in China in 2020 can reach 2100 ten thousand, and the blind person can reach 567 ten thousand. The incidence rate of glaucoma in China is 0.68% in general population, and the incidence rate is higher and higher along with the increase of age, and can reach 4% -7% after 65 years. With the progress of aging, the birth of new technology and the improvement of detection rate, the glaucoma patient population is further expanded.
For the treatment of glaucoma, the principle of reducing intraocular pressure, preventing or slowing down damage to the optic nerve of a patient as much as possible, and preserving existing vision has been used. Laser trabeculoplasty treatment may be used when traditional medications are poorly effective, or when patients cannot tolerate long-term medications; minimally Invasive Glaucoma Surgery (MIGS) with implanted aqueous humor drainage devices can be performed when laser trabeculoplasty treatment also fails to bring eye pressure down to a safe range or maximum tolerance drug treatment fails; MIGS is to improve aqueous outflow by various methods without damaging conjunctiva and sclera, and finally achieve the aim of reducing intraocular pressure. The MIGS apparatus has the advantages of very outstanding advantages of small tissue damage and small postoperative adverse reaction, and can be used for treating refractory glaucoma of more complicated disease conditions by being used for patients with open angle glaucoma or being used in combination with other operation modes (cataract phacoemulsification operation). MIGS is particularly suitable for patients with mild to moderate glaucoma, which is most characterized by good safety.
As a permanent implant, aqueous humor drainage devices are required to have not only good biocompatibility but also structural stability.
The existing aqueous humor drainage device is mainly made of metal materials and synthetic polymer materials; the metal material has poor biocompatibility, and is prepared by adopting degradable high polymer materials in order to ensure good biocompatibility, but the high polymer materials with good biocompatibility have insufficient structural stability due to degradation.
In view of the above, providing an aqueous humor drainage device that can have both biocompatibility and structural stability is a technical problem that needs to be solved currently.
Disclosure of Invention
The invention aims to solve the technical problems that: in order to solve the problem that the aqueous humor drainage device in the prior art is difficult to have biocompatibility and structural stability, the aqueous humor drainage device is prepared from a thiol-ene material by a photocuring method, and the thiol-ene material has good biocompatibility and does not contain degradable groups, so that the biocompatibility and the structural stability of the aqueous humor drainage device can be considered, and the problem that the aqueous humor drainage device in the prior art is difficult to have the biocompatibility and the structural stability is solved.
The technical scheme adopted for solving the technical problems is as follows:
an aqueous humor drainage device is of a tubular structure; the aqueous humor drainage device is prepared from a mercaptan-alkene material by a photocuring method; the mercaptan material in the mercaptan-alkene material is at least one selected from tetrahydrodicyclopentadiene dimethyl mercaptan, 1, 10-decanedithiol, tetra (ethyl mercaptan) silane, 1,3, 5-tri (propyl mercaptan) isocyanurate and dithiothreitol; the olefinic materials in the thiol-olefinic material include a first olefinic material and a second olefinic material; the first olefinic material is maleic anhydride modified mitomycin; the second material is selected from at least one of trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4, 6-tri (allyloxy) -1,3, 5-trihydrazine, 1,3, 5-triallyl-1, 3, 5-triazine-2, 4,6 (1H, 3H, 5H) -trione and vinyl gelatin.
Alternatively, the maleic anhydride modified mitomycin is prepared as follows:
adding mitomycin, maleic anhydride and a solvent into a three-neck flask, stirring and reacting at 40 ℃, and precipitating a reaction product with ethanol to obtain maleic anhydride modified mitomycin.
Optionally, the molar ratio of the mitomycin to the maleic anhydride is 1:1.
Optionally, the vinyl gelatin is prepared according to the following method:
mixing gelatin with water, regulating pH value to be alkaline, then dripping allyl glycidyl ether to react, regulating pH value to be neutral, sequentially dialyzing, and freeze-drying to obtain vinyl gelatin.
Optionally, the mass ratio of gelatin to allyl glycidyl ether is 20:1.
optionally, the molar ratio of the first olefinic material to the second olefinic material is (0.1-1): 100.
optionally, the molar ratio of olefinic material to thiol material in the thiol-ene material is (0.9-0.99): 1.
optionally, the surface of the aqueous humor drainage device is also chemically modified by methacryloylated dextran.
The invention also aims to provide a preparation method of the aqueous humor drainage device, which comprises the following steps: according to the formula amount, mixing a mercaptan material, an alkene material and a photoinitiator, injecting the mixture into a microfluidic mould, and irradiating the mixture by ultraviolet light to obtain the aqueous humor drainage device.
Optionally, the method further comprises the following steps: adding the aqueous humor drainage device into a methylacryloyl dextran aqueous solution, and oscillating at 37 ℃ to obtain the surface modified aqueous humor drainage device.
The beneficial effects of the invention are as follows:
the aqueous humor drainage device provided by the invention is prepared from the thiol-ene material with good compatibility by a photocuring method, and the aqueous humor drainage device prepared from the material does not contain degradable groups, so that the aqueous humor drainage device can not degrade in the use process while ensuring the biocompatibility, and the stability of the aqueous humor drainage device structure is improved, and the aqueous humor drainage device can be used as a permanent implant; in addition, the maleic anhydride modified mitomycin is combined with other alkene materials to be used as alkene materials in thiol-alkene materials, and the Modified Mitomycin (MMC) is introduced into the aqueous humor drainage device, so that on one hand, the higher biological effect and long-term inhibition effect of the MMC on fibroblasts are utilized, and scar formation in the operation process is reduced; on the other hand, the modification avoids the side effects possibly caused by the introduction of MMC; therefore, by introducing the modified MMC into the aqueous humor drainage device, the toxicity of the MMC is reduced, and scar formation at the postoperative surgical site is reduced.
Drawings
The invention will be further described with reference to the drawings and examples.
FIG. 1 shows the raw gelatin of the present invention 1 H NMR spectrum;
FIG. 2 is a diagram of a vinyl gelatin according to the present invention 1 H NMR spectrum;
FIG. 3 is a nuclear magnetic resonance spectrum of MMC in the present invention;
FIG. 4 is a nuclear magnetic spectrum of MMC-MA according to the invention;
FIG. 5 is an infrared spectrum of MMC in the present invention;
FIG. 6 is an infrared spectrum of MMC-MA according to the invention.
Detailed Description
The present invention will now be described in further detail. The embodiments described below are exemplary and intended to illustrate the invention and should not be construed as limiting the invention, as all other embodiments, based on which a person of ordinary skill in the art would obtain without inventive faculty, are within the scope of the invention.
In the description of the present invention, it should be understood that the terms "first" and "second" are used merely to simplify the description and are not to be construed as indicating or implying relative importance or as implying a number of technical features which are indicated. Thus, a feature defined as "first", "second" may include one or more such feature, either explicitly or implicitly. In the description of the present invention, the meaning of "a plurality" is two or more, unless explicitly defined otherwise.
In order to solve the problem that the aqueous humor drainage device in the prior art is difficult to have biocompatibility and structural stability, the invention provides an aqueous humor drainage device which is in a tubular structure, namely the whole aqueous humor drainage device is in a tubular shape, and a drainage channel is arranged in the aqueous humor drainage device so as to drain aqueous humor in eyes of a patient to a subconjunctival space through the drainage channel, thereby reducing intraocular pressure of glaucoma patients; it should be noted that the specific shape structure, size, etc. of the aqueous humor drainage device can be selected according to the actual requirement or the corresponding prior art; the internal drainage channel can be an equal-diameter drainage channel or a non-equal-diameter drainage channel.
In order to consider the biocompatibility and the structural stability of the aqueous humor drainage device, the aqueous humor drainage device is preferably prepared from a thiol-ene material by a photocuring method, and particularly, the aqueous humor drainage device is preferably prepared from a thiol-ene material, a photoinitiator and a microfluidic combined photocuring method; further, it is preferable that the thiol material in the thiol-ene material of the present invention is at least one selected from the group consisting of tetrahydrodicyclopentadiene dimethyl thiol (DT 1), 1, 10-decanedithiol (DT 2), tetra (ethyl thiol) silane (SiTSH), 1,3, 5-tris (propyl thiol) isocyanurate (TTTSH), dithiothreitol; preferably the olefinic materials in the thiol-olefinic material include a first olefinic material and a second olefinic material; wherein the first olefinic material is maleic anhydride modified mitomycin (MMC-MA); the second material is selected from at least one of trimethylolpropane triallyl ether (triene 1), pentaerythritol triallyl ether (triene 2), 2,4, 6-tri (allyloxy) -1,3, 5-trihydrazine (triene 3), 1,3, 5-triallyl-1, 3, 5-triazine-2, 4,6 (1H, 3H, 5H) -trione (triene 4) and vinyl gelatin.
The aqueous humor drainage device provided by the invention is prepared from the thiol-ene material with good compatibility by a photocuring method, and the aqueous humor drainage device prepared from the material does not contain degradable groups, so that the aqueous humor drainage device can not degrade in the use process while ensuring the biocompatibility, and the stability of the aqueous humor drainage device structure is improved, and the aqueous humor drainage device can be used as a permanent implant; in addition, the maleic anhydride modified mitomycin is combined with other alkene materials to be used as alkene materials in thiol-alkene materials, and the Modified Mitomycin (MMC) is introduced into the aqueous humor drainage device, so that on one hand, the higher biological effect and long-term inhibition effect of the MMC on fibroblasts are utilized, and scar formation in the operation process is reduced; on the other hand, the modification avoids the side effects possibly caused by the introduction of MMC; therefore, by introducing the modified MMC into the aqueous humor drainage device, the toxicity of the MMC is reduced, and scar formation at the postoperative surgical site is reduced.
Specifically, structural formulas of DT1, DT2, siTSH and TTTSH in the invention are respectively shown as the following formulas:
in the invention, the structural formulas of triene1, triene2, triene3 and triene4 are respectively shown as the following formulas:
the preferred maleic anhydride modified mitomycin of the invention is prepared as follows:
adding mitomycin, maleic anhydride and a solvent into a three-neck flask, stirring and reacting at 40 ℃, and precipitating a reaction product with ethanol to obtain maleic anhydride modified mitomycin.
The reaction formula of the preparation method is as follows:
the solvent in the preparation method is tetrahydrofuran; preferably, the molar ratio of mitomycin to maleic anhydride is 1:1; the calculated MMC-MA yield in the preparation method can reach 78%.
The preferred vinyl gelatins of the present invention are prepared as follows:
mixing gelatin with water, regulating pH value to be alkaline, then dripping allyl glycidyl ether to react, regulating pH value to be neutral, sequentially dialyzing, and freeze-drying to obtain vinyl gelatin.
The reaction formula of the preparation method is as follows:
in the preparation process, the pH value of the solution is adjusted to 10.50 by using a sodium hydroxide aqueous solution with the concentration of 3mol/L after gelatin is mixed with water; preferably, after allyl glycidyl ether is dripped to react, hydrochloric acid solution with the concentration of 3mol/L is used for regulating the pH value to be neutral; the mass ratio of the gelatin to the allyl glycidyl ether is preferably 20:1.
in order to reduce scar formation at the surgical site and simultaneously consider the compatibility and structural stability of the aqueous humor drainage device, the molar ratio of the first alkene material to the second alkene material is preferably (0.1-1): 100; preferably the molar ratio of olefinic material to thiol material in the thiol-ene material is (0.9-0.99): 1.
further, in the preparation process of the aqueous humor drainage device, the invention preferably carries out photocuring by adding at least one of photo-initiator diphenyl- (2, 4, 6-trimethyl benzoyl) phosphorus oxide (TPO), 1-hydroxycyclohexyl phenyl ketone (184), 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone (2959), 2,4, 6-trimethyl benzoyl ethyl phenylphosphonate (TPO-L) and phenyl bis (2, 4, 6-trimethyl benzoyl) phosphine oxide (819); and preferably the molar ratio of photoinitiator to thiol-ene material is (0.5-2.5): 100.
In addition, the surface of the aqueous humor drainage device is further preferably chemically modified by the methacryloyl Dextran (DXM) so as to limit cell adhesion and diffusion by modifying the dextran on the surface of the aqueous humor drainage device, thereby reducing the risk of blockage of the aqueous humor drainage device caused by cell adhesion.
Wherein the structural formula of DXM is shown as follows:
the invention also aims to provide a preparation method of the aqueous humor drainage device, which comprises the following steps: according to the formula amount, mixing a mercaptan material, an alkene material and a photoinitiator, injecting the mixture into a microfluidic mould, and irradiating the mixture by ultraviolet light to obtain the aqueous humor drainage device.
According to the preparation method of the aqueous humor drainage device, the aqueous humor drainage device is prepared from the thiol-ene material with good compatibility through the photocuring method, and the aqueous humor drainage device prepared from the material does not contain degradable groups, so that the aqueous humor drainage device is not degraded in the use process while the biocompatibility is ensured, and the stability of the aqueous humor drainage device structure is improved, and the aqueous humor drainage device can be used as a permanent implant; by adopting the micro-fluidic and turnover mould technology, the processing technology is optimized, the production efficiency is improved, and the batch production is facilitated.
Further, the preparation method of the aqueous humor drainage device provided by the invention further comprises the following steps: adding the aqueous humor drainage device into a methylacryloyl dextran aqueous solution, and oscillating at 37 ℃ to obtain the surface modified aqueous humor drainage device.
The mass fraction of the preferred aqueous solution of the methacryloylated dextran is 15%; by modifying the surface of the aqueous humor drainage device with the methacryloyl dextran, cell adhesion and diffusion can be limited, so that the risk of blockage of the aqueous humor drainage device caused by cell adhesion can be reduced.
In order that the above objects, features and advantages of the invention will be readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.
The vinyl gelatins in the examples of the present invention and comparative examples were prepared as follows, without particular explanation:
into a round-bottomed flask (100 ml) equipped with thermometer, stirrer and reflux condenser were charged 5.935g gelatin and 60 ml water at a concentration of 3mol L -1 The pH value of the solution was adjusted to 10.50 by adding 0.29675g of allyl glycidyl ether dropwise thereto, and the reaction was carried out for 4 hours with a concentration of 3mol L -1 The pH of the reaction mixture was adjusted to neutral, dialyzed for 3 days, and freeze-dried to give vinyl gelatin.
FIGS. 1 and 2 show the starting gelatin and vinyl gelatin, respectively 1 H NMR spectra, comparing fig. 1 and fig. 2, show that vinyl gelatin shows a new vinyl peak at δ=5.35 ppm and 5.75 ppm.
The maleic anhydride-modified mitomycin in each example of the present invention and comparative example was prepared as follows, without particular explanation:
1Mol of Mitomycin (MMC), 1mol of maleic anhydride and 100ml of solvent tetrahydrofuran are added into a three-necked flask, stirred for 7 hours at 40 ℃, and the reaction product is precipitated with ethanol to obtain maleic anhydride modified mitomycin (MMC-MA) with a yield of 78%.
Fig. 3 and 4 show nuclear magnetic patterns of the starting materials MMC and maleic anhydride-modified mitomycin (MMC-MA) according to the present invention, respectively, and comparing fig. 3 and 4, it can be seen that MMC-MA shows new characteristic peaks after ring opening of maleic anhydride at δ=5.65 ppm,5.83ppm, and 6.27 ppm.
The infrared spectrograms of the raw materials MMC and maleic anhydride modified mitomycin (MMC-MA) in the invention are respectively shown in fig. 5 and 6.
Example 1
The embodiment provides an aqueous humor drainage device, and the preparation method thereof is as follows:
1mol of dithiothreitol, 0.9mol of vinyl gelatin, 0.009mol of maleic anhydride modified mitomycin MMC-MA and 0.005mol of initiator TPO are mixed, injected into a microfluidic mould, and irradiated for 30s by ultraviolet light with the wavelength of 355nm, thus obtaining an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Example 2
The embodiment provides an aqueous humor drainage device, and the preparation method thereof is as follows:
injecting 0.5mol of dithiothreitol, 0.5mol of DT1, 0.99mol of vinyl gelatin, 0.0099mol of maleic anhydride modified mitomycin MMC-MA and 0.025mol of initiator 184 into a microfluidic mould, and irradiating for 30s by ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Example 3
The embodiment provides an aqueous humor drainage device, and the preparation method thereof is as follows:
injecting 0.5mol of dithiothreitol, 0.5mol of TTTSH, 0.45mol of vinyl monomer rie 1, 0.45mol of vinyl gelatin, 0.0095mol of maleic anhydride modified mitomycin MMC-MA and 0.01mol of initiator TPO-L into a microfluidic mould, and irradiating for 30s through ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 1
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1.5mol of dithiothreitol, 0.9mol of vinyl gelatin and 0.009mol of maleic anhydride modified mitomycin MMC-MA are mixed with 0.005mol of initiator TPO, and the mixture is injected into a microfluidic mould, and the aqueous humor drainage device is obtained by irradiation of ultraviolet light with the wavelength of 355nm for 30 s; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 2
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
mixing 0.5mol of dithiothreitol, 0.9mol of vinyl gelatin and 0.009mol of maleic anhydride modified mitomycin MMC-MA with 0.005mol of initiator TPO, injecting into a microfluidic mould, and irradiating for 30s by ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 3
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.909mol of maleic anhydride modified mitomycin MMC-MA and 0.005mol of initiator TPO are mixed, injected into a microfluidic die, and irradiated for 30s by ultraviolet light with the wavelength of 355nm, and the desired aqueous humor drainage device cannot be obtained by molding.
Comparative example 4
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.909mol of vinyl gelatin and 0.005mol of initiator TPO are mixed, injected into a microfluidic mould, and irradiated for 30s by ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 5
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.9mol of vinyl gelatin, 0.015mol of maleic anhydride modified mitomycin MMC-MA and 0.005mol of initiator TPO are mixed, injected into a microfluidic mould, and irradiated for 120s by ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 6
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.9mol of gelatin and 0.009mol of maleic anhydride modified mitomycin MMC-MA are mixed with 0.005mol of initiator TPO, and the mixture is injected into a microfluidic mould, and is irradiated for 30 seconds by ultraviolet light with the wavelength of 355nm, so as to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 7
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.9mol of vinyl gelatin, 0.009mol of mitomycin MMC and 0.005mol of initiator TPO are mixed, injected into a microfluidic mould, and irradiated for 60 seconds by ultraviolet light with the wavelength of 355nm to obtain an aqueous humor drainage device; and adding the aqueous humor drainage device into a 15% mass fraction of methacrylic acid Dextran (DXM) aqueous solution, and oscillating for 7 days at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Comparative example 8
The comparative example provides an aqueous humor drainage device, which is prepared by the following steps:
1mol of dithiothreitol, 0.9mol of vinyl gelatin and 0.009mol of maleic anhydride modified mitomycin MMC-MA are mixed with 0.005mol of initiator TPO, injected into a microfluidic mould, and irradiated for 30s by ultraviolet light with the wavelength of 355nm, thus obtaining the aqueous humor drainage device.
The performance of the aqueous humor drainage devices prepared in each example and comparative example was tested as follows:
cell inhibition effect test:
the effect of cell inhibition was evaluated by the response of the cells, primary fibroblasts (10 cells/well) were cultured with fire Kong Peiyang base (DMEM) containing 10% fetal bovine serum by mass fraction. After the fibroblast cells were pelleted, the migration test was inserted into the aqueous humor drainage device to completely immerse it in the medium. After 5 days of culture, the status of fibroblasts was examined with live/dead staining and CCK-8, and the 5-day live/dead ratio of fibroblasts (HTFs) was calculated, the higher the activity of the fibroblasts, the more severe the scarring.
Cell adhesion test:
3T3 mouse embryo bromoblasts were maintained in T-75Falcon cell culture using sterile Dulbecco's modified French Kong Peiyang base (DMEM) containing 10% Fetal Bovine Serum (FBS) and 100 units/ml penicillin and 0.1mg/ml streptomycin by mass fraction. 6 samples (36 samples total) of each overlay were placed in 6 well tissue culture plates and irradiated under ultraviolet light for 10-15 minutes. Cells were seeded onto the cover film at a density of approximately 11 000 cells/cm. The cells were then incubated at 37℃for 24h with 5% carbon dioxide, and the medium was then poured off and gently rinsed once with PBS. The adherent cell number is defined as the number of viable cells per 100 x field. The percentage of control was calculated by multiplying the ratio of the percentage of viable cells on the treated substrate to the percentage of viable cells on the untreated substrate by 100. The average control adhesion per sample group was determined and statistical comparisons of the viability assays were made as described above.
Testing of mass loss rate:
degradation stability test, measured by weight change after soaking the samples in 1mol sodium hydroxide at 37 ℃ for more than 1 month at each time point of 4. The sample consisted of 10mg mechanically resected cylinders, 1.6 mm diameter and 1.2 mm high. The dry mass of each sample was used with an accuracy of 0.1. Mu.g. At each desired point in time, each sample will be removed from the solution and gently baked to absorb the wipe against the polymer surface. The mass loss is the mass in the (polytetrafluoroethylene) block measured after placing the sample on the polytetrafluoroethylene; placed in a 120 ℃ vacuum oven for 24 hours, then the samples were removed and re-weighed to determine the final lost mass. The mass loss was calculated as the change in mass percent from the initial weight to the vacuum dry mass. The data report is an average of four samples.
The test results are shown in Table 1:
as can be seen from the data in Table 1, the aqueous humor drainage devices prepared in the embodiments of the present invention have excellent structural stability, and are helpful for reducing scar formation and limiting cell adhesion and diffusion.
Comparative example 1 the amount of thiol material added to thiol-ene material was increased compared to example 1, and the aqueous humor drainage device prepared decreased cell adhesion and decreased risk of clogging of the aqueous humor drainage device, but the mass loss rate was increased and the structural stability of the aqueous humor drainage device was deteriorated.
Compared with the example 1, the comparative example 2 reduces the addition amount of the thiol material in the thiol-ene material, the adhesion of the cells of the prepared aqueous humor drainage device is increased, the risk of blockage of the aqueous humor drainage device is increased, the mass loss rate is slightly reduced, and the structural stability is poor.
Comparative example 3 in comparison with example 1, the thiol-ene material was difficult to mold according to the molding parameters of example 1 by adding only the first ene material MMC-MA to the ene material, and the prepared aqueous humor drainage device could not be prepared.
Comparative example 4 compared to example 1, the thiol-ene material with only the second material added to the ene material produced aqueous humor drainage device had significantly increased HTFs ciliated cell viability/death ratio for 5 days, increasing the risk of scarring; at the same time, the cell adhesion is slightly increased compared with that of the embodiment 1, and the risk of blockage of the aqueous humor drainage device is increased.
Comparative example 5 the amount of the first olefinic material added to the olefinic material was increased, the molding difficulty was increased, and the molding time required was prolonged as compared with example 1; although the aqueous humor drainage device can be obtained by molding, the prepared aqueous humor drainage device has the advantages that the activity/death ratio of HTFs (HTFs) ciliated cells is reduced and the scar formation risk is reduced, but the mass loss rate is increased and the structural stability is poor.
Comparative example 6 compared with example 1, the aqueous humor drainage device could not be formed by crosslinking by substituting gelatin for vinyl gelatin.
Comparative example 7 compared with example 1, MMC was used instead of MMC-MA, molding difficulty was increased, and required molding time was prolonged; the prepared aqueous humor drainage device has the advantages that the activity/death ratio of HTFs (HTFs) to ciliated cells is increased, MMC is not combined in the aqueous humor drainage device in a covalent bond mode, but is filled in the aqueous humor drainage device in a blending mode, so that the capacity of inhibiting scar formation for a long time is reduced; meanwhile, the mass loss rate is increased, and the stability of the structure is deteriorated.
Comparative example 8 compared with example 1, the aqueous humor drainage device prepared without the chemical modification of the surface of the aqueous humor drainage device by using the methacryloylated dextran has significantly increased cell adhesion, and also has increased HTFs ciliated cell activity/death ratio for 5 days, and increased scarring risk compared with example 1.
With the above-described preferred embodiments according to the present invention as an illustration, the above-described descriptions can be used by persons skilled in the relevant art to make various changes and modifications without departing from the scope of the technical idea of the present invention. The technical scope of the present invention is not limited to the description, but must be determined according to the scope of claims.
Claims (10)
1. An aqueous humor drainage device is characterized by being in a tubular structure; the aqueous humor drainage device is prepared from a mercaptan-alkene material by a photocuring method; the mercaptan material in the mercaptan-alkene material is at least one selected from tetrahydrodicyclopentadiene dimethyl mercaptan, 1, 10-decanedithiol, tetra (ethyl mercaptan) silane, 1,3, 5-tri (propyl mercaptan) isocyanurate and dithiothreitol; the olefinic materials in the thiol-olefinic material include a first olefinic material and a second olefinic material; the first olefinic material is maleic anhydride modified mitomycin; the second material is selected from at least one of trimethylolpropane triallyl ether, pentaerythritol triallyl ether, 2,4, 6-tri (allyloxy) -1,3, 5-trihydrazine, 1,3, 5-triallyl-1, 3, 5-triazine-2, 4,6 (1H, 3H, 5H) -trione and vinyl gelatin.
2. The aqueous humor drainage device of claim 1, wherein the maleic anhydride modified mitomycin is prepared according to the following method:
adding mitomycin, maleic anhydride and a solvent into a three-neck flask, stirring and reacting at 40 ℃, and precipitating a reaction product with ethanol to obtain maleic anhydride modified mitomycin.
3. The aqueous humor drainage device of claim 2, wherein the molar ratio of mitomycin to maleic anhydride is 1:1.
4. The aqueous humor drainage device according to claim 1, wherein the vinyl gelatin is prepared according to the following method:
mixing gelatin with water, regulating pH value to be alkaline, then dripping allyl glycidyl ether to react, regulating pH value to be neutral, sequentially dialyzing, and freeze-drying to obtain vinyl gelatin.
5. The aqueous humor drainage device according to claim 4, wherein the mass ratio of gelatin to allyl glycidyl ether is 20:1.
6. the aqueous humor drainage device of any one of claims 1 to 5, wherein the molar ratio of the first olefinic material to the second olefinic material is (0.1 to 1): 100.
7. the aqueous humor drainage device of claim 6, wherein the molar ratio of olefinic material to thiol material in the thiol-ene material is (0.9-0.99): 1.
8. the aqueous humor diverter of claim 7, wherein the surface of the aqueous humor diverter is further chemically modified by methacrylated dextran.
9. A method of preparing an aqueous humor drainage device according to any one of claims 1 to 8, comprising the steps of: according to the formula amount, mixing a mercaptan material, an alkene material and a photoinitiator, injecting the mixture into a microfluidic mould, and irradiating the mixture by ultraviolet light to obtain the aqueous humor drainage device.
10. The method for preparing an aqueous humor drainage device according to claim 9, further comprising the following steps: adding the aqueous humor drainage device into a methylacryloyl dextran aqueous solution, and oscillating at 37 ℃ to obtain the surface modified aqueous humor drainage device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310654610.2A CN116687661A (en) | 2023-06-05 | 2023-06-05 | Aqueous humor drainage device and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310654610.2A CN116687661A (en) | 2023-06-05 | 2023-06-05 | Aqueous humor drainage device and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116687661A true CN116687661A (en) | 2023-09-05 |
Family
ID=87840439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310654610.2A Pending CN116687661A (en) | 2023-06-05 | 2023-06-05 | Aqueous humor drainage device and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116687661A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117567698A (en) * | 2023-10-19 | 2024-02-20 | 明澈生物科技(苏州)有限公司 | Photo-curing biocompatible material and drainage tube |
| CN118059327A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, glaucoma drainage device and preparation method thereof |
| CN118059326A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, ophthalmic drainage device and preparation method thereof |
| CN118161340A (en) * | 2024-05-14 | 2024-06-11 | 明澈生物科技(苏州)有限公司 | Aqueous humor drainage tube |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5252673A (en) * | 1991-03-18 | 1993-10-12 | Agency Of Industrial Science & Technology | Macromolecular mitomycin C derivative and method for production thereof |
| US20060235367A1 (en) * | 2002-12-27 | 2006-10-19 | Seisuke Takashima | Aqueous humor drainage implant for treatment glaucoma |
| CN2860405Y (en) * | 2005-07-29 | 2007-01-24 | 广东冠昊生物科技有限公司 | Biotype artificial ligament |
| CN103221070A (en) * | 2010-08-30 | 2013-07-24 | 哈佛大学校长及研究员协会 | Shear controlled release for stenotic lesions and thrombolytic therapies |
| CN103301511A (en) * | 2013-06-20 | 2013-09-18 | 王惠 | Complex implant for fixing human skeletons |
| CN106317263A (en) * | 2016-08-23 | 2017-01-11 | 浙江理工大学 | Visible light initiating system in medical photo-curing hydrogel and photo-curing method thereof |
| CN110694120A (en) * | 2019-10-24 | 2020-01-17 | 东莞立德生物医疗有限公司 | Biomedical degradable material and preparation method thereof |
| CN113288580A (en) * | 2021-06-24 | 2021-08-24 | 明澈生物科技(广州)有限公司 | A aqueous humor drainage ware for implanting glaucoma patient is intraocular |
-
2023
- 2023-06-05 CN CN202310654610.2A patent/CN116687661A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5252673A (en) * | 1991-03-18 | 1993-10-12 | Agency Of Industrial Science & Technology | Macromolecular mitomycin C derivative and method for production thereof |
| US20060235367A1 (en) * | 2002-12-27 | 2006-10-19 | Seisuke Takashima | Aqueous humor drainage implant for treatment glaucoma |
| CN2860405Y (en) * | 2005-07-29 | 2007-01-24 | 广东冠昊生物科技有限公司 | Biotype artificial ligament |
| CN103221070A (en) * | 2010-08-30 | 2013-07-24 | 哈佛大学校长及研究员协会 | Shear controlled release for stenotic lesions and thrombolytic therapies |
| CN103301511A (en) * | 2013-06-20 | 2013-09-18 | 王惠 | Complex implant for fixing human skeletons |
| CN106317263A (en) * | 2016-08-23 | 2017-01-11 | 浙江理工大学 | Visible light initiating system in medical photo-curing hydrogel and photo-curing method thereof |
| CN110694120A (en) * | 2019-10-24 | 2020-01-17 | 东莞立德生物医疗有限公司 | Biomedical degradable material and preparation method thereof |
| CN113288580A (en) * | 2021-06-24 | 2021-08-24 | 明澈生物科技(广州)有限公司 | A aqueous humor drainage ware for implanting glaucoma patient is intraocular |
Non-Patent Citations (2)
| Title |
|---|
| 娄旭华: "两性离子聚合物高效液相色谱固定相的制备与色谱评价", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》, no. 2021, 15 January 2021 (2021-01-15) * |
| 简翠兰;聂军;: "房水引流物植入联合丝裂霉素C治疗难治性青光眼的护理", 护理学杂志, no. 18, 25 September 2012 (2012-09-25) * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117567698A (en) * | 2023-10-19 | 2024-02-20 | 明澈生物科技(苏州)有限公司 | Photo-curing biocompatible material and drainage tube |
| CN117567698B (en) * | 2023-10-19 | 2024-06-14 | 明澈生物科技(苏州)有限公司 | Photo-curing biocompatible material and drainage tube |
| CN118059327A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, glaucoma drainage device and preparation method thereof |
| CN118059326A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, ophthalmic drainage device and preparation method thereof |
| CN118059327B (en) * | 2024-01-25 | 2024-09-13 | 明澈生物科技(苏州)有限公司 | Photo-curing material, glaucoma drainage device and preparation method thereof |
| CN118059326B (en) * | 2024-01-25 | 2024-09-13 | 明澈生物科技(苏州)有限公司 | Photo-curing material, ophthalmic drainage device and preparation method thereof |
| CN118161340A (en) * | 2024-05-14 | 2024-06-11 | 明澈生物科技(苏州)有限公司 | Aqueous humor drainage tube |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN116687661A (en) | Aqueous humor drainage device and preparation method thereof | |
| DE69605778T2 (en) | USE OF A POLYMER AS A SUBSTRATE FOR CELL GROWTH | |
| EP1206293B8 (en) | Homopolymers containing crosslinkers and ocular implants made therefrom | |
| EP0800541B1 (en) | Siloxane-containing networks | |
| CA1276142C (en) | Gel of crosslinked hyaluronic acid for use as a vitreous humor substitute | |
| DE69706852T2 (en) | COPOLYMERS WITH AMPHIPHILE SEGMENTS AND CONTROLLED MORPHOLOGY; OPTHALMIC PRODUCTS AND CONTACT LENSES BASED ON THESE COPOLYMERS | |
| DE69611086T2 (en) | POLYMERIZABLE PERFLUOROALKYL ETHER MACROMER | |
| JP2005534737A (en) | Improved biomedical product composition | |
| US7556822B2 (en) | Biomedical compositions | |
| US20020128346A1 (en) | Hydrogels | |
| CN117567698B (en) | Photo-curing biocompatible material and drainage tube | |
| CN113367885B (en) | Glaucoma drainage tube, material thereof and implantation device | |
| EP0914169B1 (en) | Materials for use in glaucoma filtration devices | |
| CN110964155A (en) | Zwitterionic hydrogel with high anti-fouling performance and preparation method and application thereof | |
| Foster et al. | Internal osmotic pressure as a mechanism of retinal attachment in a vitreous substitute | |
| CN118059326B (en) | Photo-curing material, ophthalmic drainage device and preparation method thereof | |
| CN118059327B (en) | Photo-curing material, glaucoma drainage device and preparation method thereof | |
| CN116425917B (en) | Polymer elastomer material containing immune regulation group, compound, preparation method and application | |
| US5993796A (en) | Biocompatible polymeric materials, methods of preparing such materials and uses thereof | |
| CN117903373A (en) | Photo-curing material, ocular pressure reducing drainage tube and preparation method of ocular pressure reducing drainage tube | |
| Pusch | Strategies of preparing transparent latices with application to the synthesis of transparent hydrogels for intraocular lenses | |
| CN117815447A (en) | Agarose-based artificial cornea and preparation method thereof | |
| AU780010C (en) | Biomedical compositions |
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 |