WO1985003716A1 - Vision correction lens made from an aminopolysaccharide compound or an ether or ester thereof - Google Patents
Vision correction lens made from an aminopolysaccharide compound or an ether or ester thereof Download PDFInfo
- Publication number
- WO1985003716A1 WO1985003716A1 PCT/US1985/000169 US8500169W WO8503716A1 WO 1985003716 A1 WO1985003716 A1 WO 1985003716A1 US 8500169 W US8500169 W US 8500169W WO 8503716 A1 WO8503716 A1 WO 8503716A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lens
- homopolymer
- wound healing
- forming
- aminopolysaccharide
- Prior art date
Links
- 238000012937 correction Methods 0.000 title claims abstract description 23
- 150000001875 compounds Chemical class 0.000 title claims description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title claims description 21
- 150000002148 esters Chemical class 0.000 title claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000001301 oxygen Substances 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 229920001519 homopolymer Polymers 0.000 claims abstract 18
- -1 carboxylate ester Chemical class 0.000 claims description 21
- 238000005266 casting Methods 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 18
- 230000029663 wound healing Effects 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 239000000835 fiber Substances 0.000 claims description 10
- 239000000985 reactive dye Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000001408 amides Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims description 5
- 229950006780 n-acetylglucosamine Drugs 0.000 claims description 5
- 239000003431 cross linking reagent Substances 0.000 claims description 4
- 125000001033 ether group Chemical group 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims 2
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 1
- 125000003047 N-acetyl group Chemical group 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 229960002442 glucosamine Drugs 0.000 claims 1
- ILHIHKRJJMKBEE-UHFFFAOYSA-N hydroperoxyethane Chemical compound CCOO ILHIHKRJJMKBEE-UHFFFAOYSA-N 0.000 claims 1
- 125000005372 silanol group Chemical group 0.000 claims 1
- 229920006037 cross link polymer Polymers 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000975 dye Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- 229920001661 Chitosan Polymers 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
- 230000035699 permeability Effects 0.000 description 9
- 239000004014 plasticizer Substances 0.000 description 9
- 229920002101 Chitin Polymers 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- 239000010408 film Substances 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 229920001282 polysaccharide Polymers 0.000 description 7
- 239000005017 polysaccharide Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000004528 spin coating Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000004132 cross linking Methods 0.000 description 6
- 238000002386 leaching Methods 0.000 description 6
- 150000001350 alkyl halides Chemical class 0.000 description 5
- 150000001720 carbohydrates Chemical group 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000000465 moulding Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 150000003462 sulfoxides Chemical class 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000003754 machining Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XHKPPUVICXLDRJ-UHFFFAOYSA-N 2-(2-hydroxyethylsulfinyl)ethanol Chemical compound OCCS(=O)CCO XHKPPUVICXLDRJ-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 241000238424 Crustacea Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000012296 anti-solvent Substances 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 150000003016 phosphoric acids Chemical class 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- AXPJONMFIFMWMM-WDCZJNDASA-N (2r,3r,4r)-2-amino-2,3,4,5-tetrahydroxypentanal Chemical compound O=C[C@@](O)(N)[C@H](O)[C@H](O)CO AXPJONMFIFMWMM-WDCZJNDASA-N 0.000 description 1
- XURYRTPVCGEHNI-DPYQTVNSSA-N (2r,3s,4s,5r)-3-amino-2,3,4,5,6-pentahydroxyhexanal Chemical compound O=C[C@H](O)[C@](O)(N)[C@@H](O)[C@H](O)CO XURYRTPVCGEHNI-DPYQTVNSSA-N 0.000 description 1
- SPSSDDOTEZKOOV-UHFFFAOYSA-N 2,3-dichloroquinoxaline Chemical group C1=CC=C2N=C(Cl)C(Cl)=NC2=C1 SPSSDDOTEZKOOV-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- WROUWQQRXUBECT-UHFFFAOYSA-N 2-ethylacrylic acid Chemical compound CCC(=C)C(O)=O WROUWQQRXUBECT-UHFFFAOYSA-N 0.000 description 1
- IHDBZCJYSHDCKF-UHFFFAOYSA-N 4,6-dichlorotriazine Chemical group ClC1=CC(Cl)=NN=N1 IHDBZCJYSHDCKF-UHFFFAOYSA-N 0.000 description 1
- LJSMGWBQOFWAPJ-UHFFFAOYSA-N 4-methoxy-3-(naphthalen-1-ylmethyl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(CC(CC(O)=O)C(=O)OC)=CC=CC2=C1 LJSMGWBQOFWAPJ-UHFFFAOYSA-N 0.000 description 1
- ORLGPUVJERIKLW-UHFFFAOYSA-N 5-chlorotriazine Chemical group ClC1=CN=NN=C1 ORLGPUVJERIKLW-UHFFFAOYSA-N 0.000 description 1
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 206010011033 Corneal oedema Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000083869 Polyommatus dorylas Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229940117913 acrylamide Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229940124326 anaesthetic agent Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- YKCWQPZFAFZLBI-UHFFFAOYSA-N cibacron blue Chemical compound C1=2C(=O)C3=CC=CC=C3C(=O)C=2C(N)=C(S(O)(=O)=O)C=C1NC(C=C1S(O)(=O)=O)=CC=C1NC(N=1)=NC(Cl)=NC=1NC1=CC=CC=C1S(O)(=O)=O YKCWQPZFAFZLBI-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 201000004778 corneal edema Diseases 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002249 decongestive effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical group C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 1
- UNFUYWDGSFDHCW-UHFFFAOYSA-N monochlorocyclohexane Chemical compound ClC1CCCCC1 UNFUYWDGSFDHCW-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- RAFYDKXYXRZODZ-UHFFFAOYSA-N octanoyl octanoate Chemical compound CCCCCCCC(=O)OC(=O)CCCCCCC RAFYDKXYXRZODZ-UHFFFAOYSA-N 0.000 description 1
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical group N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960003504 silicones Drugs 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000008791 toxic response Effects 0.000 description 1
- YXZRCLVVNRLPTP-UHFFFAOYSA-J turquoise blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Cu+2].NC1=NC(Cl)=NC(NC=2C=C(NS(=O)(=O)C3=CC=4C(=C5NC=4NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)NC=4NC(=C6C=C(C=CC6=4)S([O-])(=O)=O)NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)N5)C=C3)C(=CC=2)S([O-])(=O)=O)=N1 YXZRCLVVNRLPTP-UHFFFAOYSA-J 0.000 description 1
- DGJTZXXNXZVULP-UHFFFAOYSA-N undecanoyl undecanoate Chemical compound CCCCCCCCCCC(=O)OC(=O)CCCCCCCCCC DGJTZXXNXZVULP-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
Definitions
- the invention relates to a vision correction lens made from an aminopolysaccharide compound. More particularly the invention relates to an oxygen perme- able, wettable, optically acceptable lens which com ⁇ prises an unsubstituted or substituted aminopolysac ⁇ charide compound having ester or ether groups.
- Vision correction lenses such as contact lenses and intraocular lenses have been known as commercial prod ⁇ ucts for over 25 years.
- An acceptable lens must be optically clear, mechanically stable, and must provide sufficient optical correction, gas permeability and wettability to insure that the lens is comfortable and safe during use.
- Gas permeability is important since the corneal surface of the eye respires by obtain ⁇ ing oxygen and other substances from tear fluid and by releasing carbon dioxide and other products of respira ⁇ tion into tear fluid.
- the intimate contact and position of the contact lens can substantially prevent the exchange of such constituents between the corneal epithelial cells and tear fluid.
- the cornea can become starved for oxygen and can accumulate harmful amounts of metabolites within the constituent cells. This can result in corneal edema (swelling) and often extreme discomfort to the wearer. Wettability of the lens is important because a nonwettable lens can be abrasive and irritating to the eye and lid and can cause significant wearer discomfort.
- a lens must have suffi- cient mechanical integrity to allow for easy cleaning and handling and maintaining the desired curvature and correction for the individual user.
- the lens should be immunologically compatible with the eye, reducing chances of allergic reaction or toxic response. Further the lens should be permanently dyeable,.. easily manufac ⁇ tured and available at low cost.
- contact lenses have been made from synthetic polymeric materials such as plastic matrices
- Miyata U.S. Patent No. 4,223,984 is primarily directed to a contact lens made from solubilized defatted transparent crosslinked collagen.
- Miyata, U.S. Patent 4,260,228 is particularly directed to an improved collagen gel soft contact lens prepared from an aldehyde crosslinked gel containing a polyhydroxy compound such as glucose.
- Miyata U.S. Patent 4,264,155 is primarily directed to an improved lens made from collagen gel to which a water soluble organic polyhydroxy polymer has been added.
- U.S. Patent 4,365,050 discloses and claims certain polymeric aminopolysaccharide compositions used in the fabrication of contact lenses which- are limited to graft and block copolymers of an acetyl glycosamine in combination with compounds selected from the group consisting of silicone, collagen, acrylonitrile, acryl- amide, methacrylates ,- alkyl methacrylates, alkyl amino alkylethacrylates, hydroxyalkyl methacrylates, pyrol- lidones, and vinyl derivatives of pyrollidone.
- the first aspect of the invention is a hard or a soft contact lens which can be made from the aminopolysac ⁇ charide compounds of the invention.
- the second aspect of the invention is methods of forming the aminopoly- saccharide compounds useful in forming vision correction lenses.
- a third aspect of the invention is an intraocu ⁇ lar lens which can be surgically placed in the eye to replace or supplement the natural lens.
- a lens blank or lens replica ' is an unfinished lens, having an approximately circular mass which can be ground, polished or otherwise shaped to the desired surface finish and dimensions of the lens.
- the lens blank or replica can have the approxi- mate dimensions of about 3/4 to 1 inch in diameter and about 5/8 to 1 inch in thickness (about 19 to 25 milli ⁇ meters in diameter and about 15 to 25 millimeters thickness).
- Oxygen gas permeability values (DR) are generally expressed in units of millimeters (02)-cm* sec.-mL./mm./Hg. Measurements of oxygen permeability are typically taken at 37° C. in an oxygen consuming electrode cell (oxygen flux meter). See J.-* Falk, Polarographic Oxygen Sensor, CRC Press, 1976.
- the oxygen permeability of contact lens materials can range from about 0.1 x lO" 11 to 80 x lO" 11 D ⁇ and higher.
- Oxygen permeablity of 4 x 10"" 11 or preferably 12 x 10""--*-** DR or greater has been shown to be beneficial to eye tissue, permitting sufficient exchange of nutrients between the corneal epithelium and tear.
- Wettability is typically measured on dry samples using a Kayness contact angle measurement. Contact angles of less than 75° and preferably less than 70° can indicate beneficial wettability.
- the vision correction lenses of this invention are prepared from an unsubstituted intention ⁇ ally purified aminopolysaccharide or an ester ether or amide derivative of an aminopolysaccharide compound.
- the vision correction lenses of this invention have been found to be exceptionally oxygen permeable, highly wettable and capable of greatly extended wear.
- the lenses can be hard or soft, and can have portions of varying hardness.
- the soft lenses of the invention can have substantial mechanical stability and beneficial hydrophilicity.
- the aminopolysaccharide lenses and compounds of this invention have the additional economic advantage that they are relatively inexpensive biocom- patible materials.
- the aminopolysaccharide source used in making the lenses are naturally occurring and readily available.
- a lens of this invention can be placed in an eye which has suffered abrasions or other injury from other contact lenses which can aid in the healing process while allowing sufficient vision correc ⁇ tion to the wearer.
- the lenses can contain phys iolog ically act ive compounds for the on-s ite controlled delivery for the treatment of ocular diseas- es . Addit ionally these lenses can be irreversibly tinted by exposure to fiber reactive dyes .
- aminopolysaccharide compounds useful in this invention for preparing vision correction lenses are derived generally from natural sources and comprise repeating units of N-substituted C 5 or Cg amino- saccharides such as 2-amino ribose, 2-amino-glucose, 3-amino-galactose, including 2-(N-acetyl)-amino-glucose , 2- (N-acetyl ) -amino-galactose or mixtures thereof .
- N-acetyl-aminopolysaccharides can be found in abundance in naturally occurring substances such as in the hard shell of insects , crustaceans , mollusks , fungi , cell wal ls , etc .
- the aminopolysaccharide compounds are the major structural component in many animals and plants.
- chitin and ch itosan refer to the raw material derived from insect and crustacean shells from which a inopolysaccharides can be obtained .
- aminopolysaccharides used in forming the vision correc- tion lenses of this invention are derived from chitin and chitosan by separating the aminopolysaccharides from calcium carbonate, protein, fats, and other naturally occurring substances that make up the shell.
- a major component of naturally occurring chitin is an N-acetyl glucosamine polymer.
- chitin the major proportion of the amino groups are acetylated while in chitosan the major proportion of the amino groups are generally free of any substituent.
- Chitin and chitosan comprise a broad spectrum of aminopolysaccharide compounds which cannot be easily distinguished because polysaccharide molecules can have various branchings, various types of saccharide units and various fractions of acetylated a ine groups.
- the amino group substituents can be naturally formed or can be formed during aminopolysac ⁇ charide purification or lens manufacture.
- the vision correction lens of this invention can be made from an intentionally purified unsubstituted aminopolysaccharide compound. These compounds can be used once they are separated from the other components of chitin or chitosan.
- the unmodified substantially purified aminopolysaccharide compound has few substi ⁇ tuents on the 3, 4 and 6 hydroxyl groups of the molecule and has acetyl groups on the 2-amino group in an amount which corresponds to the naturally occurring amount characteristic of the source of the compound.
- the vision correction lenses of this invention can be made from low molecular weight esters, ethers or amides of the aminopolysaccharide compound formed by reacting the aminopolysaccharide compound hydroxyl or amino groups with essentially monomeric non-polyme iz- able ether, ester or amide forming compounds.
- Amino ⁇ polysaccharide ether compounds can be made by any ether forming reaction. The Williamson synthesis reacting an alkyl halide with a sodium salt of the polysaccharide hydroxyl group is preferred.
- Other ether type substi ⁇ tuents can be used such as silicone type ethers, borane type ethers.
- Preferred ether groups are derived by reacting an alkyl halide or an alkyl silicone halide with the aminopolysaccharide hydroxyl groups.
- a parti ⁇ cularly useful ether forming reagent for use with the aminopolysaccharide compounds of this invention are 5 lower alkyl halides or aryl substituted alkyl halides, - preferably C ⁇ Cg alkyl chlorides including methyl chloride, ethyl bromide, isopropyl iodide, tertiary butyl chloride, cyclohexyl chloride, benzyl chloride, etc.
- Methyl chloride and benzyl chloride are generally
- An appropriate catalyst to facilitate the reaction between the alkyl halides is any generally basic catalyst such as sodium hydroxide, potassium hydroxide, magnesium
- hydroxide etc.
- substantially nonreactive polar solvents such as methyl ethyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide, etc.
- Ester derivatives can be formed by "reacting the
- Hydroxyl reactive acid compounds can include carboxylic acids, carboxylic acid anhydrides, carboxylic acid halides, sulfonic acids, phosphoric acids, boric acid compounds, etc. Preferred ester
- 25 forming reagents include the reactive carboxylic anhy ⁇ dride and carboxylic acid halide compounds.
- esterifying agent for use with the aminopolysaccharide compounds of this invention are carboxylic acid anhydrides such as ri-butyric anhy-
- a preferred compound is ri-butyric anhydride for reasons of its effectiveness.
- An appropriate catalyst to facilitate the reaction between the butyric anhydride and the ' aminopolysaccharide compound is any generally acidic catalyst.
- Acidic compositions such as phosphoric acids, acidic resins, sulfonic acids and others can be used. These materials can be suspended in a substantially nonreactive but polar solvent such as methylethylketone, methylisobutylketone, N,N-dimethylformamide, and di- methylacetamide.
- Amides are prepared similarly to the ester except that the starting material usually is an aminopolysaccharide containing a large proportion of free amino groups.
- the aminopolysaccharide compounds of this inven ⁇ tion can be crosslinked in order to increase the durability, mechanical stability, and useful life.
- Biologically derived materials such as aminopolysac ⁇ charides can be biodegradable and can be slowly attached in the eye through the naturally occurring response of the eye to the foreign aminopolysaccharide substance.
- Crosslinking of the aminopolysaccharides can act to counteract the tendency of the lens to biodegrade.
- Crosslinking acts to stop biodegradation by crosslinking between hydroxyl groups between amino groups and between hydroxyl and amino groups in adjacent aminopolysac- charide molecules.
- Crosslinking can be carried out by exposing the aminopolysaccharide compound, the aminopolysaccharide compound lens blank or replica, or finished lens to a suitable crosslinking agent.
- Cross ⁇ linking agents comprise polyfunctional compounds having hydroxyl or amino reactive moieties separated by a group sufficient that the moieties can react with separate, adjacent aminopolysaccharide molecules.
- crosslinking agents which may be employed to form the contact lens compositions of the invention include di-, tri- and tetra-substituted carboxylic acid com- pounds, aliphatic aromatic diisocyanates, polyfunctional chlorofor ates, polyfunctional sulfonyl chlorides, aldehyde crosslinking agents, acrolein, dyoxal, dialde- hyde starch, etc.
- Fiber Reactive Dyes include di-, tri- and tetra-substituted carboxylic acid com- pounds, aliphatic aromatic diisocyanates, polyfunctional chlorofor ates, polyfunctional sulfonyl chlorides, aldehyde crosslinking agents, acrolein, dyoxal, dialde- hyde starch, etc.
- the lens or lens composition can be substantially permanently dyed using fiber reactive dyes, that is, those dyes containing a functional or reactive group capable of attaching the chromophore groups by forming covalent chemical bonds with hydroxyl or amino func ⁇ tional groups of the aminopolysaccharide compound
- the chromophore group can be an azo compound, which can yield a red, blue, violet, or yellow tint, an anthra- quinone compound, which can yield a royal blue tint, a phthalocyanine residue, for a turquoise blue tint, or other chromophore groups known in the art.
- suit ⁇ able dye stuffs can include a monochlorotriazine group, dichlorotriazine group, vinyl sulfone group, trichloro- pyrimidyl group, dichloroquinoxaline group, ethylene sulfonimide group, cyclic ethylene immonium-type group, and acrylamide group, among others. While most fiber reactive dyes find utility in this invention, the preferred dyes are the chlorotriazine dyes, because of their accessibility, the large amount of information available on these dyes, their relative reactivity at room temperature,, and the broad range of colors avail ⁇ able.
- the reactive group of the dye contains a chlorine
- the chlorine will combine with a hydrogen of an amino or hydroxyl group of the aminopolysaccharide compound, yielding HC1 by-pro ⁇ duct.
- a covalent bond thus forms between the carbon atom of the dye and the amino or hydoxyl group of the aminopolysaccharide compound.
- Fiber reactive dyes and other suitable substances can also be used with the lenses and lens compositions of this invention to yield a substantially opaque lens.
- An opaque lens can be desirable when for medical or other reasons it is desired to shield an eye tissue from light.
- An opaque lens of this invention can in many instances be worn in place of the traditional eye patch which can be uncomfortable and cosmetically unattractive.
- Physiologically Active compounds can also be included in the lens or lens composition. These com ⁇ pounds can include antibiotics such as tetracycline, bacitracin, and neomycin, antiallergic products such as chlorphenira ine, decongestive substances such as pseudoephedrine and tetrahydrazoline, antiviral products such as idoxuridine, and other substances such as analgesics, anaesthetics, antiseptics, and others. When included in the lens, the physiologically active com ⁇ pounds can be released at a controlled rate upon the placing of the lens in the eye.
- antibiotics such as tetracycline, bacitracin, and neomycin
- antiallergic products such as chlorphenira ine
- decongestive substances such as pseudoephedrine and tetrahydrazoline
- antiviral products such as idoxuridine
- other substances such as analgesics, anaesthetics, antiseptics,
- humectants can be incorporated into the lens composition.
- Suit ⁇ able humectants can stabilize the vision correction lenses to effects of water.
- Such constituents having a significant degree of compatibility with aminopolysac ⁇ charide compounds include glycerol, ethylene glycol, propylene glycol, and sorbitol.
- a plasticizer can be particularly advantageous in the context of this invention in order to more easily compound or form the aminopolysaccharide compound. Without a plasticizer, the forces between the chains of molecules in the aminopolysaccharide compound can often be so strong as to prevent slippage of the molecules preventing the lens material from conforming to a mold.
- the plasticizer can reduce the bonding force between the chains of molecules allowing them to take the shape of the mold.
- the plasticizer can reduce the hydrogen bonding between the functional group of one polymer molecule, and functional groups of another. While the plasticizer can be removed from the lens to create the finished product, the plasticizer can also be left in the lens if nontoxic and stable.
- the mixture is suspended in a substantially nonreactive solvent, to facilitate admix- ture and reaction of the agent, the aminopolysaccharide compound, and the catalyst.
- the reaction product passes into solution.
- a precipitating amount of an anti-solvent which is substantially miscible with the nonreactive solvent is added to the filtered reaction liquor to precipitate the reaction product of the aminopolysaccharide compound and the ether-, ester- or amide-forming agent.
- anti-sol- vents include water, methanol, ethyl alcohol, etc.
- any excess agent can be removed. This can be done by hydrolysis, ion exchange, neutralization, dialysis, washing or other techniques.
- the precipitate can be collected, for example, by filtration, and washed, for example, with distilled water, to remove any remaining traces of agent, salt or other undesirable materials.
- Forming a Contact Lens The lens of this invention can be formed from the aminopolysaccharide compound by a variety of methods. Stationary casting, spin casting, molding, and lathe cutting, can be useful processes for fabricating the lenses.
- a lens-form ⁇ ing amount of a solution comprising a sufficient amount of aminopolysaccharide compound or derivatives, dis ⁇ solved or suspended in an appropriate solvent can be added to a mold for stationary casting.
- a lens blank or lens replica can be formed in this mold by removing the solvent and then the lens can be finished for use in the eye.
- the aminopolysaccharide compound can be brought into solution or suspension by combining it with acetic acid and water, for example, a solution comprising 0.5 to 5% of an aminopolysaccharide compound, 0.5 to 5% acetic acid, and water.
- aminopolysaccharide compounds are insoluble in water.
- a solubilizing amino salt forming acid such as acetic acid other appropriate compound
- a soluble salt of the aminopolysaccharide compound can form.
- the acetate salt of the amino group can form.
- This solution can be introduced into a suitable lens shaped mold.
- a suitable mold can be made of an acrylic material, with a polished hemispherical cavity and a diameter of, for example, 10-20 millimeters, and a depth of approximately 10-20 mm. Solvent is removed from the the solution in the mold. This can be accom ⁇ plished by use of a vacuum system, a heat source such as a sun lamp, or simply at ambient temperature and by any known means.
- the casting When the casting is dry, it can be removed from the mold. It is advisable to wash or neutralize the casting, in order to remove traces of acetic or other acid which may be present. This can be done by exposure of the casting to an appropriate base, for example, by soaking the casting in a 0.5% to 15% aqueous solution of sodium hydroxide. If a 5% solution is used, it is advisable to soak the casting for about an hour.
- Another method for making a lens from, an aminopoly- saccharide compound or derivative thereof involves forming the lens in a mold using high pressure using a plasticizer if necessary.
- a soft flexible film is created from the aminopolysaccharide compound, and the film is molded to form the lens blank or replica.
- the mold can be of a type known in the art, for example, made of steel and used under conditions known in the art such as 90° C. with a platen pressure of 15,000 lbs.
- the aminopolysaccharide compound can be plasticized before molding.
- a solution can be made comprising acetic acid, an amino ⁇ polysaccharide compound, a plasticizer, and an agent to disrupt the molecular structure of the aminopolysac- charide compound.
- a typical solution can be 0.5 to 5% aminopolysaccharide compound, 0.5 to 5% acetic acid, di(hydroxyethyl)sulfoxide, and lithium chloride.
- the lithium chloride can act as the disrupting agent, that is, it can break up the molecular order of the amino- polysaccharide compound, thus permitting it to interact more readily with the sulfoxide.
- the sulfoxide can work as the plasticizer, where it reduces the hydrogen bonding between molecules and thus allows the chains of molecules in the aminopolysaccharide compounds to more easily slip past one another and conform to and hold the shape of the mold.
- the mixture identified above can be thoroughly stirred to facilitate interaction of the . components. Then it can be formed into a soft flexible film, for example by pouring it onto a polyethylene film and drying. The soft flexible film can then be molded in a mold known in the art, forming a lens blank or replica.
- any traces of acetic'acid This can be done by exposing it to a base, such as a 0.5 to 15% solution of sodium hydroxide for a period of time, for example, 20 minutes.
- a base such as a 0.5 to 15% solution of sodium hydroxide for a period of time, for example, 20 minutes.
- a solution comprising acetic acid, an aminopolysaccharide compound, lithium chloride, and 15 sulfoxide a solution comprising dimethylacetamide, an aminopolysaccharide compound, lithium chloride, and a sulfoxide can be used. Where dimethylacetamide is used rather than acetic acid, it is unnecessary to neutralize the lens blank after forming it. 20 Spin Casting
- the spin casting mold is known in the art and can be made from a copolymer comprising methacrylate.
- a solution can be made of an aminopolysaccharide compound, 25 acetic acid or other substance which will facilitate the aminopolysaccharide compound going into solution by the formation of its soluble salt, and a solvent such as water. Again, the proportions of acetic acid and the aminopolysaccharide compound are not critical and can 30 range anywhere from 0.5% to 5% or more.
- the solution is introduced into the mold and spun.
- a source of heat such as a sun lamp, a vacuum arrangement, or some other means can be used to aid in the evaporation of the water from the solution as the mold is spinning.
- the spinning action can be stopped and the lens removed. If acetic acid or some other acid has been used to bring the aminopolysaccharide compound into solution, the acid in the lens blank should be neutralized. Preferably the lens blank is then thoroughly washed to remove caustic or other impurities. As known in the art, the curvature and thickness of the lens will be in part determined by the speed of rotation of the mold, the duration of spinning and the viscosity of the solution.
- a lens of the present invention can be made by machining or lathe cutting. Machining or lathe cutting involves obtaining a solid mass of the aminopolysaccharide compound lens material and removing with a lathe or other means the excess material, to yield a lens blank. With certain amino ⁇ polysaccharide compounds, a powder can be obtained and pressed together in a hot press to yield the solid mass of the substance. From this mass, a lens blank or lens replica can be machined. The lens blank or replica can then, be machined and polished finished to form a lens.
- a solution can be made comprising the aminopolysaccharide compound and acetic acid -in water.
- One layer of this solution can be evaporated down to a thin film, a second layer can be poured on top of it and evaporated down, and so on. Layers of the solution can repeatedly be evaporated until a workable thickness of the aminopoly ⁇ saccharide compound can be obtained.
- a workable thickness will be at least about 1/10 of an inch thick, or preferably, for reasons of ease in handling, at least about 1/8 of an inch thick. From this build-up of layers, a lens blank or lens replica can be machined, and then finished to form a lens.
- Example 1 Preparation of an Intentionally Purified Aminopolysaccharide Ester Compound, Namely, An Aminopolysaccharide Butyrate Into a suitable reaction vessel was charged and mixed 12 milliliters of liquid methanesulfonic acid and 18 milliliters of n-butyric anhydride. To this mixture, with kneading, at room temperature, was added 3 grams of raw chitin powder derived from crab. After kneading for 1 hour, the mixture resembled a paste.
- the product was tested for oxygen permeability at 37° C. using an oxygen flux meter and found to have an oxygen permeability -of 14 x lO"-*--*- ml (02)-cm-*-/sec-mL- mm Hg.
- the wettability of the product was determined by visual observation of the contact angle made with water, and the rate of wetting by water. The product was found to be adequately wettable without added wetting agent.
- Example 2 Contact lens from an Aminopolysaccharide Compound using a Stationary Casting Process
- an acrylic mold having a polished hemispheri- cal cavity of 14 millimeters in diameter was placed 1 milliliter of a 10% aqueous solution of poly-N-acetyl glucosamine derived from raw chitosan, and 1% acetic acid.
- the solution in the mold was allowed to dry at room temperature for 2 days. After 2 days, the dry casting was removed from the mold and placed into a
- the casting was allowed to soak in this solution for 1 hour and then washed 5 times with distilled water.
- the casting was a
- a 2% solution of poly-N-acetyl glucosamine derived from raw chitosan in 100 milliliters of water containing 2% acetic acid was plasticized by treatment with 1 gram di (hydroxyethyl)sulfoxide having a melting point of 112-113° C. and 1 gram lithium chloride. This mixture was thoroughly stirred.
- a soft flexible film was ob ⁇ tained by accumulating layers of material onto a poly- ethylene film and air-drying. The film was then molded ' in a steel mold at 90° C. under a platen pressure of 15,000 lbs., forming a lens blank. The lens blank was removed from the mold, and immersed in a 10% sodium hydroxide solution for 20 minutes. The lens blank was then repeatedly washed with distilled water until clear.
- This lens blank was observed to be soft, hydro- philic, water absorbing, and oxygen permeable.
- Example 5 One hundred milligrams of Cibacron blue TG-4, a fiber reactive dye produced by the Ciba-Geigy Company, was dissolved in 10 milliliters of water. Into the solution was placed a contact lens prepared by the stationary casting process shown in Example 2. The lens was soaked for 1 hour, removed from the solution, and then soaked for 30 minutes in 10 milliliters of a 1% sodium hydroxide solution. The lens was removed from the solution and then washed exhaustively with distilled water to obtain a tinted blue lens. The lens was placed in a bottle containing 25 milliliters of water for six months. An examination of the contents of the bottle revealed that no observable leaching of the dye from the lens had occurred.
- Example 6 Example 5 was repeated exactly with the exception that a lens obtained by the spin-casting process of Example 3 was used in the place of the lens obtained by the stationary casting process. No leaching of the dye could be observed.
- Example 7 Example 7
- Example 5 was repeated exactly with the exception that a lens obtained by the molding of an aminopolysac ⁇ charide compound derived from chitosan was used in the place of the lens obtained by the stationary casting process. Again, no leaching of the dye could be ob ⁇ served.
- Example 2 Into 15 milliliters of an aqueous 1% formaldehyde solution was placed the lens blank of Example 2, for 30 minutes. The lens blank was removed from solution and washed with 15 milliliters of distilled water 3 times.
- a semi-flexible lens blank was obtained.
- Example 8 was repeated exactly with the exception that 15 milliliters of an aqueous 1% glutaraldehyde solution was used in place of the 15 milliliters of an aqueous formaldehyde solution. The results were the same.
Abstract
An oxygen permeable, wettable, optically acceptable vision correction lens can be made from homopolymers of aminoglycans, substituted aminoglycans, or crosslinked polymers thereof.
Description
VISION CORRECTION LENS MADE FROM AN AMINOPOLYSACCHARIDE COMPOUND OR AN ETHER OR ESTER THEREOF
Field of the Invention The invention relates to a vision correction lens made from an aminopolysaccharide compound. More particularly the invention relates to an oxygen perme- able, wettable, optically acceptable lens which com¬ prises an unsubstituted or substituted aminopolysac¬ charide compound having ester or ether groups. Background of the Invention Vision correction lenses such as contact lenses and intraocular lenses have been known as commercial prod¬ ucts for over 25 years. An acceptable lens must be optically clear, mechanically stable, and must provide sufficient optical correction, gas permeability and wettability to insure that the lens is comfortable and safe during use. Gas permeability is important since the corneal surface of the eye respires by obtain¬ ing oxygen and other substances from tear fluid and by releasing carbon dioxide and other products of respira¬ tion into tear fluid. The intimate contact and position of the contact lens can substantially prevent the exchange of such constituents between the corneal epithelial cells and tear fluid. As a result the cornea can become starved for oxygen and can accumulate harmful amounts of metabolites within the constituent cells. This can result in corneal edema (swelling) and often extreme discomfort to the wearer. Wettability of the lens is important because a nonwettable lens can be abrasive and irritating to the eye and lid and can cause significant wearer discomfort. A lens must have suffi- cient mechanical integrity to allow for easy cleaning and handling and maintaining the desired curvature and correction for the individual user. The lens should be immunologically compatible with the eye, reducing
chances of allergic reaction or toxic response. Further the lens should be permanently dyeable,.. easily manufac¬ tured and available at low cost.
In the past contact lenses have been made from synthetic polymeric materials such as plastic matrices
■ based on polyacrylate, poly ethacrylate, polyhydroxy- ethylmethacrylate, cellulose acetate butyrate, sili- cones, etc. More recently contact lenses have, been made from collagen, a naturally occurring protein. Miyata, U.S. Patent No. 4,223,984 is primarily directed to a contact lens made from solubilized defatted transparent crosslinked collagen. Miyata, U.S. Patent 4,260,228 is particularly directed to an improved collagen gel soft contact lens prepared from an aldehyde crosslinked gel containing a polyhydroxy compound such as glucose.
Miyata, U.S. Patent 4,264,155 is primarily directed to an improved lens made from collagen gel to which a water soluble organic polyhydroxy polymer has been added.
Ivani, U.S. Patent 4,365,050 discloses and claims certain polymeric aminopolysaccharide compositions used in the fabrication of contact lenses which- are limited to graft and block copolymers of an acetyl glycosamine in combination with compounds selected from the group consisting of silicone, collagen, acrylonitrile, acryl- amide, methacrylates ,- alkyl methacrylates, alkyl amino alkylethacrylates, hydroxyalkyl methacrylates, pyrol- lidones, and vinyl derivatives of pyrollidone. Brief Description of the Invention I have found that an unsubstituted intentionally purified aminopolysaccharide compound or the ester and ether or amide derivatives of an aminopolysaccharide compound provide sufficient wettability, oxygen perme¬ ability, mechanical stability and optical clarity necessary for an effective vision correction lens. The first aspect of the invention is a hard or a soft contact lens which can be made from the aminopolysac¬ charide compounds of the invention. The second aspect of the invention is methods of forming the aminopoly-
saccharide compounds useful in forming vision correction lenses. A third aspect of the invention is an intraocu¬ lar lens which can be surgically placed in the eye to replace or supplement the natural lens. In this invention a lens blank or lens replica ' is an unfinished lens, having an approximately circular mass which can be ground, polished or otherwise shaped to the desired surface finish and dimensions of the lens. The lens blank or replica can have the approxi- mate dimensions of about 3/4 to 1 inch in diameter and about 5/8 to 1 inch in thickness (about 19 to 25 milli¬ meters in diameter and about 15 to 25 millimeters thickness). Oxygen gas permeability values (DR) are generally expressed in units of millimeters (02)-cm* sec.-mL./mm./Hg. Measurements of oxygen permeability are typically taken at 37° C. in an oxygen consuming electrode cell (oxygen flux meter). See J.-* Falk, Polarographic Oxygen Sensor, CRC Press, 1976. The oxygen permeability of contact lens materials can range from about 0.1 x lO"11 to 80 x lO"11 Dκ and higher. Oxygen permeablity of 4 x 10""11 or preferably 12 x 10""--*-** DR or greater has been shown to be beneficial to eye tissue, permitting sufficient exchange of nutrients between the corneal epithelium and tear. Wettability is typically measured on dry samples using a Kayness contact angle measurement. Contact angles of less than 75° and preferably less than 70° can indicate beneficial wettability.
Detailed Discussion of the Invention Briefly, the vision correction lenses of this invention are prepared from an unsubstituted intention¬ ally purified aminopolysaccharide or an ester ether or amide derivative of an aminopolysaccharide compound. The vision correction lenses of this invention have been found to be exceptionally oxygen permeable, highly wettable and capable of greatly extended wear. The lenses can be hard or soft, and can have portions of varying hardness. The soft lenses of the invention can
have substantial mechanical stability and beneficial hydrophilicity. The aminopolysaccharide lenses and compounds of this invention have the additional economic advantage that they are relatively inexpensive biocom- patible materials. The aminopolysaccharide source used in making the lenses are naturally occurring and readily available.
We have found that the lenses can be beneficial to eyes which have been abused, damaged, or injured. Aminopolysaccharide compounds have been shown to be useful in bandages, sutures, powders, etc. and can promote wound healing. A lens of this invention can be placed in an eye which has suffered abrasions or other injury from other contact lenses which can aid in the healing process while allowing sufficient vision correc¬ tion to the wearer.
We have also found that the lenses can contain phys iolog ically act ive compounds for the on-s ite controlled delivery for the treatment of ocular diseas- es . Addit ionally these lenses can be irreversibly tinted by exposure to fiber reactive dyes .
The aminopolysaccharide compounds useful in this invention for preparing vision correction lenses are derived generally from natural sources and comprise repeating units of N-substituted C5 or Cg amino- saccharides such as 2-amino ribose, 2-amino-glucose, 3-amino-galactose, including 2-(N-acetyl)-amino-glucose , 2- (N-acetyl ) -amino-galactose or mixtures thereof . Useful N-acetyl-aminopolysaccharides can be found in abundance in naturally occurring substances such as in the hard shell of insects , crustaceans , mollusks , fungi , cell wal ls , etc . In nature the aminopolysaccharide compounds are the major structural component in many animals and plants. For the purposes of this applica- tion chitin and ch itosan refer to the raw material derived from insect and crustacean shells from which a inopolysaccharides can be obtained . Generally the aminopolysaccharides used in forming the vision correc-
tion lenses of this invention are derived from chitin and chitosan by separating the aminopolysaccharides from calcium carbonate, protein, fats, and other naturally occurring substances that make up the shell. A major component of naturally occurring chitin is an N-acetyl glucosamine polymer. In chitin, the major proportion of the amino groups are acetylated while in chitosan the major proportion of the amino groups are generally free of any substituent. Chitin and chitosan comprise a broad spectrum of aminopolysaccharide compounds which cannot be easily distinguished because polysaccharide molecules can have various branchings, various types of saccharide units and various fractions of acetylated a ine groups. The amino group substituents can be naturally formed or can be formed during aminopolysac¬ charide purification or lens manufacture.
The vision correction lens of this invention can be made from an intentionally purified unsubstituted aminopolysaccharide compound. These compounds can be used once they are separated from the other components of chitin or chitosan. The unmodified substantially purified aminopolysaccharide compound has few substi¬ tuents on the 3, 4 and 6 hydroxyl groups of the molecule and has acetyl groups on the 2-amino group in an amount which corresponds to the naturally occurring amount characteristic of the source of the compound.
The vision correction lenses of this invention can be made from low molecular weight esters, ethers or amides of the aminopolysaccharide compound formed by reacting the aminopolysaccharide compound hydroxyl or amino groups with essentially monomeric non-polyme iz- able ether, ester or amide forming compounds. Amino¬ polysaccharide ether compounds can be made by any ether forming reaction. The Williamson synthesis reacting an alkyl halide with a sodium salt of the polysaccharide hydroxyl group is preferred. Other ether type substi¬ tuents can be used such as silicone type ethers, borane type ethers. Preferred ether groups are derived by
reacting an alkyl halide or an alkyl silicone halide with the aminopolysaccharide hydroxyl groups. A parti¬ cularly useful ether forming reagent for use with the aminopolysaccharide compounds of this invention are 5 lower alkyl halides or aryl substituted alkyl halides, - preferably Cι~Cg alkyl chlorides including methyl chloride, ethyl bromide, isopropyl iodide, tertiary butyl chloride, cyclohexyl chloride, benzyl chloride, etc. Methyl chloride and benzyl chloride are generally
10 preferred in this reaction since they react smoothly in good yield and without substantial degradation. An appropriate catalyst to facilitate the reaction between the alkyl halides is any generally basic catalyst such as sodium hydroxide, potassium hydroxide, magnesium
15 hydroxide, etc. These materials can be suspended or dissolved in substantially nonreactive polar solvents such as methyl ethyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide, etc.
Ester derivatives can be formed by "reacting the
20 polysaccharide hydroxyl groups with a hydroxyl reactive acid compound. Hydroxyl reactive acid compounds can include carboxylic acids, carboxylic acid anhydrides, carboxylic acid halides, sulfonic acids, phosphoric acids, boric acid compounds, etc. Preferred ester
25 forming reagents include the reactive carboxylic anhy¬ dride and carboxylic acid halide compounds.
A particularly useful esterifying agent for use with the aminopolysaccharide compounds of this invention are carboxylic acid anhydrides such as ri-butyric anhy-
30 dride, valeric anhydride, propionic anhydride, isobuty- ric anhydride, caproic anhydride, caprylic anhydride, heptanoic anhydride, nonylic anhydride, undecylic anhydride, succinic anhydride and maleic anhydride. In this invention, the carboxylic acid anhydrides are
3.5 generally preferred since they react smoothly, in good yield, and without substantial degradation. A preferred compound is ri-butyric anhydride for reasons of its effectiveness. An appropriate catalyst to facilitate
the reaction between the butyric anhydride and the' aminopolysaccharide compound is any generally acidic catalyst. Acidic compositions such as phosphoric acids, acidic resins, sulfonic acids and others can be used. These materials can be suspended in a substantially nonreactive but polar solvent such as methylethylketone, methylisobutylketone, N,N-dimethylformamide, and di- methylacetamide. Amides are prepared similarly to the ester except that the starting material usually is an aminopolysaccharide containing a large proportion of free amino groups.
Crosslinking The aminopolysaccharide compounds of this inven¬ tion can be crosslinked in order to increase the durability, mechanical stability, and useful life. Biologically derived materials such as aminopolysac¬ charides can be biodegradable and can be slowly attached in the eye through the naturally occurring response of the eye to the foreign aminopolysaccharide substance. Crosslinking of the aminopolysaccharides can act to counteract the tendency of the lens to biodegrade. Crosslinking acts to stop biodegradation by crosslinking between hydroxyl groups between amino groups and between hydroxyl and amino groups in adjacent aminopolysac- charide molecules. These bonds can cause the functional groups of the aminopolysaccharide compound to be less subject to biodegrading substances in tear fluid such as enzymes and antibodies. Crosslinking can be carried out by exposing the aminopolysaccharide compound, the aminopolysaccharide compound lens blank or replica, or finished lens to a suitable crosslinking agent. Cross¬ linking agents comprise polyfunctional compounds having hydroxyl or amino reactive moieties separated by a group sufficient that the moieties can react with separate, adjacent aminopolysaccharide molecules. Examples of useful crosslinking agents which may be employed to form the contact lens compositions of the invention include di-, tri- and tetra-substituted carboxylic acid com-
pounds, aliphatic aromatic diisocyanates, polyfunctional chlorofor ates, polyfunctional sulfonyl chlorides, aldehyde crosslinking agents, acrolein, dyoxal, dialde- hyde starch, etc. Fiber Reactive Dyes
The lens or lens composition can be substantially permanently dyed using fiber reactive dyes, that is, those dyes containing a functional or reactive group capable of attaching the chromophore groups by forming covalent chemical bonds with hydroxyl or amino func¬ tional groups of the aminopolysaccharide compound The chromophore group can be an azo compound, which can yield a red, blue, violet, or yellow tint, an anthra- quinone compound, which can yield a royal blue tint, a phthalocyanine residue, for a turquoise blue tint, or other chromophore groups known in the art. Other suit¬ able dye stuffs can include a monochlorotriazine group, dichlorotriazine group, vinyl sulfone group, trichloro- pyrimidyl group, dichloroquinoxaline group, ethylene sulfonimide group, cyclic ethylene immonium-type group, and acrylamide group, among others. While most fiber reactive dyes find utility in this invention, the preferred dyes are the chlorotriazine dyes, because of their accessibility, the large amount of information available on these dyes, their relative reactivity at room temperature,, and the broad range of colors avail¬ able.
Where the reactive group of the dye contains a chlorine, it is expected that the chlorine will combine with a hydrogen of an amino or hydroxyl group of the aminopolysaccharide compound, yielding HC1 by-pro¬ duct. A covalent bond thus forms between the carbon atom of the dye and the amino or hydoxyl group of the aminopolysaccharide compound. Fiber reactive dyes and other suitable substances can also be used with the lenses and lens compositions of this invention to yield a substantially opaque lens. An opaque lens can be desirable when for medical or
other reasons it is desired to shield an eye tissue from light. An opaque lens of this invention can in many instances be worn in place of the traditional eye patch which can be uncomfortable and cosmetically unattractive.
For a discussion of fiber reactive dyes, see Beech, W. F., Fiber Reactive Dyes, Logos Press, Ltd., London, 1970.
Physiologically Active Compounds Physiologically active compounds can also be included in the lens or lens composition. These com¬ pounds can include antibiotics such as tetracycline, bacitracin, and neomycin, antiallergic products such as chlorphenira ine, decongestive substances such as pseudoephedrine and tetrahydrazoline, antiviral products such as idoxuridine, and other substances such as analgesics, anaesthetics, antiseptics, and others. When included in the lens, the physiologically active com¬ pounds can be released at a controlled rate upon the placing of the lens in the eye.
Other Components If desired, other constituents such as humectants can be incorporated into the lens composition. Suit¬ able humectants can stabilize the vision correction lenses to effects of water. Such constituents having a significant degree of compatibility with aminopolysac¬ charide compounds include glycerol, ethylene glycol, propylene glycol, and sorbitol.
A plasticizer can be particularly advantageous in the context of this invention in order to more easily compound or form the aminopolysaccharide compound. Without a plasticizer, the forces between the chains of molecules in the aminopolysaccharide compound can often be so strong as to prevent slippage of the molecules preventing the lens material from conforming to a mold. The plasticizer can reduce the bonding force between the chains of molecules allowing them to take the shape of the mold. The plasticizer can reduce the hydrogen
bonding between the functional group of one polymer molecule, and functional groups of another. While the plasticizer can be removed from the lens to create the finished product, the plasticizer can also be left in the lens if nontoxic and stable.
Methods of Making Suitable Substituted Aminopolysaccharide Compound Turning now to the methods of making a substituted aminopolysaccharide compound which can be used in forming the oxygen permeable, wettable, optically clear lens of the invention, a mixture comprising an ether- forming, ester-forming or amide-forming agent such as an alkyl halide, carboxylic acid anhydride or an acid chloride, a naturally occurring raw chitin comprising an aminopolysaccharide compound, and a catalyst which facilitates a reaction between the ether- , ester- or amide-forming agent and the aminopolysaccharide compound can be formed. Second, the mixture is suspended in a substantially nonreactive solvent, to facilitate admix- ture and reaction of the agent, the aminopolysaccharide compound, and the catalyst. As the aminopolysaccharide compound and the agent react, the reaction product passes into solution. In order to isolate the deriva- tized aminopolysaccharide, a precipitating amount of an anti-solvent, which is substantially miscible with the nonreactive solvent is added to the filtered reaction liquor to precipitate the reaction product of the aminopolysaccharide compound and the ether-, ester- or amide-forming agent. Examples of appropriate anti-sol- vents include water, methanol, ethyl alcohol, etc. Next, any excess agent can be removed. This can be done by hydrolysis, ion exchange, neutralization, dialysis, washing or other techniques.
Last, the precipitate can be collected, for example, by filtration, and washed, for example, with distilled water, to remove any remaining traces of agent, salt or other undesirable materials.
Forming a Contact Lens The lens of this invention can be formed from the aminopolysaccharide compound by a variety of methods. Stationary casting, spin casting, molding, and lathe cutting, can be useful processes for fabricating the lenses.
Stationary Lens Casting To form a lens by stationary casting, a lens-form¬ ing amount of a solution comprising a sufficient amount of aminopolysaccharide compound or derivatives, dis¬ solved or suspended in an appropriate solvent can be added to a mold for stationary casting. A lens blank or lens replica can be formed in this mold by removing the solvent and then the lens can be finished for use in the eye. In more detail, the aminopolysaccharide compound can be brought into solution or suspension by combining it with acetic acid and water, for example, a solution comprising 0.5 to 5% of an aminopolysaccharide compound, 0.5 to 5% acetic acid, and water. Generally, aminopolysaccharide compounds are insoluble in water. However, with the addition of a solubilizing amino salt forming acid such as acetic acid other appropriate compound, a soluble salt of the aminopolysaccharide compound can form. When acetic acid is used, the acetate salt of the amino group can form. This solution can be introduced into a suitable lens shaped mold. A suitable mold can be made of an acrylic material, with a polished hemispherical cavity and a diameter of, for example, 10-20 millimeters, and a depth of approximately 10-20 mm. Solvent is removed from the the solution in the mold. This can be accom¬ plished by use of a vacuum system, a heat source such as a sun lamp, or simply at ambient temperature and by any known means. When the casting is dry, it can be removed from the mold. It is advisable to wash or neutralize the casting, in order to remove traces of acetic or other acid which may be present. This can be done by exposure of the casting to an appropriate base, for
example, by soaking the casting in a 0.5% to 15% aqueous solution of sodium hydroxide. If a 5% solution is used, it is advisable to soak the casting for about an hour.
Following this procedure, it is advisable to further cleanse the casting to remove traces of the strong base. This can be done by washing the casting, for example, repetitively rinsing it with distilled water.
High Pressure Lens Fabrication
Another method for making a lens from, an aminopoly- saccharide compound or derivative thereof involves forming the lens in a mold using high pressure using a plasticizer if necessary. In this method, first a soft flexible film is created from the aminopolysaccharide compound, and the film is molded to form the lens blank or replica. The mold can be of a type known in the art, for example, made of steel and used under conditions known in the art such as 90° C. with a platen pressure of 15,000 lbs.
In order for the lens blank or lens replica to hold the shape of the mold, the aminopolysaccharide compound can be plasticized before molding. First, a solution can be made comprising acetic acid, an amino¬ polysaccharide compound, a plasticizer, and an agent to disrupt the molecular structure of the aminopolysac- charide compound. A typical solution can be 0.5 to 5% aminopolysaccharide compound, 0.5 to 5% acetic acid, di(hydroxyethyl)sulfoxide, and lithium chloride. The lithium chloride can act as the disrupting agent, that is, it can break up the molecular order of the amino- polysaccharide compound, thus permitting it to interact more readily with the sulfoxide. The sulfoxide can work as the plasticizer, where it reduces the hydrogen bonding between molecules and thus allows the chains of molecules in the aminopolysaccharide compounds to more easily slip past one another and conform to and hold the shape of the mold.
The mixture identified above can be thoroughly stirred to facilitate interaction of the . components.
Then it can be formed into a soft flexible film, for example by pouring it onto a polyethylene film and drying. The soft flexible film can then be molded in a mold known in the art, forming a lens blank or replica.
5 It is preferable to neutralize the lens blank to remove
' any traces of acetic'acid. This can be done by exposing it to a base, such as a 0.5 to 15% solution of sodium hydroxide for a period of time, for example, 20 minutes.
It is then advisable to remove traces of the base, or
10 for example by repeatedly washing the lens blank with water, preferably for reasons of purity, distilled water.
Instead of a solution comprising acetic acid, an aminopolysaccharide compound, lithium chloride, and 15 sulfoxide, a solution comprising dimethylacetamide, an aminopolysaccharide compound, lithium chloride, and a sulfoxide can be used. Where dimethylacetamide is used rather than acetic acid, it is unnecessary to neutralize the lens blank after forming it. 20 Spin Casting
Another method for forming a lens involves spin casting. The spin casting mold is known in the art and can be made from a copolymer comprising methacrylate. A solution can be made of an aminopolysaccharide compound, 25 acetic acid or other substance which will facilitate the aminopolysaccharide compound going into solution by the formation of its soluble salt, and a solvent such as water. Again, the proportions of acetic acid and the aminopolysaccharide compound are not critical and can 30 range anywhere from 0.5% to 5% or more. The solution is introduced into the mold and spun. A source of heat such as a sun lamp, a vacuum arrangement, or some other means can be used to aid in the evaporation of the water from the solution as the mold is spinning. When 3.5 the lens blank or lens replica is dry, the spinning action can be stopped and the lens removed. If acetic acid or some other acid has been used to bring the aminopolysaccharide compound into solution, the acid in
the lens blank should be neutralized. Preferably the lens blank is then thoroughly washed to remove caustic or other impurities. As known in the art, the curvature and thickness of the lens will be in part determined by the speed of rotation of the mold, the duration of spinning and the viscosity of the solution.
Machining It is also envisioned that a lens of the present invention can be made by machining or lathe cutting. Machining or lathe cutting involves obtaining a solid mass of the aminopolysaccharide compound lens material and removing with a lathe or other means the excess material, to yield a lens blank. With certain amino¬ polysaccharide compounds, a powder can be obtained and pressed together in a hot press to yield the solid mass of the substance. From this mass, a lens blank or lens replica can be machined. The lens blank or replica can then, be machined and polished finished to form a lens.
For certain aminopolysaccharide compounds, such as the aminopolysaccharide derived from chitosan, it is preferred to form a solid mass from the solution. A solution can be made comprising the aminopolysaccharide compound and acetic acid -in water. One layer of this solution can be evaporated down to a thin film, a second layer can be poured on top of it and evaporated down, and so on. Layers of the solution can repeatedly be evaporated until a workable thickness of the aminopoly¬ saccharide compound can be obtained. Generally, a workable thickness will be at least about 1/10 of an inch thick, or preferably, for reasons of ease in handling, at least about 1/8 of an inch thick. From this build-up of layers, a lens blank or lens replica can be machined, and then finished to form a lens.
The following specific Examples which include the best mode were prepared and tested as described.
Example 1 Preparation of an Intentionally Purified Aminopolysaccharide Ester Compound, Namely, An Aminopolysaccharide Butyrate Into a suitable reaction vessel was charged and mixed 12 milliliters of liquid methanesulfonic acid and 18 milliliters of n-butyric anhydride. To this mixture, with kneading, at room temperature, was added 3 grams of raw chitin powder derived from crab. After kneading for 1 hour, the mixture resembled a paste. To the resulting paste was added 70 milliliters acetone, to the thus- formed acetone solution was added, with vigorous stir¬ ring, 500 milliliters of ice water, forming a precipi¬ tate comprising a colorless amorphous powder. The precipitate was washed with 300 milliliters of water, 3 times. It was then suspended in 300 milliliters of water and neutralized to a pH of 7.0 using 7 milliliters of 1% NH4OH. The suspension was boiled for 5 minutes. Next the precipitate was collected by filtration, washed 3 times with 300 milliliter portions of water and dried overnight at 105° C. to yield 4.1 grams of the perbuty- rated aminopolysaccharide compound.
The product was tested for oxygen permeability at 37° C. using an oxygen flux meter and found to have an oxygen permeability -of 14 x lO"-*--*- ml (02)-cm-*-/sec-mL- mm Hg.
The wettability of the product was determined by visual observation of the contact angle made with water, and the rate of wetting by water. The product was found to be adequately wettable without added wetting agent.
Example 2 Contact lens from an Aminopolysaccharide Compound using a Stationary Casting Process Into an acrylic mold having a polished hemispheri- cal cavity of 14 millimeters in diameter was placed 1 milliliter of a 10% aqueous solution of poly-N-acetyl glucosamine derived from raw chitosan, and 1% acetic acid. The solution in the mold was allowed to dry at
room temperature for 2 days. After 2 days, the dry casting was removed from the mold and placed into a
5% aqueous solution of sodium hydroxide. The casting was allowed to soak in this solution for 1 hour and then washed 5 times with distilled water. The casting was a
- strong, clear, soft lens blank with excellent optics and a water content of 49%. The oxygen permeability of the lens blank was tested at 37° C. using an oxygen flux meter and found to be 7 x 10"11 ml(02)-cm2/sec-mL-mm Hg. Example 3
• Preparation of an Aminopolysaccharide Compound Lens by Spin Casting An acrylic mold for spin casting was made from a 16 millimeter' diameter button of a copolymer of 2-hy- droxyethylmethacrylate and methyl methacrylate. The inside curvature of the mold was 12.5 millimeters. The mold was held on .the shaft of a rotating spindle by a grip arrangement.
Into the mold was poured in a quantity to substan- tially fill it, a 4%- aqueous solution of poly-N-acetyl glucosamine derived from raw chitosan. The spindle was rotated while a 275 watt sunlamp was held over the mold at a distance of 8 centimeters. When the lens was dry, the spindle was stopped, the mold removed, and the lens blank removed from the mold. The lens blank was then soaked for 1 hour in a 10% NaOH solution. After soak¬ ing, the lens blank was washed thoroughly with distilled water.
A soft, clear, hydrophilic, water absorbing, oxygen permeable lens blank with excellent optics was obtained.
Example 4 Preparation of an Aminopolysaccharide Lens by Molding of an Aminopolysaccharide Compound Derived from Chitosan
A 2% solution of poly-N-acetyl glucosamine derived from raw chitosan in 100 milliliters of water containing 2% acetic acid was plasticized by treatment with 1 gram
di (hydroxyethyl)sulfoxide having a melting point of 112-113° C. and 1 gram lithium chloride. This mixture was thoroughly stirred. A soft flexible film was ob¬ tained by accumulating layers of material onto a poly- ethylene film and air-drying. The film was then molded ' in a steel mold at 90° C. under a platen pressure of 15,000 lbs., forming a lens blank. The lens blank was removed from the mold, and immersed in a 10% sodium hydroxide solution for 20 minutes. The lens blank was then repeatedly washed with distilled water until clear.
This lens blank was observed to be soft, hydro- philic, water absorbing, and oxygen permeable.
Example 5 One hundred milligrams of Cibacron blue TG-4, a fiber reactive dye produced by the Ciba-Geigy Company, was dissolved in 10 milliliters of water. Into the solution was placed a contact lens prepared by the stationary casting process shown in Example 2. The lens was soaked for 1 hour, removed from the solution, and then soaked for 30 minutes in 10 milliliters of a 1% sodium hydroxide solution. The lens was removed from the solution and then washed exhaustively with distilled water to obtain a tinted blue lens. The lens was placed in a bottle containing 25 milliliters of water for six months. An examination of the contents of the bottle revealed that no observable leaching of the dye from the lens had occurred.
Example 6 Example 5 was repeated exactly with the exception that a lens obtained by the spin-casting process of Example 3 was used in the place of the lens obtained by the stationary casting process. No leaching of the dye could be observed. Example 7
Example 5 was repeated exactly with the exception that a lens obtained by the molding of an aminopolysac¬ charide compound derived from chitosan was used in the
place of the lens obtained by the stationary casting process. Again, no leaching of the dye could be ob¬ served.
Example 8 Crosslinking of an Aminopolysaccharide
Lens Derived from Raw Chitosan
Into 15 milliliters of an aqueous 1% formaldehyde solution was placed the lens blank of Example 2, for 30 minutes. The lens blank was removed from solution and washed with 15 milliliters of distilled water 3 times.
A semi-flexible lens blank was obtained.
Example 9
Example 8 was repeated exactly with the exception that 15 milliliters of an aqueous 1% glutaraldehyde solution was used in place of the 15 milliliters of an aqueous formaldehyde solution. The results were the same.
Example 10 Wound Healing Property of.Contact Lens Based on Aminopolysaccharide
Fifty lenses were made by the stationary casting process as previously described. Incisions were made in the eyes of rabbits and the lenses were placed over these incisions. Accelerated healing of wounds was observed.
The following Table summarizes the experimental results presented in the above described Examples:
TABLE OF RESULTS
Tinted by Cross¬ Cross-
Oxygen Exposure linking linking
Permeability to Fiber Subjective with with Glutar- IDK/J-J Wettability Reactive Dye Results Formaldehyde aldehyde
Aminopoly¬ 14 x lO-11 No added saccharide wetting butyrate agent contact needed lens material
Stationary 7 x 10"11 no leaching strong. semi- semi- cast of dye clear, soft. flexible flexible aminopoly¬ excellent lens blank lens blank saccharide optics. obtained obtained lens contains
49% water
Spin cast no leaching clear, soft. aminopoly¬ of dye excellent saccharide optics, hydro* lens philic, water absorbing, oxygen permeable
Molded no leaching soft, hydro- aminopoly¬ of dye philic, water saccharide absorbing, lens oxygen permeable
The foregoing Examples and discussion is a descrip¬ tion of the invention. However, since many embodiments can be made without departing from the spirit and scope of the invention, the invention resides in the claims hereinafter appended.
Claims
rece ve y e n erna ona ureau on ay . . ; new claims 18-35 added (3 pages)] the vision correction lens also contains a physiologi¬ cally active compound dispersed throughout the lens material.
16. A method of forming a vision correction lens which comprises the steps of:
(a) adding a lens forming amount of a solu¬ tion of a homopolymer of an aminoglycan or a crosslinked homopolymers thereof in an appropriate solvent into a mold for stationary casting; (b) forming a lens blank or lens replica, and finishing the lens.
17. A method of forming a vision correction lens which comprises the steps of:
(a) plasticizing a homopolymer of an amino- glycan or a crosslinkled homopolymer thereof dis¬ solved in an appropriate solvent to form a plas- ticized lens material;
(b) forming the plasticizing material into a lens blank or lens replica; and (c) finishing the lens.
18. An oxygen permeable, wettable, optically acceptable wound healing lens consisting essentially of a homopolymer of an aminoglycan.
19. The wound healing lens of claim 18 wherein the amino groups of the hompolymer of the aminoglycan have amide substituents.
20. The wound healing lens of claim 19 wherein the amide substituents are of natural origin.
21. The wound healing lens of claim 29 wherein the amide substituents are of synthetic origin.
22. The wound healing lens of claim 18 wherein the homopolymer is crosslinked.
23. The wound healing lens of claim 18 wherein the aminoglycan comprises a glucosamine, an N-acetyl glucosamine, a galactosamine, and N-acetyl galacto¬ samine, or mixtures thereof.
24. The wound healing lens of claim 18 wherein the homopolymer is an ester of the homopolymer.
25. The wound healing lens of cliam 24 wherein the ester of the homopolymer is a carboxylate ester.
26. The wound healing lens of cliam 25 wherein the carboxylate ester is abutyrate, an acetate, a benzoate, or a succinate ester.
27. The wound healing lens of claim 18 wherein the homopolymer is an ether of the homopolymer.
28. The wound healing lens of claim 27 wherein the ester is a methyl ether, an ethyl ether, a hydroxyl ethyl ether, or an isopropyl ether.
29. The wound healing lens of claim 26 wherein the ether is a silanol ether.
30. The wound healing lens of claim 18 wherein the lens is colored by reacting the homopolymer with a fiber reactive dye.
31. The wound healing lens of claim 22 wherein the homopolymer is crosslinked using an aldehyde com¬ pound crosslinking agent.
32. The wound healing lens of claim 18 wherein the vision correction lens also contains a physiologi¬ cally active compound dispersed throughout the lens material.
33. The lens of claim 18 wherein the lens para¬ meters provide optical vision correction. 34. A method of forming a vision correction lens which comprises the steps of:
(a) adding a lens forming amount of a solution of a homopolymer of an aminoglycan or a crosslinked homopolymer thereof in an appropriate solvent into a mold for stationary casting;
(b) forming a lens blank or lens replica, and finishing the lens.
35. A method of forming a vision correction lens which comprises the steps of: (a) plasticizing a homopolymer of an amino¬ glycan or a crosslinked homopolymer thereof dis¬ solved in an appropriate solvent to form a plas- ticized lens material;
(b) forming the plasticizing material into a lens blank or lens replica; and
(c) finishing the lens.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US580,518 | 1984-02-15 | ||
US06/580,518 US4532267A (en) | 1984-02-15 | 1984-02-15 | Vision correction lens made from an aminopolysaccharide compound or an ether or ester thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1985003716A1 true WO1985003716A1 (en) | 1985-08-29 |
Family
ID=24321429
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1985/000169 WO1985003716A1 (en) | 1984-02-15 | 1985-01-31 | Vision correction lens made from an aminopolysaccharide compound or an ether or ester thereof |
Country Status (5)
Country | Link |
---|---|
US (1) | US4532267A (en) |
EP (1) | EP0172227A4 (en) |
JP (1) | JPS61501729A (en) |
CA (1) | CA1235264A (en) |
WO (1) | WO1985003716A1 (en) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4716224A (en) * | 1984-05-04 | 1987-12-29 | Seikagaku Kogyo Co. Ltd. | Crosslinked hyaluronic acid and its use |
US4863907A (en) * | 1984-06-29 | 1989-09-05 | Seikagaku Kogyo Co., Ltd. | Crosslinked glycosaminoglycans and their use |
JPH07110893B2 (en) * | 1984-11-30 | 1995-11-29 | 大西 靖彦 | Matrix polymer manufacturing method |
US4883864A (en) * | 1985-09-06 | 1989-11-28 | Minnesota Mining And Manufacturing Company | Modified collagen compound and method of preparation |
US4851513A (en) * | 1985-09-06 | 1989-07-25 | Minnesota Mining And Manufacturing Company | Viscoelastic collagen solution for opthalmic use and method of preparation |
US4713446A (en) * | 1985-09-06 | 1987-12-15 | Minnesota Mining And Manufacturing Company | Viscoelastic collagen solution for ophthalmic use and method of preparation |
US5300494A (en) * | 1986-06-06 | 1994-04-05 | Union Carbide Chemicals & Plastics Technology Corporation | Delivery systems for quaternary and related compounds |
US4946870A (en) * | 1986-06-06 | 1990-08-07 | Union Carbide Chemicals And Plastics Company Inc. | Delivery systems for pharmaceutical or therapeutic actives |
JP2564520B2 (en) * | 1986-08-21 | 1996-12-18 | ユニチカ株式会社 | Contact lens manufacturing method |
US5103840A (en) * | 1990-05-07 | 1992-04-14 | Kavoussi Harold P | Viscoelastic collagen gel for ophthalmic surgery |
US5157093A (en) * | 1990-05-10 | 1992-10-20 | Ciba-Geigy Corporation | Hydroxyethyl cellulose derivatives containing pendant (meth)acryloyl units bound through urethane groups and hydrogel contact lenses made therefrom |
US6692525B2 (en) | 1992-02-28 | 2004-02-17 | Advanced Medical Optics, Inc. | Intraocular lens |
JP3662253B2 (en) * | 1994-03-14 | 2005-06-22 | 生化学工業株式会社 | Eye mounting material |
US5597811A (en) * | 1995-04-10 | 1997-01-28 | Amerchol Corporation | Oxirane carboxylic acid derivatives of polyglucosamines |
US6264841B1 (en) | 1995-06-30 | 2001-07-24 | Helen E. A. Tudor | Method for treating contaminated liquids |
US5789462A (en) * | 1995-09-13 | 1998-08-04 | Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) | Photocured crosslinked-hyaluronic acid contact lens |
JP4049411B2 (en) * | 1997-06-27 | 2008-02-20 | 株式会社メニコン | Rigid contact lens ring and hard contact lens composite using the same |
US6468306B1 (en) | 1998-05-29 | 2002-10-22 | Advanced Medical Optics, Inc | IOL for inhibiting cell growth and reducing glare |
WO2013112875A1 (en) * | 2012-01-25 | 2013-08-01 | The University Of Akron | Wound dressings with enhanced gas permeation and other beneficial properties |
GB2501943B (en) * | 2012-05-10 | 2020-09-23 | Zeiss Carl Meditec Ag | Ophthalmic viscoelastic device |
Citations (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3332897A (en) * | 1964-12-21 | 1967-07-25 | Nat Starch Chem Corp | Process of grafting monomers onto polysaccharides, and acylating product to obtain an ester |
US3414530A (en) * | 1965-12-23 | 1968-12-03 | Agriculture Usa | Graft polymers of polyalkylene oxides on starch and dextrin |
US3632754A (en) * | 1968-02-12 | 1972-01-04 | Lescarden Ltd | Use of chitin for promoting wound healing |
US3770673A (en) * | 1971-11-04 | 1973-11-06 | R Slagel | Chitosan graft copolymer for making paper products of improved dry strength |
US3847897A (en) * | 1971-09-07 | 1974-11-12 | Ralston Purina Co | Microcrystalline chitin |
US3892731A (en) * | 1973-11-23 | 1975-07-01 | Univ Delaware | Solvents for and purification of chitin |
US3988411A (en) * | 1974-02-11 | 1976-10-26 | American Cyanamid Company | Spinning and shaping poly-(N-acetyl-D-glucosamine) |
US4029727A (en) * | 1975-04-16 | 1977-06-14 | The University Of Delaware | Chitin films and fibers |
US4059457A (en) * | 1976-02-19 | 1977-11-22 | The University Of Delaware | Chitin solution |
US4063016A (en) * | 1975-12-15 | 1977-12-13 | University Of Delaware | Chitin complexes with alcohols and carbonyl compounds |
US4168112A (en) * | 1978-01-05 | 1979-09-18 | Polymer Technology Corporation | Contact lens with a hydrophilic, polyelectrolyte complex coating and method for forming same |
US4223984A (en) * | 1979-04-04 | 1980-09-23 | Opticol Corporation | Collagen soft contact lens |
US4242291A (en) * | 1979-05-09 | 1980-12-30 | Battelle Development Corporation | Collagen reconstitution |
US4260228A (en) * | 1980-01-21 | 1981-04-07 | Opticol Corporation | Collagen gel contact lens and method of preparation |
US4264155A (en) * | 1979-07-09 | 1981-04-28 | Opticol Corporation | Collagen contact lens |
US4264493A (en) * | 1978-10-18 | 1981-04-28 | Battista Orlando A | Natural protein polymer hydrogels |
US4365050A (en) * | 1981-07-15 | 1982-12-21 | Ivani Edward J | Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions |
US4416814A (en) * | 1981-03-23 | 1983-11-22 | Battista Orlando A | Protein polymer hydrogels |
US4451629A (en) * | 1981-01-12 | 1984-05-29 | Toyo Contact Lens Co., Ltd. | Contact lens and process for preparing the same |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5241797B2 (en) * | 1974-04-05 | 1977-10-20 | ||
US3998411A (en) * | 1976-02-17 | 1976-12-21 | Mcdonnell Douglas Corporation | Speed overshoot correction system |
DE2963348D1 (en) * | 1978-10-18 | 1982-09-02 | Essilor Int | Hydrogels from natural protein polymers, their production and soft contact lenses made from them |
US4268131A (en) * | 1979-04-11 | 1981-05-19 | Opticol Corporation | Fiber collagen contact lens |
JPS5678854A (en) * | 1979-11-30 | 1981-06-29 | Ricoh Co Ltd | Copying method for reciprocative scanning of original |
JPS5694322A (en) * | 1979-12-27 | 1981-07-30 | Mitsubishi Rayon Co Ltd | Contact lens |
JPS56149014A (en) * | 1980-04-22 | 1981-11-18 | Agency Of Ind Science & Technol | Soft contact lens |
US4440541A (en) * | 1982-05-20 | 1984-04-03 | Polaroid Corporation | Polarizer: dichroic dye in oriented polyacrylic acid/chitosan complex sheet |
-
1984
- 1984-02-15 US US06/580,518 patent/US4532267A/en not_active Expired - Fee Related
-
1985
- 1985-01-22 CA CA000472558A patent/CA1235264A/en not_active Expired
- 1985-01-31 JP JP60500813A patent/JPS61501729A/en active Pending
- 1985-01-31 EP EP19850901178 patent/EP0172227A4/en not_active Withdrawn
- 1985-01-31 WO PCT/US1985/000169 patent/WO1985003716A1/en not_active Application Discontinuation
Patent Citations (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3332897A (en) * | 1964-12-21 | 1967-07-25 | Nat Starch Chem Corp | Process of grafting monomers onto polysaccharides, and acylating product to obtain an ester |
US3414530A (en) * | 1965-12-23 | 1968-12-03 | Agriculture Usa | Graft polymers of polyalkylene oxides on starch and dextrin |
US3632754A (en) * | 1968-02-12 | 1972-01-04 | Lescarden Ltd | Use of chitin for promoting wound healing |
US3847897A (en) * | 1971-09-07 | 1974-11-12 | Ralston Purina Co | Microcrystalline chitin |
US3770673A (en) * | 1971-11-04 | 1973-11-06 | R Slagel | Chitosan graft copolymer for making paper products of improved dry strength |
US3892731A (en) * | 1973-11-23 | 1975-07-01 | Univ Delaware | Solvents for and purification of chitin |
US3988411A (en) * | 1974-02-11 | 1976-10-26 | American Cyanamid Company | Spinning and shaping poly-(N-acetyl-D-glucosamine) |
US4029727A (en) * | 1975-04-16 | 1977-06-14 | The University Of Delaware | Chitin films and fibers |
US4063016A (en) * | 1975-12-15 | 1977-12-13 | University Of Delaware | Chitin complexes with alcohols and carbonyl compounds |
US4059457A (en) * | 1976-02-19 | 1977-11-22 | The University Of Delaware | Chitin solution |
US4168112A (en) * | 1978-01-05 | 1979-09-18 | Polymer Technology Corporation | Contact lens with a hydrophilic, polyelectrolyte complex coating and method for forming same |
US4264493A (en) * | 1978-10-18 | 1981-04-28 | Battista Orlando A | Natural protein polymer hydrogels |
US4223984A (en) * | 1979-04-04 | 1980-09-23 | Opticol Corporation | Collagen soft contact lens |
US4242291A (en) * | 1979-05-09 | 1980-12-30 | Battelle Development Corporation | Collagen reconstitution |
US4264155A (en) * | 1979-07-09 | 1981-04-28 | Opticol Corporation | Collagen contact lens |
US4260228A (en) * | 1980-01-21 | 1981-04-07 | Opticol Corporation | Collagen gel contact lens and method of preparation |
US4451629A (en) * | 1981-01-12 | 1984-05-29 | Toyo Contact Lens Co., Ltd. | Contact lens and process for preparing the same |
US4416814A (en) * | 1981-03-23 | 1983-11-22 | Battista Orlando A | Protein polymer hydrogels |
US4365050A (en) * | 1981-07-15 | 1982-12-21 | Ivani Edward J | Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions |
Non-Patent Citations (7)
Title |
---|
Arch Ophthalmol, Volume 97, December 1979, RONALD C. PRUETT et al, "Hyaluronic Acid Vitreous Substitute", pages 2325-2330 * |
KYU-HYUNG CHO, "Secret Family Prescriptions: Collection of special Medicaments for Sovereign Remedies, Volumes I & II, 10th Edition, published 1979 by Bumjin Moonhwa-SA (Seoul, Kores), see pages 26, 27, 262, 263 & 496 * |
PRUBBEN, "The Discovery of a Potent Pure Chemical Wound-Healing Accelerator", The American Journal of Surgery, pages 561-564, May 1970 * |
R.A.A. MUZZARELLI, "Chitin", published 1977 by Pergaman Press (New York), see pages 69-78. * |
See also references of EP0172227A4 * |
The Condensed Chemical Dictionary, Sixth Edition, Reinhold Publishing Corporation, New York, 1961, pages 251 & 581 * |
The Merck Index, Eigth Edition Merck & Co., Inc., N.Y., 1968, page 537 * |
Also Published As
Publication number | Publication date |
---|---|
EP0172227A1 (en) | 1986-02-26 |
CA1235264A (en) | 1988-04-19 |
EP0172227A4 (en) | 1987-10-20 |
US4532267A (en) | 1985-07-30 |
JPS61501729A (en) | 1986-08-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4532267A (en) | Vision correction lens made from an aminopolysaccharide compound or an ether or ester thereof | |
CA1158463A (en) | Collagen contact lens | |
US4447562A (en) | Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions | |
EP0763754B1 (en) | Photocured crosslinked-hyaluronic acid contact lens | |
EP0701704B1 (en) | Material to be worn on the eyeball | |
US4365050A (en) | Amino-polysaccharides and copolymers thereof for contact lenses and ophthalmic compositions | |
EP0167363B1 (en) | Crosslinked glycosaminoglycans and their use | |
US4946450A (en) | Glucan/collagen therapeutic eye shields | |
JP5968447B2 (en) | Chitosan and / or chitin complex with enhanced physical properties and uses thereof | |
CN101967282B (en) | Sparingly water-soluble transparent silk fibroin film and preparation method thereof | |
JPS6145608B2 (en) | ||
JPH0352842B2 (en) | ||
JPH07508196A (en) | Azlactone functional base material, prosthetic cornea, and its production and utilization | |
EP0256139A1 (en) | Soft contact lens and process for its production | |
JPH04275346A (en) | Compatibel mixture containing chitosan | |
CN113926001B (en) | Bionic cornea and preparation method thereof | |
JPH1156897A (en) | Collagen ophthalmologic surgery assisting agent | |
SE454842B (en) | COMPOSITION FOR APPLICATION FOR Ophthalmological applications containing an aqueous solution of a high molecular weight polymer and a loose polymeric substance | |
US4309534A (en) | Renatured chitosan and process of making same | |
CN116650700A (en) | Chitosan copolymer hemostatic dressing and preparation method thereof | |
CN1394875A (en) | Method for extracting fimbrin | |
CA1095445A (en) | Collagen soft contact lens | |
CN115990969B (en) | Bionic biological material and preparation method thereof | |
EP0077295A1 (en) | Contact lenses of polyvinyl alcohol cross-linked by borate | |
JP2564520B2 (en) | Contact lens manufacturing method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Designated state(s): JP |
|
AL | Designated countries for regional patents |
Designated state(s): AT BE CH DE FR GB LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1985901178 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1985901178 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1985901178 Country of ref document: EP |