WO2002039930A1 - Film for medical use and process for the production thereof, and artificial cornea with the use of the same and process for the production thereof - Google Patents
Film for medical use and process for the production thereof, and artificial cornea with the use of the same and process for the production thereof Download PDFInfo
- Publication number
- WO2002039930A1 WO2002039930A1 PCT/JP2001/000917 JP0100917W WO0239930A1 WO 2002039930 A1 WO2002039930 A1 WO 2002039930A1 JP 0100917 W JP0100917 W JP 0100917W WO 0239930 A1 WO0239930 A1 WO 0239930A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- membrane
- porous layer
- artificial cornea
- medical
- pore
- Prior art date
Links
- 210000004087 cornea Anatomy 0.000 title claims description 164
- 238000000034 method Methods 0.000 title claims description 49
- 238000004519 manufacturing process Methods 0.000 title claims description 32
- 239000012528 membrane Substances 0.000 claims description 125
- 230000003287 optical effect Effects 0.000 claims description 85
- 239000000463 material Substances 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 41
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 150000003839 salts Chemical group 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 7
- 238000005266 casting Methods 0.000 claims description 6
- 239000012780 transparent material Substances 0.000 claims description 6
- 230000001376 precipitating effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 230000008016 vaporization Effects 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 64
- 210000001519 tissue Anatomy 0.000 description 52
- 239000000243 solution Substances 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000011780 sodium chloride Substances 0.000 description 32
- 239000011148 porous material Substances 0.000 description 25
- 229920002635 polyurethane Polymers 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- 238000000605 extraction Methods 0.000 description 20
- 238000002054 transplantation Methods 0.000 description 16
- 239000011521 glass Substances 0.000 description 13
- 239000004814 polyurethane Substances 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 10
- 230000009545 invasion Effects 0.000 description 10
- 230000035515 penetration Effects 0.000 description 10
- 241000700605 Viruses Species 0.000 description 9
- 238000004108 freeze drying Methods 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 238000007710 freezing Methods 0.000 description 7
- 230000008014 freezing Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000000853 adhesive Substances 0.000 description 6
- 230000001070 adhesive effect Effects 0.000 description 6
- -1 alkali metal salts Chemical class 0.000 description 6
- 238000000465 moulding Methods 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 6
- 229920006264 polyurethane film Polymers 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 241000283977 Oryctolagus Species 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 238000001000 micrograph Methods 0.000 description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 241000425571 Trepanes Species 0.000 description 4
- 210000001742 aqueous humor Anatomy 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000005553 drilling Methods 0.000 description 4
- 238000005304 joining Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000004382 visual function Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 210000002159 anterior chamber Anatomy 0.000 description 3
- 238000000748 compression moulding Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 239000004925 Acrylic resin Substances 0.000 description 2
- 229920000178 Acrylic resin Polymers 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- 229920002396 Polyurea Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 229920000800 acrylic rubber Polymers 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- LWBPNIJBHRISSS-UHFFFAOYSA-L beryllium dichloride Chemical compound Cl[Be]Cl LWBPNIJBHRISSS-UHFFFAOYSA-L 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 230000004397 blinking Effects 0.000 description 2
- FLJPGEWQYJVDPF-UHFFFAOYSA-L caesium sulfate Chemical compound [Cs+].[Cs+].[O-]S([O-])(=O)=O FLJPGEWQYJVDPF-UHFFFAOYSA-L 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 210000000795 conjunctiva Anatomy 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
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- 239000003814 drug Substances 0.000 description 2
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- 238000001704 evaporation Methods 0.000 description 2
- 238000001746 injection moulding Methods 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010061217 Infestation Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- OFOVNSGKJOWGHM-UHFFFAOYSA-M [Na+].[Cl-].C1CCOC1 Chemical compound [Na+].[Cl-].C1CCOC1 OFOVNSGKJOWGHM-UHFFFAOYSA-M 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- XBJJRSFLZVLCSE-UHFFFAOYSA-N barium(2+);diborate Chemical compound [Ba+2].[Ba+2].[Ba+2].[O-]B([O-])[O-].[O-]B([O-])[O-] XBJJRSFLZVLCSE-UHFFFAOYSA-N 0.000 description 1
- AYJRCSIUFZENHW-DEQYMQKBSA-L barium(2+);oxomethanediolate Chemical compound [Ba+2].[O-][14C]([O-])=O AYJRCSIUFZENHW-DEQYMQKBSA-L 0.000 description 1
- 229910052790 beryllium Inorganic materials 0.000 description 1
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 1
- 229910001627 beryllium chloride Inorganic materials 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- JXIFJZDKEMVWLB-UHFFFAOYSA-N calcium boric acid hydrogen borate Chemical class B([O-])([O-])O.B(O)(O)O.[Ca+2] JXIFJZDKEMVWLB-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
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- 239000000284 extract Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 238000001259 photo etching Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001485 poly(butyl acrylate) polymer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000909 polytetrahydrofuran Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- SDRZXZKXVBHREH-UHFFFAOYSA-M potassium;dihydrogen phosphate;phosphoric acid Chemical class [K+].OP(O)(O)=O.OP(O)([O-])=O SDRZXZKXVBHREH-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- CBXWGGFGZDVPNV-UHFFFAOYSA-N so4-so4 Chemical class OS(O)(=O)=O.OS(O)(=O)=O CBXWGGFGZDVPNV-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- LNDCCSBWZAQAAW-UHFFFAOYSA-M sodium hydrogen sulfate sulfuric acid Chemical compound [Na+].OS(O)(=O)=O.OS([O-])(=O)=O LNDCCSBWZAQAAW-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
Definitions
- the present invention relates to a medical membrane and a method for manufacturing the same. Further, the present invention relates to an artificial cornea for replacing a cornea whose function has been reduced or lost due to an eye tissue disease or the like, and restoring visual function, The present invention relates to an artificial cornea and a method for producing the same, wherein the medical film is used as a support for surrounding and supporting at least a part of an optical part of the artificial cornea. Background art
- an artificial cornea is provided with an optical part made of a transparent (translucent) material and a fixing part for supporting the optical part by fixing the optical part to eye tissue of a human body. It is composed of As such an artificial cornea, the present inventors have already consisted of an optical part which is a transparent (translucent) material and a support part surrounding the optical part. In addition, an artificial cornea made of a flexible material in which the supporting portion has a fine interstitial structure has been proposed (Japanese Patent Application Laid-Open No. 91-182762).
- the present inventors have proposed an artificial corneal prosthesis in which, when the corneal prosthesis is implanted, a collar portion protruding radially outward is provided on a support portion on the side in contact with the inside of the eye. (International Publication No. WO98 / 20813).
- the supporting portion of the artificial cornea has been made of a porous material such as a nonwoven fabric or a sponge, and a tissue invades the supporting portion.
- the transplanted artificial cornea It is used to be more firmly fixed.
- the general method of fixing the supporting membrane to the artificial corneal body is as follows: a) A fixing method such as a clip; b) The optical part is placed in the hole of the supporting part (sbonge). Fixing method that allows polymer to penetrate, c) Fixing method by dissolving both joining surfaces with a solvent in which the material of the support and optics are both soluble, d) —General This is a fixing method using a typical adhesive.
- the fixing part is easily detached and the durability is problematic.
- the fixing method in b It is difficult to control the degree of penetration of the optical member polymer into the hole of the support, and the penetration of the support blocks the tissue penetration hole of the support.
- the fixing method of c the material of the supporting portion is dissolved by the soluble solvent and the pores are closed.
- the fixing method d) has a problem that the adhesive closes the hole.
- Japanese Patent Publication No. 4-158859 / 1991 discloses an artificial cornea using a porous fluorine resin as a support. Adhesion to the support and the artificial corneal body is performed by bonding with an adhesive, or the configuration of the optical unit in the mode where the support is installed in advance. At the same time when the raw material monomer is polymerized and molded, a method of bonding the optical part and the support part is described. However, as described above, the hole of the support part is closed. There is a drawback.
- the conventional corneal prosthesis support portion has the above-mentioned eye contact. Due to the use of porous materials, the potential for infection by bacteria, viruses, etc., from external forces, may occur in some cases. Can not be denied.
- the present invention has been made in view of the prior art, and provides a medical film and a method for manufacturing the same, which can be bonded to a device substrate while maintaining a porous structure.
- the purpose is to do so.
- the present invention relates to the manufacture of artificial corneas and their manufacture having a support where the porous structure for tissue penetration is retained without being destroyed during assembly.
- the aim is to provide a method.
- the present invention also provides a non-porous layer that can prevent the invasion or infection of bacteria, viruses, etc. from the outside, and a porous layer that can invade tissues.
- An object of the present invention is to provide a medical membrane having a layer, an artificial cornea using the medical membrane, and a method for producing the same. Disclosure of the invention
- the present invention relates to a medical membrane in which two or more porous layers and two or more non-porous layers are laminated.
- the present invention relates to the medical membrane, wherein a non-porous layer is present on at least one surface of the membrane.
- the present invention relates to a medical membrane in which each layer of the membrane is made of the same flexible material.
- the present invention also relates to the present invention.
- the present invention relates to a method for producing the medical film, comprising:
- the present invention is a.
- the present invention relates to a method for producing the medical film, comprising:
- the present invention relates to the method for producing the medical membrane, wherein the pore-forming agent is a salt.
- the present invention relates to a method for producing the medical membrane, wherein the ratio of the pore-forming agent to the total weight of the membrane material and the pore-forming agent is 95% by weight or less.
- the present invention is a.
- the present invention also relates to an artificial corneal membrane comprising the medical membrane.
- the present invention relates to a membrane for a support portion of an artificial cornea, comprising the medical membrane.
- the present invention is a.
- the support part is formed by an artificial cornea consisting of the support part film.
- the present invention relates to the artificial cornea, wherein a surface of the non-porous layer of the support portion is used as a contact surface with a main body.
- the collar portion protrudes outward from the side surface of the optical portion so that the rear surface and the rear surface of the optical portion are flush with each other, and at least the side surface of the optical portion is provided.
- the non-porous layer surface of the supporting portion surrounding a part relates to the human cornea, which is joined to the front surface of the collar portion.
- the present invention relates to the artificial cornea having a protruding portion in which the hub portion protrudes outward from a supporting portion.
- the present invention relates to the artificial cornea, wherein a hole extending from a rear surface of the collar portion to a porous layer of a support portion is provided.
- the present invention is a.
- An artificial cornea made of an optically transparent material, having an optical part having a front surface, a rear surface, and side surfaces, and a hub part protruding outward from a side surface of the optical part.
- FIG. 1 is a scanning micrograph of a two-layer film composed of a porous layer 2 and a non-porous layer 3 produced by the salt extraction method in Example 1.
- FIG. 2 is a scanning micrograph of a two-layer film composed of a porous layer 2 and a non-porous layer 3 produced by a freeze-drying method in Example 3.
- FIG. 3 is a scanning micrograph of a three-layer film composed of the non-porous layer 3aZ porous layer 2 / non-porous layer 3b produced by the salt extraction method in Example 4. is there .
- FIG. 4 is a schematic cross-sectional view showing one embodiment of the artificial cornea of the present invention.
- FIGS. 5 (a) and 5 (b) are schematic plan views of the artificial cornea 4 of FIG. 4, respectively.
- FIG. 5 (a) is a view from the front side of the artificial cornea 4 (above the schematic sectional view).
- FIG. 5 (b) is a view from the back side of the artificial cornea 4 (the lower side of the schematic cross-sectional view).
- FIG. 6 is a scanning micrograph of a bonding portion between the support portion 6 and the collar portion of the artificial cornea prepared in Example 5.
- FIG. 7 (a) and 7 (b) are schematic views showing one embodiment of the artificial cornea of the present invention.
- FIG. 7 (a) is a schematic sectional view
- FIG. 7 (b) is a schematic plan view seen from the back side of the artificial cornea 4 of FIG. 7 (a).
- FIG. 8 is a schematic cross-sectional view of one embodiment showing a transplantation state of a full-thickness transplant in which all layers of the cornea are replaced with the artificial cornea of the present invention.
- FIG. 9 (a) is a tissue-stained photograph of a partial cross section of the cornea 10 of a Japanese white rabbit transplanted with the artificial cornea 4 of the present invention, and shows the artificial cornea 4 and the rabbit cornea. 10 shows the state of the interface.
- Fig. 9 (b) is a sketch drawing for explaining the tissue staining photograph of Fig. 9 (a). is there .
- Best Mode for Carrying Out the Invention The medical film of the present invention is a film in which two or more porous layers and non-porous layers are laminated as described above. However, a membrane having a non-porous layer at least on one surface is preferred.
- the medical membrane of the present invention has at least one porous layer and at least one non-porous layer, respectively, even if the total number of layers is two or three or more. Okay.
- the pore size of the pores of the porous layer of the medical membrane according to the present invention can be appropriately set according to the purpose of the present invention, but is preferably a size suitable for invasion of cell tissue. No. Specifically, it is 1 to 500 / m, preferably 5 to 200 ⁇ , and more preferably 10 to 150.
- the porosity of the porous layer is not particularly limited as long as the purpose of the present invention can be achieved.
- the medical membranes used in the present invention include artificial corneal membranes, skin coating membranes, artificial vascular materials, and medical membranes such as drug supply membranes and transdermal drug supply membranes. It is necessary to get a touch.
- the material of the medical membrane of the present invention is preferably one that is excellent in biocompatibility, and can achieve the purpose of the present invention. As far as they are concerned, they are not particularly limited.
- Examples of the above-mentioned materials include bio-derived polymers represented by various synthetic polymers and collagens; and biodegradable polymers represented by polylactic acid. Molecules, etc. are exposed.
- each of the porous layer and the non-porous layer can be prepared by selecting each of the above-mentioned materials. It is preferred that the layers are made of the same flexible material.
- One method for producing a medical membrane according to the present invention comprises, for example, a step of mixing a solution (A) in which the membrane material is dissolved in a solvent 1 and a pore-forming agent, and (b) A step of precipitating the pore-forming agent in the solution (A); (c) a step of evaporating the solvent 1; and (c) a step of dissolving the pore-forming agent in the solvent 2.
- This is a method consisting of a process of producing (hereinafter, referred to as a pore forming agent addition extraction method).
- a solution (A) in which the membrane material is dissolved in solvent 1 and a pore-forming agent insoluble in solvent 1 are mixed.
- the mixed solution is cast after stirring, and is allowed to stand until the pore-forming agent precipitates in the solution.
- the solvent 1 is vaporized to obtain a mixture of the membrane material and the pore-forming agent.
- the mixture has a two-layer structure consisting of a lower layer in which the membrane material and the pore-forming agent coexist and an upper layer consisting only of the membrane material.
- the pore-forming agent is extracted from this mixture using a solvent 2 in which the pore-forming agent is soluble and the membrane material is insoluble.
- the pore-forming agent organic compounds such as salts, saccharides, and macromolecules are used, and among them, the point force is that it is inexpensive and easy to form into particles. It is preferable to use salt.
- the method of using a salt as the pore-forming agent is hereinafter referred to as a salt-addition extraction method among the pore-forming agent addition extraction methods.
- the weight ratio of salt to the total weight of the membrane material and salt is such that a non-porous layer is formed in the upper layer of the membrane, and the salt layer is formed in the lower layer.
- the porous layer is formed by extracting As formed, it is 10-95% by weight, preferably 50-90% by weight, more preferably 60-85% by weight.
- the salt ratio is 10% by weight or less, the proportion of the porous layer portion in the membrane tends to decrease, and when the salt ratio is higher than 95% by weight, a non-porous layer is formed. There is a tendency not to be.
- Solvent 1 used in the salt addition extraction method of the present invention can be used for any solvent in which the membrane material to be used is soluble and the salt is insoluble.
- the membrane material is polyurethane and the salt is sodium chloride, tetrahydrofuran, 1,4-dioxane, ⁇ , ⁇ — Dimethylform amide and ,, ⁇ — dimethylacetamide, etc. can be used.
- the concentration of the membrane material solution ( ⁇ ) is 0.5 to 20% by weight, preferably 1 to 10% by weight, and more preferably 1 to 10% by weight. 5 to 7.0% by weight.
- the solvent 2 used in the salt extraction method of the present invention may be any solvent in which the membrane material is insoluble and the salt is soluble.
- the solvent in particular, things like water, methanol and glycerin are identified.
- the salt used in the salt extraction method of the present invention is one that is insoluble in the solvent 1 that dissolves the membrane material and can be dissolved in the solvent 2 that extracts the salt.
- Examples include, but are not limited to, alkali metal salts and alkaline earth metal salts, such as lithium chloride, beryllium chloride, and sodium chloride.
- Hydrochlorides such as trium, magnesium chloride, potassium chloride, calcium chloride, cesium chloride, nordium chloride; lithium sulfate, sulfuric acid Sulfates such as beryllium, sodium sulfate, magnesium sulfate, potassium sulfate, calcium sulfate, cesium sulfate, barium sulfate; Or sodium hydrogen sulfate Hydrogen sulfate; lithium carbonate, sodium carbonate, magnesium carbonate, potassium carbonate, calcium carbonate, cesium carbonate, barium carbonate, etc.
- Carbonates such as: sodium bicarbonate, sodium bicarbonate, etc .; sodium bicarbonate; sodium phosphate, magnesium phosphate, potassium phosphate Phosphates such as lime, calcium phosphate, nordium phosphate; sodium borate, potassium borate, calcium borate Borates such as um and barium borate are available.
- salts other than the above-mentioned alkaline metals and alkaline earth metals such as aluminum sulfate, ammonium chloride, ammonium sulfate, etc., may be used. No. They may also be used in the form of hydrates.
- the particle size is :! 5500 ⁇ , preferably 5 2200 zm, more preferably 10 ⁇ : 150 / ⁇ .
- the purpose of the present invention is to be used.
- the production conditions can be appropriately changed depending on the properties of the pore-forming agent to be used.
- Another method for producing a medical membrane according to the present invention is as follows: (a) a nonporous solution prepared by previously preparing a solution (B) obtained by dissolving a membrane material in a solvent 3; (B) freezing the solution while the nonporous membrane surface is dissolved or swollen in the solution (B), and removing the solvent 3 under reduced pressure.
- This method (hereinafter referred to as freeze-drying method) is used.
- a nonporous membrane is prepared by casting a membrane material solution and evaporating a solvent (cast method).
- a membrane material solution (B) in which the membrane material is dissolved in a solvent 3 is cast.
- the surface of the non-porous membrane Is dissolved or swollen in the membrane material solution (B), and is frozen below the freezing point of the solution (B).
- a membrane having a two-layer structure in which a porous layer and a non-porous layer are integrated by freeze-drying can be obtained. (See Figure 2).
- a nonporous film can be produced by a compression molding method, a spray molding method, a cutting molding method, or the like.
- the concentration of the membrane material solution (B) is 0.5 to 20% by weight, preferably; 110% by weight, more preferably 1.5-7% by weight.
- the solvent 3 used in the freeze-drying method of the present invention may be any solvent that dissolves and swells the porous layer material and the non-porous layer material.
- the porous layer material and the non-porous layer material are both poly- tan, 1,4-dioxane, tetrahydrofuran, N , N — Dimethylformamide and N, N — Dimethylacetamide can be used.
- the freezing temperature can be appropriately changed according to the membrane material and the solvent, but the freezing temperature must be lower than the freezing point of the membrane material solution (B).
- Non-porous layer of the present invention A membrane having a three-layer structure of a porous layer / a non-porous layer can be produced by using a pore-forming agent-added extraction method.
- a nonporous membrane is first prepared by a cast method or the like. Thereafter, a two-layer film is formed on the film by using the pore-forming-agent-addition extraction method, thereby obtaining a three-layer film as shown in FIG. And can be done.
- the three-layer membrane of the porous layer Z, the non-porous layer Z, and the porous layer can be obtained by a combination of a pore-forming-agent-added extraction method and a freeze-drying method.
- a two-layer film of a non-porous layer and a porous layer is prepared by using the pore-forming agent addition extraction method, and the freeze-drying method is performed on the non-porous layer. This is what you get.
- the artificial cornea of the present invention is made of an optically transparent material, and has an optical part having a front surface, a rear surface, and a side surface, and an external part from the side surface of the optical part. It has a human corneal body consisting of a protruding hub and a support part surrounding at least a part of the side surface of the optical part. The one using the medical membrane as a support part. Furthermore, the human cornea of the present invention replaces the entire layer, superficial layer or deep layer of the cornea in consideration of the state of the cornea having a reduced or lost function, and It restores visual function.
- the optical section used for the artificial cornea of the present invention is made of an optically transparent material. Such an optical part is located almost at the center of the artificial cornea, and fulfills its visual function by maintaining transparency (transparency).
- the material used for the optical part is harmless to the human body because the inner surface (rear surface) of the artificial cornea may come into direct contact with the aqueous humor in the eye. It is preferred that it be excellent in safety, such as contact with living organisms such as contact lenses, intraocular lenses, etc., or transplantation into living organisms. Material It is possible to use the used materials.
- Examples of the above materials include acrylic resins and polybutyl acrylates represented by, for example, polymethyl methacrylate. Polyester, Polyurethane, Silicon, etc., represented by acrylic elastomers, polyethylene terephthalates, etc.
- Non-hydrous materials such as polystyrene; poly 2 — hydroxy shechil methacrylate, poly vinyl alcohol, poly N — hydro hydrate such as biel pyrrolidone The raw materials are extinguished, and one or more of these materials are selected and used.
- the planar shape of the optical section is not particularly limited, and may be any shape as long as there is no problem in practical use. In order to prevent deformation due to the pressure of the corneal surface, and in the case of ordinary corneal transplantation, it is often the case that a corneal replacement part is removed with a circular treadpan. Considering the points and the like, the shape is preferably a circle.
- the planar shape of the optical section is circular, its diameter is determined unequivocally because the diameter differs depending on the size of the portion of the eye tissue to be replaced with the artificial cornea. I can't do that.
- the reason is that the diameter between the ends of the support portion (outer diameter of the support portion) differs depending on the size of the tissue to be replaced, and therefore, the component part of the optical portion is required.
- the diameter of the part is determined in consideration of the width of the supporting part where the visual function is not impaired and the suturing property and the penetration of eye tissue can be exhibited. In consideration of these facts, and from a practical point of view, it is preferable that the diameter of the optical section is usually about 2 to 8 mm, particularly about 3 to 7 mm. Yes.
- the thickness of the optical section is preferably at least about 0.1 mm from the viewpoint of mechanical strength. Thickness
- the thickness of the central part and the peripheral part may be changed, and for example, at least one of the optical parts is required.
- the part should be a spherical surface. In particular, in order to provide a lens power to the optical unit, it is sufficient to provide spherical surfaces having different curvatures on the front surface and the rear surface of the optical unit.
- the thickness of the optical part, the support part, and the collar at the boundary between the optical part and the support part the thickness of the optical part is smaller than the sum of the thickness of the support part and the thickness of the collar. There are no restrictions, no matter how large or large. However, since the irritation due to friction with the eyelid conjunctiva during blinking can be reduced, the thickness of the optical part is determined by the sum of the thickness of the support part and the collar part. It is also preferred that they are small or similar.
- the artificial cornea of the present invention is provided with a torso portion projecting outward from the side of the optical portion, and the optical portion and the torso portion are combined to form an artificial cornea body.
- optical part and the collar part of the artificial cornea of the present invention may be integrated or separate.
- the tongue protrudes outward from the side of the optical part, but the tongue is located on the side of the optical part so that its rear surface and the rear surface of the optical part are flush with each other. And are preferred.
- the collar serves as an adhesive substrate portion between the artificial corneal body and the support.
- the supporting portion is used for suturing to eye tissue, the supporting portion is preferably bonded to the front surface of the collar portion.
- the material used for the collar is harmless to the human body, As far as it is excellent in safety and achieves the purpose of the present invention, there is no particular limitation, for example, in the above-mentioned optical section. The same materials used can be used.
- the lid portion protrudes outward from the side surface of the optical unit, and its planar shape is not particularly limited as long as the object of the present invention can be achieved. However, it is preferable that the annular shape is used in order to uniformly adhere to the supporting portion having an appropriate annular shape.
- the inner diameter of the collar is the same as the diameter of the optical part, and the outer diameter of the collar serves as a joint board with the support.
- the diameter of the optical part is preferably at least 0.5 mm or more.
- the outer diameter of the collar portion may be larger or smaller than the outer diameter of the support portion. From these facts, it is preferable that the outer diameter of the tongue portion is about 2.5 to 20 mm.
- the collar be provided with a curvature, and that the curvature be approximately equal to the curvature of the cornea. It is better.
- the thickness of the collar (in the direction of the optical axis of the eye) is such that in the case of full-thickness transplantation, it is easy to insert the inside of the eye and the distance between the collar and the iris. It is 1 mm or less, preferably 0.05 to 0.5 mm, taking into account the separation of the anterior chamber and the volume of the anterior chamber, and so as not to adversely affect the eyes. This is desirable. In the case of superficial or deep layer transplantation, the thickness should be 1 mm or less, preferably 0.05 to 0.5 mm, considering the thickness of the cornea. No.
- the thickness of the brim portion is at least 0.05 mm, for example. .
- the artificial cornea of the present invention is provided with a protruding portion in which the collar portion protrudes outside of the supporting portion. That is, the outer diameter of the collar portion is made larger than the outer diameter of the support portion, and such a protruding portion can be provided.
- the protruding portion of the collar is located in the eye chamber adjacent to the inner surface (posterior surface) of the cornea, and the artificial cornea floats outward from the cornea. Plays the role of a stopper for preventing climbing.
- the protruding portion has a shape such that the corneal incision wound surface, which is a wound, is captured from the inside of the eye chamber, and the proliferation of cell tissue from the corneal incision wound surface.
- the protrusion into the posterior surface of the artificial cornea is physically blocked and prevented at the protruding portion.
- the prosthesis of the artificial cornea can be prevented from rising or falling off, and the cell tissue grown from the corneal incision wound surface can be optically clarified.
- the optical part does not reach the rear surface, and the transparent part of the optical part (transparency) is reliably maintained. Also, in the case of superficial or deep layer transplantation, the protruding part is placed between the corneal layers to further prevent the artificial cornea from rising and falling off. You can do what you want.
- the protruding portion protrudes outward from the support portion, and the shape thereof is such that the shape is excellent in safety and can achieve the object of the present invention.
- the support portion is formed so as to protrude in an annular shape radially outward, so that the effect of the present invention can be effectively exhibited. Is preferred.
- the collar portion protrudes more than 0.05 mm radially outward from the support portion in the radial direction, and furthermore, it is easy to insert into the eye. Considering,
- a support is used for fixing the artificial cornea body including the optical part to eye tissue. That is, the artificial cornea is fixed by suturing the supporting portion and the eye tissue (cornea).
- the support section is characterized by using a medical film having a porous layer and a non-porous layer, and surrounds at least a part of the side face of the optical section. It is set up to support it.
- the outer side surface of the support is in contact with at least a part of the incision wound surface of the incised cornea.
- the support used in the present invention has a porous layer
- the surrounding eye tissue is inserted into the pores of the porous layer of the support.
- Invasion results in the artificial cornea and the ocular tissue becoming tightly and affinity-bound, such as by anchoring.
- the porous structure of the porous layer is not destroyed by using the surface of the non-porous layer for adhesion between the supporting portion and the brim portion of the artificial corneal body. Adhesion is possible, and a sufficient hole for penetration of ocular tissue can be secured.
- a porous layer and a non-porous layer are alternately laminated, and at least one layer is laminated on each layer. It is preferable that the number of layers is 2 Or, a value of 3 is more preferred. It is even more preferred that the non-porous layer be present on at least one surface.
- the supporting portion has flexibility. Since the supporting portion has flexibility, suturing of the eye tissue and the artificial cornea can be easily performed through the supporting portion, and it is easy to conform to the incision shape of the eye tissue. Furthermore, physical pressure on the eye tissue is reduced.
- the shape stability of the support portion is greatly improved by including the non-porous layer.
- the cut surface is crushed by the presence of the non-porous layer. It has the advantage that it can be molded without any problems.
- the support portion has a mechanical strength not to be broken by suturing, and has a hole through which the surrounding ocular tissue can enter. It is preferred that it be of biocompatibility, such as contact with or in contact with living organisms such as contact lenses, intraocular lenses, etc. Materials that can be used for transplantation can be used.
- Examples of the above-mentioned materials include, for example, an acrylic resin represented by a polymethyl methacrylate, a polyacryl acrylate, and the like. Polyester, polyurethane, silica, etc. represented by acrylic elastomers, polyethylene terrefu, and evening rates Non-hydrous materials such as polystyrene, polypropylene, and Teflon; Poly 2—Hydroxy Shechil Methacrylate, Polyvinyl Alcohol, Polystyrene Re-N—Hydrophilic materials such as vinyl pyrrolidone; bio-derived materials such as collagen; polylactic acid, polyglycolic acid and their Biodegradable polymers such as copolymers are used, and one or more of these are selected and used.
- an acrylic resin represented by a polymethyl methacrylate, a polyacryl acrylate, and the like.
- Polyester, polyurethane, silica, etc. represented by acrylic elastomers, polyethylene terrefu, and evening rates
- the average pore size into which the cell tissue can enter is 1 to 500 ⁇ m, preferably 5 to 200 / im, more preferably 10 to 150 ⁇ m. m. Therefore, even the porous layer portion of the support portion used in the present invention has a porous layer having a pore diameter in a range of almost this range. You should.
- the multiporous structure is preferably a bicontinuous structure so that ocular tissue can penetrate.
- the state of the pores on the front surface thereof is not limited, and there are no pores and no pores. It may be in any state, such as dotted or porous. If the front surface is non-porous, it can prevent invasion and infection of bacteria, viruses, etc. Also, in the open state, the tissue that has developed on the front surface of the support portion and the tissue that has penetrated into the hole of the support portion interact through the hole and interact with each other. Can be done.
- the planar shape of the support portion is not particularly limited, and may be any shape as long as there is no problem in practical use, but it is usually a circular treadpan. Concentric circles are often removed because they often remove the corneal replacement, maintain their mechanical strength, and prevent deformation due to intraocular pressure. Preferably, it is annular.
- the inner diameter is usually about the same as the diameter of the optical portion.
- the outer diameter cannot be determined unconditionally because it differs depending on the size of the portion of the eye tissue to be replaced with the artificial cornea, and the like, but it is not usually determined.
- the incised eye tissue at the replacement site (cut The size should be the same as the size of the corneal segment (excluded), or about 0.5 mm, for example, about 4 to 20 mm, especially about 5 to 16 mm. This is preferable in practical terms.
- the thickness of the support portion is not absolutely normal, but is usually about 0.01 to 3 mm, especially about 0 :! About 2.5 mm is preferable in practical terms.
- the thickness of the support portion is almost the same as the thickness of the corneal incision section in the case of full-thickness transplantation in order to reduce irritation due to friction with the eyelid conjunctiva during blinking. It is preferred that it be or is somewhat thin.
- the sum of the thickness of the support part and the brim part is almost the same as the thickness of the corneal incision section, or is slightly thinner. And are preferred.
- the porous layer needs to be thick enough to allow the penetration of the ocular tissue, and the thickness is preferably at least 0.05 mm That is all.
- the non-porous layer in the support portion of the present invention needs to have a thickness that can sufficiently serve as an adhesive surface, and the thickness is small. It is at least 0.001 mm.
- the support portion has a curvature substantially equal to the curvature of the cornea.
- the porous structure of the support is used. Since the nutrients from the aqueous humor may not be sufficiently supplied to the ocular tissue that has entered, it is necessary to supply nutrients from the rear side of the collar so that nutrients can be supplied. It may have a through-hole reaching the porous layer of the support.
- the knuckle portion has a protruding portion that protrudes outside the support portion, nutrients are supplied to the corneal portion that comes into contact with the protruding portion.
- the protruding portion may have a through hole.
- the shape of the through-hole is not particularly limited as long as the purpose of the present invention can be achieved, and for example, a circular shape, a square shape, a rectangular shape, and the like are defined. .
- the order to perform the functions will have a transmission of nutrients aqueous humor or al, the area of its is Ru Ah at 1 X 10- 6 mm 2 or more In order to maintain the strength of the collar portion, the thickness is preferably 100 mm 2 or less.
- the atmosphere of the through hole is usually 1 X 10 6 ⁇ : LOOmm 2 about, and the Oh Ru this in 1 X 10- 2 ⁇ 30mm 2 about is good or was not in a practical point of view to the Ku.
- the number of through-holes provided in the flange portion is not particularly limited as long as the object of the present invention can be achieved.
- the number of through-holes may be one, and a plurality of through-holes may be provided. But it may be.
- the state of distribution of the through-holes if there is a protruding portion of the eye tissue in the supporting portion, the corneal tissue on the brim portion of the protruding portion is present.
- the density of the through-holes in the brim portion be uniform.
- the center of the through hole is uniformly present on a concentric ring centered on the optical department.
- the artificial cornea of the present invention comprises the optical part, collar, and support part as described above.
- conjunctival valve covering, mucosal covering, amniotic covering, covering with an appropriate infection prevention sheet, etc. Is applied to part or all of the front of the transplant site. By covering the transplant site with these living tissues or sheets, intraocular infections and the like can be prevented.
- a medical membrane having a three-layer structure of a non-porous layer Z, a porous layer, and a non-porous layer is used as a support for the artificial cornea, and the outer surface of the support is defined as a non-porous layer.
- FIGS. 1, 2 and 3 are all scanning micrographs showing one embodiment of the medical film of the present invention.
- the medical membrane 1 of the present invention has a structure in which a porous layer 2 and a non-porous layer 3 are laminated.
- the medical membrane 1 of the present invention has a two-layer structure in FIGS. 1 and 2, and a three-layer structure of a non-porous layer 3 a / porous layer 2 / non-porous layer 3 b in FIG. , But is not limited to these, and may have two, three, or more layers.
- the medical membrane 1 of the present invention thus obtained comprises a porous layer 2 having a uniform pore size and a non-porous layer 3, and the surface of the non-porous layer is used as a bonding surface.
- the porous structure can be bonded to various medical substrates without destroying the porous structure.
- the three-layer film as shown in FIG. 3 has non-porous layers 3a and 3b, one of which is used as a bonding surface, and the other is sterilized from the outside, and It can be used as a layer to prevent invasion and infection of viruses and the like.
- FIG. 4 is a schematic cross-sectional view showing one embodiment of the artificial cornea of the present invention
- FIGS. 5 (a) and 5 (b) are schematic plan views corresponding to the schematic cross-sectional view of FIG. It is.
- One embodiment of the artificial cornea 4 is a case where a medical film having a two-layer structure of a non-porous layer 3 and a porous layer 2 is used as the support 6.
- FIG. 5 (a) is viewed from the front side of the artificial cornea 4 (upper side of the schematic cross-sectional view)
- FIG. 5 (b) is the posterior side of the artificial cornea 4. (Lower side of schematic sectional view).
- FIG. 5 (a) is viewed from the front side of the artificial cornea 4 (upper side of the schematic cross-sectional view)
- FIG. 5 (b) is the posterior side of the artificial cornea 4. (Lower side of schematic sectional view).
- FIG. 5 (a) is viewed from the front side of the artificial cornea 4 (upper side of the schematic cross-section
- FIG. 5 (a) the front surface of the support portion 6 schematically shows that holes are scattered, and the open state of the front surface and the distribution state of the holes are shown. There is no particular limitation, and the state may be non-porous, dotted with holes, or porous.
- FIG. 5 (b) shows that the surface 3c of the non-porous layer 3 of the support portion 6 is adhered to the front surface 7a of the collar portion 7 (see FIG. 5B). See Figure 4).
- the artificial cornea 4 in FIG. 4 includes an optical part 5 having a front surface 5a, a rear surface 5b, and a side surface 5c, a support part 6 surrounding the side surface 5c of the optical unit 5, and the like. And a flange portion 7 projecting outward from a side surface 5 of the optical portion 5 to cover a rear surface 6a of the support portion 6 and adhered to a front surface 7a thereof. Further, a protruding portion 8 of a tongue portion 7 protruding outward from the support portion 6 is provided. The projection 7 protrudes outward from the side surface 5c of the optical unit 5 so that the rear surface 7b and the rear surface 5b of the optical unit 5 are flush with each other. Further, the artificial cornea 4 of the present invention is characterized in that the medical membrane is used as the support portion 6.
- the artificial cornea 4 shown in FIG. 4 has an integrated optical cornea composed of an optical part 5, a collar part 7, and a protruding part 8 of the collar part 7, and a support part. It is bonded to 6.
- the hub part may be integrated with a part of the optical part or may be separate from the optical part.
- the cornea is not limited to the number of components as described above.
- the integrated part of the optical part, the nose part and the projection part of the head part can be obtained by, for example, compression molding, injection molding, cutting molding, or the like.
- the 4 is a medical membrane of the present invention having a two-layer structure of a porous layer 2 and a non-porous layer 3, and is manufactured by the method described above. be able to .
- the non-porous layer 3 is present on one surface of the support portion 6, and the surface 3c of the non-porous layer 3 is bonded to the front surface 7a of the collar portion 7 of the artificial corneal body. Used for surfaces.
- the artificial cornea of the present invention has a great feature in its supporting portion.
- the support is, for example, shown in FIGS.
- Various membranes having a porous layer and a non-porous layer as shown in Fig. 3 can be used. Anything that can achieve the objectives of the invention is irrelevant.
- the method of bonding the support portion and the artificial corneal body collar according to the present invention is to bond using a soluble solvent to both the material of the support and the artificial corneal body collar.
- the method of bonding using an adhesive etc. is required.
- the artificial cornea of the present invention thus obtained can be used to penetrate ocular tissues by using the non-porous layer of the support for the bonding surface when bonding the support to the main body. It is bonded without blocking or crushing the pores in the porous layer of the support part that serves as a scaffold for the porosity, and has a porous structure after transplantation of the human cornea.
- the penetration of the eye tissue into the stratum corneum allows the artificial cornea and the eye tissue to be well fused.
- the outer surface of the support also has a non-porous layer, it can prevent the invasion and infection of bacteria, viruses, etc. from the outside. It is a thing.
- Fig. 6 shows a scanning microscope in which the medical membrane of the present invention is used as a support for an artificial cornea, and a portion of the artificial cornea that is adhered to the collar of the artificial cornea is observed from the lateral direction of the artificial cornea. It is a photograph.
- the knuckle portion 7 and the support portion 6 of the artificial cornea are firmly adhered to the non-porous layer 3 of the support portion 6 and the front surface 7a of the brim portion 7. . Further, it is shown that the pores of the porous layer 2 are not closed or crushed by the bonding.
- the artificial cornea 4 shown in FIGS. 7 (a) and 7 (b) has an optical part 5 having a front surface 5a, a rear surface 5b and a side surface 5c, and a side surface of the optical unit 5. 5c A part formed integrally with the flange 7 protruding outward from the force and the protrusion 8 of the flange 7 and the support 6 are separately manufactured.
- the surface 3c of the non-porous layer 3 which is the rear surface 6a of the support portion 6 and the front surface 7a of the metal portion 7 were adhered using a solvent or the like as appropriate. That is, it can be obtained by providing a through-hole 9 extending from the rear surface 7b of the collar portion 7 to the porous layer 2 of the support portion 6.
- the brim portion 7 protrudes beyond the support portion 6.
- the projecting portion of the hub is not an essential component, but the hub preferably has a projecting portion.
- the artificial cornea 4 shown in FIGS. 4, 6 and 7 (a) has a curvature, but the artificial cornea of the present invention has However, it is not limited to the presence or absence of curvature.
- FIG. 8 is a schematic cross-sectional view of one embodiment showing an implanted state when the entire cornea is replaced with an artificial cornea (all-layer implant).
- the outer side surface 6b of the support portion 6 and the incision wound surface 10a of the cornea 10 are in contact with each other.
- the protruding portion 8 of the tongue portion 7 is located in the eye chamber so as to be adjacent to the inner surface (rear surface) 10b of the cornea 10. ing .
- the artificial cornea is fixed by suturing the support portion 6 and the cornea 10 with the suture 11.
- FIG. 9 (a) shows the cross section of the interface between the artificial cornea 4 and the rabbit cornea 10 for the cornea 10 of a Japanese white rabbit transplanted with the artificial cornea 4 during the transplantation period. This is a photograph observed by toluidine blue tissue staining two months later, and FIG. 9 (b) is a sketch for explaining FIG. 9 (a). .
- FIG. 9 (a) only the cell tissue portion was stained.
- the porous layer 2 the non-porous layer 3
- the material portion of the artificial cornea 4 at the protruding portion 8 of the lid portion 7 and the collar portion 7 is not stained.
- FIG. 9 (a) the stained tissue is shown in black because it is black and white, but in fact it is almost blue-violet.
- FIG. 9 (b) is a sketch diagram of FIG. 9 (a), reference numerals 2, 3, 3c, 7, 7a and 7a in FIG. 9 (a)
- Fig. 9 (a) is black and white.
- FIG. 9 (a) it can be seen that the eye tissue of the rabbit cornea 10 has penetrated into the portion corresponding to the hole 2a of the porous layer 2 of the support portion 6 and has been fused at the interface. I do. Further, no ocular tissue of the rabbit cornea 10 is present at the position where the non-porous layer 3, the protrusion 7 and the protrusion 8 of the hook 7 are present.
- the non-porous layer 3 and the tongue portion 7 are firmly adhered to the front surface 3c of the non-porous layer 3 and the front surface 7a of the tongue portion 7, and the collar is further
- the protruding part 8 of the part 7 is the rotation of the eye tissue to the posterior surface of the artificial cornea It is also observed that the intrusion is blocked.
- a medical membrane 1 comprising the porous layer 2 and the non-porous layer 3 shown in FIG. 1 was produced.
- a medical membrane was produced by changing the pore diameter of the porous layer from the membrane described in Example 1.
- Example 3 [Preparation of two-layer membrane by freeze-drying method] A medical membrane 1 composed of a porous layer 2 and a non-porous layer 3 shown in Fig. 2 was produced.
- a commercially available polyurethan for medical use was dissolved in tetrahydrofuran to prepare a solution having a concentration of 4.0% by weight. 6.3 g of the solution was cast on a glass cylinder having a diameter of 4 cm, and the tetrahedral port was vaporized.
- the cast membrane of polyurethan ( A non-porous layer 3) was prepared. 1.5 g of a 1,4-dioxane solution of 5.0% by weight of polyurethane was cast on the prepared membrane, and the surface of the non-porous layer 3 was dissolved in the solution.
- the solution was frozen at 20 ° C in a swollen state.
- the 1,4-dioxane was sublimated and removed under reduced pressure to obtain a polyurethane film.
- the cross section of the prepared membrane was observed in the same manner as in Example 1 except that the magnification was set to 75 times.
- the membrane 1 formed a two-layer structure of a porous layer 2 and a non-porous layer 3. It was confirmed that they were working.
- the interface was integrated, and it was observed that the porous layer 2 had continuous pores having a diameter of about 10 to 50 ⁇ m.
- the overall thickness of the membrane was 0.5 mm, and the thickness of the non-porous layer 3 was 0.1 mm.
- polyurethan for medical use was dissolved in tetrahydrofuran to prepare a solution having a concentration of 5.0% by weight. Then, the solution l.O.Og is cast on a glass jar with a diameter of 4 cm, and the tetrahydrofuran is vaporized to obtain a polyurethan cas. A membrane (non-porous layer 3b) was produced. Polyurethane and sodium chloride were added to a 4.0% polyurethan solution in tetrahydrofuran. Sodium chloride was mixed and dispersed so that the weight ratio of sodium chloride to the total weight of the stream was 70% by weight.
- sodium chloride those selected using a sieve having openings of 53 ⁇ m and 106 ⁇ m were used. 8.2 g of a suspension of the above tetrahydrofuran solution in which sodium chloride was sufficiently dispersed was cast on a cast membrane. Sodium chloride was precipitated in the solution, and then tetrahydrofuran was vaporized and removed. The resulting mixed membrane of polyurethane and sodium chloride was immersed in distilled water to extract sodium chloride. This was dried to obtain a polyurethane film.
- the film had a three-layer structure in which the porous layer 2 was sandwiched between the non-porous layers 3 from both sides. The situation was confirmed. In addition, the interface was integrated, and it was observed that the porous layer 2 had continuous pores having a diameter of about 50 to 100 111. Further, the overall thickness of the membrane 1 was 0.8 mm, and the thickness of each of the non-porous layers 3a and 3b was 0.2 mm.
- Example 5 Production of artificial cornea using membrane of Example 1
- the optical part 5 and the tongue part 7 protruding from the side surface 5c of the optical part 5 to the outside of the ring.
- the body of the artificial cornea shown in Figs. 4, 5 (a) and 5 (b) with the projection 8 of the corneal body (the optics is 0.9mm thick, 4.0mm outer diameter, front The radius of curvature was 8.0 mm, the rear surface had a radius of curvature of 7.1 mm, and the knob had a thickness of 0.2 mm, an outer diameter of 7.5 mm, a front surface radius of curvature of 7.3 mm, and a rear surface radius of curvature of lmm).
- the polyurea silicone membrane described in Example 1 is punched into a donut shape using a 4 mm and 7 mm diameter trepan. Then, the non-porous layer 3 is fitted to the optical part 5 of the artificial corneal body such that the non-porous layer 3 is on the rear side of the support part 6, and the surface 3c of the non-porous layer 3 of the polyurethane film is The front surface 7a of the tongue portion 7 of the cornea body was bonded to the front surface 7a using tetrahydrofuran (see Fig. 4).
- Figure 6 shows the result of observing the bonding portion between the collar 7 and the support 6 of the fabricated artificial corneal body. It was confirmed that the non-porous layer 3 of the support portion 6 and the front surface 7a of the collar portion 7 of the artificial corneal body were firmly adhered. In addition, it was confirmed that the porous layer 2 of the support portion 6 was present without being closed or crushed by the bonding.
- Example 6 Production of artificial cornea using membrane obtained from Example 2
- the main body of the artificial cornea was prepared in the same manner as in Example 5.
- the optical section has a thickness of 0.5 mm, an outer diameter of 4.0 mm, a front curvature radius of 8. Omm, and a rear curvature radius of 7.5 mm.
- the collar section has a thickness of 0.1 mm and an outer diameter of 7 mm. .5mm, front radius of curvature 7.6mm, rear radius of curvature 7.5mm.
- the polyurea membrane described in Example 2 As the supporting portion of the artificial cornea, the polyurea membrane described in Example 2 was used. This film is punched out in a donut shape using a 4 mm and 8 mm diameter trepan, and the optical part of the artificial corneal body is placed so that the non-porous layer is on the back side. Then, the surface of the non-porous layer of the polyurethan film and the front surface of the collar portion of the artificial corneal body were bonded using tetrahydrofuran. The support and the main body of the obtained artificial cornea were firmly adhered to each other, and it was confirmed that the pores of the porous layer of the support were not crushed.
- the artificial cornea 4 prepared in Example 5 was applied to an excimer laser (laser gas: KrF, oscillation wavelength: 248 nm, device: INDEX 846 manufactured by Sumitomo Heavy Industries, Ltd.).
- the perforated portion 7 of the artificial cornea 4 and the non-porous layer 3 of the support portion 6 are perforated by using a square having a square shape of 0.5 mm ⁇ 0.5 mm shown in FIG.
- Six through-holes 9 were formed at equal intervals on a concentric ring centered on the optical part 5.
- Example 8 Transplantation of artificial cornea
- the main body of the artificial cornea was prepared in the same manner as in Example 5. (2) Preparation of support
- the film formed a two-layer structure of a porous layer and a non-porous layer.
- the interface was integrated, and it was observed that the porous layer had continuous pores having a diameter of about 30 to 50 ⁇ m.
- the overall thickness of the membrane was 0.7 mm, and the thickness of the non-porous layer was 0.05 mm.
- Bonding was performed in the same manner as in Example 5 except that the membrane prepared in the above (2) was used as a support for the artificial cornea.
- the support and the main body of the obtained artificial cornea were firmly adhered to each other, and it was confirmed that the pores of the porous layer of the support were not crushed.
- the artificial cornea prepared as described above was sterilized with ethylenoxide and then transplanted into the cornea of a Japanese white rabbit.
- all layers of the cornea of a Japanese white rabbit were punched out with a 6.5 mm diameter trepan, and the punched-out portion of the cornea had a protruding portion of the inner surface of the cornea.
- the artificial cornea is inserted so as to be located in the eye chamber so as to be adjacent to the (rear surface), and the peripheral cornea and the supporting portion of the artificial cornea are joined using a nylon suture. I did it by doing
- FIGS. 9 (a) and 9 (b) Histological observation of the artificial corneal transplant eye (trisymbol monochromatic color) revealed that the artificial cornea support 6 had a porous structure as shown in FIGS. 9 (a) and 9 (b). It was observed that the ocular tissue (corneal tissue) penetrated into the hole 2a of the layer 2, and the artificial cornea 4 and the cornea 10 of the Japanese white rabbit were firmly fused. By doing so, the pore structure of the porous layer 2 of the support portion 6 is not destroyed during the production of the artificial cornea (adhesion of the collar portion 7 of the main body and the support portion 6), and the eye is not damaged.
- the medical film having the non-porous layer of the present invention on its surface is used in combination with another medical substrate, for example, the adhesion between the medical substrate and the film
- the surface of the non-porous layer is used as the bonding surface, so that the bonding can be performed without affecting the porous structure of the porous layer. It is possible to join.
- the non-porous layer is used for the interface with the outside world, invasion of bacteria, viruses, etc. from the outside. It can prevent infestation and prevent infection.
- the presence of the non-porous layer provides excellent shape stability of the film itself, and also facilitates molding.
- a porous layer and a non-porous layer alternately laminated in two or three layers are preferably used.
- the nonporous layer surface of the supporting portion is used for the bonding surface with the artificial corneal body, so that the porous structure of the porous layer is not destroyed by the bonding.
- the upper and lower surfaces are both non-porous layers, and if there is a porous layer between them, one surface of the non-porous layer is the main body. The other surface is at the interface with the outside world, and has an effect as an infection-preventing layer.
- the pores of the porous layer are unnecessarily closed by a conventionally difficult joining method.
- the non-porous layer of the supporting portion is used for the bonding surface with the artificial corneal body, and the supporting portion is bonded.
- an artificial cornea can be produced without destroying the structure of the porous layer.
- an area of the porous layer having a hole for penetration of eye tissue is secured, and after implantation of the artificial cornea into the eye, good penetration of eye tissue occurs.
- the artificial cornea and the host cornea are firmly connected.
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Abstract
A film for medical use wherein at least two porous and non-porous layers are laminated. An artificial cornea wherein the above film is used as a supporting member so as to provide a supporting member capable of maintaining the porous structure without any damage or a supporting member whereby the invasion of bacteria, viruses, etc. from outside or infection therewith can be prevented.
Description
明 糸田 医療用 膜お よ びそ の 製法 、 な ら び に それ を 用 い た 人工角 膜お よ びそ の 製法 技術分野 Akira Itoda Medical membrane and its manufacturing method, and artificial cornea and its manufacturing technology using it
本発 明 は、 医療用 膜お よ びそ の製造方法 に 関す る 。 ま た本発明 は、 眼組織疾患な ど に よ り 角膜の機能が低 下 ま た は喪失 し た角 膜 を 置換 し 、 視覚機能 を 回復 さ せ る た め の 人工角 膜 に お い て 、 該医療用 膜 を そ の 人工角 膜の 光学部 の少な く と も 一部 を取 り 囲 んで支持す る 支持部 と し て用 い る 人工角膜お よ びそ の 製造方法 に 関す る 。 背景技術 The present invention relates to a medical membrane and a method for manufacturing the same. Further, the present invention relates to an artificial cornea for replacing a cornea whose function has been reduced or lost due to an eye tissue disease or the like, and restoring visual function, The present invention relates to an artificial cornea and a method for producing the same, wherein the medical film is used as a support for surrounding and supporting at least a part of an optical part of the artificial cornea. Background art
人工角膜は、 一般 に 、 透明性 （透光性） 材料か ら な る 光学部 と 、 人体 の 眼組織 に 固定す る こ.と に よ り 、 前記光 学部 を支持す る た め の支持部 と か ら 構成 さ れて い る 。 こ の よ う な 人工角 膜 と し て 、 本発 明者 ら はすで に 、 透明性 (透光性） 材料で あ る 光学部 と 光学部 を取 り 囲 む支持部 と か ら な り 、 該支持部が微細 間 隙構造 を 有す る 可撓性材 料か ら な る 人工角 膜 を 提案 し て い る （特 開平 9一 182762 号） 。 さ ら に は 、 本発 明者 ら は、 人工角膜 を移植 し た 際 に 眼の 内部 に接す る 側 の支持部 に放射状外方 に突出 し た ツ バ部が設 け ら れた 人工角膜 を 提案 し て い る （ 国 際公開 第 WO98/20813号公報） 。 In general, an artificial cornea is provided with an optical part made of a transparent (translucent) material and a fixing part for supporting the optical part by fixing the optical part to eye tissue of a human body. It is composed of As such an artificial cornea, the present inventors have already consisted of an optical part which is a transparent (translucent) material and a support part surrounding the optical part. In addition, an artificial cornea made of a flexible material in which the supporting portion has a fine interstitial structure has been proposed (Japanese Patent Application Laid-Open No. 91-182762). Furthermore, the present inventors have proposed an artificial corneal prosthesis in which, when the corneal prosthesis is implanted, a collar portion protruding radially outward is provided on a support portion on the side in contact with the inside of the eye. (International Publication No. WO98 / 20813).
人工角膜 に お け る 前記支持部 は、 以前 よ り 不織布や ス ポ ン ジな ど の多孔質構造 を有す る 膜材料が使用 さ れてお り 、 組織が該支持部 中 に 侵入 し て 、 移植 し た 人工角 膜が
よ り 強固 に 固定 さ れ る よ う に用 レ ら れて い る 。 The supporting portion of the artificial cornea has been made of a porous material such as a nonwoven fabric or a sponge, and a tissue invades the supporting portion. The transplanted artificial cornea It is used to be more firmly fixed.
そ の支持部用 膜の 一般的な 人工角 膜本体へ の 固定方法 は、 a ) ク リ ッ プな どで の 固定法、 b ) 支持部 （ス ボ ン ジ） の孔 内 に光学部分 の ポ リ マ ー を浸透 さ せ る 固定法、 c ) 支持部、 光学部 の材料が と も に可溶な溶媒で両方 の 接合面 を溶か し て接合 さ せ る 固定法、 d ) —般的な接着 剤 を 用 い る 固定法な ど で あ る 。 The general method of fixing the supporting membrane to the artificial corneal body is as follows: a) A fixing method such as a clip; b) The optical part is placed in the hole of the supporting part (sbonge). Fixing method that allows polymer to penetrate, c) Fixing method by dissolving both joining surfaces with a solvent in which the material of the support and optics are both soluble, d) —General This is a fixing method using a typical adhesive.
し か し なが ら 、 a ) の ク リ ッ プな どで の 物理的な 固定 方法 で は、 固定部が離脱 し 易 く 、 耐久性 に 問題があ り 、 b ) の 固定方法で は、 光学部材ポ リ マー の支持部 の孔 内 への浸透 の程度 を 制御す る こ と が困難で あ り 、 それ ら の 浸透 に よ り 、 支持部 の組織侵入用 の孔が塞がれて し ま う と い う 欠点が あ る 。 ま た 、 c ) の 固定方法で は、 可溶性 溶媒 に よ り 支持部 の材料が溶解 し 孔が閉塞す る 。 さ ら に そ の 溶解の程度 を 制御す る こ と も 困難で あ る 。 そ し て 、 d ) の 固定方法で も 接着剤が孔 を 塞 ぐ と い う 問題点が あ る 。 However, in the physical fixing method such as the clip in a), the fixing part is easily detached and the durability is problematic.In the fixing method in b), It is difficult to control the degree of penetration of the optical member polymer into the hole of the support, and the penetration of the support blocks the tissue penetration hole of the support. There is a drawback. Further, in the fixing method of c), the material of the supporting portion is dissolved by the soluble solvent and the pores are closed. Furthermore, it is difficult to control the degree of its dissolution. Also, the fixing method d) has a problem that the adhesive closes the hole.
た と え ば、 特 開平 4— 1 5 8 8 5 9号で は、 多孔性 フ ッ 素樹 脂 を 支持部 と し て用 い た 人工角 膜が開示 さ れて い る 。 そ の支持部お よ び人工角 膜本体 と の 接着方法 と し て は接着 剤 に よ る 接着、 ま た は あ ら か じ め支持部 を 設置 し た モ ー ル ド 内 で光学部 の構成原料モ ノ マ ー を重合 し て成形す る と 同 時 に 、 光学部 と 支持部 と を 接着す る 方法が記載 さ れ て い る が、 前記 の よ う に支持部 の孔 を塞 い で し ま う と い う 欠点が あ る 。 For example, Japanese Patent Publication No. 4-158859 / 1991 discloses an artificial cornea using a porous fluorine resin as a support. Adhesion to the support and the artificial corneal body is performed by bonding with an adhesive, or the configuration of the optical unit in the mode where the support is installed in advance. At the same time when the raw material monomer is polymerized and molded, a method of bonding the optical part and the support part is described. However, as described above, the hole of the support part is closed. There is a drawback.
こ の た め 、 多孔質構造 を保持 し た ま ま デバイ ス 基板 と 接合で き る 膜の 開発が望 ま れて い る 。 For this reason, development of a film that can be bonded to a device substrate while maintaining a porous structure has been desired.
さ ら に 、 従来 の 人工角 膜の支持部 は、 前記 の よ う な 目
的 の た め多孔質 の材料が使用 さ れて き た の で、 場合 に よ つ て は外部力ゝ ら の細菌 、 ウ ィ ルス な ど に よ る 感染が引 き 起 こ さ れ る 可能性が否定で き なか っ た 。 In addition, the conventional corneal prosthesis support portion has the above-mentioned eye contact. Due to the use of porous materials, the potential for infection by bacteria, viruses, etc., from external forces, may occur in some cases. Could not be denied.
こ の た め 、 外部か ら の細菌、 ウ ィ ルス な ど の侵入、 感 染 を 防 ぐ こ と の で き る 支持部用 膜の 開発 も 併せて望 ま れ て い る 。 For this reason, there is also a demand for the development of a support membrane that can prevent invasion of bacteria and viruses from the outside and infection.
本発 明 は、前記従来技術 に鑑みて な さ れた も の で あ り 、 多孔質構造 を保持 し た ま ま 、 デバイ ス 基板 に接合で き る 医療用 膜お よ びそ の 製造方法 を提供す る こ と を 目 的 と す る 。 と く に は、 本発 明 は、 組織侵入 の た め の多孔質構造 が組み立て の 際 に破壊 さ れ る こ と な く 保持 さ れた支持部 を有す る 人工角 膜お よ びそ の 製造方法 を 提供す る こ と を 目 的 と す る 。 ま た本発 明 は、 外部か ら の細菌、 ウ ィ ルス な ど の侵入、 ま た は感染 を 防 ぐ こ と の で き る 非多孔質層 、 お よ び組織侵入 の た め の多孔質層 を有す る 医療用 膜お よ び こ の 医療用 膜 を用 い た 人工角 膜、 そ し て こ れ ら の 製造 方法 を提供す る こ と を 目 的 と す る 。 発 明 の 開示 The present invention has been made in view of the prior art, and provides a medical film and a method for manufacturing the same, which can be bonded to a device substrate while maintaining a porous structure. The purpose is to do so. In particular, the present invention relates to the manufacture of artificial corneas and their manufacture having a support where the porous structure for tissue penetration is retained without being destroyed during assembly. The aim is to provide a method. The present invention also provides a non-porous layer that can prevent the invasion or infection of bacteria, viruses, etc. from the outside, and a porous layer that can invade tissues. An object of the present invention is to provide a medical membrane having a layer, an artificial cornea using the medical membrane, and a method for producing the same. Disclosure of the invention
本発 明 は、 多孔質 層 お よ び非多孔質 層 が 2 層以上積層 し て い る 医療用 膜に 関す る 。 The present invention relates to a medical membrane in which two or more porous layers and two or more non-porous layers are laminated.
本発 明 は、 前記膜の 少 な く と も一表面 に 非多孔質層 が 存在す る 前記 医療用 膜 に 関す る 。 The present invention relates to the medical membrane, wherein a non-porous layer is present on at least one surface of the membrane.
本発 明 は、 前記膜の 各層 が 同材質 の可撓性材料か ら な る 医療用 膜 に 関す る 。 The present invention relates to a medical membrane in which each layer of the membrane is made of the same flexible material.
本発 明 は ま た 、 The present invention also
( a )膜材料 を溶媒 1 に溶解 させた溶液 （A ) と孔形成剤 を混 合す る 工程、
(b)孔形成剤 を溶液 （A)中 で沈殿 さ せ る 工程、(a) a step of mixing a solution (A) in which a membrane material is dissolved in a solvent 1 and a pore-forming agent, (b) a step of precipitating the pore-forming agent in the solution (A);
(c)そ の の ち 、 溶媒 1 を気化 さ せ る 工程、 お よ び (c) after that, a step of vaporizing the solvent 1, and
(d)孔形成剤 を溶媒 2 に よ り 溶解抽 出す る 工程 (d) a step of dissolving and extracting the pore-forming agent in the solvent 2
か ら な る 前記医療用 膜の製造方法 に 関す る 。 The present invention relates to a method for producing the medical film, comprising:
本発 明 は、 The present invention
(a)膜材料 を溶媒 1 に溶解 させた溶液 （A) と孔形成剤 を混 合 し 、あ ら か じ め用 意 し た非多孔質膜上 に流延す る 工程、( a ) mixing a solution (A) in which a membrane material is dissolved in a solvent 1 and a pore-forming agent, and casting the mixture on a previously prepared non-porous membrane;
(b)孔形成剤 を 溶液 （A)中 で沈殿 さ せ る 工程、 (b) a step of precipitating the pore-forming agent in the solution (A);
(c)そ の の ち 、 溶媒 1 を気化 さ せ る 工程、 お よ び (c) after that, a step of vaporizing the solvent 1, and
(d)孔形成剤 を 溶媒 2 に よ り 溶解抽 出す る 工程 (d) a step of dissolving and extracting the pore-forming agent from the solvent 2
か ら な る 前記医療用 膜の製造方法 に 関す る 。 The present invention relates to a method for producing the medical film, comprising:
本発 明 は、 孔形成剤が塩で あ る 前記医療用膜の製造方 法 に 関す る 。 The present invention relates to the method for producing the medical membrane, wherein the pore-forming agent is a salt.
本発 明 は 、 膜材料 と 孔形成剤 の総重量 にお け る 孔形成 剤 の割合が 95重量 ％ 以下であ る前記医療用 膜の製造方法 に 関す る 。 The present invention relates to a method for producing the medical membrane, wherein the ratio of the pore-forming agent to the total weight of the membrane material and the pore-forming agent is 95% by weight or less.
本発 明 は、 The present invention
( a )膜材料 を溶媒 3 に溶解 さ せた溶液 （ B )を 、 あ ら か じ め 用 意 し た非多孔質膜上 に流延す る 工程、 お よ び (a) a step of casting a solution (B) obtained by dissolving a membrane material in a solvent 3 onto a previously prepared nonporous membrane, and
( b )非多孔質膜表面が溶液 （ B )に溶解 または膨潤 した状態 で溶液 （B)を凍結 し 、 減圧下で溶媒 3 を 除去す る 工程 か ら な る 前記 医療用膜の製造方法 に 関す る 。 (b) the method for producing a medical membrane according to the above, comprising a step of freezing the solution (B) with the nonporous membrane surface dissolved or swollen in the solution (B) and removing the solvent 3 under reduced pressure; About.
本発 明 は ま た 、 前記 医療用 膜か ら な る 人工角膜用 膜 に 関す る 。 The present invention also relates to an artificial corneal membrane comprising the medical membrane.
本発明 は、 前記 医療用 膜か ら な る 人工角 膜の支持部用 膜に 関する 。 The present invention relates to a membrane for a support portion of an artificial cornea, comprising the medical membrane.
本発 明 は、 The present invention
( a )光学的 に透 明 な 素材か ら な り 、 前面 と 後面 と 側面 と
を有す る 光学部 と 、 光学部 の側面か ら 外側 に突 出 し た ッ ノ 部か ら な る 本体、 お よ び (a) It is made of an optically transparent material and has a front surface, a rear surface, and side surfaces. And a main body consisting of an optical part having a projection, a notch protruding outward from the side of the optical part, and
( b )該光学部 の側面 の 少な く と も 一部 を取 り 囲む支持部 よ り な る 人工角膜 にお い て 、 そ の支持部が前記支持部用 膜か ら な る 人工角 膜に 関す る 。 (b) In an artificial cornea consisting of a support part surrounding at least a part of the side surface of the optical part, the support part is formed by an artificial cornea consisting of the support part film. About.
本発明 は、 前記支持部の 非多孔質層表面 を本体 と の 接 合面 に用 い る 前記 人工角膜に 関す る 。 The present invention relates to the artificial cornea, wherein a surface of the non-porous layer of the support portion is used as a contact surface with a main body.
本発明 は、 前記 ツバ部がそ の後面 と光学部 の後面 と が 同一面 にな る よ う に光学部 の側面か ら 外側 に突出 し てお り 、 光学部の側面 の 少 な く と も 一部 を取 り 囲 む支持部 の 非多孔質層表面が該ツバ部の前面 と接合 してい る 前記人 ェ角膜に 関す る 。 According to the present invention, the collar portion protrudes outward from the side surface of the optical portion so that the rear surface and the rear surface of the optical portion are flush with each other, and at least the side surface of the optical portion is provided. The non-porous layer surface of the supporting portion surrounding a part relates to the human cornea, which is joined to the front surface of the collar portion.
本発 明 は、 前記 ッ バ部が支持部よ り 外側 に張 り 出 し て い る 突 出部分 を有す る 前記人工角膜 に 関す る 。 The present invention relates to the artificial cornea having a protruding portion in which the hub portion protrudes outward from a supporting portion.
本発明 は、 前記 ツ バ部 の後面か ら 支持部 の多孔質層 ま で達す る 孔が設 け ら れて い る 前記人工角 膜 に 関す る 。 The present invention relates to the artificial cornea, wherein a hole extending from a rear surface of the collar portion to a porous layer of a support portion is provided.
本発 明 は、 The present invention
( a )光学的 に 透 明 な 素材か ら な り 、 前面 と 後面 と 側面 と を有す る 光学部 と 、 光学部 の側面か ら 外側 に突 出 し た ッ バ部か ら な る 人工角膜本体 を作製す る 工程、 (a) An artificial cornea made of an optically transparent material, having an optical part having a front surface, a rear surface, and side surfaces, and a hub part protruding outward from a side surface of the optical part. The process of making the body,
( b )前記 医療用 膜 を 作製す る 工程、 お よ び (b) a step of producing the medical film, and
( c )該光学部 の 側面 の 少 な く と も 一部 を 取 り 囲 む 支持 部 と し て 、 （b )で得 ら れた 医療用 膜 を 用 い 、 該膜の 非多 孔 質層 表面 を （a )の 本体 と の 接合面 と し て 、 本体 と 該膜 を 接合す る 工程 (c) using the medical membrane obtained in (b) as a support part surrounding at least a part of the side face of the optical section, and using a non-porous layer of the membrane. Bonding the main body and the film by using the surface as a bonding surface with the main body of (a).
か ら な る 前記人工角 膜 の製造方法 に 関す る 。 図面 の簡単な説明
図 1 は、 実施例 1 で塩添加抽 出法 に よ り 作製 さ れた多 孔質層 2 お よ び非多孔質層 3 か ら な る 2 層膜の走査顕微 鏡写真で あ る 。 The present invention relates to a method for producing the artificial cornea. Brief description of the drawings FIG. 1 is a scanning micrograph of a two-layer film composed of a porous layer 2 and a non-porous layer 3 produced by the salt extraction method in Example 1.
図 2 は、 実施例 3 で凍結乾燥法 に よ り 作製 さ れた 多孔 質層 2 お よ び非多孔質層 3 か ら な る 2 層膜の 走査顕微鏡 写真で あ る 。 FIG. 2 is a scanning micrograph of a two-layer film composed of a porous layer 2 and a non-porous layer 3 produced by a freeze-drying method in Example 3.
図 3 は、 実施例 4 で塩添加抽 出法 に よ り 作製 さ れた非 多孔質層 3 a Z多孔質層 2 /非多孔質層 3 b か ら な る 3 層膜の走査顕微鏡写真で あ る 。 FIG. 3 is a scanning micrograph of a three-layer film composed of the non-porous layer 3aZ porous layer 2 / non-porous layer 3b produced by the salt extraction method in Example 4. is there .
図 4 は、 本発 明 の 人工角膜の一実施態様 を示す概略断 面 図で あ る 。 FIG. 4 is a schematic cross-sectional view showing one embodiment of the artificial cornea of the present invention.
図 5 (a)お よ び 5 (b)はそれぞれ、 図 4 の 人工角膜 4 の 概略平面 図 で あ る 。 図 5 (a)は人工 角 膜 4 の 前面側 （概 略断面 図 の 上側） か ら みた 図 で あ る 。 図 5 (b)は人工 角 膜 4 の後面側 （概略断面 図 の 下側） か ら みた 図で あ る 。 FIGS. 5 (a) and 5 (b) are schematic plan views of the artificial cornea 4 of FIG. 4, respectively. FIG. 5 (a) is a view from the front side of the artificial cornea 4 (above the schematic sectional view). FIG. 5 (b) is a view from the back side of the artificial cornea 4 (the lower side of the schematic cross-sectional view).
図 6 は、 実施例 5 で作製 さ れた 人工角 膜の支持部 6 と ツ バ部 と の接着部分 の 走査顕微鏡写真で あ る 。 FIG. 6 is a scanning micrograph of a bonding portion between the support portion 6 and the collar portion of the artificial cornea prepared in Example 5.
図 7 (a)お よ び 7 (b)は、 本発 明 の 人工角 膜の一実施態 様 を示す概略図 で あ る 。 図 7 (a)は概略断面 図、 図 7 (b) は 図 7 ( a ) の 人 工角 膜 4 の 後面側 か ら 見た 概略平面 図 で あ る 。 7 (a) and 7 (b) are schematic views showing one embodiment of the artificial cornea of the present invention. FIG. 7 (a) is a schematic sectional view, and FIG. 7 (b) is a schematic plan view seen from the back side of the artificial cornea 4 of FIG. 7 (a).
図 8 は、 本発 明 の 人工角膜 に よ り 角 膜の全層 を置換 し た全層移植 の移植状態 を表わす一実施態様の概略断面図 で あ る 。 FIG. 8 is a schematic cross-sectional view of one embodiment showing a transplantation state of a full-thickness transplant in which all layers of the cornea are replaced with the artificial cornea of the present invention.
図 9 (a)は本発 明 の 人工角 膜 4 を 移植 し た 日 本 白 色 家 兎 の 角 膜 10の部分的断面 の組織染色写真で あ り 、 該人工 角 膜 4 と 該家兎角 膜 10の 界面 の 状態 を 示す。 図 9 (b)は 図 9 (a)の 組織染色写真 を 説 明す る た め の ス ケ ッ チ 図 で
あ る 。 発明 を実施する た め の 最 良 の 形態 本発 明 の 医療用 膜 と は、 前記 し た よ う に多孔質層お よ び非多孔質 層 が 2 層 以上積層 し て い る 膜で あ り 、 少な く と も一表面 に 非多孔質 層が存在す る 膜が好 ま し い 。 FIG. 9 (a) is a tissue-stained photograph of a partial cross section of the cornea 10 of a Japanese white rabbit transplanted with the artificial cornea 4 of the present invention, and shows the artificial cornea 4 and the rabbit cornea. 10 shows the state of the interface. Fig. 9 (b) is a sketch drawing for explaining the tissue staining photograph of Fig. 9 (a). is there . Best Mode for Carrying Out the Invention The medical film of the present invention is a film in which two or more porous layers and non-porous layers are laminated as described above. However, a membrane having a non-porous layer at least on one surface is preferred.
さ ら に 、 本発 明 の 医療用 膜は、 多孔質層お よ び非多孔 質層 をそれぞれ少な く と も 1 層ずつ 有 し 、 全体で 2 層 ま た は 3 層以上で あ っ て も よ い 。 Furthermore, the medical membrane of the present invention has at least one porous layer and at least one non-porous layer, respectively, even if the total number of layers is two or three or more. Okay.
本発明 に お け る 医療用膜の多孔質 層 の孔 の孔径 は 、 本 発明 の 目 的 に合わせて適宜設定で き る が、 細胞組織の侵 入 に適 し た大 き さ が好 ま し い 。 具体的 に は 1 〜 5 0 0 / mで あ り 、 好 ま し く は 5 〜 2 0 0 μ πι、 よ り 好 ま し く は 1 0〜： 1 5 0 で あ る 。 ま た多孔 質層 の 多孔度 は、 本発 明 の 目 的 を 達成 し 得 る も の で あ れ ば と く に 限定 はな い 。 The pore size of the pores of the porous layer of the medical membrane according to the present invention can be appropriately set according to the purpose of the present invention, but is preferably a size suitable for invasion of cell tissue. No. Specifically, it is 1 to 500 / m, preferably 5 to 200 μππ, and more preferably 10 to 150. The porosity of the porous layer is not particularly limited as long as the purpose of the present invention can be achieved.
本発 明 に お け る 医療用膜の用 途 と し て は、 人工角膜用 膜、 皮膚被覆膜、 人工血管材料 、 お よ び医薬品供給膜や 経皮薬品供給膜な ど の 医療用 パ ッ チな ど が あ げ ら れ る 。 The medical membranes used in the present invention include artificial corneal membranes, skin coating membranes, artificial vascular materials, and medical membranes such as drug supply membranes and transdermal drug supply membranes. It is necessary to get a touch.
本発 明 の 医療用 膜の 材料 と し て は、 生体適合性 にす ぐ れた も ので あ る こ と が好 ま し く 、 本発 明 の 目 的 を達成 し 得 る も の で あ る か ぎ り 、 特 に 限定 さ れ る も の で はな い 。 The material of the medical membrane of the present invention is preferably one that is excellent in biocompatibility, and can achieve the purpose of the present invention. As far as they are concerned, they are not particularly limited.
前記 の ご と き材料 と し て は、 さ ま ざ ま な合成高分子お よ びコ ラ ー ゲ ン に 代表 さ れ る 生体 由 来高分子 ； ポ リ 乳酸 に代表 さ れ る 生分解性高分子な どが あ げ ら れ る 。 Examples of the above-mentioned materials include bio-derived polymers represented by various synthetic polymers and collagens; and biodegradable polymers represented by polylactic acid. Molecules, etc. are exposed.
本発 明 の 医療用 膜に お い て 、 多孔質層 お よ び非多孔質 層 の 各層 は、 前記 の材料か ら それぞれ選択 し て作製す る こ と がで き る が、 と く に両層 と も に 同材質 の 可撓性材料 か ら な る も の が好 ま し い 。
本発明 に お け る 医療用膜の 1 つ の 製造方法 は、 た と え ば )前記膜材料 を溶媒 1 に溶解 さ せた溶液 （A )と孔形成 剤 を混合す る 工程、 （b )孔形成剤 を溶液 （A )中 で沈殿 さ せ る 工程 、 （c )そ の の ち 、 溶媒 1 を 気化 さ せ る 工程 、 お よ び （ c )孔形成剤 を 溶媒 2 に よ り 溶解抽 出 す る 工程 か ら な る 方法 （以下、 孔形成剤添加抽 出法 と い う ） で あ る 。 In the medical membrane of the present invention, each of the porous layer and the non-porous layer can be prepared by selecting each of the above-mentioned materials. It is preferred that the layers are made of the same flexible material. One method for producing a medical membrane according to the present invention comprises, for example, a step of mixing a solution (A) in which the membrane material is dissolved in a solvent 1 and a pore-forming agent, and (b) A step of precipitating the pore-forming agent in the solution (A); (c) a step of evaporating the solvent 1; and (c) a step of dissolving the pore-forming agent in the solvent 2. This is a method consisting of a process of producing (hereinafter, referred to as a pore forming agent addition extraction method).
さ ら に詳 し く は、膜材料 を溶媒 1 に溶解 さ せた溶液 （A ) と 、 溶媒 1 に不溶 の孔形成剤 を 混合す る 。 こ の混合液 を 撹拌後流延 し 、 孔形成剤が溶液 中 で沈殿す る ま で静置す る 。 そ の の ち 、 溶媒 1 を気化 さ せ る こ と に よ り 膜材料 と 孔形成剤 と の混合物 を得る 。 混合物 は膜材料 と孔形成剤 が共存す る 下層 と 膜材料の みか ら な る 上層 の 2 層構造 を 有す る 。 つ ぎ に 、 孔形成剤が可溶で膜材料が不溶 の溶媒 2 を 用 い て 、 こ の混合物か ら 孔形成剤 を 抽 出す る 。 こ れ に よ り 、 た と え ば図 1 に示すよ う な 、 孔形成剤抽 出 に よ り 形成 さ れた多孔質層 と 、 非多孔質層 を 有す る 2 層膜が 作製 さ れ る 。 More specifically, a solution (A) in which the membrane material is dissolved in solvent 1 and a pore-forming agent insoluble in solvent 1 are mixed. The mixed solution is cast after stirring, and is allowed to stand until the pore-forming agent precipitates in the solution. After that, the solvent 1 is vaporized to obtain a mixture of the membrane material and the pore-forming agent. The mixture has a two-layer structure consisting of a lower layer in which the membrane material and the pore-forming agent coexist and an upper layer consisting only of the membrane material. Next, the pore-forming agent is extracted from this mixture using a solvent 2 in which the pore-forming agent is soluble and the membrane material is insoluble. As a result, a two-layer film having a porous layer formed by extracting a pore-forming agent and a non-porous layer, for example, as shown in FIG. 1, is produced. .
こ こ で 、 孔形成剤 と し て は、 塩、 糖類お よ び高分子な ど の有機化合物が あ げ ら れ、 な か で も安価で粒子状 に 形 成 し やす い と い う 点力、 ら 、 塩 を 用 い る の が好 ま し い。 こ の孔形成剤 と し て塩を 用 い る 方法 を 、 以下、 孔形成剤添 加抽 出法 の な かで も塩添加抽 出 法 と い う 。 Here, as the pore-forming agent, organic compounds such as salts, saccharides, and macromolecules are used, and among them, the point force is that it is inexpensive and easy to form into particles. It is preferable to use salt. The method of using a salt as the pore-forming agent is hereinafter referred to as a salt-addition extraction method among the pore-forming agent addition extraction methods.
つ ぎに孔形成剤添加抽 出法 にお ける さ ま ざまな条件 を、 具体的 に塩添加抽 出法 を用 い て 説明す る が、 こ れ ら に 限 定 さ れ る も の で はな い 。 Next, various conditions in the pore-forming agent-added extraction method will be specifically described using a salt-added extraction method.However, the present invention is not limited to these. Absent .
こ の塩添加抽 出法 に お い て 、 膜材料 と 塩の総重量 に 占 め る 塩の重量割合 は、 膜の 上層部 に 非多孔質層が形成 さ れ、 そ の下層部で は塩 を抽 出す る こ と に よ り 多孔質層 が
形成 さ れ る よ う に 、 10〜95重量 ％ 、 好 ま し く は 50〜 90 重量 ％ 、 さ ら に好 ま し く は 60〜 85重量 ％ で あ る 。 塩割合 が 10重量 ％ 以下で は膜中 の多孔質層 部分 の 占 め る 割合が 低 く な る 傾向 が あ り 、 95重量 ％ よ り も 高 い場合 に は非多 孔質層が形成 さ れな い 傾向が あ る 。 In this salt extraction method, the weight ratio of salt to the total weight of the membrane material and salt is such that a non-porous layer is formed in the upper layer of the membrane, and the salt layer is formed in the lower layer. The porous layer is formed by extracting As formed, it is 10-95% by weight, preferably 50-90% by weight, more preferably 60-85% by weight. When the salt ratio is 10% by weight or less, the proportion of the porous layer portion in the membrane tends to decrease, and when the salt ratio is higher than 95% by weight, a non-porous layer is formed. There is a tendency not to be.
本発明 の塩添加抽出法 に用 い ら れ る 溶媒 1 は、 用 い る 膜材料が溶解 し 、 塩が不溶 の溶媒で あ れ ば ど の よ う な も ので も 使用 で き る が、 た と え ば、 膜材料がポ リ ウ レ タ ン で、 塩が塩化 ナ ト リ ウ ム の場合 に は、 テ ト ラ ヒ ド ロ フ ラ ン、 1 ， 4 一 ジォ キサ ン 、 Ν , Ν — ジ メ チ ルホルム ア ミ ド お よ び Ν ， Ν — ジ メ チルァセ ト ア ミ ド な どが使用 で き る 。 Solvent 1 used in the salt addition extraction method of the present invention can be used for any solvent in which the membrane material to be used is soluble and the salt is insoluble. For example, if the membrane material is polyurethane and the salt is sodium chloride, tetrahydrofuran, 1,4-dioxane, Ν, Ν — Dimethylform amide and ，, Ν — dimethylacetamide, etc. can be used.
本発明 の塩添加抽 出法 に お け る 膜材料溶液 （Α)の濃度 は 0. 5〜 20重量 ％ 、 好 ま し く は 1 〜 ： 10重量 ％ 、 さ ら に 好 ま し く は 1. 5〜 7. 0重量 ％ で あ る 。 In the salt extraction method of the present invention, the concentration of the membrane material solution (は) is 0.5 to 20% by weight, preferably 1 to 10% by weight, and more preferably 1 to 10% by weight. 5 to 7.0% by weight.
本発明 の塩添加抽 出法 に用 い ら れ る 溶媒 2 は、 膜材料 が不溶で 、 塩が溶解す る 溶媒で あ れ ば ど の よ う な も の で も よ い 。 具体的 に は、 水、 メ タ ノ ー ルお よ びグ リ セ リ ン の よ う な も の があ げ ら れ る 。 The solvent 2 used in the salt extraction method of the present invention may be any solvent in which the membrane material is insoluble and the salt is soluble. In particular, things like water, methanol and glycerin are identified.
本発明 の塩添加抽 出法 にお い て使用 す る 塩は、 膜材料 を溶解さ せ る 溶媒 1 に不溶で 、 か つ 塩を 抽 出す る 溶媒 2 に溶解 し 得 る も の で あ れば、 特 に 限定 はな い が、 具体的 に は アルカ リ 金属塩、 ア ルカ リ 土類金属塩の よ う な塩が あ り 、 塩化 リ チ ウ ム 、 塩化ベ リ リ ウ ム 、 塩化ナ ト リ ウ ム 、 塩化マ グネ シ ウ ム 、 塩化カ リ ウ ム 、 塩化 カ ル シ ウ ム 、 塩 化セ シ ウ ム 、 塩化ノ リ ゥ ム な ど の塩酸塩 ； 硫酸 リ チ ウ ム 、 硫酸ベ リ リ ウ ム 、 硫酸ナ ト リ ウ ム 、 硫酸マ グネ シ ウ ム 、 硫酸 カ リ ウ ム 、 硫酸カ ル シ ウ ム 、 硫酸セ シ ウ ム 、 硫酸バ リ ウ ム な ど の 硫酸塩 ； ま た は硫酸水素ナ ト リ ウ ム な ど の
硫酸水素塩 ； 炭酸 リ チ ウ ム 、 炭酸ナ ト リ ウ ム 、 炭酸マ グ ネ シ ゥ ム 、 炭酸カ リ ウ ム 、 炭酸カ ル シ ウ ム 、 炭酸セ シ ゥ ム 、 炭酸バ リ ウ ム な ど の 炭酸塩 ； 炭酸水素 カ リ ウ ム 、 炭 酸水素 ナ ト リ ウ ム な ど の炭酸水素塩； リ ン酸ナ ト リ ウ ム 、 リ ン酸マ グネ シ ウ ム 、 リ ン酸カ リ ウ ム 、 リ ン酸カ ル シ ゥ ム 、 リ ン酸ノ リ ゥ ム な ど の リ ン酸塩 ； ホ ウ酸ナ ト リ ゥ ム 、 ホ ウ酸カ リ ウ ム 、 ホ ウ 酸カ ル シ ウ ム 、 ホ ウ酸バ リ ウ ム な ど の ホ ウ酸塩な どが あ げ ら る 。 さ ら に は硫酸ア ル ミ ニ ゥ ム 、 塩化 ア ンモ ニ ゥ ム 、 硫酸 ア ンモ ニ ゥ ム な ど の前記 ァ ルカ リ 金属、ア ル力 リ 土類金属以外 の塩 を用 い て も よ い 。 ま た 、 こ れ ら は水和物 の形で用 い ら れて も よ い 。 そ の粒 子径 は 、 ：！ 〜 5 0 0 μ πι、 好 ま し く は 5 〜 2 0 0 z m、 よ り 好 ま し く は 1 0〜： 1 5 0 /ζ πιで あ る 。 The salt used in the salt extraction method of the present invention is one that is insoluble in the solvent 1 that dissolves the membrane material and can be dissolved in the solvent 2 that extracts the salt. Examples include, but are not limited to, alkali metal salts and alkaline earth metal salts, such as lithium chloride, beryllium chloride, and sodium chloride. Hydrochlorides such as trium, magnesium chloride, potassium chloride, calcium chloride, cesium chloride, nordium chloride; lithium sulfate, sulfuric acid Sulfates such as beryllium, sodium sulfate, magnesium sulfate, potassium sulfate, calcium sulfate, cesium sulfate, barium sulfate; Or sodium hydrogen sulfate Hydrogen sulfate; lithium carbonate, sodium carbonate, magnesium carbonate, potassium carbonate, calcium carbonate, cesium carbonate, barium carbonate, etc. Carbonates such as: sodium bicarbonate, sodium bicarbonate, etc .; sodium bicarbonate; sodium phosphate, magnesium phosphate, potassium phosphate Phosphates such as lime, calcium phosphate, nordium phosphate; sodium borate, potassium borate, calcium borate Borates such as um and barium borate are available. Furthermore, salts other than the above-mentioned alkaline metals and alkaline earth metals, such as aluminum sulfate, ammonium chloride, ammonium sulfate, etc., may be used. No. They may also be used in the form of hydrates. The particle size is :! 5500 μπι, preferably 5 2200 zm, more preferably 10〜: 150 / ζπι.
本発 明 の孔形成剤添加抽 出法 に お い て、 前記塩の 代わ り に前述 し た糖類お よ び高分子な ど の有機化合物な ど を 使用 す る 場合は、 本発 明 の 目 的 を達成 し 得 る よ う に 、 用 い る 孔 形成剤の 性質 に よ っ て作製条件 を適宜変更 し て行 な う こ と がで き る 。 In the extraction method using the pore-forming agent of the present invention, when the above-mentioned organic compounds such as saccharides and polymers are used in place of the above-mentioned salts, the purpose of the present invention is to be used. In order to achieve the target, the production conditions can be appropriately changed depending on the properties of the pore-forming agent to be used.
本発 明 にお け る 医療用膜の も う 1 つ の製造方法は、 （a ) 膜材料 を 溶媒 3 に 溶解 さ せ た 溶液 （ B ) を 、 あ ら か じ め 用 意 し た 非多孔質膜上 に 流延す る 工程 、 （ b )非多孔 質膜表 面が溶液 （ B )に溶解 ま た は膨潤 し た状態で溶液を凍結 し 、 減圧下で溶媒 3 を 除去す る 工程か ら な る 方法 （以下、 凍 結乾燥法 と い う ） で あ る 。 Another method for producing a medical membrane according to the present invention is as follows: (a) a nonporous solution prepared by previously preparing a solution (B) obtained by dissolving a membrane material in a solvent 3; (B) freezing the solution while the nonporous membrane surface is dissolved or swollen in the solution (B), and removing the solvent 3 under reduced pressure. This method (hereinafter referred to as freeze-drying method) is used.
さ ら に詳 し く は、 ま ず膜材料溶液 を 流延 し て溶媒 を気 化 さ せ る こ と に よ り （キ ャ ス ト 法） 非多孔質膜 を作製す る 。 得 ら れた非多孔質膜上 に 、 膜材料 を溶媒 3 に溶解 し た膜材料溶液 （ B )を 流延す る 。 つ い で 、 非多孔質膜表面
が膜材料溶液 （ B )に 溶解 ま た は膨潤 し た 状態で 、 こ れ を 溶液 （ B )の 凝 固点以下で凍結 す る 。 凍結後 に 減圧下 で溶 媒 3 を 昇華除去す る こ と に よ り 、 凍結乾燥 に よ る 多孔質 層 と 非多孔質層 の 一体化 し た 2 層 構造 を有す る 膜が得 ら れ る （ 図 2 参照） 。 More specifically, first, a nonporous membrane is prepared by casting a membrane material solution and evaporating a solvent (cast method). On the obtained non-porous membrane, a membrane material solution (B) in which the membrane material is dissolved in a solvent 3 is cast. The surface of the non-porous membrane Is dissolved or swollen in the membrane material solution (B), and is frozen below the freezing point of the solution (B). By sublimating and removing the solvent 3 under reduced pressure after freezing, a membrane having a two-layer structure in which a porous layer and a non-porous layer are integrated by freeze-drying can be obtained. (See Figure 2).
非多孔質膜の 作製方法は該キ ャ ス ト 法の ほか に 、 圧縮 成形法、 射 出成形法お よ び切削成形法な どがあ る 。 In addition to the cast method, a nonporous film can be produced by a compression molding method, a spray molding method, a cutting molding method, or the like.
本発 明 の 凍結乾燥法 に お い て 、 膜材料溶液 （ B )の 濃度 は 0 . 5〜 2 0重量 ％ 、 好 ま し く は ；！ 〜 1 0重量 ％ 、 さ ら に 好 ま し く は 1 . 5〜 7 重量 ％ で あ る 。 In the freeze-drying method of the present invention, the concentration of the membrane material solution (B) is 0.5 to 20% by weight, preferably; 110% by weight, more preferably 1.5-7% by weight.
本発 明 の 凍結乾燥法 に用 い ら れ る 溶媒 3 は、 多孔質層 材料、 非多孔質層材料 を溶解、 膨潤 さ せる も の で あ れ ば ど の よ う な も の で も よ い 。 た と え ば、 多孔質層材料お よ び非多孔質 層材料が と も にポ リ ゥ レ タ ン の場合 に は 1 ， 4 — ジ ォキサ ン 、 テ ト ラ ヒ ド ロ フ ラ ン 、 N , N — ジ メ チ ルホルム ア ミ ド お よ び N， N — ジ メ チル ァセ ト ア ミ ド な どが使用 で き る 。 The solvent 3 used in the freeze-drying method of the present invention may be any solvent that dissolves and swells the porous layer material and the non-porous layer material. . For example, when the porous layer material and the non-porous layer material are both poly- tan, 1,4-dioxane, tetrahydrofuran, N , N — Dimethylformamide and N, N — Dimethylacetamide can be used.
凍結温度 は、 膜材料お よ び溶媒 に合わせて適宜変更す る こ と がで き る が、 膜材料溶液 （ B )の 凝 固 点以下 の 温度 でな ければな ら な い 。 The freezing temperature can be appropriately changed according to the membrane material and the solvent, but the freezing temperature must be lower than the freezing point of the membrane material solution (B).
本発 明 の 非多孔質層 多孔質層 /非多孔質層 の 3 層構 造 の膜は、 孔形成剤添加抽 出法 を用 い て作製す る こ と が で き る 。 Non-porous layer of the present invention A membrane having a three-layer structure of a porous layer / a non-porous layer can be produced by using a pore-forming agent-added extraction method.
具体的な 手法 は、 ま ずキ ャ ス ト 法な ど の方法 に よ り 、 あ ら か じ め 非多孔質膜 を 作製す る 。 そ の の ち 、 そ の膜上 に 、 前記孔 形成剤添加抽 出法 を用 い て 2 層膜を作製す る こ と に よ り 、 図 3 に示す よ う な 3 層膜を得 る こ と がで き る 。
ま た 、 多孔質層 Z非多孔質層 Z多孔質層 の 3 層膜は、 孔形成剤添加抽 出法お よ び凍結乾燥法の 組み合わせで得 る こ と がで き る 。 具体的 に は、 前記孔形成剤添加抽 出法 を 用 い て、 非多孔質層 、 多孔質層 の 2 層膜 を作製 し 、 そ の 非多孔質 層上で前記凍結乾燥法 を実施す る こ と に よ り 得 る こ と がで き る 。 As a specific technique, a nonporous membrane is first prepared by a cast method or the like. Thereafter, a two-layer film is formed on the film by using the pore-forming-agent-addition extraction method, thereby obtaining a three-layer film as shown in FIG. And can be done. In addition, the three-layer membrane of the porous layer Z, the non-porous layer Z, and the porous layer can be obtained by a combination of a pore-forming-agent-added extraction method and a freeze-drying method. Specifically, a two-layer film of a non-porous layer and a porous layer is prepared by using the pore-forming agent addition extraction method, and the freeze-drying method is performed on the non-porous layer. This is what you get.
同様 に し て、 本発 明 に も と づき こ れ ら の製造方法 を適 宜組み合わせ る こ と に よ っ て 、 多孔質層 お よ び非多孔質 層 が交互に積層 し た 3 層以上 の膜 を作製す る こ と がで き る 。 Similarly, by appropriately combining these manufacturing methods based on the present invention, three or more layers in which a porous layer and a non-porous layer are alternately laminated are obtained. A film can be produced.
本発 明 の 人工角 膜は、 前記 し た よ う に 、 光学的 に 透明 な素材か ら な り 、 前面 と 後面 と 側面 と を有す る光学部お よ び光学部 の側面か ら 外側 に突出 し た ッ バ部か ら な る 人 ェ角膜本体 と 、 該光学部 の側面 の 少な く と も 一部 を 取 り 囲 む支持部 と を有す る も の で あ っ て 、 か つ該支持部 と し て前記医療用膜 を用 い た も の を い う 。 さ ら に本発明 の人 ェ角膜は、 機能が低下 ま た は喪失 し た角 膜 に つ い て 、 そ の状態 を考 慮 し 、 角 膜の 全層 、 表層 ま た は深層 を 置換 し 、 視覚機能 を 回復 さ せ る も ので あ る 。 As described above, the artificial cornea of the present invention is made of an optically transparent material, and has an optical part having a front surface, a rear surface, and a side surface, and an external part from the side surface of the optical part. It has a human corneal body consisting of a protruding hub and a support part surrounding at least a part of the side surface of the optical part. The one using the medical membrane as a support part. Furthermore, the human cornea of the present invention replaces the entire layer, superficial layer or deep layer of the cornea in consideration of the state of the cornea having a reduced or lost function, and It restores visual function.
本発 明 の 人工角 膜 に用 い ら れ る 光学部 は光学的 に透明 な素材か ら な る 。 か か る 光学部は、 人工角膜の ほ ぼ 中央 に位置 し 、 透明性 （透光性） を保つ こ と でそ の視覚機能 を果たす も の で あ る 。 The optical section used for the artificial cornea of the present invention is made of an optically transparent material. Such an optical part is located almost at the center of the artificial cornea, and fulfills its visual function by maintaining transparency (transparency).
前記光学部 に 用 い ら れ る 材料 は、 人工角 膜の 内面 （後 面） が眼内 の 房水 に 直接接触す る こ と が あ る た め 、 人体 に対 し て無害で あ り 、 安全性 にす ぐれた も の で あ る こ と が好 ま し く 、 た と え ば コ ン タ ク ト レ ンズ、 眼内 レ ン ズな ど の 生体 に 接触 し た り 、 生体 内 に移植す る 材料 と し て用
い ら れて い る 材料な ど を 用 レ¾ る こ と がで き る 。 The material used for the optical part is harmless to the human body because the inner surface (rear surface) of the artificial cornea may come into direct contact with the aqueous humor in the eye. It is preferred that it be excellent in safety, such as contact with living organisms such as contact lenses, intraocular lenses, etc., or transplantation into living organisms. Material It is possible to use the used materials.
前記 の ご と き 材料 と し て は、 た と え ばポ リ メ チル メ タ ク リ レ 一 ト な ど で代表 さ れ る ア ク リ ル樹脂、 ポ リ ブチル ァ ク リ レ一 ト な どで代表 さ れる ァ ク リ ル系 エ ラ ス ト マ一 、 ポ リ エチ レ ン テ レ フ タ レ一 ト な ど で代表 さ れ る ポ リ エス テル、 ポ リ ウ レ タ ン 、 シ リ コ ー ン な ど の 非含水性材料 ； ポ リ 2 — ヒ ド ロ キ シェチル メ タ ク リ レー ト 、 ポ リ ビ エル ア ル コ ール 、 ポ リ N — ビエル ピ ロ リ ド ン な ど の含水性材 料が あ げ ら れ、 こ れ ら の なか か ら 1 種ま た は 2 種以上が 選択 し て用 い ら れ る 。 Examples of the above materials include acrylic resins and polybutyl acrylates represented by, for example, polymethyl methacrylate. Polyester, Polyurethane, Silicon, etc., represented by acrylic elastomers, polyethylene terephthalates, etc. Non-hydrous materials such as polystyrene; poly 2 — hydroxy shechil methacrylate, poly vinyl alcohol, poly N — hydro hydrate such as biel pyrrolidone The raw materials are extinguished, and one or more of these materials are selected and used.
前記光学部 の平面形状は、 と く に 限定がな く 、 実用 上 支障がな い か ぎ り 、 い かな る 形状で あ っ て も よ い が、 機 械的強度 を 保ち 、 眼内か ら の圧力 に よ る 変形 を 防止す る と い う 点や 、 通常 の角膜移植 に お い て は、 円 形 の ト レパ ンで角 膜置換部 を 除去す る こ と が多 い と い っ た点な ど を 考慮す る と 、 円 形で あ る こ と が好 ま し い 。 The planar shape of the optical section is not particularly limited, and may be any shape as long as there is no problem in practical use. In order to prevent deformation due to the pressure of the corneal surface, and in the case of ordinary corneal transplantation, it is often the case that a corneal replacement part is removed with a circular treadpan. Considering the points and the like, the shape is preferably a circle.
前記光学部 の 平面形状が円 形で あ る 場合、そ の直径 は、 人工角膜 に 置換 さ れ る 眼組織 の部位 の大 き さ な ど に よ つ て異な る の で一概 に は決定す る こ と がで き な い 。 そ の理 由 は、 支持部 の端部間 の径 （支持部 の外径） は、 置換 さ れ る 組織径 の大 き さ に よ っ て 異な る た め 、 そ の構成部位 で あ る 光学部 の 直径 は、 視覚機能 を 損な わず、 か つ 縫合 性、 眼組織侵入性が発現 さ れ う る 支持部 の 幅 を鑑みて決 定 さ れ る と い っ た こ と で あ る 。 こ れ ら の こ と を考慮 し 、 さ ら に 実用 面 か ら 、 該光学部 の 直径 は、 通常、 2 〜 8 m m程度、 と く に は 3 〜 7 m m程度で あ る こ と が好 ま し い 。 If the planar shape of the optical section is circular, its diameter is determined unequivocally because the diameter differs depending on the size of the portion of the eye tissue to be replaced with the artificial cornea. I can't do that. The reason is that the diameter between the ends of the support portion (outer diameter of the support portion) differs depending on the size of the tissue to be replaced, and therefore, the component part of the optical portion is required. It is said that the diameter of the part is determined in consideration of the width of the supporting part where the visual function is not impaired and the suturing property and the penetration of eye tissue can be exhibited. In consideration of these facts, and from a practical point of view, it is preferable that the diameter of the optical section is usually about 2 to 8 mm, particularly about 3 to 7 mm. Yes.
ま た 、 前記光学部 の厚.さ は、 機械的強度 の点か ら 、 少 な く と も 0 . 1 m m程度で あ る こ と が好 ま し い 。 か 力 る 厚 さ
は、 必要 に よ り 屈 折度数 を付与 さ せ る ばあ い に は、 中 心 部 と 周辺部 と の厚 さ を変 えれ ばよ く 、 た と え ば前記光学 部 の少な く と も 一部 を球面 と すれ ばよ い 。 と く に 、 前記 光学部 に レ ンズ度数 を付与す る ばあ い に は、 該光学部 の 前面お よ び後面 にそれぞれ曲率が異な る 球面 を設 けれ ば よ い 。 光学部 と 支持部の境界 に お け る 光学部、 支持部、 ツ バ部 の厚み に つ い て 、 光学部 の 厚み は、 支持部 の厚み と ツ バ部 の厚み の和 よ り も 小 さ く て も 大き く て も 、 ま た 同程度で あ っ て も よ く 制限はな い 。 し か し 、 瞬 目 の 際 の 瞼結膜 と の 摩擦 に よ る 刺激 を低減 さ せ る こ と がで き る た め 、 光学部 の厚みは、 支持部 と ツ バ部 の厚みの和 よ り も 小 さ い 、 ま た は 同程度で あ る こ と が好 ま し い 。 The thickness of the optical section is preferably at least about 0.1 mm from the viewpoint of mechanical strength. Thickness In order to provide the refractive index as necessary, the thickness of the central part and the peripheral part may be changed, and for example, at least one of the optical parts is required. The part should be a spherical surface. In particular, in order to provide a lens power to the optical unit, it is sufficient to provide spherical surfaces having different curvatures on the front surface and the rear surface of the optical unit. Regarding the thickness of the optical part, the support part, and the collar at the boundary between the optical part and the support part, the thickness of the optical part is smaller than the sum of the thickness of the support part and the thickness of the collar. There are no restrictions, no matter how large or large. However, since the irritation due to friction with the eyelid conjunctiva during blinking can be reduced, the thickness of the optical part is determined by the sum of the thickness of the support part and the collar part. It is also preferred that they are small or similar.
本発明 の 人工角膜は、 光学部側面よ り 外側 に突 出 し た ッ バ部が設 け ら れて お り 、 前記光学部 と 該 ッ バ部 を合わ せて人工角 膜本体 と す る 。 The artificial cornea of the present invention is provided with a torso portion projecting outward from the side of the optical portion, and the optical portion and the torso portion are combined to form an artificial cornea body.
本発 明 の 人工角 膜の光学部 と ツ バ部 は一体で あ っ て も よ い し 、 別体で あ っ て も よ レ 。 The optical part and the collar part of the artificial cornea of the present invention may be integrated or separate.
ッ Λ部 は光学部側面カゝ ら 外側 に 突 出 し て い る が、 ッ バ 部 はそ の後面 と 光学部 の後面 と が 同一面 と な る よ う に光 学部側面 に位置す る こ と が好 ま し い 。 The tongue protrudes outward from the side of the optical part, but the tongue is located on the side of the optical part so that its rear surface and the rear surface of the optical part are flush with each other. And are preferred.
こ れ ら の こ と よ り 、 た と え ば光学部、 ッ ノ 部一体か ら な る 本体 を 切削加工 に て作製す る 際 に は、 作製作業が容 易 と な る 。 From these facts, for example, when a main body including an optical part and a tongue part is manufactured by cutting, the manufacturing operation is facilitated.
該ツ バ部 は、 人工角 膜本体 と 支持部 と の 接着基板部位 と し て の役割 を果たす。 The collar serves as an adhesive substrate portion between the artificial corneal body and the support.
該支持部 は、 眼組織 と の縫合 に用 い る た め 、 支持部 は ツ バ部 の前面 に接着 さ れ る こ と が好 ま し い 。 Since the supporting portion is used for suturing to eye tissue, the supporting portion is preferably bonded to the front surface of the collar portion.
前記 ツ バ部 に用 い ら れ る 材料 は、人体 に対 し て無害で 、
安全性 にす ぐれた も の で あ り 、 本発 明 の 目 的 を達成 し う る も の で あ る か ぎ り 、 と く に 限定がな く 、 た と え ば前記 光学部な ど に用 い ら れ る 材料 と 同 じ も の を用 い る こ と が で き る 。 The material used for the collar is harmless to the human body, As far as it is excellent in safety and achieves the purpose of the present invention, there is no particular limitation, for example, in the above-mentioned optical section. The same materials used can be used.
前記 ッバ部 は光学部側面か ら 外側 に突 出 し てお り 、 そ の平面形状 は、 本発明 の 目 的 を達成 し得 る も ので あ る か ぎ り 、 と く に 限定がな い が、 円 環状 の形状が適 当 で あ る 支持部 と 均一 に接着す る た め に 円環状で あ る こ と が好 ま し い 。 The lid portion protrudes outward from the side surface of the optical unit, and its planar shape is not particularly limited as long as the object of the present invention can be achieved. However, it is preferable that the annular shape is used in order to uniformly adhere to the supporting portion having an appropriate annular shape.
ツバ部の 平面形状が 円環状で あ る 場合 、 前記ッバ部 の 内径は光学部 の径 と 同径で あ り 、 ま た 、 そ の外径 は支持 部 と の 接合基板 と し て の役割 を 果たすた め光学部の径 ょ り も 、 少な く と も 0. 5 mm以上大 き い こ と が好 ま し い 。 ま た 、 ツ バ部 の外径 は、 支持部 の外径 よ り 大き く て も よ い し 、 小 さ く て も よ い。 こ れ ら の こ と よ り ッノ 部の外径 は 2. 5〜 20 m m程度が好 ま し い 。 When the planar shape of the collar is annular, the inner diameter of the collar is the same as the diameter of the optical part, and the outer diameter of the collar serves as a joint board with the support. In order to fulfill the requirements, the diameter of the optical part is preferably at least 0.5 mm or more. Further, the outer diameter of the collar portion may be larger or smaller than the outer diameter of the support portion. From these facts, it is preferable that the outer diameter of the tongue portion is about 2.5 to 20 mm.
本発 明 の 人工角 膜に お い て 、 ツ バ部 に は曲率が付与 さ れて い た方が望ま し く 、 そ の 曲率 は角 膜の 曲率 と 同等程 度で あ る こ と が望 ま し い 。 In the artificial cornea of the present invention, it is desirable that the collar be provided with a curvature, and that the curvature be approximately equal to the curvature of the cornea. It is better.
ま た 、 前記 ツ バ部の厚 さ （ 眼 の光軸方 向） は、 全層移 植 の 場合 に お い て は眼 の 内部へ の挿入 し やす さ 、 ツ バ部 と 虹彩 ま で の 間 隔、 前眼房の容積の確保な ど を考慮 し 、 眼 に 悪影響 を 与 え る お それ を な く す た め 、 1 mm以下 、 好 ま し く は 0. 05〜 0. 5mmで あ る こ と が望ま し い 。 ま た 、 表層 ま た は深層移植の 場合 に お い て は角 膜の厚み を考慮 し 、 1 mm以下、 好 ま し く は 0. 05〜 0. 5 mmで あ る こ と が 望 ま し い 。 Also, the thickness of the collar (in the direction of the optical axis of the eye) is such that in the case of full-thickness transplantation, it is easy to insert the inside of the eye and the distance between the collar and the iris. It is 1 mm or less, preferably 0.05 to 0.5 mm, taking into account the separation of the anterior chamber and the volume of the anterior chamber, and so as not to adversely affect the eyes. This is desirable. In the case of superficial or deep layer transplantation, the thickness should be 1 mm or less, preferably 0.05 to 0.5 mm, considering the thickness of the cornea. No.
なお 、 前記 ッバ部 を 強度的な側面か ら み る と 、 通常 の
眼圧 （ 2 0 m m H g程度） か ら 最高 5 0 m m H gの圧力 に お い て も 、 極端な変形 を起 こ す こ と な く 耐 え う る 強度 を有す る よ う な材質や厚 さ で あ る こ と が好 ま し い 。 し たが っ て 、 か か る 強度的な側面か ら み る と 、 た と え ば該 ツバ部 の厚 さ は、 少な く と も 0 . 0 5 m mで あ る こ と が好 ま し い 。 In addition, when viewed from the side of strength, A material that can withstand extreme pressures from intraocular pressure (approximately 20 mm Hg) to a maximum of 50 mmHg without causing extreme deformation. It is preferable that the thickness be as small as possible. Therefore, from the viewpoint of such strength, it is preferable that the thickness of the brim portion is at least 0.05 mm, for example. .
ま た 、 本発明 の 人工角膜は、 ツ バ部が該支持部 よ り も 外側 に突出 し て い る 突 出部分が設 け ら れて い る こ と が好 ま し い 。 すな わ ち 、 ツバ部 の外径 を 支持部の外径 よ り 大 き く し 、 か か る 突出部分 を 設 け る こ と ができ る 。 In addition, it is preferable that the artificial cornea of the present invention is provided with a protruding portion in which the collar portion protrudes outside of the supporting portion. That is, the outer diameter of the collar portion is made larger than the outer diameter of the support portion, and such a protruding portion can be provided.
全層移植 の 場合 に は、 該 ツ バ部 の 突出部分は角 膜の 内 面 （後面） と 隣接す る よ う 眼房 内 に位置 し 、 人工角 膜が 角 膜か ら 外界方向 に浮 き 上が る こ と を 防止す る ス ト ツ パ 一 の役 目 を果たす。 ま た 、 該突出部分は傷 口 で あ る 角 膜 切 開創面 を 眼房内側か ら キ ャ ッ プす る よ う な形 と な り 、 角 膜切 開創面か ら の細胞組織 の 増殖 に よ る 人工角膜後面 へ の 回 り 込み を突 出部分で物理的 に せき 止め 、阻止す る 。 そ の結果、 人工角 膜の浮上が り や脱落の 防止 を さ ら に確 固 た る も の に す る こ と がで き 、 ま た 角膜切 開 創面か ら 増 殖 し た細胞組織が光学部後面 ま で到達す る こ と も な く 、 光学部 のす ぐれた透明性 （透光性） が確実 に 維持 さ れ る 。 ま た 、 表層 ま た は深層移植 の 場合 に も 、 角膜層 間 に突 出 部分 を 設置す る こ と に よ り 、 人工角 膜の浮き 上が り や脱 落 の 防止 を さ ら に確固 た る も の にす る こ と がで き る 。 In the case of full-thickness transplantation, the protruding portion of the collar is located in the eye chamber adjacent to the inner surface (posterior surface) of the cornea, and the artificial cornea floats outward from the cornea. Plays the role of a stopper for preventing climbing. In addition, the protruding portion has a shape such that the corneal incision wound surface, which is a wound, is captured from the inside of the eye chamber, and the proliferation of cell tissue from the corneal incision wound surface. The protrusion into the posterior surface of the artificial cornea is physically blocked and prevented at the protruding portion. As a result, the prosthesis of the artificial cornea can be prevented from rising or falling off, and the cell tissue grown from the corneal incision wound surface can be optically clarified. The optical part does not reach the rear surface, and the transparent part of the optical part (transparency) is reliably maintained. Also, in the case of superficial or deep layer transplantation, the protruding part is placed between the corneal layers to further prevent the artificial cornea from rising and falling off. You can do what you want.
前記突 出部分は、 支持部よ り も 外側 に 突出 し てお り 、 そ の形状 は、 安全性 にす ぐれ、 本発明 の 目 的 を達成 し う る も の で あ る か ぎ り 、 と く に 限定がな い が、 支持部の放 射状外方 に 円環状 に突出す る よ う に 形成 さ れて い る こ と が、 本発 明 の効果 を有効 に発現 さ せ る う えで好 ま し い 。
た と え ば、 光学部 の 透 明性 （透光性） の維持お よ び人 ェ角 膜の脱落防止 と い っ た突出部分 の効果が充分 に発現 さ れ る よ う に す る た め に は、 前記 ツ バ部 は、 支持部か ら 放射状半径方向外方 に 0 . 0 5 m m以上突出 し て い る こ と が 好 ま し く 、ま た 眼 の 内部へ の挿入 し やす さ を考慮す る と 、The protruding portion protrudes outward from the support portion, and the shape thereof is such that the shape is excellent in safety and can achieve the object of the present invention. Although not particularly limited, the support portion is formed so as to protrude in an annular shape radially outward, so that the effect of the present invention can be effectively exhibited. Is preferred. For example, in order to maintain the transparency of the optical part (transparency) and prevent the cornea from falling off, the effects of the protruding parts such as the cornea can be sufficiently exhibited. Preferably, the collar portion protrudes more than 0.05 mm radially outward from the support portion in the radial direction, and furthermore, it is easy to insert into the eye. Considering,
2 m m以下突 出 し て い る こ と が好 ま し く 、 通常 0 . 1〜 ： L m m程度突 出 し て い る こ と が好 ま し い 。 It is preferable that it protrudes 2 mm or less, usually 0.1 to: It is preferable that it protrudes about L mm.
本発明 の 人工角膜に お い て は、 前記光学部 を含む 人工 角 膜本体 を眼組織 に固 定する ため に支持部が用 い ら れる。 つ ま り 、 支持部 と 眼組織 （角 膜） と を縫合す る こ と に よ り 、 人工角 膜は固定 さ れ る 。 In the artificial cornea of the present invention, a support is used for fixing the artificial cornea body including the optical part to eye tissue. That is, the artificial cornea is fixed by suturing the supporting portion and the eye tissue (cornea).
前記支持部は、 多孔質層 お よ び非多孔質層 を有す る 医 療用 膜 を用 い る こ と を 特徴 と し 、 前記光学部側面の 少な く と も 一部 を取 り 囲 ん で支持す る よ う に 設 け ら れ る 。 The support section is characterized by using a medical film having a porous layer and a non-porous layer, and surrounds at least a part of the side face of the optical section. It is set up to support it.
人工角膜が角 膜に移植 さ れた 際、 前記支持部 の外側 の 側面 は、 切 開 さ れた角 膜の切 開 創面 の少 な く と も 一部 と 接触 し て い る 。 When the artificial cornea is implanted in the cornea, the outer side surface of the support is in contact with at least a part of the incision wound surface of the incised cornea.
本発明 に用 い ら れ る 支持部が多孔質層 を有す る こ と に よ り 、 人工角 膜 を移植 し た の ち 、 周 囲 の 眼組織が該支持 部 の多孔質層 の孔 に侵入 し 、 人工角膜 と 眼組織 と が結果 と し て投錨作用 な ど に よ っ て親和 的 に強 固 に結合す る よ う に な る 。 さ ら に 、 非多孔質層 の表面 を支持部 と 人工角 膜本体 の ツ バ部 と の接着 に用 い る こ と に よ り 、 多孔質層 の多孔質構造 を 破壊す る こ と な く 接着で き 、 眼組織侵入 の た め の孔 を充分 に確保す る こ と が可能 と な る 。 Since the support used in the present invention has a porous layer, after the artificial cornea is implanted, the surrounding eye tissue is inserted into the pores of the porous layer of the support. Invasion results in the artificial cornea and the ocular tissue becoming tightly and affinity-bound, such as by anchoring. Furthermore, the porous structure of the porous layer is not destroyed by using the surface of the non-porous layer for adhesion between the supporting portion and the brim portion of the artificial corneal body. Adhesion is possible, and a sufficient hole for penetration of ocular tissue can be secured.
本発 明 の 人工角膜の 支持部 と し て は、 多孔質層 と 非多 孔質層 と が交互 に積層 さ れてお り 、 少な く と も 各 1 層ず つ 積層 さ れて い る も の が好 ま し く 、 そ の 中 で も 積層数 2
ま た は 3 の も の がよ り 好 ま し い 。 ま た 、 非多孔質層 が少 な く と も一表面 に存在す る こ と が さ ら に好 ま し い 。 As the support for the artificial cornea of the present invention, a porous layer and a non-porous layer are alternately laminated, and at least one layer is laminated on each layer. It is preferable that the number of layers is 2 Or, a value of 3 is more preferred. It is even more preferred that the non-porous layer be present on at least one surface.
ま た 、 本発明 に お い て は、 前記支持部が柔軟性 を有す る こ と が好 ま し い 。支持部が柔軟性 を有す る こ と に よ り 、 支持部 を介 して眼組織 と人工角 膜 と の縫合が容易 にな り 、 ま た眼組織 の切 開形状 に適合 し やす く 、 さ ら に は眼組織 へ の物理的圧迫 が軽減 さ れ る 。 Further, in the present invention, it is preferable that the supporting portion has flexibility. Since the supporting portion has flexibility, suturing of the eye tissue and the artificial cornea can be easily performed through the supporting portion, and it is easy to conform to the incision shape of the eye tissue. Furthermore, physical pressure on the eye tissue is reduced.
さ ら に は 、 本発明 に お い て は前記支持部が柔軟性 を有 す る 場合に も 、 非多孔質層 を含む こ と に よ っ て 、 支持部 の形状安定性が非常 に 向上す る 。 ま た、 ト レパ ン な ど を 用 い た支持部の 円環状形状へ の型抜 きな ど の成形 の 際 に も 、 非多孔質層 の存在 に よ り 切断面がつ ぶ さ れ る こ と な く 成形可能 と な る と い う 利点が あ る 。 Furthermore, in the present invention, even when the support portion has flexibility, the shape stability of the support portion is greatly improved by including the non-porous layer. . In addition, when molding such as die cutting of the support into an annular shape using a trepan or the like, the cut surface is crushed by the presence of the non-porous layer. It has the advantage that it can be molded without any problems.
前記支持部は、 縫合 に よ っ て裂 けな い 程度 の機械的強 度 を有 し 、 ま た周 囲 の 眼組織が内部 に入 り 込む こ と がで き る 孔 を有 し 、 さ ら に は生体適合性 にす ぐれた も の で あ る こ と が好 ま し く 、 た と え ばコ ン タ ク ト レ ンズ、 眼 内 レ ンズな どの 生体 に接触 し た り 、 生体内 に移植す る 材料 と し て用 い ら れて レ る 材料な ど を 用 い る こ と がで き る 。 The support portion has a mechanical strength not to be broken by suturing, and has a hole through which the surrounding ocular tissue can enter. It is preferred that it be of biocompatibility, such as contact with or in contact with living organisms such as contact lenses, intraocular lenses, etc. Materials that can be used for transplantation can be used.
前記 の ご と き 材料 と し て は、 た と え ばポ リ メ チル メ タ ク リ レ 一 ト な ど で代表 さ れ る ア ク リ ル樹脂、 ポ リ プチル ァ ク リ レー ト な どで代表 さ れる ァ ク リ ル系 エ ラ ス ト マ一、 ポ リ エチ レ ン テ レ フ 夕 レ ー ト な ど で代表 さ れ る ポ リ エス テル、 ポ リ ウ レ タ ン 、 シ リ コ ー ン 、 ポ リ プ ロ ピ レ ン 、 テ フ ロ ン な ど の 非含水性材料 ； ポ リ 2 — ヒ ド ロ キ シェチル メ タ ク リ レ ー ト 、 ポ リ ビ エル ア ル コ ール、 ポ リ N — ビニ ル ピ ロ リ ド ン な ど の含水性材料 ； コ ラ ー ゲ ン な ど の 生体 由 来材料 ； ポ リ 乳酸、 ポ リ グ リ コ ール酸お よ びそれ ら の
共重合体な ど の 生分解性高分子な どがあ げ ら れ、 こ れ ら の な か カゝ ら 1 種 ま た は 2 種以上が選択 し て用 い ら れ る 。 Examples of the above-mentioned materials include, for example, an acrylic resin represented by a polymethyl methacrylate, a polyacryl acrylate, and the like. Polyester, polyurethane, silica, etc. represented by acrylic elastomers, polyethylene terrefu, and evening rates Non-hydrous materials such as polystyrene, polypropylene, and Teflon; Poly 2—Hydroxy Shechil Methacrylate, Polyvinyl Alcohol, Polystyrene Re-N—Hydrophilic materials such as vinyl pyrrolidone; bio-derived materials such as collagen; polylactic acid, polyglycolic acid and their Biodegradable polymers such as copolymers are used, and one or more of these are selected and used.
な お 、 細胞組織が侵入可能な平均的な孔径 は 、 1 〜 5 0 0 μ m , 好 ま し く は 5 〜 2 0 0 /i m、 よ り 好 ま し く は 1 0〜 1 5 0 μ m程度 で あ る 。 し た が っ て 、 本発 明 に 用 い ら れ る 支持 部 の 多孔質層部分 に つ い て も 、 ほ ぼ こ の範囲 の孔径 を有 す る 多孔質層 を有す る も ので あ ればよ い 。 ま た 、 そ の多 孔構造 は眼組織が侵入す る よ う 、 共連続構造で あ る こ と が好 ま し い 。 The average pore size into which the cell tissue can enter is 1 to 500 μm, preferably 5 to 200 / im, more preferably 10 to 150 μm. m. Therefore, even the porous layer portion of the support portion used in the present invention has a porous layer having a pore diameter in a range of almost this range. You should. Also, the multiporous structure is preferably a bicontinuous structure so that ocular tissue can penetrate.
多孔質層が支持部の一表面 に存在 し 、 人工角膜の 前面 に位置す る 場合 にお い て、 そ の 前表面 にお け る 孔 の存在 状態 に 限定 はな く 、 無孔、 孔 の点在、 多孔 な ど如何な る 状態で あ っ て も よ い 。 前表面が無孔状態 の場合、 細菌、 ウィ ルス な どの侵入お よび感染 を防止する こ とができ る 。 ま た 、 開孔状態 の 場合、 支持部 の 前表面上 に進展 し た組 織 と 支持部 の孔 内 に侵入 し た組織は、 孔 を介 し て相 互作 用 を 及 ぼ し合 い 存在す る こ と が可能 と な る 。 When the porous layer is present on one surface of the support and is located in front of the artificial cornea, the state of the pores on the front surface thereof is not limited, and there are no pores and no pores. It may be in any state, such as dotted or porous. If the front surface is non-porous, it can prevent invasion and infection of bacteria, viruses, etc. Also, in the open state, the tissue that has developed on the front surface of the support portion and the tissue that has penetrated into the hole of the support portion interact through the hole and interact with each other. Can be done.
前記支持部 の 平面形状は、 と く に 限定がな く 、 実用 上 支障がな い か ぎ り 、 い か な る 形状で あ っ て も よ いが、 通 常 円 形 の ト レパ ン で角 膜置換部 を 除去す る こ と が多 い と い う 点、 ま た機械的強度 を保ち 、 眼内か ら の圧力 に よ る 変形 を 防止す る と い う 点か ら 、 同心 円 の環状で あ る こ と が好 ま し レ 。 The planar shape of the support portion is not particularly limited, and may be any shape as long as there is no problem in practical use, but it is usually a circular treadpan. Concentric circles are often removed because they often remove the corneal replacement, maintain their mechanical strength, and prevent deformation due to intraocular pressure. Preferably, it is annular.
前記支持部 の平面形状が同 心 円 の環状で あ る ばあ い 、 そ の 内径は、 通常、 前記光学部の直径 と 同程度 と す る 。 ま た 、 そ の外径 は、 人工角膜 に 置換 さ れ る 眼組織の 部位 の大 き さ な ど に よ っ て異な る の で一概に は決定す る こ と がで き な い が、 通常、 置換部位 の 切 開 さ れた 眼組織 （切
除 し た角 膜片） の大き さ と 同 じ で あ る か 、 0. 5mm程度大 き く すれ ばよ く 、 た と え ば 4 〜 20mm程度、 と く に は 5 〜 16mm程度 で あ る こ と が実用 面で好 ま し い 。 As long as the planar shape of the support portion is a concentric annular shape, the inner diameter is usually about the same as the diameter of the optical portion. In addition, the outer diameter cannot be determined unconditionally because it differs depending on the size of the portion of the eye tissue to be replaced with the artificial cornea, and the like, but it is not usually determined. The incised eye tissue at the replacement site (cut The size should be the same as the size of the corneal segment (excluded), or about 0.5 mm, for example, about 4 to 20 mm, especially about 5 to 16 mm. This is preferable in practical terms.
ま た 、 前記支持部の厚 さ は、 一概 に は い え な い が、 通 常、 0. 01〜 3 mm程度、 と く に は 0. ：！〜 2. 5 mm程度で あ る こ と が実用 面で好 ま し い 。 と く に 、 該支持部の厚 さ は、 瞬 目 の際 の瞼結膜 と の摩擦 によ る刺激 を低減 させる ため、 全層移植の場合、 角膜切 開 断面 の厚 さ と ほ ぼ同 じ で あ る か 、 も し く は幾分薄い こ と が好 ま し い 。 ま た 、 表層 、 深 層移植 の場合、 支持部 と ツ バ部 の厚みの和 は、 角 膜切 開 断面 の厚 さ と ほ ぼ同 じ で あ る か 、 も し く は幾分薄 い こ と が好 ま し い 。 Also, the thickness of the support portion is not absolutely normal, but is usually about 0.01 to 3 mm, especially about 0 :! About 2.5 mm is preferable in practical terms. In particular, the thickness of the support portion is almost the same as the thickness of the corneal incision section in the case of full-thickness transplantation in order to reduce irritation due to friction with the eyelid conjunctiva during blinking. It is preferred that it be or is somewhat thin. In addition, in the case of superficial or deep layer transplantation, the sum of the thickness of the support part and the brim part is almost the same as the thickness of the corneal incision section, or is slightly thinner. And are preferred.
本発 明 の支持部 にお い て、 多孔質層 は眼組織侵入部分 を確保で き る 厚 さ が必要で あ り 、 そ の厚 さ は、 好 ま し く は少な く と も 0. 05mm以上で あ る 。 ま た 、 本発明 の支持 部 に お け る 非多孔質層 は、 接着面 と し て の役割 を 充分果 たす こ と の で き る 厚 さ が必要で あ り 、 そ の厚 さ は少な く と も 0. 001mm以上で あ る 。 In the support of the present invention, the porous layer needs to be thick enough to allow the penetration of the ocular tissue, and the thickness is preferably at least 0.05 mm That is all. In addition, the non-porous layer in the support portion of the present invention needs to have a thickness that can sufficiently serve as an adhesive surface, and the thickness is small. It is at least 0.001 mm.
なお 、 本発明 に お い て は、 支持部 に は、 角膜の 曲率 と 同程度 の 曲率 を 与 え る こ と が好 ま し い 。 In the present invention, it is preferable that the support portion has a curvature substantially equal to the curvature of the cornea.
本発 明 の 人工角 膜の ツバ部お よ びそ こ に接着 さ れ る 支 持部 の 非多孔質層 が非物質透過性 の材料か ら な る 場合 に は、 支持部 の多孔質構造 に入 り 込ん だ眼組織 に房水か ら の栄養分が充分 に 供給 さ れな い こ と も あ り う る の で 、 栄 養分の 供給 を可能 と す る た め 、 そ の ツバ部 の後面か ら 支 持部の 多孔質層 に達す る 貫通孔 を有 し て も よ い 。 ま た 、 ッノ 部が支持部 よ り も 外側 に 突出 し た突 出部分 を有す る 場合 に は、 突出部分 と 接触す る 角 膜部位 に栄養分 を 供給
す る た め 、 突出部分 に貫通孔 を 有 し て い て も よ い 。 When the collar of the artificial cornea of the present invention and the non-porous layer of the support bonded thereto are made of a non-permeable material, the porous structure of the support is used. Since the nutrients from the aqueous humor may not be sufficiently supplied to the ocular tissue that has entered, it is necessary to supply nutrients from the rear side of the collar so that nutrients can be supplied. It may have a through-hole reaching the porous layer of the support. In addition, when the knuckle portion has a protruding portion that protrudes outside the support portion, nutrients are supplied to the corneal portion that comes into contact with the protruding portion. For the sake of simplicity, the protruding portion may have a through hole.
貫通孔 の 形状 は、 本発明 の 目 的 を 達成 し得 る も の で あ る か ぎ り と く に 限定はな く 、 た と え ば円 形、 正方形 、 長 方形 な ど が あ げ ら れ る 。 The shape of the through-hole is not particularly limited as long as the purpose of the present invention can be achieved, and for example, a circular shape, a square shape, a rectangular shape, and the like are defined. .
貫通孔 の 大き さ に は と く に 限定 はな い が、 房水か ら の 栄養分 の 透過 と い う 機能 を果たすた め に は、 そ の面積が 1 X 10— 6mm2以上で あ る こ と が好 ま し く 、 ま た前記 ツ バ 部 の 強度 を 保持す る た め に は、 100mm2以下で あ る こ と が好 ま し い 。 Large bets limited flowers are in Ku in the through hole, the order to perform the functions will have a transmission of nutrients aqueous humor or al, the area of its is Ru Ah at 1 X 10- 6 mm 2 or more In order to maintain the strength of the collar portion, the thickness is preferably 100 mm 2 or less.
よ っ て 、 貫通孔 の 大 き さ は、 通常 1 X 10 6〜： LOOmm2 程度 、 と く に は 1 X 10— 2〜 30mm2程度で あ る こ と が実用 面で好 ま し い 。 And Tsu good, the atmosphere of the through hole is usually 1 X 10 6~: LOOmm 2 about, and the Oh Ru this in 1 X 10- 2 ~ 30mm 2 about is good or was not in a practical point of view to the Ku.
ツ バ部 に設 け ら れ る 貫通孔 の個数 も 、 本発明 の 目 的 を 達成 し 得 る か ぎ り と く に限定がな く 、 貫通孔 は 1 つ で あ つ て も よ く 、 複数で あ っ て も よ い 。 The number of through-holes provided in the flange portion is not particularly limited as long as the object of the present invention can be achieved. The number of through-holes may be one, and a plurality of through-holes may be provided. But it may be.
貫通孔 の分布 の 状態 に も と く に 限定はな い が、 支持部 内 の 眼組織お ょ ぴッ バ部の 突 出部分が存在す る 場合 に は 突出部分 の ツバ部上 の 角膜組織が均一 に 代謝維持 さ れ る よ う にす る た め に 、 ツ バ部 に お け る 貫通孔 の存在密度が 均一で あ る こ と が好 ま し い 。 と く に貫通孔 の 中 心が、 光 学部 を 中 心 と し た 同心 円 の環上 に均一 に存在す る こ と が 好 ま し レ 。 Although there is no particular limitation on the state of distribution of the through-holes, if there is a protruding portion of the eye tissue in the supporting portion, the corneal tissue on the brim portion of the protruding portion is present. In order to maintain the metabolism uniformly, it is preferable that the density of the through-holes in the brim portion be uniform. In particular, it is preferable that the center of the through hole is uniformly present on a concentric ring centered on the optical department.
ツ バ部 に貫通孔 を形成 さ せ る 方法 に は と く に 限定がな く 、 た と え ば There is no particular limitation on the method of forming the through hole in the collar portion.
(ィ）エ キ シ マ レー ザ一 な ど の フ ォ ト エ ッ チ ン グ を 用 い る 穿孔方法、 (A) Drilling method using photo-etching such as excimer laser
(口） ド リ ル、 針な ど を用 い る 穿孔方法、 (Mouth) Drilling method using a drill, needle, etc.
(ハ）圧縮成形機、 射出成形機 な ど を 用 い て成形す る 際 に 、
適切な型 を 用 い る こ と に よ り 孔 を作製す る 方法 な どが あ げ ら れ る 。 (C) When molding using a compression molding machine, injection molding machine, etc., The method of making a hole by using an appropriate mold is required.
前記方法 の な か で も 、 と く に （ィ）エキ シ マ レ一ザ一 で 穿孔 して貫通孔 を設 ける方法 を採用 する こ と が好 ま し い。 こ れは、 エ キ シマ レーザー を用 い て穿孔す る 場合、 マ ス ク を 適宜選択す る こ と に よ り 、 孔 の形状、 大き さ を 比較 的容易 に設定す る こ と がで き る ほか 、 た と え ばッ バ部 の 材料 の 物性 に よ り （口）の よ う な機械 的 な 穿孔方法 を 適用 す る こ と がで き な い場合 に も 、 エキ シマ レ一ザ一を用 い れ ば穿孔が可能で あ る か ら で あ る 。 Among the above-mentioned methods, it is particularly preferable to adopt a method of (a) piercing with an excimer laser to form a through hole. This is because, when drilling using an excimer laser, the shape and size of the holes can be set relatively easily by selecting the mask appropriately. In addition, if the mechanical drilling method such as (mouth) cannot be applied due to the physical properties of the material of the hub part, the excimer laser This is because piercing is possible by using piercing.
本発 明 の 人工角 膜は、 前記 の ご と き光学部、 ツ バ部お よ び支持部か ら な る も の で あ る が、該人工角 膜に お い て、 眼内へ の細菌、 ウ ィ ルス な ど の侵入 を 防止す る 方法 と し て は、 人工角 膜移植後、 た と え ば結膜弁被覆、 粘膜被覆、 羊膜被覆、 適切な感染防止 シー ト に よ る 被覆な ど を移植 部位前面の一部 ま たは全域 に施す方法な どがあ げ ら れる 。 こ れ ら 生体組織 ま た は シ一 ト に よ り 移植部位 を覆 う こ と に よ っ て 、 眼内感染な ど を 防止す る こ と がで き る 。 The artificial cornea of the present invention comprises the optical part, collar, and support part as described above. In order to prevent invasion of viruses, etc., after artificial corneal transplantation, for example, conjunctival valve covering, mucosal covering, amniotic covering, covering with an appropriate infection prevention sheet, etc. Is applied to part or all of the front of the transplant site. By covering the transplant site with these living tissues or sheets, intraocular infections and the like can be prevented.
ま た 、 人工角 膜の支持部 と し て非多孔質層 Z多孔質層 Z非多孔質 層 の 3 層構造 を 有す る 医療用 膜を用 い 、 支持 部外界表面 を 非多孔質層 と す る こ と に よ つ て も 、 眼内へ の細菌、 ウ ィ ルス な ど の侵入 を 防止す る こ と がで き る 。 In addition, a medical membrane having a three-layer structure of a non-porous layer Z, a porous layer, and a non-porous layer is used as a support for the artificial cornea, and the outer surface of the support is defined as a non-porous layer. By doing so, it is possible to prevent bacteria, viruses, and the like from entering the eye.
こ こ で、 本発 明 の 医療用 膜お よ び人工角 膜の実施態様 を 以下 の 図 面 に基づい て説明す る 。 Here, embodiments of the medical membrane and the artificial cornea of the present invention will be described with reference to the following drawings.
図 1 、 2 お よ び 3 は い ずれ も 、 本発 明 の 医療用 膜の一 実施態様 を 示す走査顕微鏡写真で あ る 。 FIGS. 1, 2 and 3 are all scanning micrographs showing one embodiment of the medical film of the present invention.
図 1 、 2 お よ び 3 に お い て、 本発 明 の 医療用 膜 1 は、 多孔質層 2 および非多孔質層 3 が積層 し た構造 を有する 。
本発明 の 医療用 膜 1 は、 図 1 お よ び 2 で は 2 層構造 を 有 し 、 図 3 で は非多孔質層 3 a /多孔質層 2 /非多孔質層 3 b の 3 層構造 を有す る が、 こ れ ら に 限定 さ れる も の で はな く 、 2 層 、 3 層 ま た はそれ以上で あ っ て も よ い 。 1, 2 and 3, the medical membrane 1 of the present invention has a structure in which a porous layer 2 and a non-porous layer 3 are laminated. The medical membrane 1 of the present invention has a two-layer structure in FIGS. 1 and 2, and a three-layer structure of a non-porous layer 3 a / porous layer 2 / non-porous layer 3 b in FIG. , But is not limited to these, and may have two, three, or more layers.
か く し て得 ら れ る 本発明 の 医療用 膜 1 は、 均質な孔径 を 有す る 多孔質層 2 と 非多孔質 層 3 と か ら な り 、 非多孔 質層表面 を 接合面 に用 い る こ と に よ り 、 様々 な 医療用 基 材 に多孔質構造 を 破壊 さ れ る こ と な く 接合す る こ と がで き る 。 ま た 、 図 3 の よ う な 3 層膜は非多孔質層 3 a お よ び 3 b を有 し 、 一方 を 接合面 と し て用 い 、 も う 一方 を外 部か ら の殺菌、 ウ ィ ルス な ど の 侵入お よ び感染 を 防 ぐ層 と し て用 い る こ と がで き る 。 The medical membrane 1 of the present invention thus obtained comprises a porous layer 2 having a uniform pore size and a non-porous layer 3, and the surface of the non-porous layer is used as a bonding surface. As a result, the porous structure can be bonded to various medical substrates without destroying the porous structure. Also, the three-layer film as shown in FIG. 3 has non-porous layers 3a and 3b, one of which is used as a bonding surface, and the other is sterilized from the outside, and It can be used as a layer to prevent invasion and infection of viruses and the like.
図 4 は本発明 の 人工角膜の一実施態様 を示す概略断面 図 で あ り 、 図 5 (a)お よ び 5 (b)は、 共 に 図 4 の概略断面 図 に対応 し た概略平面 図で あ る 。 前記人工角膜 4 の一実 施態様 は、 支持部 6 と し て非多孔質層 3 /多孔質層 2 の 2 層構造 を 有す る 医療用膜を用 い た 場合 の も ので あ る 。 こ れ ら 概略平面 図 はそれぞれ、 図 5 (a)が人工角 膜 4 の 前面側（概略断面 図 の 上側）か ら みた も の で あ り 、図 5 (b) が人工角膜 4 の後面側 （概略断面 図 の下側） か ら みた も の で あ る 。 図 5 (a)に お い て 、 支持部 6 の 前表面 は、 孔 が点在 し て い る こ と を模式的 に示 し て い る が、 前表面 の 開 孔状態ゃ 孔 の 分布状態 に制限 はな く 、 無孔 、 孔 の点在、 多孔状態な ど い か な る 状態であ っ て も よ い 。ま た 図 5 (b) に お い て は、 支持部 6 の 非多孔質層 3 の 表面 3 c がツ バ 部 7 の 前面 7 a に接着 し て レ る こ と を示 し て い る （ 図 4 参照） 。 FIG. 4 is a schematic cross-sectional view showing one embodiment of the artificial cornea of the present invention, and FIGS. 5 (a) and 5 (b) are schematic plan views corresponding to the schematic cross-sectional view of FIG. It is. One embodiment of the artificial cornea 4 is a case where a medical film having a two-layer structure of a non-porous layer 3 and a porous layer 2 is used as the support 6. In each of these schematic plan views, FIG. 5 (a) is viewed from the front side of the artificial cornea 4 (upper side of the schematic cross-sectional view), and FIG. 5 (b) is the posterior side of the artificial cornea 4. (Lower side of schematic sectional view). In FIG. 5 (a), the front surface of the support portion 6 schematically shows that holes are scattered, and the open state of the front surface and the distribution state of the holes are shown. There is no particular limitation, and the state may be non-porous, dotted with holes, or porous. FIG. 5 (b) shows that the surface 3c of the non-porous layer 3 of the support portion 6 is adhered to the front surface 7a of the collar portion 7 (see FIG. 5B). See Figure 4).
なお 、 図 5 (a)お よ び 5 (b)中 の 図 4 と 同 じ参照符号 は
図 4 と 同 じ参照符号の 領域 を示す も の で あ る 。 The same reference numerals as in FIG. 4 in FIGS. 5 (a) and 5 (b) The same reference numerals as those in FIG. 4 indicate the areas.
図 4 に お け る 人工角 膜 4 は、 前面 5 a 、 後面 5 b お よ び側面 5 c と を有す る 光学部 5 、 光学部 5 の側面 5 c を 取 り 囲む支持部 6 、 な ら びに該光学部 5 の側面 5 じ か ら 外側 に突 出 し該支持部 6 の後面 6 a を 覆 っ てそ の 前面 7 a で接着 し て い る ツ バ部 7 と を 有 し 、 さ ら に該支持部 6 よ り も外側 に突 出 し た ッ ノ 部 7 の突 出部分 8 が設 け ら れ て レ る 。 ま た ッ ノ 部 7 はそ の後面 7 b と 光学部 5 の後面 5 b と が 同一面 に な る よ う に光学部 5 の 側面 5 c か ら 外 側 に突出 し て い る 。 ま た本発明 の人工角 膜 4 は該支持部 6 と し て 、 前記 医療用 膜を用 い る こ と が特徴で あ る 。 The artificial cornea 4 in FIG. 4 includes an optical part 5 having a front surface 5a, a rear surface 5b, and a side surface 5c, a support part 6 surrounding the side surface 5c of the optical unit 5, and the like. And a flange portion 7 projecting outward from a side surface 5 of the optical portion 5 to cover a rear surface 6a of the support portion 6 and adhered to a front surface 7a thereof. Further, a protruding portion 8 of a tongue portion 7 protruding outward from the support portion 6 is provided. The projection 7 protrudes outward from the side surface 5c of the optical unit 5 so that the rear surface 7b and the rear surface 5b of the optical unit 5 are flush with each other. Further, the artificial cornea 4 of the present invention is characterized in that the medical membrane is used as the support portion 6.
ま た 、 図 4 に示 さ れ る 人工角 膜 4 は、 光学部 5 、 ツバ 部 7 お よ びツバ部 7 の突出部分 8 と か ら な る 人工角膜本 体が一体で あ り 、 支持部 6 と 接着 さ れた も の で あ る 。 し か し なが ら 、 本発明 に お い て 、 該 ッ バ部 は、 光学部 の一 部 と 一体で あ っ て も よ く 、 別体で あ っ て も よ く 、 本発 明 の 人工角 膜は前記 の ご と き構成部品 の数 に 限定 さ れ る も の で はな い 。 光学部、 ッノ 部お よ びッバ部の突出部分 の 一体化部品 は、 た と え ば圧縮成形 、 射出 成形、 切削成形 な ど に よ っ て得 る こ と がで き る 。 In addition, the artificial cornea 4 shown in FIG. 4 has an integrated optical cornea composed of an optical part 5, a collar part 7, and a protruding part 8 of the collar part 7, and a support part. It is bonded to 6. However, in the present invention, the hub part may be integrated with a part of the optical part or may be separate from the optical part. The cornea is not limited to the number of components as described above. The integrated part of the optical part, the nose part and the projection part of the head part can be obtained by, for example, compression molding, injection molding, cutting molding, or the like.
ま た 、 図 4 の支持部 6 は、 多孔質層 2 と 非多孔質層 3 の 2 層構造 を有す る 、 本発明 の 医療用 膜で あ り 、 前記 し た方法 に よ り 製造す る こ と がで き る 。 該支持部 6 に お い て 、 非多孔質層 3 は支持部 6 の一表面 に存在 し 、 非多孔 質層 3 の 表面 3 c は人工角膜本体 の ツ バ部 7 の前面 7 a と の接着面 に用 い ら れ る 。 4 is a medical membrane of the present invention having a two-layer structure of a porous layer 2 and a non-porous layer 3, and is manufactured by the method described above. be able to . In the support portion 6, the non-porous layer 3 is present on one surface of the support portion 6, and the surface 3c of the non-porous layer 3 is bonded to the front surface 7a of the collar portion 7 of the artificial corneal body. Used for surfaces.
なお 、 本発明 の 人工角膜は、 前記 し た よ う に 、 そ の支 持部 に大 き な特徴が あ る 。 該支持部 は、 た と え ば図 1 〜
3 に示 さ れ る よ う な 、 多孔質層 お よ び非多孔質層 を 有す る 種々 の膜 を使用 す る こ と がで き る が、 本発明 の 医療用 膜で あ れば本発 明 の 目 的 を達成 し 得 る 限 り ど の よ う な も の で も よ い 。 As described above, the artificial cornea of the present invention has a great feature in its supporting portion. The support is, for example, shown in FIGS. Various membranes having a porous layer and a non-porous layer as shown in Fig. 3 can be used. Anything that can achieve the objectives of the invention is irrelevant.
本発 明 の支持部 と 人工角 膜本体 ツ バ部 と の接着方法 は 支持部お よ び人工角膜本体 ツ バ部 の両材料 に対す る 可溶 性溶媒 を用 い 接着す る か 、 ま た は接着剤な ど を用 い て接 着す る 方法な どが あ げ ら れ る 。 The method of bonding the support portion and the artificial corneal body collar according to the present invention is to bond using a soluble solvent to both the material of the support and the artificial corneal body collar. The method of bonding using an adhesive etc. is required.
前記接着 の 際 に は、 眼組織の 侵入の足場 と な る 多孔質 層 の多孔質構造 を 確保す る た め 、 支持部 の非多孔質層 を 接着面 に用 い る こ と が必要で あ る 。 At the time of the bonding, it is necessary to use a non-porous layer of the support portion for the bonding surface in order to secure a porous structure of the porous layer that serves as a scaffold for invasion of eye tissue. .
か く し て得 ら れ る 本発明 の 人工角膜は、 支持部 と 本体 と の接着 に 際 し て支持部の 非多孔質層 を 接着面 に用 い る こ と に よ っ て 、 眼組織侵入の足場 と な る 支持部の多孔質 層 の孔 を塞 い だ り 、 潰 し た り す る こ と な く 接着 さ れ、 人 ェ角膜の移植後 に は多孔質構造 の確保 さ れた多孔質層 内 へ眼組織が侵入す る こ と に よ り 、 人工角膜 と 眼組織 と が 良好 に癒合す る も ので あ る 。 さ ら に は、 支持部 の外界表 面 に も 非多孔質層 を有す る 場合 に は外部か ら の細菌、 ゥ ィ ルス な ど の侵入お よ び感染 を 防 ぐ こ と がで き る も の で あ る 。 The artificial cornea of the present invention thus obtained can be used to penetrate ocular tissues by using the non-porous layer of the support for the bonding surface when bonding the support to the main body. It is bonded without blocking or crushing the pores in the porous layer of the support part that serves as a scaffold for the porosity, and has a porous structure after transplantation of the human cornea. The penetration of the eye tissue into the stratum corneum allows the artificial cornea and the eye tissue to be well fused. Furthermore, if the outer surface of the support also has a non-porous layer, it can prevent the invasion and infection of bacteria, viruses, etc. from the outside. It is a thing.
図 6 は本発明 の 医療用 膜 を 人工角 膜の支持部 と し て用 い 、 人工角 膜本体 の ツ バ部 に接着 し た接着部分 を 人工角 膜の横方向か ら 観察 し た走査顕微鏡写真で あ る 。 Fig. 6 shows a scanning microscope in which the medical membrane of the present invention is used as a support for an artificial cornea, and a portion of the artificial cornea that is adhered to the collar of the artificial cornea is observed from the lateral direction of the artificial cornea. It is a photograph.
図 6 にお い て 、人工角 膜の ッ ノ'部 7 お よ び支持部 6 は、 支持部 6 の 非多孔質層 3 と ツバ部 7 の 前面 7 a と で強固 に接着 し て い る 。 さ ら に 、 接着 に よ っ て多孔質層 2 の孔 が塞がれた り 、 潰 さ れて い な い こ と が示 さ れて レゝ る 。
図 7 (a)お よ び 7 (b)に示 さ れた 人工角 膜 4 は、 前面 5 a 、 後面 5 b お よ び側面 5 c と を有す る 光学部 5 、 光学 部 5 の側面 5 c 力ゝ ら 外側 に突出 し た ッバ部 7 お よ びッバ 部 7 の突出部分 8 を 一体成形 し た部品 と 支持部 6 と を そ れぞれ別 々 に作製 し て お き 、 こ れ ら を た と え ば適宜溶媒 な ど を用 い て支持部 6 の後面 6 a で あ る 非多孔質層 3 の 表面 3 c と ッ ノ 部 7 の 前面 7 a と で接着 し た の ち 、 ツ バ 部 7 の後面 7 b か ら 支持部 6 の 多孔質層 2 に達す る 貫通 孔 9 を設 け る こ と に よ っ て得 る こ と がで き る 。 In FIG. 6, the knuckle portion 7 and the support portion 6 of the artificial cornea are firmly adhered to the non-porous layer 3 of the support portion 6 and the front surface 7a of the brim portion 7. . Further, it is shown that the pores of the porous layer 2 are not closed or crushed by the bonding. The artificial cornea 4 shown in FIGS. 7 (a) and 7 (b) has an optical part 5 having a front surface 5a, a rear surface 5b and a side surface 5c, and a side surface of the optical unit 5. 5c A part formed integrally with the flange 7 protruding outward from the force and the protrusion 8 of the flange 7 and the support 6 are separately manufactured. For example, the surface 3c of the non-porous layer 3 which is the rear surface 6a of the support portion 6 and the front surface 7a of the metal portion 7 were adhered using a solvent or the like as appropriate. That is, it can be obtained by providing a through-hole 9 extending from the rear surface 7b of the collar portion 7 to the porous layer 2 of the support portion 6.
図 7 ( a )お よ び 7 ( b )にお い て は、 該貫通孔 9 が設 け ら れて い る た め 、 支持部 6 内 の多孔質層 2 の孔 内 に入 り 込 んだ眼組織に該貫通孔 9 を通 し て房水か ら の栄養分 を 供 給す る こ と がで き る 。 In FIGS. 7 (a) and 7 (b), since the through-holes 9 are provided, they penetrate into the holes of the porous layer 2 in the support portion 6. Nutrients from aqueous humor can be supplied to the ocular tissue through the through holes 9.
なお 、 図 7 (a)お よ び 7 (b)中 の 図 4 と 同 じ参照符号 は 図 4 と 同 じ参照符号 の領域 を示 し て い る 。 Note that the same reference numerals as in FIG. 4 in FIGS. 7 (a) and 7 (b) indicate the areas of the same reference numerals as in FIG.
ま た 、 図 4 、 5 (a) , 5 (b)、 6 、 7 (a)お よ び 7 (b)の 人工角膜 4 は い ずれ も ツバ部 7 が支持部 6 よ り も 突 出 し た部分 8 を有 し て い る 。 本発明 の 人工角 膜にお い て該 ッ バ部の突出部分 は必須 の構成部分で はな い が、 ッバ部 は 突出部分 を有す る こ と が好 ま し い 。 Further, in all of the artificial corneas 4 shown in FIGS. 4, 5 (a), 5 (b), 6, 7 (a), and 7 (b), the brim portion 7 protrudes beyond the support portion 6. Has part 8 In the artificial cornea of the present invention, the projecting portion of the hub is not an essential component, but the hub preferably has a projecting portion.
さ ら に 、 図 4 、 6 お よ び 7 (a)に 示 さ れた 人工角 膜 4 は、 い ずれ も 曲率が付与 さ れた も の で あ る が、 本発 明 の 人工角 膜は、 曲率 の有無 に 限定 さ れ る も の で はな い 。 In addition, the artificial cornea 4 shown in FIGS. 4, 6 and 7 (a) has a curvature, but the artificial cornea of the present invention has However, it is not limited to the presence or absence of curvature.
図 8 は、 角 膜の 全層 を 人工角 膜 に 置換 し た場合 （全層 移植） の移植状態 を表わす一実施態様 の 概略断面 図で あ る 。 支持部 6 の外側 の 側面 6 b と 角 膜 10の切 開 創面 10 a と は接触 し て い る 。 ま た、 ッノ 部 7 の突 出部分 8 は、 角 膜 10の 内面 （後面） 10bに 隣接す る よ う 眼房 内 に位置 し
て い る 。 図 8 に お い て は、 支持部 6 と 角 膜 10と を縫合糸 11に よ り 縫合す る こ と に よ り 、 人工角膜は固定 さ れ る 。 FIG. 8 is a schematic cross-sectional view of one embodiment showing an implanted state when the entire cornea is replaced with an artificial cornea (all-layer implant). The outer side surface 6b of the support portion 6 and the incision wound surface 10a of the cornea 10 are in contact with each other. The protruding portion 8 of the tongue portion 7 is located in the eye chamber so as to be adjacent to the inner surface (rear surface) 10b of the cornea 10. ing . In FIG. 8, the artificial cornea is fixed by suturing the support portion 6 and the cornea 10 with the suture 11.
な お 、 図 8 中 の 図 4 と 同 じ参照符号は、 図 4 と 同 じ 参 照符号 の領域 を 示 し て い る 。 Note that the same reference numerals as in FIG. 4 in FIG. 8 indicate the areas of the same reference numerals as in FIG.
図 9 (a)は人工角 膜 4 を移植 し た 日 本 白 色家兎 の角 膜 1 0に つ い て 、 該 人工角 膜 4 と 該家兎角 膜 10の 界面 の 断面 を 、 移植期 間 2 力 月 後 に 、 ト ルイ ジ ン ブルー組織染色 に よ り 観察 し た写真で あ り 、 図 9 (b)は図 9 (a)を説明 す る た め の ス ケ ッ チ 図で あ る 。 FIG. 9 (a) shows the cross section of the interface between the artificial cornea 4 and the rabbit cornea 10 for the cornea 10 of a Japanese white rabbit transplanted with the artificial cornea 4 during the transplantation period. This is a photograph observed by toluidine blue tissue staining two months later, and FIG. 9 (b) is a sketch for explaining FIG. 9 (a). .
本写真 図 9 (a)に お い て は、 細胞組織部分 の み染色 さ れてお り 、 図 9 (b)を参照す る と支持部 6 の 多孔質層 2 、 非多孔質層 3 、 ッパ部 7 お よ びツバ部 7 の突出部分 8 の 人工角膜 4 の材料部分は染色 さ れて い な い 。 In FIG. 9 (a), only the cell tissue portion was stained. Referring to FIG. 9 (b), the porous layer 2, the non-porous layer 3, The material portion of the artificial cornea 4 at the protruding portion 8 of the lid portion 7 and the collar portion 7 is not stained.
な お 、 図 9 (a)は 、 白 黒 で あ る た め 、 染色 さ れ た 組織 は黒 く 示さ れて い る が、 実際 はお お よそ青紫 に染色 さ れ て い る 。 In FIG. 9 (a), the stained tissue is shown in black because it is black and white, but in fact it is almost blue-violet.
図 9 (a)の ス ケ ッ チ 図で あ る 図 9 (b)を参照す る と 、 図 9 (a)に お い て参照 符号 2 、 3 、 3 c 、 7 、 7 a お よ び 8 で示 さ れた領域は実際 に は 白 色 ま た は透明で あ る が、 図 9 ( a )が 白 黒で あ る た め 、 図 9 ( a )に は表わ さ れて い な レ 。 図 9 (a) に お い て 、 支持部 6 の 多孔 質 層 2 の 孔 2 a に相 当 する部分 に該家兎角膜 10の眼組織が侵入 し界面で 融合 し て い る こ と がわ か る 。 さ ら に 、 非多孔質 層 3 、 ッ バ部 7 お よ びッ ノ 部 7 の突出部分 8 が存在す る 位置 に 、 該家兎角膜 10の 眼組織が全 く 存在 して いな い こ と か ら 、 非多孔質層 3 と ッノ 部 7 と が、 非多孔質層 3 の表面 3 c と ッノ 部 7 の 前面 7 a と で強 固 に 接着 し てお り 、 さ ら に ツ バ部 7 の突出部分 8 が眼組織 の 人工角膜後面へ の 回 り
込み を 阻止 し て い る 様子 も観察 さ れ る 。 Referring to FIG. 9 (b), which is a sketch diagram of FIG. 9 (a), reference numerals 2, 3, 3c, 7, 7a and 7a in FIG. 9 (a) Although the area shown in Fig. 8 is actually white or transparent, it is not shown in Fig. 9 (a) because Fig. 9 (a) is black and white. Les. In FIG. 9 (a), it can be seen that the eye tissue of the rabbit cornea 10 has penetrated into the portion corresponding to the hole 2a of the porous layer 2 of the support portion 6 and has been fused at the interface. I do. Further, no ocular tissue of the rabbit cornea 10 is present at the position where the non-porous layer 3, the protrusion 7 and the protrusion 8 of the hook 7 are present. Therefore, the non-porous layer 3 and the tongue portion 7 are firmly adhered to the front surface 3c of the non-porous layer 3 and the front surface 7a of the tongue portion 7, and the collar is further The protruding part 8 of the part 7 is the rotation of the eye tissue to the posterior surface of the artificial cornea It is also observed that the intrusion is blocked.
つ ぎ に 、 本発明 の 医療用膜 を 以下 の実施例 に も と づい て さ ら に詳細 に説明す る が、 本発 明 はか か る 実施例 の み に 限定 さ れ る も の で はな い 。 Next, the medical membrane of the present invention will be described in more detail based on the following examples, but the present invention is not limited to only these examples. Absent .
実施例 1 〔塩添加抽 出法 に よ る 2 層膜の 作製〕 Example 1 [Preparation of two-layer film by salt extraction method]
図 1 に示す多孔質層 2 お よ び非多孔質 層 3 か ら な る 医 療用 膜 1 を 作製 し た 。 A medical membrane 1 comprising the porous layer 2 and the non-porous layer 3 shown in FIG. 1 was produced.
市販の 医療用 ポ リ ウ レ タ ン を テ ト ラ ヒ ド ロ フ ラ ン に溶 解 さ せ濃度 5. 0重量 ％ の溶液 を作製 し た 。 そ の ポ リ ウ レ タ ン の テ ト ラ ヒ ド ロ フ ラ ン溶液 に 、 ポ リ ウ レ タ ン と 塩化 ナ ト リ ゥ ム の 総重量 に お け る 塩化 ナ ト リ ゥ ム の重量割合 が 60重量 ％ と な る よ う に塩化ナ ト リ ゥ ム を混合 し分散 さ せた 。 塩化ナ ト リ ゥ ム は 目 開 き が 32 μ πιお よ び 53 μ ΐηの ふ る い を用 い て選別 し た も の を 用 い た。 Commercially available medical polyurethane was dissolved in tetrahydrofuran to prepare a 5.0% by weight solution. The weight ratio of sodium chloride to the total weight of polyurethan and sodium chloride in the polyurethan solution in tetrahydrofuran Sodium chloride was mixed and dispersed so that the weight ratio became 60% by weight. The sodium chloride used was one that had been screened using a sieve with openings of 32 μπι and 53 μπη.
塩化ナ ト リ ウ ム が充分 に分散 し た 前記 テ ト ラ ヒ ド ロ フ ラ ン溶液の懸濁溶液 を 直径 4 cmの ガ ラ ス シ ヤ ー レ に 12. 9 g 流延 し た 。 ガ ラ ス シ ャ ー レ を ガ ラ ス デ シ ケ 一 夕 一内 に 、 密封状態で 22時間 静置 し 、 塩化ナ ト リ ウ ム を溶液 中 で沈殿 さ せた 。 そ の の ち 、 ガ ラ ス デシ ケ一 夕一を 開 放 し 、 テ ト ラ ヒ ド ロ フ ラ ン を 気化 さ せ除去 し た 。 得 ら れた ポ リ ゥ レ タ ンお よ び塩化ナ ト リ ゥ ム 混合膜を 蒸留水 中 に 浸漬 し 、 塩化ナ ト リ ウ ム を抽出 し た 。 こ れ を 乾燥 し ポ リ ウ レ タ ン膜 を得た 。 12.9 g of a suspension of the tetrahydrofuran solution in which sodium chloride was sufficiently dispersed was cast on a glass cylinder having a diameter of 4 cm. The glass shale was allowed to stand in a glass desiccator overnight for 22 hours in a sealed state to precipitate sodium chloride in the solution. After that, the glass desiccator was released, and tetrahydrofuran was vaporized and removed. The obtained mixture of polyester and sodium chloride was immersed in distilled water to extract sodium chloride. This was dried to obtain a polyurethane film.
作製 し た膜の 断面 を 日 本電子 （株）製 の 走査顕微鏡 JSM — 5410LVに て 、 倍率 50倍で観察 し た結果、 図 1 に 示す よ う に膜 1 は多孔質層 2 と 非多孔質層 3 の 2 層構造 を形 成 し て い る 様子が確認 さ れた 。 ま た 、 そ の界面 は一体化 し てお り 、 多孔質層 2 に は径が 30〜50 z m程度の 連続孔
が存在す る 様子が観察 さ れた 。 さ ら に 、 膜の全体の厚み は 0. 7mmで あ り 、 そ の う ち 非多孔質層 3 の厚み は 0. 2m mで あ つ に 。 As a result of observing the cross section of the fabricated film with a scanning microscope JSM-5410LV manufactured by Nippon Denshi Co., Ltd. at a magnification of 50 times, as shown in FIG. The formation of a two-layer structure of layer 3 was confirmed. In addition, the interface is integrated, and the porous layer 2 has continuous pores having a diameter of about 30 to 50 zm. It was observed that there existed. Furthermore, the overall thickness of the membrane is 0.7 mm, and the thickness of the non-porous layer 3 is 0.2 mm.
実施例 2 〔塩添加抽 出法 に よ る 2 層膜の作製〕 Example 2 [Preparation of two-layer film by salt extraction method]
多孔質層 の孔径 を実施例 1 記載 の膜 と 変 えて 医療用 膜 を 作製 し た 。 A medical membrane was produced by changing the pore diameter of the porous layer from the membrane described in Example 1.
市販 の 医療用 ポ リ ウ レ タ ン を テ ト ラ ヒ ド ロ フ ラ ン に溶 解 さ せ濃度 3. 0重量 ％ の 溶液 を作製 し た 。 そ の ポ リ ウ レ タ ン の テ ト ラ ヒ ド ロ フ ラ ン溶液 に 、 ポ リ ウ レ タ ン と 塩化 ナ ト リ ゥ ム の総重量に お け る 塩化ナ ト リ ゥ ム の 重量割合 が 70重量 ％ と な る よ う に塩化ナ ト リ ゥ ム を混合 し分散 さ せた。 塩化 ナ ト リ ゥ ム は 目 開 き が 53 μ mお よ び 106 mの ふ る い を用 いて選別 し た も の を用 い た 。 Commercially available medical polyurethane was dissolved in tetrahydrofuran to prepare a 3.0 wt% solution. The weight ratio of sodium chloride to the total weight of polyurethan and sodium chloride in the polytetrahydrofuran tetrahydrofuran solution Sodium chloride was mixed and dispersed so that the weight ratio became 70% by weight. The sodium chloride used was selected by using a sieve having openings of 53 μm and 106 m.
塩化 ナ ト リ ウ ム が充分 に分散 し た前記テ ト ラ ヒ ド ロ フ ラ ン溶液の 懸濁溶液を直径 6 cmの ガ ラ ス シ ャ 一 レ に 19. 3 g 流延 し た 。 ガ ラ ス シ ャ ー レ を ガ ラ ス デ シ ケ 一 夕 一内 に 、 密封状態で 2 時間静置 し 、 塩化 ナ ト リ ウ ム を溶液中 で沈殿 さ せ た。 そ の の ち 、 ガ ラ ス デ シ ケ一 夕 一 を 開放 し 、 テ ト ラ ヒ ド ロ フ ラ ン を気化 さ せ除去 し た 。 得 ら れた ポ リ ウ レ タ ンお よ び塩化ナ ト リ ウ ム 混合膜 を蒸留水 中 に浸漬 し 、 塩化ナ ト リ ウ ム を抽 出 し た 。 こ れ を 乾燥 し ポ リ ウ レ タ ン膜 を得 た 。 19.3 g of a suspension of the tetrahydrofuran solution in which sodium chloride was sufficiently dispersed was cast onto a glass cylinder having a diameter of 6 cm. The glass shale was allowed to stand in a glass dessicator overnight for 2 hours in a sealed state to precipitate sodium chloride in the solution. After that, the glass desiccator was opened, and the tetrahydrofuran was vaporized and removed. The resulting mixed membrane of polyurethane and sodium chloride was immersed in distilled water to extract sodium chloride. This was dried to obtain a polyurethane film.
作製 し た膜の 断面 を 、 実施例 1 と 同様 に し て観察 し た 結果、 膜は非多孔質層 と 多孔質層 の 2 層構造 を形成 し て い る 様子が確認 さ れた 。 ま た 、 そ の界面 は一体化 し てお り 、 多孔質 層 に は径が 50〜 100 μ m程度 の連続孔が存在す る 様子が観察さ れた 。 さ ら に 、 膜の全体 の厚みは 0. 4mm で あ り 、 そ の う ち 非多孔質層 の厚み は 0. 05 mmで あ っ た 。
実施例 3 〔凍結乾燥法 に よ る 2 層膜の作製〕 図 2 に 示す多孔質層 2 お よ び非多孔質層 3 か ら な る 医 療用 膜 1 を作製 し た。 As a result of observing the cross section of the fabricated film in the same manner as in Example 1, it was confirmed that the film formed a two-layer structure of a non-porous layer and a porous layer. In addition, the interface was integrated, and it was observed that continuous pores having a diameter of about 50 to 100 μm were present in the porous layer. Further, the overall thickness of the membrane was 0.4 mm, and the thickness of the non-porous layer was 0.05 mm. Example 3 [Preparation of two-layer membrane by freeze-drying method] A medical membrane 1 composed of a porous layer 2 and a non-porous layer 3 shown in Fig. 2 was produced.
市販 の 医療用 ポ リ ウ レ タ ン を テ ト ラ ヒ ド ロ フ ラ ン に溶 解 さ せ、 濃度 4. 0重量 ％ の 溶液 を 作製 し た。 そ の溶液 6. 3 g を 直径 4 cmの ガ ラ ス シ ャ ー レ に 流延 し 、 テ ト ラ ヒ ド 口 フ ラ ン を気化 さ せポ リ ウ レ タ ン の キ ャ ス ト 膜 （非多孔 質層 3 ) を作製 し た 。 作製 し た 膜上 に濃度 5. 0重量 ％ の ポ リ ウ レ タ ン の 1 , 4 - ジォキサ ン溶液を 1. 5 g 流延 し 、 非多孔質 層 3 の表面が該溶液 に溶解 ま た は膨潤 し た 状態 で 一 20 °C で溶液 を 凍結 し た 。 減圧下で 1 ， 4 - ジ ォキサ ン を 昇華除去 し ポ リ ウ レ タ ン膜 を得 た。 A commercially available polyurethan for medical use was dissolved in tetrahydrofuran to prepare a solution having a concentration of 4.0% by weight. 6.3 g of the solution was cast on a glass cylinder having a diameter of 4 cm, and the tetrahedral port was vaporized. The cast membrane of polyurethan ( A non-porous layer 3) was prepared. 1.5 g of a 1,4-dioxane solution of 5.0% by weight of polyurethane was cast on the prepared membrane, and the surface of the non-porous layer 3 was dissolved in the solution. The solution was frozen at 20 ° C in a swollen state. The 1,4-dioxane was sublimated and removed under reduced pressure to obtain a polyurethane film.
作製 し た膜の 断面 を 、 倍率 を 75倍 と し た ほか は実施例 1 と 同様 に し て観察 し た結果、 膜 1 は多孔質層 2 と 非多 孔質層 3 の 2 層構造 を 形成 し て い る 様子が確認 さ れた 。 ま た 、 そ の界面 は一体化 し て お り 、 多孔質層 2 に は径が 10〜 50 μ m程度 の連続孔 が存在す る 様子が観察 さ れた 。 さ ら に 、 膜の全体 の厚み は 0. 5mmで あ り 、 そ の う ち 非多 孔質層 3 の厚み は 0. 1mmで あ っ た。 The cross section of the prepared membrane was observed in the same manner as in Example 1 except that the magnification was set to 75 times. As a result, the membrane 1 formed a two-layer structure of a porous layer 2 and a non-porous layer 3. It was confirmed that they were working. In addition, the interface was integrated, and it was observed that the porous layer 2 had continuous pores having a diameter of about 10 to 50 μm. Further, the overall thickness of the membrane was 0.5 mm, and the thickness of the non-porous layer 3 was 0.1 mm.
実施例 4 〔塩添加抽 出法 に よ る 3 層膜の作製〕 Example 4 [Preparation of three-layer film by salt extraction method]
図 3 に示す多孔質層 2 お よ び非多孔質層 3 a お よ び 3 b か ら な る 医療用膜 1 を作製 し た 。 A medical membrane 1 composed of the porous layer 2 and the non-porous layers 3a and 3b shown in FIG. 3 was produced.
市販の 医療用 ポ リ ウ レ タ ン を テ 卜 ラ ヒ ド ロ フ ラ ン に溶 解 さ せ、 濃度 5. 0重量 ％ の溶液 を 作製 し た 。 つ い でそ の 溶液 lO. O g を直径 4 cmの ガ ラ ス シ ャ ー レ に 流延 し 、 テ ト ラ ヒ ド ロ フ ラ ン を 気化 さ せ、 ポ リ ウ レ タ ン キ ャ ス ト 膜 (非多孔 質層 3 b ) を 作製 し た 。 濃度 4. 0 % のポ リ ウ レ タ ン の テ ト ラ ヒ ド ロ フ ラ ン溶液 に ポ リ ウ レ タ ン と 塩化ナ
ト リ ゥ ム の 総重量 に お け る 塩化 ナ ト リ ゥ ム の重量割合が 70重量 ％ と な る よ う に塩化ナ ト リ ウ ム を混合 し分散 さ せ た 。 塩化ナ ト リ ウ ム は、 目 開 き が 53 μ mお よ び 106 μ mの ふ る い を用 い て選別 し た も の を用 い た 。 塩化ナ ト リ ウ ム が充分 に分散 し た 前記テ ト ラ ヒ ド ロ フ ラ ン溶液の懸濁溶 液 8. 2 g を キ ャ ス ト 膜上 に 流延 し た 。 塩化 ナ ト リ ウ ム を 溶液中 に沈殿 さ せ、 そ の の ち テ ト ラ ヒ ド ロ フ ラ ン を 気化 さ せ除去 し た。 得 ら れたポ リ ウ レ タ ンお よ び塩化ナ 卜 リ ゥ ム混合膜 を蒸留水 中 に浸漬 し 、 塩化ナ ト リ ウ ム を抽 出 し た 。 こ れ を乾燥 し て 、 ポ リ ウ レ タ ン膜 を得た。 Commercially available polyurethan for medical use was dissolved in tetrahydrofuran to prepare a solution having a concentration of 5.0% by weight. Then, the solution l.O.Og is cast on a glass jar with a diameter of 4 cm, and the tetrahydrofuran is vaporized to obtain a polyurethan cas. A membrane (non-porous layer 3b) was produced. Polyurethane and sodium chloride were added to a 4.0% polyurethan solution in tetrahydrofuran. Sodium chloride was mixed and dispersed so that the weight ratio of sodium chloride to the total weight of the stream was 70% by weight. As the sodium chloride, those selected using a sieve having openings of 53 μm and 106 μm were used. 8.2 g of a suspension of the above tetrahydrofuran solution in which sodium chloride was sufficiently dispersed was cast on a cast membrane. Sodium chloride was precipitated in the solution, and then tetrahydrofuran was vaporized and removed. The resulting mixed membrane of polyurethane and sodium chloride was immersed in distilled water to extract sodium chloride. This was dried to obtain a polyurethane film.
作製 し た膜の 断面 を実施例 1 と 同様 に し て観察 し た結 果、 膜は多孔質層 2 が非多孔質層 3 に両側か ら 挟 ま れた 3 層構造 を 形成 し て い る 様子が確認 さ れた 。 ま た 、 そ の 界面 は一体化 し てお り 、 多孔質層 2 に は径が 50〜100 111 程度 の連続孔が存在す る 様子が観察 さ れた 。 さ ら に 、 膜 1 の全体の厚み は 0. 8mmで あ り 、 そ の う ち 非多孔質層 3 a お よ び 3 b の厚み はそれぞれ 0. 2mmで あ っ た 。 As a result of observing the cross section of the fabricated film in the same manner as in Example 1, the film had a three-layer structure in which the porous layer 2 was sandwiched between the non-porous layers 3 from both sides. The situation was confirmed. In addition, the interface was integrated, and it was observed that the porous layer 2 had continuous pores having a diameter of about 50 to 100 111. Further, the overall thickness of the membrane 1 was 0.8 mm, and the thickness of each of the non-porous layers 3a and 3b was 0.2 mm.
実施例 5 〔実施例 1 の膜を用 い た 人工角膜の作製〕 Example 5 [Production of artificial cornea using membrane of Example 1]
( 1 ) 人工角膜の本体 の作製 (1) Fabrication of artificial cornea body
透明 なポ リ メ チル メ タ ク リ レ ー ト を 切削加工す る こ と に よ り 、 光学部 5 、 光学部 5 の側面 5 c か ら 環状外側 に 突 出 し た ッ ノ 部分 7 お よ びそ の突 出部分 8 がー体 と な つ た 図 4 、 5 (a)お よ び 5 (b)に示す人工角膜の本体 （光学 部 は、 厚み 0. 9mm、 外径 4. 0mm、 前面 曲率半径 8. 0mm、 後面 曲率半径 7. 1mmで 、 ッ ノ 部は、 厚み 0. 2mm、 外径 7. 5mm、 前面 曲率半径 7. 3mm、 後面 曲率半径 7. lmm) を 作製 し た。 By cutting a transparent polymer metal acrylate, the optical part 5 and the tongue part 7 protruding from the side surface 5c of the optical part 5 to the outside of the ring. The body of the artificial cornea shown in Figs. 4, 5 (a) and 5 (b) with the projection 8 of the corneal body (the optics is 0.9mm thick, 4.0mm outer diameter, front The radius of curvature was 8.0 mm, the rear surface had a radius of curvature of 7.1 mm, and the knob had a thickness of 0.2 mm, an outer diameter of 7.5 mm, a front surface radius of curvature of 7.3 mm, and a rear surface radius of curvature of lmm).
( 2 ) 支持部の作製お よ び本体 と の接着
人工角膜 4 の支持部 6 と し て 、 実施例 1 記載の ポ リ ウ レ 夕 ン膜を 直径 4 mmお よ び 7 mmの ト レパ ン を用 い て ド 一ナ ツ 状 に打ち 抜 き 、 非多孔質層 3 が支持部 6 の後面側 と な る よ う に 人工角 膜本体 の光学部 5 に はめ 合わせ、 ポ リ ウ レ タ ン膜の 非多孔質層 3 の表面 3 c と 人工角 膜本体 の ッ ノ 部 7 の 前面 7 a と を テ ト ラ ヒ ド ロ フ ラ ン を 用 レ て 接着 し た （ 図 4 参照） 。 (2) Preparation of the support part and adhesion to the main body As the supporting portion 6 of the artificial cornea 4, the polyurea silicone membrane described in Example 1 is punched into a donut shape using a 4 mm and 7 mm diameter trepan. Then, the non-porous layer 3 is fitted to the optical part 5 of the artificial corneal body such that the non-porous layer 3 is on the rear side of the support part 6, and the surface 3c of the non-porous layer 3 of the polyurethane film is The front surface 7a of the tongue portion 7 of the cornea body was bonded to the front surface 7a using tetrahydrofuran (see Fig. 4).
作製 し た 人工角膜本体の ツバ部 7 と 支持部 6 と の接着 部分 を観察 し た 結果 を 図 6 に示す。 支持部 6 の 非多孔質 層 3 と 人工角 膜本体の ツバ部 7 の前面 7 a と が強 固 に接 着 し て い る こ と が確認 さ れた 。 ま た 、 支持部 6 の多孔質 層 2 は、 接着 に よ り そ の孔が塞がれた り 、 潰 さ れ る こ と な く 存在す る 様子が確認さ れた 。 Figure 6 shows the result of observing the bonding portion between the collar 7 and the support 6 of the fabricated artificial corneal body. It was confirmed that the non-porous layer 3 of the support portion 6 and the front surface 7a of the collar portion 7 of the artificial corneal body were firmly adhered. In addition, it was confirmed that the porous layer 2 of the support portion 6 was present without being closed or crushed by the bonding.
実施例 6 〔実施例 2 よ り 得 ら れた膜 を用 い た 人工角 膜の 作製〕 Example 6 [Production of artificial cornea using membrane obtained from Example 2]
( 1 ) 人工角 膜本体の作製 (1) Fabrication of artificial cornea body
人工角膜 の本体 を実施例 5 と 同様 に し て作製 し た 。 た だ し 、 光学部 は、 厚み 0. 5 mm、 外径 4. 0 mm、 前面 曲 率 半径 8. Omm、 後面 曲率半径 7. 5 mmで、 ツ バ部は厚み 0. lmm、 外径 7. 5mm、 前面 曲率半 径 7. 6mm、 後面 曲 率半 径 7. 5mmと し た。 The main body of the artificial cornea was prepared in the same manner as in Example 5. However, the optical section has a thickness of 0.5 mm, an outer diameter of 4.0 mm, a front curvature radius of 8. Omm, and a rear curvature radius of 7.5 mm. The collar section has a thickness of 0.1 mm and an outer diameter of 7 mm. .5mm, front radius of curvature 7.6mm, rear radius of curvature 7.5mm.
( 2 ) 支持部 の作製お よ び本体 と の接着 (2) Preparation of support part and adhesion to main body
人工角膜 の支持部 と し て 、 実施例 2 記載 の ポ リ ウ レ 夕 ン膜を 用 い た 。 こ の膜 を 直径 4 mmお よ び 8 mmの ト レパ ン を用 い ド 一 ナ ツ 状 に打ち 抜 き 、 非多孔質層が後面側 と な る よ う に 人工角 膜本体 の光学部 に はめ 合わせ 、 ポ リ ウ レ タ ン膜の 非多孔質層表面 と 人工角 膜本体の ツ バ部 の 前 面 と を テ ト ラ ヒ ド ロ フ ラ ン を用 い て接着 し た 。
得 ら れた 人工角 膜の 支持部 と 本体は強固 に 接着 し て い て、 支持部 の多孔質層 の孔が潰 さ れて い な い こ と が確認 さ れた 。 As the supporting portion of the artificial cornea, the polyurea membrane described in Example 2 was used. This film is punched out in a donut shape using a 4 mm and 8 mm diameter trepan, and the optical part of the artificial corneal body is placed so that the non-porous layer is on the back side. Then, the surface of the non-porous layer of the polyurethan film and the front surface of the collar portion of the artificial corneal body were bonded using tetrahydrofuran. The support and the main body of the obtained artificial cornea were firmly adhered to each other, and it was confirmed that the pores of the porous layer of the support were not crushed.
実施例 7 〔人工角 膜の 穿孔〕 Example 7 (Perforation of artificial cornea)
実施例 5 に て作製 し た 人工角 膜 4 を エ キ シマ レ ーザ一 ( レーザー ガ ス ： K r F 、 発振波長 ： 248 nm、 装置 ： 住 友重機械工業 （株）製の INDEX 846 ) を 用 い て 人工角 膜 4 の ツ バ部 7 、 お よ び支持部 6 の非多孔質層 3 の 穿孔 を行な い 、 図 7 に示 さ れ る 0. 5mm X 0. 5mmの正方形 の貫 通孔 9 を 、 光学部 5 を 中心 と し た 同心 円 の環上 に均等 間 隔で 6 個作製 し た 。 The artificial cornea 4 prepared in Example 5 was applied to an excimer laser (laser gas: KrF, oscillation wavelength: 248 nm, device: INDEX 846 manufactured by Sumitomo Heavy Industries, Ltd.). The perforated portion 7 of the artificial cornea 4 and the non-porous layer 3 of the support portion 6 are perforated by using a square having a square shape of 0.5 mm × 0.5 mm shown in FIG. Six through-holes 9 were formed at equal intervals on a concentric ring centered on the optical part 5.
なお、 得 ら れた 人工角膜 4 の後面か ら 実施例 1 と 同様 に し て観察 し た結果、 レーザー 照射 に よ っ て作製 し た孔 9 か ら 支持部 6 の 多孔質層 2 を確認する こ と がで き た 。 実施例 8 〔人工角 膜の移植〕 Observation was made from the back side of the obtained artificial cornea 4 in the same manner as in Example 1, and as a result, the porous layer 2 of the support portion 6 was confirmed from the holes 9 formed by laser irradiation. I was able to do this. Example 8 (Transplantation of artificial cornea)
( 1 ) 人工角 膜本体 の作製 (1) Fabrication of artificial corneal body
人工角 膜の本体 を 実施例 5 と 同様 に し て作製 し た 。 ( 2 ) 支持部 の 作製 The main body of the artificial cornea was prepared in the same manner as in Example 5. (2) Preparation of support
市販 の 医療用 ポ リ ウ レ タ ン を テ ト ラ ヒ ド ロ フ ラ ン に溶 解 さ せ濃度 4. 0重量 ％ の溶液 を 作製 し た 。 そ の ポ リ ウ レ タ ン の テ ト ラ ヒ ド ロ フ ラ ン溶液 に 、 ポ リ ウ レ タ ン と 塩化 ナ ト リ ウ ム の総重量 に お け る 塩化ナ ト リ ゥ ム の 重量割合 が 70重量 ％ と な る よ う に塩化ナ ト リ ゥ ム を混合 し 分散 さ せた 。 塩ィ匕 ナ ト リ ゥ ム は 目 開 き が 32 μ mお よ び 53 μ mの ふ る い を 用 い て選別 し た も の を 用 い た。 Commercially available medical polyurethane was dissolved in tetrahydrofuran to prepare a 4.0% by weight solution. The weight ratio of sodium chloride to the total weight of polyurethan and sodium chloride in the tetrahydrofuran solution of the polyurethane Sodium chloride was mixed and dispersed so as to be 70% by weight. For Shii-Dani, we used those that were screened using sieves with openings of 32 μm and 53 μm.
塩化ナ ト リ ウ ム が充分 に分散 し た前記テ ト ラ ヒ ド ロ フ ラ ン溶液 の懸濁溶液 を直径 6 c mの ガ ラ ス シ ヤ ー レ に 24. 6 g 流延 し た 。 ガ ラ ス シ ャ ー レ を ガ ラ ス デ シ ケ 一 夕一内
に 、 密封状態で 72時間静置 し 、 塩化ナ ト リ ウ ム を 溶液 中 で沈殿 さ せ た 。 そ の の ち 、 ガ ラ ス デシ ケ一 タ ー を 開 放 し 、 テ ト ラ ヒ ド ロ フ ラ ン を気化 さ せ除去 し た 。 得 ら れた ポ リ ウ レ タ ンお よ び塩化ナ ト リ ゥ ム 混合膜を 蒸留水 中 に浸漬 し 、 塩化ナ ト リ ウ ム を抽 出 し た 。 こ れ を乾燥 し ポ リ ウ レ タ ン膜 を得 た 。 24.6 g of a suspension of the above tetrahydrofuran solution in which sodium chloride was sufficiently dispersed was cast on a glass flask having a diameter of 6 cm. Place the glassware in the glass dessert Then, the mixture was allowed to stand in a sealed state for 72 hours to precipitate sodium chloride in the solution. After that, the glass desiccator was released, and the tetrahydrofuran was vaporized and removed. The obtained mixed membrane of polyurethane and sodium chloride was immersed in distilled water to extract sodium chloride. This was dried to obtain a polyurethane film.
作製 し た膜の 断面 を 、 実施例 1 と 同様 に し て観察 し た 結果、 膜は多孔質層 と 非多孔質層 の 2 層構造 を形成 し て い る 様子が確認 さ れた。 ま た 、 そ の界面 は一体化 し てお り 、 多孔質層 に は径が 30〜 50 ^ m程度 の 連続孔が存在す る 様子が観察 さ れた 。 さ ら に 、 膜の全体 の厚みは 0. 7mm で あ り 、 そ の う ち 非多孔質層 の厚みは 0. 05mmで あ つ た 。 As a result of observing the cross section of the fabricated film in the same manner as in Example 1, it was confirmed that the film formed a two-layer structure of a porous layer and a non-porous layer. In addition, the interface was integrated, and it was observed that the porous layer had continuous pores having a diameter of about 30 to 50 ^ m. Furthermore, the overall thickness of the membrane was 0.7 mm, and the thickness of the non-porous layer was 0.05 mm.
( 3 ) 支持部 と 本体 と の接着 (3) Adhesion between support and main body
人工角 膜 の 支持部 と し て 、 前記 （2)に て 作製 し た膜 を 使用 し た ほか は実施例 5 と 同様 に し て接着 し た 。 Bonding was performed in the same manner as in Example 5 except that the membrane prepared in the above (2) was used as a support for the artificial cornea.
得 ら れた 人工角 膜の支持部 と 本体は強固 に接着 し て い て、 支持部 の 多孔質層 の孔が潰 さ れて い な い こ と が確認 さ れた 。 The support and the main body of the obtained artificial cornea were firmly adhered to each other, and it was confirmed that the pores of the porous layer of the support were not crushed.
( 4 ) 人工角 膜の移植 (4) Transplantation of artificial cornea
前記 に て作製 し た 人工角膜 を エチ レ ン ォキサイ ド に て 滅菌 し た の ち 、 日 本 白 色家兎 の 角 膜に移植 し た 。 移植手 術は、 日 本 白 色家兎の 角 膜の全層 を直径 6. 5mmの ト レ パ ンで打 ち 抜 き 、 打ち 抜 い た部分 に ッ バ部 の突出部分が角 膜の 内面 （後面） に 隣接す る よ う 眼房内 に位置す る よ う に 人工角膜 を揷入 し 、 周辺の 角 膜 と 人工角 膜の支持部 と を ナイ ロ ン縫合糸 を 用 い て鏠合す る こ と に よ り 行な っ た The artificial cornea prepared as described above was sterilized with ethylenoxide and then transplanted into the cornea of a Japanese white rabbit. In the transplantation procedure, all layers of the cornea of a Japanese white rabbit were punched out with a 6.5 mm diameter trepan, and the punched-out portion of the cornea had a protruding portion of the inner surface of the cornea. The artificial cornea is inserted so as to be located in the eye chamber so as to be adjacent to the (rear surface), and the peripheral cornea and the supporting portion of the artificial cornea are joined using a nylon suture. I did it by doing
(図 8 参照） 。 手術 は容易 に実施 さ れ、 人工角 膜 と ホ ス ト 角 膜の 間 の 接合状態 は非常 に 良好で あ っ た 。
人工角 膜移植 眼の術後の経過 は 良好で あ り 、 術後 6 力 月 経過時点 に お い て も 、 人工角 膜 と ホス ト 角 膜の 間 に 隙 間 はな く 接合状態 は良好で あ り 人工角膜の浮 き上 が り や 脱落は観察 さ れて い な い 。 ま た 、 光学部 の後面 に組織は 存在せず、 そ の 透光性は維持 さ れて い る 。 ホ ス ト 角 膜は 混濁 し て お ら ず、 前眼房は深 く 形成 さ れてお り 、 静穏な 前眼部 の 状態が保たれて い る 。 ま た 人工角膜の本体 と 支 持部 は はずれ る こ と な く 、 強固 に接着 し て い る 様子が観 察 さ れて い る 。 (See Figure 8). The operation was easy and the connection between the artificial cornea and the host cornea was very good. Artificial keratoplasty The postoperative course of the eye is good, and even at 6 months after the operation, there is no gap between the artificial cornea and the host cornea, and the joint condition is good. Yes No rising or falling of the artificial cornea has been observed. In addition, no tissue exists on the rear surface of the optical section, and the translucency is maintained. The host cornea is not turbid, the anterior chamber is deeply formed, and the calm anterior eye condition is maintained. In addition, it is observed that the main body of the artificial cornea and the supporting portion do not come off and are firmly adhered.
人工角膜移植眼の組織学的観察 ( ト ルィ ジ ン ブル一 染 色） に よ り 、 図 9 ( a )お よ び 9 ( b )に示す よ う に 、 人工角 膜支持部 6 の多孔質層 2 の孔 2 a 内 に 眼組織（角 膜組織） が侵入 し 、 人工角膜 4 と 日 本 白 色家兎の 角 膜 1 0が強固 に 癒合 し て い る 様子が観察さ れた 。 こ れ に よ り 、 人工角 膜 作製 （本体の ツ バ部 7 と支持部 6 の 接着） の 際 に 、 支持 部 6 の多孔質層 2 の孔構造が破壊 さ れ る こ と な く 、 眼組 織 （角膜組織） が侵入す る 孔 2 a が確保 さ れて い る こ と が示 さ れ、 支持部 6 の 非多孔質層 3 の表面 3 c を本体 の ツバ部 7 と の接着面 と し て用 い る 有用 性が確認 さ れた 。 産業上 の利用 可能性 Histological observation of the artificial corneal transplant eye (trisymbol monochromatic color) revealed that the artificial cornea support 6 had a porous structure as shown in FIGS. 9 (a) and 9 (b). It was observed that the ocular tissue (corneal tissue) penetrated into the hole 2a of the layer 2, and the artificial cornea 4 and the cornea 10 of the Japanese white rabbit were firmly fused. By doing so, the pore structure of the porous layer 2 of the support portion 6 is not destroyed during the production of the artificial cornea (adhesion of the collar portion 7 of the main body and the support portion 6), and the eye is not damaged. It is shown that the hole 2a through which the tissue (corneal tissue) penetrates is secured, and the surface 3c of the non-porous layer 3 of the support section 6 is bonded to the brim section 7 of the main body. Its usefulness was confirmed. Industrial applicability
本発 明 の 非多孔質層 を表面 に有す る 医療用膜を 、 ほか の 医療用 基材 と 複合 さ せて使用 す る 場合 、 た と え ば、 医 療用基材 と 膜 と の接着、接合 の工程 を経て複合化す る 際、 そ の 非多孔質層表面 を 接着面 と し て用 い る こ と に よ り 、 多孔質層 の多孔構造 に影響 を 与 え る こ と な く 接着接合す る こ と を 可能 と す る 。 ま た 、 非多孔質層 を外界 と の界面 に用 い た場合 に は、 外部か ら の細菌 、 ウ ィ ルス な ど の侵
入 を 阻止 し 、 感染 を 防止す る こ と がで き る 。 ま た可撓性 材料 を 用 い て膜を 作製 し た場合 は、 非多孔質層 の存在 に よ り 膜 自 体の形状安定性 に優れ、ま た成形 も 容易 と な る 。 When the medical film having the non-porous layer of the present invention on its surface is used in combination with another medical substrate, for example, the adhesion between the medical substrate and the film When the composite is formed through the joining process, the surface of the non-porous layer is used as the bonding surface, so that the bonding can be performed without affecting the porous structure of the porous layer. It is possible to join. In addition, when the non-porous layer is used for the interface with the outside world, invasion of bacteria, viruses, etc. from the outside. It can prevent infestation and prevent infection. Further, when a film is produced using a flexible material, the presence of the non-porous layer provides excellent shape stability of the film itself, and also facilitates molding.
と く に 、 人工角膜の支持部 と し て は、 多孔質層 と 非多 孔質層 が交互 に 2 ま た は 3 層 に積層 さ れて い る も の が好 ま し く 用 い ら れ る 。 In particular, as a support for an artificial cornea, a porous layer and a non-porous layer alternately laminated in two or three layers are preferably used. .
2 層 の場合 に は、 支持部の 非多孔質層表面 を 人工角膜 本体 と の接着面 に用 い る た め 、 多孔質層 の多孔質構造が 接着 に よ り 破壊 さ れ る こ と な く 確保 さ れ、 さ ら に 3 層 の 場合 に は、 上下 の 面が と も に 非多孔質層 で、 そ の 間 に多 孔質層 が存在す る 場合、 非多孔質層 の一表面 は本体 と の 接着面 、 も う 一表面は外界 と の 界面 に存在 し 、 感染防止 層 と し て の効果が あ る 。 In the case of two layers, the nonporous layer surface of the supporting portion is used for the bonding surface with the artificial corneal body, so that the porous structure of the porous layer is not destroyed by the bonding. In the case of three layers, the upper and lower surfaces are both non-porous layers, and if there is a porous layer between them, one surface of the non-porous layer is the main body. The other surface is at the interface with the outside world, and has an effect as an infection-preventing layer.
さ ら に、 人工角 膜本体 と 支持部 と の接合 にお い て は、 従来の よ う に コ ン ト ロ ー ル困難な接合法 に よ り 多孔質層 の孔 を必要以上 に塞いで し ま う と い う 問題点があ っ たが、 本発明 の よ う に 、 支持部 の 非多孔質層 を 人工角膜本体 と の 接着面 に 用 い て接着す る こ と に よ り 、 支持部 の 多孔質 層 の構造 を 破壊す る こ と な く 、 人工角膜を作製する こ と がで き る 。 こ れ に よ り 、 眼組織侵入 の た め の孔 を有す る 多孔質 層 の 領域が確保 さ れ、 人工角 膜の 眼への移植後 に は 良好な 眼組織の侵入が起 こ り 、 人工角 膜 と ホ ス ト 角膜 が強固 に結合す る 。
In addition, in joining the artificial corneal body and the supporting portion, the pores of the porous layer are unnecessarily closed by a conventionally difficult joining method. However, as in the present invention, the non-porous layer of the supporting portion is used for the bonding surface with the artificial corneal body, and the supporting portion is bonded. Thus, an artificial cornea can be produced without destroying the structure of the porous layer. As a result, an area of the porous layer having a hole for penetration of eye tissue is secured, and after implantation of the artificial cornea into the eye, good penetration of eye tissue occurs. The artificial cornea and the host cornea are firmly connected.
Claims
1. 多孔質層お よ び非多孔質層 が 2 層以上積層 し て い る 医療用膜。 1. A medical membrane in which two or more porous and non-porous layers are laminated.
2. 前記膜 の少な く と も一表面 に 非多孔質層 が存在す る 請求 の範 囲第 1 項記載 の 医療用 膜。 2. The medical membrane according to claim 1, wherein a non-porous layer is present on at least one surface of the membrane.
3. 前記膜 の各層が 同材質 の 可撓性材料か ら な る 請求 の 範囲第 1 項 ま た は第 2 項記載の 医療用膜。 3. The medical film according to claim 1, wherein each layer of the film is made of a flexible material of the same material.
4. (a)膜材料 を溶媒 1 に溶解 さ せた溶液 （A)と孔形成剤 を温合す る 工程、 4. (a) a step of heating the solution (A) in which the membrane material is dissolved in solvent 1 and the pore-forming agent,
(b)孔形成剤 を溶液 （A)中 で沈殿 さ せ る 工程、 (b) a step of precipitating the pore-forming agent in the solution (A);
(c)そ の の ち 、 溶媒 1 を気化 さ せ る 工程、 お よ び (c) after that, a step of vaporizing the solvent 1, and
(d)孔形成剤 を溶媒 2 に よ り 溶解抽 出す る 工程 (d) a step of dissolving and extracting the pore-forming agent in the solvent 2
か ら な る 請求の範囲第 1 項、 第 2 項 ま た は第 3 項記載 の 医療用 膜の製造方法。 4. The method for producing a medical film according to claim 1, wherein the method comprises claim 1.
5. (a)膜材料 を溶媒 1 に溶解 さ せた溶液 （A) と孔形成剤 を混合 し 、 あ ら か じ め 用 意 し た 非多孔質膜上 に流延す る 工程、 5. (a) a step of mixing the solution (A) in which the membrane material is dissolved in the solvent 1 and the pore-forming agent, and casting the mixture on a nonporous membrane prepared in advance;
(b)孔形成剤 を溶液 （A)中 で沈殿 さ せ る 工程、 (b) a step of precipitating the pore-forming agent in the solution (A);
(c)そ の の ち 、 溶媒 1 を気化 さ せ る 工程、 お よ び (c) after that, a step of vaporizing the solvent 1, and
(d)孔形成剤 を溶媒 2 に よ り 溶解抽 出す る 工程 (d) a step of dissolving and extracting the pore-forming agent in the solvent 2
か ら な る 請求 の範囲第 1 項、 第 2 項 ま た は第 3 項記載 の 医療用 膜の製造方法。 4. The method for producing a medical film according to claim 1, wherein the method comprises claim 1.
6. 孔形成剤が塩で あ る 請求 の範囲第 4 項 ま た は第 5 項 記載 の方法。 6. The method according to claim 4 or 5, wherein the pore-forming agent is a salt.
7. 膜材料 と 孔形成剤 の 総重量 に お け る 孔形成剤 の割合 が 95重量 ％ 以下で あ る 請求 の 範囲第 4 項、 第 5 項 ま た は第 6 項記載の方法。
7. The method according to claim 4, wherein the ratio of the pore-forming agent to the total weight of the membrane material and the pore-forming agent is 95% by weight or less.
8. (a)膜材料 を溶媒 3 に溶解 さ せた溶液 （B)を 、 あ ら か じ め 用 意 し た 非多孔質膜上 に流延す る 工程、 お よ び (b)非多孔質膜表面が溶液 （B)に溶解 ま たは膨潤 し た状 態で溶液 （ B )を 凍結 し 、 減圧下で溶媒 3 を 除去す る ェ 口 か ら な る 請求 の範 囲第 1 項、 第 2 項 ま た は第 3 項記載 の 医療用 膜の 製造方法。 8. (a) A step of casting a solution (B) obtained by dissolving the membrane material in solvent 3 onto a previously prepared nonporous membrane, and (b) a step of casting a nonporous membrane. Claim 1, wherein the solution (B) is frozen in a state where the surface of the porous membrane is dissolved or swollen in the solution (B), and the solvent 3 is removed under reduced pressure. 3. The method for producing a medical membrane according to paragraph 2 or 3.
9. 請求の 範囲第 1 項、 第 2 項 ま た は第 3 項記載 の 医療 用 膜か ら な る 人工角膜用 膜。 9. An artificial corneal membrane comprising the medical membrane according to claim 1, 2, or 3.
10. 請求の 範囲第 1 項、 第 2 項 ま た は第 3 項記載の 医療 用 膜か ら な る 人工角膜の支持部用 膜。 10. A membrane for a support portion of an artificial cornea, comprising the medical membrane according to claim 1, 2, or 3.
11. (a)光学的 に透明 な素材か ら な り 、前面 と 後面 と 側面 と を有す る 光学部 と 、 光学部の側面か ら 外側 に突 出 し た ッ バ部か ら な る 本体、 お よ び 11. (a) A body made of an optically transparent material, having an optical part with front, rear, and side surfaces, and a hub that protrudes outward from the side of the optical part. , and
(b)該光学部 の側面 の 少 な く と も 一部 を 取 り 囲 む支持 部 (b) a support that surrounds at least a portion of the side of the optical section
よ り な る 人工角 膜 にお い て 、 そ の支持部が請求 の 範 囲 第 10項記載 の支持部用 膜か ら な る 人工角膜。 An artificial cornea, wherein the supporting portion comprises the supporting portion film according to claim 10.
12. 前記支持部 の非多孔質層表面 を 本体 と の 接合面 に用 い る 請求の範 囲第 11項記載の人工角膜。 12. The artificial cornea according to claim 11, wherein a surface of the non-porous layer of the support portion is used as a joint surface with a main body.
13. ツ バ部がそ の後面 と 光学部の後面 と が同 一面 に な る よ う に光学部 の側面か ら 外側 に突 出 し て お り 、 光学部 の側面 の 少な く と も 一部 を取 り 囲 む支持部の 非多孔質 層表面が該ツバ部 の前面 と 接合 し て い る 請求 の範 囲第 11項 ま た は第 12項記載 の 人工角 膜。 13. The collar protrudes outward from the side of the optical unit so that the rear surface and the rear surface of the optical unit are flush with each other, and at least a part of the side surface of the optical unit. 13. The artificial cornea according to claim 11, wherein the surface of the non-porous layer of the supporting portion surrounding the supporting portion is joined to the front surface of the collar portion.
14. 前記 ツ バ部が支持部 よ り 外側 に 張 り 出 し て い る 突 出 部分 を有す る 請求 の範 囲 11項、第 12項 ま た は第 13項記 載の 人工角 膜。
14. The artificial cornea according to claim 11, wherein the collar has a protruding portion projecting outward from a support portion.
15. ツバ部 の後面か ら 支持部 の多孔質層 ま で達す る 孔 が 設 け ら れて い る 請求の 範囲第 11項、 第 12項、 第 13項、 ま た は第 14項記載 の 人工角膜。 15. A hole defined from the back surface of the collar portion to the porous layer of the support portion is provided, according to claim 11, 12, 13, or 14, Artificial cornea.
16. ( a )光学的 に透明 な 素材か ら な る り 、前面 と 後面 と 側 面 と を 有す る 光学部 と 、 光学部 の側面か ら 外側 に突 出 し た ツ バ部か ら な る 人工角膜本体 を作製す る 工程、 (b)前記医療用 膜 を 作製す る 工程、 お よ び 16. (a) An optical part that is made of an optically transparent material and has an anterior surface, a posterior surface, and a side surface, and a collar part that protrudes outward from the side surface of the optical part. (B) a step of preparing the medical membrane, and (b) a step of preparing the medical membrane.
( c )該光学部 の側面 の 少な く と も 一部 を 取 り 囲 む支持 部 と し て 、 （b)で得 ら れた 医療用 膜 を 用 い 、 該膜の 非 多孔質 層 表面 を （a)の 本体 と の 接合面 と し て 、 本体 と 該膜を 接合す る 工程 (c) The medical film obtained in (b) is used as a support that surrounds at least a part of the side surface of the optical unit, and the surface of the non-porous layer of the film is used as the support. (A) the step of bonding the main body and the membrane as a bonding surface with the main body
か ら な る 請求 の範 囲第 11項、 第 12項、 第 13項、 第 14 項 ま た は第 15項記載の 人工角膜の製造方法。
The method for producing an artificial cornea according to claim 11, claim 12, claim 13, claim 14, or claim 15, which comprises the claim.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002542307A JPWO2002039930A1 (en) | 2000-11-17 | 2001-02-09 | Medical membrane and method for producing the same, and artificial cornea using the same and method for producing the same |
| AU2001232260A AU2001232260A1 (en) | 2000-11-17 | 2001-02-09 | Film for medical use and process for the production thereof, and artificial cornea with the use of the same and process for the production thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000351815 | 2000-11-17 | ||
| JP2000/351815 | 2000-11-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002039930A1 true WO2002039930A1 (en) | 2002-05-23 |
Family
ID=18824800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2001/000917 WO2002039930A1 (en) | 2000-11-17 | 2001-02-09 | Film for medical use and process for the production thereof, and artificial cornea with the use of the same and process for the production thereof |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPWO2002039930A1 (en) |
| AU (1) | AU2001232260A1 (en) |
| WO (1) | WO2002039930A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008093451A (en) * | 2002-08-09 | 2008-04-24 | Ottawa Health Research Inst | Ocular implant |
| JP2011139898A (en) * | 2009-12-08 | 2011-07-21 | Jms Co Ltd | Porous member, method for causing porosity, and method for manufacturing the porous member |
| KR101796801B1 (en) * | 2009-08-13 | 2017-11-10 | 아큐포커스, 인크. | Masked intraocular implants and lenses |
| US11338067B2 (en) * | 2017-03-30 | 2022-05-24 | Marquette University | Synthetic prosthesis for use in osteo-odonto-keratoprosthesis (OOKP) surgery |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04158859A (en) * | 1990-10-23 | 1992-06-01 | Seiko Epson Corp | artificial cornea |
| WO1995020367A1 (en) * | 1987-07-07 | 1995-08-03 | Jacob Labarre Jean T | Intraocular prostheses |
| JPH09182762A (en) * | 1995-12-28 | 1997-07-15 | Menicon Co Ltd | Artificial cornea |
| WO1998020813A1 (en) * | 1996-11-13 | 1998-05-22 | Menicon Co., Ltd. | Artificial cornea |
-
2001
- 2001-02-09 JP JP2002542307A patent/JPWO2002039930A1/en active Pending
- 2001-02-09 WO PCT/JP2001/000917 patent/WO2002039930A1/en active Application Filing
- 2001-02-09 AU AU2001232260A patent/AU2001232260A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995020367A1 (en) * | 1987-07-07 | 1995-08-03 | Jacob Labarre Jean T | Intraocular prostheses |
| JPH04158859A (en) * | 1990-10-23 | 1992-06-01 | Seiko Epson Corp | artificial cornea |
| JPH09182762A (en) * | 1995-12-28 | 1997-07-15 | Menicon Co Ltd | Artificial cornea |
| WO1998020813A1 (en) * | 1996-11-13 | 1998-05-22 | Menicon Co., Ltd. | Artificial cornea |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008093451A (en) * | 2002-08-09 | 2008-04-24 | Ottawa Health Research Inst | Ocular implant |
| KR101796801B1 (en) * | 2009-08-13 | 2017-11-10 | 아큐포커스, 인크. | Masked intraocular implants and lenses |
| JP2011139898A (en) * | 2009-12-08 | 2011-07-21 | Jms Co Ltd | Porous member, method for causing porosity, and method for manufacturing the porous member |
| US11338067B2 (en) * | 2017-03-30 | 2022-05-24 | Marquette University | Synthetic prosthesis for use in osteo-odonto-keratoprosthesis (OOKP) surgery |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001232260A1 (en) | 2002-05-27 |
| JPWO2002039930A1 (en) | 2004-03-18 |
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