CN104825493A - Biological sheep membrane for ocular surface treatment and preparation method thereof - Google Patents
Biological sheep membrane for ocular surface treatment and preparation method thereof Download PDFInfo
- Publication number
- CN104825493A CN104825493A CN201510228017.7A CN201510228017A CN104825493A CN 104825493 A CN104825493 A CN 104825493A CN 201510228017 A CN201510228017 A CN 201510228017A CN 104825493 A CN104825493 A CN 104825493A
- Authority
- CN
- China
- Prior art keywords
- amniotic membrane
- bioamnion
- cut
- treatment
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 241001494479 Pecora Species 0.000 title abstract 12
- 239000012528 membrane Substances 0.000 title abstract 12
- 238000004381 surface treatment Methods 0.000 title abstract 2
- 238000005520 cutting process Methods 0.000 claims abstract description 52
- 230000001954 sterilising effect Effects 0.000 claims abstract description 34
- 239000000463 material Substances 0.000 claims abstract description 31
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 29
- 210000001691 amnion Anatomy 0.000 claims description 223
- 238000000034 method Methods 0.000 claims description 26
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 23
- 210000002826 placenta Anatomy 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 22
- 238000005070 sampling Methods 0.000 claims description 16
- 239000000020 Nitrocellulose Substances 0.000 claims description 12
- 229920001220 nitrocellulos Polymers 0.000 claims description 12
- 235000011187 glycerol Nutrition 0.000 claims description 11
- 238000004321 preservation Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 238000004806 packaging method and process Methods 0.000 claims description 10
- 239000002504 physiological saline solution Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 230000001681 protective effect Effects 0.000 claims description 9
- 238000010894 electron beam technology Methods 0.000 claims description 6
- 230000005251 gamma ray Effects 0.000 claims description 6
- 230000005865 ionizing radiation Effects 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 3
- 238000009434 installation Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 16
- 241000700605 Viruses Species 0.000 abstract description 10
- 230000005855 radiation Effects 0.000 abstract description 7
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 230000008439 repair process Effects 0.000 abstract description 5
- 241000894006 Bacteria Species 0.000 abstract 1
- 230000002411 adverse Effects 0.000 abstract 1
- 230000007794 irritation Effects 0.000 abstract 1
- 231100000241 scar Toxicity 0.000 abstract 1
- 239000000047 product Substances 0.000 description 25
- 230000015556 catabolic process Effects 0.000 description 13
- 238000006731 degradation reaction Methods 0.000 description 12
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 238000004080 punching Methods 0.000 description 10
- 239000000428 dust Substances 0.000 description 9
- 206010023683 lagophthalmos Diseases 0.000 description 9
- 238000007789 sealing Methods 0.000 description 9
- 230000002779 inactivation Effects 0.000 description 8
- 108010035532 Collagen Proteins 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000050051 Chelone glabra Species 0.000 description 4
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 4
- 102000013275 Somatomedins Human genes 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000003954 umbilical cord Anatomy 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 3
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 3
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 2
- 208000009043 Chemical Burns Diseases 0.000 description 2
- 208000018380 Chemical injury Diseases 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 210000001136 chorion Anatomy 0.000 description 2
- 210000000589 cicatrix Anatomy 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 230000008472 epithelial growth Effects 0.000 description 2
- 229920001903 high density polyethylene Polymers 0.000 description 2
- 239000004700 high-density polyethylene Substances 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 102000002734 Collagen Type VI Human genes 0.000 description 1
- 108010043741 Collagen Type VI Proteins 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000008971 epithelial apoptosis Effects 0.000 description 1
- 230000009786 epithelial differentiation Effects 0.000 description 1
- 210000002219 extraembryonic membrane Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229920002529 medical grade silicone Polymers 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002362 mulch Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses a biological sheep membrane for ocular surface treatment and a preparation method thereof. The biological sheep membrane is prepared from sheep membrane through steps of rapid material obtaining, rapid material cutting, and radiation sterilization. The provided biological sheep membrane and preparation method have the following advantages: (1) various natural active components in sheep membrane can be effectively preserved; (2) the anti-inflammation and scar-resistant functions of natural active components in sheep membrane can be effectively preserved; (3) at the same time, the bacteria and viruses in the sheep membrane are completely killed, and thus the safety of the biological sheep membrane can be guaranteed; (4) the biological sheep membrane can be used to repair the damaged tissues, in the early period of treatment, the biological sheep membrane can promote the epithelization; and at the same time the biological sheep membrane can solve the problems that: (a) the material degrades too fast, and the curative effect cannot be achieved; (b) the material degrades too slowly, and the adverse irritation is generated on normal tissue.
Description
[technical field]
The present invention relates to field of medical materials, be specifically related to a kind of bioamnion for the treatment of eye table and preparation method thereof.
[background technology]
Amniotic membrane, from cytotrophoblast derivation, is the internal layer of the two-layer fetal membrane of people, and by epithelium layer, basement membrane becomes with without blood vessel matrix group.Comprise multiple collagen protein and laminin，LN, fibronectin, glycosaminoglycans, hyaluronic acid etc. in fresh amnion, these active substances can promote epithelial sticking to divide a word with a hyphen at the end of a line, and induction epithelial differentiation, prevents epithelial apoptosis; Multiple somatomedin is also comprised in amnion cell and substrate, as nerve growth factor (NGF), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforminggrowthfactor-α (TGF-α), transforming growth factor-beta 1 (TGF-β 1), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF); In addition, also comprise inhibiting angiogenesis, the albumen of antiinflammatory and some native protein enzyme inhibition factors in amnion cell and substrate, these factor component can promote epithelial growth, suppress inflammatory reaction, suppress fibrous tissue hyperplasia and new vessels to be formed.
The good action that amnion transplantation is played in various diseases, injury in treating process is obtained for confirmation in large quantity research.Large quantity research report proves: these abundant active substance, nutritional labeling, various somatomedin contained in amniotic membrane, and the characteristic such as basement membrane structure is the basis that amniotic membrane is used widely in field of tissue engineering technology.Amniotic membrane has good biocompatibility, produce immunological rejection hardly after heteroplastic transplantation, therefore amniotic membrane can as a kind of desirable organizational project repair materials, for different tissue injurys, by different mode process, for treatment and the reparation of Various Tissues damage.
Because fresh amnion and cold preservation amniotic membrane at utmost can retain various natural collagen and active factors composition, therefore Clinical practice effect is better.But this kind of amniotic membrane is without viral inactivation treatment, there is virus disseminating hidden danger.Current domestic amniotic membrane product, mostly is the product through Various Complex processing procedures such as lyophilizing, dry, the de-cells of wind (drying in the air).These products are in the process treatment process such as multigelation, drying and de-cell, have lost mass efficient composition, and there is multiple induced protein degeneration factor (as the selection of cryoprotective agent and freeze drying protectant in preparation technology, the selection etc. of freezing rate), the various physicochemical property of protein denaturation, amniotic membrane is easily caused to reduce, thus directly cause amniotic membrane easily to be torn in operation, need repeatedly to change, extend operating time; Postoperative inflammatory reaction is strong, amniotic membrane fast degradation.Especially some production technology is through high strength process such as de-cell, repeatedly cleanings, and amniotic membrane large losses natural collagen and active factors, cause totally unfavorable impact to amniotic membrane Clinical practice effect.
Publication number is the amniotic membrane product of the U.S. Patent Publication of US006152142A and US006326019B1 is cesarean Placenta Hominis is cleaned up rear blunt separation to remove chorion, epithelium is upwards laid on cellulose nitrate filter paper, be stored in afterwards in the conserving liquid of DMEM ︰ glycerol by 1:1 proportions, and frozen in-80 DEG C of refrigerators.Prepared amniotic membrane, without de-cell, drying and sterilization treatment, therefore remains the integrity of amniotic membrane composition and structure preferably; But long-term cryogenic retain costs is higher, and it does not carry out sterilizing and viral inactivation treatment to amniotic membrane, and Clinical practice safety can not get ensureing.
Number of patent application be 201010113960.0 Chinese invention patent application disclose one at low temperatures (-20 ~ 4 DEG C) use matrigel amnion stroma is rebuild and repairs, employing colored dyes dyes, sterilize with Co 60 after plastic film mulch, drying, thus save amnioic epithelium and substrate preferably, but under lower than zero degree condition, carry out amnion stroma reconstruction, final kept dry, not only complex process, and amniotic membrane structure can by destruction to a certain extent, mechanical performance reduces, and affects Clinical practice; In amniotic membrane preparation process, through repeatedly rinsing, in amniotic membrane, effective ingredient runs off in a large number with washing liquid, reduces Clinical practice effect.
Application number be CN03150838.3, CN200480023933.7 and 200410075361.9 Chinese invention patent application in disclose a kind of can the room temperature preparation method of bioamnion of preserving, by the chorion blunt separation of Placenta Hominis, be layered on after cleaning on nitrocellulose filter paper, pack after lyophilization, 60Coradiation sterilizing.Prepared amniotic membrane, similar with above-mentioned patented method, have passed through lyophilization, to a certain extent destruction is caused to amniotic membrane, make it become fragile, easily tear in Clinical practice;
In sum; how to protect not being destroyed of amniotic membrane structure, at utmost retain each effective constituents in fresh amnion, and ensure its safety; can effectively be applied to clinical, be prepare the key issue that bioamnion is applied to the solution of eye table treatment needs.
[summary of the invention]
The object of the invention is to the deficiency existed for the above prior art, a kind of bioamnion for the treatment of eye table is provided, the natural structure of the complete reservation fresh amnion of energy and active component, retain identical treatment effect, and guarantee that bioamnion is without any virus disseminating hidden danger.
Another object of the present invention is to provide a kind of preparation method of the bioamnion for the treatment of eye table.
To achieve these goals, the present invention is achieved in that the bioamnion for the treatment of eye table, take amniotic membrane as raw material, and to cut and irradiation sterilization step is made through drawing materials fast, fast, its thickness is 0.02-0.1mm.
For the preparation method of bioamnion for eye table treatment, be take amniotic membrane as raw material, cut and irradiation sterilization step through drawing materials fast, fast, finally obtaining bioamnion; They concrete steps comprised are as follows:
(1) draw materials fast
In 1 ~ 3 minute, the amniotic membrane outside Placenta Hominis is obtained, fresh amnion is put into the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 1 ~ 10 minute and be cooled to 2 ~ 10 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment;
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spreads on nitrocellulose filter, is amniotic membrane diaphragm at 1 ~ 3 minute interior clipping, and loading containing mass percent concentration is in the glycerine water solution packaging bag of 50% ~ 90%, sealing;
(3) irradiation sterilization
By the amniotic membrane diaphragm after (2) step process, under the low-temperature protection condition of-25 ~-4 DEG C, adopt sterilization by ionizing radiation process, namely obtain bioamnion product; Low-temperature protection is adopted to carry out irradiation sterilization; the aseptic level requirement of aseptic medical equipment product can be reached; again can the simultaneously various virus of deactivation; and at utmost can protect the activity of bioamnion; maintain the ability of its natural anti-inflammatory, anti-cicatrix and guiding epithelization as far as possible, make it be finally effectively applied to Ocular surface damage treatment.
Described ionizing radiation can be radiated by gamma-ray or high-energy electron beam irradiation, and dosage is 20 ~ 30kGy, stored refrigerated at immediately bioamnion product being placed in-90 ~-10 DEG C after irradiation.
Amniotic membrane sampling device is adopted to draw materials in described (1) step; described amniotic membrane sampling device comprises funnel-form housing and the large cutting knife of butt end of hollow; the large cutting knife of installation butt end of the butt end of described funnel-form housing; the large cutting knife of described butt end arranges detachable protective cover, can by complete for large for butt end cutting knife nested covering.Drawing materials of amniotic membrane can be completed in very short time, avoid amniotic membrane to be exposed to for a long time reduction that normal temperature condition causes amniotic membrane activity, ensure that amniotic membrane suppresses cicatrix to reduce effect of inflammation; Damage when also can effectively avoid peeling off, amniotic membrane caused and destruction.
Adopt amniotic membrane Scissoring device cutting amniotic membrane diaphragm in described (2) step, described amniotic membrane cutting means, comprises dull and stereotyped carrier and cut-off knife, and some described cut-off knife arrangements are fixed on described dull and stereotyped carrier side on the surface; The length of side of described cut-off knife is 11 ~ 70mm, and thickness is 0.1 ~ 0.5mm.In very short time, got amniotic membrane can be cut to rapidly required size shape, effectively avoid amniotic membrane to be exposed to for a long time further reduction that normal temperature condition causes amniotic membrane activity, ensure amniotic membrane implant after the ability of anti-cicatrix anti-inflammatory.
The length of described amniotic membrane diaphragm is 10 ~ 70mm, and width is rectangle or the square of 10 ~ 70mm, also can be cut to trapezoidal, circular, the triangle amniotic membrane diaphragm of similar size.
The bioamnion that the present invention obtains; while guaranteeing the biological safety of bioamnion; the natural activity function of effective reservation and performance amniotic membrane; bootable epithelial growth when being applied to Ocular surface damage; new vessels is suppressed to grow into cornea; later stage suppresses cicatrization, effectively can form long term physical barrier protection wound surface, have fabulous potential applicability in clinical practice.
Above-mentioned amniotic membrane sampling device, can make the amniotic membrane outside Placenta Hominis cut rapidly and obtain, and reduces amniotic membrane and draws materials the action required time.The amniotic membrane cutting means of the present invention, cuts amniotic membrane by multiple evenly distributed small-sized cut-off knife punching press, rapidly amniotic membrane can be cut into required specification and size, greatly reduce amniotic membrane and cut the action required time.Verify through the present inventor, under there is operator the condition of long-time amniotic membrane cutting experience, adopt manual operations to utilize universal cutter to cut acquired amniotic membrane, need just can cut for 1 ~ 2 hour, and be comparatively difficult to ensure demonstrate,prove cut that the size of amniotic membrane is homogeneous to meet the demands.
Compared with existing product, Advantageous Effects of the present invention is:
(1) integrated artistic process intensity is low, adopts low-temperature protection process, effectively can retain the various active skull cap components of amniotic membrane, comprise collagen, somatomedin, anti-inflammatory factors etc.; Bioamnion of the present invention is carried out to the detection of mentioned component, result shows that bioamnion prepared by the present invention differs less with the various active skull cap components content of fresh amnion, illustrates that preparation method of the present invention effectively can retain the various natural components of amniotic membrane;
(2) amniotic membrane sampling device and amniotic membrane cutting means is adopted, amniotic membrane can be completed from the whole process process of sterilizing of drawing materials (before sterilizing operating time the shortest can be 1 ~ 2 hour) within the shortest time, and adopt low-temperature protection irradiation sterilization effectively to retain the innate efficacy of the anti-cicatrix of anti-inflammatory of the various active skull cap components of amniotic membrane; Carry out the outer experiment in vivo of dependent body by bioamnion to detect, result shows that bioamnion prepared by the present invention has the biological activity equal with fresh amnion;
(3) while the active effect retaining amniotic membrane active skull cap components and these compositions, aseptic level and the inactivation of virus effect of the bioamnion finally prepared can also be ensured, ensure that the basic demand that bioamnion uses as medical apparatus and instruments is met, ensure that the biological safety of bioamnion; Low-temperature protection irradiation sterilization method, through the checking of irradiation sterilization virus inactivation technology, can ensure each viroid (as HIV, HBV, HCV, syphilis etc.) deactivation completely, drastically increase the safety of Clinical practice;
(4) for the bioamnion of Ocular surface damage reparation; degradation speed and injury repairing speed match; both the demand of tissue injury's restoration and protection material had been met; effectively can play again treatment early promotion epithelization; later stage suppresses synulotic therapeutic efficiency, avoids material premature breakdown simultaneously and does not reach therapeutic purposes and cross slow degraded normal tissue generation pessimal stimulation.
[accompanying drawing explanation]
Fig. 1 is the perspective view of amniotic membrane sampling device;
Fig. 2 is the perspective view of amniotic membrane die cut device;
Fig. 3 is the bioamnion for preparing of the present invention and fresh amnion main component detection by quantitative comparing result figure;
Fig. 4 is that the bioamnion for preparing of the present invention and fresh amnion suture strength detect comparing result figure;
Fig. 5 is the bioamnion for preparing of the present invention and fresh amnion external degradation Performance Detection comparing result figure;
Fig. 6 is the bioamnion vitro cytotoxicity testing result figure that the present invention prepares;
Fig. 7 is the bioamnion vitro lymphocyte proliferation testing result figure that the present invention prepares;
Fig. 8 is that the bioamnion that the present invention prepares repairs result figure for the chemical burn of lagophthalmos table.
[detailed description of the invention]
Below in conjunction with the drawings and specific embodiments, explanation is described in detail to the present invention.
Embodiment 1
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 1 minute is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 1 minute and be cooled to 10 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopting amniotic membrane Scissoring device amniotic membrane to be cut to length in 1 minute is 70mm, the square amniotic membrane diaphragm of width 70mm, it is in the glycerine water solution packaging bag of 50% that amniotic membrane diaphragm cutting obtained again loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-25 DEG C, adopt 20kGy high energy electron beams sterilization treatment, namely obtain bioamnion product.Stored refrigerated at immediately bioamnion product being placed in-90 DEG C after irradiation.
The bioamnion that the present embodiment prepares has good biocompatibility, vitro cytotoxicity and the display of vitro lymphocyte proliferation assay testing result are as shown in Figure 6 and Figure 7, bioamnion is without vitro cytotoxicity, non-stimulated or suppress lymphocytic immunogenicity, as the treatment of eye table, there is good safety.
Embodiment 2
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 3 minutes is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 10 minutes and be cooled to 2 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane being cut to length in 3 minutes is 10mm, width is the rectangle amniotic membrane diaphragm of 15mm, then amniotic membrane diaphragm loading cutting obtained is in the glycerine water solution packaging bag of 60% containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization;
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-4 DEG C, adopt 30kGy gamma ray radiation sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-10 DEG C after irradiation.
The bioamnion that the present embodiment prepares, effectively can retain all kinds of natural constituent of amniotic membrane, detect through kit, each active component that result display bioamnion retains, as shown in Figure 3, no significant difference compared with fresh amnion, has good potential applicability in clinical practice as the treatment of eye table.
Embodiment 3
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 2 minutes is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 5 minutes and be cooled to 6 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane is cut to the circular amniotic membrane diaphragm that diameter is 50mm in 2 minutes, it is in the glycerine water solution packaging bag of 90% that amniotic membrane diaphragm cutting obtained again loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization;
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-16 DEG C, adopt 25kGy gamma ray radiation sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-25 DEG C after irradiation.
The bioamnion that the present embodiment prepares, can effectively retain amniotic membrane native collagen structures, retain the good mechanical performance of fresh amnion and degradation property, instron tensile strength tester is adopted to carry out suture strength detection to the bioamnion that fresh amnion and the present embodiment prepare, external degradation experiment is adopted to detect the content of degradation products of different degradation time point, result shows that the bioamnion suture strength that the present embodiment prepares and external degradation performance and fresh amnion are without significant difference (see Fig. 4 and Fig. 5), have good potential applicability in clinical practice.
Embodiment 4
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
(1) amniotic membrane sampling device fast fetching in 3 minutes is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 8 minutes and be cooled to 8 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spreads on nitrocellulose filter, adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane being cut to length in 2 minutes is 70mm, and width is 40mm, and height is the trapezoidal amniotic membrane diaphragm of 40mm.It is in the glycerine water solution packaging bag of 80% that amniotic membrane diaphragm cutting obtained loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-10 DEG C, adopt high energy electron beams sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-80 DEG C after irradiation.
The bioamnion that the present embodiment prepares, can effectively retain amniotic membrane natural bioactive, there is the effect of the anti-inflammatory of fresh amnion, anti-angiogenicization, anti-cicatrix, Promotive union, detect through the experiment of lagophthalmos chemical burn animal pattern, result display aftertreatment Be very effective, amniotic membrane degradation speed and injury repairing speed match, rabbit cornea is without vascularization cicatrization, transparent cleaning, NIP, without rejection, has splendid therapeutical effect (see Fig. 8).
Embodiment 5
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 1 minute is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 3 minutes and be cooled to 9 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane is cut to the triangle amniotic membrane diaphragm that the length of side is 10mm in 3 minutes, it is in the glycerine water solution packaging bag of 75% that amniotic membrane diaphragm cutting obtained again loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-20 DEG C, adopt gamma ray radiation sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-60 DEG C after irradiation.
Bioamnion prepared by the present embodiment cuts sterilizing at low temperatures, stored refrigerated, effectively can ensure the amniotic membrane natural constituent contained by bioamnion and activity, has a good application prospect in the clinical practice of eye table.
Embodiment 6
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 2 minutes is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 4 minutes and be cooled to 7 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast;
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane being cut to length in 2 minutes is 45mm, width is the rectangle amniotic membrane diaphragm of 55mm, then amniotic membrane diaphragm loading cutting obtained is in the glycerine water solution packaging bag of 50% containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization;
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-8 DEG C, adopt 28kGy gamma ray radiation sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-16 DEG C after irradiation.
The bioamnion that the present embodiment prepares, can the various virus of complete inactivation, and detect through virus inactivation technology confirmatory experiment, inactivation of virus effect all can reach 4-6 a more than log, guarantees all kinds of inactivation of virus.
Embodiment 7
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
Amniotic membrane sampling device fast fetching in 1 minute is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 1 minute and be cooled to 10 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spread on nitrocellulose filter, adopting amniotic membrane Scissoring device amniotic membrane to be cut to length in 1 minute is 70mm, the square amniotic membrane diaphragm of width 70mm, it is in the glycerine water solution packaging bag of 65% that amniotic membrane diaphragm cutting obtained again loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-18 DEG C, adopt 25kGy high energy electron beams sterilization treatment, namely obtain bioamnion product.Stored refrigerated at immediately bioamnion product being placed in-80 DEG C after irradiation.
Embodiment 8
For the preparation method of the bioamnion of eye table treatment, its step is as follows:
(1) draw materials fast
(1) amniotic membrane sampling device fast fetching in 3 minutes is adopted to obtain the amniotic membrane outside Placenta Hominis, got fresh amnion is put into rapidly the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane to complete in 8 minutes and be cooled to 8 DEG C of cold preservations, and in 1 hour, be transported to dust proof workshop carry out subsequent treatment.
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spreads on nitrocellulose filter, and adopt the punching press amniotic membrane Scissoring device of our company's invention, amniotic membrane being cut to length in 3 minutes is 15mm, and width is the rectangle amniotic membrane diaphragm of 10mm.It is in the glycerine water solution packaging bag of 50% that amniotic membrane diaphragm cutting obtained loads containing a small amount of mass percent concentration, sealing.
(3) irradiation sterilization
By the amniotic membrane after (2) step process, under the low-temperature protection condition of-10 DEG C, adopt high energy electron beams sterilization treatment, namely obtain bioamnion product; Stored refrigerated at immediately bioamnion product being placed in-80 DEG C after irradiation.
In following example, amniotic membrane is that puerpera signs informed consent postscript, cuts that stripping obtains from discarded natural labor or cesarean Placenta Hominis, is the waste products departing from live body.
The quick sampling device of described amniotic membrane, as shown in Figure 1, comprise the funnel-form housing 1 of hollow, the little cutting knife of taper end 2 and the large cutting knife 5 of butt end, the large cutting knife 5 of butt end is installed in the butt end end of described funnel-form housing 1, the taper end of described funnel-form housing 1 arranges the little cutting knife 2 of taper end, and the sidewall of the little cutting knife 2 of described taper end arranges opening 4; The little cutting knife 2 of taper end can be made when pressing down to scatter in center radiation shape, radial taper end little cutting knife 2 can be utilized to be separated with Placenta Hominis by the amniotic membrane on Placenta Hominis by rotatable hopper shape housing 1.At the dismountable fixing band 3 of described taper end little cutting knife 2 arranged outside, for the fixing little cutting knife 2 of described taper end.The little cutting knife of described taper end 2 is the dismountable end being installed on funnel-form housing 1 taper end of some blade units.Opening 4 is set between adjacent knife blades unit.The large cutting knife 5 of described butt end arranges detachable protective cover 6, and described protective sleeve 6 can by complete for large for butt end cutting knife nested covering, as press down rotate taper end little cutting knife time personnel hand-holding part.Wherein, the length of described funnel-form housing 1 is 15 ~ 25cm; Wall thickness is 2 ~ 5mm.Described taper end little cutting knife 2 diameter 2 ~ 5cm, length 15 ~ 30cm, thickness 0.2 ~ 0.5mm, for for amniotic membrane around ring cutting umbilical cord.Described opening 4 length is 15 ~ 30cm, for pressing down rotatable hopper shape housing to amniotic membrane ring cutting around umbilical cord.Diameter 15 ~ 30cm, length 1 ~ 2cm, the thickness 2 ~ 5mm of the large cutting knife 5 of described butt end, for cutting rapidly the amniotic membrane of placental edge.Described funnel-form housing 1, the large cutting knife of butt end 5 and taper end little cutting knife 2 material are rustless steel; Protective cover 6 material is medical grade PMMA plastics or high density polytetrafluoroethylplastic plastic; Fixing band 4 material is medical grade silicon rubber.
The present invention is first hand-held funnel-form housing 1 in use, lays down the protective cover 6 on the large cutting knife 5 of described butt end, presses down the large cutting knife 5 of butt end and cut placental edge amniotic membrane intersection, removes all amniotic membranes outside Placenta Hominis, installs butt end protective cover 6.Then taper end is fixed with fixing band 3, umbilical cord is penetrated from the little cutting knife 2 of taper end, pass from the large cutting knife 5 of butt end, hand-held butt end protective cover 6 and part funnel-form housing 1, press down amniotic membrane ring cutting around rotatable hopper shape housing 1 pair of umbilical cord, removal fixing band 3 after completing, hand-held butt end protective cover 6 and partial shell 1 again, little for taper end cutting knife 2 is aimed at amnion ring earnestly mouth press down funnel-form housing 1, the little cutting knife 2 of taper end is scattered in center radiation shape, rotatable hopper shape housing 1 can utilize radial taper end little cutting knife 2 to be separated with Placenta Hominis by the amniotic membrane on Placenta Hominis again, obtain amniotic membrane on Placenta Hominis.
Adopt the present invention greatly can shorten the operating time of peeling off amniotic membrane on Placenta Hominis of drawing materials, in average 1 ~ 3 minute, get final product complete operation.Before comparing operator under the condition of long period training and practical operation, only to operate amniotic membrane on Placenta Hominis from the complete stripping of Placenta Hominis by hand, at least need 10 ~ 30 minutes; Use the present invention greatly can improve operating efficiency, effectively shorten amniotic membrane and draw materials the time.
As shown in Figure 2, described punching press amniotic membrane Scissoring device comprises dull and stereotyped carrier 7 and cut-off knife 8, and some described cut-off knife 8 arrangements are fixed on described dull and stereotyped carrier 7 side on the surface.The size dimension of described dull and stereotyped carrier 7 is 20 ~ 30cm, and thickness is 2 ~ 10mm.Minimum spacing between adjacent described cut-off knife 8 is 0.1 ~ 0.5mm.The length of side of described cut-off knife 8 is 3 ~ 10mm, and thickness is 0.1 ~ 0.5mm.Described dull and stereotyped carrier 7 and cut-off knife 8 material are rustless steel.The edge of a knife shape of described cut-off knife can be square, triangle, circle, trapezoidal or rectangle.When using this device, first amniotic membrane and filter paper are laid in hypothermia operation table, then hand-held dull and stereotyped 7 by cut-off knife 8 towards amniotic membrane, be rapidly to lower punching press and amniotic membrane can be cut into required specification and shape.Preferably, the size dimension of described dull and stereotyped carrier 7 is 23 ~ 28cm, and thickness is 4 ~ 6mm.Minimum spacing between adjacent described cut-off knife 8 is 0.2 ~ 0.4mm.The length of side of described cut-off knife 8 is 25 ~ 45mm, and thickness is 0.2 ~ 0.4mm.Optimum, the size dimension of described dull and stereotyped carrier 7 is 25cm, and thickness is 5mm.Minimum spacing between adjacent described cut-off knife 8 is 0.3mm.The length of side of described cut-off knife 8 is 30mm, and thickness is 0.3mm.Above-mentioned size is saved when cutting most, and can meet the various requirement of operation.The edge of a knife shape of described cut-off knife can be square, triangle, circle, trapezoidal or rectangle.
Using method of the present invention cuts amniotic membrane by multiple evenly distributed small-sized cut-off knife punching press; rapidly amniotic membrane batch can be cut into required specification and size; greatly reduce amniotic membrane and cut the action required time; in 1 ~ 3 minute, an amniotic membrane is cut into the clinical amniotic membrane being suitable for specification and size; operation fast; cut and obtain amniotic membrane and be also applicable to clinical operation demand, meet the demand that industrialized scaleization is produced.
Below for above-described embodiment, Binding experiment data, accompanying drawing data are analyzed:
Fig. 3 is the bioamnion for preparing of the present invention and fresh amnion main component detection by quantitative comparing result figure.In figure, COL I is NTx, and COL III is III Collagen Type VI, and COL IV is type Ⅳ collagen, bFGF is basic fibroblast growth factor, and EGF is epidermal growth factor, and TIMP is Expression of TIMP, HGF is hepatocyte growth factor, and KGF is cutin somatomedin.BA represents bioamnion prepared by the present invention, and FAM represents fresh amnion.All kinds of natural collagen that bioamnion comprises and factor component content and natural fresh amniotic membrane no significant difference can be found out by picture display.
Fig. 4 is that the bioamnion for preparing of the present invention and fresh amnion suture strength detect comparing result figure.Sample number into spectrum 1 in figure, 2 bioamnions prepared for the present invention, 3,4 is fresh amnion.Picture display can find out that bioamnion prepared by the present invention has the close suture strength be equal to fresh amnion.
Accompanying drawing 5 is the bioamnion for preparing of the present invention and fresh amnion external degradation Performance Detection comparing result figure.In figure, Hyp is amniotic membrane external degradation product hydroxyproline, and time is degradation time, and FAM is fresh amnion, and BA is bioamnion prepared by the present invention.Picture display can find out the bioamnion that the present invention prepares and fresh amnion degradation property no significant difference.
Fig. 6 is the bioamnion vitro cytotoxicity testing result figure that the present invention prepares.In figure, BA represents bioamnion prepared by the present invention, and CK represents blank group, and PE represents high density polyethylene (HDPE) negative control group, and DMSO represents divinylsulfone positive controls.Vertical coordinate percentage rate represents the In vitro culture rate of increase of L929 cell.Picture display can find out that the body outer cell proliferation rate of bioamnion and blank group and negative control group is without significant difference, all about 100%.And positive controls cell proliferation rate is lower than 20%, show that bioamnion has good Cyto-compatibility in vitro.
Fig. 7 is the bioamnion vitro lymphocyte proliferation testing result figure that the present invention prepares.In figure, BA represents bioamnion prepared by the present invention, and CK represents blank group, and FAM represents fresh amnion.Vertical coordinate percentage rate represents the human lymphocyte In vitro culture rate of increase.Picture display can find out that bioamnion and fresh amnion group are compared with blank group, all do not cause the external abnormality proliferation of human lymphocyte or apoptosis, shows that bioamnion has good immunogenicity.
Fig. 8 is that each significant observation time point that bioamnion that the present invention prepares is applied to lagophthalmos table burn treating repairs situation comparing result figure.In figure, A is that after the modeling of lagophthalmos burn, lagophthalmos off-balancesheet is seen, B carries out the lagophthalmos off-balancesheet after debridement treatment to burn area to see, C is that the lagophthalmos off-balancesheet after sewing up the bioamnion prepared of the present invention is seen, and D is that the bioamnion prepared through the present invention is treated the lagophthalmos off-balancesheet after month and seen.Picture display can find out that namely bioamnion shows good therapeutic effect after surgery, lagophthalmos inflammatory reaction reduces, complete epithelization rapidly, there is not later stage cicatrix or blood vessel hyperplasia, amniotic membrane degradation rate and tissue repair speed match, final corneal restoration result and healthy eyes there was no significant difference.
More than describe preferred embodiment of the present invention in detail, should be appreciated that the ordinary skill of this area just design according to the present invention can make many modifications and variations without the need to creative work.Therefore, all technical staff in the art according to the present invention's design on prior art basis by logical analysis, reasoning or according to the available technical scheme of limited experiment, all should by among the determined protection domain of these claims.
Claims (6)
1. for the bioamnion of eye table treatment, it is characterized in that, take amniotic membrane as raw material, and to cut and irradiation sterilization step is made through drawing materials fast, fast, its thickness is 0.02 ~ 0.1mm.
2., for a preparation method for the bioamnion of eye table treatment, it is characterized in that, the step comprised is as follows:
(1) draw materials fast
In 1 ~ 3 minute, the amniotic membrane outside Placenta Hominis is obtained, amniotic membrane is put into the transport bottle of prepackage physiological saline solution, depart from parent at amniotic membrane and complete in 1 ~ 10 minute and be cooled to 2 ~ 10 DEG C of cold preservations;
(2) cut fast
By the amniotic membrane that (1) step obtains, epithelial surface upwards, spreads on nitrocellulose filter, is amniotic membrane diaphragm at 1 ~ 3 minute interior clipping, and loading containing mass percent concentration is in the glycerine water solution packaging bag of 50% ~ 90%;
(3) irradiation sterilization
By the amniotic membrane diaphragm after (2) step process, under the low-temperature protection condition of-25 ~-4 DEG C, adopt sterilization by ionizing radiation process, namely obtain bioamnion product.
3. according to the preparation method of a kind of bioamnion for the treatment of eye table according to claim 2, it is characterized in that, described ionizing radiation is radiated by gamma-ray or high-energy electron beam irradiation, dosage is 20 ~ 30kGy, stored refrigerated at immediately bioamnion product being placed in-90 ~-10 DEG C after irradiation.
4. according to the preparation method of a kind of bioamnion for the treatment of eye table according to claim 2; it is characterized in that; amniotic membrane sampling device is adopted to draw materials in described (1) step; described amniotic membrane sampling device comprises funnel-form housing and the large cutting knife of butt end of hollow; the large cutting knife of installation butt end of the butt end of described funnel-form housing, the large cutting knife of described butt end arranges detachable protective cover.
5. according to the preparation method of a kind of bioamnion for the treatment of eye table according to claim 2, it is characterized in that, novel amniotic membrane Scissoring device cutting amniotic membrane diaphragm is adopted in described (2) step, described amniotic membrane cutting means, comprise dull and stereotyped carrier and cut-off knife, some described cut-off knife arrangements are fixed on described dull and stereotyped carrier side on the surface; The length of side of described cut-off knife is 11 ~ 70mm, and thickness is 0.1 ~ 0.5mm.
6., according to the preparation method of a kind of bioamnion for the treatment of eye table according to claim 2, it is characterized in that, the length of described amniotic membrane diaphragm is 10 ~ 70mm, and width is rectangle or the square of 10 ~ 70mm; Or be cut to trapezoidal, circular or triangle amniotic membrane diaphragm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510228017.7A CN104825493B (en) | 2015-05-06 | 2015-05-06 | Biological amniotic membrane for ocular surface treatment and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510228017.7A CN104825493B (en) | 2015-05-06 | 2015-05-06 | Biological amniotic membrane for ocular surface treatment and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104825493A true CN104825493A (en) | 2015-08-12 |
| CN104825493B CN104825493B (en) | 2020-02-21 |
Family
ID=53803946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510228017.7A Active CN104825493B (en) | 2015-05-06 | 2015-05-06 | Biological amniotic membrane for ocular surface treatment and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104825493B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109069697A (en) * | 2016-12-16 | 2018-12-21 | 厦门大开生物科技有限公司 | A kind of irradiation sterilization method and its sterilizing cornea of cornea |
| CN109939263A (en) * | 2019-03-29 | 2019-06-28 | 广州锐澄医疗技术有限公司 | A kind of preparation method of heterogeneity biological amnion product |
| CN110101910A (en) * | 2019-05-15 | 2019-08-09 | 南京医科大学附属口腔医院 | A kind of bioamnion and preparation method thereof guiding bone regeneration around implant bone tissue regeneration |
| CN114917413A (en) * | 2022-06-14 | 2022-08-19 | 健诺维(成都)生物科技有限公司 | Amniotic membrane loaded with recombinant polypeptide and preparation method thereof |
| CN115845141A (en) * | 2023-03-02 | 2023-03-28 | 健诺维(成都)生物科技有限公司 | Preparation method and application of dry amnion |
| CN117442646A (en) * | 2023-12-21 | 2024-01-26 | 广州瑞泰生物科技有限公司 | Eye surface lubricating liquid and preparation process, quality control method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6152142A (en) * | 1997-02-28 | 2000-11-28 | Tseng; Scheffer C. G. | Grafts made from amniotic membrane; methods of separating, preserving, and using such grafts in surgeries |
| CN1522568A (en) * | 2003-09-03 | 2004-08-25 | 江西省科学院住友生物工程技术有限公 | Amnia preservation and handling method |
| CN103520780A (en) * | 2013-10-24 | 2014-01-22 | 陕西瑞盛生物科技有限公司 | Biological amnion and preparation method thereof |
| CN104083803A (en) * | 2013-04-01 | 2014-10-08 | 陕西佰傲再生医学有限公司 | Biomembrane for ocular surface restoration and preparation method thereof |
-
2015
- 2015-05-06 CN CN201510228017.7A patent/CN104825493B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6152142A (en) * | 1997-02-28 | 2000-11-28 | Tseng; Scheffer C. G. | Grafts made from amniotic membrane; methods of separating, preserving, and using such grafts in surgeries |
| CN1522568A (en) * | 2003-09-03 | 2004-08-25 | 江西省科学院住友生物工程技术有限公 | Amnia preservation and handling method |
| CN104083803A (en) * | 2013-04-01 | 2014-10-08 | 陕西佰傲再生医学有限公司 | Biomembrane for ocular surface restoration and preparation method thereof |
| CN103520780A (en) * | 2013-10-24 | 2014-01-22 | 陕西瑞盛生物科技有限公司 | Biological amnion and preparation method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109069697A (en) * | 2016-12-16 | 2018-12-21 | 厦门大开生物科技有限公司 | A kind of irradiation sterilization method and its sterilizing cornea of cornea |
| CN109939263A (en) * | 2019-03-29 | 2019-06-28 | 广州锐澄医疗技术有限公司 | A kind of preparation method of heterogeneity biological amnion product |
| CN110101910A (en) * | 2019-05-15 | 2019-08-09 | 南京医科大学附属口腔医院 | A kind of bioamnion and preparation method thereof guiding bone regeneration around implant bone tissue regeneration |
| CN114917413A (en) * | 2022-06-14 | 2022-08-19 | 健诺维(成都)生物科技有限公司 | Amniotic membrane loaded with recombinant polypeptide and preparation method thereof |
| CN115845141A (en) * | 2023-03-02 | 2023-03-28 | 健诺维(成都)生物科技有限公司 | Preparation method and application of dry amnion |
| CN117442646A (en) * | 2023-12-21 | 2024-01-26 | 广州瑞泰生物科技有限公司 | Eye surface lubricating liquid and preparation process, quality control method and application thereof |
| CN117442646B (en) * | 2023-12-21 | 2024-03-26 | 广州瑞泰生物科技有限公司 | Eye surface lubricating liquid and preparation process, quality control method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104825493B (en) | 2020-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104825493A (en) | Biological sheep membrane for ocular surface treatment and preparation method thereof | |
| US10994913B2 (en) | Support and packaging for membranes | |
| JP5226914B2 (en) | Granular acellular tissue matrix | |
| JP4555576B2 (en) | Surgical device for skin treatment or examination | |
| JP6845145B2 (en) | Composition consisting of collagen and micronized placental tissue and its preparation and usage | |
| US10143777B2 (en) | Fenestration kits for making fenestrated placental tissue allografts and methods of using the same | |
| CN104055795B (en) | A kind of injectable implant and preparation method thereof | |
| US10568914B1 (en) | Human birth tissue laminate and methods of use | |
| CN105983094A (en) | Preparation method of sterile collagen liquid having bio-activity and preparation method of sterile collagen dressing having bio-activity | |
| US20220267655A1 (en) | Medical adhesive and the preparation method and use thereof | |
| CN100368534C (en) | Bioderived amniotic membrane, composite bioderived amniotic membrane and preparation method thereof | |
| CN104826166B (en) | A kind of biomembrane for glaucoma treatment and preparation method thereof | |
| CN109157676A (en) | A kind of preparation method for remolding compound bio amnion | |
| CN109479871A (en) | Frozen stock solution, preparation method, application and China's Tong Shi glue tissue cryopreservation methods | |
| KR101139434B1 (en) | Manufacturing method for dressing material using porcine skin | |
| WO2023039833A1 (en) | Use of collagen particles to promote hair follicle formation or angiogenesis | |
| US20210393852A1 (en) | Meshed umbilical cord tissue grafts | |
| Ashtiani et al. | Repairing injured skin: biologics, skin substitutes, and scaffolds | |
| CN108030914A (en) | A kind of Matrigel raw material and preparation method and application | |
| US20170224870A1 (en) | Method of packaging amniotic membrane | |
| CN111888526A (en) | Skin sheet for mixed transplantation of heterogeneous species | |
| JP2002336344A (en) | Culture cell sheet package and method of fabrication for the same | |
| CN108969804A (en) | A kind of preparation method of allogeneic dressing skin | |
| US20170080127A1 (en) | Biologically active graft for skin replacement therapy | |
| TWI791290B (en) | Use of collagen particles in hair follicles formation or angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Yanli Inventor after: Liu Bowen Inventor after: Wang Erhao Inventor after: He Haina Inventor after: Ye Weichu Inventor after: Luo Jinrong Inventor after: Wang Enguang Inventor after: Lin Yongliang Inventor after: Xie Lijun Inventor before: Liu Bowen Inventor before: Wang Erhao Inventor before: Liu Yanli Inventor before: He Haina Inventor before: Ye Weichu Inventor before: Luo Jinrong Inventor before: Wang Enguang Inventor before: Lin Yongliang Inventor before: Xie Lijun |
|
| CB03 | Change of inventor or designer information | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170516 Address after: 510663 Guangdong province high tech Industrial Development Zone of Guangzhou Science City D406 skim Springs Road No. 3 Guangzhou international business incubator District real D Applicant after: GUANGZHOU YOUSHIQING BIOTECHNOLOGY CO.,LTD. Applicant after: Liu Yanli Address before: 510663 Guangdong city of Guangzhou province high tech Industrial Development Zone of Guangzhou science city leaders Road International Business Incubator area D room 406 Applicant before: GUANGZHOU YOUSHIQING BIOTECHNOLOGY CO.,LTD. |
|
| TA01 | Transfer of patent application right | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 510530 Guangdong Province, Guangzhou high tech Industrial Development Zone Ruitailu No. 2 building two layer B01 B Applicant after: GUANGZHOU RUITAI BIOLOGICAL TECHNOLOGY CO.,LTD. Applicant after: Liu Yanli Address before: 510663 Guangdong province high tech Industrial Development Zone of Guangzhou Science City D406 skim Springs Road No. 3 Guangzhou international business incubator District real D Applicant before: GUANGZHOU YOUSHIQING BIOTECHNOLOGY CO.,LTD. Applicant before: Liu Yanli |
|
| CB03 | Change of inventor or designer information |
Inventor after: Lin Yongliang Inventor after: Liu Yanli Inventor after: He Haina Inventor after: Liu Bowen Inventor after: Wang Erhao Inventor after: Ye Weichu Inventor after: Luo Jinrong Inventor after: Wang Enguang Inventor after: Xie Lijun Inventor before: Liu Yanli Inventor before: Liu Bowen Inventor before: Wang Erhao Inventor before: He Haina Inventor before: Ye Weichu Inventor before: Luo Jinrong Inventor before: Wang Enguang Inventor before: Lin Yongliang Inventor before: Xie Lijun |
|
| CB03 | Change of inventor or designer information | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20200115 Address after: Room D406, Zone D, Guangzhou International Business Incubator, No. 3, juaquan Road, Science City, Guangzhou hi tech Industrial Development Zone, Guangzhou 510530, Guangdong Province Applicant after: GUANGZHOU RUITAI BIOLOGICAL TECHNOLOGY CO.,LTD. Address before: 510530 Guangdong Province, Guangzhou high tech Industrial Development Zone Ruitailu No. 2 building two layer B01 B Applicant before: GUANGZHOU RUITAI BIOLOGICAL TECHNOLOGY CO.,LTD. Applicant before: Liu Yanli |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A biological amniotic membrane for ocular surface treatment and its preparation method Granted publication date: 20200221 Pledgee: CITIC Bank Co.,Ltd. Guangzhou Branch Pledgor: GUANGZHOU RUITAI BIOLOGICAL TECHNOLOGY CO.,LTD. Registration number: Y2024980033656 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |