CN101404998A - 组织胶原合成促进用口服剂 - Google Patents
组织胶原合成促进用口服剂 Download PDFInfo
- Publication number
- CN101404998A CN101404998A CNA2007800103881A CN200780010388A CN101404998A CN 101404998 A CN101404998 A CN 101404998A CN A2007800103881 A CNA2007800103881 A CN A2007800103881A CN 200780010388 A CN200780010388 A CN 200780010388A CN 101404998 A CN101404998 A CN 101404998A
- Authority
- CN
- China
- Prior art keywords
- hydroxyproline
- skin
- oral
- salt
- collagen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000008186 Collagen Human genes 0.000 title claims abstract description 43
- 108010035532 Collagen Proteins 0.000 title claims abstract description 43
- 229920001436 collagen Polymers 0.000 title claims abstract description 43
- 230000001737 promoting effect Effects 0.000 title claims abstract description 30
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 19
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 18
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims abstract description 67
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims abstract description 67
- 229960002591 hydroxyproline Drugs 0.000 claims abstract description 51
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims abstract description 51
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 230000037303 wrinkles Effects 0.000 claims abstract description 26
- 230000005764 inhibitory process Effects 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 12
- 230000029663 wound healing Effects 0.000 claims description 12
- 239000004615 ingredient Substances 0.000 claims description 10
- 230000000694 effects Effects 0.000 abstract description 12
- 238000002360 preparation method Methods 0.000 abstract description 12
- 230000035876 healing Effects 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 206010072170 Skin wound Diseases 0.000 abstract 2
- 238000007665 sagging Methods 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 description 39
- 210000001519 tissue Anatomy 0.000 description 18
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 11
- 208000014674 injury Diseases 0.000 description 8
- 230000008733 trauma Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- -1 on the other hand Polymers 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- FGMPLJWBKKVCDB-BYPYZUCNSA-N (2s)-1-hydroxypyrrolidine-2-carboxylic acid Chemical compound ON1CCC[C@H]1C(O)=O FGMPLJWBKKVCDB-BYPYZUCNSA-N 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229960002429 proline Drugs 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000007902 hard capsule Substances 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 235000013599 spices Nutrition 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 229960005261 aspartic acid Drugs 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 2
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 125000003047 N-acetyl group Chemical group 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000006229 amino acid addition Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 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
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
- IGHBXJSNZCFXNK-UHFFFAOYSA-N 4-chloro-7-nitrobenzofurazan Chemical compound [O-][N+](=O)C1=CC=C(Cl)C2=NON=C12 IGHBXJSNZCFXNK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000187643 Amycolatopsis Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 239000004470 DL Methionine Substances 0.000 description 1
- 241001495437 Dactylosporangium Species 0.000 description 1
- 206010013183 Dislocation of vertebra Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- HVIBGVJOBJJPFB-OFQRNFBNSA-N Gly-Pro-Hyp Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)C(O)CC1 HVIBGVJOBJJPFB-OFQRNFBNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241001655322 Streptomycetales Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 1
- 229960004874 choline bitartrate Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- PMMYEEVYMWASQN-QWWZWVQMSA-N cis-4-hydroxy-D-proline Chemical compound O[C@H]1C[NH2+][C@@H](C([O-])=O)C1 PMMYEEVYMWASQN-QWWZWVQMSA-N 0.000 description 1
- 230000007691 collagen metabolic process Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000010251 cutis laxa Diseases 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 108010017349 glycyl-prolyl-hydroxyproline Proteins 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000008729 phenylalanine Nutrition 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
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012744 reinforcing agent Substances 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000037394 skin elasticity Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000036561 sun exposure Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- BJBUEDPLEOHJGE-QWWZWVQMSA-N trans-3-hydroxy-D-proline Chemical compound O[C@@H]1CCN[C@H]1C(O)=O BJBUEDPLEOHJGE-QWWZWVQMSA-N 0.000 description 1
- PMMYEEVYMWASQN-IUYQGCFVSA-N trans-4-hydroxy-D-proline Chemical compound O[C@@H]1CN[C@@H](C(O)=O)C1 PMMYEEVYMWASQN-IUYQGCFVSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
- A23G3/44—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing peptides or proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrrole Compounds (AREA)
Abstract
本发明的目的在于提供安全且具有优良效果的组织胶原合成促进用口服剂、皮肤的创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂。根据本发明，可以提供含有羟基脯氨酸或其盐作为有效成分的组织胶原合成促进用口服剂、皮肤的创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂。
Description
技术领域
本发明涉及含有羟基脯氨酸或其盐作为有效成分的组织胶原合成促进用口服剂、皮肤创伤治愈用口服剂、以及皮肤皱纹或松弛的抑制或改善用口服剂。
背景技术
胶原是填充生物体组织的细胞与细胞、或者细胞集团与细胞集团的间隙的细胞外基质的主要蛋白质成分，据说在哺乳动物中占身体总蛋白质的近30％(参照非专利文献1)。
胶原形成纤维状或膜状的构造体，作为基本功能，起到组织的结构维持、支撑、结合和增强等作用，大多存在于皮肤、骨、腱、韧带、角膜、血管等中。伴随这些组织的老化引起的皱纹和松弛、骨质疏松等的主要原因认为是组织胶原的减少、变性等。另据报道，实际长期的日光照射会使组织胶原显著减少(参照非专利文献2)，并且随年龄增大生物体成分的新陈代谢的减弱成为胶原新陈代谢减弱的诱因而进行(参照非专利文献3)。
作为促进胶原合成的物质，已知生长因子TGF β-1(参照非专利文献4)、植物提取物(参照专利文献1)、胶原分解物(参照专利文献2～5)或者氨基酸组合物(参照专利文献6)等。更具体而言，已知作为通过口服具有胶原合成促进作用的胶原分解物的特征序列的Gly-Pro-Hyp三肽，另一方面，已知Gly、Pro、Hyp等胶原构成氨基酸与胶原中的构成比相等的氨基酸组合物不显示胶原合成促进作用(参照专利文献4)。
另一方面，已知口服羟基脯氨酸的N-酰化衍生物具有胶原合成促进作用(非专利文献4)，含有羟基脯氨酸的N-乙酰基衍生物的外用剂在欧洲作为创伤的治疗药物使用。另外，已知羟基脯氨酸及羟基脯氨酸的N-酰化衍生物的对培养人成纤维细胞的胶原合成促进作用、通过外用对皱纹形成的抑制或者改善作用(专利文献7)。但是，口服羟基脯氨酸的胶原合成促进作用、皮肤的创伤治愈促进作用、皮肤的皱纹或松弛的抑制或改善作用未知。
专利文献1：日本特开2004-35527号公报
专利文献2：日本特开平7-278012号公报
专利文献3：日本特开2000-201649号公报
专利文献4：日本特开2001-131084号公报
专利文献5：日本特开2003-137807号公报
专利文献6：日本特开2005-289928号公报
专利文献7：国际公开第2000/051561号小册子
非专利文献1：「生化学辞典 第1版」、东京化学同人、1984年、p.480
非专利文献2：「加齢と皮膚」、清至书院、1986年、p.35
非专利文献3：「老化のメカニズムと制御」、アイピ一シ一、1993年、p.151
非专利文献4：「エクスペリメンタル·アンド·モレキユラ一·パソロジ一」(Experimental & Molecular Pathology)、1978年、第28卷第1期、p.58-64
发明内容
本发明的目的在于提供安全且具有优良效果的组织胶原合成促进用口服剂、皮肤的创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂。
本发明涉及以下(1)～(10)。
(1)一种组织胶原合成促进用口服剂，其含有羟基脯氨酸或其盐作为有效成分；
(2)上述(1)的胶原合成促进用口服剂，其中，组织为皮肤；
(3)一种组织胶原合成促进方法，其特征在于，口服有效量的羟基脯氨酸或其盐；
(4)羟基脯氨酸或其盐在制造组织胶原合成促进用口服剂中的应用；
(5)一种皮肤的创伤治愈促进用口服剂，其含有羟基脯氨酸或其盐作为有效成分；
(6)一种皮肤的创伤治愈促进方法，其特征在于，口服有效量的羟基脯氨酸或其盐；
(7)羟基脯氨酸或其盐在制造皮肤的创伤治愈促进用口服剂中的应用；
(8)一种皮肤皱纹或松弛的抑制或改善用口服剂，其含有羟基脯氨酸或其盐作为有效成分；
(9)一种皮肤皱纹或松弛的抑制或改善方法，其特征在于，口服有效量的羟基脯氨酸或其盐；
(10)羟基脯氨酸或其盐在制造皮肤皱纹或松弛的抑制或改善用口服剂中的应用。
发明效果
根据本发明，可以提供含有羟基脯氨酸或其盐作为有效成分的、安全且具有优良效果的组织胶原合成促进用口服剂、皮肤的创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂。
附图说明
图1是表示口服羟基脯氨酸后血清中的游离羟基脯氨酸浓度的图；
图2是表示口服羟基脯氨酸后皮肤中的游离羟基脯氨酸浓度的图。
具体实施方式
本发明中使用的羟基脯氨酸，可以是任意一种羟基脯氨酸的立体异构体。即，存在通过羟基脯氨酸的脯氨酸为D型或L型、羟基的位置为3位或4位、以及其立体异构体为顺式或反式而得到的8种立体异构体，本发明中可以使用任意一种化合物。
作为具体的羟基脯氨酸，可以列举顺式-4-羟基-L-脯氨酸、顺式-4-羟基-D-脯氨酸、顺式-3-羟基-L-脯氨酸、顺式-3-羟基-D-脯氨酸、反式-4-羟基-L-脯氨酸、反式-4-羟基-D-脯氨酸、反式-3-羟基-L-脯氨酸和反式-3-羟基-D-脯氨酸。
羟基脯氨酸作为胶原中的主要构成氨基酸成分，并且也是作为弹性蛋白的构成氨基酸而在自然界广泛存在的一种氨基酸，可以通过例如将来自猪或牛等动物的胶原酸解，通过常规方法纯化而制造。
反式-4-羟基-L-脯氨酸，可以使用由拟无枝菌酸菌(Amycolatopsis)属或指孢囊菌(Dactylosporangium)属分离的脯氨酸4位羟化酶(日本特开平7-313179)制造。另外，顺式-3-羟基-L-脯氨酸，可以使用由链霉菌(Streptomyces)属分离的脯氨酸3位羟化酶(日本特开平7-322885)制造(バイオインダストリ一、14卷、31期、1997年)。
使用上述微生物来源的酶制造的羟基脯氨酸，质量优良，更优选作为本发明中使用的羟基脯氨酸。
作为羟基脯氨酸的盐，可以列举酸加成盐、金属盐、铵盐、有机胺加成盐、氨基酸加成盐等。
作为酸加成盐，可以列举盐酸盐、硫酸盐、硝酸盐、磷酸盐等无机酸盐，醋酸盐、马来酸盐、富马酸盐、柠檬酸盐、苹果酸盐、乳酸盐、α-酮戊二酸盐、葡糖酸盐、辛酸盐等有机酸盐。
作为金属盐，可以列举钠盐、钾盐等碱金属盐，镁盐、钙盐等碱土金属盐，铵盐，锌盐等。
作为铵盐，可以列举铵、四甲基铵等的盐。
作为有机胺加成盐，可以列举吗啉、哌啶等的盐。
作为氨基酸加成盐，可以列举甘氨酸、苯丙氨酸、赖氨酸、天冬氨酸、谷氨酸等的盐。
本发明的组织胶原合成促进用口服剂、皮肤创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂，含有羟基脯氨酸或其盐，根据需要可以含有药理学上容许的一种或两种以上的载体，并且根据需要还可以含有其它用于治疗的有效成分。
本发明的组织胶原合成促进用口服剂、皮肤创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂，可以通过将羟基脯氨酸或其盐与根据需要的载体一起混合，利用制剂学技术领域公知的任意方法制造。
将本发明的组织胶原合成促进用口服剂、皮肤创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂制剂化时，可以使用赋形剂、粘合剂、崩解剂、润滑剂、分散剂、悬浮剂、乳化剂、稀释剂、缓冲剂、抗氧化剂、细菌抑制剂等添加剂。
制剂的剂型可以列举片剂、散剂、颗粒剂、乳剂、糖浆剂、胶囊剂等。
制剂的剂型为糖浆剂等液体制剂的情况下，可以添加水，蔗糖、山梨糖醇、果糖等糖类，聚乙二醇、丙二醇等二醇类，蓖麻油、橄榄油、大豆油等油类，对羟基苯甲酸酯类等防腐剂，草莓香料、薄荷等香料类等进行制剂化。
另外，可以添加适合口服的物质进行制剂化，例如为片剂、散剂、颗粒剂等的情况下，可以添加赋形剂，如乳糖、白糖、葡萄糖、蔗糖、甘露醇、山梨糖醇等糖类，马铃薯、小麦、玉米等的淀粉，碳酸钙、硫酸钙、碳酸氢钠、氯化钠等无机物，甘草粉、龙胆粉等植物粉末等；崩解剂，如淀粉、琼脂、明胶粉末、结晶纤维素、羧甲基纤维素钠、羧甲基纤维素钙、碳酸钙、碳酸氢钠、藻酸钠等；润滑剂，如硬脂酸镁、滑石、氢化植物油、聚乙二醇、硅油等；粘合剂，如聚乙烯醇、羟丙基纤维素、甲基纤维素、乙基纤维素、羧甲基纤维素、明胶、淀粉糊液等；表面活性剂，如脂肪酸酯等；增塑剂，如甘油等。
另外，在适合口服的制剂中，可以添加一般的饮食品中使用的添加剂，例如，甜味料、着色料、保存料、增稠稳定剂、抗氧化剂、发色剂、漂白剂、防霉剂、胶基、苦味料、酶、光泽剂、酸味料、调味料、乳化剂、增强剂、制造用剂、香料、香辣调味料提取物等。
适合口服的制剂可以是原状，或者也可以是例如粉末食品、薄片状食品、瓶装食品、罐装食品、蒸煮食品、胶囊食品、药片状、流动食品、饮剂等形态。另外，也可以作为组织胶原合成促进用、皮肤创伤治愈促进用、或者皮肤皱纹或松弛的抑制或改善用健康食品、功能食品、营养辅助食品、特定保健用食品等饮食品使用。
本发明的口服剂中的羟基脯氨酸或其盐的浓度，根据口服剂的种类、给用该口服剂所期待的效果等适当选择，以羟基脯氨酸或其盐的形式，通常为0.1～100重量％、优选0.5～70重量％、特别优选1～50重量％。
本发明的口服剂的给药量根据给药形态、服用者年龄、体重等而不同，对成人而言一天的羟基脯氨酸或其盐通常为5mg～5000mg、优选50mg～5000mg、更优选500mg～5000mg，一天一次或分数次给药。给药周期没有特别限制，通常是1天～1年，优选1周～3个月。
另外，本发明的口服剂不仅可以用于人，也可以用于人以外的动物(以下，称为非人动物)。
作为非人动物，可以列举哺乳类、鸟类、爬虫类、两栖类、鱼类等人以外的动物。
非人动物给药时的给药量，根据动物的年龄、种类等不同，体重1kg每天的羟基脯氨酸或其盐通常为0.1mg～100mg、优选1mg～100mg、更优选10mg～100mg，一天一次或数次给药。
给药周期没有特别限制，通常是1天～1年，优选1周～3个月。
以下，列举考查羟基脯氨酸对皮肤的胶原合成促进效果、创伤治愈促进效果及皮肤皱纹或松弛的改善效果的试验例。
试验例1
试验使用HOS：HR-1小鼠(雌性、7周大、自日本SLC公司购入)。
将反式-4-羟基-L-脯氨酸(协和发酵工业株式会社制造，以下，简称羟基脯氨酸)溶解于纯化水中达到50mg/ml，以500mg/kg口服给药。0.5、1、2、4、6、24小时后，在乙醚吸入麻醉下从腹部大静脉采血得到血清。另外，颈椎脱臼后取背部皮肤，冷冻粉碎后，利用水提取得到皮肤提取物。
该血清和该皮肤提取物中的羟基脯氨酸量，用等量的2％(w/v)磺基水杨酸进行除蛋白处理后，用NBD-Cl(4-氯-7-硝基-2，1，3-苯并噁二唑，东京化成工业公司制造)标记仲氨基，通过使用ODS柱(4.6cmφ×15cm、GL科学公司制造)的高效液相色谱法分析。
结果如图1和图2所示。可以看出：口服的羟基脯氨酸迅速地移动到血液中和皮肤中。
试验例2
将29周大的F344/DuCrlCrlj大鼠(雄性、自日本チヤ一ルスリバ一株式会社购入)12只分成两组，每组6只。
第一组大鼠自由摄取实施例5所述的饲料7天、第二组大鼠自由摄取比较例1所述的对照饲料7天。在戊巴比妥腹腔内注射麻醉下将腹部用理发推子剃毛，在皮下两个部位插入切割为约150mg的海绵(アイバロン公司制造、2mm厚、约38mm×12mm)并缝合，再饲养7天后取出海绵。
对一片海绵使用6N盐酸20ml使其在110℃下反应18小时进行酸热分解。得到的酸热分解物用1M硼酸缓冲液(pH＝10.6)稀释10倍后，通过与试验例1同样的方法测定羟基脯氨酸量，作为大鼠胶原合成能力和组织修复能力的指标。
值以平均值±标准偏差表示，统计学上显著性差异检验通过student-t检验进行。
表1
结果如表1所示。摄取羟基脯氨酸的第一组大鼠中，来自热分解的胶原的羟基脯氨酸量显著增加，因此皮肤的胶原合成被促进，可知其结果是组织修复即创伤治愈被促进。
试验例3
将苦恼于慢性皮肤干燥、皮肤粗糙的47岁至65岁的女性21名作为受试者，将她们分为两组，两周的观察期后，使第一组受试者(9名)服用实施例6所述的硬胶囊，早晚各两枚胶囊共4周，使第二组受试者(12名)服用比较例2所述的硬胶囊，早晚各两枚胶囊共4周。试验通过平行组间双盲试验进行。硬胶囊的服用开始时及服用结束后，对受试者进行提问以下1～3的问题，以回答“1”的为一阶段、回答“10”的为十阶段，通过十阶段法评价受试者的皮肤。
问题1：请评价你面部的皱纹水平。
1.整个面部有皱纹。10.完全没有皱纹。
问题2：请评价你面部的皮肤弹性。
1.没有弹性。10.有极强的弹性。
问题3：请评价你面部皮肤有无张力。
1.完全没有张力。2.有张力。
上述评价中，问题1中，阶段越高，表示受试者感受到皮肤皱纹改善，问题2和问题3中，阶段越高，表示受试者感受到与皮肤松弛相关的弹性和张力都变高。另外，改善率(％)根据式1计算。
式1：
改善率(％)＝服用后的阶段平均值/服用前的阶段平均值×100得到的结果如表2所示。另外，表中的值表示平均值。
表2
从表2可以看出，通过服用反式-4-羟基-L-脯氨酸，面部皱纹以及松弛得到改善。
以上的试验例表示：口服的羟基脯氨酸转移到皮肤中，具有胶原合成促进效果、创伤治愈效果及皮肤皱纹或松弛改善效果。
以下，列举本发明的实施例。
实施例1
含羟基脯氨酸的片剂的制造
通过常规方法制造含有反式-4-羟基-L-脯氨酸的片剂。即，将下述各成分均匀混合，并将该混合物通过单冲式压片机压片，得到直径5mm、重量15mg的组织胶原合成促进用片剂。
表3
成分 量(g)
反式-4-羟基-L-脯氨酸 10.0
乳糖 90.0
干燥玉米淀粉 2.0
滑石 1.8
硬脂酸镁 0.2
实施例2
含羟基脯氨酸的颗粒剂的制造
将实施例1中得到的片剂粉碎、制粒、整粒，得到20-50目的皮肤创伤治愈促进用颗粒剂。
实施例3
含羟基脯氨酸的饮料的制造
通过将下述各成分搅拌溶解至均匀，并添加纯化水使总量为1000ml，制造含有反式-4-羟基-L-脯氨酸的组织胶原合成促进用饮料。另外，下述成分中的适量，对于香料、色素是指通常的饮料制造中所使用的量，对于纯化水是指加上其它成分使总量为1000ml所需要的量。
表4
成分 量(g)
反式-4-羟基-L-脯氨酸 5.0
苯甲酸钠 1.0
果糖 10.0
香料 适量
色素 适量
纯化水 适量
实施例4
含羟基脯氨酸的糖果的制造
通过常规方法制造由下述各成分组成的含有反式-4-羟基-L-脯氨酸的皮肤创伤治愈促进用糖果。
表5
成分 量(g)
N-乙酰基反式-4-羟基-L-脯氨酸 1.00
粉末山梨糖醇 98.75
香料 0.20
山梨糖醇晶种 0.05
实施例5
含羟基脯氨酸的动物饲料的制造
通过常规方法制造由下述各成分组成的含有反式-4-羟基-L-脯氨酸的动物饲料。
表6
成分 量(g)
反式-4-羟基-L-脯氨酸 1.0
酪蛋白 25.0
蔗糖 40.2
纤维素 5.0
酒石酸氢胆碱 0.2
DL-蛋氨酸 0.4
L-天冬氨酸 6.7
玉米淀粉 12.0
玉米油 5.0
AIN76组成的维生素混合
(未添加胆碱) 3.5
AIN76组成的矿物质混合 3.5
实施例6
含羟基脯氨酸的胶囊的制造
分别称量下述各成分后，投入混合机中，充分混合均匀后，通过常规方法密封入硬型明胶胶囊中，制造每一枚胶囊含有约500mg反式-4-羟基-L-脯氨酸的硬胶囊。
表7
成分 量(g)
反式-4-羟基-L-脯氨酸 500.0
微晶纤维素 97.5
胶态二氧化硅 12.5
硬脂酸镁 12.5
比较例1
将实施例5的反式-4-羟基-L-脯氨酸替换为L-天冬氨酸，制造动物饲料。
比较例2
将实施例6的反式-4-羟基-L-脯氨酸替换为玉米淀粉，制造胶囊。
工业上的利用可能性
根据本发明，可以提供含有羟基脯氨酸或其盐作为有效成分的组织胶原合成促进用口服剂、皮肤创伤治愈促进用口服剂、或者皮肤皱纹或松弛的抑制或改善用口服剂。
Claims (10)
1.一种组织胶原合成促进用口服剂，其含有羟基脯氨酸或其盐作为有效成分。
2.如权利要求1所述的胶原合成促进用口服剂，其中，组织为皮肤。
3.一种组织胶原合成促进方法，其特征在于，口服有效量的羟基脯氨酸或其盐。
4.羟基脯氨酸或其盐在制造组织胶原合成促进用口服剂中的应用。
5.一种皮肤的创伤治愈促进用口服剂，其含有羟基脯氨酸或其盐作为有效成分。
6.一种皮肤的创伤治愈促进方法，其特征在于，口服有效量的羟基脯氨酸或其盐。
7.羟基脯氨酸或其盐在制造皮肤的创伤治愈促进用口服剂中的应用。
8.一种皮肤皱纹或松弛的抑制或改善用口服剂，其含有羟基脯氨酸或其盐作为有效成分。
9.一种皮肤皱纹或松弛的抑制或改善方法，其特征在于，口服有效量的羟基脯氨酸或其盐。
10.羟基脯氨酸或其盐在制造皮肤皱纹或松弛的抑制或改善用口服剂中的应用。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP079921/2006 | 2006-03-23 | ||
| JP2006079921 | 2006-03-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101404998A true CN101404998A (zh) | 2009-04-08 |
Family
ID=38541156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800103881A Pending CN101404998A (zh) | 2006-03-23 | 2007-03-23 | 组织胶原合成促进用口服剂 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US20090062371A1 (zh) |
| EP (1) | EP1997490B1 (zh) |
| JP (1) | JP5188388B2 (zh) |
| CN (1) | CN101404998A (zh) |
| WO (1) | WO2007111238A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101779733A (zh) * | 2010-03-29 | 2010-07-21 | 济南环亿生物科技有限公司 | 一种提高畜禽肌肉中胶原蛋白的饲料添加剂及其生产方法和应用 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101629517B1 (ko) | 2007-06-01 | 2016-06-13 | 교와 핫꼬 바이오 가부시키가이샤 | 경구 조성물 |
| WO2013137382A1 (ja) * | 2012-03-15 | 2013-09-19 | 協和発酵バイオ株式会社 | 骨代謝改善剤 |
| WO2016086104A1 (en) * | 2014-11-25 | 2016-06-02 | Ionis Pharmaceuticals, Inc. | Modulation of ube3a-ats expression |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932638A (en) * | 1967-09-14 | 1976-01-13 | Franco-Chimie S.A.R.L. | Compositions and methods for wound healing |
| JP3122705B2 (ja) | 1993-09-07 | 2001-01-09 | 協和醗酵工業株式会社 | トランス−４−ヒドロキシ−ｌ−プロリンの製造法 |
| JP3492776B2 (ja) | 1993-09-07 | 2004-02-03 | 協和醗酵工業株式会社 | シス−３−ヒドロキシ−ｌ−プロリンの製造法 |
| JP3782122B2 (ja) | 1994-04-11 | 2006-06-07 | サンスター株式会社 | 経口摂取用新陳代謝促進剤およびそれを配合した食品 |
| US5827874A (en) * | 1995-05-05 | 1998-10-27 | Meyer; Hans | Methods of treating pain and inflammation with proline |
| FR2770777B1 (fr) * | 1997-11-10 | 2000-02-25 | Fabre Pierre Dermo Cosmetique | Composition synergique associant de l'acs et/ou de l'adn a de l'hydroxyproline ainsi que leurs applications en nutritherapie et en cosmetologie |
| JP4023648B2 (ja) | 1999-01-13 | 2007-12-19 | 日本ハム株式会社 | 皮膚代謝促進物及び機能性食品 |
| ATE420621T1 (de) * | 1999-03-02 | 2009-01-15 | Kyowa Hakko Kogyo Kk | N-acetylhydroxyprolin zur verbesserung der feuchtigkeitsspeicherungsfunktion der epidermis |
| JP3802721B2 (ja) | 1999-11-05 | 2006-07-26 | 株式会社ファンケル | 生体コラーゲン合成促進剤 |
| JP2003137807A (ja) | 2001-11-01 | 2003-05-14 | Miyagi Kagaku Kogyo Kk | コラーゲン産生促進剤、それを含む化粧品、食品および医薬品ならびに皮膚疾患の予防または改善用外用剤 |
| JP2004035527A (ja) | 2002-07-08 | 2004-02-05 | Matsuura Yakugyo Kk | コラーゲン合成促進剤 |
| KR100864384B1 (ko) * | 2002-09-30 | 2008-10-20 | 교와 핫꼬 고교 가부시끼가이샤 | 욕창의 예방제 또는 치료제 |
| US7318934B2 (en) * | 2002-10-29 | 2008-01-15 | Medical Nutrition Usa, Inc. | Method for treating wounds to promote healing |
| EP1559425A4 (en) * | 2002-11-01 | 2007-12-19 | Kyowa Hakko Kogyo Kk | PERORAL PREPARATION FOR THE PREVENTION OR TREATMENT OF ATOPIC DERMATITIS |
| JP2004315384A (ja) * | 2003-04-14 | 2004-11-11 | Kyowa Hakko Kogyo Co Ltd | 美白剤 |
| JP4815752B2 (ja) | 2004-04-01 | 2011-11-16 | 味の素株式会社 | アミノ酸含有飲食品 |
| US20070293559A1 (en) * | 2004-09-21 | 2007-12-20 | Erika Kagami | Orally Administered Agent For Preventing Or Improving Dry Station Of Skin |
| JP2006345824A (ja) * | 2005-06-20 | 2006-12-28 | Schnee Weisse:Kk | 海洋深層水とフカヒレとからなる組成物と該組成物を使用した食品用栄養補助材、化粧品および栄養補助食品 |
| US20070065396A1 (en) * | 2005-09-21 | 2007-03-22 | Tracie Martyn International, Llc | Topical macqui berry formulation |
-
2007
- 2007-03-23 CN CNA2007800103881A patent/CN101404998A/zh active Pending
- 2007-03-23 WO PCT/JP2007/055977 patent/WO2007111238A1/ja active Application Filing
- 2007-03-23 US US12/280,846 patent/US20090062371A1/en not_active Abandoned
- 2007-03-23 EP EP07739418.7A patent/EP1997490B1/en not_active Not-in-force
- 2007-03-23 JP JP2008506867A patent/JP5188388B2/ja not_active Expired - Fee Related
-
2013
- 2013-04-04 US US13/856,566 patent/US9433605B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101779733A (zh) * | 2010-03-29 | 2010-07-21 | 济南环亿生物科技有限公司 | 一种提高畜禽肌肉中胶原蛋白的饲料添加剂及其生产方法和应用 |
| CN101779733B (zh) * | 2010-03-29 | 2012-12-26 | 济南环亿生物科技有限公司 | 一种提高畜禽肌肉中胶原蛋白的饲料添加剂及其生产方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2007111238A1 (ja) | 2009-08-13 |
| EP1997490B1 (en) | 2018-05-02 |
| EP1997490A1 (en) | 2008-12-03 |
| US20130225650A1 (en) | 2013-08-29 |
| EP1997490A4 (en) | 2013-07-31 |
| US20090062371A1 (en) | 2009-03-05 |
| US9433605B2 (en) | 2016-09-06 |
| JP5188388B2 (ja) | 2013-04-24 |
| WO2007111238A1 (ja) | 2007-10-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101702851B1 (ko) | 발모촉진, 탈모예방과 모낭개선용 식용귀뚜라미 조성물 | |
| RU99120189A (ru) | Препараты для лечения метаболического синдрома, содержащие гормон роста человека в комбинации с ингибитором синтеза кортзола | |
| CN102365086A (zh) | 紫外线损伤减轻用组合物 | |
| KR20100014572A (ko) | 오스테오칼신 함유 추출물의 제조방법 | |
| CN102481278A (zh) | 紫外线损伤减轻组合物 | |
| CN101404998A (zh) | 组织胶原合成促进用口服剂 | |
| JP5523663B2 (ja) | 歯根−歯周組織形成促進用医薬組成物 | |
| JP5819209B2 (ja) | 幹細胞から褐色脂肪細胞への分化促進剤 | |
| CN1299679C (zh) | 褥疮的预防剂或治疗剂 | |
| KR20200140749A (ko) | 꾸지뽕나무를 유효성분으로 함유하는 근육 질환 개선, 치료 또는 예방용, 또는 근 기능 개선용 조성물 | |
| CN1708300A (zh) | 特应性皮炎的预防或治疗用口服剂 | |
| TW201138812A (en) | Sebum secretion suppressing agent and food, drink and composition produced by using the same | |
| JP5885784B2 (ja) | 経口組成物 | |
| JP2006069967A (ja) | 白髪抑制用組成物およびそれを含有する化粧料及び飲食タイプの化粧料 | |
| JP4442949B2 (ja) | 抗骨粗鬆症剤 | |
| CN106176510A (zh) | 一种用于美容保健的口服物及相应的美容保健组合物 | |
| WO2019131274A1 (ja) | 緑茶抽出物由来の発酵物の製造方法及び緑茶抽出物由来の麹発酵物 | |
| KR19980075409A (ko) | 수용성이 개선된 프로폴리스 추출물 | |
| WO2010119804A1 (ja) | 抗精神疲労剤 | |
| KR100497945B1 (ko) | 성장호르몬 분비촉진용 생약추출물 | |
| JP2002306129A (ja) | 美容効果に優れた食品 | |
| CN106163510A (zh) | 褪黑素分泌调节剂、褪黑素分泌调节方法 | |
| JP6753662B2 (ja) | 抗糖化剤 | |
| JP2004292325A (ja) | 筋肉増強剤および筋肉減衰の予防または治療剤 | |
| TW470749B (en) | Propolis extract with improved water-solubility |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: XIEHE FERMENTATION BIOCHEMICAL CO., LTD. Free format text: FORMER OWNER: KYOWA HAKKO KOGYO CO., LTD. Effective date: 20090619 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20090619 Address of the applicant after: Tokyo, Japan Applicant after: Kyowa Hakko Bio Co., Ltd. Address of the applicant before: Tokyo, Japan Applicant before: Kyowa Hakko Kogyo Co., Ltd. |
|
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090408 |