JP2004331564A - Skin collagen production enhancer - Google Patents
Skin collagen production enhancer Download PDFInfo
- Publication number
- JP2004331564A JP2004331564A JP2003129508A JP2003129508A JP2004331564A JP 2004331564 A JP2004331564 A JP 2004331564A JP 2003129508 A JP2003129508 A JP 2003129508A JP 2003129508 A JP2003129508 A JP 2003129508A JP 2004331564 A JP2004331564 A JP 2004331564A
- Authority
- JP
- Japan
- Prior art keywords
- lactoferrin
- collagen production
- skin
- skin collagen
- promoting
- 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
- 230000037319 collagen production Effects 0.000 title claims abstract description 68
- 239000003623 enhancer Substances 0.000 title abstract 3
- 108010063045 Lactoferrin Proteins 0.000 claims abstract description 89
- 102000010445 Lactoferrin Human genes 0.000 claims abstract description 89
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims abstract description 89
- 229940078795 lactoferrin Drugs 0.000 claims abstract description 89
- 235000021242 lactoferrin Nutrition 0.000 claims abstract description 89
- 235000013305 food Nutrition 0.000 claims abstract description 14
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
- 108091005804 Peptidases Proteins 0.000 claims abstract description 11
- 239000004365 Protease Substances 0.000 claims abstract description 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 2
- 230000001737 promoting effect Effects 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 12
- 102000008186 Collagen Human genes 0.000 abstract description 15
- 108010035532 Collagen Proteins 0.000 abstract description 15
- 229920001436 collagen Polymers 0.000 abstract description 15
- 238000002360 preparation method Methods 0.000 abstract description 7
- 230000037303 wrinkles Effects 0.000 abstract description 6
- 206010013786 Dry skin Diseases 0.000 abstract description 4
- 108010019160 Pancreatin Proteins 0.000 abstract description 4
- 229940055695 pancreatin Drugs 0.000 abstract description 4
- 108090000284 Pepsin A Proteins 0.000 abstract description 3
- 102000057297 Pepsin A Human genes 0.000 abstract description 3
- 229940111202 pepsin Drugs 0.000 abstract description 3
- 230000003247 decreasing effect Effects 0.000 abstract description 2
- 230000002708 enhancing effect Effects 0.000 abstract 2
- 210000003491 skin Anatomy 0.000 description 72
- 230000000694 effects Effects 0.000 description 10
- 102000035195 Peptidases Human genes 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 239000006210 lotion Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 235000019419 proteases Nutrition 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- -1 patches Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000007665 sagging Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229960002591 hydroxyproline Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 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 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001341 hydroxy propyl starch Substances 0.000 description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 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 2
- 239000001993 wax Substances 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 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
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 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
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000283086 Equidae 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
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 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 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000282887 Suidae Species 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 108090001109 Thermolysin Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940009868 aluminum magnesium silicate Drugs 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical compound NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229940100242 glycol stearate Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000036620 skin dryness Effects 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Cosmetics (AREA)
Abstract
Description
【０００１】
【発明の属する技術分野】
本発明は、皮膚の荒れ、シワ、弾性低下等を防止するのに有用な皮膚コラーゲン産生促進剤、皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料に関する。さらに詳しくは、本発明は、 ラクトフェリン及び／またはラクトフェリンをタンパク質分解酵素で分解して得られるラクトフェリン分解物を有効成分とする皮膚コラーゲン産生促進剤に関する。
【０００２】
【従来の技術】
近年、皮膚のメカニズムに関する研究が進められ、皮膚の乾燥感や肌荒れ等の原因としてマクロ的には、加齢による新陳代謝の減衰によるもののほかに、太陽光（紫外線）、乾燥、酸化等の作用が複雑に関与していることが確認されてきた。これらの因子による作用によって、真皮の最も主要なマトリックス成分であるコラーゲン繊維が顕著に減少していることが明らかとなってきた。コラーゲン繊維によって保たれていた皮膚のハリや弾力性といった張力保持機構が紫外線等の作用によって、破壊されると、皮膚はシワやたるみを増した状態になる。また、コラーゲンはその分子中に水分を保持することができ、それにより、皮膚をしっとりとした状態に保つことにも役立っているから、外的因子により、コラーゲンが破壊されると肌は、乾燥し、荒れた状態になる。
以上のことから、真皮層の主要な成分の一つであるコラーゲンの生合成を促進させることにより、皮膚のシワやたるみを防止でき、しかも安全性の点でも問題のない皮膚コラーゲン産生促進剤が望まれていた。
【０００３】
ラクトフェリン及びその分解物については、細胞への病原菌付着防止作用があること（特許文献１参照。）、抗ウイルス作用があること（特許文献２参照。）等が知られている。また、上皮細胞成長因子と混合することにより、上皮細胞成長因子単独の皮膚細胞賦活化作用を高めること（特許文献３参照。）が開示されている。しかし、ラクトフェリン及びその分解物がコラーゲン産生促進作用を持ち、皮膚コラーゲン産生促進剤として有用であることについては知られていない。
【０００４】
【先行技術文献】
【特許文献１】
特開平３−２２０１３０号公報
【特許文献２】
特開平１−２３３２２６号公報
【特許文献３】
特開平７−１９６５２９号公報
【０００５】
【発明が解決しようとする課題】
本発明は、皮膚の乾燥感や肌荒れ、シワやたるみを防止でき、しかも安全性の点でも問題のない、コラーゲンの生合成を促進する物質を有効成分とする皮膚コラーゲン産生促進剤を提供することを課題とする。また、本発明は、そのような物質を配合した皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料を提供することを課題とする。
【０００６】
【課題を解決するための手段】
本発明者らは、これらの課題を解決するために、広く食品素材に含まれているコラーゲン産生促進作用を示す物質について、鋭意、探索を進めていたところ、ラクトフェリンあるいはそのラクトフェリンをペプシンやパンクレアチン等のタンパク質分解酵素で分解して得られるラクトフェリン分解物が、皮膚のコラーゲン量を増加させることができる、すなわち、コラーゲン産生促進作用があることを見出した。そして、このラクトフェリンやラクトフェリン分解物を皮膚コラーゲン産生促進剤、皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料の有効成分として利用できることを見出し、本発明を完成するに至った。
【０００７】
したがって、本発明は、この皮膚コラーゲン産生促進活性を有するラクトフェリンあるいはラクトフェリンをタンパク質分解酵素で分解して得られるラクトフェリン分解物を有効成分とする皮膚コラーゲン産生促進剤に関する。また、本発明は、これらのラクトフェリンやラクトフェリン分解物を配合した皮膚コラーゲン産生促進用飲食品や皮膚コラーゲン産生促進用化粧料に関する。
【０００８】
本発明で皮膚コラーゲン産生促進剤とは、経口投与あるいは塗布等により、皮膚コラーゲン産生促進効果を発揮するものを言うものとする。また、本発明では、この皮膚コラーゲン産生促進剤のうち、粉末剤、顆粒剤、錠剤、カプセル剤、ドリンク剤等に製剤化してそのまま、あるいは製剤化した後、栄養剤や飲食品等に配合して経口投与するものを皮膚コラーゲン産生促進用飲食品と言うものとする。また、本発明では、皮膚コラーゲン産生促進剤のうち、軟膏、ゲル、クリーム、スプレー剤、貼付剤、ローション等に製剤化して肌に塗布するものを皮膚コラーゲン産生促進用化粧料と言うものとする。また、本発明では、医薬品であるが、製剤化してそのまま経口投与するものを便宜上、前記皮膚コラーゲン産生促進用飲食品の中に含め、医薬品であるが、製剤化して肌に塗布するものを便宜上、前記皮膚コラーゲン産生促進用化粧料の中に含めるものとする。
【０００９】
【発明の実施の形態】
本発明の皮膚コラーゲン産生促進剤の特徴は、ラクトフェリンあるいはラクトフェリンをタンパク質分解酵素で分解して得られるラクトフェリン分解物を有効成分とすることにある。
【００１０】
ラクトフェリンは哺乳動物の乳から調製する。給源としては、ウシ、水牛、ヒト、ブタ、ヒツジ、ヤギ、ウマ等の乳があげられる。ラクトフェリンは、公知の物質であって、市販されているものであるが、それを製造するには、公知の方法、例えばスルホン化担体を用いてラクトフェリンを精製する方法（特開平３−１０９４００号公報）を工業的に有利に利用することができる。また、本発明では、遺伝子工学的手法により生産されたラクトフェリンも使用し得る。
【００１１】
ラクトフェリン分解物は、上記のラクトフェリンをトリプシン、パンクレアチン、キモトリプシン、ペプシン、パパイン、カリクレイン、カテプシン、サーモライシン、Ｖ８プロテアーゼ等のタンパク質分解酵素で分子量が１０，０００以下となるように限定分解したペプチド混合物である。分子量の下限は５００以上が好ましい。
【００１２】
本発明の皮膚コラーゲン産生促進剤は、経口投与或いは塗布することにより、皮膚コラーゲン産生促進効果を発揮する。
本発明の皮膚コラーゲン産生促進剤を経口投与するに際しては、有効成分であるラクトフェリンあるいはラクトフェリン分解物をそのままの状態で用いることもできるが、常法に従い、粉末剤、顆粒剤、錠剤、カプセル剤、ドリンク剤等に製剤化して用いることもできる。本発明において、粉末剤、顆粒剤、錠剤、カプセル剤等の経口剤は、例えば、澱粉、乳糖、白糖、マンニット、カルボキシメチルセルロース、コーンスターチ、無機塩類等を用いて常法によって製剤化される。この種の製剤には、前記賦形剤の他に、結合剤、崩壊剤、界面活性剤、滑沢剤、流動性促進剤、着色料、香料等を適宜使用することが出来る。より具体的には、結合剤としては、例えば、澱粉、デキストリン、アラビアガム末、ゼラチン、ヒドロキシプロピルスターチ、カルボキシメチルセルロースナトリウム、メチルセルロース、結晶性セルロース、エチルセルロース、ポリビニルピロリドンが挙げられる。また、崩壊剤としては、例えば、澱粉、ヒドロキシプロピルスターチ、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、架橋カルボキシメチルセルロースナトリウム、結晶性セルロース等が挙げられる。界面活性剤としては、大豆レシチン、蔗糖脂肪酸エステル等が、滑沢剤としては、タルク、ロウ、蔗糖脂肪酸エステル、水素添加植物油等が、流動性促進剤としては無水ケイ酸、乾燥水酸化アルミニウム、ケイ酸マグネシウム等が挙げられる。
【００１３】
さらには、これらのラクトフェリンやラクトフェリン分解物をそのままあるいは製剤化した後、これを栄養剤や飲食品等に配合することも可能である。また、ビタミンＣ等従来からコラーゲン産生に有効な作用をもつと考えられている成分とともにラクトフェリンやラクトフェリン分解物を配合すれば、一層の皮膚コラーゲン産生促進作用が期待できる。なお、ラクトフェリンあるいはラクトフェリン分解物は、比較的熱に対して安定であるので、ラクトフェリンあるいはラクトフェリン分解物を含む原料を通常行われるような条件で加熱殺菌することも可能である。
【００１４】
本発明の皮膚コラーゲン産生促進剤を塗布するに際しては、その使用目的に応じて、通常用いられる公知の成分に配合することによって、液剤、固形剤、半固形剤等の各種剤形に調製することが可能で、好ましい組成物として軟膏、ゲル、クリーム、スプレー剤、貼付剤、ローション、粉末等が挙げられる。例えば、本発明の皮膚コラーゲン産生促進剤をワセリン等の炭化水素、ステアリルアルコール、ミリスチン酸イソプロピル等の高級脂肪酸低級アルキルエステル、ラノリン等の動物性油脂、グリセリン等の多価アルコール、グリセリン脂肪酸エステル、モノステアリン酸ポリエチレングリコール等の界面活性剤、無機塩、ロウ、樹脂、水及び、要すればパラオキシ安息香酸メチル、パラオキシ安息香酸ブチル等の保存料に混合することによって、皮膚コラーゲン産生促進用化粧料や医薬品を製造することができる。
【００１５】
本発明の皮膚コラーゲン産生促進剤の経口投与による有効量は、その製剤形態、投与方法、使用目的、及びこれを適用される患者の年齢、体重、病状により適宜規定され一定でないが、ラットを用いた動物実験の結果によると、皮膚コラーゲン産生促進作用を示すためにはラクトフェリンあるいはラクトフェリン分解物をラット体重１ｋｇ当たり２０ｍｇ以上摂取する必要があることが判った。したがって、外挿法によると、通常、成人一人当たり一日２０ｍｇ以上のラクトフェリンあるいはラクトフェリン分解物を摂取すれば効果が期待できるので、この必要量を確保できるよう飲食品に配合するか、あるいは、医薬として投与すれば良い。なお、投与は必要に応じて一日数回に分けて行うことも可能である。
【００１６】
本発明の皮膚コラーゲン産生促進剤の塗布による有効量は、剤形により異なるが、適用する組成物全量を基準として、好ましくは、０．００１〜２重量％となるように、ラクトフェリンあるいはラクトフェリン分解物を配合すればよい。ただし、入浴剤のように使用時に希釈されるものは、さらに配合量を増やすことができる。
【００１７】
次に、実施例及び試験例を示して本発明を詳細に説明するが、これらは単に本発明の実施態様を例示するのみであり、本発明はこれらによって何ら限定されるものではない。
【００１８】
【実施例１】
陽イオン交換樹脂であるスルホン化キトパール（富士紡績社製）４００ｇを充填したカラム（直径５ｃｍ×高さ３０ｃｍ）を脱イオン水で十分に洗浄した後、このカラムに未殺菌脱脂乳４０ ｌ （ｐＨ ６．７）を流速２５ｍｌ／ｍｉｎで通液した。通液後、カラムを脱イオン水で十分洗浄し、２．０Ｍ塩化ナトリウムを含む ０．０２Ｍ炭酸緩衝液（ｐＨ ７．０）で溶出した。そしてラクトフェリンを含有する溶出画分をＳ−Ｓｅｐｈａｒｏｓｅ ＦＦカラム（アマシャムバイオサイエンス社製）に吸着させ、脱イオン水で十分洗浄し、１０ｍＭリン酸緩衝液（ｐＨ７．０）で平衡化した後、０〜２．０Ｍ塩化ナトリウムのリニアグラジエントで吸着した画分を溶出し、ラクトフェリンを含む画分を回収した。そしてその画分をＨｉＬｏａｄ １６／６０ Ｓｕｐｅｒｄｅｘ ７５ ｐｇ（アマシャムバイオサイエンス社製）を用いたゲル濾過クロマトグラフィーで処理し、ラクトフェリン８．０ｇを得た。なお、このようにして得られたラクトフェリンの純度は９６％であり、そのまま皮膚コラーゲン産生促進剤として使用可能である。
【００１９】
【実施例２】
実施例１で得られたラクトフェリン１ｇを水２００ｍｌに溶解し、最終濃度が０．０１重量％となるようタンパク質分解酵素であるパンクレアチン（シグマ社製）を加え、３７℃で５時間酵素処理した。そして、９０℃で５分間加熱処理して酵素を失活させた後、凍結乾燥してラクトフェリン分解物 ０．８ｇを得た。なお、このようにして得られたラクトフェリン分解物の分子量は、１０，０００以下であり、そのまま皮膚コラーゲン産生促進剤として使用可能である。
【００２０】
【実施例３】
実施例１で得られたラクトフェリン１ｇを水２００ｍｌに懸濁し、最終濃度が０．０１重量％となるようタンパク質分解酵素であるトリプシン（シグマ社製）を加え、３７℃で５時間酵素処理した。そして、９０℃で５分間加熱処理して酵素を失活させた後、凍結乾燥してラクトフェリン分解物 ０．９ｇを得た。なお、このようにして得られたラクトフェリン分解物の分子量は、１０，０００以下であり、そのまま皮膚コラーゲン産生促進剤として使用可能である。
【００２１】
【試験例１】
実施例１で得られたラクトフェリン及び実施例２で得られたラクトフェリン分解物について、ラットを用いた動物実験によりコラーゲン産生促進作用を調べた。７週齢のＷｉｓｔａｒ系雄ラットを、生理食塩水投与群（Ａ群）、実施例１で得られたラクトフェリンをラット体重１ｋｇ当たり２０ｍｇ投与する群（Ｂ群）、実施例１で得られたラクトフェリンをラット体重１ｋｇ当たり２００ｍｇ投与する群（Ｃ群）、実施例２で得られたラクトフェリン分解物をラット体重１ｋｇ当たり２０ｍｇ投与する群（Ｄ群）、実施例２で得られたラクトフェリン分解物をラット体重１ｋｇ当たり２００ｍｇ投与する群（Ｅ群）の５試験群（ｎ＝６）に分け、それぞれを毎日１回ゾンデで投与して１０週間飼育した。
皮膚のコラーゲン量については、ラットの真皮をＮｉｍｎｉらの方法（Ａｒｃｈ． Ｂｉｏｃｈｅｍ． Ｂｉｏｐｈｙｓ， ２９２頁， １９６７年 参照）に準じて処理した後、可溶性画分に含まれるヒドロキシプロリン量を測定した。ヒドロキシプロリンはコラーゲンのみに含まれる特殊なアミノ酸で、コラーゲンを構成する全アミノ酸の約１０％を占めることからコラーゲン量の推定ができる。（浅野隆司ら，Ｂｉｏ Ｉｎｄｕｓｔｏｒｙ，１２頁， ２００１年 参照）。その結果を表１に示す。
【００２２】
【表１】
また、※は対照群であるＡ群と比較して有意差があることを示す（ｐ＜０．０５）。
【００２３】
これによると、１０週間後の可溶性画分中ヒドロキシプロリン量は、Ａ群に比べ、Ｂ群、Ｃ群、Ｄ群及びＥ群で有意に高い値を示した。
このことから、ラクトフェリン及びラクトフェリン分解物には皮膚コラーゲン産生促進作用があることが明らかとなり、皮膚コラーゲン産生促進剤として有用であることが示された。
また、この皮膚コラーゲン産生促進作用はラクトフェリンまたはラクトフェリン分解物をラット体重１ｋｇ当たり最低２０ｍｇ投与した場合に認められることが明らかとなった。
【００２４】
【実施例４】
表２に示す配合の皮膚コラーゲン産生促進用飲料を常法により製造した。製造した飲料の風味は良好で、常温１年間保存によっても風味が劣化することはなく、沈殿等の問題もなかった。
【００２５】
【表２】
【実施例５】
表３に示す配合のドウを常法により作製し、成形した後、焙焼して皮膚コラーゲン産生促進用ビスケットを製造した。
【００２７】
【表３】
【実施例６】
表４に示す配合の皮膚コラーゲン産生促進剤を常法により製造した。
【００２９】
【表４】
【試験例２】
市販のラクトフェリン（シグマ社製）及び実施例２と同様の方法で市販のラクトフェリンをタンパク質分解酵素で処理して得られたラクトフェリン分解物について、正常ヒト線維芽細胞株〔白人女性の皮膚より採取されたＣＣＤ４５ＳＫ（ＡＴＣＣＲＬ １５０６）〕を用いた実験によりコラーゲン産生促進作用を調べた。１０容量％ウシ胎児血清（以下ＦＢＳと略記）含有変法イーグル培地（ＭＥＭ、１０‐１０１、大日本製薬社製）を用いて、正常ヒト線維芽細胞株を４×１０４個／ウエル／０．４ｍｌとなるように２４ウエルプレートに播種して、５％炭酸ガス、飽和水蒸気下、３７℃で２４時間培養した後、０．６容量％ＦＢＳ含有変法イーグル培地に置換した。そして、市販のラクトフェリン（シグマ社製）及び実施例２と同様の方法で市販のラクトフェリンをタンパク質分解酵素で処理して得られたラクトフェリン分解物を、各ウエルに０．１容量％となるように添加（ｎ＝６）して、２４時間培養した後、β―アミノプロピオニトリルを５０μｇ／ｍｌ、トリチウム−Ｌ−プロリンを１μＣｉ／ｍｌとなるように添加して、さらに２４時間培養して培養液を得た。このようにして得られた培養液より、Ｗｅｂｓｔｅｒらの方法（Ａｎａｌｙｔｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ，２２０頁，１９７９年 参照）に従いコラーゲン画分を分画し、コラーゲン画分に取り込まれた放射能を測定した。なお、対照として、ラクトフェリン及びラクトフェリン分解物を添加しないで同様の試験を行った。その結果を表５に示す。
【００３１】
【表５】
また、※は対照群と比較して有意差があることを示す（ｐ＜０．０５）。
【００３２】
これによると、ラクトフェリン及びラクトフェリン分解物を添加した群は、ラクトフェリン及びラクトフェリン分解物を添加していない群（対照）に比べていずれも２倍程度のコラーゲン産生促進能を示した。
このことから、ラクトフェリン及びラクトフェリン分解物には、皮膚線維芽細胞に働きかけ、コラーゲン産生を促進する作用があることが明らかとなり、皮膚コラーゲン産生促進剤として有用であることが示された。
【００３３】
【実施例７】
表６に示す配合の化粧水を常法により製造した。
【００３４】
【表６】
【実施例８】
表７に示す配合のクリームを常法により製造した。
【００３６】
【表７】
【試験例３】
実施例７で得られた化粧水及び実施例８で得られたクリームを用いて、実使用テストを行った。比較品としては、ラクトフェリンを除いた以外は実施例７及び８と同じ配合のものを用いた。
顔面のたるみや小ジワが認められる乾燥肌を有する成人女子２０人を、それぞれ１０人ずつ無作為に２群（Ａ、Ｂ群）に、また、手に肌荒れが認められる女子２０人を、それぞれ１０人ずつ無作為に２群（Ｃ、Ｄ群）に分け、Ａ群の顔面には本発明品の化粧水を、Ｂ群の顔面には比較品の化粧水を、Ｃ群の手指には本発明品のクリームを、Ｄ群の手指には比較品のクリームを、それぞれ１日２回通常の使用状態と同様に１０日間塗布してもらった。その結果、本発明品の化粧水は、比較品の化粧水に比べて、乾燥感の改善、肌荒れの改善が顕著であり、皮膚コラーゲン産生促進効果に優れていることが実証された。また、本発明品のクリームについても、比較品のクリームに比べて、乾燥感、肌荒れの顕著な改善がみられ、肌荒れ等の自然増悪抑制効果を有することが明らかとなった。
【００３８】
【発明の効果】
本発明によりラクトフェリン及び／またはラクトフェリン分解物を有効成分とする皮膚コラーゲン産生促進剤、皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料が提供される。
本発明の皮膚コラーゲン産生促進剤、皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料は、皮膚のコラーゲン産生を促進させる作用を有し、皮膚のシワやたるみ、乾燥感や肌荒れの予防や治療に有用である。[0001]
TECHNICAL FIELD OF THE INVENTION
TECHNICAL FIELD The present invention relates to a skin collagen production promoter, a food and drink for promoting skin collagen production, and a cosmetic for promoting skin collagen production, which are useful for preventing skin roughness, wrinkles, and decreased elasticity. More specifically, the present invention relates to a skin collagen production promoter containing lactoferrin and / or a lactoferrin hydrolyzate obtained by decomposing lactoferrin with a protease, as an active ingredient.
[0002]
[Prior art]
In recent years, studies on the mechanism of the skin have been promoted. Macroscopic causes of skin dryness and rough skin include the effects of sunlight (ultraviolet rays), drying, and oxidation, in addition to the decrease in metabolism due to aging. Complex involvement has been identified. The effects of these factors have revealed that collagen fibers, the most major matrix component of the dermis, have been significantly reduced. When the tension holding mechanism such as firmness and elasticity of the skin held by the collagen fibers is destroyed by the action of ultraviolet rays or the like, the skin becomes wrinkled or sagged. Collagen can also retain moisture in its molecules, which helps to keep the skin moist, so if external factors destroy the collagen, the skin will dry out Then, it becomes rough.
From the above, by promoting the biosynthesis of collagen, one of the main components of the dermis layer, a skin collagen production promoter that can prevent skin wrinkles and sagging and has no problem in terms of safety. Was desired.
[0003]
It is known that lactoferrin and its decomposed product have an effect of preventing adhesion of pathogenic bacteria to cells (see Patent Document 1) and an antiviral effect (see Patent Document 2). In addition, it discloses that the skin cell activating effect of epidermal growth factor alone is enhanced by mixing with epidermal growth factor (see Patent Document 3). However, it has not been known that lactoferrin and its degradation product have a collagen production promoting action and are useful as a skin collagen production promoter.
[0004]
[Prior art documents]
[Patent Document 1]
JP-A-3-220130 [Patent Document 2]
JP-A-1-233226 [Patent Document 3]
JP-A-7-196529
[Problems to be solved by the invention]
The present invention provides a skin collagen production promoter containing a substance that promotes the biosynthesis of collagen as an active ingredient, which can prevent dry feeling, rough skin, wrinkles and sagging of the skin, and has no problem in terms of safety. As an issue. Another object of the present invention is to provide a food and drink for promoting skin collagen production and a cosmetic for promoting skin collagen production, which contain such a substance.
[0006]
[Means for Solving the Problems]
In order to solve these problems, the present inventors have been intensively searching for a substance that has a collagen production promoting effect widely contained in food materials, and found that lactoferrin or the lactoferrin was converted to pepsin or pancreatin. It has been found that a lactoferrin hydrolyzate obtained by decomposing with a proteolytic enzyme can increase the amount of collagen in the skin, that is, has a collagen production promoting action. Then, they have found that this lactoferrin or a lactoferrin hydrolyzate can be used as an active ingredient of a skin collagen production promoter, a skin collagen production promotion food / beverage product, and a skin collagen production promotion cosmetic, and completed the present invention.
[0007]
Accordingly, the present invention relates to a skin collagen production promoting agent comprising lactoferrin having the skin collagen production promoting activity or a lactoferrin hydrolyzate obtained by decomposing lactoferrin with a protease, as an active ingredient. In addition, the present invention relates to a food and drink for promoting skin collagen production and a cosmetic for promoting skin collagen production, in which these lactoferrin and lactoferrin hydrolyzate are blended.
[0008]
In the present invention, the skin collagen production promoter refers to a substance that exhibits a skin collagen production promotion effect by oral administration or application. Further, in the present invention, of this skin collagen production promoter, it is formulated into powders, granules, tablets, capsules, drinks, etc., and as it is, or after being formulated, it is added to nutrients, foods and drinks, etc. What is orally administered is referred to as a food and drink for promoting skin collagen production. In the present invention, among the skin collagen production promoters, those formulated into ointments, gels, creams, sprays, patches, lotions and the like and applied to the skin are referred to as skin collagen production promotion cosmetics. . Further, in the present invention, for convenience, pharmaceuticals, which are formulated and administered orally as they are, are included in the food and drink for promoting skin collagen production, and pharmaceuticals, which are formulated and applied to the skin for convenience. And the cosmetic for promoting the production of skin collagen.
[0009]
BEST MODE FOR CARRYING OUT THE INVENTION
A feature of the skin collagen production promoter of the present invention is that lactoferrin or a lactoferrin hydrolyzate obtained by decomposing lactoferrin with a protease is used as an active ingredient.
[0010]
Lactoferrin is prepared from mammalian milk. Sources include milk from cows, buffaloes, humans, pigs, sheep, goats, horses, and the like. Lactoferrin is a known substance and is commercially available. To produce it, a known method, for example, a method of purifying lactoferrin using a sulfonated carrier (Japanese Unexamined Patent Publication No. 3-109400) ) Can be advantageously used industrially. In the present invention, lactoferrin produced by a genetic engineering technique can also be used.
[0011]
The lactoferrin hydrolyzate is a peptide mixture obtained by subjecting the above lactoferrin to limited digestion with a protease such as trypsin, pancreatin, chymotrypsin, pepsin, papain, kallikrein, cathepsin, thermolysin, or V8 protease to have a molecular weight of 10,000 or less. is there. The lower limit of the molecular weight is preferably 500 or more.
[0012]
The skin collagen production promoter of the present invention exerts a skin collagen production promoting effect by oral administration or application.
When orally administering the skin collagen production promoter of the present invention, the active ingredient lactoferrin or lactoferrin hydrolyzate can be used as it is, but according to a conventional method, powders, granules, tablets, capsules, It can also be formulated into drinks and used. In the present invention, oral preparations such as powders, granules, tablets, capsules and the like are formulated by a conventional method using, for example, starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salts and the like. In this type of preparation, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a colorant, a flavor, and the like can be appropriately used in addition to the above-mentioned excipients. More specifically, examples of the binder include starch, dextrin, gum arabic, gelatin, hydroxypropyl starch, sodium carboxymethylcellulose, methylcellulose, crystalline cellulose, ethylcellulose, and polyvinylpyrrolidone. Examples of the disintegrant include starch, hydroxypropyl starch, carboxymethylcellulose, sodium carboxymethylcellulose, crosslinked sodium carboxymethylcellulose, and crystalline cellulose. As a surfactant, soybean lecithin, sucrose fatty acid ester, etc., as a lubricant, talc, wax, sucrose fatty acid ester, hydrogenated vegetable oil, etc., as a fluidity promoter, silicic anhydride, dried aluminum hydroxide, And magnesium silicate.
[0013]
Furthermore, these lactoferrin or lactoferrin hydrolyzate can be used as it is or after being formulated, and then added to nutritional supplements, foods and drinks, and the like. Further, when lactoferrin or a lactoferrin hydrolyzate is blended together with a component which has been conventionally considered to have an effective effect on collagen production, such as vitamin C, a further action of promoting skin collagen production can be expected. In addition, since lactoferrin or a lactoferrin hydrolyzate is relatively stable to heat, it is also possible to heat-sterilize a raw material containing lactoferrin or a lactoferrin hydrolyzate under ordinary conditions.
[0014]
When applying the skin collagen production promoter of the present invention, depending on the purpose of use, it may be prepared into various dosage forms such as liquid preparation, solid preparation, semi-solid preparation, etc. by blending it with commonly used known components. Preferred compositions include ointments, gels, creams, sprays, patches, lotions, powders and the like. For example, the skin collagen production promoter of the present invention may be a hydrocarbon such as petrolatum, stearyl alcohol, lower alkyl esters of higher fatty acids such as isopropyl myristate, animal oils such as lanolin, polyhydric alcohols such as glycerin, glycerin fatty acid esters, By mixing with surfactants such as polyethylene glycol stearate, inorganic salts, waxes, resins, water and, if necessary, preservatives such as methyl parahydroxybenzoate and butyl parahydroxybenzoate, cosmetics for promoting skin collagen production, Pharmaceuticals can be manufactured.
[0015]
Although the effective amount of the skin collagen production promoter of the present invention by oral administration is appropriately defined depending on the formulation form, administration method, purpose of use, and the age, weight, and medical condition of the patient to which the agent is applied, it is not constant. According to the results of animal experiments, lactoferrin or a lactoferrin hydrolyzate must be taken in an amount of 20 mg or more per kg of rat body weight in order to exhibit a skin collagen production promoting effect. Therefore, according to the extrapolation method, the effect can usually be expected if ingesting 20 mg or more of lactoferrin or a lactoferrin hydrolyzate per adult per day. Should be administered as The administration can be carried out several times a day, if necessary.
[0016]
The effective amount of the skin collagen production promoter of the present invention by application varies depending on the dosage form, but is preferably lactoferrin or a lactoferrin hydrolyzate such that it is preferably 0.001 to 2% by weight based on the total amount of the applied composition. May be blended. However, the amount of a substance that is diluted at the time of use, such as a bathing agent, can be further increased.
[0017]
Next, the present invention will be described in detail with reference to Examples and Test Examples, which merely exemplify embodiments of the present invention, and the present invention is not limited thereto.
[0018]
Embodiment 1
A column (diameter 5 cm × height 30 cm) packed with 400 g of a cation exchange resin sulfonated chitopearl (manufactured by Fuji Boseki Co., Ltd.) was sufficiently washed with deionized water, and then 40 l of unsterilized skim milk (pH 6.7) was passed at a flow rate of 25 ml / min. After the passage, the column was sufficiently washed with deionized water, and eluted with a 0.02 M carbonate buffer (pH 7.0) containing 2.0 M sodium chloride. Then, the eluted fraction containing lactoferrin was adsorbed on an S-Sepharose FF column (manufactured by Amersham Bioscience), washed thoroughly with deionized water, equilibrated with 10 mM phosphate buffer (pH 7.0), and The adsorbed fraction was eluted with a linear gradient of ２．０2.0 M sodium chloride, and the fraction containing lactoferrin was collected. Then, the fraction was subjected to gel filtration chromatography using HiLoad 16/60 Superdex 75 pg (manufactured by Amersham Bioscience) to obtain 8.0 g of lactoferrin. The lactoferrin thus obtained has a purity of 96% and can be used as it is as a skin collagen production promoter.
[0019]
Embodiment 2
1 g of the lactoferrin obtained in Example 1 was dissolved in 200 ml of water, pancreatin (manufactured by Sigma) as a protease was added to a final concentration of 0.01% by weight, and the mixture was subjected to an enzyme treatment at 37 ° C. for 5 hours. . Then, the enzyme was inactivated by heating at 90 ° C. for 5 minutes, and then freeze-dried to obtain 0.8 g of a lactoferrin hydrolyzate. The lactoferrin hydrolyzate thus obtained has a molecular weight of 10,000 or less and can be used as it is as a skin collagen production promoter.
[0020]
Embodiment 3
1 g of the lactoferrin obtained in Example 1 was suspended in 200 ml of water, and trypsin (Sigma), which is a protease, was added to a final concentration of 0.01% by weight, followed by enzyme treatment at 37 ° C. for 5 hours. Then, the enzyme was inactivated by heat treatment at 90 ° C. for 5 minutes, followed by freeze-drying to obtain 0.9 g of a lactoferrin hydrolyzate. The lactoferrin hydrolyzate thus obtained has a molecular weight of 10,000 or less and can be used as it is as a skin collagen production promoter.
[0021]
[Test Example 1]
The lactoferrin obtained in Example 1 and the lactoferrin hydrolyzate obtained in Example 2 were examined for the effect of promoting collagen production by animal experiments using rats. Seven-week-old Wistar male rats were administered with saline (Group A), lactoferrin obtained in Example 1 at 20 mg / kg body weight (Group B), and lactoferrin obtained in Example 1. , A group administered with 200 mg / kg of rat body weight (Group C), a group administered with the lactoferrin hydrolyzate obtained in Example 2 at 20 mg / kg rat weight (Group D), and a lactoferrin hydrolyzate obtained in Example 2 with rat The test group (n = 6) was divided into five test groups (group E) in which 200 mg was administered per kg of body weight, and each was administered once daily with a sonde and bred for 10 weeks.
Regarding the amount of collagen in the skin, the dermis of rats was treated according to the method of Nimni et al. (See Arch. Biochem. Biophys, p. 292, 1967), and the amount of hydroxyproline contained in the soluble fraction was measured. Hydroxyproline is a special amino acid contained only in collagen and occupies about 10% of all amino acids constituting collagen, so that the amount of collagen can be estimated. (See Takashi Asano et al., Bio Industry, page 12, 2001). Table 1 shows the results.
[0022]
[Table 1]
In addition, * indicates that there is a significant difference compared to the control group A (p <0.05).
[0023]
According to this, the amount of hydroxyproline in the soluble fraction after 10 weeks was significantly higher in the B, C, D and E groups than in the A group.
From this, it became clear that lactoferrin and the lactoferrin hydrolyzate had a skin collagen production promoting action, and it was shown to be useful as a skin collagen production promoting agent.
It was also found that this skin collagen production promoting effect was observed when lactoferrin or a lactoferrin hydrolyzate was administered at least 20 mg per kg of rat body weight.
[0024]
Embodiment 4
A beverage for promoting skin collagen production having the composition shown in Table 2 was produced by a conventional method. The flavor of the produced beverage was good, and the flavor did not deteriorate even after storage at room temperature for one year, and there was no problem such as precipitation.
[0025]
[Table 2]
Embodiment 5
A dough having the composition shown in Table 3 was prepared by a conventional method, molded, and then roasted to produce a skin collagen production promoting biscuit.
[0027]
[Table 3]
Embodiment 6
A skin collagen production promoter having the formulation shown in Table 4 was produced by a conventional method.
[0029]
[Table 4]
[Test Example 2]
For a commercially available lactoferrin (manufactured by Sigma) and a lactoferrin hydrolyzate obtained by treating a commercially available lactoferrin with a protease in the same manner as in Example 2, a normal human fibroblast cell line [collected from the skin of a white female] The effect of promoting collagen production was examined by an experiment using CCD45SK (ATCCRL1506). Using a modified Eagle's medium (MEM, 10-101, manufactured by Dainippon Pharma Co., Ltd.) containing 10% by volume of fetal bovine serum (hereinafter abbreviated as FBS), 4 × 10 4 normal human fibroblast cell lines / well / 0 The cells were inoculated in a 24-well plate so as to have a volume of 0.4 ml, cultured at 37 ° C. for 24 hours under 5% carbon dioxide gas and saturated steam, and then replaced with a modified Eagle medium containing 0.6% by volume of FBS. Then, a commercially available lactoferrin (manufactured by Sigma) and a lactoferrin hydrolyzate obtained by treating a commercially available lactoferrin with a protease in the same manner as in Example 2 were added to each well in an amount of 0.1% by volume. After adding (n = 6) and culturing for 24 hours, β-aminopropionitrile is added at 50 μg / ml and tritium-L-proline is added at 1 μCi / ml, and culturing is further performed for 24 hours. A liquid was obtained. From the culture solution thus obtained, a collagen fraction was fractionated according to the method of Webster et al. (See Analytical Biochemistry, page 220, 1979), and the radioactivity incorporated in the collagen fraction was measured. In addition, as a control, the same test was performed without adding lactoferrin and a lactoferrin hydrolyzate. Table 5 shows the results.
[0031]
[Table 5]
* Indicates that there is a significant difference compared to the control group (p <0.05).
[0032]
According to this, the group to which lactoferrin and the lactoferrin hydrolyzate were added showed about twice the ability to promote collagen production as compared to the group to which lactoferrin and the lactoferrin hydrolyzate were not added (control).
From this, it was clarified that lactoferrin and lactoferrin hydrolyzate act on skin fibroblasts to promote collagen production, and were shown to be useful as a skin collagen production promoter.
[0033]
Embodiment 7
A lotion having the composition shown in Table 6 was produced by a conventional method.
[0034]
[Table 6]
Embodiment 8
A cream having the composition shown in Table 7 was produced by a conventional method.
[0036]
[Table 7]
[Test Example 3]
An actual use test was performed using the lotion obtained in Example 7 and the cream obtained in Example 8. As a comparative product, the same formulation as in Examples 7 and 8 was used except that lactoferrin was omitted.
Twenty adult women with dry skin with sagging face and fine wrinkles are observed in two groups (A and B groups) at random, and 20 women with rough skin on their hands. Ten groups were randomly divided into two groups (groups C and D), the lotion of the present invention was applied to the face of group A, the comparative lotion was applied to the face of group B, and the hands of group C were applied to the fingers. The cream of the present invention and the cream of the comparative product were applied to the fingers of the group D twice a day for 10 days in the same manner as in a normal use state. As a result, it was demonstrated that the lotion of the product of the present invention has a remarkable improvement in dry feeling and skin roughness as compared with the lotion of the comparative product, and has an excellent skin collagen production promoting effect. In addition, the cream of the present invention also showed a remarkable improvement in dry feeling and rough skin as compared with the cream of the comparative product, and it was clarified that it had an effect of suppressing natural deterioration such as rough skin.
[0038]
【The invention's effect】
The present invention provides a skin collagen production promoter, a food / drink for promoting skin collagen production, and a cosmetic for promoting skin collagen production, comprising lactoferrin and / or lactoferrin hydrolyzate as an active ingredient.
The skin collagen production promoter, skin collagen production promotion food / beverage product and skin collagen production promotion cosmetic of the present invention have an action of promoting skin collagen production, and prevent skin wrinkles and sagging, dryness and rough skin. And is useful for treatment.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003129508A JP2004331564A (en) | 2003-05-07 | 2003-05-07 | Skin collagen production enhancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003129508A JP2004331564A (en) | 2003-05-07 | 2003-05-07 | Skin collagen production enhancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2004331564A true JP2004331564A (en) | 2004-11-25 |
Family
ID=33505327
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003129508A Pending JP2004331564A (en) | 2003-05-07 | 2003-05-07 | Skin collagen production enhancer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2004331564A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008024703A (en) * | 2006-06-23 | 2008-02-07 | Rohto Pharmaceut Co Ltd | Composition having collagen production-promoting ability and/or fibroblast proliferation-promoting ability |
| WO2010071132A1 (en) | 2008-12-15 | 2010-06-24 | カルピス株式会社 | Peptide for inhibiting skin aging |
| JP2010209043A (en) * | 2009-03-12 | 2010-09-24 | Kuroisutaazu :Kk | Skin care preparation |
| JP2016121109A (en) * | 2014-12-25 | 2016-07-07 | 国立大学法人東京農工大学 | Epidermis basement membrane protectant |
| US10016481B2 (en) | 2011-10-04 | 2018-07-10 | Megmilk Snow Brand Co., Ltd. | Sensation-improving agent |
| JP2020094047A (en) * | 2018-12-06 | 2020-06-18 | 株式会社Ｎｒｌファーマ | Agents for improving or variegating normal bacterial flora of skin and compositions containing the same |
| JPWO2023281657A1 (en) * | 2021-07-07 | 2023-01-12 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04334310A (en) * | 1991-05-01 | 1992-11-20 | Ichimaru Pharcos Co Ltd | Agent for suppressing formation of lipid peroxide |
| JPH06199687A (en) * | 1992-08-07 | 1994-07-19 | Morinaga Milk Ind Co Ltd | Antioxidant |
| JPH08151331A (en) * | 1994-09-30 | 1996-06-11 | Snow Brand Milk Prod Co Ltd | Bone-strengthening agent |
| JPH09191856A (en) * | 1996-01-17 | 1997-07-29 | Snow Brand Milk Prod Co Ltd | Nutrient-replenishing composition |
| JP2000136148A (en) * | 1998-10-28 | 2000-05-16 | Meiji Milk Prod Co Ltd | Composition for inhibiting adhesion to cell |
| JP2001226289A (en) * | 2000-02-16 | 2001-08-21 | Snow Brand Milk Prod Co Ltd | Hepatic function ameliorative agent |
| JP2002087974A (en) * | 2000-09-12 | 2002-03-27 | Maruzen Pharmaceut Co Ltd | Prophylactic and therapeutic agent for inflammatory disease |
| JP2002145737A (en) * | 2000-11-10 | 2002-05-22 | Yashiro Kogyo Kk | Cosmetic with formulated ancient saltwater |
| JP2003095970A (en) * | 2001-09-27 | 2003-04-03 | Maruzen Pharmaceut Co Ltd | Skin cosmetic, and drink and food |
-
2003
- 2003-05-07 JP JP2003129508A patent/JP2004331564A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04334310A (en) * | 1991-05-01 | 1992-11-20 | Ichimaru Pharcos Co Ltd | Agent for suppressing formation of lipid peroxide |
| JPH06199687A (en) * | 1992-08-07 | 1994-07-19 | Morinaga Milk Ind Co Ltd | Antioxidant |
| JPH08151331A (en) * | 1994-09-30 | 1996-06-11 | Snow Brand Milk Prod Co Ltd | Bone-strengthening agent |
| JPH09191856A (en) * | 1996-01-17 | 1997-07-29 | Snow Brand Milk Prod Co Ltd | Nutrient-replenishing composition |
| JP2000136148A (en) * | 1998-10-28 | 2000-05-16 | Meiji Milk Prod Co Ltd | Composition for inhibiting adhesion to cell |
| JP2001226289A (en) * | 2000-02-16 | 2001-08-21 | Snow Brand Milk Prod Co Ltd | Hepatic function ameliorative agent |
| JP2002087974A (en) * | 2000-09-12 | 2002-03-27 | Maruzen Pharmaceut Co Ltd | Prophylactic and therapeutic agent for inflammatory disease |
| JP2002145737A (en) * | 2000-11-10 | 2002-05-22 | Yashiro Kogyo Kk | Cosmetic with formulated ancient saltwater |
| JP2003095970A (en) * | 2001-09-27 | 2003-04-03 | Maruzen Pharmaceut Co Ltd | Skin cosmetic, and drink and food |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008024703A (en) * | 2006-06-23 | 2008-02-07 | Rohto Pharmaceut Co Ltd | Composition having collagen production-promoting ability and/or fibroblast proliferation-promoting ability |
| WO2010071132A1 (en) | 2008-12-15 | 2010-06-24 | カルピス株式会社 | Peptide for inhibiting skin aging |
| US9067972B2 (en) | 2008-12-15 | 2015-06-30 | Calpis Co., Ltd. | Skin aging-inhibiting peptide |
| JP2010209043A (en) * | 2009-03-12 | 2010-09-24 | Kuroisutaazu :Kk | Skin care preparation |
| US10016481B2 (en) | 2011-10-04 | 2018-07-10 | Megmilk Snow Brand Co., Ltd. | Sensation-improving agent |
| JP2016121109A (en) * | 2014-12-25 | 2016-07-07 | 国立大学法人東京農工大学 | Epidermis basement membrane protectant |
| JP2020094047A (en) * | 2018-12-06 | 2020-06-18 | 株式会社Ｎｒｌファーマ | Agents for improving or variegating normal bacterial flora of skin and compositions containing the same |
| JPWO2023281657A1 (en) * | 2021-07-07 | 2023-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9763868B2 (en) | Skin collagen production-promoting agent | |
| JP6259209B2 (en) | Collagen production promoter | |
| JP4698935B2 (en) | Skin collagen production promoter | |
| KR100980352B1 (en) | Skin collagen production promoter | |
| JP5955499B2 (en) | Skin collagen production promoter | |
| KR101789355B1 (en) | Skin collagen production-promoting agent | |
| JP2004331564A (en) | Skin collagen production enhancer | |
| JP4698934B2 (en) | Skin collagen production promoter | |
| JP5955631B2 (en) | Hyaluronic acid production promoter | |
| JP5955630B2 (en) | Hyaluronic acid production promoter | |
| JP5783484B2 (en) | Skin collagen production promoter | |
| JP5955632B2 (en) | Hyaluronic acid production promoter | |
| WO2012043713A1 (en) | Skin collagen production-promoting agent | |
| WO2012043711A1 (en) | Skin collagen production-promoting agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060428 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090710 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090907 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20100319 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100413 |