CN113876623B - Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production - Google Patents
Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production Download PDFInfo
- Publication number
- CN113876623B CN113876623B CN202111123265.7A CN202111123265A CN113876623B CN 113876623 B CN113876623 B CN 113876623B CN 202111123265 A CN202111123265 A CN 202111123265A CN 113876623 B CN113876623 B CN 113876623B
- Authority
- CN
- China
- Prior art keywords
- hyaluronic acid
- acid oligosaccharide
- mass ratio
- oligosaccharide composition
- skin
- 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.)
- Active
Links
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 242
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 236
- -1 hyaluronic acid oligosaccharide Chemical class 0.000 title claims abstract description 173
- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 170
- 239000000203 mixture Substances 0.000 title claims abstract description 92
- 230000001737 promoting effect Effects 0.000 title claims description 22
- 230000037319 collagen production Effects 0.000 title claims description 16
- 230000009759 skin aging Effects 0.000 title abstract description 15
- 230000032683 aging Effects 0.000 claims abstract description 22
- 239000002537 cosmetic Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims description 7
- 210000003491 skin Anatomy 0.000 abstract description 39
- 108010035532 Collagen Proteins 0.000 abstract description 25
- 102000008186 Collagen Human genes 0.000 abstract description 25
- 229920001436 collagen Polymers 0.000 abstract description 25
- 210000004207 dermis Anatomy 0.000 abstract description 15
- 210000002950 fibroblast Anatomy 0.000 abstract description 12
- 230000036541 health Effects 0.000 abstract description 9
- 239000007924 injection Substances 0.000 abstract description 9
- 238000002347 injection Methods 0.000 abstract description 9
- 239000002253 acid Substances 0.000 abstract description 7
- 230000003712 anti-aging effect Effects 0.000 abstract description 6
- 230000037303 wrinkles Effects 0.000 abstract description 6
- 230000003020 moisturizing effect Effects 0.000 abstract description 4
- 230000002500 effect on skin Effects 0.000 abstract description 3
- 230000001815 facial effect Effects 0.000 abstract description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 71
- 239000000243 solution Substances 0.000 description 43
- 239000000047 product Substances 0.000 description 19
- 238000001819 mass spectrum Methods 0.000 description 12
- 238000010586 diagram Methods 0.000 description 11
- 210000002615 epidermis Anatomy 0.000 description 11
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- KIUKXJAPPMFGSW-XZLGHBIVSA-N beta-D-GlcpA-(1->3)-beta-D-GlcpNAc-(1->4)-beta-D-GlcpA-(1->3)-D-GlcpNAc Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-XZLGHBIVSA-N 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 150000002482 oligosaccharides Chemical class 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 210000001339 epidermal cell Anatomy 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 238000000108 ultra-filtration Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940099552 hyaluronan Drugs 0.000 description 6
- 238000001728 nano-filtration Methods 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102000012422 Collagen Type I Human genes 0.000 description 5
- 108010022452 Collagen Type I Proteins 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 210000001156 gastric mucosa Anatomy 0.000 description 4
- 238000005461 lubrication Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000012188 paraffin wax Substances 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 210000001835 viscera Anatomy 0.000 description 4
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 3
- 229920002492 poly(sulfone) Polymers 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005728 strengthening Methods 0.000 description 3
- 238000005670 sulfation reaction Methods 0.000 description 3
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 description 2
- 102000001974 Hyaluronidases Human genes 0.000 description 2
- 102000016776 Midkine Human genes 0.000 description 2
- 108010092801 Midkine Proteins 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 206010051246 Photodermatosis Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 125000000600 disaccharide group Chemical group 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229940014041 hyaluronate Drugs 0.000 description 2
- 229960002773 hyaluronidase Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002356 laser light scattering Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008845 photoaging Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000007665 sagging Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 230000019635 sulfation Effects 0.000 description 2
- 230000036561 sun exposure Effects 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 150000004044 tetrasaccharides Chemical class 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102000001187 Collagen Type III Human genes 0.000 description 1
- 108010069502 Collagen Type III Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 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
- 241000545744 Hirudinea Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical group CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000012641 Pigmentation disease Diseases 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 201000010251 cutis laxa Diseases 0.000 description 1
- XYZMOVWWVXBHDP-UHFFFAOYSA-N cyclohexyl isocyanide Chemical compound [C-]#[N+]C1CCCCC1 XYZMOVWWVXBHDP-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 150000002772 monosaccharides Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000037370 skin discoloration Effects 0.000 description 1
- 230000004215 skin function Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- 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
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Birds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Physical Education & Sports Medicine (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
The invention provides a use of a hyaluronic acid oligosaccharide composition in resisting skin aging, wherein the hyaluronic acid oligosaccharide composition comprises hyaluronic acid oligosaccharide with a uronic acid structure at a reducing end. The hyaluronic acid oligosaccharide composition of the invention has a relatively small molecular weight and an uronic acid at the reducing end. Can remarkably promote the generation of collagen of dermal fibroblast, increase the collagen content in dermis, reduce the generation of wrinkles, and have certain anti-aging activity. Meanwhile, the unique triple helix structure of the collagen can strongly lock 30 times of moisture, so that the skin is durable and moist, glossy and tender. The hyaluronic acid oligosaccharide composition of the invention can be used for preparing cosmetics for resisting aging and moisturizing, medical appliances such as facial injections, microneedle products and oral health care products.
Description
Technical Field
The invention belongs to the technical field of bioengineering, and particularly relates to application of a hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen generation.
Background
Hyaluronic Acid (HA) is a glycosaminoglycan that is ubiquitous in the extracellular matrix, consisting of disaccharide repeats of N-acetamido glucose and glucuronic acid. Hyaluronic acid is widely used in the fields of medicine, food, cosmetics, etc. The molecular weight of hyaluronic acid is one of the basic parameters characterizing the characteristics of hyaluronic acid, and the biological properties of HA are closely related to the molecular weight of hyaluronic acid. Macromolecular hyaluronic acid (HMW-HA) generally plays a role in maintaining cellular homeostasis, while small hyaluronic acid (LMW-HA) and oligomeric hyaluronic acid (o-HA) perform a bioactive function.
The main methods for preparing small molecule hyaluronic acid are physical degradation, chemical degradation and enzymatic degradation. The physical method mainly comprises means of heating, irradiation and the like. The hyaluronic acid product prepared by the method has poor stability. However, hydrolysis and oxidative degradation are often used in chemical laws, and some chemical reagents may be introduced in the chemical laws, which may easily affect the properties of hyaluronic acid and quality control of products. The enzymolysis method uses specific enzyme to break the glycosidic bond in hyaluronic acid to obtain small molecule hyaluronic acid. The specificity of the shearing glycosidic bond can be improved by using a specific enzyme, and the small-molecule hyaluronic acid with concentrated pure molecular weight distribution and higher purity can be obtained.
Skin aging, also called skin aging, refers to the aging damage of skin functions, which causes the protection ability, regulation ability and the like of the skin to the body to decline, so that the skin cannot adapt to the change of the internal and external environments, and the overall appearance conditions such as color, luster, shape, texture and the like are changed. Aging of skin is classified into endogenous aging and exogenous aging. Endogenous aging refers to natural aging of skin with aging, which is manifested by skin whitening, appearance of fine wrinkles, reduced elasticity, and loose skin. The most important causes of extrinsic aging are photoaging due to sun exposure, manifested by wrinkles, skin sagging, rough, yellowish or yellowish skin discoloration, telangiectasia, pigmentation, etc.
However, the structure of the material generally affects its biological activity, and oligosaccharides also exhibit complex and close structure-activity relationships. Non-patent literature 1(Han W,Song L,Wang Y,et al.Preparation,characterization,and inhibition of hyaluronic acid oligosaccharides in triple-negative breast cancer[J].Biomolecules,2019,9(9):436.) selectively produced Hyaluronic Acid Oligosaccharides (HAOs) with different degrees of polymerization and reduced ends by varying the hydrochloric acid concentration, and data from molecular docking simulation of HAOs with CD44 and TLR4 using MOE software showed that HAOs binding capacity to CD44 and TLR4 increased with increasing degrees of polymerization of HAOs, while binding capacity increased significantly when HAOs was GlcNAc residue at the reduced end and not significantly changed when GlcA residue at the reduced end. Non-patent literature 2(Yao W,Chen M,Dou X,et al.Unravel a neuroactive sHA sulfation pattern with neurogenesis activity by a library of defined oligosaccharides[J].European journal of medicinal chemistry,2019,163:583-596.) discloses that sulfated hyaluronic acid (sHA) has good biological functions, and that a specific sulfation pattern plays a key role in regulating the binding pattern between glycosaminoglycan and protein, demonstrating that sHA tetrasaccharide with 6-O-sulfation (sHA-6S) has an important role in promoting the growth of rat E18 hippocampal neuron axons in vitro. Non-patent literature 3(Solera C,Macchione G,Maza S,et al.Chondroitin sulfate tetrasaccharides:synthesis,three-dimensional structure and interaction with midkine[J].2016.) uses a fluorescence polarization competition assay to analyze the relative binding affinity of synthetic compounds and reveals interactions between synthetic chondroitin-like tetraose and midkine. It can be seen that HAOs differences in degree of polymerization, steric structure, or residues have different effects on biological activity or create new functions. This is very worthy of intensive research. There has also been no study in the prior art of ultra-small molecular weight hyaluronic acid having uronic acid end groups in improving skin aging or in promoting collagen formation.
Therefore, the structure-activity relationship of the HA substances is further researched to obtain more beneficial active substances and effects, and the method HAs very important significance for expanding the application of HA.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides an application of a hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production.
In particular, the invention relates to the following aspects:
1. use of an oligosaccharide composition of hyaluronic acid in the treatment of skin ageing, characterised in that the oligosaccharide composition of hyaluronic acid comprises an oligosaccharide of the structure of formula (I):
wherein X is H, K, na, ca or Zn, preferably Na;
n is an integer selected from 0 to 5;
in the hyaluronic acid oligosaccharide composition,
The mass ratio of the hyaluronic acid oligosaccharide of n=1 is 35-70%, the mass ratio of the hyaluronic acid oligosaccharide of n=0 is 5-40%, the mass ratio of the hyaluronic acid oligosaccharide of n=2 is 10-50%, the mass ratio of the hyaluronic acid oligosaccharide of n=3 is 1-15%, the mass ratio of the hyaluronic acid oligosaccharide of n=4 is 0.1-10%, and the mass ratio of the hyaluronic acid oligosaccharide of n=5 is 0.01-5%.
2. The use according to claim 1, wherein the hyaluronic acid oligosaccharide composition is anti-skin aging by promoting collagen production and/or epidermal cell proliferation and differentiation.
3. The use according to item 1, characterized in that in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid oligosaccharides with n=1 is 40-60%; the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-20%; the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 20-40%; the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 3-8%; the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 1-5%; the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-1.5%.
4. The use according to claim 1, wherein the weight average molecular weight of the hyaluronic acid oligosaccharide composition is 1kDa or less.
5. The use according to claim 1, wherein the hyaluronic acid oligosaccharide composition is applied to the skin, preferably by means of a cosmetic or medical device.
6. The use according to claim 5, characterized in that the hyaluronic acid oligosaccharide composition is present in the cosmetic or medical device in a mass concentration of 0.0001% to 5%, preferably 0.001% to 1%.
7. Use of a hyaluronic acid oligosaccharide composition for promoting collagen production, characterized in that the hyaluronic acid oligosaccharide composition comprises a hyaluronic acid oligosaccharide of the structure shown in formula (I):
wherein X is H, K, na, ca or Zn, preferably Na;
n is an integer selected from 0 to 5;
in the hyaluronic acid oligosaccharide composition,
The mass ratio of the hyaluronic acid oligosaccharide of n=1 is 35-70%, the mass ratio of the hyaluronic acid oligosaccharide of n=0 is 5-40%, the mass ratio of the hyaluronic acid oligosaccharide of n=2 is 10-50%, the mass ratio of the hyaluronic acid oligosaccharide of n=3 is 1-15%, the mass ratio of the hyaluronic acid oligosaccharide of n=4 is 0.1-10%, and the mass ratio of the hyaluronic acid oligosaccharide of n=5 is 0.01-5%.
8. The use according to claim 7, wherein the hyaluronic acid oligosaccharide composition is used for preparing a health product for promoting collagen production, or for preparing a health product for protecting and strengthening organs, or for preparing a health product for protecting gastric mucosa, or for preparing a health product for supplementing calcium, or for preparing a joint lubrication injection, and preferably the hyaluronic acid oligosaccharide composition has a mass concentration of 0.001% -1% in the health product or injection.
9. The use according to item 7, characterized in that in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid oligosaccharides with n=1 is 40-60%; the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-20%; the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 20-40%; the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 3-8%; the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 1-5%; the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-1.5%.
10. The use according to item 7, wherein the weight average molecular weight of the hyaluronic acid oligosaccharide composition is 1kDa or less.
The hyaluronic acid oligosaccharide composition has smaller molecular weight, has uronic acid at the reducing end, can obviously promote the generation of collagen of dermal fibroblast, increases the content of collagen in dermis, reduces the generation of wrinkles, and has certain anti-aging activity. Meanwhile, the unique triple helix structure of the collagen can strongly lock 30 times of moisture, so that the skin is durable and moist, glossy and tender. The hyaluronic acid oligosaccharide composition of the invention can be used for preparing cosmetics and medical appliances with anti-aging and moisturizing functions. The hyaluronic acid oligosaccharide composition has the purpose of promoting collagen production, and can be further used for preparing a health-care product for promoting collagen production, or a health-care product for protecting and strengthening organs, or a health-care product for protecting gastric mucosa, or a health-care product for supplementing calcium, or a joint lubrication injection.
Drawings
FIG. 1 is a liquid phase diagram of a hyaluronic acid oligosaccharide composition.
FIG. 2 is a mass spectrum total ion flow peak diagram of the hyaluronic acid oligosaccharide composition.
FIG. 3 is an ionic strength diagram of hyaluronic acid disaccharide (HA 2).
FIG. 4 is an ionic strength diagram of hyaluronic acid tetrasaccharide (HA 4).
Fig. 5 is an ionic strength diagram of hyaluronan hexasaccharide (HA 6).
FIG. 6 is an ionic strength diagram of octasaccharide hyaluronate (HA 8).
Fig. 7 is an ionic strength diagram of hyaluronic acid decasaccharide (HA 10) and hyaluronic acid dodecasaccharide (HA 12).
FIG. 8 shows the content of collagen I secreted by fibroblasts after using samples 1-1 and 2-1.
FIG. 9 shows the content of collagen I secreted by fibroblasts after using samples 1, 1-2, 1-3.
Fig. 10 shows the structure of the 3D full-thickness skin model after using sample 1 and sample 2.
FIG. 11 is a photomicrograph of the transdermal profile of sample 4.
Detailed Description
The invention will be further illustrated with reference to the following examples, which are to be understood as merely further illustrating and explaining the invention and are not to be construed as limiting the invention.
Unless defined otherwise, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the materials and methods are described herein below. In case of conflict, the present specification, including definitions therein, will control and materials, methods, and examples, will control and be in no way limiting. The invention is further illustrated below in connection with specific examples, which are not intended to limit the scope of the invention.
Human skin ages naturally with age or with environmental stimuli, resulting in skin aging. Natural aging is endogenous aging, manifests as skin whitening, appearance of fine wrinkles, reduced elasticity, skin sagging, etc., and environmental stimulus is exogenous aging, such as photoaging caused by sun exposure. If the skin is not well maintained or decays with age, dead skin will adhere to the skin surface without falling off, thus causing a series of problems, seriously affecting beauty.
In order to solve the problem of skin aging, the invention provides a use of a hyaluronic acid oligosaccharide composition in resisting skin aging, wherein the hyaluronic acid oligosaccharide composition comprises hyaluronic acid oligosaccharide with a structure shown in a formula (I):
Wherein n is an integer selected from 0 to 5;
X is selected from H, K, na, ca or Zn, preferably Na.
In the hyaluronic acid oligosaccharide composition,
The mass ratio of the hyaluronic acid oligosaccharide of n=1 is 35-70%, the mass ratio of the hyaluronic acid oligosaccharide of n=0 is 5-40%, the mass ratio of the hyaluronic acid oligosaccharide of n=2 is 10-50%, the mass ratio of the hyaluronic acid oligosaccharide of n=3 is 1-15%, the mass ratio of the hyaluronic acid oligosaccharide of n=4 is 0.1-10%, and the mass ratio of the hyaluronic acid oligosaccharide of n=5 is 0.01-5%.
The cause of skin aging is mainly represented by the following points: 1. alterations in the extracellular matrix of the dermis layer. Collagen is the major component of the extracellular matrix of the dermis, accounting for about 90% of the proteins in the human dermis. Collagen is of a wide variety, and is commonly available in types I, II, III, V and XI. The proteins in the dermis are mainly composed of type i collagen (80%) and small amounts of type iii collagen (10%), which imparts strength and elasticity to the skin. With age, collagen fibers in the skin decrease, causing the skin to lose elasticity and wrinkles. Collagen in dermis is mainly secreted by fibroblasts, and reduction of collagen secreted by fibroblasts is also one of the major causes of aging and wrinkling. 2. A change in the structure of the base layer. After aging, the basal layer structure of human skin is relaxed and cell connection is loose, so that the substance exchange efficiency between dermis and epidermis is reduced. Thus, the epidermis is not nutritional enough, and the epidermal cells cannot proliferate and differentiate normally. Further, the epidermis is thinned, and phenomena such as looseness are generated.
For the above-described main causes of skin aging, the hyaluronic acid oligosaccharide composition may be anti-skin aging by promoting collagen production and/or epidermal cell proliferation and differentiation.
In a specific embodiment, the hyaluronic acid oligosaccharide composition is anti-skin aging by promoting collagen production.
In a specific embodiment, the hyaluronic acid oligosaccharide composition is anti-skin aging by promoting epidermal cell proliferation and differentiation.
In a specific embodiment, the hyaluronic acid oligosaccharide composition may be anti-skin aging by promoting collagen production and epidermal cell proliferation and differentiation.
The hyaluronic acid oligosaccharide or hyaluronic acid oligosaccharide (oligosaccharides of HA, abbreviated as oligo-HA) in the present invention is a hyaluronic acid molecular fragment with a molecular weight below 10 4 Da and a number of monosaccharide residues of 2-25 (generally 4-16). oligo-HA belongs to a small molecule polysaccharide, and its properties are very different from those of common hyaluronic acid. Studies show that Oligo-HA HAs biological activities of resisting oxidation, regulating immunity, resisting inflammation, promoting wound healing, promoting angiogenesis, resisting tumor, etc. Particularly, because of the small molecular size, the skin moisturizing gel can penetrate into the stratum corneum of the skin to exert the effects of deep moisturizing and moistening, and can be widely applied to cosmetics.
The hyaluronic acid oligosaccharide composition of the invention comprises hyaluronic acid oligosaccharides with a structure shown in a formula (I):
As can be seen from the formula (I), the reducing end of the hyaluronic acid oligosaccharide of the invention is an uronic acid structure.
Wherein n is an integer from 0 to 5, for example n may be 0,1, 2, 3,4 or 5, and X is H, K, na, ca or Zn, preferably Na. When n=0, the hyaluronic acid oligosaccharide is disaccharide, when n=1, the hyaluronic acid oligosaccharide is tetrasaccharide, when n=2, the hyaluronic acid oligosaccharide is hexasaccharide, when n=3, the hyaluronic acid oligosaccharide is octasaccharide, when n=4, the hyaluronic acid oligosaccharide is decasaccharide, and when n=5, the hyaluronic acid oligosaccharide is dodecasaccharide. Therefore, in the hyaluronic acid oligosaccharide composition of the invention, the mass ratio of the tetraose is 35-70%; the mass ratio of disaccharide is 5-40%; the mass ratio of the hexasaccharide is 10-50%; the mass ratio of the octasaccharide is 1-15%; the mass ratio of the decasaccharide is 0.1-10%; the mass ratio of the dodecaose is 0.01-5%.
The mass ratio of the hyaluronic acid oligosaccharide tetrasaccharide is 35-70%, for example 35％、36％、37％、38％、39％、40％、41％、42％、43％、44％、45％、46％、47％、48％、49％、50％、51％、52％、53％、54％、55％、56％、57％、58％、59％、60％、31％、62％、63％、64％、65％、66％、67％、68％、69％、70％,, preferably 40-60%.
The mass ratio of hyaluronic acid oligosaccharide disaccharide is 5-40%, for example 5％、6％、7％、8％、9％、10％、11％、12％、13％、14％、15％、16％、17％、18％、19％、20％、21％、22％、23％、24％、25％、26％、27％、28％、29％、30％、31％、32％、33％、34％、35％、36％、37％、38％、39％、40％,% and preferably 5-20%.
The mass ratio of the hyaluronic acid oligosaccharide hexasaccharide is 10-50%, for example 10％、11％、12％、13％、14％、15％、16％、17％、18％、19％、20％、21％、22％、23％、24％、25％、26％、27％、28％、29％、30％、31％、32％、33％、34％、35％、36％、37％、38％、39％、40％、41％、42％、43％、44％、45％、46％、47％、48％、49％、50％,, preferably 20-40%.
The mass ratio of the hyaluronic acid oligosaccharide octasaccharide is 1-15%, for example, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, preferably 3-8%.
The content of hyaluronic acid oligosaccharide and decasaccharide is 0.1-10%, for example 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, preferably 1-5%.
The content of hyaluronic acid oligosaccharide is 0.01-5%, for example 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, preferably 0.01-1.5%.
In a specific embodiment, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide is 5-40%, the mass ratio of hyaluronic acid tetrasaccharide is 35-70%, the mass ratio of hyaluronic acid hexasaccharide is 10-50%, the mass ratio of hyaluronic acid octasaccharide is 1-15%, the mass ratio of hyaluronic acid decasaccharide is 0.1-10%, and the mass ratio of hyaluronic acid dodecasaccharide is 0.01-5%.
In a specific embodiment, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide is 5-20%, the mass ratio of hyaluronic acid tetrasaccharide is 40-60%, the mass ratio of hyaluronic acid hexasaccharide is 20-40%, the mass ratio of hyaluronic acid octasaccharide is 3-8%, the mass ratio of hyaluronic acid decasaccharide is 1-5%, and the mass ratio of hyaluronic acid dodecasaccharide is 0.01-1.5%.
In a specific embodiment, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide is 5-10%, the mass ratio of hyaluronic acid tetrasaccharide is 45-55%, the mass ratio of hyaluronic acid hexasaccharide is 30-40%, the mass ratio of hyaluronic acid octasaccharide is 2-8%, the mass ratio of hyaluronic acid decasaccharide is 1-2%, and the mass ratio of hyaluronic acid dodecasaccharide is 0.01-1%.
In a specific embodiment, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide is 10%, the mass ratio of hyaluronic acid tetrasaccharide is 50%, the mass ratio of hyaluronic acid hexasaccharide is 33%, the mass ratio of hyaluronic acid octasaccharide is 5%, the mass ratio of hyaluronic acid decasaccharide is 1%, and the mass ratio of hyaluronic acid dodecasaccharide is 1%.
In a specific embodiment, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide is 9%, the mass ratio of hyaluronic acid tetrasaccharide is 49%, the mass ratio of hyaluronic acid hexasaccharide is 32%, the mass ratio of hyaluronic acid octasaccharide is 7%, the mass ratio of hyaluronic acid decasaccharide is 2%, and the mass ratio of hyaluronic acid dodecasaccharide is 1%.
Further, the weight average molecular weight of the hyaluronic acid oligosaccharide composition is 1kDa or less, and may be, for example 1kDa、990Da、980Da、970Da、960Da、950Da、940Da、930Da、920Da、910Da、900Da、890Da、880Da、870Da、860Da、850Da、840Da、830Da、820Da、810Da、800Da、790Da、780Da、770Da、760Da、750Da、740Da、730Da、720Da、710Da、700Da.
In the use of the present invention for preventing skin aging, the hyaluronic acid oligosaccharide composition may be directly or indirectly applied to the skin, for example, may be applied by external application, injection, oral administration, or the like.
In the use of the present invention for preventing skin aging, the hyaluronic acid oligosaccharide composition is useful for cosmetics, medical devices, and further suitable for skin. For example, the hyaluronic acid oligosaccharide composition may be formulated into cosmetics for anti-skin aging alone or together with other active ingredients.
Further, when the hyaluronic acid oligosaccharide composition is used in cosmetics, medical devices, the mass concentration of the hyaluronic acid oligosaccharide composition in cells is 0.0001% -0.1%. The hyaluronic acid oligosaccharide composition may be contained in the cosmetic or medical device at a mass concentration of 0.0001% to 5%, for example, 0.0001%, 0.001%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, preferably 0.001% to 1%, in terms of the surface area of the cell-human facial skin and the transdermal state of the hyaluronic acid oligosaccharide composition.
The invention also provides application of the hyaluronic acid oligosaccharide composition in promoting collagen production.
The viscera and tissues contain collagen, and collagen is arranged below the epidermis structures of the viscera, and can protect and strengthen the viscera, so that the hyaluronic acid oligosaccharide composition can be used for preparing health care products for protecting and strengthening the viscera.
Collagen is a main component of muscle tissue, and can provide needed nutrition for muscle and protect gastric mucosa, so that the hyaluronic acid oligosaccharide composition can be used for preparing health care products for protecting gastric mucosa.
Collagen is also a calcium-adhering net rack, and locks bone calcium and prevents calcium loss, so that the hyaluronic acid oligosaccharide composition can be used for preparing calcium-supplementing health-care products.
The collagen can also effectively repair articular cartilage, restore the lubrication of the articular cartilage surface and reduce friction. The hyaluronic acid oligosaccharide composition can be used for preparing joint lubrication injection.
In a specific embodiment, the hyaluronic acid oligosaccharide composition may be present in the health care product or injection at a concentration of 0.0001% -5%, for example, 0.0001%, 0.001%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, preferably 0.001% -1%.
Examples
EXAMPLE 1 preparation of hyaluronic acid oligosaccharide composition
4L of water is added into a 5L reactor, the temperature is controlled to be 30 ℃, 4X 10 7 U of hyaluronidase (the enzyme is leech hyaluronidase expressed by pichia pastoris engineering bacteria, the preparation method is described in CN 103695448A) is added, the system enzyme activity is 1X 10 4 U/mL, 5g of hyaluronic acid (molecular weight is 100 kDa) is added, after the hyaluronic acid is completely dissolved, an enzymolysis reactant is separated by ultrafiltration to obtain a product stock solution, and the product stock solution is concentrated by nanofiltration to obtain a product concentrate. The system was kept at 30℃and stirred for reaction for 12h. Wherein the ultrafiltration adopts an ultrafiltration membrane with a molecular weight cutoff of 1kDa, and the nanofiltration adopts a nanofiltration membrane with a molecular weight cutoff of 200 Da. After the reaction is finished, collecting nanofiltration concentrated solution, adding active carbon for adsorption, filtering and collecting filtrate, and performing spray drying, wherein the air inlet temperature is 120 ℃ and the air outlet temperature is 60 ℃. The hyaluronic acid oligosaccharide composition was obtained with a product yield of 84%.
The oligosaccharide composition of hyaluronic acid is analyzed for oligosaccharide distribution by using a high performance liquid chromatograph, and specific chromatographic conditions are as follows:
chromatographic column: SUPERDEX 200 10/300GL
Column temperature: 40 DEG C
A detector: ultraviolet-visible spectroscopic detector
Mobile phase: 1mol/L ammonium sulfate solution
Sample injection concentration: 0.5%
Sample injection amount: 20 mu L
Flow rate: 2ml/min
Detection wavelength: 200nm.
As a result, as shown in fig. 1, in the hyaluronic acid oligosaccharide composition, the mass ratio of hyaluronic acid disaccharide was 9.35%, the mass ratio of hyaluronic acid tetrasaccharide was 47.84%, the mass ratio of hyaluronic acid hexasaccharide was 32.92%, the mass ratio of hyaluronic acid octasaccharide was 6.04%, the mass ratio of hyaluronic acid decasaccharide was 1.48%, and the mass ratio of hyaluronic acid dodecasaccharide was 0.42%.
The average molecular weight of the hyaluronic acid oligosaccharide composition was measured using a laser light scattering instrument (model: DAWN HELEOS-II) and was 920Da.
Comparative example 1 preparation of hyaluronic acid oligosaccharide composition
The higher molecular weight hyaluronic acid oligosaccharide composition was prepared with reference to the method described in CN112646055A, the specific preparation method being as follows:
1) Pretreatment: dissolving 50g of high molecular weight hyaluronic acid with molecular weight of 1000kDa in 30 times of water, regulating the pH value of the solution to 8.5 by using 0.1mol/L sodium methoxide solution, fully stirring and swelling at room temperature, slowly heating to 90 ℃, hydrolyzing at constant temperature for 4 hours, leaching and filtering, repeating the leaching operation on filter residues, and combining the two filtrates for later use;
2) Neutral salt fractional precipitation: heating the solution obtained in the step 1) to 40 ℃, adding 25% of magnesium sulfate solid by weight of the solution, stirring and completely dissolving, performing ultrafiltration by using a sulfonated polysulfone ultrafiltration membrane of 0.1 mu m, then adding 43% of magnesium sulfate solid by weight of the solution into the filtrate again, stirring and completely dissolving, standing for precipitation, performing filtration, ultrafiltration and drying, and then adding 6 times of purified water into the dried precipitate for redissolution;
3) And (3) filtering and purifying: carrying out ultrafiltration pretreatment on the solution obtained in the step 2) by a sulfonated polysulfone microfiltration membrane with the molecular weight cutoff of 4kDa under the membrane permeation pressure of 0.3 MPa; and carrying out nanofiltration concentration on the permeate through a sulfonated polysulfone nanofiltration membrane with the molecular weight cutoff of 2kDa, and finally obtaining concentrated solution, and carrying out vacuum freeze drying on the concentrated solution to obtain the hyaluronic acid oligosaccharide composition.
The average molecular weight of the hyaluronic acid oligosaccharide composition was measured using a laser light scattering instrument (model: DAWN HELEOS-II) and was 2682Da.
Test examples
Test example 1
(1) Mass spectrometry detection
The hyaluronan oligosaccharide compositions of examples 1 to 1 were characterized by ESI-MS and mass spectrometry was performed under the following conditions: ion source parameter ESI, nebulizer pressure: 30psi; the flow rate of the desolventizing gas is 50L/h; the temperature is 400 ℃; negative ion mode.
As a result, as shown in FIGS. 3 to 7, a mass spectrum peak [ M ] appearing at 1.380min on the mass spectrum total ion flow peak diagram (FIG. 2) was 397.1, identified as hyaluronan disaccharide (FIG. 3); the mass spectrum peak [ M ] appearing at 3.649min on the mass spectrum total ion flow peak diagram is 776.2, identified as hyaluronan tetraose (FIG. 4); the mass spectrum peak [ M ] appearing at 5.612min on the mass spectrum total ion flow peak diagram is 1155.3, identified as hyaluronan hexasaccharide (FIG. 5); the mass spectrum peak [ M ] appearing at 6.724min on the mass spectrum total ion flow peak diagram is 1535.5, identified as octasaccharide hyaluronate (FIG. 6); the mass spectrum peak [ M ] appearing at 7.257min on the mass spectrum total ion flow peak diagram was 1913.5, identified as hyaluronic acid dodecasaccharide (FIG. 7), and the mass spectrum peak [ M ] appearing thereafter was 2292.6, identified as hyaluronic acid dodecasaccharide.
(2) Reduction end identification of hyaluronic acid oligosaccharide compositions
The hyaluronic acid oligosaccharide compositions obtained in example 1 and comparative example 1 were subjected to reduction end identification.
The reducing end of the hyaluronan oligosaccharide composition was determined colorimetrically using the Morgan-Elson reaction. N-acetylglucosamine is shown as the reducing end if it turns red, and uronic acid is shown as the reducing end if it does not turn red.
Reaction buffer: basic boric acid solution (1.73 g h3bo3 and 0.78g KOH in 10ml water, 0.8g ml-1K2CO 3.) of p-dimethylaminobenzaldehyde solution (2 g p-dimethylaminobenzaldehyde solution in 2.5ml concentrated hydrochloric acid and 7.5ml glacial acetic acid, diluted with 4 volumes of glacial acetic acid before use) was added to one tenth of its volume.
Mu.l of 10g/L hyaluronic acid oligosaccharide composition solution was taken, 110. Mu.l of alkaline boric acid solution was added, boiled for 4min, 1.5ml of p-dimethylaminobenzaldehyde was added, and incubated at 37℃for 20min.
Hyaluronic acid (molecular weight 1500 kDa), hyaluronic acid tetrasaccharide (HA 4, purchased from Sigma, reduced end N-acetylglucosamine) solution was used as control.
The results are shown in Table 1, and the hyaluronic acid oligosaccharide compositions prepared in example 1 and comparative example 1 were not reddish by Moran-Elson reaction, demonstrating uronic acid at the reducing end.
TABLE 1
| Morgan-Elson reaction results | |
| Example 1 | Does not turn red |
| Comparative example 1 | Does not turn red |
Test example 2
The hyaluronic acid oligosaccharide compositions of example 1 and comparative example 1 were weighed 10mg each, dispersed in 10mL of DMEM medium, and sterilized and filtered through a 0.22 μm filter membrane to obtain sample 1 and sample 2 having a mass concentration of 0.1%, respectively.
Test example 2-1 collagen content measurement
Collagen determines the physical properties of human tissues, including skin. Collagen in the dermis is mainly secreted by fibroblasts. The present invention evaluates the effect of hyaluronic acid compositions on promotion of collagen production by assessing the effect of hyaluronic acid compositions on the ability of fibroblasts to secrete expressed collagen.
1. Sample preparation
20. Mu.L of sample 1 and sample 2 were added to 1.98mL of 10% FBS-DMEM medium, respectively, to prepare 0.001% final mass concentration solutions to obtain samples 1-1 and 2-1.
Sample 1 was taken and added to 10% FBS-DMEM medium to prepare solutions with final mass concentrations of 0.001%, 0.01% and 0.0001% respectively to obtain samples 1-1, 1-2 and 1-3.
2. Human fibroblast collagen I secretion experiment
Human fibroblasts were plated in 96-well plates at a density of 1 ten thousand per well and placed in an incubator for culturing for 24 hours. The supernatant was discarded, and samples 1, 1-2, 1-3, 2-1 were added to the well plate at 200. Mu.L per well. Placed in an incubator for 48h of incubation. The supernatant was collected, and after ten times dilution of the supernatant with DMEM medium, collagen i in the supernatant was quantified using the Human Col i Elisa Kit. The results are shown in fig. 8 and 9, wherein the control group is a test group to which no sample was added.
3. Results display
As shown in fig. 8, sample 1-1 increased the secretion amount of collagen I by 33%, while sample 2-1 had no significant difference in the secretion amount of procollagen I compared to the control group.
As shown in FIG. 9, samples 1, 1-2, and 1-3 all had a remarkable collagen production promoting effect, indicating that the hyaluronic acid oligosaccharide composition of example 1 had a collagen secretion promoting effect on fibroblasts at a mass concentration of 0.0001% -0.1%. Especially when the mass concentration is 0.001%.
Test examples 2-2 3D skin model
The present invention evaluates the effect of hyaluronic acid compositions on epidermal cell proliferation and differentiation by evaluating the effect of hyaluronic acid compositions on the tissue structure of 3D full-thickness skin models.
The 3D full-layer skin model is an active tissue similar to the human skin structure, which is formed by reconstructing normal human skin cells in vitro by using a tissue engineering technology and adopting a proper culture medium. The role of the sample in anti-aging can be judged by evaluating the tissue structure of the 3D skin model. The basal layer is a substance exchange barrier between dermis and epidermis, and the more stable the basal layer structure is, the more nutrients the epidermis can absorb, the better the epidermal cells can proliferate and differentiate, thus achieving the anti-aging effect.
1. Construction of 3D full-layer skin model
The collagen and the human dermal fibroblast are combined to form a dermis layer of the 3D full-layer skin model, and then the dermis layer is inoculated with human keratinocytes to form a epidermis layer, so that the complete skin model with a dermis-epidermis structure is obtained. Then, sample 1 and sample 2 are added respectively to treat the same.
2. Paraffin tissue section of 3D full-layer skin model
The tissue is put into an embedding box, and is respectively put into 4% paraformaldehyde, 70% ethanol-water solution, 80% ethanol-water solution, 90% ethanol-water solution, 95% ethanol-water solution, absolute ethanol I, absolute ethanol II, methylcyclohexane I and methylcyclohexane II for gradient dehydration, and each cylinder of solution is 1h. After dehydration, the tissue is embedded in paraffin, trimmed and cut into paraffin sections with the thickness of 5 mu m.
3. Hematoxylin-eosin staining of 3D full-thickness skin model
The paraffin sections are respectively put into methylcyclohexane I, methylcyclohexane II, absolute ethyl alcohol, 95% ethanol-water solution, 80% ethanol-water solution, 70% ethanol-water solution and distilled water to be soaked for 10min for dewaxing and rehydration. Placing into hematoxylin dye solution for dyeing for 8min, and then sequentially placing into hydrochloric acid-ethanol solution for differentiation for 2s and ammonia water solution for bluing for 1min. Then dyeing for 1min with eosin solution, and finally dewatering in 70% ethanol-water solution, 95% ethanol-water solution, absolute ethanol and methylcyclohexane solution, and sealing with neutral resin. And photographing under a microscope. The results are shown in FIG. 10. Wherein, the control group is a test group to which no sample was added.
4. Results display
As shown in fig. 10, after the addition of sample 1, the basal layer cells of the 3D full-layer skin model were tightly connected, the epidermal layer was well differentiated, the structure was complete, and the structures of the acantha layer and the granular layer were clear, as compared with the control group and sample 2. It is shown that sample 1 has good anti-aging effect.
Test example 3 transdermal verification of hyaluronic acid oligosaccharide composition
1. Sample fluorescent labeling
2G of the hyaluronic acid oligosaccharide composition of example 1 was dispersed in 40mL of water to prepare a 50mg/mL solution, and 20mL of the solution was added and mixed. To the 60mL solution was added 500. Mu.L of a 50mg/mL 5-hydroxyfluorescein solution, 25. Mu.L of cyclohexylisonitrile, 100. Mu.L of a 25% acetaldehyde solution, and the reaction was stirred at room temperature for 5 hours. 40mL of the fluorescence-labeled solution was removed, and 560mL of the supernatant of the ice-ethanol solution of saturated sodium chloride was added to produce a fluorescence-labeled hyaluronic acid precipitate. The solution was transferred to a centrifuge tube, centrifuged at 4000 Xg for 10 minutes, the supernatant removed, and the fluorescein labeled example 1 removed.
2. Fluorescent markers transdermal
15Mg of the fluorescent-labeled example 1 was dissolved in 1mL of water to prepare sample 4 having a final mass concentration of 1.5%. A manual transdermal apparatus was loaded with 25mm diameter pigskin using 15mL of 1 XPBS as the receiving solution. The receiving solution is heated in a water bath at the temperature of (32.0+/-0.1) DEG C, and balanced for 1 hour under the condition of constant-speed magnetic stirring (300+/-5) r/min. Sample 4 was added in 500. Mu.L to the upper layer of the skin and capped. And (5) taking off the pigskin and airing after 20 hours.
3. Frozen section of pigskin
Taking the dried pigskin, placing the pigskin in OCT and rapidly cooling the pigskin in liquid nitrogen. Cut into sections of 10. Mu.M in a frozen microtome and observed under a fluorescence microscope.
4. Results display
As shown in fig. 11, sample 4 had fluorescent brightness in both the epidermis and dermis layers, which indicated that sample 4 penetrated both the epidermis and dermis layers well. The above results demonstrate that example 1 is permeable and stays in the dermis and epidermis for its function.
Claims (7)
1. Use of a hyaluronic acid oligosaccharide composition for the preparation of a product for combating skin ageing by promoting collagen production, characterized in that the hyaluronic acid oligosaccharide composition comprises a hyaluronic acid oligosaccharide of the structure of formula (I):
Formula (I);
wherein X is H, K, na, ca or Zn;
n is an integer selected from 0 to 5;
in the hyaluronic acid oligosaccharide composition,
The mass ratio of the hyaluronic acid oligosaccharide with n=1 is 35-70%, the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-40%, the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 10-50%, the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 1-15%, the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 0.1-10%, and the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-5%;
The weight average molecular weight of the hyaluronic acid oligosaccharide composition is less than or equal to 1 kDa.
2. The use according to claim 1, characterized in that in the hyaluronic acid oligosaccharide composition the mass ratio of hyaluronic acid oligosaccharides with n = 1 is 40-60%; the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-20%; the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 20-40%; the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 3-8%; the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 1-5%; the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-1.5%.
3. The use according to claim 1, wherein the hyaluronic acid oligosaccharide composition is applied to the skin.
4. The use according to claim 3, wherein the application to the skin is by means of a cosmetic or medical device, and the hyaluronic acid oligosaccharide composition is present in the cosmetic or medical device in a concentration of 0.0001% to 5% by mass.
5. The use according to claim 4, characterized in that the hyaluronic acid oligosaccharide composition is present in the cosmetic or medical device in a concentration of 0.001% -1% by mass.
6. Use of a hyaluronic acid oligosaccharide composition for preparing a cosmetic product for promoting collagen production, characterized in that the hyaluronic acid oligosaccharide composition comprises a hyaluronic acid oligosaccharide of the structure shown in formula (I):
Formula (I);
wherein X is H, K, na, ca or Zn;
n is an integer selected from 0 to 5;
in the hyaluronic acid oligosaccharide composition,
The mass ratio of the hyaluronic acid oligosaccharide with n=1 is 35-70%, the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-40%, the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 10-50%, the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 1-15%, the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 0.1-10%, and the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-5%;
The weight average molecular weight of the hyaluronic acid oligosaccharide composition is less than or equal to 1 kDa.
7. The use according to claim 6, characterized in that in the hyaluronic acid oligosaccharide composition the mass ratio of hyaluronic acid oligosaccharides with n = 1 is 40-60%; the mass ratio of the hyaluronic acid oligosaccharide with n=0 is 5-20%; the mass ratio of the hyaluronic acid oligosaccharide with n=2 is 20-40%; the mass ratio of the hyaluronic acid oligosaccharide with n=3 is 3-8%; the mass ratio of the hyaluronic acid oligosaccharide with n=4 is 1-5%; the mass ratio of the hyaluronic acid oligosaccharide with n=5 is 0.01-1.5%.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111123265.7A CN113876623B (en) | 2021-09-24 | 2021-09-24 | Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production |
| PCT/CN2022/119005 WO2023040952A1 (en) | 2021-09-17 | 2022-09-15 | Hyaluronic acid oligosaccharide composition, and preparation method therefor and use thereof |
| TW111135223A TW202320812A (en) | 2021-09-17 | 2022-09-16 | Hyaluronic acid oligosaccharide composition, and preparation method therefor and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111123265.7A CN113876623B (en) | 2021-09-24 | 2021-09-24 | Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113876623A CN113876623A (en) | 2022-01-04 |
| CN113876623B true CN113876623B (en) | 2024-06-14 |
Family
ID=79006562
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111123265.7A Active CN113876623B (en) | 2021-09-17 | 2021-09-24 | Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113876623B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023040952A1 (en) * | 2021-09-17 | 2023-03-23 | 华熙生物科技股份有限公司 | Hyaluronic acid oligosaccharide composition, and preparation method therefor and use thereof |
| CN114609296B (en) * | 2022-03-29 | 2024-01-05 | 水羊化妆品制造有限公司 | Detection method for enzymatic hydrolysis hyaluronic acid oligosaccharide mixture |
| CN116023523A (en) * | 2022-12-29 | 2023-04-28 | 水羊化妆品制造有限公司 | Ultra-small molecular weight sodium hyaluronate and preparation method thereof |
| CN116370346A (en) * | 2023-03-07 | 2023-07-04 | 华熙生物科技股份有限公司 | Composition for maintaining skin steady state and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111040048A (en) * | 2019-12-21 | 2020-04-21 | 南京汉欣医药科技有限公司 | Ultra-low molecular weight hyaluronic acid and preparation method thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1300412B1 (en) * | 2000-07-07 | 2009-12-30 | Seikagaku Corporation | Hyaluronic acid oligosaccharide fractions and drugs containing the same |
| CN101507733B (en) * | 2009-04-02 | 2011-03-30 | 北京中生奥普寡肽技术研究所 | Nano micromolecule hyaluronic acid and preparation method thereof |
| JP2011057607A (en) * | 2009-09-09 | 2011-03-24 | Toshitsu Kagaku Kenkyusho:Kk | Composition containing hyaluronic acid and hyaluronic acid oligo-saccharide |
| WO2013123791A1 (en) * | 2012-02-21 | 2013-08-29 | 华熙福瑞达生物医药有限公司 | Bacillus, hyaluronic acid enzyme, and uses thereof |
| CN103695448B (en) * | 2013-07-29 | 2016-08-17 | 江南大学 | A kind of hyaluronic acid enzyme coding gene and fermenting and producing thereof and purification process |
| CN105037529A (en) * | 2015-07-10 | 2015-11-11 | 山东大学 | Novel biomaterial of collagen modified by hyaluronic acid oligosaccharide, and preparation method therefor |
| KR20170107331A (en) * | 2016-03-15 | 2017-09-25 | 티앤에이치글로벌바이오텍 주식회사 | Cosmetic compositions for regulating collagen and anti-wrinkle |
| CN108619000A (en) * | 2018-05-13 | 2018-10-09 | 广州圣幽兰生物科技有限公司 | The hyaluronic acid oligosaccharide and collagen oligopeptide stoste of nano-spray moisturizing instrument |
| CN109097421B (en) * | 2018-08-14 | 2021-03-26 | 江南大学 | Method for preparing hyaluronic acid odd oligosaccharide by double-enzyme hydrolysis |
| CN109988739B (en) * | 2018-11-27 | 2021-10-19 | 常熟理工学院 | Method for efficiently preparing micromolecular chondroitin sulfate and micromolecular hyaluronic acid by one-step method |
| CN112156033B (en) * | 2020-10-16 | 2021-05-28 | 南京百姿雅生物科技有限公司 | Essence containing ultra-small molecule sodium hyaluronate and preparation method thereof |
| CN112646055A (en) * | 2020-11-13 | 2021-04-13 | 沧州硕金生物科技有限公司 | Preparation method of low-molecular-weight hyaluronic acid |
-
2021
- 2021-09-24 CN CN202111123265.7A patent/CN113876623B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111040048A (en) * | 2019-12-21 | 2020-04-21 | 南京汉欣医药科技有限公司 | Ultra-low molecular weight hyaluronic acid and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| "Effect of hyaluronan tetrasaccharides on epidermal differentiation in normal human epidermal keratinocytes";M. Kage 等;《International Journal of Cosmetic Science》;20141231;第36卷;第109-115页 * |
| "Expression of Hyaluronan Synthase and Collagen Type I mRNA by Hyaluronan Tetrasaccharides in Normal Human Dermal Fibroblasts";Madoka KAGE 等;《日本香粧品学会誌》;20131231;第37卷(第1期);第1-5页 * |
| 吕梦娴."透明质酸四糖和六糖的制备及生物活性研究".《 中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》.2017,第7页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113876623A (en) | 2022-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113876623B (en) | Application of hyaluronic acid oligosaccharide composition in resisting skin aging and promoting collagen production | |
| Zhu et al. | Structural characterization and in vitro antioxidant activities of chondroitin sulfate purified from Andrias davidianus cartilage | |
| CN106397545B (en) | A kind of hydrogel material and its preparation method and application | |
| CN102836465A (en) | Silk-fibroi and hyaluronic-acid (HA) composite gel for injection and preparation and application thereof | |
| CN115517997A (en) | Cosmetic composition and preparation method and application thereof | |
| CN101925613A (en) | Mixed butyric-formic esters of acid polysaccharides, and their preparation and use as skin cosmetics | |
| CN116725933B (en) | Whitening, moisturizing and repairing mask and preparation method thereof | |
| JP2019023218A (en) | Method for acquiring mixture of neutral oligosaccharides extracted from flaxseed | |
| CN113801904A (en) | Hyaluronic acid oligosaccharide composition and preparation method and application thereof | |
| CN114288308A (en) | Hyaluronic acid oligosaccharide composition mainly containing tetrasaccharide and preparation method and application thereof | |
| CN114146223A (en) | Recombinant collagen compound injection and preparation method thereof | |
| KR20160126795A (en) | Cosmetic materials and process for producing the same | |
| CN112870102A (en) | Cosmetic composition containing glycerol glucoside and preparation method and application thereof | |
| CN114317661A (en) | Method for preparing multiple active collagen | |
| CN108977488A (en) | Skin is intensively repaired with elastin laminin and preparation method thereof | |
| CN115873143B (en) | Microsphere with core-shell double-layer structure and preparation method and application thereof | |
| CN111374906A (en) | Composition with anti-aging effect and preparation method thereof | |
| CN116284495B (en) | All-trans retinoic acid low-molecular hyaluronate derivative and preparation method and application thereof | |
| US20190365637A1 (en) | Cytomimetic formulations and methods of manufacturing the same | |
| WO2023040952A1 (en) | Hyaluronic acid oligosaccharide composition, and preparation method therefor and use thereof | |
| CN116687800A (en) | Sodium hyaluronate composite solution for injection and preparation method thereof | |
| CN109453104B (en) | Spot-fading skin-refreshing essence and preparation process thereof | |
| Dhasmana et al. | Fabrication and evaluation of herbal beads to slow cell ageing | |
| CN114437242B (en) | Usnic polysaccharide, preparation method and application thereof | |
| CN117297998A (en) | Anti-aging composition, anti-aging skin care product and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |