CN115192771A - 一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 - Google Patents
一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 Download PDFInfo
- Publication number
- CN115192771A CN115192771A CN202110399905.0A CN202110399905A CN115192771A CN 115192771 A CN115192771 A CN 115192771A CN 202110399905 A CN202110399905 A CN 202110399905A CN 115192771 A CN115192771 A CN 115192771A
- Authority
- CN
- China
- Prior art keywords
- gel
- hyaluronic acid
- copolymer
- polydeoxyribonucleotide
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920001577 copolymer Polymers 0.000 title claims abstract description 57
- 229940088594 vitamin Drugs 0.000 claims abstract description 32
- 239000011782 vitamin Substances 0.000 claims abstract description 32
- 229930003231 vitamin Natural products 0.000 claims abstract description 31
- 235000013343 vitamin Nutrition 0.000 claims abstract description 31
- 150000001413 amino acids Chemical class 0.000 claims abstract description 28
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 15
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 15
- 239000011707 mineral Substances 0.000 claims abstract description 15
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 14
- 150000003722 vitamin derivatives Chemical class 0.000 claims abstract description 14
- 239000000499 gel Substances 0.000 claims description 79
- 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 claims description 55
- 229920002674 hyaluronan Polymers 0.000 claims description 53
- 229960003160 hyaluronic acid Drugs 0.000 claims description 53
- 229940024606 amino acid Drugs 0.000 claims description 27
- 235000001014 amino acid Nutrition 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 238000004132 cross linking Methods 0.000 claims description 17
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 14
- 235000006708 antioxidants Nutrition 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000011259 mixed solution Substances 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003589 local anesthetic agent Substances 0.000 claims description 12
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 10
- 239000000017 hydrogel Substances 0.000 claims description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 7
- 229930003268 Vitamin C Natural products 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 235000019154 vitamin C Nutrition 0.000 claims description 7
- 239000011718 vitamin C Substances 0.000 claims description 7
- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 claims description 5
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 5
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
- 229960000304 folic acid Drugs 0.000 claims description 5
- 235000019152 folic acid Nutrition 0.000 claims description 5
- 239000011724 folic acid Substances 0.000 claims description 5
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims description 4
- 108010087806 Carnosine Proteins 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical class [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004473 Threonine Substances 0.000 claims description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 4
- 229960003589 arginine hydrochloride Drugs 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 claims description 4
- 229940044199 carnosine Drugs 0.000 claims description 4
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 claims description 4
- 239000010949 copper Chemical class 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 4
- 229960000310 isoleucine Drugs 0.000 claims description 4
- 229960005337 lysine hydrochloride Drugs 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000004474 valine Substances 0.000 claims description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 3
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 3
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical class [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 229960003067 cystine Drugs 0.000 claims description 3
- 238000007872 degassing Methods 0.000 claims description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 229960002591 hydroxyproline Drugs 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052711 selenium Inorganic materials 0.000 claims description 3
- 239000011669 selenium Chemical class 0.000 claims description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 239000011701 zinc Chemical class 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 abstract description 25
- 238000006731 degradation reaction Methods 0.000 abstract description 17
- 210000002950 fibroblast Anatomy 0.000 abstract description 17
- 230000015556 catabolic process Effects 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 15
- 239000002131 composite material Substances 0.000 abstract description 14
- 235000010755 mineral Nutrition 0.000 abstract description 12
- 235000015097 nutrients Nutrition 0.000 abstract description 11
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 9
- 239000000758 substrate Substances 0.000 abstract description 9
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 abstract description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 abstract description 8
- 239000012634 fragment Substances 0.000 abstract description 6
- 230000004913 activation Effects 0.000 abstract description 5
- 210000001626 skin fibroblast Anatomy 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000000945 filler Substances 0.000 abstract description 3
- 238000012423 maintenance Methods 0.000 abstract description 3
- 210000004927 skin cell Anatomy 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 18
- 102000008186 Collagen Human genes 0.000 description 13
- 108010035532 Collagen Proteins 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 229920001436 collagen Polymers 0.000 description 13
- 230000000052 comparative effect Effects 0.000 description 13
- 229920000642 polymer Polymers 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000002500 effect on skin Effects 0.000 description 8
- 239000000835 fiber Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 210000004177 elastic tissue Anatomy 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 229920002385 Sodium hyaluronate Polymers 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229960005015 local anesthetics Drugs 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012475 sodium chloride buffer Substances 0.000 description 5
- 229940010747 sodium hyaluronate Drugs 0.000 description 5
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IIEOSQHRZNUOOC-UHFFFAOYSA-J tetrasodium dihydrogen phosphate hydrogen phosphate chloride Chemical compound [Cl-].[Na+].P(=O)(O)(O)[O-].[Na+].P(=O)(O)([O-])[O-].[Na+].[Na+] IIEOSQHRZNUOOC-UHFFFAOYSA-J 0.000 description 5
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 230000037067 skin hydration Effects 0.000 description 4
- 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 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229960005069 calcium Drugs 0.000 description 3
- 229910000365 copper sulfate Inorganic materials 0.000 description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 238000010894 electron beam technology Methods 0.000 description 3
- 229940014041 hyaluronate Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 3
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000009759 skin aging Effects 0.000 description 3
- 235000019156 vitamin B Nutrition 0.000 description 3
- 239000011720 vitamin B Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 102000016942 Elastin Human genes 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 229920002549 elastin Polymers 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000001678 irradiating effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229960001763 zinc sulfate Drugs 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- SHKUUQIDMUMQQK-UHFFFAOYSA-N 2-[4-(oxiran-2-ylmethoxy)butoxymethyl]oxirane Chemical compound C1OC1COCCCCOCC1CO1 SHKUUQIDMUMQQK-UHFFFAOYSA-N 0.000 description 1
- 102000007471 Adenosine A2A receptor Human genes 0.000 description 1
- 108010085277 Adenosine A2A receptor Proteins 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010075016 Ceruloplasmin Proteins 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 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
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010081750 Reticulin Proteins 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 241000209501 Spirodela Species 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000005262 alpha decay Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000005255 beta decay Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- VJVOFLWZDWLHNR-MRCUWXFGSA-N icosan-9-yl (z)-docos-13-enoate Chemical compound CCCCCCCCCCCC(CCCCCCCC)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC VJVOFLWZDWLHNR-MRCUWXFGSA-N 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 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
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000004800 psychological effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 230000036560 skin regeneration Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- -1 surgical protection Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940046001 vitamin b complex Drugs 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 239000011670 zinc gluconate Substances 0.000 description 1
- 235000011478 zinc gluconate Nutrition 0.000 description 1
- 229960000306 zinc gluconate Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/21—Acids
- A61L2300/214—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/258—Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种含透明质酸‑多聚脱氧核糖核苷酸共聚物的凝胶,所述凝胶包含透明质酸‑多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质和抗氧剂。与现有技术相比,本发明的复合凝胶具有以下优点:共聚物的加入可以形成具有致密网络结构的凝胶空间,减缓复合凝胶注入皮肤后其中营养成分的释放速率,延长营养成分的释放时间,为皮肤成纤维细胞持续提供底物,从而起到延长复合凝胶作用时间的效果;共聚物具有更好的抗降解效果。注入皮肤后一方面延长凝胶作为填充剂的维持时间,另一方面可以从中缓慢释放出PDRN片段,为皮肤细胞的活化提供底物;凝胶为成纤维细胞实现最佳功能提供良好的胞外基质微环境。
Description
技术领域
本发明属于高分子材料制备技术领域,具体涉及一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途。
背景技术
随着经济的发展和社会的进步,人们愈发重视外在形象,皮肤由于其浅表外露性而具有较强的心理效应。修复皮肤老化、恢复皮肤健康状态逐渐成为人们关注的热点之一。其中,注射美容是一种常用的微创整形手段。
人皮肤成纤维细胞是组成皮肤真皮的主要结构成分,其可合成和分泌胶原纤维、弹性纤维、网状纤维、透明质酸等细胞外基质。胶原纤维的主要组成成分是胶原蛋白,皮肤中主要为I型和III型,占真皮细胞间质的90%;弹性纤维的主要组成成分是弹性蛋白,约占真皮细胞间质的5%。胶原纤维是真皮细胞外基质的主要结构蛋白,宛如钢筋搭建成的皮肤支架,起着支撑、抗牵拉的作用,使皮肤充盈;弹性纤维是另一种重要的真皮细胞外基质结构蛋白,围绕着胶原纤维排列,能拉长到原长度的几倍,在张力松弛后很快恢复到原来的大小和形状,使皮肤具有弹性;透明质酸是真皮细胞外基质的重要组成成分,具有优良的锁水功能,是天然的保湿因子,可增强皮肤水合,为真皮胶原纤维和弹性纤维的合成提供优越的外部环境,维持皮肤水润。
皮肤老化的主要因素是成纤维细胞功能障碍和成纤维细胞生物合成活性的降低。随着衰老成纤维细胞产量减少,由其合成的透明质酸、胶原蛋白、弹性蛋白和其他细胞外基质成分也随之减少;与之相反,负责降解胶原蛋白的酶生成量增加。尽管衰老成纤维细胞功能障碍不断恶化的确切机制尚不清楚,但是有研究表明可能的重要原因之一是活性氧生成和消除的失衡,导致氧化应激增加。另外,越来越多的证据表明,除了生化信号外,成纤维细胞能否实现最佳功能主要取决于它们与周围微环境的相互机械作用。成纤维细胞与周围细胞外基质之间的机械张力可能对于成纤维细胞的生理功能以及胶原蛋白和胶原水解酶合成的正常平衡至关重要。
注射美容将皮肤修复所需的营养成分直接注射至真皮层甚至皮下组织,为皮肤提供供营养成分,促进皮肤再生。
目前市场上已有几种添加复合营养成分的皮肤美容溶液或凝胶,例如专利 CN104189952B公开了一种由高分子多糖、氨基酸、水溶性维生素、肌肽组成的纠正皮肤褶皱注射液及其制备方法。但是已有产品往往因添加营养成分多且复杂从而影响安全性,或因添加营养成分少而影响效果。
发明内容
针对现有技术存在的上述问题,本发明提供一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途。凝胶中包含透明质酸-多聚脱氧核糖核苷酸共聚物,原料均为人体内源性物质,交联过程未添加化学交联剂、光引发剂等杂质。另外凝胶添加可以促进人体皮肤成纤维细胞活化并为成纤维细胞提供底物,各成分均为具有多年临床使用经验的物质,保证产品安全性。
具体来说,本发明涉及如下方面:
1、一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,其特征在于,所述凝胶包含透明质酸-多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质和抗氧剂。
2、根据项1所述的凝胶,其特征在于,在所述凝胶中,所述透明质酸-多聚脱氧核糖核苷酸共聚物的质量百分比为0.5%~5%,优选为1%~3%,所述水溶性氨基酸的质量百分比为0.002%~5%,优选为0.003%~1%,所述水溶性维生素的质量百分比为0.0005%~0.5%,优选为0.0005%~0.05%,所述矿物质的质量百分比为0.0001%~0.05%,优选为0.0005%~0.01%,所述抗氧剂的质量百分比为 0.1%~3%,优选为0.2%~2%。
3、根据项1所述的凝胶,其特征在于,所述凝胶还包含局麻药,在所述凝胶中,所述局麻药的质量百分比为0.2%~0.4%。
4、根据项1所述的凝胶,其特征在于,所述透明质酸-多聚脱氧核糖核苷酸共聚物是由分子量为50万Da~300万Da,优选为150万Da~300万Da的透明质酸或其盐,与分子量为5万Da~100万Da的多聚脱氧核糖核苷酸交联得到。
5、根据项4所述的凝胶,其特征在于,所述透明质酸-多聚脱氧核糖核苷酸共聚物的制备方法包括以下步骤:
将透明质酸或其盐和多聚脱氧核糖核苷酸溶于水,脱气后形成混合溶液;
将所述混合溶液在高能射线下进行辐照交联,得到透明质酸-多聚脱氧核糖核苷酸共聚物水凝胶;
将所述水凝胶粉碎、干燥后,得到透明质酸-多聚脱氧核糖核苷酸共聚物。
6、根据项5所述的凝胶,其特征在于,在所述混合溶液中,所述透明质酸或其盐和多聚脱氧核糖核苷酸的质量比为1:1~10:1,优选为1:1~5:1。
7、根据项1所述的凝胶,其特征在于,所述水溶性氨基酸选自甘氨酸、脯氨酸、羟脯氨酸、盐酸赖氨酸、异亮氨酸、亮氨酸、丝氨酸、丙氨酸、天冬氨酸、酪氨酸、谷氨酸、苯丙氨酸、盐酸精氨酸、缬氨酸、苏氨酸、盐酸组氨酸、色氨酸、甲硫氨酸、胱氨酸和半胱氨酸中的一种或两种以上。
8、根据项1所述的凝胶,其特征在于,所述水溶性维生素选自维生素B1、维生素B2、烟酰胺、维生素B6、维生素B12、叶酸和维生素C中的一种或两种以上。
9、根据项1所述的凝胶,其特征在于,所述水溶性矿物质选自钙、锌、铜、硒的可溶性无机盐或有机盐中的一种或两种以上。
10、根据项1所述的凝胶,其特征在于,所述抗氧剂选自甘露醇、甘油、肌肽中的一种或两种以上。
11、根据项3所述的凝胶,其特征在于,所述局麻药选自盐酸利多卡因。
12、根据项1-11任一项所述的凝胶在注射美容中的用途。
与现有技术相比,本发明具有以下优点:
1、HA-PDRN共聚物的加入可以形成具有致密网络结构的凝胶空间,减缓复合凝胶注入皮肤后其中营养成分的释放速率,延长营养成分的释放时间,为皮肤成纤维细胞持续提供底物,从而起到延长复合凝胶作用时间的效果。
2、HA-PDRN共聚物较HA+PDRN或交联HA+PDRN简单的物理混合方式,具有更好的抗降解效果。注入皮肤后一方面延长凝胶作为填充剂的维持时间,另一方面可以从中缓慢释放出PDRN片段,为皮肤细胞的活化提供底物。
3、复合凝胶的各营养成分是基于人体皮肤老化的机理进行添加,一方面为成纤维细胞实现最佳功能提供良好的胞外基质微环境;一方面为成纤维细胞提供足够的底物来保证其完成生物合成;同时抵抗氧化应激对成纤维细胞的影响。
具体实施方式
下面结合实施例进一步说明本发明,应当理解,实施例仅用于进一步说明和阐释本发明,并非用于限制本发明。
除非另外定义,本说明书中有关技术的和科学的术语与本领域内的技术人员所通常理解的意思相同。虽然在实验或实际应用中可以应用与此间所述相似或相同的方法和材料,本文还是在下文中对材料和方法做了描述。在相冲突的情况下,以本说明书包括其中定义为准,另外,材料、方法和例子仅供说明,而不具限制性。以下结合具体实施例对本发明作进一步的说明,但不用来限制本发明的范围。
本发明提供一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,所述凝胶包含透明质酸-多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质和抗氧剂。
其中,透明质酸(HA)是由(1→3)-2-乙酰氨基-2-脱氧-β-D-葡萄糖 -(1→4)-O-β-D-葡糖醛酸双糖重复单位所组成的直链多聚糖,其广泛存在于皮肤、眼玻璃体、软骨和关节滑液等许多结缔组织中,起到保湿、营养和修复等生理作用。HA具有良好的理化性能和生物相容性,常应用于美容整形、创面敷料、眼科手术、关节腔注射、手术防护、药物载体、化妆品原料等领域。注射至真皮后,在真皮细胞外基质中诱导机械张力,增强皮肤水合,维持皮肤水润,为真皮胶原纤维和弹性纤维的合成提供优越的外部环境。
多聚脱氧核糖核苷酸(Polydeoxyribonucleotide,PDRN)是分子量介于 50KDa和1,500KDa之间的脱氧核糖核苷酸的混合物,它来源于鳟鱼或鲑鱼精子DNA,其DNA碎片与人体构成最相似。PDRN是一种专利注册药物,具有多种活性:组织修复、抗缺血和抗炎。有研究发现PDRN在伤口修复中,可以作为成纤维细胞生长刺激物;再者,DNA分解形成的核苷酸与腺苷A2A受体结合,双向调节相关炎性及抗炎因子,可发挥持续抗炎作用,同时减少愈合所需的时间,促进人体细胞再生。用于注射美容,可以激活皮肤自愈能力,刺激皮肤内部不断生成生长因子,促进成纤维细胞活性。
将透明质酸和多聚脱氧核糖核苷酸交联形成共聚物能够提高透明质酸和多聚脱氧核糖核苷酸的稳定性,使得具有更好的抗降解效果。当透明质酸-多聚脱氧核糖核苷酸共聚物注入皮肤后一方面延长凝胶作为填充剂的维持时间,另一方面可以从中缓慢释放出PDRN片段,为皮肤细胞的活化提供底物。同时透明质酸-多聚脱氧核糖核苷酸共聚物的加入可以形成具有致密网络结构的凝胶空间,减缓复合凝胶注入皮肤后其中营养成分的释放速率,延长营养成分的释放时间,为皮肤成纤维细胞持续提供底物,从而起到延长复合凝胶作用时间的效果。
透明质酸-多聚脱氧核糖核苷酸共聚物可以由不同的分子量的透明质酸或其盐,以及不同分子量的多聚脱氧核糖核苷酸交联得到。本文所述的透明质酸或其盐包括透明质酸及其各种形式的盐,优选为透明质酸可溶性盐,包括但不限于透明质酸钠、透明质酸钙、透明质酸镁、透明质酸钾、透明质酸锌等。
在一个具体的实施方式中,透明质酸-多聚脱氧核糖核苷酸共聚物由分子量为50万Da~300万Da的透明质酸或其盐,与分子量为5万Da~100万Da的多聚脱氧核糖核苷酸交联得到。例如,所述透明质酸或其盐的分子量可以为50 万Da、60万Da、70万Da、80万Da、90万Da、100万Da、110万Da、120 万Da、130万Da、140万Da、150万Da、160万Da、170万Da、180万Da、190万Da、200万Da、210万Da、220万Da、230万Da、240万Da、250万 Da、260万Da、270万Da、280万Da、290万Da、300万Da。多聚脱氧核糖核苷酸的分子量可以为5万Da、10万Da、20万Da、30万Da、40万Da、50 万Da、60万Da、70万Da、80万Da、90万Da、100万Da。
透明质酸-多聚脱氧核糖核苷酸共聚物的交联方法不作限定,在一个具体的实施方式中,所述透明质酸-多聚脱氧核糖核苷酸共聚物的制备方法包括以下步骤:
将透明质酸或其盐和多聚脱氧核糖核苷酸溶于水,脱气后形成混合溶液;
将所述混合溶液在高能射线下进行辐照交联,得到透明质酸-多聚脱氧核糖核苷酸共聚物水凝胶;
将所述水凝胶粉碎、干燥后,得到透明质酸-多聚脱氧核糖核苷酸共聚物。
高能射线是指日常放射性工作中常遇到的几种电离射线,包括γ射线、X 射线、电子束(Electron beam,EB)等。高能射线辐照可有效诱导聚合物产生自由基,形成共价交联的网络结构。高能射线的辐射交联法具有独特的优势:无需添加引发剂,产物纯净、安全,更适合生物医用领域的材料制备;单体选择范围大,或可直接从聚合物出发合成;可在常温或者低温下进行,运行费用较低;可一步完成水凝胶的合成和杀菌,降低了成本等。根据制备过程的不同,辐射交联可分为两种方法:先辐照固态聚合物使其交联,再加入水使其溶胀形成水凝胶;直接辐照聚合物水溶液,使其交联形成水凝胶。由于第一种方法交联效率低,所以常用的为水溶液状态进行辐射交联。在水溶液状态,水辐解生成的自由基(·OH、·H等)通过夺取高分子链上的氢产生大分子自由基,从而引发交联反应。
在高能射线辐照下,高分子聚合物活化会发生多种化学变化。例如分子链之间形成化学键,即辐照交联,分子主链断裂,即辐照降解,不同分子之间共聚,即接枝或嵌段共聚等。因此,在高能射线辐照下很难推测透明质酸分子和 PDRN分子之间的具体聚合方式,在本发明中我们旨在考察辐照反应的具体条件,以得到高收率、低PDRN残留率的HA-PDRN共聚物制备方法。
根据现有文献,我们推测,透明质酸和多聚脱氧核糖核苷酸反应生成透明质酸-多聚脱氧核糖核苷酸共聚物过程,具体为,在水溶液中,水经电子束辐解生成自由基·H和·OH,生成的自由基进攻透明质酸分子链中的羧基和PDRN 分子链中的酰胺,生成透明质酸和PDRN大分子自由基,大分子自由基之间生成共价键聚合。当然在此过程中同时存在HA链间交联、HA主链降解、HA链内交联等,因此反应条件的筛选至关重要。理想的反应条件是达到共聚与降解的平衡状态。在一个具体的实施方式中,生成的共聚物的结构如下式所示。
在一个具体的实施方式中,所述高能射线为γ射线。γ射线,又称γ粒子流,是原子核能级跃迁退激时释放出的射线,是波长短于0.01埃的电磁波。γ射线首先由法国科学家P.V.维拉德发现,是继α、β射线后发现的第三种原子核射线。放射性原子核在发生α衰变、β衰变后产生的新核往往处于高能量级,要向低能级跃迁,辐射出γ光子。原子核衰变和核反应均可产生γ射线。其为波长短于0.2埃的电磁波。γ射线的波长比X射线要短,所以γ射线具有比X 射线还要强的穿透能力。
在一个具体的实施方式中,γ射线辐射的剂量为10~30kGy,例如可以为10 kGy、15kGy、20kGy、25kGy、30kGy。
在一个具体的实施方式中,在所述混合溶液中,所述透明质酸或其盐和多聚脱氧核糖核苷酸的质量比为1:1~10:1,例如可以为1:1、2:1、3:1、4:1、5:1、 6:1、7:1、8:1、9:1、10:1,优选为1:1~5:1。
在一个具体的实施方式中,在所述混合溶液中所述透明质酸或其盐的质量占比为0.05%~5%,即所述透明质酸或其盐的质量为所述混合溶液质量的0.05%~5%。例如可以为0.05%、0.1%、0.5%、1%、1.5%、2%、2.5%、3%、3.5%、 4%、4.5%、5%。
在一个具体的实施方式中,在所述混合溶液中所述多聚脱氧核糖核苷酸的质量占比为0.05%~2%,即所述多聚脱氧核糖核苷酸的质量为所述混合溶液质量的0.05%~2%。例如可以为0.05%、0.1%、0.2%、0.3%、0.4%、0.5%、0.6%、0.7%、 0.8%、0.9%、1%、1.1%、1.2%、1.3%、1.4%、1.5%、1.6%、1.7%、1.8%、1.9%、 2%。
上述步骤中的粉碎、干燥可采用现有已知的粉碎或干燥方法。其中,干燥方法优选为冷冻干燥。
本发明凝胶中的水溶性氨基酸,结合成纤维细胞恢复活性最需的维生素、矿物质,可以为成纤维细胞合成胶原纤维和弹性纤维提供底物,复原皮肤原有构造,让皮肤恢复弹性和紧致状态。在一个具体的实施方式中,所述水溶性氨基酸选自甘氨酸、脯氨酸、羟脯氨酸、盐酸赖氨酸、异亮氨酸、亮氨酸、丝氨酸、丙氨酸、天冬氨酸、酪氨酸、谷氨酸、苯丙氨酸、盐酸精氨酸、缬氨酸、苏氨酸、盐酸组氨酸、色氨酸、甲硫氨酸、胱氨酸和半胱氨酸中的一种或两种以上。
水溶性维生素(Water-soluble vitamins)是可溶于水而不溶于非极性有机溶剂的一类维生素,包括维生素B族和维生素C。这类维生素除碳、氢、氧元素外,有的还含有氮硫等元素。与脂溶性维生素不同,水溶性维生素在人体内储存较少,从肠道吸收后进入人体的多余的水溶性维生素大多从尿中排出。在一个具体的实施方式中,所述水溶性维生素选自维生素B1、维生素B2、烟酰胺、维生素B6、维生素B12、叶酸和维生素C中的一种或两种以上。
在一个具体的实施方式中,水溶性矿物质选自钙、锌、铜、硒的可溶性无机盐或有机盐中的至少一种。例如可以为氯化铜、硫酸铜、蓝铜胜肽、葡糖酸锌、硫酸锌、葡糖酸钙、氯化钙、硫酸钙中的一种或两种以上。
抗氧剂是一类化学物质,当其在聚合物体系中仅少量存在时,就可延缓或抑制聚合物氧化过程的进行,从而阻止聚合物的老化并延长其使用寿命,又被称为“防老剂”。在一个具体的实施方式中,所述抗氧剂选自甘露醇、甘油、肌肽中的一种或两种以上。
在一个具体的实施方式中,上述凝胶中各组分的质量百分比如下:所述透明质酸-多聚脱氧核糖核苷酸共聚物的质量百分比为0.5%~5%,例如可以为0.5%、 1%、2%、3%、4%、5%,优选为1%~3%;所述水溶性氨基酸的质量百分比为 0.002%~5%,例如可以为0.002%、0.003%、0.1%、0.5%、1%、2%、3%、4%、 5%,优选为0.003%~1%;所述水溶性维生素的质量百分比为0.0005%~0.5%,例如可以为0.0005%、0.001%、0.01%、0.05%、0.1%、0.2%、0.3%、0.4%、0.5%,优选为0.0005%~0.05%;所述矿物质的质量百分比为0.0001%~0.05%,例如可以为0.0001%、0.0005%、0.001%、0.01%、0.02%、0.03%、0.04%、0.05%,优选为0.0005%~0.01%;所述抗氧剂的质量百分比为0.1%~3%,例如可以为0.1%、 0.2%、0.5%、1%、2%、3%,优选为0.2%~2%。
进一步地,本发明的凝胶还可以包含局麻药。局麻药即局部麻醉药(localanaesthetics),是一类能在用药局部可逆性的阻断感觉神经冲动发生与传递的药品,简称“局麻药”。在保持意识清醒的情况下,可逆的引起局部组织痛觉消失。一般的,局麻药的作用局限于给药部位并随药物从给药部位扩散而迅速消失。在一个具体实施方式中,在所述凝胶中,所述局麻药的质量百分比为0.2%~0.4%。在一个具体的实施方式中,所述局麻药选自盐酸利多卡因。
本发明还提供一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,其由透明质酸-多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质、抗氧剂和生理缓冲液构成。其中各组分的选择及含量如上所述,生理缓冲液为磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0)。
本发明还提供一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,其由透明质酸-多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质、抗氧剂、局麻药和生理缓冲液构成。其中各组分的选择及含量如上所述,生理缓冲液为磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0)。
本发明还进一步提供上述凝胶物在注射美容中的用途。
本发明的含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,由于HA-PDRN 共聚物的加入可以形成具有致密网络结构的凝胶空间,减缓复合凝胶注入皮肤后各氨基酸和维生素的释放率,72h时仍有部分未释放完全;提高了凝胶中HA 和PDRN的降解时间,使得HA和PDRN降解时间均不小于60min,相对于 HA+PDRN或交联HA+PDRN简单的物理混合方式,具有更好的抗降解效果。
实施例
下面结合实施例进一步说明本发明,应当理解,实施例仅用于进一步说明和阐释本发明,并非用于限制本发明。
下述实施例中所使用的实验方法如无特殊要求,均为常规方法。
下述实施例和对比例中所使用的透明质酸钠均为华熙生物科技股份有限公司生产。其他材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
(1)制备透明质酸-多聚脱氧核糖核苷酸(HA-PDRN)共聚物
称取透明质酸钠(分子量150万Da)2g,PDRN(分子量50万Da)1g,加入100g去离子水,搅拌溶解。将溶解后溶液抽真空除去气泡。将除气泡后的溶液转移至密封容器中,置于60Co辐照源下,剂量20kGy进行辐照。辐照结束后,取出容器。离心后将胶液进行分离,取上清液比较溶液中PDRN残留率,取凝胶粉碎冷冻干燥后得到HA-PDRN共聚物粉末。
(2)配制凝胶
将HA-PDRN共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质,抗氧剂,局麻药和生理缓冲液按照以下用量混合均匀,配制成凝胶。100ml凝胶体系中,HA-PDRN共聚物为3mg;水溶性氨基酸共1mg:其中,甘氨酸0.2mg、脯氨酸0.4mg、盐酸赖氨酸0.1mg、异亮氨酸0.05mg、亮氨酸0.05mg、盐酸精氨酸0.1mg、缬氨酸0.05mg、苏氨酸0.05mg;水溶性维生素共0.05mg:其中,维生素B1 0.01mg、维生素B2 0.01mg、烟酰胺0.02mg、维生素B6 0.01mg;水溶性矿物质共0.01mg:其中,硫酸铜0.0025mg,硫酸锌0.0025mg,氯化钙 0.005mg;抗氧剂共2mg,其中,甘露醇1mg,甘油1mg;盐酸利多卡因0.4mg;余量为磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0)生理缓冲液。
实施例2-5
实施例2-5与实施例1的不同在于,HA-PDRN共聚物的含量不同,其他反应条件均与实施例1相同。
实施例6-8
实施例6-8与实施例1的不同在于,透明质酸的分子量不同,其他反应条件均与实施例1相同。
实施例9-10
实施例9-10与实施例1的不同在于,PDRN的分子量不同,其他反应条件均与实施例1相同。
对比例1
对比例1与实施例1的区别在于,将HA-PDRN共聚物替换为透明质酸和PDRN,其他反应条件均与实施例1相同。其中,在凝胶中透明质酸和PDRN 的占比共计3%,具体的,透明质酸钠的加入量为2mg,PDRN的加入量为1mg。
对比例2
对比例2与实施例1的区别在于,将HA-PDRN共聚物替换为交联透明质酸和PDRN,其他反应条件均与实施例1相同。其中,在凝胶中交联透明质酸和PDRN的占比共计3%,具体的,交联透明质酸的加入量为2mg,PDRN的加入量为1mg。
其中交联透明质酸的制备方法如下:取BDDE 0.01g与5mL 1wt%氢氧化钠溶液混合均匀,然后加入透明质酸钠(150万Da)1.0g搅拌使其溶解均匀。将上述反应物密封,静置于3℃下反应15h,然后静置于50℃反应3h。将最终反应产物切割成约1cm3的小方块,置于纯化水中透析,所得凝胶块经60目筛网粉碎,冷冻干燥,即得交联HA粉末。
具体的各实施例和对比例的反应条件如表1所示。
表1各实施例和对比例的反应条件
试验例1累计释放率试验
1、实验方法:将实施例1~10和对比例1~2共计12种凝胶样品,每种各 10g,封于透析袋中,置于溶出度试验仪中,接收液为100ml PBS(pH7.0~7.4),37℃循环水浴进行释放度试验。于试验开始后的第1h,4h,8h,24h,48h,72h 各取5ml溶出液,再补加5ml接收液,分别检测溶出液中各氨基酸和维生素含量,计算累计释放率(%)。
2、各成分检测方法
2.1接收液样品的处理:取样后,用0.22μm滤膜过滤,作供试样品。检测和计算其中的氨基酸和维生素的累计释放率。
2.2水溶性氨基酸检测方法:使用氨基酸自动分析仪,调用仪器内置的测样方法进行测试,各个氨基酸的对照品均购自中检院。配制一定浓度的氨基酸对照品溶液,分别取空白对照溶液、对照品溶液、供试样品溶液20μL注入氨基酸分析仪,记录色谱图,以外标法计算供试样品中各氨基酸含量,扣除皮肤中的固有含量,乘以相应的稀释倍数,即得。
2.3水溶性维生素检测方法:维生素B1、维生素B2、维生素B6、烟酰胺、叶酸含量检测方法参考王德刚等人的HPLC法(王德刚,严慧如,马萍,刘俊华.HPLC法测定多维元素泡腾片中5种B族维生素[J].药物分析杂志.2010, 30(7):1271-1275);维生素B12检测方法参考徐硕等人的HPLC法(徐硕,金鹏飞,邝咏梅,等.HPLC法测定复合维生素B片中的微量叶酸、维生素B12和生物素[J].药物分析杂志.2018,38(6):1091-1097);维生素C检测方法参考陈曦娟的HPLC法(河南省新蔡县食品药品检验所(463500)陈曦娟.高效液相色谱法检测维生素C片中维生素C含量的分析[J].药品检验.2019:180)。检测含量扣除皮肤中的固有含量,乘以相应的稀释倍数,即得。
3、各成分累计释放率(%)计算:溶出杯中的药物量,加上前面取样时已取走的药物量,除以最初样品加入量,得到释放率。
4、试验结果
各样品中水溶性氨基酸和水溶性维生素的累计释放率如下表2所示。
表2水溶性氨基酸和水溶性维生素的累计释放率(%)
由表2数据可以看出:对比例1的复合凝胶中各氨基酸和维生素释放率最快,4h即释放完全;其次是对比例2,8h释放完全;实施例1~10的复合凝胶中各氨基酸和维生素的释放率慢,72h时仍有部分未释放完全,实施例5由于共聚物含量过少,释放速率较其他实施例均快。这表明含有合适比例的 HA-PDRN共聚物的凝胶体系可以缓慢释放其中的营养成分。
试验例2体外降解试验
分别取细菌HA酶(源自芽孢杆菌CGMCC No.5744)和脱氧核糖核酸酶I (源于牛胰腺)适量,溶于磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0) 配制成细菌HA酶活300U/ml、脱氧核糖核酸酶I酶活100U/ml的混合酶液。然后向混合酶液中加入5mmol/L的Ca2+和Mn2 +作为激活剂。分别称量实施例 1~10和对比例1~2的凝胶样品适量,加入混合酶液4ml,涡旋混匀,使得初始酶解液中HA-PDRN浓度约为8mg/ml。将反应物置于37℃水浴摇床中,每隔10min取样50μL供试液,供试液加入3mL磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0)稀释,0.22μm滤膜过滤,立即使用紫外分光光度计测定232nm 处和260nm处的吸光度。其中,232nm处为透明质酸经细菌HA酶降解后产生的不饱和双糖结构的吸收值,反应了透明质酸链的降解情况;260nm处为降解出的游离PDRN片段的吸收值,反应的是PDRN片段从聚合物上降解下来的情况。以磷酸氢二钠-磷酸二氢钠-氯化钠缓冲液(pH 7.0)作空白对照。当吸光度趋于稳定时,作为酶解终点。结果如表3所示。
表3体外降解结果
由表2可知,对比例1大约20min时HA和PDRN均降解完全;对比例2 大约50min时交联HA降解完全,大约20min时PDRN降解完全;实施例1~10 中,除实施例5由于共聚物含量过低降解时间稍短外,其他实施例的HA和 PDRN降解时间均不小于60min。可见HA-PDRN共聚物的凝胶体系较 HA+PDRN或交联HA+PDRN的物理混合的凝胶体系到达酶解终点的时间更长,即更稳定,体外抗降解能力更好。
Claims (10)
1.一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶,其特征在于,所述凝胶包含透明质酸-多聚脱氧核糖核苷酸共聚物,水溶性氨基酸,水溶性维生素,水溶性矿物质和抗氧剂。
2.根据权利要求1所述的凝胶,其特征在于,在所述凝胶中,所述透明质酸-多聚脱氧核糖核苷酸共聚物的质量百分比为0.5%~5%,优选为1%~3%,所述水溶性氨基酸的质量百分比为0.002%~5%,优选为0.003%~1%,所述水溶性维生素的质量百分比为0.0005%~0.5%,优选为0.0005%~0.05%,所述矿物质的质量百分比为0.0001%~0.05%,优选为0.0005%~0.01%,所述抗氧剂的质量百分比为0.1%~3%,优选为0.2%~2%。
3.根据权利要求1所述的凝胶,其特征在于,所述凝胶还包含局麻药,在所述凝胶中,所述局麻药的质量百分比为0.2%~0.4%。
4.根据权利要求1所述的凝胶,其特征在于,所述透明质酸-多聚脱氧核糖核苷酸共聚物是由分子量为50万Da~300万Da,优选为150万Da~300万Da的透明质酸或其盐,与分子量为5万Da~100万Da的多聚脱氧核糖核苷酸交联得到。
5.根据权利要求4所述的凝胶,其特征在于,所述透明质酸-多聚脱氧核糖核苷酸共聚物的制备方法包括以下步骤:
将透明质酸或其盐和多聚脱氧核糖核苷酸溶于水,脱气后形成混合溶液;
将所述混合溶液在高能射线下进行辐照交联,得到透明质酸-多聚脱氧核糖核苷酸共聚物水凝胶;
将所述水凝胶粉碎、干燥后,得到透明质酸-多聚脱氧核糖核苷酸共聚物。
6.根据权利要求5所述的凝胶,其特征在于,在所述混合溶液中,所述透明质酸或其盐和多聚脱氧核糖核苷酸的质量比为1:1~10:1,优选为1:1~5:1。
7.根据权利要求1所述的凝胶,其特征在于,所述水溶性氨基酸选自甘氨酸、脯氨酸、羟脯氨酸、盐酸赖氨酸、异亮氨酸、亮氨酸、丝氨酸、丙氨酸、天冬氨酸、酪氨酸、谷氨酸、苯丙氨酸、盐酸精氨酸、缬氨酸、苏氨酸、盐酸组氨酸、色氨酸、甲硫氨酸、胱氨酸和半胱氨酸中的一种或两种以上。
8.根据权利要求1所述的凝胶,其特征在于,所述水溶性维生素选自维生素B1、维生素B2、烟酰胺、维生素B6、维生素B12、叶酸和维生素C中的一种或两种以上。
9.根据权利要求1所述的凝胶,其特征在于,所述水溶性矿物质选自钙、锌、铜、硒的可溶性无机盐或有机盐中的一种或两种以上。
10.根据权利要求1所述的凝胶,其特征在于,所述抗氧剂选自甘露醇、甘油、肌肽中的一种或两种以上。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110399905.0A CN115192771B (zh) | 2021-04-14 | 2021-04-14 | 一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110399905.0A CN115192771B (zh) | 2021-04-14 | 2021-04-14 | 一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115192771A true CN115192771A (zh) | 2022-10-18 |
CN115192771B CN115192771B (zh) | 2024-02-27 |
Family
ID=83573725
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110399905.0A Active CN115192771B (zh) | 2021-04-14 | 2021-04-14 | 一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115192771B (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115737470A (zh) * | 2022-11-25 | 2023-03-07 | 润辉生物技术(威海)有限公司 | 一种肌肽-pdrn复合物及其制备方法和应用 |
CN116098827A (zh) * | 2022-12-07 | 2023-05-12 | 华熙生物科技股份有限公司 | 寡肽在提高维生素和/或氨基酸稳定性中的应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994025078A1 (fr) * | 1993-04-30 | 1994-11-10 | Laboratoires Sebbin | Utilisation d'hydrogels a base d'acide hyaluronique et/ou de polydesoxyribonucleotides comme materiaux de remplissage de protheses et protheses en resultant |
JP2008001763A (ja) * | 2006-06-21 | 2008-01-10 | Gunma Univ | デオキシリボ核酸を安定に含むゲル組成物の製造方法及び該方法により得られたゲル組成物 |
EP2407147A2 (en) * | 2010-07-14 | 2012-01-18 | Mastelli S.R.L. | Composition with bio-rigenerative, restorative and eutrophying activity |
CN104189952A (zh) * | 2014-08-05 | 2014-12-10 | 北京爱美客生物科技有限公司 | 纠正皮肤褶皱注射液及其制备方法 |
CH711092A2 (de) * | 2015-05-18 | 2016-11-30 | Labo Cosprophar Ag | Dermokosmetisches biorevitalisierendes Kit zur äusserlichen Anwendung mit schnellem Eintritt mittels zugehörigem Präzisionsapplikator. |
CN108289825A (zh) * | 2015-11-24 | 2018-07-17 | 株式会社Bmi韩国 | 含透明质酸衍生物和dna片段的注射用透明质酸组合物及其应用 |
-
2021
- 2021-04-14 CN CN202110399905.0A patent/CN115192771B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994025078A1 (fr) * | 1993-04-30 | 1994-11-10 | Laboratoires Sebbin | Utilisation d'hydrogels a base d'acide hyaluronique et/ou de polydesoxyribonucleotides comme materiaux de remplissage de protheses et protheses en resultant |
JP2008001763A (ja) * | 2006-06-21 | 2008-01-10 | Gunma Univ | デオキシリボ核酸を安定に含むゲル組成物の製造方法及び該方法により得られたゲル組成物 |
EP2407147A2 (en) * | 2010-07-14 | 2012-01-18 | Mastelli S.R.L. | Composition with bio-rigenerative, restorative and eutrophying activity |
CN104189952A (zh) * | 2014-08-05 | 2014-12-10 | 北京爱美客生物科技有限公司 | 纠正皮肤褶皱注射液及其制备方法 |
CH711092A2 (de) * | 2015-05-18 | 2016-11-30 | Labo Cosprophar Ag | Dermokosmetisches biorevitalisierendes Kit zur äusserlichen Anwendung mit schnellem Eintritt mittels zugehörigem Präzisionsapplikator. |
CN108289825A (zh) * | 2015-11-24 | 2018-07-17 | 株式会社Bmi韩国 | 含透明质酸衍生物和dna片段的注射用透明质酸组合物及其应用 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115737470A (zh) * | 2022-11-25 | 2023-03-07 | 润辉生物技术(威海)有限公司 | 一种肌肽-pdrn复合物及其制备方法和应用 |
CN116098827A (zh) * | 2022-12-07 | 2023-05-12 | 华熙生物科技股份有限公司 | 寡肽在提高维生素和/或氨基酸稳定性中的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN115192771B (zh) | 2024-02-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN115192771B (zh) | 一种含透明质酸-多聚脱氧核糖核苷酸共聚物的凝胶及其用途 | |
EP3107587B1 (en) | Dermocosmetic filler and uses thereof for aesthetic purposes | |
Oprea et al. | Cellulose/chondroitin sulfate hydrogels: Synthesis, drug loading/release properties and biocompatibility | |
CN109806182B (zh) | 一种含透明质酸和氨基酸的组合物及其制备方法和应用 | |
CN112294668B (zh) | 透明质酸注射液 | |
EP2222713B1 (en) | Mixed butyric-formic esters of acid polysaccharides, and their preparation and use as skin cosmetics | |
Muramatsu et al. | In vitro degradation behavior of freeze-dried carboxymethyl-chitin sponges processed by vacuum-heating and gamma irradiation | |
WO2021077681A1 (zh) | 一种用于水光注射的透明质酸凝胶组合物及其制备方法 | |
CN111297727A (zh) | 一种美塑治疗组合物及其应用 | |
WO2012143876A1 (en) | A sterile and injectable aqueous formulation for administration in the intra-articular space of an intra-articular joint | |
CN110812253A (zh) | 一种用于水光注射的透明质酸凝胶及其使用方法 | |
CN113679046A (zh) | 促进透明质酸与胶原蛋白相互作用的组合物及其应用 | |
CN114522223A (zh) | 一种纠正皮肤褶皱的注射液及其生产工艺 | |
CN113278170A (zh) | 一种化学交联透明质酸水凝胶及其制备方法与应用 | |
WO2019106671A1 (en) | Methods of preventing or treating neurogenic shock | |
CA3101408A1 (en) | Hydrogel composition comprising a crosslinked polymer | |
Lee et al. | Preparation of injectable forms of immobilized protein drugs using UV-curable gelatin derivatives | |
CN114478829B (zh) | 一种透明质酸交联活性材料组合物、制备方法及应用 | |
EP4053290A1 (en) | Low molecular weight chondroitin sulfate, composition containing same, and preparation method therefor and use thereof | |
CN114163667A (zh) | 隔离用交联凝胶、制备方法及应用 | |
CN107522876B (zh) | 一种复合凝胶的制备方法及其在诱导干细胞成软骨分化中的应用 | |
CN115197341B (zh) | 一种透明质酸-多聚脱氧核糖核苷酸共聚物及其制备方法和用途 | |
Chung et al. | Degradation of oligo [poly (ethylene glycol) fumarate] hydrogels through stimulus-mediated pendent group cyclization | |
Li et al. | Interstitial Injection of Hydrogels with High‐Mechanical Conductivity Relieves Muscle Atrophy Induced by Nerve Injury | |
RU2782921C1 (ru) | Протез синовиальной жидкости и способ его получения |
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 |