CN111228260B - 一种包含雷帕霉素的组合物及其用途 - Google Patents
一种包含雷帕霉素的组合物及其用途 Download PDFInfo
- Publication number
- CN111228260B CN111228260B CN202010137707.2A CN202010137707A CN111228260B CN 111228260 B CN111228260 B CN 111228260B CN 202010137707 A CN202010137707 A CN 202010137707A CN 111228260 B CN111228260 B CN 111228260B
- Authority
- CN
- China
- Prior art keywords
- rapamycin
- gel
- group
- skin
- chitosan
- 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
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 37
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 229960002930 sirolimus Drugs 0.000 title claims abstract description 36
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 229920001661 Chitosan Polymers 0.000 claims abstract description 27
- 239000000499 gel Substances 0.000 claims abstract description 26
- 239000000017 hydrogel Substances 0.000 claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 20
- 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 abstract description 19
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 19
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 19
- 230000032683 aging Effects 0.000 claims abstract description 7
- 239000002537 cosmetic Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 239000003086 colorant Substances 0.000 claims description 3
- 230000010355 oscillation Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 238000002604 ultrasonography Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000006378 damage Effects 0.000 abstract description 3
- 229940045110 chitosan Drugs 0.000 abstract description 2
- 230000009044 synergistic interaction Effects 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 22
- 102100033254 Tumor suppressor ARF Human genes 0.000 description 8
- 150000004676 glycans Chemical class 0.000 description 7
- 229920001282 polysaccharide Polymers 0.000 description 7
- 239000005017 polysaccharide Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 102000008186 Collagen Human genes 0.000 description 6
- 108010035532 Collagen Proteins 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 6
- 238000011580 nude mouse model Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 5
- 210000004207 dermis Anatomy 0.000 description 5
- -1 hyaluronic acid ester Chemical class 0.000 description 5
- 230000009759 skin aging Effects 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000002500 effect on skin Effects 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- 238000009987 spinning Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000037303 wrinkles Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 229940010747 sodium hyaluronate Drugs 0.000 description 3
- 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 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 230000003712 anti-aging effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- KIUKXJAPPMFGSW-YXBJCWEESA-N (2s,4s,5r,6s)-6-[(2s,3r,5s,6r)-3-acetamido-2-[(3s,4r,5r,6r)-6-[(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]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(O[C@@H]3[C@@H]([C@@H](O)C(O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)C(C(O)=O)O1 KIUKXJAPPMFGSW-YXBJCWEESA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 229940114069 12-hydroxystearate Drugs 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 235000009328 Amaranthus caudatus Nutrition 0.000 description 1
- 240000001592 Amaranthus caudatus Species 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 239000005714 Chitosan hydrochloride Substances 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 101000634900 Homo sapiens Transcriptional-regulating factor 1 Proteins 0.000 description 1
- 229920002752 Konjac Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 241001506137 Rapa Species 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004283 Sodium sorbate Substances 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 102100029446 Transcriptional-regulating factor 1 Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 235000012741 allura red AC Nutrition 0.000 description 1
- 239000004191 allura red AC Substances 0.000 description 1
- 235000012735 amaranth Nutrition 0.000 description 1
- 239000004178 amaranth Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000004301 calcium benzoate Substances 0.000 description 1
- 235000010237 calcium benzoate Nutrition 0.000 description 1
- MCFVRESNTICQSJ-RJNTXXOISA-L calcium sorbate Chemical compound [Ca+2].C\C=C\C=C\C([O-])=O.C\C=C\C=C\C([O-])=O MCFVRESNTICQSJ-RJNTXXOISA-L 0.000 description 1
- 235000010244 calcium sorbate Nutrition 0.000 description 1
- 239000004303 calcium sorbate Substances 0.000 description 1
- HZQXCUSDXIKLGS-UHFFFAOYSA-L calcium;dibenzoate;trihydrate Chemical compound O.O.O.[Ca+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 HZQXCUSDXIKLGS-UHFFFAOYSA-L 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 235000012730 carminic acid Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000032677 cell aging Effects 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- CEZCCHQBSQPRMU-UHFFFAOYSA-L chembl174821 Chemical compound [Na+].[Na+].COC1=CC(S([O-])(=O)=O)=C(C)C=C1N=NC1=C(O)C=CC2=CC(S([O-])(=O)=O)=CC=C12 CEZCCHQBSQPRMU-UHFFFAOYSA-L 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- HWDGVJUIHRPKFR-UHFFFAOYSA-I copper;trisodium;18-(2-carboxylatoethyl)-20-(carboxylatomethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18-dihydroporphyrin-21,23-diide-2-carboxylate Chemical compound [Na+].[Na+].[Na+].[Cu+2].N1=C(C(CC([O-])=O)=C2C(C(C)C(C=C3C(=C(C=C)C(=C4)[N-]3)C)=N2)CCC([O-])=O)C(=C([O-])[O-])C(C)=C1C=C1C(CC)=C(C)C4=N1 HWDGVJUIHRPKFR-UHFFFAOYSA-I 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 235000013980 iron oxide Nutrition 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000000252 konjac Substances 0.000 description 1
- 235000019823 konjac gum Nutrition 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 231100001095 no nephrotoxicity Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- 235000013758 sodium copper chlorophyllin Nutrition 0.000 description 1
- 229940079841 sodium copper chlorophyllin Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- 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
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- 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
- 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
- A61K8/736—Chitin; Chitosan; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/18—Antioxidants, e.g. antiradicals
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Birds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
本发明涉及药物领域,公开了一种包含雷帕霉素的组合物及其用途。本发明所述组合物包含雷帕霉素和水凝胶材料,其中雷帕霉素均匀分布在凝胶材料中,所述凝胶材料为透明质酸凝胶或/和壳聚糖凝胶。本发明应用透明质酸或壳聚糖等凝胶成分与雷帕霉素形成组合物,应用于老化皮肤的损伤修复,不仅能快速发挥雷帕霉素的作用,还能使其与凝胶成分发挥协同增效,从而缩短起效时间,提高皮肤修复和抗衰的效果。
Description
技术领域
本发明涉及药物领域,具体是涉及一种包含雷帕霉素的组合物及其用途。
背景技术
雷帕霉素是科学家于1975年首次从智利复活节岛的土壤中发现的一种由土壤链霉菌分泌的次生代谢物,该药物以发现岛屿的名称Rapa Nui来命名。研究人员发现该药物对人体有多种作用:1977年发现具有免疫抑制作用,1989年开始把RAPA作为治疗器官移植的排斥反应的新药进行试用,从动物实验及临床应用的效果看,是一种疗效好、低毒、无肾毒性的新型免疫抑制剂。现在经常作为维持移植器官免疫能力的药物(特别是肾移植),以减缓器官移植手术后的免疫排斥反应。
皮肤衰老和真性皱纹是人类衰老不可避免的问题,现有的护肤产品或医疗美容产品无法真正逆转这一问题。Drexel大学医学院研究人员Christina Lee Chung等发表在Geroscience上的一项研究“Topical rapamycin reduces markers of senescence andaging in human skin:an exploratory,prospective,randomized trial”首次在36位参与者中开展临床试验,发现通过外抹含有雷帕霉素的乳霜可以在8个月后减少皮肤皱纹和下垂、改善肤色,并改善胶原蛋白表达、抑制P16蛋白表达。然而,在上述研究中雷帕霉素起效时间太长,8个月后才出现明显效果,不利于临床应用和市场转化。
多糖水凝胶是多糖利用的一个重要方面,水凝胶是一类具有三维交联网络结构,能够吸收并保持大量水分,而又不溶于水的功能高分子材料。多糖水凝胶在化妆品中的应用主要有以下功能:1)提高化妆品的增黏功能;2)长时间有效的给予肌肤水分和油分;3)具有补充皮肤水分,使角质柔软,保持皮肤不干燥的作用。
CN109942905A公开一种复合水凝胶材料及其制备方法,由聚乙烯醇、壳聚糖、透明质酸钠复合而成的海绵状水凝胶材料,以壳聚糖和透明质酸钠为主要原料,通过加入聚乙烯醇,利用冻融循环法制备出了物理交联的聚乙烯醇/壳聚糖/透明质酸钠复合水凝胶。
CN106963982A公开了一种具有抗菌保湿适宜组织粘附的修复材料及其制备方法和应用,所述修复材料的制备方法如下:S1.对透明质酸进行巯基化修饰;S2.对壳聚糖进行马来酰化改性S3.将纳米纺丝纤维经多巴胺溶液浸泡后充分水洗,然后将纳米纺丝纤维依次浸入巯基化透明质酸溶液和马来酰化壳聚糖溶液中吸附,吸附完后洗脱;S4.重复吸附、洗脱步骤若干次后即得巯基化透明质酸和马来酰化壳聚糖交替吸附的修复材料。
CN109602686A公开了一种水凝胶化妆品组合物,包括水凝胶组分和透明质酸溶液,所述水凝胶组分每100份中包括原料的质量份数为壳聚糖:1~3份;保湿剂:1~10份;促透皮吸收剂:0.1~1份;中草药提取物:1~15份;植物油:0.4~1份;植物精油:0.001~0.01份,去离子水添加至100份。
然而,现有的多糖亲水性水凝胶产品的皮肤修复以及抗衰老的功效还不能达到令人满意的作用。
发明内容
本发明的目的是为了克服上述背景技术的不足,提供一种包含雷帕霉素的组合物及其用途,该组合物将雷帕霉素粉末加入凝胶材料中,使其分布均匀,用于皮肤修复和抗衰老,起效快,效果好。
为达到本发明的目的,本发明包含雷帕霉素的组合物包含雷帕霉素和水凝胶材料。
进一步的,所述的水凝胶材料为多糖类亲水凝胶材料。
进一步的,所述的多糖类亲水凝胶材料选自透明质酸或其衍生物、壳聚糖或其衍生物。
本发明所述的透明质酸分子量通常在1KDa-10,000KDa之间,优选在800KDa-3,000KDa之间,特别优选在1,000KDa-2,800Kda之间。
本发明所述的壳聚糖的分子量通常在1kDa-300kDa之间,优选在10kDa-100kDa之间,特别优选在40kDa-60kDa之间。
本发明所述的透明质酸衍生物选自透明质酸盐、透明质酸酯等,优选的,所述的透明质酸衍生物为透明质酸钠盐或透明质酸钾盐。
本发明所述的壳聚糖衍生物选自壳聚糖季铵盐、壳聚糖羧酸盐、壳聚糖醋酸盐或壳聚糖盐酸盐。
进一步的,所述的组合物中雷帕霉素分布在水凝胶材料中,所述水凝胶材料为透明质酸凝胶或/和壳聚糖凝胶。
进一步地,所述雷帕霉素通过超声震荡的方式均匀分布在水凝胶材料中。
进一步地,所述透明质酸凝胶或/和壳聚糖凝胶的制备方法为本领域常规方法,例如壳聚糖凝胶的制备方法可以是利用非离子型亲水性聚合物(聚乙烯醇等)与壳聚糖共混,用戊二醛或甲醛等做交联剂来形成壳聚糖基互穿网络水凝胶。
进一步地,所述雷帕霉素在组合物中的浓度为7-13μM。
优选地,所述雷帕霉素在组合物中的浓度为9-11μM。
更优选的,所述雷帕霉素在组合物中的浓度为7、8、9、10、11、12、13μM。
进一步地,所述包含雷帕霉素的组合物还包含药学上可接受的赋形剂,例如稳定剂、抗氧剂、助溶剂、增溶剂、着色剂等。
稳定剂例如是变性淀粉、卡拉胶、果胶、魔芋胶、黄原胶、羧甲基纤维素钠、海藻酸钠、酪朊酸钠、微晶纤维素。
增溶剂例如是聚氧化乙烯单油酸山梨醇酐酯、吐温-80、维生素E琥珀酸聚乙二醇酯、甘油-聚乙二醇氧基硬脂酸酯、PEG-32硬脂酸棕榈酸甘油酯、十二烷基硫酸钠、单月桂酸山梨醇酐酯、聚乙二醇、聚乙二醇、聚乙二醇-12-羟基硬脂酸酯、聚乙烯吡咯烷酮等。
助溶剂例如是乙醇、丙二醇、聚山梨酯、聚氧化乙烯/聚氧化丙烯表面活性剂、维生素E琥珀酸聚乙二醇酯、环糊精等。
抗氧化剂例如是生育酚、生育酚乙酸、苯甲酸钠、苯甲酸钙、苯甲酸钾、山梨酸钠、山梨酸钙、山梨酸钾、抗坏血酸等。
着色剂例如是亮蓝、日落黄、叶绿素、叶绿素铜钠盐、诱惑红、氧化铁、苋菜红或胭脂红。
本领域技术人员应该理解,除透明质酸凝胶或/和壳聚糖凝胶之外的其他多糖类亲水性凝胶材料也适用于本发明。
另一方面,本发明还提供了一种上述包含雷帕霉素的组合物的用途,即将所述组合物用于皮肤损伤修复或者抗皮肤衰老,例如是用于衰老皮肤上修复皮肤或者抗衰老。
另一方面,本发明还提供了一种上述包含雷帕霉素的组合物的用途,所述的用途为用于制备皮肤损伤修复或者抗皮肤衰老的化妆品或药品。
进一步的,所述的化妆品可为凝露、膏霜、啫喱、眼霜、面膜等形式。
进一步的,所述的药品可为擦剂、膏剂、贴剂等形式。
与现有技术相比,本发明将透明质酸或壳聚糖等水凝胶成分与雷帕霉素形成组合物,应用于老化皮肤的损伤修复,不仅能快速发挥雷帕霉素的作用,还能使其与水凝胶成分发挥协同增效,从而缩短起效时间(每日涂抹一次,持续4周即可),提高皮肤修复和抗衰的效果。
附图说明
图1是第12周时裸鼠背部同一区域皮肤观察结果,其中NC为正常组;Model为模型组;
图2是裸鼠皮肤HE染色组织病理观察及真皮厚度测量结果,其中柱状图纵坐标为真皮层厚度(dermal thickness);
图3是裸鼠皮肤Massion染色组织病理观察及胶原比例测量结果,其中柱状图纵坐标为胶原含量(collegen ratio);
图4是裸鼠皮肤组织real time PCR检测p16表达情况。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。本发明的附加方面和优点将在下面的描述中部分给出,部分将从下面的描述中变得明显,或通过本发明的实践了解到。应当理解,以下描述仅仅用以解释本发明,并不用于限定本发明。
实施例1
分别制备透明质酸凝胶、壳聚糖凝胶,将雷帕霉素通过超声震荡的方式均匀分布在透明质酸凝胶、壳聚糖凝胶中,雷帕霉素的浓度为10μM,获得雷帕霉素-透明质酸组合物(记作LT)与雷帕霉素-壳聚糖组合物(记作LK)。
实施例2
造模与干预:取40只6周龄大的SPF级雄性裸鼠,随机分成5组:正常组(NC)、模型组(Model)、LT组、LK组、LY(不含凝胶的雷帕霉素生理盐水液体,雷帕霉素的浓度为10μM)组,每组10只。正常组外,其余各组动物每天背部皮下注射D-gal(1000mg/kg,皮下注射)8周,背部左右可进行对比。允许所有动物自由获取水和食物,并且每天观察背部注射部位皮肤的变化。拍照记录。在第8周开始每天在LT组、LK组、LY组分别涂抹一次雷帕霉素-透明质酸、雷帕霉素-壳聚糖和雷帕霉素液体,共4周,对照组涂抹生理盐水。第12周时处死小鼠,取背部同一区域小块皮肤进行组织学检查,进行HE和Masson染色,用image J软件测量长度和区域面积。
Real time PCR检测:用Trizol法提取皮肤组织总RNA。用TAKARA逆转录试剂盒将总RNA逆转录成cDNA。SYBR反应体系:SYBR green 10μl,RNase-Free Water 8μl,cDNA 1μl,上游引物和下游引物各0.5μl进行上机。反应条件:95℃下持续6min,95℃下5s,60℃下30s,共有35个循环,每个样本设置3个复孔,以Actin作为内参,检测各组p16表达水平,用2-ΔΔCt法计算mRNA相对表达量。
第12周时裸鼠背部同一区域皮肤观察结果如图1所示,造模后模型组呈现明显的皮肤皱纹,而经过含雷帕霉素的各组干预后,皱纹有不同程度缓解。其中LT组和LK组裸鼠皱纹明显比LY组更少、更浅,且与正常组几乎相同,说明LT组和LK组比LY组缓解皱纹的效果更好。
组织病理观察如图2、3所示,正常组表皮层、真皮层完整,染色正常;模型组真皮层明显变薄,且染色较浅,说明真皮组织和胶原含量减少;统计结果表明,LT组、LK组和LY组的真皮层及胶原含量均多于模型组,其中LT组和LK组真皮层厚度(dermal thickness)和胶原含量(collegen ratio)高于LY组。
p16蛋白是皮肤细胞衰老的关键标志,p16含量较低的皮肤衰老细胞较少,较高水平的p16可导致老年人常见的皮肤萎缩现象,这与脆弱的皮肤容易撕裂、伤口愈合缓慢、受伤后感染或并发症的风险增加有关。Real time PCR结果表明,模型组皮肤衰老指标p16显著上调,经LT、LK和LY干预后,p16表达显著下调,其中LT组和LK组的作用优于LY组,尤其是LK组,p16蛋白与正常组几乎相同。上述结果说明,4周内LT组、LK组和LY组均有修复皮肤衰老的作用,LT组和LK组的作用明显优于LY组。
本领域的技术人员容易理解,以上所述仅为本发明的实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (6)
1.包含雷帕霉素和水凝胶材料的组合物的用途,其特征在于,所述的用途为用于制备抗皮肤衰老的化妆品或药品,所述的组合物中雷帕霉素分布在水凝胶材料中,所述水凝胶材料为透明质酸凝胶或/和壳聚糖凝胶。
2.根据权利要求1所述的用途,其特征在于,所述雷帕霉素通过超声震荡的方式分布在凝胶材料中。
3.根据权利要求1所述的用途,其特征在于,所述雷帕霉素在组合物中的浓度为7-13 μM。
4.根据权利要求3所述的用途,其特征在于,所述雷帕霉素在组合物中的浓度为9-11 μM。
5.根据权利要求1所述的用途,其特征在于,所述组合物还包含药学上可接受的赋形剂。
6.根据权利要求5所述的用途,其特征在于,所述药学上可接受的赋形剂为稳定剂、抗氧剂、助溶剂、增溶剂、着色剂中的一种或多种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010137707.2A CN111228260B (zh) | 2020-03-02 | 2020-03-02 | 一种包含雷帕霉素的组合物及其用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010137707.2A CN111228260B (zh) | 2020-03-02 | 2020-03-02 | 一种包含雷帕霉素的组合物及其用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111228260A CN111228260A (zh) | 2020-06-05 |
CN111228260B true CN111228260B (zh) | 2021-06-29 |
Family
ID=70876760
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010137707.2A Active CN111228260B (zh) | 2020-03-02 | 2020-03-02 | 一种包含雷帕霉素的组合物及其用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111228260B (zh) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101366715A (zh) * | 2007-08-15 | 2009-02-18 | 上海医药工业研究院 | 一种雷帕霉素组合物及其制备方法 |
CN105663027B (zh) * | 2016-04-01 | 2018-12-18 | 中国人民解放军广州军区武汉总医院 | 西罗莫司外用制剂、其制备方法及用途 |
-
2020
- 2020-03-02 CN CN202010137707.2A patent/CN111228260B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN111228260A (zh) | 2020-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100676937B1 (ko) | 피부미용 및 상처치료용 수용성 필름 및 그 제조방법 | |
AU2008307152B2 (en) | Composition and method for dermal regeneration | |
CN103083713B (zh) | 一种无菌聚合创面覆盖物敷料 | |
CN105816911B (zh) | 一种含生长因子的修复凝胶及其制备方法 | |
CN101977589B (zh) | 皮肤病学使用的壳聚糖凝胶、其制备方法及其用途 | |
CN106822988B (zh) | 海藻纤维功能性敷料及其应用、海藻纤维功能性敷料贴 | |
CN107185031B (zh) | 一种具有生物活性的医用敷料及其制备方法 | |
JP2010512220A5 (zh) | ||
CN110237054B (zh) | 一种疤痕修复材料及其制备方法 | |
CN113368300B (zh) | 一种eps与贻贝提取物复配修复皮肤屏障敷料及其制备方法 | |
CN110507845A (zh) | 生物复合透气敷料及其制备方法 | |
CN105012960A (zh) | 成膜凝胶组合物、其用途及护创材料 | |
CN106420381A (zh) | 青蒿素类成分或其组合物在皮肤护理中的新应用 | |
CN104622897A (zh) | 一种治疗皮肤病的护肤液及其制备方法 | |
CN107550753A (zh) | 一种具有皮肤修复、抗衰老功能的组合物及其制备方法 | |
US11235016B2 (en) | Use of a vegetal extract as an active agent in tissue re-epithelizing and cicatrizing processes | |
CN111420023B (zh) | 含i型胶原和透明质酸的复合物及制备和用途 | |
CN111228260B (zh) | 一种包含雷帕霉素的组合物及其用途 | |
CN110711161A (zh) | 一种免洗型的舒敏修护精华面膜 | |
CN111973656B (zh) | 一种含有抑菌促愈合组合物的口腔溃疡制剂 | |
CN106943316A (zh) | 可促进皮肤再生的乳液及其制备方法 | |
JP2005022980A (ja) | 化粧用パックシート及びその製造方法 | |
Fitriani et al. | Membrane of Usnic Acid in Solid Dispersion and Effectiveness in Burn Healing | |
Khokhlenkova | Prospects of using biopolymeric films in medicine and pharmacy | |
CN1515315A (zh) | 一种含表皮生长因子和白及的稳定组合物 |
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 |