CN119280077B - Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide - Google Patents
Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide Download PDFInfo
- Publication number
- CN119280077B CN119280077B CN202411847006.2A CN202411847006A CN119280077B CN 119280077 B CN119280077 B CN 119280077B CN 202411847006 A CN202411847006 A CN 202411847006A CN 119280077 B CN119280077 B CN 119280077B
- Authority
- CN
- China
- Prior art keywords
- polycaprolactone
- palmitoyl
- blue copper
- copper peptide
- phase solution
- 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
- MVORZMQFXBLMHM-QWRGUYRKSA-N Gly-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 MVORZMQFXBLMHM-QWRGUYRKSA-N 0.000 title claims abstract description 103
- 241000530268 Lycaena heteronea Species 0.000 title claims abstract description 100
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 title claims abstract description 99
- 239000004005 microsphere Substances 0.000 title claims abstract description 92
- 238000002360 preparation method Methods 0.000 title claims abstract description 52
- 229920001610 polycaprolactone Polymers 0.000 claims abstract description 112
- 239000004632 polycaprolactone Substances 0.000 claims abstract description 112
- 229920000642 polymer Polymers 0.000 claims abstract description 53
- 239000012488 sample solution Substances 0.000 claims abstract description 30
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 17
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 14
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 14
- HPQUMJNDQVOTAZ-UHFFFAOYSA-N 2,2-dihydroxypropanoic acid Chemical compound CC(O)(O)C(O)=O HPQUMJNDQVOTAZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 64
- 239000012071 phase Substances 0.000 claims description 52
- 239000008346 aqueous phase Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- 210000004209 hair Anatomy 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000000839 emulsion Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 238000007789 sealing Methods 0.000 claims description 7
- 230000003779 hair growth Effects 0.000 claims description 5
- 230000003656 anti-hair-loss Effects 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 210000004761 scalp Anatomy 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000002453 shampoo Substances 0.000 claims description 2
- BXGYYDRIMBPOMN-UHFFFAOYSA-N 2-(hydroxymethoxy)ethoxymethanol Chemical group OCOCCOCO BXGYYDRIMBPOMN-UHFFFAOYSA-N 0.000 claims 1
- 238000000265 homogenisation Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 38
- 150000001875 compounds Chemical class 0.000 abstract description 19
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 13
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 9
- 229920001184 polypeptide Polymers 0.000 abstract description 8
- KSQJASGRYBQJGS-UHFFFAOYSA-N 2-hydroxyethoxymethanediol Chemical compound OCCOC(O)O KSQJASGRYBQJGS-UHFFFAOYSA-N 0.000 abstract description 6
- 230000036564 melanin content Effects 0.000 abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000000523 sample Substances 0.000 description 22
- 230000014509 gene expression Effects 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- -1 polyoxypropylene Polymers 0.000 description 15
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 14
- 229930006000 Sucrose Natural products 0.000 description 14
- 229920001451 polypropylene glycol Polymers 0.000 description 14
- 239000005720 sucrose Substances 0.000 description 14
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- 201000001441 melanoma Diseases 0.000 description 11
- 239000013642 negative control Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 108010038983 glycyl-histidyl-lysine Proteins 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000001737 promoting effect Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 238000006116 polymerization reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 5
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 5
- 101000864646 Homo sapiens Dickkopf-related protein 1 Proteins 0.000 description 5
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 210000003780 hair follicle Anatomy 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 3
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 229940126864 fibroblast growth factor Drugs 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 230000009583 hair follicle growth Effects 0.000 description 3
- 229940047122 interleukins Drugs 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N 1,4-Benzenediol Natural products OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 102100028256 Collagen alpha-1(XVII) chain Human genes 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- 101100317380 Danio rerio wnt4a gene Proteins 0.000 description 2
- 102100029109 Endothelin-3 Human genes 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 108010010285 Forkhead Box Protein L2 Proteins 0.000 description 2
- 102100035137 Forkhead box protein L2 Human genes 0.000 description 2
- 101000762375 Homo sapiens Bone morphogenetic protein 3 Proteins 0.000 description 2
- 101000860679 Homo sapiens Collagen alpha-1(XVII) chain Proteins 0.000 description 2
- 101000841213 Homo sapiens Endothelin-3 Proteins 0.000 description 2
- 101000896557 Homo sapiens Eukaryotic translation initiation factor 3 subunit B Proteins 0.000 description 2
- 101000988834 Homo sapiens Hypoxanthine-guanine phosphoribosyltransferase Proteins 0.000 description 2
- 101000934753 Homo sapiens Keratin, type II cytoskeletal 75 Proteins 0.000 description 2
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 description 2
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 2
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 2
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 102100025367 Keratin, type II cytoskeletal 75 Human genes 0.000 description 2
- 102100022430 Melanocyte protein PMEL Human genes 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 229920012196 Polyoxymethylene Copolymer Polymers 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 2
- 102000003425 Tyrosinase Human genes 0.000 description 2
- 108060008724 Tyrosinase Proteins 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 101150010310 WNT-4 gene Proteins 0.000 description 2
- 102000052548 Wnt-4 Human genes 0.000 description 2
- 108700020984 Wnt-4 Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical group [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000013020 embryo development Effects 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920000903 polyhydroxyalkanoate Polymers 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical group [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000009489 vacuum treatment Methods 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 102000009310 vitamin D receptors Human genes 0.000 description 2
- 108050000156 vitamin D receptors Proteins 0.000 description 2
- 102100033875 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Human genes 0.000 description 1
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 1
- 108010072151 Agouti Signaling Protein Proteins 0.000 description 1
- 102100038154 Agouti-signaling protein Human genes 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 description 1
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 1
- 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 1
- 102100024301 COMM domain-containing protein 3 Human genes 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102100031673 Corneodesmosin Human genes 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 102100026359 Cyclic AMP-responsive element-binding protein 1 Human genes 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 102100034579 Desmoglein-1 Human genes 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 101000640851 Homo sapiens 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Proteins 0.000 description 1
- 101000773083 Homo sapiens 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- 101000909562 Homo sapiens COMM domain-containing protein 3 Proteins 0.000 description 1
- 101000710899 Homo sapiens Cannabinoid receptor 1 Proteins 0.000 description 1
- 101000777796 Homo sapiens Corneodesmosin Proteins 0.000 description 1
- 101000855516 Homo sapiens Cyclic AMP-responsive element-binding protein 1 Proteins 0.000 description 1
- 101000924316 Homo sapiens Desmoglein-1 Proteins 0.000 description 1
- 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 1
- 101000972291 Homo sapiens Lymphoid enhancer-binding factor 1 Proteins 0.000 description 1
- 101001038034 Homo sapiens Lysophosphatidic acid receptor 6 Proteins 0.000 description 1
- 101000973778 Homo sapiens NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 1
- 101001131829 Homo sapiens P protein Proteins 0.000 description 1
- 101001073427 Homo sapiens Prostaglandin E2 receptor EP1 subtype Proteins 0.000 description 1
- 101000666172 Homo sapiens Protein-glutamine gamma-glutamyltransferase E Proteins 0.000 description 1
- 101001098560 Homo sapiens Proteinase-activated receptor 2 Proteins 0.000 description 1
- 101001116937 Homo sapiens Protocadherin alpha-4 Proteins 0.000 description 1
- 101000664703 Homo sapiens Transcription factor SOX-10 Proteins 0.000 description 1
- 101000652337 Homo sapiens Transcription factor SOX-21 Proteins 0.000 description 1
- 101000920026 Homo sapiens Tumor necrosis factor receptor superfamily member EDAR Proteins 0.000 description 1
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 102100039065 Interleukin-1 beta Human genes 0.000 description 1
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- 102100020679 Krueppel-like factor 6 Human genes 0.000 description 1
- 102100022699 Lymphoid enhancer-binding factor 1 Human genes 0.000 description 1
- 102100040406 Lysophosphatidic acid receptor 6 Human genes 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 102100037258 Membrane-associated transporter protein Human genes 0.000 description 1
- 102000013760 Microphthalmia-Associated Transcription Factor Human genes 0.000 description 1
- 108010050345 Microphthalmia-Associated Transcription Factor Proteins 0.000 description 1
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 1
- 102100034574 P protein Human genes 0.000 description 1
- 102100035842 Prostaglandin E2 receptor EP1 subtype Human genes 0.000 description 1
- 102100038094 Protein-glutamine gamma-glutamyltransferase E Human genes 0.000 description 1
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 102100024261 Protocadherin alpha-4 Human genes 0.000 description 1
- 108091007563 SLC45A2 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000003568 TRPV3 Human genes 0.000 description 1
- 102100038808 Transcription factor SOX-10 Human genes 0.000 description 1
- 102100030247 Transcription factor SOX-21 Human genes 0.000 description 1
- 101150043371 Trpv3 gene Proteins 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102100030810 Tumor necrosis factor receptor superfamily member EDAR Human genes 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 102000055102 bcl-2-Associated X Human genes 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000032341 cell morphogenesis Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- FHCMNWPYOVQOAO-UHFFFAOYSA-N dihydroxymethoxymethanediol Chemical compound OC(O)OC(O)O FHCMNWPYOVQOAO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000034756 hair follicle development Effects 0.000 description 1
- 230000003661 hair follicle regeneration Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- 229960004705 kojic acid Drugs 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 108010091287 palmitoyl-glycyl-histidyl-lysine Proteins 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003658 preventing hair loss Effects 0.000 description 1
- 102000006581 rab27 GTP-Binding Proteins Human genes 0.000 description 1
- 108010033990 rab27 GTP-Binding Proteins Proteins 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/025—Explicitly spheroidal or spherical shape
-
- 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products 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
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/85—Polyesters
-
- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61Q19/04—Preparations for care of the skin for chemically tanning the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/12—Preparations containing hair conditioners
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses preparation and application of a microsphere completely loaded with palmitoyl blue copper peptide, belongs to the field of polypeptide preparations, and particularly relates to a microsphere loaded with palmitoyl blue copper peptide. The invention adopts polyvinyl alcohol as a water-soluble polymer to prepare a water-phase solution, adopts a polycaprolactone-based polymer as an oil-soluble polymer to prepare an oil-phase solution, and prepares a sample solution from palmitoyl blue copper peptide and absolute ethyl alcohol, and then prepares the loaded palmitoyl blue copper peptide microsphere from the water-phase solution, the oil-phase solution and the sample solution together, wherein the polycaprolactone-based polymer is polycaprolactone and block polycaprolactone, the block polycaprolactone is obtained by reacting a polyhydroxy compound with absolute cyclohexanolide, the polyhydroxy compound is prepared by reacting 2, 2-dihydroxypropionic acid with ethylene glycol bishydroxymethyl ether, and the loaded palmitoyl blue copper peptide microsphere prepared by the invention has better slow release effect and the effect of improving the melanin content under the common use of the polycaprolactone and the block polycaprolactone with specific use amount.
Description
Technical Field
The invention belongs to the field of polypeptide preparations, and particularly relates to preparation and application of a microsphere completely loaded with palmitoyl blue copper peptide.
Background
The amino acid sequence of the copper peptide is glycyl-L-histidyl-L-lysine, namely GHK, the small-molecule tripeptide can regulate copper ion concentration in cells, and tripeptide GHK in human blood plasma shows strong binding force with Cu 2+, and can form complex copper peptide GHK-Cu. Has effects of promoting wound healing, inhibiting inflammatory factor, promoting skin keratinocyte growth, promoting collagen synthesis, reducing photodamage, preventing alopecia, and promoting hair growth. Copper peptide is a high hydrophilic substance, most of the hydrophilic substance is insoluble in phospholipid according to the similar principle of skin compatibility, and cannot freely enter and exit cell membranes, so that the skin has limited permeation and transport capacity on the skin of the hydrophilic substance, and the bioavailability is low.
Studies have shown that GHK-Cu has poor biostability, and that when applied to wounds or damaged skin, only 0.05% to 0.15% of the GHK-Cu is absorbed, or CHK-Cu is injected into the cortex or to the wound margin, over 95% is rapidly cleared within 1 min. The half-life period of GHK-Cu is about 20min, and it is rapidly degraded and then metabolized. Thus, modification of structures to improve stability and permeability of polypeptides is a major direction of current research.
Palmitoyl blue copper peptide has the effect that the biological innovation of Zhejiang surge peptide introduces a lipophilic group palmitoyl group to carry out structural modification and reconstruction on a Lys side chain of GHK-Cu, so that a novel copper peptide Pal-GHK-Cu with a lipophilic group is successfully synthesized.
The conventional blue copper peptide has the mechanism of regulating cell proliferation and migration, reducing inflammation, promoting angiogenesis and promoting synthesis and regulation of certain proteins, is safe and low in allergy rate, and has potential application prospect in hair blackening treatment. Blue copper peptides have been shown to stimulate keratinocytes as growth factors for various differentiated cells. Studies show that GHK-Cu can stimulate in vitro hair follicle elongation, increase Bcl-2 protein expression in hair papilla cells, reduce Bax expression and promote cell proliferation. Researchers demonstrated that maintenance of GHK-Cu accelerates hair growth after human hair transplantation. Hair papilla cells are specific fibroblasts and are critical for hair follicle growth. The palmitoyl group is connected, so that short chain amino acid is protected, and the lipophilicity and stability of GHK-Cu are improved. Proved by researches, the palmitoyl blue copper peptide has better bioavailability, stability and application safety compared with the copper peptide. The dual characteristics of Pal-GHK show that the peptide has wide application prospect in skin cell research and great potential in strengthening extracellular matrix. In addition, the palmitoyl modified blue copper peptide not only has the conventional hair-growing capability, but also has the outstanding effects of blacking, white hair and the like by activating a tyrosinase signal channel. The scalp nourishing and blackening hair-generating composition has a composite effect for middle-aged and elderly people. No component has the effects at the same time. However, the ideal active ingredient needs to have not only specificity and pharmacological activity but also sufficient reach the target site to act. The effect of palmitoyl blue copper peptide alone is difficult to achieve.
The microsphere is a skeleton type microspherical entity formed by dissolving or dispersing an active substance in a high polymer material, and the particle size range of the microsphere is 1-250 mu m. The biodegradable polymer is used as a conveying carrier of the polypeptide, the polypeptide is embedded, the stability of the medicine can be improved, the toxic and side effects of the medicine on surrounding tissues and non-target tissue cells can be reduced in a targeted manner, and the like. In addition, the targeting of the microspheres can concentrate the active ingredients in a target area, control the release speed, prolong the action time and improve the curative effect. The microsphere has unique advantages as a novel carrier, has great development potential, and is one of hot spots for research on sustained and controlled release preparations in recent years. The palmitoyl blue copper peptide can be loaded in the microsphere, and can be endowed with more application scenes of medical appliances and cosmetics.
Numerous microsphere preparation patents are currently available, mostly for the loading of hydrophilic active ingredients, like water-soluble polypeptides, requiring a W/O/W system, complicated preparation process and limited encapsulation efficiency, CN111836654a discloses a polycaprolactone microsphere filler comprising vitamin C and a preparation method thereof, specifically comprising (a) preparing a dispersed phase by dissolving polycaprolactone in a first solvent and vitamin C in a second solvent, and then uniformly mixing the two solutions to prepare a single solution, (b) preparing an emulsion by mixing the dispersed phase with an aqueous solution (continuous phase) comprising a surfactant, (C) forming microspheres by extracting an organic solvent from the dispersed phase in the emulsion prepared in step (b) into the continuous phase and evaporating, and (d) recovering the microspheres from the continuous phase of step (C) to prepare polycaprolactone microspheres. Compared with a single emulsion method, the method is more complicated, particularly in the production process, and the encapsulation efficiency is lower than that of the single emulsion method. The burst release phenomenon can occur in the later period of the slow release process, which is unfavorable for the action of the encapsulating ingredient. CN118121719a discloses a medicine slow-release porous silica gel material, a preparation method and application thereof, the method is that porous microspheres are prepared, firstly, the microspheres are prepared by using a placeholder, then the placeholder is melted off, and finally, the microspheres are immersed in an aqueous solution to adsorb target polypeptide. The method has low loading rate, serious waste of valuable medicaments, more adsorption among the porous medicaments is under the action of Van der Waals force, and the release of the valuable medicaments is easy in the process of storing the medicaments, so that the storage challenge is very large. The initial entry of the porous loaded microspheres into the human body is likely to cause the drug burst phenomenon.
Disclosure of Invention
The invention aims to provide a preparation and application of a microsphere completely loaded with palmitoyl blue copper peptide, which has good stability, good loading effect, good encapsulation effect and good slow release effect.
The technical scheme adopted by the invention for achieving the purpose is as follows:
A preparation method of palmitoyl blue copper peptide-loaded microspheres comprises the following steps:
mixing a sample solution with an oil phase solution, adding a water phase solution, mixing to form emulsion, performing vacuum sealing treatment, and finally performing separation treatment to obtain palmitoyl blue copper peptide-loaded microspheres;
the sample solution contains palmitoyl blue copper peptide, the oil phase solution contains oil-soluble polymer, the oil-soluble polymer comprises at least 1 of polycaprolactone-based polymer, polylactic acid-based polymer, polyhydroxyalkanoate-based polymer and polyglycolide-lactide copolymer, and the polycaprolactone-based polymer comprises polycaprolactone and/or block polycaprolactone;
The block polycaprolactone has a polyhydroxy structure formed by 2, 2-dihydroxypropionic acid and ethylene glycol bishydroxymethyl ether, and a polycaprolactone structure. The block polycaprolactone has a branched chain structure, the polycaprolactone is of a linear structure, and in an optional range, the block polycaprolactone and the polycaprolactone are used as oil-soluble polymers, so that a coating site for palmitoyl blue copper peptide can be provided in the process of mutually crossing and winding, palmitoyl blue copper peptide can be better loaded, the stability of palmitoyl blue copper can be improved, and the toxic and side effects of palmitoyl blue copper on surrounding tissues and non-target tissue cells can be reduced in a targeted manner. The targeting property of the palmitoyl blue copper peptide-loaded microsphere can also enable the active ingredient to be concentrated in a target area, delay the release speed of palmitoyl blue copper peptide, prolong the action time and improve the curative effect, even if the release speed is slower, the palmitoyl blue copper peptide-loaded microsphere is better concentrated in the target area under the coating of the block polycaprolactone and the polycaprolactone, and the effect of the palmitoyl blue copper peptide-loaded microsphere is improved.
Preferably, the solvent of the sample solution is absolute ethanol, or the solvent of the oil phase solution is DCM, or the water phase solution contains water-soluble polymer and water.
More preferably, the content of palmitoyl blue copper peptide in the sample solution is 2-5000ppm, or the content of the oil-soluble polymer in the oil phase solution is 1-25wt%, or the water-soluble polymer comprises polyvinylpyrrolidone or polyvinyl alcohol, or the content of the water-soluble polymer in the aqueous phase solution is 0.1-1.2wt%.
Preferably, the volume ratio of the sample solution to the oil phase solution is 1:100-1:5, or the volume ratio of the sample solution to the aqueous phase solution is 1:1000-1:25.
Preferably, the oil-soluble polymer is a polycaprolactone-based polymer, including polycaprolactone and blocked polycaprolactone.
More preferably, the polycaprolactone and blocked polycaprolactone are used in an amount of 1:0.5 to 3 in the polycaprolactone-based polymer.
Preferably, in the process of mixing to form emulsion, homogenizing treatment is adopted to form emulsion, and vacuum sealing treatment is adopted to vacuumize for 2-6h by adopting a water pump.
Preferably, in the separation treatment, the product of the vacuum sealing treatment is subjected to filtration, centrifugation and freeze-drying treatment.
Preferably, the preparation of the palmitoyl blue copper peptide-loaded microsphere can also comprise the preparation of polyhydroxy compounds and the preparation of block polycaprolactone.
More preferably, in the preparation of the polyhydroxy compound, 2-dihydroxypropionic acid and ethylene glycol bis-hydroxymethyl ether are mixed, a catalyst, a water-carrying agent and a polymerization inhibitor are added for reaction for 6-24 hours at the temperature of 100-130 ℃, the reaction is adjusted to be neutral after the reaction is finished, and the polyhydroxy compound is obtained by washing with saturated sodium chloride solution and distilling under reduced pressure.
More preferably, in the preparation of the polyhydroxy compound, ethylene glycol bis-hydroxymethyl ether is used in an amount of 40 to 60% by weight of 2, 2-dihydroxypropionic acid.
More preferably, in the preparation of the polyhydroxy compound, the catalyst is cerium sulfate, and the catalyst is used in an amount of 0.5 to 3wt% of 2, 2-dihydroxypropionic acid.
More preferably, in the preparation of the polyhydroxy compound, the water-carrying agent is cyclohexane, and the use amount of the water-carrying agent is 80-120wt% of 2, 2-dihydroxypropionic acid.
More preferably, in the preparation of the polyhydroxy compound, the polymerization inhibitor is hydroquinone and the polymerization inhibitor is used in an amount of 1 to 3wt% of 2, 2-dihydroxypropionic acid.
More preferably, in the preparation of the block polycaprolactone, the polyhydroxy compound and the anhydrous polycaprolactone are mixed, the catalyst is added, the reaction is carried out for 10-48 hours at 100-130 ℃ under the nitrogen atmosphere, after the reaction is completed, the cooling is carried out, the dichloromethane is added, the glacial ethyl ether is then added, the precipitation is carried out, and the block polycaprolactone is obtained after filtration and drying.
More preferably, in the preparation of the blocked polycaprolactone, the polyhydroxy compound is used in an amount of 10 to 30% by weight of the anhydrous polycaprolactone.
More preferably, in the preparation of the block polycaprolactone, the catalyst is stannous octoate, and the catalyst is used in an amount of 0.2-2wt% of the anhydrous polycaprolactone.
More preferably, in the preparation of the block polycaprolactone, dichloromethane is used for dissolving the crude product, and glacial diethyl ether is used for precipitating and precipitating, and the dichloromethane and the glacial diethyl ether are used in proper amounts.
Preferably, in the preparation of the aqueous phase solution, the water-soluble polymer is added into water, and dissolved and cooled at 80-90 ℃ to obtain the aqueous phase solution.
More preferably, the water-soluble polymer comprises polyvinylpyrrolidone or polyvinyl alcohol in the preparation of the aqueous solution, and the content of the water-soluble polymer in the aqueous solution is 0.1 to 1.2wt%.
Preferably, in the preparation of the oil phase solution, the oil-soluble polymer is added into the oil phase solvent, and is dissolved by shaking to obtain the oil phase solution.
More preferably, in the preparation of the oil phase solution, the oil-soluble polymer includes at least 1 of a polycaprolactone-based polymer, a polylactic acid-based polymer, a polyhydroxyalkanoate-based polymer, and a polyglycolide-lactide copolymer.
More preferably, in the preparation of the oil phase solution, the oil phase solvent includes at least 1 of DCM, DMF and DMSO.
More preferably, the oil phase solution is prepared such that the oil soluble polymer is present in the oil phase solution in an amount of 1 to 25wt%.
More preferably, in the preparation of the oil phase solution, the polycaprolactone-based polymer comprises polycaprolactone and/or blocked polycaprolactone.
More preferably, in the preparation of the oil phase solution, the polycaprolactone and the blocked polycaprolactone are used in an amount of 1:0.5-3 in the polycaprolactone-based polymer.
Preferably, in the preparation of the sample solution, the sample is added into the sample solvent, and is dissolved by shaking to obtain the sample solution.
More preferably, in the preparation of the sample solution, the sample comprises palmitoyl blue copper peptide, the sample solvent comprises absolute ethyl alcohol, and the content of the sample in the sample solution is 2-5000ppm.
Preferably, in the preparation of the palmitoyl blue copper peptide-loaded microsphere, a sample solution and an oil phase solution are mixed, then an aqueous phase solution is added, and the mixture is homogenized to form a blue copper peptide emulsion, and the blue copper peptide-loaded microsphere is obtained through vacuum treatment for 2-6 hours after sealing, filtration, washing and freeze-drying.
More preferably, in the preparation of the palmitoyl blue copper peptide-loaded microsphere, the volume ratio of the sample solution to the oil phase solution is 1:100-1:5.
More preferably, in the preparation of the palmitoyl blue copper peptide-loaded microsphere, the volume ratio of the sample solution to the aqueous phase solution is 1:1000-1:25.
Preferably, sucrose polyoxypropylene ether can be added into the aqueous phase solution for preparing the invention, and the use amount of the sucrose polyoxypropylene ether is 0.5-4wt% of the water-soluble polymer. The invention can further use polyvinyl alcohol and sucrose polyoxypropylene ether together in aqueous phase solution, the polyvinyl alcohol and the sucrose polyoxypropylene ether can lead the palmitoyl blue copper peptide microsphere to be more reasonably coated in microsphere sites formed by polycaprolactone and block polycaprolactone, thereby slowing the release speed of palmitoyl blue copper peptide in the obtained palmitoyl blue copper peptide-carrying microsphere, but ensuring that palmitoyl blue copper peptide is better concentrated in a target area and improving the effect of palmitoyl blue copper peptide-carrying microsphere.
The invention discloses palmitoyl blue copper peptide-loaded microspheres prepared by the preparation method.
The invention discloses application of the palmitoyl blue copper peptide-loaded microsphere in preparing shampoo products and/or hair care products and/or scalp injection nourishing products and/or hair growth and hair loss prevention products and/or blackness products.
The invention adopts the polyvinyl alcohol as a water-soluble polymer to prepare a water-phase solution, adopts the polycaprolactone-based polymer as an oil-soluble polymer to prepare an oil-phase solution, and prepares the palmitoyl blue copper peptide-loaded microsphere by the water-phase solution, the oil-phase solution and the sample solution together, wherein the polycaprolactone-based polymer is polycaprolactone and block polycaprolactone, the block polycaprolactone is obtained by reacting a polyhydroxy compound and anhydrous cyclohexane, and the polyhydroxy compound is prepared by reacting 2, 2-dihydroxypropionic acid and ethylene glycol bishydroxymethyl ether, so that the palmitoyl blue copper peptide-loaded microsphere has better slow release effect and the effect of improving the melanin content under the common use of the polycaprolactone with specific use amount and the block polycaprolactone. Therefore, the invention is the preparation and application of the microsphere with the complete load of palmitoyl blue copper peptide, which has good stability, good loading effect, good encapsulation effect and good slow release effect.
Drawings
FIG. 1 is an electron microscope image of palmitoyl blue copper peptide-loaded microspheres.
FIG. 2 is a graph showing relative gene expression in hair papilla cells.
FIG. 3 is a graph showing relative gene expression of A375 cells.
FIG. 4 is a graph showing melanin content.
Fig. 5 is a graph of release rate.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The concept of the present application will be described with reference to the accompanying drawings. It should be noted that the following descriptions of the various concepts are only for making the content of the present application easier to understand, and are not meant to limit the scope of the present application, and at the same time, the embodiments of the present application and the features in the embodiments may be combined with each other without conflict. The application will be described in detail below with reference to the drawings in connection with embodiments.
Example 1 preparation method of palmitoyl blue copper peptide-loaded microspheres
And (3) preparing an aqueous phase solution, namely adding the water-soluble polymer into water, and dissolving and cooling at 85 ℃ to obtain the aqueous phase solution. The water-soluble polymer included polyvinyl alcohol, and the content of the water-soluble polymer in the aqueous phase solution was 0.6wt%.
The preparation of the oil phase solution comprises the steps of adding an oil-soluble polymer into an oil phase solvent, and oscillating and dissolving to obtain the oil phase solution. The oil-soluble polymer is a polycaprolactone-based polymer, and the polycaprolactone-based polymer is polycaprolactone. The oil phase solvent was DCM. The content of the oil-soluble polymer in the oil phase solution was 15wt%.
And (3) preparing a sample solution, namely adding the sample into a sample solvent, and oscillating for dissolving to obtain the sample solution. The sample is palmitoyl blue copper peptide, the sample solvent is absolute ethyl alcohol, and the content of the sample in the sample solution is 1000ppm.
And (3) preparing the palmitoyl blue copper peptide-loaded microspheres, namely mixing a sample solution with an oil phase solution, adding the water phase solution, homogenizing to form blue copper peptide emulsion, sealing, performing vacuum treatment for 4 hours, filtering, washing and freeze-drying to obtain the palmitoyl blue copper peptide-loaded microspheres. The volume ratio of the sample solution to the oil phase solution is 1:10, and the volume ratio of the sample solution to the water phase solution is 1:100.
Example 2 preparation method of palmitoyl blue copper peptide-loaded microspheres
The difference between this example and example 1 is that the oil-phase solution is prepared in which the oil-soluble polymer is a polycaprolactone-based polymer, the polycaprolactone-based polymer is a polycaprolactone and a block polycaprolactone, and the amount of polycaprolactone and block polycaprolactone used in the polycaprolactone-based polymer is 1:0.8.
The preparation of polyhydroxy compound includes mixing 2, 2-dihydroxypropionic acid and glycol bis-hydroxymethyl ether, adding catalyst, water carrying agent and polymerization inhibitor, reacting at 120 deg.c for 12 hr, regulating to neutrality, washing with saturated sodium chloride solution, and vacuum distilling to obtain polyhydroxy compound. The consumption of ethylene glycol bis-hydroxymethyl ether is 50wt% of 2, 2-dihydroxypropionic acid, the catalyst is cerium sulfate, the consumption of the catalyst is 1.5wt% of 2, 2-dihydroxypropionic acid, the water-carrying agent is cyclohexane, the consumption of the water-carrying agent is 100wt% of 2, 2-dihydroxypropionic acid, the polymerization inhibitor is hydroquinone, and the consumption of the polymerization inhibitor is 2wt% of 2, 2-dihydroxypropionic acid.
The preparation of the block polycaprolactone comprises the steps of mixing polyhydroxy compound and anhydrous cyclohexane, adding a catalyst, reacting for 24 hours at 120 ℃ under the nitrogen atmosphere, cooling after the reaction is finished, adding dichloromethane, adding glacial ethyl ether, precipitating, filtering, and drying to obtain the block polycaprolactone. The usage amount of the polyhydroxy compound is 20wt% of the anhydrous cyclohexane, the catalyst is stannous octoate, and the usage amount of the catalyst is 1.2wt% of the anhydrous cyclohexane. The dichloromethane is used to dissolve the crude product, the glacial ethyl ether is used to precipitate, and a proper amount of dichloromethane and glacial ethyl ether can be used.
Example 3 preparation method of palmitoyl blue copper peptide-loaded microspheres
This example differs from example 2 in that the oil phase solution is prepared in which the oil-soluble polymer is a polycaprolactone-based polymer and the polycaprolactone-based polymer is a polycaprolactone and the polycaprolactone-block, and the amount of polycaprolactone and polycaprolactone-block used is 1:2.4.
Example 4 preparation method of palmitoyl blue copper peptide-loaded microspheres
This example is different from example 3 in that a water phase solution is prepared, and sucrose polyoxypropylene ether is further added to the water phase solution, wherein the sucrose polyoxypropylene ether is used in an amount of 0.8wt% of the water-soluble polymer.
Example 5 preparation method of palmitoyl blue copper peptide-loaded microsphere
This example differs from example 4 in the preparation of an aqueous phase solution to which sucrose polyoxypropylene ether was also added, the sucrose polyoxypropylene ether being used in an amount of 3.2% by weight of the water-soluble polymer.
Comparative example 1 preparation method of palmitoyl blue copper peptide-loaded microsphere
This example differs from example 1 in that the oil phase solution was prepared in which the oil-soluble polymer was a polycaprolactone-based polymer, which was a block polycaprolactone, and the block polycaprolactone was synthesized as in example 2.
Comparative example 2 preparation method of palmitoyl blue copper peptide-loaded microsphere
The difference between this example and example 2 is that the oil-soluble polymer is a polycaprolactone-based polymer, the polycaprolactone-based polymer is a polycaprolactone and a block polycaprolactone, and the amount of polycaprolactone and block polycaprolactone used in the polycaprolactone-based polymer is 1:0.3.
The specific proportion has good effect
Comparative example 3 preparation method of palmitoyl blue copper peptide-loaded microsphere
This example differs from example 2 in that the oil phase solution is prepared in which the oil-soluble polymer is a polycaprolactone-based polymer and the polycaprolactone-based polymer is a polycaprolactone and the polycaprolactone-block, and the amount of polycaprolactone and polycaprolactone-block used is 1:3.5.
Test example:
The invention carries out electron microscope characterization on the palmitoyl blue copper peptide-loaded microsphere prepared in the embodiment 1, and the result is shown in figure 1, and the particle size of the palmitoyl blue copper peptide-loaded microsphere prepared by the method in the embodiment 1 is 10-50 mu m.
1. Regulation and control test of anti-drop hair-fixing gene
The influence of palmitoyl blue copper peptide microspheres on the expression of the hair papilla cell anti-hair loss and hair fixation related genes is analyzed by utilizing a Luminex200 suspension chip multiple detection system technology and combining QGP methods.
The experiment used papilla cells plated in 24 well plates at a density of 6 x10 4 cells per well, 0.5 mL per well volume. Cell well plates were cultured in an incubator 24 h. The experiment is divided into a negative control and a sample group, wherein each group comprises 3 compound holes, and the sample group is the palmitoyl blue copper peptide-loaded microsphere prepared in the example 1.
The invention detects the effect of palmitoyl blue copper peptide-loaded microspheres prepared in the embodiment 1 on the expression of 25 genes in hair papilla cells, wherein the 2 genes are FGF7、VEGFA、LPAR6、EDAR、IGF1、ITGA6、KRT75、FOXL2、VDR、SOX21、WNT4、BMP3、COL17A1、TGM3、TGFB1、DKK1、IL6、AR、TRPV3、SRD5A2、TNF、ESR1、ACE2、TBP、HPRT1, respectively, have promotion effect on the expression of FGF7, IGF1, KRT75, VDR, COL17A1 and other genes, and can down regulate the relative expression quantity of DKK1 and IL6 genes. As shown in FIG. 2, NC is a negative control group, and the sample is palmitoyl blue copper peptide-loaded microsphere prepared in example 1, compared with the negative control group, the sample group can significantly up-regulate relative expression amounts of FGF7, IGF1, FOXL2, WNT4 and BMP3 genes (p < 0.01), and can significantly down-regulate relative expression amounts of DKK1 and IL6 genes (p < 0.01). The result shows that the palmitoyl blue copper peptide-loaded microsphere prepared by the invention has an adjusting effect on partial anti-hair loss and hair fixing genes.
According to current studies, FGF7 is a member of the Fibroblast Growth Factor (FGF) family. FGF family members are involved in a variety of biological processes such as embryonic development, cell growth, morphogenesis, and tissue repair. FGF7 has an important role in wound re-epithelialization, hair development, and early lung organogenesis. Dickkopf related protein (DKKI) is an important antagonist of the Wnt signaling pathway, which plays an important regulatory role in hair follicle development and regeneration. When DKK1 is continuously over-expressed during embryo development, hair follicles cannot be generated, and when DKK1 is over-expressed after birth, the growth of the hair follicles is inhibited. In addition, interleukins (ILs) include IL-1a, IL-1B, IL-6, etc., which exert effects on the extracellular matrix of dermal papilla and intracellular cAMP levels that regulate hair follicle growth. ILs stimulation causes hair follicle malnutrition in anagen phase such as deformation and shrinkage of hair papilla, abnormal cavitation of hair matrix cells and abnormal keratosis of hair bulb, and can inhibit hair follicle and hair growth.
2. Test of blackening promoting Gene
The influence of palmitoyl blue copper peptide-loaded microspheres prepared in example 1 on the gene expression in melanoma cells A375 is analyzed by adopting QGP method of Luminex200 suspension chip multiplex detection system.
The present invention uses a375 cells plated in 24 well plates at a density of 6 x 10 4 cells per well, 0.5 mL per well volume. Cell well plates were cultured in an incubator 24 h. The experiment is divided into a negative control and a sample group, wherein each group comprises 3 compound holes, and the sample group is the palmitoyl blue copper peptide-loaded microsphere prepared in the example 1.
The study totally detects the expression of 36 genes, wherein 36 genes are PTGS2、PTGER1、CREB1、ASIP、EDN3、COMMD3、MET、MCIR、HGF、DCT、F2RL1、OCA2、IL1RN、KIT、NQO1、HPRT1、TP53、CNR1、LEF1、MITF、RAB27A、PMEL、TNF、SLC45A2、IL1A、KLF6、TBP、CPX3、DSG1、LICAM、TYR、POMC、SOX10、TYRP1、TGFB1、CDSN, respectively, and the palmitoyl blue copper peptide-loaded microsphere prepared in the embodiment 1 has a regulating effect on related genes such as TYP, KIT, POMC, PMEL, OCA2, PTGS2, IL1A and the like in melanoma cells A375. As shown in FIG. 3, NC is a negative control group, and the sample is the palmitoyl blue copper peptide-loaded microsphere prepared in example 1, and compared with the negative control group, the palmitoyl blue copper peptide-loaded microsphere prepared in example 1 can significantly up-regulate the relative expression amount of DCT and POMC genes (P < 0.01), the relative expression amount of EDN3 and TYR genes (P < 0.05), and can significantly reduce the relative expression amount of IL1A genes (P < 0.01). The result shows that the palmitoyl blue copper peptide-loaded microsphere prepared by the invention can regulate the expression quantity of different related genes in melanoma cells A375.
In conclusion, the palmitoyl blue copper peptide-loaded microsphere prepared by the invention can change the intracellular gene expression level when being used for treating melanoma cells A375, and has promotion and inhibition effects on melanin synthesis related genes such as DCT, tyrosinase activity related genes such as TYP and other related genes.
3. Melanin content test
The invention explores the influence of palmitoyl blue copper peptide-loaded microspheres on the content of melanin in cells through human melanoma cells A375.
The experiment is divided into a negative control group, a positive control group and a sample group, wherein the negative control group is a complete DMEM medium without any treatment, the positive control group is a complete DMEM medium containing 1mg/mL kojic acid, and the sample group is a complete DMEM medium containing palmitoyl blue copper peptide microspheres prepared in examples 1-5 or comparative examples 1-3.
After the palmitoyl blue copper peptide-loaded microspheres are applied to human melanoma cells A375, the content of melanin in the human melanoma cells A375 is shown as a figure 4, wherein NC is a negative control group, PC is a positive control group, S1 is example 1, S2 is example 2, S3 is example 3, S4 is example 4, S5 is example 5, D1 is comparative example 1, D2 is comparative example 2, D3 is comparative example 3, and compared with the NC group, the content of melanin in the human melanoma cells A375 treated by the palmitoyl blue copper peptide-loaded microspheres of example 1 is obviously increased, so that the content of melanin in the human melanoma cells A375 is obviously increased, and the content of melanin in the human melanoma cells A375 in the PC group is greatly reduced, compared with example 1, the prepared palmitoyl blue peptide-loaded microspheres have the effect of improving the content of polycaprolactone and the polycaprolactone in the polycaprolactone group, and the polycaprolactone in the polycaprolactone group is better than that the polycaprolactone group is used in the polycaprolactone group, and the polycaprolactone group is 3 is used, and the polycaprolactone-containing the polycaprolactone-3 is used singly, and the effect of the polycaprolactone-based on the polycaprolactone-3 is better than the effect of the polycaprolactone-based on the polycaprolactone-A-3. Examples 4 to 5 compared with example 3 show that when preparing the palmitoyl blue copper peptide-loaded microspheres, sucrose polyoxypropylene ether can be added when polyvinyl alcohol exists in the aqueous phase solution, and after the palmitoyl blue copper peptide-loaded microspheres are prepared by the oil phase solution and the sample solution together with the polyvinyl alcohol and the sucrose polyoxypropylene ether, the content of melanin in human melanoma cells A375 can be further improved, and the performance of the palmitoyl blue copper peptide-loaded microspheres can be improved by the joint use of the polyvinyl alcohol and the sucrose polyoxypropylene ether.
4. Release Effect test of palmitoyl blue copper peptide
The test sample in the experiment is the palmitoyl blue copper peptide-loaded microsphere prepared in the examples 1-5 or the comparative examples 1-4, 0.2 g of the test sample is accurately weighed, placed in a 15mL centrifuge tube containing 9.8gPSB of solution, sealed and placed in a shaking incubator for constant-temperature shaking at 37 ℃ and 150 r/min. And (3) centrifugally sampling for 5mL hours, and detecting the polypeptide content in the sample by utilizing high performance liquid chromatography. The release rate of the palmitoyl blue copper peptide-loaded microspheres was calculated.
The test results of the release of the palmitoyl blue copper peptide are shown in fig. 5, wherein S1 is example 1, S2 is example 2, S3 is example 3, S4 is example 4, S5 is example 5, D1 is comparative example 1, D2 is comparative example 2, D3 is comparative example 3, and examples 2-3 are compared with example 1, and show that the prepared palmitoyl blue copper peptide-loaded microsphere has higher slow release effect when polycaprolactone and block polycaprolactone are jointly adopted as oil-soluble polymers, and the increase of the ratio of the block polycaprolactone and the slow release effect of the palmitoyl blue copper peptide-loaded microsphere can be improved when the polycaprolactone and the block polycaprolactone are used, and examples 1-3 are compared with comparative examples 1-3, and are superior to the use of polycaprolactone or the block polycaprolactone alone, and the use amount of polycaprolactone and the block polycaprolactone satisfy the specific proportion relationship and only have the effect of improving the slow release effect of the palmitoyl blue peptide-loaded microsphere. Examples 4 to 5 compared with example 3 show that when the palmitoyl blue copper peptide-loaded microspheres are prepared, sucrose polyoxypropylene ether can be added when polyvinyl alcohol exists in the aqueous phase solution, and after the palmitoyl blue copper peptide-loaded microspheres are prepared by the combination of the polyvinyl alcohol and the sucrose polyoxypropylene ether and the oil phase solution and the sample solution, the slow release effect of the palmitoyl blue copper peptide-loaded microspheres can be further improved, and the use of the polyvinyl alcohol and the sucrose polyoxypropylene ether can also improve the slow release performance of the palmitoyl blue copper peptide-loaded microspheres.
The above examples and/or embodiments are merely for illustrating the preferred embodiments and/or implementations of the present technology, and are not intended to limit the embodiments and implementations of the present technology in any way, and any person skilled in the art should be able to make some changes or modifications to the embodiments and/or implementations without departing from the scope of the technical means disclosed in the present disclosure, and it should be considered that the embodiments and implementations are substantially the same as the present technology.
The principles and embodiments of the present application have been described herein with reference to specific examples, the description of which is intended only to facilitate an understanding of the method of the present application and its core ideas. The foregoing is merely illustrative of the preferred embodiments of the application, and it will be appreciated that numerous modifications, adaptations and variations of the application can be made by those skilled in the art without departing from the principles of the application, and that other features and advantages of the application can be combined in any suitable manner, and that no improvement in the design or design of the application is intended to be applied directly to other applications.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411847006.2A CN119280077B (en) | 2024-12-16 | 2024-12-16 | Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411847006.2A CN119280077B (en) | 2024-12-16 | 2024-12-16 | Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN119280077A CN119280077A (en) | 2025-01-10 |
| CN119280077B true CN119280077B (en) | 2025-04-04 |
Family
ID=94169133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411847006.2A Active CN119280077B (en) | 2024-12-16 | 2024-12-16 | Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN119280077B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429876A (en) * | 2011-12-14 | 2012-05-02 | 深圳翰宇药业股份有限公司 | Liraglutide sustained-release microsphere preparation and preparation method thereof |
| CN111886031A (en) * | 2018-01-10 | 2020-11-03 | G2G生物公司 | Collagen peptide-containing polycaprolactone microsphere filler and preparation method thereof |
| CN116554449A (en) * | 2023-05-16 | 2023-08-08 | 华东理工大学 | A preparation method of absorbable block copolymer microspheres with controllable segment structure |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070224150A1 (en) * | 2005-03-24 | 2007-09-27 | Yongji Chung | Growth factor for hair and skin treatment |
| CN118078674B (en) * | 2024-04-24 | 2024-07-09 | 杭州湃肽生化科技有限公司 | Liposome encapsulating blue copper peptide or its composition and its use in hair growth |
-
2024
- 2024-12-16 CN CN202411847006.2A patent/CN119280077B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429876A (en) * | 2011-12-14 | 2012-05-02 | 深圳翰宇药业股份有限公司 | Liraglutide sustained-release microsphere preparation and preparation method thereof |
| CN111886031A (en) * | 2018-01-10 | 2020-11-03 | G2G生物公司 | Collagen peptide-containing polycaprolactone microsphere filler and preparation method thereof |
| CN116554449A (en) * | 2023-05-16 | 2023-08-08 | 华东理工大学 | A preparation method of absorbable block copolymer microspheres with controllable segment structure |
Also Published As
| Publication number | Publication date |
|---|---|
| CN119280077A (en) | 2025-01-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2015343845B2 (en) | Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement | |
| US9114094B2 (en) | Method of use and preparation of HSA fusion protein composition for skincare | |
| WO2013142192A1 (en) | Methods and compositions for regenerating and repairing damaged tissue using nonviable irradiated or lyophilized pluripotent stem cells | |
| JPH0661262B2 (en) | Method of stimulating cell proliferation | |
| EP3744347A1 (en) | Composition for skin diseases treatment use | |
| CN117679395B (en) | A polypeptide-coated quercetin molecular capsule and preparation method thereof | |
| JP3159419B2 (en) | Cosmetics | |
| EP3888625A1 (en) | Composition for scalp and hair | |
| WO2007107856A1 (en) | Magnolia champaca oil, its process of preparation and compositions comprising it | |
| Kay et al. | Enhancement of human lymphocyte natural killing function by non-opioid fragments of β-endorphin | |
| CN119280077B (en) | Preparation and application of microspheres fully loaded with palmitoyl blue copper peptide | |
| CN114931516A (en) | Emulsion containing nitric oxide liposome and preparation method thereof | |
| CN115025054A (en) | Preparation method of nano composition with lactoferrin as carrier | |
| JPWO2004024185A1 (en) | Pharmaceutical or cosmetic | |
| CN118078674A (en) | Liposome encapsulating blue copper peptide or composition thereof and use thereof in hair growth | |
| KR102775224B1 (en) | Method for producing lactoferrin derivative having functions such as antioxidant, whitening, anti-inflammatory and skin protection, and skin treatment ointment and cosmetic composition comprising the same | |
| JP3117823B2 (en) | Collagen metabolic activator | |
| JP2003519663A (en) | Use of Dictyotal extract in the manufacture of a topical pharmaceutical composition | |
| RU2847265C2 (en) | Tetrapeptide derivative, cosmetic composition or pharmaceutical composition and use thereof | |
| CN120137891B (en) | Stem cell exosomes and application thereof in preparation of anti-aging and beautifying cosmetics or drugs | |
| KR102824097B1 (en) | Nanoparticle comprising biotin, Manufacturing method thereof, and Use thereof | |
| EP4520341A1 (en) | Composition for wound treatment comprising stem cell-derived extracellular vesicles with enhanced efficacy | |
| JP2002541074A (en) | Use of vitamin C analogs for increasing the level of skin cell differentiation and / or proliferation | |
| CN119033915A (en) | A composition for promoting hair growth | |
| CN121800866A (en) | Double-target 5 alpha-reductase and adiponectin receptor cyclic peptide, application and preparation method |
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 |