CN118105341A - Smearing preparation system for treating androgenetic alopecia and preparation method thereof - Google Patents
Smearing preparation system for treating androgenetic alopecia and preparation method thereof Download PDFInfo
- Publication number
- CN118105341A CN118105341A CN202410227186.8A CN202410227186A CN118105341A CN 118105341 A CN118105341 A CN 118105341A CN 202410227186 A CN202410227186 A CN 202410227186A CN 118105341 A CN118105341 A CN 118105341A
- Authority
- CN
- China
- Prior art keywords
- choline
- ionic liquid
- geranic acid
- acid ionic
- 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.)
- Pending
Links
- 201000004384 Alopecia Diseases 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 42
- 201000002996 androgenic alopecia Diseases 0.000 title claims abstract description 29
- 206010068168 androgenetic alopecia Diseases 0.000 title claims abstract description 19
- 239000002608 ionic liquid Substances 0.000 claims abstract description 104
- 239000003814 drug Substances 0.000 claims abstract description 38
- 239000004480 active ingredient Substances 0.000 claims abstract description 23
- 150000008442 polyphenolic compounds Chemical class 0.000 claims abstract description 23
- 235000013824 polyphenols Nutrition 0.000 claims abstract description 23
- 231100000360 alopecia Toxicity 0.000 claims abstract description 18
- 230000002280 anti-androgenic effect Effects 0.000 claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 239000000051 antiandrogen Substances 0.000 claims abstract description 10
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 29
- 229960003632 minoxidil Drugs 0.000 claims description 27
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims description 24
- 239000004530 micro-emulsion Substances 0.000 claims description 21
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 16
- 238000009472 formulation Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 15
- 229960001231 choline Drugs 0.000 claims description 13
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 13
- ZHYZQXUYZJNEHD-VQHVLOKHSA-N geranic acid Chemical compound CC(C)=CCC\C(C)=C\C(O)=O ZHYZQXUYZJNEHD-VQHVLOKHSA-N 0.000 claims description 13
- 229930008392 geranic acid Natural products 0.000 claims description 13
- 238000010438 heat treatment Methods 0.000 claims description 13
- ZHYZQXUYZJNEHD-UHFFFAOYSA-N trans-geranic acid Natural products CC(C)=CCCC(C)=CC(O)=O ZHYZQXUYZJNEHD-UHFFFAOYSA-N 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 13
- 239000012498 ultrapure water Substances 0.000 claims description 13
- XMOCLSLCDHWDHP-IUODEOHRSA-N epi-Gallocatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-IUODEOHRSA-N 0.000 claims description 12
- 239000002502 liposome Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 238000010025 steaming Methods 0.000 claims description 9
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 8
- XMOCLSLCDHWDHP-UHFFFAOYSA-N L-Epigallocatechin Natural products OC1CC2=C(O)C=C(O)C=C2OC1C1=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-UHFFFAOYSA-N 0.000 claims description 8
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 8
- 235000012000 cholesterol Nutrition 0.000 claims description 8
- DZYNKLUGCOSVKS-UHFFFAOYSA-N epigallocatechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3cc(O)c(O)c(O)c3 DZYNKLUGCOSVKS-UHFFFAOYSA-N 0.000 claims description 8
- LVJJFMLUMNSUFN-UHFFFAOYSA-N gallocatechin gallate Natural products C1=C(O)C=C2OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C1OC(=O)C1=CC(O)=C(O)C(O)=C1 LVJJFMLUMNSUFN-UHFFFAOYSA-N 0.000 claims description 8
- 229940067606 lecithin Drugs 0.000 claims description 8
- 239000000787 lecithin Substances 0.000 claims description 8
- 235000010445 lecithin Nutrition 0.000 claims description 8
- 229940030275 epigallocatechin gallate Drugs 0.000 claims description 6
- XMOCLSLCDHWDHP-SWLSCSKDSA-N (+)-Epigallocatechin Natural products C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-SWLSCSKDSA-N 0.000 claims description 4
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims description 4
- LSHVYAFMTMFKBA-PZJWPPBQSA-N (+)-catechin-3-O-gallate Chemical compound O([C@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-PZJWPPBQSA-N 0.000 claims description 4
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 claims description 4
- WMBWREPUVVBILR-GHTZIAJQSA-N (+)-gallocatechin gallate Chemical compound O([C@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-GHTZIAJQSA-N 0.000 claims description 4
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 claims description 4
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 claims description 4
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 4
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims description 4
- LSHVYAFMTMFKBA-UHFFFAOYSA-N ECG Natural products C=1C=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-UHFFFAOYSA-N 0.000 claims description 4
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 4
- 239000001263 FEMA 3042 Substances 0.000 claims description 4
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 4
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims description 4
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 4
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000005487 catechin Nutrition 0.000 claims description 4
- 229950001002 cianidanol Drugs 0.000 claims description 4
- 239000011248 coating agent Substances 0.000 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 claims description 4
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 claims description 4
- 229960004845 drospirenone Drugs 0.000 claims description 4
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 claims description 4
- 235000012734 epicatechin Nutrition 0.000 claims description 4
- 229960002568 ethinylestradiol Drugs 0.000 claims description 4
- 229960004039 finasteride Drugs 0.000 claims description 4
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 4
- 229960001285 quercetin Drugs 0.000 claims description 4
- 235000005875 quercetin Nutrition 0.000 claims description 4
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 claims description 4
- 229960002256 spironolactone Drugs 0.000 claims description 4
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims description 4
- 229940033123 tannic acid Drugs 0.000 claims description 4
- 235000015523 tannic acid Nutrition 0.000 claims description 4
- 229920002258 tannic acid Polymers 0.000 claims description 4
- DQKGOGJIOHUEGK-UHFFFAOYSA-M hydron;2-hydroxyethyl(trimethyl)azanium;carbonate Chemical group OC([O-])=O.C[N+](C)(C)CCO DQKGOGJIOHUEGK-UHFFFAOYSA-M 0.000 claims description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims description 2
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims description 2
- 235000019743 Choline chloride Nutrition 0.000 claims description 2
- 229960003178 choline chloride Drugs 0.000 claims description 2
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims description 2
- 229940075419 choline hydroxide Drugs 0.000 claims description 2
- DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 claims description 2
- 229960003843 cyproterone Drugs 0.000 claims description 2
- 230000000887 hydrating effect Effects 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 abstract description 15
- 210000003780 hair follicle Anatomy 0.000 abstract description 13
- 230000036542 oxidative stress Effects 0.000 abstract description 5
- 230000001737 promoting effect Effects 0.000 abstract description 5
- 230000003660 hair regeneration Effects 0.000 abstract description 4
- 230000004888 barrier function Effects 0.000 abstract description 3
- 210000000434 stratum corneum Anatomy 0.000 abstract description 3
- 230000007812 deficiency Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 58
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 20
- 230000035617 depilation Effects 0.000 description 18
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 16
- 229960001712 testosterone propionate Drugs 0.000 description 16
- 230000002354 daily effect Effects 0.000 description 14
- 210000004209 hair Anatomy 0.000 description 13
- 239000011259 mixed solution Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 10
- 229960000304 folic acid Drugs 0.000 description 10
- 235000019152 folic acid Nutrition 0.000 description 10
- 239000011724 folic acid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000011543 agarose gel Substances 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- VBVAVBCYMYWNOU-UHFFFAOYSA-N coumarin 6 Chemical compound C1=CC=C2SC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 VBVAVBCYMYWNOU-UHFFFAOYSA-N 0.000 description 5
- 238000009792 diffusion process Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- 230000003698 anagen phase Effects 0.000 description 4
- 239000003098 androgen Substances 0.000 description 4
- 208000024963 hair loss Diseases 0.000 description 4
- 230000003676 hair loss Effects 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 230000001172 regenerating effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 2
- 229960001842 estramustine Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000003659 hair regrowth Effects 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000012764 semi-quantitative analysis Methods 0.000 description 2
- 230000003797 telogen phase Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000003778 catagen phase Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002951 depilatory effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 230000031774 hair cycle Effects 0.000 description 1
- 230000009583 hair follicle growth Effects 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 230000003662 hair growth rate Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a smearing preparation system for treating androgenetic alopecia and a preparation method thereof, belonging to the technical field of medicines. The smearing preparation system of the invention is a carrier based on choline-geranic acid ionic liquid and is loaded with an anti-androgenetic alopecia medicine and polyphenol active ingredients. The smearing preparation system can effectively help the medicine to pass through the stratum corneum barrier of the skin, prolong the residence time of the medicine on the skin, reduce the administration frequency and the administration dosage and improve the compliance of patients. The invention loads the antiandrogen alopecia medicine and polyphenol active ingredients in the carrier based on choline-geranic acid ionic liquid, effectively regulates the microenvironment around the hair follicle, simultaneously regulates and controls the oxidative stress and the vascularization deficiency around the hair follicle, plays a role in promoting hair regeneration, and provides a new strategy for developing a novel smearing preparation for treating androgenetic alopecia.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a smearing preparation system for treating androgenetic alopecia and a preparation method thereof, in particular to a smearing preparation system taking choline-geranic acid ionic liquid as a carrier and simultaneously loading antiandrogenic alopecia medicines and polyphenol active ingredients and a preparation method thereof.
Background
Alopecia is a skin condition characterized by excessive or abnormal hair loss and a reduction in the number of hairs. Androgenetic alopecia (Androgenetic alopecia, AGA) is the most common chronic alopecia disorder among all types of alopecia. Over 50% of people worldwide have trouble with hair loss, and the prevalence of hair loss increases with age. AGA is a clinical manifestation of sub-health, and although it does not endanger life, the appearance change caused by hair loss can add serious psychological burden to the patient, reducing the quality of life. In general, healthy hair growth follows a continuous cycle, including anagen, catagen and telogen, during which the number of hairs remains dynamically balanced. However, excessive androgens interfere with the hair growth cycle by reducing the duration of the anagen phase and extending the stationary phase. AGA causes complex and perifollicular microenvironment disorders are a major cause. In addition, AGA patients exhibit defects in angiogenesis, and Vascular Endothelial Growth Factor (VEGF) expression is reduced, and VEGF is a key factor in promoting vascular endothelial cell proliferation and increasing vascular permeability. Thus, there is insufficient nutrient delivery to the hair follicle to meet the need for continued hair follicle growth, thereby limiting the passage of hair follicles from telogen to anagen.
Common treatment means for AGA include oral medication, topical treatment, surgical hair implantation, and the like. Among them, topical treatment is a non-invasive means of administration that has good patient compliance and reduces systemic adverse effects compared to oral administration. Minoxidil is the only FDA approved external preparation for the treatment of AGA. It plays an important role in vasodilation, distending vascular smooth muscle and increasing vascular endothelial growth factor expression in a dose-dependent manner. Regulation of vascularization by minoxidil stimulates proliferation and differentiation of hair follicle epithelial cells, which younger the atrophic hair follicle. Thus, minoxidil can extend the duration of the anagen phase, thereby promoting hair regrowth. However, the therapeutic effect of minoxidil alone is not ideal for some patients. The polyphenol active ingredient has good antioxidant activity, can effectively reduce the active oxygen level, and can inhibit the apoptosis induced by active oxygen. Considering the pathogenesis of AGA, combining an anti-androgenic alopecia drug with a polyphenol based active ingredient is thought to achieve a better therapeutic effect for androgenic alopecia.
The problem of low transdermal permeability of the currently clinically used smearing preparation for treating androgenetic alopecia is not ignored. This results in frequent dosing and low bioavailability with limited therapeutic efficacy. In recent years, ionic liquids have been attracting attention in transdermal drug delivery, solving the challenges of drug local delivery. It can overcome the barrier of horny layer, and can raise transdermal transcell transport and paracellular transport and increase transdermal permeation of medicine by destroying cell integrity, fluidization, establishing diffusion channel and extracting lipid component from horny layer. Therefore, transdermal application of ionic liquids is expected to achieve treatment of alopecia.
Disclosure of Invention
The invention aims to provide a smearing preparation system for treating androgenetic alopecia and a preparation method thereof. The smearing preparation system is used for cooperatively delivering the anti-androgenic alopecia medicine and the polyphenol active ingredients through a carrier based on choline-geranic acid ionic liquid. The smearing preparation system can simultaneously regulate oxidative stress and insufficient vascularization to remodel the microenvironment around the hair follicle, thereby promoting hair regeneration and providing a safe and efficient treatment means for AGA treatment.
According to a first aspect of the present invention there is provided a spread formulation system which is a choline-geranic acid ionic liquid based carrier, the spread formulation system being loaded with an anti-androgenic alopecia drug and a polyphenol based active ingredient.
Preferably, the carrier based on the choline-geranic acid ionic liquid is choline-geranic acid ionic liquid solution, choline-geranic acid ionic liquid self-microemulsion or choline-geranic acid ionic liquid liposome.
Preferably, the choline in the choline-geranyl ionic liquid-based carrier is choline bicarbonate, choline hydroxide, or choline chloride.
Preferably, the ratio of the amounts of choline and geranic acid species in the choline-geranic acid ionic liquid based carrier is 1: (1-2).
Preferably, the choline-geranic acid ionic liquid solution comprises 20-60 parts by volume of choline-geranic acid ionic liquid and 40-80 parts by volume of absolute ethyl alcohol;
The choline-geranic acid ionic liquid self-microemulsion comprises 10-20 parts by volume of choline-geranic acid ionic liquid, 10-80 parts by volume of ultrapure water and 10-80 parts by volume of absolute ethyl alcohol.
The choline-geranic acid ionic liquid liposome comprises 30-50 parts by mass of choline-geranic acid ionic liquid, 42-58 parts by mass of lecithin and 8-12 parts by mass of cholesterol.
Preferably, the anti-androgenic alopecia drug is at least one of minoxidil, finasteride, estrol cyproterone, drospirenone, ethinyl estradiol, spironolactone, baritinib, li Texi tinib and pontine;
The polyphenols active ingredient is at least one of epigallocatechin gallate, catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, tannic acid, and quercetin.
According to another aspect of the present invention, there is provided a method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with absolute ethyl alcohol to obtain choline-geranic acid ionic liquid solution;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid solution obtained in the step (2), and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
According to another aspect of the present invention, there is provided a method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with ultrapure water and absolute ethyl alcohol to obtain choline-geranic acid ionic liquid self-microemulsion;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid obtained in the step (2) from the microemulsion, and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
According to another aspect of the present invention, there is provided a method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) And (3) performing ultrasonic film-removing on the choline-geranic acid ionic liquid, lecithin, cholesterol and the anti-androgenetic alopecia medicine obtained in the step (1) by using ultrapure water containing polyphenol active ingredients, and stirring and hydrating to obtain the choline-geranic acid ionic liquid liposome loaded with the anti-androgenetic alopecia medicine and the polyphenol active ingredients.
According to another aspect of the present invention there is provided the use of any one of the spread formulation systems for the manufacture of a medicament for the treatment of androgenic alopecia.
In general, compared with the prior art, the above technical solution conceived by the present invention mainly has the following technical advantages:
(1) The choline-geranic acid ionic liquid solution is prepared based on the choline-geranic acid ionic liquid, and the choline-geranic acid ionic liquid self-microemulsion and the choline-geranic acid ionic liquid liposome are innovatively used for treating androgenic alopecia, can effectively relieve oxidative stress and promote angiogenesis, and comprehensively improve microenvironment around hair follicles, so that hair regeneration is promoted.
(2) The coating preparation system provided by the invention has high maximum drug loading capacity, and can simultaneously load hydrophilic drugs and lipophilic drugs.
(3) The smearing preparation system provided by the invention does not need extra catalysts, initiators and the like in the preparation process, avoids the introduction of toxic substances, and has good biocompatibility; the preparation process is simple and efficient, the adopted instrument and equipment foundation is not required to be subjected to conditions such as high temperature and the like, the controllable degree is high, and the industrial mass production is easy.
(4) The smearing preparation system provided by the invention can effectively help the medicine to pass through the stratum corneum barrier of the skin, so that the medicine is efficiently delivered to hair follicles, and the residence time of the medicine in the skin is prolonged. Therefore, the application preparation system can realize lower administration frequency and administration dosage when in use, and has high patient compliance.
(5) The invention solves the problems from the pathogenesis of AGA, creatively and synergistically delivers the antiandrogen alopecia medicine and the polyphenol active ingredients, simultaneously regulates and controls oxidative stress and vascularization deficiency, comprehensively improves the microenvironment around the hair follicle, provides a solution for the problems of poor single medicine use effect and frequent recurrence in the current AGA treatment, and has clinical application value.
Drawings
FIG. 1 is a photograph showing the properties of choline-geranic acid ionic liquid obtained in example 1.
FIG. 2 is a photograph showing the properties of choline-geranic acid ionic liquid solutions obtained in example 2.
FIG. 3 is a photograph showing the properties of the choline-geranic acid ionic liquid self-microemulsion obtained in example 3, wherein the left side of the figure shows the choline-geranic acid ionic liquid self-microemulsion before being put into agarose gel, the right side of the figure shows the choline-geranic acid ionic liquid self-microemulsion after being put into agarose gel, and the microemulsion is formed.
FIG. 4 is an image of a laser scanning confocal microscope observing choline-geranic acid ionic liquid obtained according to example 3 before (left) and after (right) placement of the microemulsion into agarose gel.
FIG. 5 is a photograph showing the properties of choline-geranic acid ionic liquid liposome obtained in example 5.
FIGS. 6-7 are cytotoxicity evaluations of choline-geranic acid ionic liquid obtained according to example 1 on human hair papilla cells and human umbilical vein endothelial cells, respectively.
Fig. 8 shows the transdermal penetration of coumarin 6 in different formulations by laser scanning confocal microscopy.
FIG. 9 shows the residence of the choline-geranic acid ionic liquid solution obtained according to example 2 on the skin of mice.
Fig. 10 is a comparison of hair regrowth following various treatments in androgenetic alopecia model mice.
Fig. 11 is coverage of regenerated hair after various treatments in androgenic alopecia model mice.
FIGS. 12-13 are respectively a semi-quantitative analysis of DHE immunofluorescence staining results and DHE positive expression of skin tissue of the back of mice treated differently in androgen-derived alopecia model mice.
FIGS. 14-15 are, respectively, semi-quantitative analysis of CD31 immunohistochemical staining results and average vessel number of back skin tissue of mice treated differently in androgen-derived alopecia model mice.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.
The invention provides a preparation method of a smearing preparation system for treating androgenetic alopecia, which comprises the following steps:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with absolute ethyl alcohol to obtain choline-geranic acid ionic liquid solution;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid solution obtained in the step (2), and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
Preferably, the volume part of the choline-geranic acid ionic liquid is 20-60 parts, and the volume part of the absolute ethyl alcohol is 40-80 parts.
Preferably, the folic acid in the step (1) is purified folic acid obtained by mixing 60 parts by volume of folic acid with 40 parts by volume of acetone and then recrystallizing at-80 ℃ for at least 5 times.
Preferably, the temperature of the heating and stirring in the step (1) is 35-45 ℃; the drying temperature in the step (1) is 55-65 ℃, and the drying time is 48-72 h.
The invention also provides a preparation method of the smearing preparation system for treating androgenetic alopecia, which comprises the following steps:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with ultrapure water and absolute ethyl alcohol to obtain choline-geranic acid ionic liquid self-microemulsion;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid obtained in the step (2) from the microemulsion, and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
Preferably, the volume part of the choline-geranic acid ionic liquid is 10-20 parts, the volume part of the ultrapure water is 10-80 parts, and the volume part of the absolute ethyl alcohol is 10-80 parts.
Preferably, the folic acid in the step (1) is purified folic acid obtained by mixing 60 parts by volume of folic acid with 40 parts by volume of acetone and then recrystallizing at-80 ℃ for at least 5 times.
Preferably, the temperature of the heating and stirring in the step (1) is 35-45 ℃; the drying temperature in the step (1) is 55-65 ℃, and the drying time is 48-72 h.
The invention also provides a preparation method of the smearing preparation system for treating androgenetic alopecia, which comprises the following steps:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid, lecithin, cholesterol and the antiandrogen alopecia medicine spin membrane obtained in the step (1) are subjected to ultrasonic membrane removal by using ultrapure water containing polyphenol active ingredients, and stirred and hydrated to obtain the choline-geranic acid ionic liquid liposome loaded with the antiandrogen alopecia medicine and the polyphenol active ingredients.
Preferably, the choline-geranic acid ionic liquid is 30-50 parts by mass, the lecithin is 42-58 parts by mass, and the cholesterol is 8-12 parts by mass.
Preferably, the folic acid in the step (1) is purified folic acid obtained by mixing 60 parts by volume of folic acid with 40 parts by volume of acetone and then recrystallizing at-80 ℃ for at least 5 times.
Preferably, the temperature of the heating and stirring in the step (1) is 35-45 ℃; the drying temperature in the step (1) is 55-65 ℃, and the drying time is 48-72 h.
Preferably, the temperature of the spinning film in the step (2) is 40-45 ℃; the ultrasonic demolding time in the step (2) is 3-10 min; the hydration temperature in the step (2) is 40-45 ℃; the hydration time in the step (2) is 20-30 min.
The following are specific examples
Example 1
The choline-geranic acid ionic liquid is prepared in the embodiment, and the specific process comprises the following steps:
step one: 60 parts by volume of folic acid and 40 parts by volume of acetone are mixed and recrystallized at-80 ℃ for at least 5 times to remove impurities, so as to obtain purified geranic acid.
Step two: adding a choline bicarbonate solution (80%, w/w) into the purified geranic acid prepared in the step one, heating and stirring for 12h at 40 ℃, performing rotary evaporation for 2h at 60 ℃ to remove most of water, and then vacuum drying the obtained liquid at 60 ℃ for 72h to obtain the choline-geranic acid ionic liquid. As shown in fig. 1, the liquid was a pale yellow viscous liquid.
Example 2
The choline-geranic acid ionic liquid solution is prepared in the embodiment, and the specific process comprises the following steps:
Choline-geranic acid ionic liquid was prepared according to example 1, and was thoroughly mixed with absolute ethanol, wherein the volume ratio of choline-geranic acid ionic liquid to absolute ethanol was 1:4, to obtain choline-geranic acid ionic liquid solution (designated sCGIL). As shown in fig. 2, sCGIL is a colorless clear transparent solution.
Example 3
The choline-geranic acid ionic liquid self-microemulsion is prepared in the embodiment, and the specific process comprises the following steps:
Choline-geranic acid ionic liquid was prepared according to example 1, and choline-geranic acid ionic liquid, ultrapure water and absolute ethanol were thoroughly mixed, wherein the volume ratio of choline-geranic acid ionic liquid, ultrapure water and absolute ethanol was 10:50:40, to obtain choline-geranic acid ionic liquid self-microemulsion (designated eCGIL).
Example 4
ECGIL was prepared as in example 3 and placed in agarose gel (10 wt%) wells to examine its self-emulsifying properties. As shown in FIG. 3, eCGIL was a colorless clear transparent solution before being placed in the agarose gel wells, and turned to milky white after 20min of placement in the agarose gel wells. As shown in FIG. 4, eCGIL was placed in agarose gel wells to form a micron-sized emulsion, confirming that eCGIL was able to form self-microemulsions during administration with a diffusion rate of absolute ethyl alcohol in the skin greater than that of ultrapure water.
Example 5
Choline-geranic acid ionic liquid was prepared as in example 2, and choline-geranic acid ionic liquid, lecithin and cholesterol were spin-coated at 40 ℃ for 30min, wherein the mass ratio of choline-geranic acid ionic liquid, lecithin and cholesterol was 40:50:10. Then adding ultrapure water, performing ultrasonic film removal for 5min, and performing hydration stirring at 40 ℃ for 30min to obtain choline-geranic acid ionic liquid liposome (named lCGIL). As shown in fig. 5, lCGIL is a milky yellow solution.
Example 6
SCGIL was prepared as in example 2 and the safety of sCGIL on human papilla cells (DPC) and Human Umbilical Vein Endothelial Cells (HUVEC) was evaluated using a cytotoxicity assay. DPC and HUVEC were inoculated into 96-well plates at a density of 8×10 3/well, respectively. Cells were allowed to adhere by culturing in an incubator at 37℃with 5% CO 2 for 24h. And adding sCGIL of 1, 2, 5, 10, 20, 50, 100 and 200 mug/mL of the cells to the adherent cells for incubation for 24 hours, taking the DMEM cultured cells as a control example, and continuously placing the 96-well plates into an incubator for culture for 24 hours. mu.L of 5mg/mL MTT solution was added to each well in a clean bench, and the 96-well plate was further incubated in an incubator in the dark for 4 hours. The medium in the wells was removed, 150. Mu.L of DMSO solution was added to each well and incubated at 37℃for 10min on a shaking table to allow crystallization to develop well. The absorbance of each well in a 96-well plate was measured at 490nm using an enzyme-labeled instrument and the relative cell viability was calculated according to the following formula:
Wherein, the administration hole is a hole for inoculating cells and administering, the control hole is a hole for inoculating cells but not administering, and the blank hole is a hole for neither inoculating cells nor administering.
As shown in FIGS. 6 and 7, the cell viability of both DPC and HUVEC after treatment was greater than 85% and did not affect cell activity, confirming good cell compatibility with sCGIL prepared according to example 2.
Example 7
SCGIL was prepared as in example 2, eCGIL as in example 3, lCGIL as in example 5, and then equal amounts of coumarin 6 (C6) were added to give C6@sCGIL, C6@eCGIL, C6@lCGIL, respectively. The in vitro transdermal penetration experiment adopts a diffusion cell, and the effective diffusion area is 1.77cm 2. The pigskin is held between the feeding and receiving reservoirs with the cuticle facing the feeding reservoir. 17mL PBS buffer solution is added into the receiving tank, the water bath temperature of the diffusion tank is adjusted to be 32+/-1 ℃, and the rotating speed is 300rpm. To the donor pool were added 500. Mu.L of the Free coumarin 6 suspension (designated Free C6), C6@sCGIL, C6@eCGIL, C6@lCGIL, respectively, at a dark place. And sealing the upper end of the donor pool by using a sealing film, and placing the water for volatilization. After 24h of percutaneous infiltration, the pig skin was removed, the solution remaining on the surface of the pig skin was carefully washed and gently wiped dry with filter paper. The treated pigskin samples were frozen and stained with DAPI. The penetration of coumarin 6 into the skin was observed by laser scanning confocal, and the results are shown in fig. 8. The results show that the C6 fluorescence in Free C6 stays almost exclusively on the stratum corneum surface and hardly reaches the deep skin. And the C6 fluorescence in C6@sCGIL, C6@eCGIL and C6@lCGIL reaches the epidermis layer and the dermis layer, and shows good transdermal penetration promoting effect.
Example 8
SCGIL was prepared as in example 2, and the hydrophobic fluorescent dye DiR and the hydrophilic fluorescent dye ICG were added to sCGIL, respectively, to give DiR@sCGIL, ICG@sCGIL. C57BL/6 mice of 6-7 weeks old were selected, and after back dehairing, the Free DiR solution (named Free DiR, diR dose 0.75 mg/kg), diR@sCGIL (DiR dose 0.75 mg/kg), free ICG solution (named Free ICG, ICG dose 0.25 mg/kg) and ICG@sCGIL (ICG dose 0.25 mg/kg) were topically applied. Living fluorescence images of 12h, 24h, 48h, 72h, 96h and 120h after application were monitored using a near infrared small animal living imaging system. As a result, as shown in FIG. 9, the Free DiR showed almost no fluorescence signal after 24 hours, while the fluorescence signal in DiR@sCGIL remained at a high level for 96 hours. Free ICG solutions metabolize faster, the fluorescent signal level remains at a lower level, and this weaker fluorescent signal is barely detectable after 72 hours. Whereas the fluorescence signal of ICG in ICG@sCGIL was very strong up to 96 h. These results show that sCGIL can prolong the residence time of different drugs in skin, which is beneficial to the exertion of the drug effect.
Example 9
Evaluation of therapeutic efficacy of Choline-geranic acid ionic liquid solutions carrying minoxidil and epigallocatechin gallate on androgen-derived alopecia mice
SCGIL was prepared as in example 2, and minoxidil loading gave M@scGAL (minoxidil: 1 mg/20. Mu.L). sCGIL was prepared as in example 2 and EGCG loaded to give E@sCGIL (EGCG: 200. Mu.g/20. Mu.L). sCGIL was prepared as in example 2, and loading minoxidil and EGCG gave ME@sCGIL (minoxidil: 1 mg/20. Mu.L, EGCG: 200. Mu.g/20. Mu.L). In addition, minoxidil and EGCG were dissolved in PBS buffer (minoxidil: 1 mg/20. Mu.L, EGCG: 200. Mu.g/20. Mu.L), and free minoxidil and EGCG mixed solution (ME) was prepared.
C57BL/6 mice with the age of 6-7 weeks are selected, back hair is shaved by an electric shaver, and then dehairing is carried out by using dehairing paste. An AGA mouse model was established using testosterone propionate solution, administration and modeling were performed simultaneously, and the groups were set as follows:
(1) Modeling module (named Model): the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days.
(2) ME group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of ME was locally applied to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(3) SCGIL groups: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, at days 1, 3, 5, 7, 9, 11 and 13 after depilation, 20 μl of sCGIL was locally applied to the depilation area, respectively.
(4) M@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of m@scgil was applied locally to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(5) E@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of e@scgil was applied locally to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(6) ME@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of me@scgil was applied locally to the dehairing area on days 1, 3,5, 7, 9, 11 and 13, respectively, after dehairing.
(7) Commercially available 2% minoxidil group (designated cMXD): the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. At the same time, 100. Mu.L of a commercially available 2% minoxidil solution was topically applied to the dehaired area every day on days 1-13 after dehairing.
Animals were photographed on days 1, 10, 14, 21, 28 after dehairing. The results are shown in fig. 10, where the me@scgil group showed the fastest hair growth rate and the new hair evenly covered the entire dehairing area with the best hair regeneration effect. The regenerative hair coverage on day 28 was measured by ImageJ software and the regenerative hair coverage was calculated by the following formula: regenerative hair coverage (%) =a D28/A0 ×100. Wherein a D28 is the regenerative hair coverage area at day 28 and a 0 is the back dehairing area of the mice. The results are shown in fig. 11, where the me@scgil group regenerated hair coverage reached 84.98%, significantly higher than 47.41% for cMXD group. The smearing preparation system provided by the invention has an effect better than that of 2% minoxidil sold in the market under the condition of reducing the administration frequency and the administration dosage, and has high application value and popularization value.
In this embodiment, the choline-geranic acid ionic liquid solution may be replaced with one of a choline-geranic acid ionic liquid self-microemulsion, a choline-geranic acid ionic liquid liposome.
In this embodiment, minoxidil may be replaced with or include one or more of finasteride, estramustine, drospirenone, ethinyl estradiol, spironolactone, baritinib, li Texi tinib, and pontine.
In this embodiment, epigallocatechin gallate may be replaced with or further include one or more of catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, tannic acid, and quercetin.
Example 10
Regulation and evaluation of micro-environment around hair follicle by choline-geranic acid ionic liquid solution carrying minoxidil and epigallocatechin gallate
SCGIL was prepared as in example 2, and minoxidil loading gave M@scGAL (minoxidil: 1 mg/20. Mu.L). sCGIL was prepared as in example 2 and EGCG loaded to give E@sCGIL (EGCG: 200. Mu.g/20. Mu.L). sCGIL was prepared as in example 2, and loading minoxidil and EGCG gave ME@sCGIL (minoxidil: 1 mg/20. Mu.L, EGCG: 200. Mu.g/20. Mu.L). In addition, minoxidil and EGCG were dissolved in PBS buffer (minoxidil: 1 mg/20. Mu.L, EGCG: 200. Mu.g/20. Mu.L), and free minoxidil and EGCG mixed solution (ME) was prepared.
C57BL/6 mice with the age of 6-7 weeks are selected, back hair is shaved by an electric shaver, and then dehairing is carried out by using dehairing paste. An AGA mouse model was established using testosterone propionate solution, administration and modeling were performed simultaneously, and the groups were set as follows:
(1) Modeling module (named Model): the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days.
(2) ME group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of ME was locally applied to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(3) SCGIL groups: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, at days 1, 3, 5, 7, 9, 11 and 13 after depilation, 20 μl of sCGIL was locally applied to the depilation area, respectively.
(4) M@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of m@scgil was applied locally to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(5) E@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of e@scgil was applied locally to the dehairing area on days 1, 3, 5, 7, 9, 11 and 13, respectively, after dehairing.
(6) ME@sCGIL group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. Meanwhile, 20 μl of me@scgil was applied locally to the dehairing area on days 1, 3,5, 7, 9, 11 and 13, respectively, after dehairing.
(7) Commercial 2% minoxidil group: the testosterone propionate solution was injected subcutaneously back daily after depilation for a total of 28 days. At the same time, 100. Mu.L of a commercially available 2% minoxidil solution was topically applied to the dehaired area every day on days 1-13 after dehairing.
On day 14 after dehairing, mice were sacrificed from cervical dislocation, the skin of the back administration area was removed, fixed in 4% paraformaldehyde, and after paraffin sections, DHE immunofluorescence staining and CD31 immunohistochemical staining were performed, respectively. The results in fig. 12 and 13 show that the me@scgil group significantly down-regulates DHE expression, scavenges excess reactive oxygen species in skin cells in the depilatory region, and has a statistical difference compared to the Model group. The results of fig. 14 and 15 show that a large number of new blood vessels appear around the hair follicle in the administration area of the me@scgil group, exhibiting excellent pro-angiogenic ability. Therefore, ME@sCGIL can effectively improve the microenvironment of oxidative stress and insufficient vascularization around the AGA hair follicle.
In this embodiment, the choline-geranic acid ionic liquid solution may be replaced with one of a choline-geranic acid ionic liquid self-microemulsion, a choline-geranic acid ionic liquid liposome.
In this embodiment, minoxidil may be replaced with or include one or more of finasteride, estramustine, drospirenone, ethinyl estradiol, spironolactone, baritinib, li Texi tinib, and pontine.
In this embodiment, epigallocatechin gallate may be replaced with or further include one or more of catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, tannic acid, and quercetin.
It will be readily appreciated by those skilled in the art that the foregoing description is merely a preferred embodiment of the invention and is not intended to limit the invention, but any modifications, equivalents, improvements or alternatives falling within the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (10)
1. A coating preparation system, which is characterized in that the coating preparation system is a carrier based on choline-geranic acid ionic liquid, and the coating preparation system is loaded with an anti-androgenetic alopecia medicine and polyphenol active ingredients.
2. The spread formulation system according to claim 1, wherein the choline-geranic acid ionic liquid based carrier is a choline-geranic acid ionic liquid solution, a choline-geranic acid ionic liquid self-microemulsion, or a choline-geranic acid ionic liquid liposome.
3. The spread formulation system according to claim 1, wherein the choline in the choline-geranic acid ionic liquid based carrier is choline bicarbonate, choline hydroxide, or choline chloride.
4. The spread formulation system according to claim 1, wherein the choline-geranic acid ionic liquid based carrier has a choline to geranic acid mass ratio of 1: (1-2).
5. The spread formulation system according to claim 2, wherein the choline-geranic acid ionic liquid solution comprises 20 to 60 parts by volume choline-geranic acid ionic liquid and 40 to 80 parts by volume absolute ethanol;
The choline-geranic acid ionic liquid self-microemulsion comprises 10-20 parts by volume of choline-geranic acid ionic liquid, 10-80 parts by volume of ultrapure water and 10-80 parts by volume of absolute ethyl alcohol;
The choline-geranic acid ionic liquid liposome comprises 30-50 parts by mass of choline-geranic acid ionic liquid, 42-58 parts by mass of lecithin and 8-12 parts by mass of cholesterol.
6. The spread formulation system of claim 1, wherein the anti-androgenic alopecia drug is at least one of minoxidil, finasteride, estrol cyproterone, drospirenone, ethinyl estradiol, spironolactone, baritinib, li Texi tinib, and pontine;
The polyphenols active ingredient is at least one of epigallocatechin gallate, catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, tannic acid, and quercetin.
7. A method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with absolute ethyl alcohol to obtain choline-geranic acid ionic liquid solution;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid solution obtained in the step (2), and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
8. A method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) The choline-geranic acid ionic liquid obtained in the step (1) is fully mixed with ultrapure water and absolute ethyl alcohol to obtain choline-geranic acid ionic liquid self-microemulsion;
(3) Adding the antiandrogen alopecia medicine and the polyphenol active ingredient into the choline-geranic acid ionic liquid obtained in the step (2) from the microemulsion, and fully dissolving to obtain the clear transparent uniform medicine-carrying smearing preparation.
9. A method of preparing a spread formulation system comprising the steps of:
(1) Mixing the choline solution with the purified geranic acid solution, heating and stirring, steaming in a rotary way and drying in a vacuum way to obtain choline-geranic acid ionic liquid;
(2) And (3) performing ultrasonic film-removing on the choline-geranic acid ionic liquid, lecithin, cholesterol and the anti-androgenetic alopecia medicine obtained in the step (1) by using ultrapure water containing polyphenol active ingredients, and stirring and hydrating to obtain the choline-geranic acid ionic liquid liposome loaded with the anti-androgenetic alopecia medicine and the polyphenol active ingredients.
10. Use of a spread formulation system according to any one of claims 1-6 for the preparation of a medicament for the treatment of androgenic alopecia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410227186.8A CN118105341A (en) | 2024-02-29 | 2024-02-29 | Smearing preparation system for treating androgenetic alopecia and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410227186.8A CN118105341A (en) | 2024-02-29 | 2024-02-29 | Smearing preparation system for treating androgenetic alopecia and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118105341A true CN118105341A (en) | 2024-05-31 |
Family
ID=91217726
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410227186.8A Pending CN118105341A (en) | 2024-02-29 | 2024-02-29 | Smearing preparation system for treating androgenetic alopecia and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118105341A (en) |
-
2024
- 2024-02-29 CN CN202410227186.8A patent/CN118105341A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109431829B (en) | Hydroxyasiaticoside liposome and preparation method and application thereof | |
| US20230130577A1 (en) | Use of acellular adipose tissue extract in promoting hair growth and retention | |
| KR101003532B1 (en) | Composition for hair tonic or treating or preventing hair loss | |
| US20100172865A1 (en) | Methods of enhancing hair growth | |
| CN109528725A (en) | A kind of oxide containing di-amino-pyrimidine and the nano-composition of pyrrole alkyl amino pyrimidine oxide and the preparation method and application thereof | |
| CN111195230B (en) | Method for preparing flexible liposome | |
| CN113056257A (en) | Semisolid oil-based pharmaceutical composition containing pirfenidone for tissue repair | |
| AU6489300A (en) | Use of rhamnolipids in wound healing, treatment and prevention of gum disease and periodontal regeneration | |
| JP2003534359A (en) | Use of a biguanide derivative for producing a medicament having a scar-forming action | |
| Sauer et al. | The multiple uses of azelaic acid in dermatology: mechanism of action, preparations, and potential therapeutic applications | |
| Li et al. | Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia | |
| CA2724318A1 (en) | Compositions for the treatment of hair loss | |
| CN118105341A (en) | Smearing preparation system for treating androgenetic alopecia and preparation method thereof | |
| WO1991001624A2 (en) | Use of calcium antagonists for treating scars | |
| US20120164242A1 (en) | Novel methods for modulating melanin production | |
| US20110217260A1 (en) | Method of enhancing eyelash and eye brow hair growth | |
| KR20170134746A (en) | Combinations of natural substances comprising at least one glycyrrhetinic acid and at least one excipient, and their use in cosmetic applications | |
| WO2003006009A1 (en) | Compositions for reducing or preventing cellulite in mammalian skin | |
| CN114681403A (en) | Minoxidil carrier with high drug loading rate and encapsulation rate, gel and preparation thereof | |
| JP2019509333A (en) | Composition for preventing, improving or treating hair loss comprising deoxycholic acid as an active ingredient | |
| EP4183404A1 (en) | Composition for preventing hair loss or promoting hair growth comprising extract of above-ground part of carrots | |
| JPH05194214A (en) | Wound curing promoter | |
| KR102465464B1 (en) | Composition for Hair care comprising Vitagen | |
| EP4070782A2 (en) | Composition for hair regeneration comprising macrophage-derived extracellular vesicle mimetics | |
| US20240307485A1 (en) | Ws635 uses thereof in medicine |
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 |