CN106794192B - 包含齐墩果酸衍生物及其药学上可接受的盐的用于防止脱发或促进毛发生长的组合物 - Google Patents
包含齐墩果酸衍生物及其药学上可接受的盐的用于防止脱发或促进毛发生长的组合物 Download PDFInfo
- Publication number
- CN106794192B CN106794192B CN201580047539.5A CN201580047539A CN106794192B CN 106794192 B CN106794192 B CN 106794192B CN 201580047539 A CN201580047539 A CN 201580047539A CN 106794192 B CN106794192 B CN 106794192B
- Authority
- CN
- China
- Prior art keywords
- chemical formula
- composition
- pharmaceutically acceptable
- acceptable salt
- hair
- 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.)
- Expired - Fee Related
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 29
- 150000003839 salts Chemical class 0.000 title claims abstract description 18
- 230000003779 hair growth Effects 0.000 title claims abstract description 17
- 230000001737 promoting effect Effects 0.000 title claims abstract description 12
- 230000003658 preventing hair loss Effects 0.000 title abstract description 11
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical class C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 title abstract description 6
- 239000000126 substance Substances 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 23
- 201000004384 Alopecia Diseases 0.000 claims description 13
- 231100000360 alopecia Toxicity 0.000 claims description 7
- GXWUEMSASMVWKO-GNLHUFSQSA-N (4as,6ar,6as,6br,10s,12ar,14br)-10-[(2s,3r,4s,5s)-4,5-dihydroxy-3-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid Chemical compound O([C@@H]1[C@@H](O)[C@@H](O)CO[C@H]1O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CCC2C1(C)C)C)(C)CC[C@]1(CCC(C[C@@H]14)(C)C)C(O)=O)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GXWUEMSASMVWKO-GNLHUFSQSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 7
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 20
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 20
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 20
- 229940041967 corticotropin-releasing hormone Drugs 0.000 description 20
- KLVRDXBAMSPYKH-RKYZNNDCSA-N corticotropin-releasing hormone (human) Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)C)C(C)C)C1=CNC=N1 KLVRDXBAMSPYKH-RKYZNNDCSA-N 0.000 description 20
- 210000004209 hair Anatomy 0.000 description 18
- 239000002537 cosmetic Substances 0.000 description 11
- 230000003698 anagen phase Effects 0.000 description 9
- 230000003778 catagen phase Effects 0.000 description 8
- 210000003780 hair follicle Anatomy 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 6
- -1 TGFβ-2 Proteins 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000003676 hair loss Effects 0.000 description 5
- 208000024963 hair loss Diseases 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- FYSAXYBPXKLMJO-IFECXJOTSA-N (4as,6ar,6as,6br,8ar,10s,12ar,14bs)-10-[(2s,3r,4s,5s)-4-hydroxy-5-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,1 Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2C([C@H]3[C@]([C@@H]4[C@@]([C@@]5(CC[C@]6(CCC(C)(C)C[C@H]6C5=CC4)C(O)=O)C)(C)CC3)(C)CC2)(C)C)OC[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@@H]1O FYSAXYBPXKLMJO-IFECXJOTSA-N 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 2
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 2
- 208000004631 alopecia areata Diseases 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 229940089468 hydroxyethylpiperazine ethane sulfonic acid Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229940100243 oleanolic acid Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 102000010970 Connexin Human genes 0.000 description 1
- 108050001175 Connexin Proteins 0.000 description 1
- 208000003024 Diffuse alopecia Diseases 0.000 description 1
- 102100033299 Glia-derived nexin Human genes 0.000 description 1
- FYSAXYBPXKLMJO-UHFFFAOYSA-N Hederacolchiside A1 Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C3C(C4C(C5(CCC6(CCC(C)(C)CC6C5=CC4)C(O)=O)C)(C)CC3)(C)CC2)(C)C)OCC(OC2C(C(O)C(O)C(CO)O2)O)C1O FYSAXYBPXKLMJO-UHFFFAOYSA-N 0.000 description 1
- 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000554910 Pulsatilla cernua var. koreana Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 101150109862 WNT-5A gene Proteins 0.000 description 1
- 102000043366 Wnt-5a Human genes 0.000 description 1
- 108700020483 Wnt-5a Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 206010068168 androgenetic alopecia Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 108010025261 astressin B Proteins 0.000 description 1
- BGFHNAZIBICPLD-IXILWOCFSA-N astressin b Chemical compound C([C@@H](C(=O)N[C@](C)(CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)NC1C(N[C@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCNC(=O)CC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@](C)(CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)=O)NC(=O)[C@@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(C)=O)C1=CNC=N1 BGFHNAZIBICPLD-IXILWOCFSA-N 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000031774 hair cycle Effects 0.000 description 1
- 210000004919 hair shaft Anatomy 0.000 description 1
- 239000008266 hair spray Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000002438 stress hormone Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Birds (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供用于防止脱发或促进毛发生长的组合物，所述组合物包含齐墩果酸衍生物及其药学上可接受的盐作为有效成分。
Description
技术领域
本发明涉及用于防止脱发或促进毛发生长的组合物，所述组合物包含齐墩果酸衍生物及其药学上可接受的盐作为有效成分。
背景技术
促肾上腺皮质素释放激素(Corticotropin releasing hormone，CRH)为下丘脑-垂体-肾上腺轴(Hypothalamic-Pituitary-Adrenal axis，HPA轴)的主要成分之一，被精神压力所活化。CRH为由41个氨基酸组成的肽，是HPA轴的主要引发物质，并对压力作出响应，因此在脊椎动物的激素及神经递质级联中起到重要作用。
严重的精神-心理性(psycho-emotional)压力会对毛发生长带来显著的影响，并且导致斑秃。已有报道称，CRH会阻碍毛发生长(毛干伸长(hair shaft elongation))，并且在人毛囊的体外培养中促进毛基质角质形成细胞(hair matrix keratinocytes)的细胞凋亡(Ito N，et al.，Human hair follicles display a functional equivalent of thehypothalamic-pituitary-adrenal(HPA)axis and synthesize cortisol，FASEB J.19(2005)1332-4)。此外，已有报道称，CRH的受体拮抗剂在CRH过表达脱毛小鼠中能够诱导毛发的生长(Lixin Wang，et al.，CRH receptor antagonist astressin-B reverses andprevents alopecia in CRH over-expressing mice，Plos One.6(2011)e16377-e16385)。此外，已有报道称，经过培养的人毛囊会对CRH刺激产生反应，并且显示HPA轴，包括反馈系统(监管反馈系统(regulatory feedback systems))(Natsuho Ito,et al.，Human hairfollicles display a functional equivalent of the hypothalamic-pituitary-adrenal(HPA)axis and synthesize cortisol，Faseb J.19(2005)1332-4)。
因此，CRH对人毛发生长起到重要作用，尤其，可以期待将可调节通过CRH得到调节的细胞因子的表达的物质作为用于防止脱发或促进毛发生长的物质而有效利用。
发明内容
要解决的技术问题
本发明人评价了CRH对在毛发形成中起到重要作用的人毛乳头细胞(human hairdermal papilla cell)所带来的影响，并发现了CRH能够抑制毛乳头细胞中的与毛发生长相关的细胞因子，即，抑制KGF、TGFβ-2、Wnt5a及Nexin(连接蛋白)的表达，并且查明在毛囊培养系统中的毛发周期中能够促进从生长期到退化期的转变。本发明人为了确认能够阻断包括CRH的受体拮抗剂在内的CRH的作用的物质，从安全性得到认证的多种天然物及其提取物分离了多种化合物，并为了找到对CRH的受体具有拮抗效果的物质，将其作为对象而进行了广泛的搜索。结果发现特定齐墩果酸衍生物能够显著抑制CRH所引起的生长期毛发转变为退化期毛发的现象。
因此，本发明的目的在于，提供用于防止脱发或促进毛发生长的组合物，所述组合物包含齐墩果酸衍生物及其药学上可接受的盐作为有效成分。
技术方案
根据本发明一实施方式，提供用于防止脱发或促进毛发生长的组合物，所述组合物包含下述化学式1或化学式2的化合物或其药学上可接受的盐作为有效成分：
<化学式1>
<化学式2>
本发明的组合物中，所述脱发可以为压力性脱发。
发明效果
通过本发明查明了具有所述化学式1或2的化学结构的特定齐墩果酸衍生物能够显著抑制毛发的生长期-退化期转变，并且查明了这是对压力激素CRH的受体的拮抗作用所引起的。因此，所述化学式1或化学式2的化合物或其药学上可接受的盐能够有效用于防止脱发(尤其防止压力性脱发)或促进毛发生长的组合物。
具体实施方式
本发明提供用于防止脱发或促进毛发生长的组合物，所述组合物包含下述化学式1或化学式2的化合物或其药学上可接受的盐作为有效成分：
<化学式1>
<化学式2>
所述化学式1的化合物为公知物质，其化学名为3-O-β-D-吡喃葡萄糖基(1→3)-α-L-吡喃鼠李糖基(1→2)[β-D-吡喃葡萄糖基(1→4)]-α-L-吡喃阿拉伯糖基齐墩果酸(3-O-β-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl(1→2)[β-D-glucopyranosyl(1→4)]-α-L-arabinopyranosyl oleanolic acid)，CAS号为106577-41-7。所述化学式2的化合物也是公知物质，其化学名为齐墩果酸-3-O-α-L-吡喃鼠李糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→4)]-α-L-吡喃阿拉伯糖苷(Oleanolic acid-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranoside)，CAS号为106577-39-3，也被称为“多被银莲花皂苷R13(Raddeanoside R13)”或“Hederacolchiside A1”。所述化学式1及化学式2的化合物可以通过公知文献，例如Wei Li et al，Oleanane-type triterpenoidsaponins from the roots of Pulsatilla koreana and their apoptosis-inducingeffects on HL-60human promyelocytic leukemia cells,Arch.Pharm.Res.(2013)36，pp768-774等中公开的方法来得到。所述化学式1或化学式2的化合物的盐包括常规的药学上可接受的盐，例如，可以为钠盐等碱金属盐、钙盐等碱土金属盐等形式，但并不限定于此。
本发明的组合物能够有效适用于防止脱发，所述脱发可根据脱发形状包括斑秃症、弥漫性脱发症等脱发，并且根据脱发原因包括压力性脱发、女性型脱发等脱发。本发明的组合物尤其优选适用于多种原因造成的脱发中的压力性脱发。
本发明的组合物可以以药学组合物和/或化妆品组合物的形态进行制剂化。例如，本发明的组合物可以是包含所述化学式1或化学式2的化合物或其药学上可接受的盐作为有效成分的用于防止脱发或促进毛发生长的药学组合物形态。此外，本发明的组合物可以是包含所述化学式1或化学式2的化合物或其药学上可接受的盐的用于防止脱发或促进毛发生长的化妆品组合物的形态。
就所述药学组合物而言，所述组合物可以包含药学上可接受的载体，并可以通过常规的方法制剂化为液剂、悬浮液、乳剂、涂剂(lotion)、软膏剂、冻干制剂等非口服剂型。优选地，可制剂化为外用液剂、乳剂、软膏剂等经皮施用剂型。所述药学上可接受的载体包括磷酸盐缓冲盐水(phosphate buffered saline)、纯净水、无菌水等水性稀释剂或溶剂，并包括丙二醇(propylene glycol)、聚乙二醇、橄榄油等非水性稀释剂或溶剂。此外，根据需要可以包含湿润剂、芳香剂、防腐剂等。所述药学组合物中所含有的所述化学式1或化学式2的化合物或其药学上可接受的盐的施用量会根据患者的状态及体重、疾病的程度、药物形态、施用途径及时间有所不同，但是可以由本领域技术人员适当地选择。例如，所述化学式1或化学式2的化合物或其药学上可接受的盐可以以一天0.01～1000mg/kg，优选以0.1～100mg/kg的用量施用，上述施用可以采用一天进行一次施用的方式，也可以采用一天分几次来施用的方式。
就本发明的化妆品组合物而言，所述组合物可以是包含所述化学式1或化学式2的化合物或其药学上可接受的盐作为有效成分的化妆品组合物的形态。本发明的化妆品组合物可以使用所述化学式1或化学式2的化合物或其药学上可接受的盐，并通过常规的化妆品制备方法制备成多种形态。例如，本发明的化妆品组合物可以制备成含有所述化学式1或化学式2的化合物或其药学上可接受的盐的化妆产品、洗发剂、生发水、发乳、发胶、头皮精华液、生发油等形态，这些可以用常规的洗液、收敛液及保湿液进行稀释后使用。此外，所述化妆品组合物可以包含化妆品组合物领域中常规使用的稳定剂、增溶剂、维生素、颜料及香料等常规的助剂。本发明的化妆品组合物中，所述化学式1或化学式2的化合物或其药学上可接受的盐的含量可以是实现防止脱发或促进毛发生长的效果所需的有效的量，例如，相对于组合物总重量，该含量可以为0.001～50重量％，优选可以为约1～20重量％。
下面，通过实施例对本发明进行更详细的说明。但是，这些实施例仅用于例示本发明，本发明的范围并不限定于这些实施例。
实施例：在人毛发培养实验中化学式1及化学式2的化合物对生长期-退化期转变所带来的影响的评价
将正常的人头皮组织(Bundang Cha医院)在70％乙醇中洗涤2分钟，在磷酸盐缓冲盐水(phosphate buffered saline，PBS)中洗涤2分钟，然后在5X抗生素-抗真菌剂(5XAnti-anti)(Gibco)中洗涤2分钟，在PBS中洗涤2分钟，由此预防污染，然后选取对应于生长期的毛囊，并在威廉斯培养基(William's medium)(包含胰岛素、氢化可的松(hydrocortisone)、羟乙基哌嗪乙磺酸(HEPES)、抗生素-抗真菌剂(Anti-anti))(下面，在没有其他标记的情况下称为“培养基”)中培养一天，由此使用了继续维持生长期的毛囊。
选取生长期中的毛囊，并在24-孔细胞培养容器中在一个孔放置一个毛囊并与上述培养基一起培养，其中，每一个组使用了20个毛囊。实验分为对照组、阳性对照组、实验组等3个组来实施。对照组是在所述培养基中培养3天、6天。阳性对照组是在包含CRH 10-6M的培养基中进一步培养3天、6天。就实验组而言，在分别包含0.5uM的化学式1及化学式2的化合物的培养基中进行预处理2小时，然后加入CRH 10-6M并进一步培养3天、6天。将各个组培养3天、6天后，使用立体显微镜观察了生长期及退化期的毛发的数量。上述实验结果如下述表1所示。
[表1]
根据化学式1及化学式2的化合物的生长期-退化期转变的抑制效果
从所述表1的结果可以知道，在对照组中，培养3天、6天后分别有15％和60％的毛发从生长期转变为退化期。在阳性对照组中，则由于CRH的影响培养3天和6天后分别有60％和95％的毛发转变为退化期。在用化学式1的化合物处理的实验组中，培养3天和6天后分别只有25％和35％的毛发转变为退化期。在用化学式2的化合物处理的实验组中，培养3天和6天后分别只有10％和10％的毛发转变为退化期。从上述结果可知，CRH能够促进生长期毛发转变为退化期毛发，化学式1及化学式2的化合物可有效阻断CRH的影响，从而能够很好地维持生长期的毛发。
Claims (1)
1.下述化学式1的化合物或齐墩果酸-3-O-α-L-吡喃鼠李糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→4)]-α-L-吡喃阿拉伯糖苷或它们的药学上可接受的盐在制备用于防止压力性脱发或促进毛发生长的组合物中的用途：
<化学式1>
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140117819A KR101703677B1 (ko) | 2014-09-04 | 2014-09-04 | 사포닌 유도체 및 이의 약학적으로 허용가능한 염을 포함하는 탈모방지 또는 발모촉진용 조성물 |
| KR1020140117829A KR101703682B1 (ko) | 2014-09-04 | 2014-09-04 | 라데아노사이드 유도체 및 이의 약학적으로 허용가능한 염을 포함하는 탈모방지 또는 발모촉진용 조성물 |
| KR10-2014-0117819 | 2014-09-04 | ||
| KR10-2014-0117829 | 2014-09-04 | ||
| PCT/KR2015/008964 WO2016036051A1 (ko) | 2014-09-04 | 2015-08-27 | 올레아놀산 유도체 및 이의 약학적으로 허용가능한 염을 포함하는 탈모방지 또는 발모촉진용 조성물 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106794192A CN106794192A (zh) | 2017-05-31 |
| CN106794192B true CN106794192B (zh) | 2020-06-12 |
Family
ID=55440052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580047539.5A Expired - Fee Related CN106794192B (zh) | 2014-09-04 | 2015-08-27 | 包含齐墩果酸衍生物及其药学上可接受的盐的用于防止脱发或促进毛发生长的组合物 |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP3189842B1 (zh) |
| CN (1) | CN106794192B (zh) |
| ES (1) | ES2765486T3 (zh) |
| WO (1) | WO2016036051A1 (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113768861A (zh) * | 2021-10-09 | 2021-12-10 | 热休(厦门)细胞生物科技有限公司 | 一种具有防脱育发功能的外泌体美容液及其制备方法 |
| CN114366687B (zh) * | 2022-01-06 | 2023-08-22 | 中国药科大学 | 齐酞酸在促进毛发生长中的应用 |
| JPWO2023238945A1 (zh) * | 2022-06-10 | 2023-12-14 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6293215A (ja) * | 1985-10-18 | 1987-04-28 | Shiseido Co Ltd | 養毛料 |
| FR2673840A1 (fr) * | 1991-03-14 | 1992-09-18 | Lvmh Rech | Composition cosmetique ou pharmaceutique, notamment dermatologique, contenant de l'oxyacanthine, en particulier destinee a stimuler la pousse des cheveux ou a retarder leur chute. |
| JP3754762B2 (ja) * | 1995-09-05 | 2006-03-15 | 邦郎 辻 | 発毛促進剤 |
| JPH10265328A (ja) * | 1997-03-27 | 1998-10-06 | Nippon Flour Mills Co Ltd | 化粧料、ペットフード、リパーゼ阻害剤及びそれを含む食品 |
| JP2006206468A (ja) * | 2005-01-26 | 2006-08-10 | Kitasato Inst:The | サポニンからなる抗アポトーシス剤 |
| US20060067905A1 (en) * | 2005-04-01 | 2006-03-30 | Sederma Sas | Formulations and method for treating baldness |
| BRPI0905267A2 (pt) * | 2009-03-04 | 2011-01-11 | Maria Cristiane Bartasson | desenvolvimento de um creme cosmético contendo saponinas extraìdas da hera como ativos e a aplicação de nanotecnologia |
| ES2396075B1 (es) * | 2011-08-24 | 2013-12-27 | Mario LÓPEZ SÁNCHEZ | Composición cosmética de administración tópica. |
-
2015
- 2015-08-27 EP EP15837593.1A patent/EP3189842B1/en active Active
- 2015-08-27 WO PCT/KR2015/008964 patent/WO2016036051A1/ko active Application Filing
- 2015-08-27 CN CN201580047539.5A patent/CN106794192B/zh not_active Expired - Fee Related
- 2015-08-27 ES ES15837593T patent/ES2765486T3/es active Active
Non-Patent Citations (1)
| Title |
|---|
| 几种齐墩果酸糖缀合物的合成;曲峰等;《有机化学》;20031231;第23卷(第3期);第249-257页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2765486T3 (es) | 2020-06-09 |
| WO2016036051A1 (ko) | 2016-03-10 |
| EP3189842A4 (en) | 2018-02-07 |
| CN106794192A (zh) | 2017-05-31 |
| EP3189842B1 (en) | 2019-10-30 |
| EP3189842A1 (en) | 2017-07-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20110036682A (ko) | ＮＦκＢ-억제제 및 비-레티노이드 콜라겐 촉진제를 포함하는 조성물 | |
| JP2015178485A (ja) | 育毛用組成物 | |
| KR20060123256A (ko) | 모발의 태모화 방법 및 조성물 | |
| JP2011246442A (ja) | 光老化抑制剤および皮膚菲薄化抑制剤 | |
| CN106794192B (zh) | 包含齐墩果酸衍生物及其药学上可接受的盐的用于防止脱发或促进毛发生长的组合物 | |
| KR20100122455A (ko) | 탈모 방지 또는 육모 촉진을 위한 조성물 | |
| JP2006282597A (ja) | 毛乳頭細胞増殖促進剤、血管内皮増殖因子（ｖｅｇｆ）産生促進剤、養毛・育毛剤 | |
| CN110548031A (zh) | 包含乌地那非作为活性成分的用于增强脂肪干细胞的生发诱导能力的组合物 | |
| TW201711678A (zh) | 含有大豆皂苷的生長毛髮和/或修復毛髮促進用組合物 | |
| KR101703682B1 (ko) | 라데아노사이드 유도체 및 이의 약학적으로 허용가능한 염을 포함하는 탈모방지 또는 발모촉진용 조성물 | |
| KR101703677B1 (ko) | 사포닌 유도체 및 이의 약학적으로 허용가능한 염을 포함하는 탈모방지 또는 발모촉진용 조성물 | |
| CN111447937A (zh) | 作为自噬促进剂的协同组合物 | |
| JP5438239B1 (ja) | シコニン誘導体を有するペリオスチンの発現抑制剤 | |
| JP6368219B2 (ja) | エストロゲン受容体β活性化剤 | |
| JPH10265340A (ja) | メチレンジオキシベンゼン環−脂肪族化合物含有頭部用組成物 | |
| JPS63211214A (ja) | 養毛料 | |
| TW201636013A (zh) | 含有補骨脂定的生髮及/或育髮促進用組合物及其應用 | |
| JP2021519769A (ja) | 皮膚障壁機能異常の改善用組成物 | |
| JP4268329B2 (ja) | 養毛料、毛髪退行期移行抑制剤等の予防あるいは治療用組成物 | |
| KR101578849B1 (ko) | 진세노사이드 C-Mx1을 포함하는 두피 및 모근 강화를 통한 모발 성장 촉진용 샴푸 및 컨디셔너 조성물 | |
| KR101984276B1 (ko) | 베르베린 하이드로클로라이드를 유효성분으로 포함하는 체모성장 저해용 조성물 | |
| KR20150051075A (ko) | 팔마틴을 유효성분으로 포함하는 체모성장 저해용 조성물 | |
| JPH10245393A (ja) | トリテルペン類を含有する組成物 | |
| KR20150085964A (ko) | 워고닌을 포함하는 모발 성장 촉진용 화장료 또는 약학 조성물 | |
| KR20150085686A (ko) | 프로토파낙사디올을 포함하는 모발 성장 촉진용 화장료 또는 약학 조성물 |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200612 Termination date: 20200827 |