WO2023149225A1 - 皮膚外用組成物 - Google Patents
皮膚外用組成物 Download PDFInfo
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- WO2023149225A1 WO2023149225A1 PCT/JP2023/001623 JP2023001623W WO2023149225A1 WO 2023149225 A1 WO2023149225 A1 WO 2023149225A1 JP 2023001623 W JP2023001623 W JP 2023001623W WO 2023149225 A1 WO2023149225 A1 WO 2023149225A1
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- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 102000003425 Tyrosinase Human genes 0.000 claims abstract description 16
- 108060008724 Tyrosinase Proteins 0.000 claims abstract description 16
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- -1 cyclic carboxamide Chemical class 0.000 claims abstract description 11
- 229940011671 vitamin b6 Drugs 0.000 claims abstract description 8
- 239000002537 cosmetic Substances 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 7
- 230000002849 elastaseinhibitory effect Effects 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 235000008160 pyridoxine Nutrition 0.000 claims description 5
- 239000011677 pyridoxine Substances 0.000 claims description 5
- 229940088594 vitamin Drugs 0.000 claims description 5
- 229930003231 vitamin Natural products 0.000 claims description 5
- 235000013343 vitamin Nutrition 0.000 claims description 5
- 239000011782 vitamin Substances 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- 230000002087 whitening effect Effects 0.000 claims description 5
- HBAIZGPCSAAFSU-UHFFFAOYSA-N 1-(2-hydroxyethyl)imidazolidin-2-one Chemical compound OCCN1CCNC1=O HBAIZGPCSAAFSU-UHFFFAOYSA-N 0.000 claims description 4
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims description 4
- 229960004172 pyridoxine hydrochloride Drugs 0.000 claims description 4
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 claims description 4
- 239000011764 pyridoxine hydrochloride Substances 0.000 claims description 4
- 230000003712 anti-aging effect Effects 0.000 claims description 3
- 230000001153 anti-wrinkle effect Effects 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 21
- 102000016387 Pancreatic elastase Human genes 0.000 abstract description 10
- 108010067372 Pancreatic elastase Proteins 0.000 abstract description 10
- 235000019158 vitamin B6 Nutrition 0.000 abstract description 4
- 239000011726 vitamin B6 Substances 0.000 abstract description 4
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 abstract description 3
- 230000000052 comparative effect Effects 0.000 description 12
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 8
- 238000011534 incubation Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 5
- 208000012641 Pigmentation disease Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000019612 pigmentation Effects 0.000 description 4
- 229910021642 ultra pure water Inorganic materials 0.000 description 4
- 239000012498 ultrapure water Substances 0.000 description 4
- 230000037303 wrinkles Effects 0.000 description 4
- GVUGADOWXGKRAE-SRVKXCTJSA-N 4-[[(2s)-1-[[(2s)-1-[[(2s)-1-(4-nitroanilino)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 GVUGADOWXGKRAE-SRVKXCTJSA-N 0.000 description 3
- 102000016942 Elastin Human genes 0.000 description 3
- 108010014258 Elastin Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229920002549 elastin Polymers 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000007665 sagging Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010014970 Ephelides Diseases 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 210000004177 elastic tissue Anatomy 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000037394 skin elasticity Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RQPKNXVVIBYOBX-KDBLBPRBSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-2-(dihydroxyamino)-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.ON(O)[C@H](C(O)=O)CC1=CC=CC=C1 RQPKNXVVIBYOBX-KDBLBPRBSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- UCNXEGMKUYUZIW-UHFFFAOYSA-N 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol dodecanoic acid Chemical compound CC1=C(O)C(CO)=C(CO)C=N1.CCCCCCCCCCCC(O)=O UCNXEGMKUYUZIW-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 102100024025 Heparanase Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010051246 Photodermatosis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- RCYWWJBNPIWJMJ-UHFFFAOYSA-N [4-(hexadecanoyloxymethyl)-5-hydroxy-6-methylpyridin-3-yl]methyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC1=CN=C(C)C(O)=C1COC(=O)CCCCCCCCCCCCCCC RCYWWJBNPIWJMJ-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000481 effect on pigmentation Effects 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010037536 heparanase Proteins 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000008845 photoaging Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940095042 pyridoxine dipalmitate Drugs 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- 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
- A61K8/67—Vitamins
-
- 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
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to an external skin composition
- an external skin composition comprising a cyclic carboxamide derivative having a specific structure or a salt thereof and vitamin B6s.
- Cyclic carboxamide derivatives have the effect of inhibiting heparanase activity, and have been proposed to be incorporated into cosmetics, for example, as wrinkle-improving agents or as whitening agents effective in preventing or suppressing pigmentation such as spots. (Patent Document 1).
- Vitamin C is known as a whitening agent and is used in cosmetics. It has been proposed that combining this with vitamin B6 will have a further improving effect on pigmentation and the like (Patent Document 2).
- Pigmentation in the skin epidermis is due to accumulation of melanin, and is thought to be greatly influenced by tyrosinase activity in melanocytes.
- elastase activity which decomposes elastic fibers (elastin) produced by dermal fibroblasts, is thought to be involved in the reduction of skin elasticity such as wrinkles.
- a composition containing a combination of a cyclic carboxamide derivative and vitamin B6 effectively inhibits tyrosinase activity and elastase activity.
- the present invention is based on these findings.
- a cyclic carboxamide derivative represented by formula (1) or a salt thereof (In the formula, R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, X is —CH 2 — or —N(R 2 )—, wherein R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and n is an integer of 1 to 3), and (B) a composition for external use on the skin, comprising vitamin B6s.
- formula (1) a cyclic carboxamide derivative represented by formula (1) or a salt thereof
- R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom
- X is —CH 2 — or —N(R 2 )—
- R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with
- R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms
- [3] The composition according to [1] or [2], wherein component (A) is 1-(2-hydroxyethyl)-2-imidazolidinone.
- [4] The composition according to any one of [1] to [3], wherein the amount of component (A) is 1 to 200 mg/mL.
- component (B) is pyridoxine or pyridoxine hydrochloride.
- the composition according to any one of [1] to [9] which is an anti-wrinkle cosmetic.
- an external skin composition that effectively inhibits tyrosinase activity and elastase activity.
- the present invention relates to an external skin composition (hereinafter sometimes referred to as composition) comprising (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, and (B) vitamin B6s.
- composition comprising (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, and (B) vitamin B6s.
- Pigmentation such as blemishes, freckles, and dullness is generally caused by accumulation of melanin, and it is believed that tyrosinase activity in melanocytes has a large effect on the accumulation of melanin in the epidermis.
- the composition according to the present invention has tyrosinase inhibitory activity and can effectively inhibit tyrosinase activity. As a result, melanin production can be suppressed, and pigmentation can be prevented and suppressed.
- the composition according to the invention is preferably a whitening cosmetic.
- whitening mainly means suppressing the production of melanin to prevent spots, freckles, dullness, and the like. Wrinkles and sagging are generally caused by aging and photoaging. One of the causes of wrinkles and sagging is a decrease in skin elasticity, which is thought to involve elastase activity that degrades elastic fibers (elastin) produced by dermal fibroblasts.
- the composition according to the present invention has elastase inhibitory activity and can effectively inhibit elastase activity. As a result, elastin degradation is suppressed, and wrinkles, sagging, hardening, etc. of the skin can be suppressed.
- the composition according to the present invention is preferably an anti-aging cosmetic, more preferably an anti-wrinkle cosmetic.
- the composition according to the invention is a tyrosinase-inhibiting active agent and/or an elastase-inhibiting active agent.
- Cyclic carboxamide derivative or salt thereof is a cyclic carboxamide derivative represented by formula (1) or a salt thereof (hereinafter sometimes referred to as component (A). The same applies to other components). There is.).
- R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom
- X is —CH 2 — or —N(R 2 )—
- R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom
- n is an integer of 1-3.
- the above hydrocarbon group is not particularly limited, and may be, for example, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a cycloalkylalkyl group, a haloalkyl group, an alkoxyalkyl group, or an alkoxycarbonylalkyl group, preferably is an alkyl group.
- R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms
- X is —CH 2 — or —NH—
- n is 1.
- Specific examples of the cyclic carboxamide derivative represented by formula (1) include the following.
- Component (A) is most preferably 1-(2-hydroxyethyl)-2-imidazolidinone.
- the (A) component may be a salt of the cyclic carboxamide derivative represented by formula (1).
- the type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt.
- inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, magnesium salts, ammonium salts and the like.
- organic salts include acetates, lactates, maleates, fumarates, tartrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, amino acid salts and the like.
- component (A) component can be blended one or two or more.
- the blending amount of component (A) is preferably 1 to 200 mg/mL, more preferably 5 to 60 mg/mL, still more preferably 10 to 40 mg/mL, relative to the total amount of the composition.
- composition according to the present invention comprises (B) vitamins B6.
- Component (B) includes, for example, pyridoxine, pyridoxine hydrochloride, pyridoxine dipalmitate, and pyridoxine dilaurate, preferably pyridoxine or pyridoxine hydrochloride.
- the blending amount of component (B) is preferably 0.05 to 10 mg/mL, more preferably 0.1 to 5 mg/mL, and still more preferably 0.5 to 2 mg/mL, relative to the total amount of the composition. .5 mg/mL.
- the blending amount of component (A) relative to the blending amount of component (B) ((A)/(B)) is preferably 0.1 to 100, more preferably 1 to 50, in mass ratio.
- the cosmetic according to the present invention can contain (C) water.
- water water used in cosmetics, quasi-drugs, etc. can be used, and for example, purified water, ultrapure water, ion-exchanged water, tap water, etc. can be used.
- the cosmetics according to the present invention can contain optional ingredients that are usually used in cosmetics and pharmaceuticals.
- optional ingredients include moisturizers, lower alcohols, thickeners, surfactants, sequestering agents, neutralizers, pH adjusters, antioxidants, preservatives, chemicals, UV absorbers, powder components, oily Ingredients, fragrances, etc. can be mentioned, and one or more of them can be blended as long as the effects of the present invention are exhibited.
- the dosage form of the composition according to the present invention is not particularly limited. , gel, and aerosol.
- the form of use is also not particularly limited, and can be in any form such as lotion, milky lotion, cream, essence, jelly, gel, ointment, pack, mask, foundation, and the like.
- the composition according to the invention can be manufactured according to conventional methods.
- composition 1-(2-Hydroxyethyl)-2-imidazolidinone as component (A) and pyridoxine as component (B) are added to ultrapure water in amounts shown in Tables 1 and 2. and stirred to prepare compositions of Examples 101, 102, 201-207 and Comparative Examples 101-104, 201-214.
- a 100 mM phosphate buffer was used as a blank instead of the tyrosinase solution. Three wells were used per treatment group. After 3 minutes, 50 ⁇ L of 2.5 mM 3,4-L-dihydroxyphenylalanine (L-DOPA, CAS No. 59-92-7, Wako) solution was added, the 96-well plate was shaken at 270 rpm for 10 seconds, and the microplate was Absorbance at 490 nm ( OD490 ) was measured using a reader (SPARK 10M, TECAN). The measured plate was incubated at 23° C. for 10 minutes and after 10 minutes the absorbance at 490 nm (OD 490 ) was measured.
- L-DOPA 3,4-L-dihydroxyphenylalanine
- Tyrosinase inhibitory activity rate 100-[ ⁇ (As10-Ab10)-(As0-Ab0) ⁇ /(Ac10-Ac0) ⁇ 100]
- Ab0 OD 490 of blank before incubation
- Ab10 OD 490 of blank after incubation
- Ac0 OD 490 of control before incubation
- Ac10 OD 490 of control after incubation
- As0 OD 490 of each example and comparative composition before incubation
- OD 490 of each example and comparative composition after incubation is. The results obtained are listed in Table 1.
- Elastase inhibitory activity rate (%) ⁇ (C-CB) - (S-SB) ⁇ / (C-CB) x 100
- C OD 415 of control
- S OD 415 of each example
- comparative composition SB blank OD 415 of each example and comparative composition is. The results obtained are listed in Table 2.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Birds (AREA)
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Abstract
Description
本発明者の検討によると、驚くべきことに、環状カルボキサミド誘導体とビタミンB6類とを組み合わせを含む組成物が、効果的にチロシナーゼ活性およびエラスターゼ活性を阻害することがわかってきた。本発明はこれらの知見に基づくものである。
[1](A)式(1)で表される環状カルボキサミド誘導体またはその塩
R1は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、
Xは、-CH2-または-N(R2)-であり、ここで、R2は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、かつ
nは、1~3の整数である)、および
(B)ビタミンB6類
を含んでなる、皮膚外用組成物。
[2](A)成分の式(1)において、
R1が、炭素数1~3のヒドロキシアルキル基であり、
Xが、-CH2-または-NH-であり、かつ
nが、1である、[1]に記載の組成物。
[3](A)成分が、1-(2-ヒドロキシエチル)-2-イミダゾリジノンである、[1]または[2]に記載の組成物。
[4](A)成分の配合量が、1~200mg/mLである、[1]~[3]のいずれかに記載の組成物。
[5](B)成分がピリドキシンまたは塩酸ピリドキシンである、[1]~[4]のいずれかに記載の組成物。
[6](B)成分の配合量が、0.05~10mg/mLである、[1]~[5]のいずれかに記載の組成物。
[7]美白化粧料である、[1]~[6]のいずれかに記載の組成物。
[8]チロシナーゼ阻害活性を有する、[1]~[7]のいずれかに記載の組成物。
[9]抗老化化粧料である、[1]~[8]のいずれかに記載の組成物。
[10]抗シワ化粧料である、[1]~[9]のいずれかに記載の組成物。
[11]エラスターゼ阻害活性を有する、[1]~[10]のいずれかに記載の組成物。
しみ、そばかす、くすみといった色素沈着は、一般的にメラニン蓄積に起因するものが多く、表皮におけるメラニンの蓄積には、メラノサイトにおけるチロシナーゼ活性が大きく影響すると考えられている。本発明による組成物はチロシナーゼ阻害活性を有しており、チロシナーゼ活性を効果的に阻害することができる。その結果、メラニンの生成を抑制することができ、色素沈着を予防および抑制することができる。したがって、本発明による組成物は、好ましくは美白化粧料である。本明細書において「美白」とは、主としてメラニンの生成を抑制し、しみ、そばかす、くすみ等を防ぐことを意味する。
一般的に加齢や光老化によって、しわやたるみが引き起こされる。しわやたるみの一因には皮膚弾力の低下があり、これには真皮繊維芽細胞が産生する弾力繊維(エラスチン)を分解するエラスターゼ活性が関与していると考えられている。本発明による組成物はエラスターゼ阻害活性を有しており、エラスターゼ活性を効果的に阻害することができる。その結果、エラスチン分解が抑制され、皮膚のしわ、たるみ、硬化等を抑制することができる。したがって、本発明による組成物は、好ましくは抗老化化粧料であり、より好ましくは抗シワ化粧料である。
好ましい一形態において、本発明による組成物は、チロシナーゼ阻害活性剤および/またはエラスターゼ阻害活性剤である。
本発明による組成物は、式(1)で表される環状カルボキサミド誘導体またはその塩(以下、(A)成分と称することがある。他の成分についても同様である。)を含んでなる。
R1は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、
Xは、-CH2-または-N(R2)-であり、ここで、R2は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、かつ
nは、1~3の整数である。
上記の炭化水素基は、特に限定されず、例えば、アルキル基、シクロアルキル基、アルケニル基、アルキニル基、シクロアルキルアルキル基、ハロアルキル基、アルコキシアルキル基、アルコキシカルボニルアルキル基であってよく、好ましくはアルキル基である。
R1が、炭素数1~3のヒドロキシアルキル基であり、
Xが、-CH2-または-NH-であり、かつ
nが、1である。
式(1)で表される環状カルボキサミド誘導体の具体例としては、例えば、以下が挙げられる。
本発明による組成物は、(B)ビタミンB6類を含んでなる。(B)成分としては、例えば、ピリドキシン、塩酸ピリドキシン、ジパルミチン酸ピリドキシン、ジラウリン酸ピリドキシンが挙げられ、好ましくはピリドキシンまたは塩酸ピリドキシンである。
本発明による化粧料は、(C)水を含むことができる。水としては、化粧品、医薬部外品等に使用される水を使用することができ、例えば、精製水、超純水、イオン交換水、水道水等を使用することができる。
本発明による組成物は、常法に従って製造することができる。
超純水中に、(A)成分として1-(2-ヒドロキシエチル)-2-イミダゾリジノンを、(B)成分としてピリドキシンを、表1および表2に記載の配合量になるように添加し、撹拌して、実施例101、102、201~207、比較例101~104、201~214の組成物を調製した。
実施例101、102、比較例101~104の組成物の、ジヒドロキシフェニルアラニン(DOPA)を基質としたチロシナーゼ活性に及ぼす効果を以下の手順で評価した。 96ウェルプレート(Corning)に20μLの各実施例および比較例組成物または対照(対照には超純水を用いた)、40μLの40units/mLチロシナーゼ(CAS No.9002-10-2、Sigma-Aldrich)溶液および100μLの100mMリン酸buffer(pH6.8)を加え、23℃で3分間インキュベートした。ブランクはチロシナーゼ溶液の代替として100mMリン酸bufferを用いた。1つの処理群に対し、3ウェルを使用した。3分後に50μLの2.5mM3,4-L-ジヒドロキシフェニルアラニン(L-DOPA、CAS No.59-92-7、和光)溶液を添加し、96ウェルプレートを270rpmで10秒間振とうし、マイクロプレートリーダー(SPARK 10M、TECAN)を用いて490nmの吸光度(OD490)を測定した。測定したプレートを23℃で10分間インキュベートし、10分後、490nmの吸光度(OD490)を測定した。
実施例および比較例のチロシナーゼ阻害活性率を次式により算出した。
チロシナーゼ阻害活性率(%)=100-[{(As10-Ab10)-(As0-Ab0)}/(Ac10-Ac0)×100]
式中、
Ab0:インキュベート前のブランクのOD490
Ab10:インキュベート後のブランクのOD490
Ac0:インキュベート前の対照のOD490
Ac10:インキュベート後の対照のOD490
As0:インキュベート前の各実施例および比較例組成物のOD490
As10:インキュベート後の各実施例および比較例組成物のOD490
である。
得られた結果を、表1に記載した。
実施例201~207、比較例201~214の組成物の、N-スクシニル-Ala-Ala-Ala-p-ニトロアニリドを基質としたエラスターゼ活性に及ぼす効果を以下の手順で評価した。
96ウェルプレートに50μLの各実施例および比較例組成物または対照(対照には超純水を用いた)、50μLの1.25μg/mLエラスターゼ酵素(CAS No.39445-21-1、Sigma-Aldrich)溶液、100μLのN-スクシニル-Ala-Ala-Ala-p-ニトロアニリド(CAS No.52299-14-6、Sigma-Aldrich)溶液を加え、270rpmで30秒間振とうした後、37℃で15分間インキュベートした。ブランクはエラスターゼ酵素の代替として0.05M Tris-HCl bufferを用いた。1つの処理群に対し、3ウェルを使用した。96ウェルプレートを270rpmで10秒間振とうし、ウェル内の色素を均一に分散した後、マイクロプレートリーダーを用いて415nmの吸光度(OD415)を測定した。
実施例および比較例のエラスターゼ阻害活性率を次式により算出した。
エラスターゼ阻害活性率(%)={(C-CB)-(S-SB)}/(C-CB)×100
式中、
C:対照のOD415
CB:対照のブランクOD415
S:各実施例および比較例組成物のOD415
SB:各実施例および比較例組成物のブランクOD415
である。
得られた結果を、表2に記載した。
評価ごとに、対照と、各実施例および比較例組成物を、対応のないt検定で有意差検定を行った。検定はいずれも両側で有意水準を5%未満とした。P値を表1および表2に記載した。
以下の表に本発明による組成物の処方例を示す。表中の数値は質量%を示す。
Claims (11)
- (A)式(1)で表される環状カルボキサミド誘導体またはその塩
R1は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、
Xは、-CH2-または-N(R2)-であり、ここで、R2は、水酸基で置換されていてもよい炭素数1~6の炭化水素基、または水素原子であり、かつ
nは、1~3の整数である)、および
(B)ビタミンB6類
を含んでなる、皮膚外用組成物。 - (A)成分の式(1)において、
R1が、炭素数1~3のヒドロキシアルキル基であり、
Xが、-CH2-または-NH-であり、かつ
nが、1である、請求項1に記載の組成物。 - (A)成分が、1-(2-ヒドロキシエチル)-2-イミダゾリジノンである、請求項1または2に記載の組成物。
- (A)成分の配合量が、1~200mg/mLである、請求項1または2に記載の組成物。
- (B)成分がピリドキシンまたは塩酸ピリドキシンである、請求項1または2に記載の組成物。
- (B)成分の配合量が、0.05~10mg/mLである、請求項1または2に記載の組成物。
- 美白化粧料である、請求項1または2に記載の組成物。
- チロシナーゼ阻害活性を有する、請求項1または2に記載の組成物。
- 抗老化化粧料である、請求項1または2に記載の組成物。
- 抗シワ化粧料である、請求項1または2に記載の組成物。
- エラスターゼ阻害活性を有する、請求項1または2に記載の組成物。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60188306A (ja) * | 1984-03-07 | 1985-09-25 | Shiseido Co Ltd | 化粧料 |
JP2004091370A (ja) | 2002-08-30 | 2004-03-25 | Taiyo Yakuhin Kogyo Kk | 美白効果増強剤 |
WO2011040496A1 (ja) | 2009-09-30 | 2011-04-07 | 株式会社資生堂 | ヘパラナーゼ活性阻害剤 |
JP2019014709A (ja) * | 2017-07-07 | 2019-01-31 | ポーラ化成工業株式会社 | 皮膚外用組成物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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JPS60188306A (ja) * | 1984-03-07 | 1985-09-25 | Shiseido Co Ltd | 化粧料 |
JP2004091370A (ja) | 2002-08-30 | 2004-03-25 | Taiyo Yakuhin Kogyo Kk | 美白効果増強剤 |
WO2011040496A1 (ja) | 2009-09-30 | 2011-04-07 | 株式会社資生堂 | ヘパラナーゼ活性阻害剤 |
JP2019014709A (ja) * | 2017-07-07 | 2019-01-31 | ポーラ化成工業株式会社 | 皮膚外用組成物 |
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