Classifications

• • 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
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
  • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
• • 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
  • A61K8/67—Vitamins
  • A61K8/673—Vitamin B group
• • 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)
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• Public Health (AREA)
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• Epidemiology (AREA)
• Dermatology (AREA)
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• Birds (AREA)
• Gerontology & Geriatric Medicine (AREA)
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• Chemical Kinetics & Catalysis (AREA)
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• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Toxicology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Cosmetics (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 2023
  • 2023-01-20 US US18/726,502 patent/US20250073151A1/en active Pending
  • 2023-01-20 EP EP23749541.1A patent/EP4473957A4/en active Pending
  • 2023-01-20 JP JP2023578466A patent/JPWO2023149225A1/ja active Pending
  • 2023-01-20 CN CN202380016166.XA patent/CN118510490A/zh active Pending
  • 2023-01-20 WO PCT/JP2023/001623 patent/WO2023149225A1/ja not_active Ceased

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