JP2006213699A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for the skin, excellent in percutaneous absorption of ubiquinones. <P>SOLUTION: The external preparation for the skin excellent in the percutaneous absorption of the ubiquinones contains a phospholipid and a glycol ether. As a result, an antiaging effect, an antiwrinkle effects and the like for imparting tenseness and elasticity to the skin are expected by the antioxidizing action, activation of cells and improvement of the metabolism caused by the efficient penetration of the ubiquinones to the skin. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin with significantly improved transdermal absorbability.

There are various types of external preparations applied to the skin and mucous membranes, such as patches, ointments, creams, lotions, solid preparations, etc., but they are blocked by the stratum corneum that prevents foreign substances from entering the outside. Therefore, it is not easy to efficiently infiltrate the skin with useful components blended in the external preparation. For this reason, various studies have been made to promote transdermal absorption. For example, as an external preparation with improved transdermal absorption, liposomes containing lecithin and a hydrophilic nonionic surfactant (Patent Document) 1: JP-A-62-95134) and absorption promoting compositions containing phospholipids and specific polyhydric alcohols (Patent Document 2: JP-A-10-194994) are known.
On the other hand, phospholipids are present in natural animals and plants such as soybeans and egg yolks, and most of them are safe and can be used in foods. They have surface-active effects, have moisturizing properties, and are blended into external preparations. Then, it is known to promote percutaneous absorption. However, the effect of combining phospholipids and glycol ethers is not known.
Ubiquinones are coenzymes also called coenzyme Q. Among them, coenzyme Q10 is a human-specific ubiquinone essential for the production of ATP (adenosine triphosphate), which is an important source of energy, in intracellular mitochondria. In addition to being used as a metabolic cardiotonic agent such as an agent for ameliorating symptoms of moderate congestive heart failure, it is known to improve the action of immune cells and leukocytes and to have a strong antioxidant effect.
Furthermore, since external preparations for skin are often applied directly to the application site, not only the transdermal absorbability of the preparation, but also excellent preparations such as a long-term stable preparation and good usability are desired. It is rare.

  An object of the present invention is to provide a skin external preparation in which transdermal absorbability of ubiquinones is remarkably improved.

As a result of intensive studies to achieve the above object, the present inventors have found that the inclusion of phospholipids and glycol ethers markedly improves the transdermal absorbability of ubiquinones, and completed the present invention. did.
That is, this invention is a skin external preparation listed to following (1)-(11).
(1) A skin external preparation containing phospholipid, glycol ether, and ubiquinones.
(2) Glycol ether is ethylene glycol monoether, ethylene glycol diether, propylene glycol monoether, propylene glycol diether, butylene glycol monoether, butylene glycol diether, diethylene glycol monoether, diethylene glycol diether, dipropylene glycol monoether The skin external preparation according to (1), which is one or more selected from the group consisting of dipropylene glycol diether and dibutylene glycol monoether or dibutylene glycol diether.
(3) The external preparation for skin according to (1) or (2), wherein the phospholipid is a hydrogenated phospholipid.
(4) The external preparation for skin according to (1) or (2), wherein the phospholipid is a non-hydrogenated phospholipid.
(5) The skin external preparation according to (1) to (3), wherein the iodine value of the hydrogenated phospholipid is 10 to 50.
(6) The external preparation for skin according to (1) to (5), wherein the ubiquinones are one or more selected from the group consisting of coenzyme Q6, coenzyme Q7, coenzyme Q8, coenzyme Q9 and coenzyme Q10.
(7) The skin external preparation according to (1) to (6), further comprising vitamins, whitening agents, anti-wrinkle agents, anti-inflammatory analgesics, antifungal agents, steroid agents, and hair restorers.
(8) The external preparation for skin according to (1) to (7), wherein the external preparation for skin is a liquid crystal type external preparation for skin.
(9) The skin external preparation according to any one of (1) to (7), wherein the skin external preparation is a microemulsion type skin external preparation.
(10) The skin external preparation according to (1) to (7), wherein the skin external preparation is a liposome-type skin external preparation.
The present invention also includes the following methods.
(11) A method for promoting percutaneous absorption of ubiquinones by containing a phospholipid, glycol ether, and ubiquinones in an external preparation for skin.
(12) A method for promoting percutaneous absorption of ubiquinones by applying phospholipids and glycol ethers simultaneously or simultaneously with the application of ubiquinones.

  Since the present invention can improve the transdermal absorbability of ubiquinones by containing phospholipids and glycol ethers, the anti-oxidation action, activation of cells, improvement of metabolism, etc. possessed by ubiquinones are effective. It can be expected to have an aging effect and an anti-wrinkle effect that gives skin tension and elasticity.

BEST MODE FOR CARRYING OUT THE INVENTION

  The external preparation for skin of the present invention contains phospholipid, glycol ether and ubiquinones. The method for promoting percutaneous absorption of ubiquinones of the present invention is characterized by containing phospholipid and glycol ether in a skin external preparation.

Examples of the phospholipid used in the present invention include glycerophospholipid and sphingophospholipid.
Glycerophospholipid is a substance having a glycerophosphoric acid skeleton, and has a fatty acid ester, a long-chain alkyl ether, a vinyl ether or the like as a lipophilic group. Specifically, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphadiylinositol, phosphatidylinositol polyphosphate, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylserine, Examples include phosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidic acid.
Sphingophospholipids have long-chain bases or long-chain fatty acids such as sphingosine and phytosphingosine, and phosphoric acid or phosphonic acid. Ceramide 1-phosphate derivatives (such as sphingomyelin), ceramide 1-phosphonic acid derivatives ( Ceramide aminoethylphosphonic acid and the like).
Among these phospholipids, glycerophospholipid is preferable, and phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol are particularly preferable.

The phospholipid used in the present invention may be a natural product extracted and purified from animals and plants, or may be chemically synthesized, and may be subjected to processing such as hydrogenation or hydroxylation. Commercial products may also be used. The natural product is preferably lecithin, which is an extract / purified product from soybean or egg yolk.
The lecithin may be non-hydrogenated lecithin, hydrogenated lecithin, hydroxylated lecithin and the like, and non-hydrogenated lecithin and hydrogenated lecithin are preferable. Among hydrogenated lecithins, partial hydrogenation is preferred, and those with a lower degree of hydrogenation are more preferred. The iodine value of lecithin is usually 10 to 50, preferably 20 to 45, and particularly preferably 30 to 45.

  The amount of the phospholipid used in the present invention is not particularly limited as long as the effects of the present invention are exhibited, but as a whole external preparation for skin, it is usually 0.01 to 15% by weight, preferably 0.05 to 10% by weight, particularly preferably 0.1 to 0.1%. It may be 8% by weight.

  In the present invention, the glycol ether is not particularly limited as long as one or both of the hydroxyl groups of glycol are etherified. The glycol may be a single oligomer, a polymer, or two or more oligomers. good. For example, ethylene glycol monoether, ethylene glycol diether, diethylene glycol monoether, diethylene glycol diether, triethylene glycol monoether, triethylene glycol diether, tetraethylene glycol monoether, tetraethylene glycol diether, polyethylene glycol monoether, propylene Glycol monoether, propylene glycol diether, dipropylene glycol monoether, dipropylene glycol diether, tripropylene glycol monoether, tripropylene glycol diether, polypropylene glycol monoether, butylene glycol monoether, butylene glycol diether, alkylene glycol Such as acetate That. Examples of ethers include alkyl ethers, alkoxy ethers, aromatic ethers, and allyl ethers. Specifically, ethyl ether, methyl ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, t-butyl ether. N-pentyl ether, n-hexyl ether, phenyl ether, vinyl ether and the like.

  Specific examples of glycol ethers include ethylene glycol monovinyl ether, ethylene glycol monoethyl ether, ethylene glycol mono-n-propyl ether, ethylene glycol monoisopropyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol monoisobutyl ether, ethylene glycol Mono-t-butyl ether, ethylene glycol mono-2-methylpentyl ether, ethylene glycol mono-n-hexyl ether, ethylene glycol mono-2,4-hexadiene ether, ethylene glycol mono-2,6,8-trimethyl-4- Ethylene glycol monoethers such as nonyl ether, ethylene glycol monophenyl ether, and ethylene glycol monomethyl phenyl ether; ethylene glycol dimethyl ether And ethylene glycol diethers such as ethylene glycol diethyl ether; diethylene glycol monomethyl ether, diethylene glycol monoethyl ether (hereinafter also referred to as ethoxy diglycol), diethylene glycol mono-n-propyl ether, diethylene glycol mono-n-butyl ether, diethylene glycol monoisobutyl ether Diethylene glycol monoethers such as diethylene glycol mono-n-hexyl ether and diethylene glycol monomethyl phenyl ether; diethylene glycol diethers such as diethylene glycol dimethyl ether and diethylene glycol divinyl ether; triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, triethylene glycol Triethylene glycol monoethers such as coal mono-n-butyl ether and triethylene glycol monovinyl ethyl ether; Triethylene glycol diethers such as triethylene glycol dimethyl ether and triethylene glycol divinyl ether; Tetraethylene glycols such as tetraethylene glycol monophenyl ether Monoether; tetraethylene glycol diether such as tetraethylene glycol diethyl ether; polyethylene glycol monoether such as polyethylene glycol monomethyl ether; propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol-n-monopropyl ether, propylene glycol mono Isopropyl ether, propylene glycol Propylene glycol monoethers such as mono-n-butyl ether, propylene glycol monoisobutyl ether, propylene glycol monoallyl ether, propylene glycol monophenyl ether; propylene glycol dimethyl ether, propylene glycol diethyl ether, propylene glycol-n-dipropyl ether, propylene glycol Propylene glycol diethers such as diisopropyl ether, propylene glycol di n-butyl ether, propylene glycol diisobutyl ether, propylene glycol diallyl ether, propylene glycol diphenyl ether; dipropylene glycol monoethyl ether, and dipropylene glycol mono-n-butyl ether, dipropylene glycol Monoisobutyl Dipropylene glycol monoethers such as ether and dipropylene glycol allyl ether; dipropylene glycol diethers such as dipropylene glycol diethyl ether and dipropylene glycol di n-butyl ether, dipropylene glycol diisobutyl ether and dipropylene glycol allyl ether; Propylene glycol monomethyl ether, tripropylene glycol monoethyl ether, and tripropylene glycol mono-ether such as tripropylene glycol mono-n-butyl ether, tripropylene glycol monoisobutyl ether, tripropylene glycol monoallyl ether; tripropylene glycol dimethyl ether, tripropylene Glycol diethyl ether and tripropylene glycol Tripropylene glycol diethers such as polypropylene n-butyl ether, tripropylene glycol diisobutyl ether, tripropylene glycol diallyl ether; polypropylene glycol monoethers such as polypropylene glycol monobutyl ether; butylene glycol monomethyl ether, butylene glycol monoethyl ether, and butylene glycol mono -butylene glycol monoethers such as n-butyl ether; butylene glycol dimethyl ether, butylene glycol diethyl ether, butylene glycol diethers such as butylene glycol di n-butyl ether; ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene Glycol mono-n-butyl ether Acetate, diethylene glycol monoethyl ether acetate, diethylene glycol mono -n- butyl ether acetate, alkylene glycol acetate and propylene glycol monomethyl ether acetate; and the like.

  Preferred glycol ethers are ethylene glycol monoether, ethylene glycol diether, diethylene glycol monoether, diethylene glycol diether, triethylene glycol monoether, tetraethylene glycol monoether, tetraethylene glycol diether, polyethylene glycol monoether, propylene glycol mono Ether, propylene glycol diether, dipropylene glycol monoether, dipropylene glycol diether, tripropylene glycol monoether, specifically ethylene glycol monovinyl ether, ethylene glycol monoethyl ether, ethylene glycol mono-n-propyl ether , Ethylene glycol monoisopropyl ether, ethyl Glycol mono-n-butyl ether, ethylene glycol monoisobutyl ether, ethylene glycol mono-t-butyl ether, ethylene glycol mono-2-methylpentyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, Diethylene glycol mono-n-propyl ether, diethylene glycol mono-n-butyl ether, diethylene glycol monoisobutyl ether, diethylene glycol mono-n-hexyl ether, diethylene glycol monomethyl phenyl ether, diethylene glycol dimethyl ether, diethylene glycol divinyl ether, diethylene glycol ethyl vinyl ether, triethyl Glycol monomethyl ether, triethylene glycol monoethyl ether, triethylene glycol mono-n-butyl ether, triethylene glycol monovinyl ethyl ether, tetraethylene glycol monophenyl ether, tetraethylene glycol diethyl ether, polyethylene glycol methyl mono ether, propylene glycol monomethyl Ether, propylene glycol monoethyl ether, propylene glycol-n-monopropyl ether, propylene glycol monoisopropyl ether, propylene glycol mono-n-butyl ether, propylene glycol phenyl ether, propylene glycol monomethyl ether, propylene glycol dimethyl ether, propylene glycol diethyl ether, Professional Pyrene glycol-n-dipropyl ether, propylene glycol diisopropyl ether, propylene glycol di n-butyl ether, propylene glycol diisobutyl ether, propylene glycol diallyl ether, propylene glycol diphenyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-butyl ether , Dipropylene glycol diethyl ether, and dipropylene glycol di n-butyl ether, dipropylene glycol diisobutyl ether, dipropylene glycol allyl ether, tripropylene glycol monomethyl ether, tripropylene glycol monoethyl ether, and tripropylene glycol mono-n-butyl ether It is.

  More preferably, the glycol ether is ethylene glycol monoether, propylene glycol monoether, dipropylene glycol monoether, specifically ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, Diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether.

  The blending amount of the glycol ether used in the present invention is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. Usually, 0.01 to 80% by weight, preferably 1 to 75% by weight, particularly preferably 5 to 70% by weight.

  Further, in the external preparation for skin of the present invention, the ratio of the glycol ether to the phospholipid is not particularly limited as long as the effect of the present invention is exerted, but when the total amount of phospholipid is 1 part by weight, usually 0.01 to 300 parts by weight, Preferably it is 0.05-100 weight part, Most preferably, it is 0.1-20 weight part.

  The ubiquinones used in the present invention are a general term for 2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone and are also called coenzyme Q. The ubiquinones have a side chain isoprene unit of usually 1 to 20, preferably 5 to 15, more preferably 6 to 10 (coenzyme Q6 to Q10: present in the organism), particularly preferably 10 (coenzyme Q10). There should be.

  The blending amount of ubiquinones used in the present invention is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. Usually, 0.001 to 5% by weight, preferably 0.005 to 3% by weight, particularly preferably 0.01 to 1% by weight.

  Since the present invention can also promote percutaneous absorption of active ingredients other than ubiquinones compounded in the external preparation for skin, the active ingredients can be further blended to add other useful actions.

In the present invention, the active ingredient is not particularly limited as long as it has a useful effect on the skin such as a pharmacologically active ingredient and a physiologically active ingredient. For example, vitamins (vitamin A, provitamin A, Vitamin E, vitamin B2, nicotinic acid, vitamin C, vitamin D, vitamin K, vitamin B1, vitamin B6, vitamin B12, folic acid, pantothenic acid, biotin, vitamin-like agent), Whitening agent, anti-wrinkle agent, anti-inflammatory analgesic agent, antifungal agent, steroid agent, hair restorer, slimming agent, local anesthetic agent, antipruritic agent, antibacterial agent, antiviral agent, keratin softener, moisturizer, astringent, antioxidant Agents, hair growth inhibitors, etc., preferably vitamin A, vitamin E, vitamin C, whitening agent, anti-wrinkle agent, anti-inflammatory analgesic agent, antifungal agent, steroid agent, hair restorer, slimming agent, Humectant, an antioxidant, particularly preferably vitamin A, vitamin E, an antioxidant.
These components can be used alone or in combination of two or more.
Specifically, the following components can be exemplified.

Examples of vitamins include retinol derivatives such as retinol and retinol acetate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, vitamin A oil, vitamin A fatty acid ester, d-δ-tocopheryl retinoate, α -Vitamin A such as tocopheryl retinoate and β-tocopheryl retinoate, β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthin, echinone and other provitamins A Vitamin E such as dl-α-tocopherol acid, dl-α-tocopherol calcium succinate, riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin '-Vitamin B2 such as sodium phosphate ester, riboflavin tetranicotinate, nicotinic acid such as methyl nicotinate, nicotinic acid, nicotinamide, ascorbic stearate, L-ascorbyl dipalmitate, tetraisopalmitic acid Vitamin C such as ascorbyl, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, magnesium ascorbate phosphate, sodium ascorbate phosphate, glucoside ascorbate, Vitamin Ds such as methyl hesperidin, ergocalciferol, cholecalciferol, vitamin Ks such as phylloquinone, farnoquinone, γ-oryzanol, di Benzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphorus Vitamin B1 such as acid salt, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate, thiamine triphosphate, thiamine triphosphate monophosphate, pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'- Vitamin B6 such as pyridoxal phosphate and pyridoxamine hydrochloride, vitamin B12 such as cyanocobalamin, hydroxocobalamin and deoxyadenosylcobalamin, folic acid such as folic acid and pteroylglutamic acid , Pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantetheine, D-panthetin, coenzyme A, pantothenic acid such as pantothenyl ethyl ether, biotins such as biotin and biotin, and carnitine And vitamin-like agents such as ferulic acid, α-lipoic acid and orotic acid.
Among them, preferred are vitamin A oil, vitamin A such as d-δ-tocopheryl retinoate, and vitamin C such as ascorbyl tetraisopalmitate, ascorbic acid, ascorbic acid glucoside, and particularly preferred vitamin A oil, d Vitamin A such as -δ-tocopheryl retinoate.

  The amount of vitamins used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  As whitening agents, placenta, arbutin, cysteine, ellagic acid, kojic acid, phytic acid, lucinol, hydroquinone; , Chamomile, licorice, gardenia, cucumber, wheat, rice, rice haiga, oryzanol, rice bran, perilla, peony, nematode, perch, soy, tea, terminaria, toki, pearl millet, hamamelis, safflower, buttonpi, yokuinin, okie Ingredients derived from plants such as oysters (Diospyros kaki) and clove, extracts, essential oils and the like can be mentioned, and arbutin, cysteine and terminaria extract are preferable.

  The blending amount of the whitening agent used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Examples of the anti-wrinkle agent include kinetin, glycolic acid, argillin, acylated glucosamine, collagen, hyaluronic acid, aloe extract, seaweed extract, maroni extract, rosemary extract, cornflower extract, and preferably kinetin.

  The compounding amount of the anti-wrinkle agent used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Anti-inflammatory analgesics include indomethacin, felbinac, methyl salicylate, glycol salicylate, allantoin or derivatives thereof, ibuprofen, ibuprofen piconol, bufexamac, butyl fenfenac, bendazac, piroxicam, ketoprofen, etc., preferably indomethacin, felbinac, It is methyl salicylate.

  The amount of the anti-inflammatory analgesic used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Antifungal agents include terbinafine hydrochloride, sulconazole nitrate, clotrimazole, isoconazole nitrate, croconazole nitrate, naconconate nitrate, miconazole nitrate, econazole nitrate, oxyconazole nitrate, bifonazole, thioconazole, ketoconazole, tolnaphthalate, tolcyclate, lirannaphthate, cyclohexane Examples include piroxolamine, exeramide, siccanin, undecylenic acid, zinc undecylenate, pyrrolnitrin, butenafine hydrochloride, amorolfine hydrochloride, neticonazole hydrochloride and the like, preferably terbinafine hydrochloride and sulconazole nitrate.

  The amount of the antifungal agent used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Steroid agents include dexamethasone acetate, dexamethasone acetate, dexamethasone propionate, dexamethasone acetate, dexamethasone valerate, prednisolone valerate acetate, hydrocortisone butyrate, hydrocortisone acetate, hydrocortisone, hydrocortisone butyrate propionate, cortisone acetate, prednisolone acetate, prednisone acetate, , Betamethasone valerate, betamethasone dipropionate, clobetasone butyrate, clobetasol propionate, diflurozone acetate, diflucortron valerate, beclomethasone propionate, flumetasone pivalate, triamcinolone acetonide, fluocinolone acetonide, fluocinonide, amcinonide, amcinonide, Difluprednate and the like, preferably hydrocortiacetate Emissions, prednisolone valerate acetate, butyrate clobetasone.

  The compounding amount of the steroid used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Hair growth agents include procyanidins, dipotassium glycyrrhizinate, capronium chloride, cephalanthin, menthol, hinokitiol, L-hydroxyproline, acetylhydroxyproline, fucoidan, capsicum tincture, cephalanthin, swellthianin, symphonginidine, flavonosteroid, immunotect, minoxidil, FGF -10 、 Emisodia extract (extract), assembly extract (extract), beetle extract (extract), flax extract (extract), hypericum extract (extract), gentian extract (extract), sage extract (extract) ), Peppermint extract (extract), Hop extract (extract), Yokuinin extract (extract), Bamboo leaf extract (extract), Ginger extract (extract), Carrot extract (extract), Body Ju extract (extract), moutan bark extract (extract) and the like, preferably procyanidins, assembly extract (extract), Mitsuishikonbu extract (extract).

  The blending amount of the hair restorer used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Examples of slimming agents include caffeine, aminophylline, theophylline, oxtriphyrin, daphyrin, diisobutylaminobenzoyloxypropyltheophylline, theobromine, diprofilin, proxyphylline, pentoxifylline and other xanthines, capsaicin, etc. , Capsaicin.

  The amount of the slimming agent used in the present invention is not particularly limited, but can be appropriately selected and used in consideration of the feeling of use and effects on the skin. The total amount of the external preparation for skin is usually 0.1 to 30% by weight, preferably 0.5 to 25% by weight, particularly preferably 1 to 20% by weight.

  Other examples of local anesthetics, antipruritics, antibacterial agents, antiviral agents, keratin softeners, moisturizers, astringents, antioxidants, and hair growth inhibitors include the following.

Local anesthetics: lidocaine, lidocaine hydrochloride, dibucaine, dibucaine hydrochloride, ethyl aminobenzoate, eucalyptus oil, eugenol, camphor, mint oil, etc.
Antipruritics: crotamiton, chlorpheniramine, chlorpheniramine maleate, diphenhydramine, diphenhydramine hydrochloride, diphenhydramine salicylate, salicylic acid, nonylic acid vanillylamide, mequitazine, camphor, thymol, eugenol, polyoxyethylene lauryl ether, comfrey extract, perilla extract, etc.

Antibacterial agents: isopropylmethylphenol, chlorhexidine gluconate, chlorhexidine hydrochloride, benzalkonium chloride, benzethonium chloride, cetyltrimethylammonium bromide, decalinium chloride, triclosan, trichlorocarbanilide and the like.
Antiviral agents: acyclovir, penciclovir, etc.

  Keratin softener: ethyl alcohol, isopropyl alcohol, propanol, butanol, polyethylene glycol, benzyl alcohol, phenylethyl alcohol, propylene carbonate, hexyl decanol, allantoin, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, triethanolamine, diisopropyl adipate, ethyl Laurylate, lanolin, fatty acid dialkyrolamide, urea, sulfur, resorcin, phytic acid, lactic acid, lactate, sodium hydroxide, potassium hydroxide, etc.

  Moisturizer: 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, diglycerin, polyethylene glycol, diglycerin trehalose, sodium hyaluronate, heparin analog, chondroitin sulfate sodium, collagen, elastin, keratin, chitin, chitosan High molecular compounds such as, amino acids such as glycine, aspartic acid, arginine, natural moisturizing factors such as sodium lactate, urea, sodium pyrrolidonecarboxylate, chamomile extract, aloe extract, aloe vera extract, hamamelis extract, rosemary extract, thyme extract, Plant extracts such as tea extract and perilla extract.

Astringent: citric acid, tartaric acid, lactic acid, aluminum chloride, aluminum sulfate, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, aluminum phenolsulfonic acid, zinc paraphenolsulfonic acid, zinc sulfate, zinc lactate, aluminum chlorohydroxide and the like.
Antioxidants: Dibutylhydroxytoluene, butylhydroxyanisole, disodium ethylenediaminetetraacetate dihydrate (hereinafter also referred to as sodium edetate), sorbic acid, sodium sulfite and the like.

  Hair growth inhibitor: isoflavone, cypress extract, docami extract, iris root extract, papain enzyme, etc.

  The amount of the local anesthetic, antipruritic agent, antibacterial agent, antiviral agent, keratin softener, moisturizer, astringent, antioxidant, hair growth inhibitor is not particularly limited as long as the effect of the present invention is exerted, Desirably, it can be appropriately selected and used within the upper limit of the amount allowed in the Pharmaceutical Affairs Law. Specifically, it can be prepared according to the purpose from the range of usually 0.001 to 20 parts by weight, preferably 0.001 to 10 parts by weight, more preferably 0.001 to 5 parts by weight per 100 parts by weight of the external preparation for skin.

  The method for preparing the external preparation for skin of the present invention is not particularly limited, and can be prepared by a conventional method by appropriately selecting and blending various components necessary for preparing an ordinary external preparation for skin. Moreover, the application amount and usage of the external preparation for skin of the present invention to the outer skin are not particularly limited, and it can be used usually by applying an appropriate amount to the outer skin such as skin several times a day.

  The external preparation for skin of the present invention can be prepared in various forms. For example, ointments, creams, liquids (including oils, lotions, emulsions, aerosols), gels (including liquid crystals, microemulsions, liposomes), patches (including packs), solids (sticks) In particular, it is useful when applied to liquids (including lotions, oils, and emulsions) and gels (including liquid crystals, microemulsions, and liposomes). Of these, gel agents (including liquid crystals, microemulsions and liposomes) are particularly preferred as an embodiment of the present invention because of the effect of stabilizing the preparation at high temperatures.

A liquid crystal is a liquid with a high degree of crystallinity, generally having a long orientation in the constituent molecules, a fluidity and viscosity that is intermediate between solid and liquid, and exhibits optical anisotropy. There are many. The liquid crystal forms a hexagonal layer and a lamellar layer, and this structure causes refraction and reflection due to colored stripes and polarized light in white light, so it is easy to identify birefringence under the microscope and visual observation of liquid crystal formation. can do.
Since liquid crystals are similar in structure to biological bilayer membranes and intercellular lipids, they have the advantage that they are easy to adapt to the skin and can promote percutaneous absorption of useful components.
In the present invention, the skin external preparation preferably contains liquid crystal.

A microemulsion is generally defined as a transparent or translucent one-liquid phase consisting of an oil-water-amphiphile, and a system in which large swollen micelles are dispersed. It is said that. The average particle size of the microemulsion is preferably 0.5 μm or less from the viewpoint of optical transparency.
Microemulsions have the advantage that the formulation is more easily absorbed into the skin from the stratum corneum than normal emulsions because the micelles dispersed are small enough to have optical transparency.

A liposome is an endoplasmic reticulum composed of a lipid bilayer assembled in a spherical shape. A structure in which multiple layers of this lipid bilayer overlap each other in an onion shape is called a multilamellar liposome.
Liposomes are similar in structure to biological bilayer membranes, and thus have an advantage that they can be easily adapted to the skin and can promote percutaneous absorption of useful components.

In the present invention, the liquid crystal type external preparation for skin indicates one containing liquid crystal in the external preparation for skin.
When the skin external preparation of the present invention is a liquid crystal type skin external preparation, prepared by adding and stirring phospholipids, water-soluble compounds, a small amount of water, etc. to glycol ether, and appropriately adding and stirring oils and oil-soluble compounds. can do. Moreover, although the liquid crystal type skin external preparation of this invention can mix | blend a small amount of water, it can prepare also as a substantially anhydrous formulation, without mix | blending water separately.

In the present invention, the microemulsion-type external preparation for skin indicates one containing a microemulsion in the external preparation for skin.
When the skin external preparation of the present invention is a microemulsion type skin external preparation, phospholipids and the like are added to and stirred in glycol ether, and oils and oil-soluble compounds are appropriately added and stirred, and then water-soluble compounds and water are added. And emulsified and prepared using a high-pressure homomixer.

In the present invention, the liposome-type external preparation for skin refers to those containing liposomes in the external preparation for skin.
When the skin external preparation of the present invention is a liposome-type skin external preparation, the preparation method is not particularly limited, and various known preparation methods can be used. For example, phospholipid, water-soluble It can be prepared by adding and stirring a compound, water and the like, and appropriately adding and stirring an oil and an oil-soluble compound.

  The skin external preparation of the present invention may further contain water, and the amount of water is not particularly limited as long as the effect of the present invention is exhibited, but is generally 0.001 to 90% by weight, preferably 0.01 to 80% as a whole. % By weight, particularly preferably 0.1 to 70% by weight.

Since the external preparation for skin of the present invention may belong to any category of pharmaceuticals, quasi-drugs, and cosmetics, it can be used for various applications. For example, anti-aging effects, anti-wrinkle effects that give skin tension and elasticity, etc. can be expected by the antioxidant action, activation of cells, improvement of metabolism, etc., so that dry pruritus, Dermatitis treatment or antipruritic agent for treating pruritus, moistness, bruise and other itching and inflammation, injury healing agent for promoting treatment of wrinkles, cracks, chapped skin, infectious skin for treating acne, etc. Drugs for treating diseases, cheilitis, cheilitis, lip cracks, sores, etc., rough hands, rough skin, rough lips, wrinkles / sag, smooth skin, smooth lips Cosmetics used for quasi-drugs, moisturizing, whitening, anti-wrinkle, etc., to keep skin and lips healthy, to give moisture to skin and lips, and to prevent dryness, moistness, cracks, red spots, rashes, etc. It can be exemplified as suitable applications.
In addition to ubiquinones, other ingredients that can be incorporated include, for example, dermatitis or antipruritics for treating pruritus and inflammation such as eczema, rash, cuts, scratches, shoe rubs, scratches, scratches, burns, suppuration Bactericidal disinfectants and wound healing agents for the promotion and prevention of exacerbation of infectious wounds, infectious skin disease treatments or antibacterial agents for treating athlete's foot, etc., finger lift, elbow, knee, heel and ankle Pharmaceuticals such as keratin softeners and anti-inflammatory analgesics for treating keratinosis and shark skin, scalp preparations such as hair growth, hair growth promotion and hair growth, hair care preparations such as shampoo and rinse, hot flashes after sunburn, skin Examples include quasi-drugs used for prevention of lip protection, odor control, etc., cosmetics used for keratin softening, cleansing, and the like.

  The external preparation for skin of the present invention does not impair quality such as storage stability and viscosity, and within the quantitative and qualitative range that does not impair the effects of the present invention, as necessary, in the pharmaceutical, quasi-drug or cosmetic field. Ingredients commonly used in the formulation, such as bases, surfactants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, etc. can do. In addition, these components can be mix | blended individually by 1 type or in combination of 2 or more types.

  Base: hydrocarbons such as paraffin, gelled hydrocarbon, ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid, oleic acid, linoleic acid Fatty acids such as tri-fatty acid glycerides such as glyceryl tri-2-ethylhexanoate (trioctanoin), highly polymerized methylpolysiloxane, dimethylsiloxane / methyl (polyoxyethylene) siloxane / methyl (polyoxypropylene) siloxane copolymer, Dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene / methylpolysiloxane copolymer, poly (oxyethylene) Oxypropylene) / methylpolysiloxane copolymer, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methylpoly Polymerized silicones such as siloxane, crosslinked methylphenyl polysiloxane, crosslinked polyether-modified silicone, crosslinked alkyl polyether-modified silicone, crosslinked alkyl-modified silicone, ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol Glycol acetates such as diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol diacetate, triethylene glycol divalerate, 2,2,4-triacetate Glycol esters such as methyl-1,3-pentanediol monoisobutyrate and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate, ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate Glycol acrylates such as acrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1,3-butylene glycol diacrylate, ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate Glycol dinitrate such as trat, 2,2 '-[1,4-phenylenedioxy] diethanol, dioxane, butylene glycol adipic acid polyester.

  Surfactant: Sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate Glyceryl fatty acids such as glyceryl monostearate and glyceryl monostearate malic acid, polyglyceryl fatty acids such as polyglyceryl monoisostearate and polyglyceryl diisostearate, propylene glycol fatty acid esters such as propylene glycol monostearate, polyoxyethylene cured Hardened castor oil derivatives such as castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, polylauric acid poly Polyoxyethylene sorbitan fatty acid esters such as xylethylene (20) sorbitan (polysorbate 20), polyoxyethylene monostearate (20) sorbitan (polysorbate 60), polyoxyethylene monooxylate (20) sorbitan (polysorbate 80), poly Oxyethylene monococonut oil fatty acid glyceryl, glycerin alkyl ether, alkyl glucoside, polyoxyethylene cetyl ether, stearylamine, oleylamine and the like.

  Thickener: Guar gum, locust bean gum, carrageenan, xanthan gum, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone , Polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, sodium polyacrylate, polyethylene glycol, bentonite, dextrin fatty acid ester, pectin and the like.

  Preservatives: Benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, paraoxybenzoic acid Methyl, phenoxyethanol, etc.

  pH adjusters: inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, sodium succinate, oxalic acid, gluconic acid, Fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, Calcium hydroxide, magnesium hydroxide, etc.), organic bases (monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.).

  These components can be used alone or in combination of two or more. Moreover, those compounding amounts are not particularly limited as long as the effects of the present invention are obtained, but can be suitably selected and used as long as the upper limit compounding amount allowed by the Pharmaceutical Affairs Law is desirable. Specifically, it can be prepared according to the purpose from the range of usually 0.001 to 20 parts by weight, preferably 0.001 to 10 parts by weight, more preferably 0.001 to 5 parts by weight per 100 parts by weight of the external preparation for skin.

  The present invention also includes a method for promoting percutaneous absorption of ubiquinones incorporated in an external preparation for skin. In the method of the present invention, promotion of percutaneous absorption of an external preparation for skin containing ubiquinones can be achieved by containing phospholipid and glycol ether.

  Furthermore, the present invention includes a method for promoting percutaneous absorption of ubiquinones by applying a combination of phospholipids, glycol ethers and ubiquinones. In the method of the present invention, percutaneous absorption of ubiquinones can be promoted by applying phospholipids and glycol ethers to the skin simultaneously with or before and after the application of ubiquinones. Among them, it is preferable to apply phospholipid and glycol ether before application of ubiquinones, or to apply phospholipid and glycol ether simultaneously with ubiquinones. Regarding the method of using phospholipid, glycol ether and ubiquinones in the present method, all the components may be contained in the same preparation or in different preparations.

  In the method of the present invention, phospholipids, glycol ethers, ubiquinones, their blending amounts, and blending ratios of phospholipids and glycol ethers are the same as those used in the above-mentioned external preparation for skin. These methods can be used in known or commonly used dosages and dosages by dividing the dosage form once to several times per day according to the formulation used.

  EXAMPLES The present invention will be specifically described below with reference to examples, but these examples do not limit the scope of the present invention. In addition, a compounding quantity etc. represent weight% altogether about purified water or a thing without the description of a unit.

Test Example 1 Transdermal absorbability test
According to the formulation shown in Table 1, phospholipid and coenzyme Q10 are dissolved in glycol ether and polyhydric alcohol and mixed with purified water heated separately. 10ml of glyceryl tri-2-ethylhexanoate was placed in the reservoir side of the skin, and after fixing the entire skin of hairless mice (strain: HR-1, 7 weeks old, male) from between the cells, donor 2 g of test drug was added to the side. Two hours after the addition of the test drug, the entire skin was removed from the cell, the stratum corneum surface was washed with ethyl acetate and purified water, the entire skin was homogenized and extracted with ethyl acetate, and coenzyme Q10 was quantified by HPLC.
The results are shown in Table 1.

It was found that the amount of coenzyme Q10 retained in the skin was significantly improved by 3.6 to 8.4 times in Examples 1 to 3 using ethoxydiglycol than in Comparative Example 1 using glycerin. It was also found that lecithin with a lower degree of hydrogenation retained more coenzyme Q10.
As described above, Examples 1 to 3 are skin external preparations with excellent transdermal absorbability capable of efficiently storing coenzyme Q10 in the skin, and the effects of coenzyme Q10 can be sufficiently expected. It is particularly useful. Further, ubiquinones having 6 to 9 isoprene units (coenzyme Q6 to Q9) have very similar physical properties to those of coenzyme Q10 having 10 isoprene units, and can be expected to exhibit almost the same behavior in percutaneous absorption.
Therefore, anti-aging effect, anti-wrinkle effect that gives skin tension and elasticity by anti-oxidation effect, activation of cells, improvement of metabolism, etc. possessed by efficient penetration of ubiquinones into skin are expected. can do.

  The formulation examples are given below. In addition, the compounding quantity in the following Examples represents weight% about all the things which have no description of a unit especially.

Claims (6)

An external preparation for skin containing phospholipid, glycol ether, and ubiquinones. Glycol ether is ethylene glycol monoether, ethylene glycol diether, propylene glycol monoether, propylene glycol diether, butylene glycol monoether, butylene glycol diether, diethylene glycol monoether, diethylene glycol diether, dipropylene glycol monoether, dipropylene The skin external preparation according to claim 1, which is one or more selected from the group consisting of glycol diether, dibutylene glycol monoether and dibutylene glycol diether. The skin external preparation according to claim 1 or 2, wherein the phospholipid is a hydrogenated phospholipid. The skin external preparation according to claim 1 or 2, wherein the phospholipid is a non-hydrogenated phospholipid. The iodine external value of hydrogenated phospholipid is 10-50, The skin external preparation in any one of Claims 1-3. The skin external preparation according to any one of claims 1 to 5, wherein the ubiquinones are one or more selected from the group consisting of coenzyme Q6, coenzyme Q7, coenzyme Q8, coenzyme Q9 and coenzyme Q10.