JP2002284697A - External skin preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external skin preparation for effectively treating or improving freckles, acne, keratosis and athlete's foot, which is low irritant to skin and is suitable for prolonged continuous application. SOLUTION: The external skin preparation is characterized by that the preparation contains Coix lachryna-jobi L. Var. ma-yuen Stapf or its extract and a dicarboxylic acid represented by formula (l) [wherein, R1 and R2 are H or lower alkyl group; n is an integer of 6-8] and/or its derivative.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an external preparation for skin. More particularly, the present invention is the following formula (1)

Embedded image (Wherein R ₁ and R ₂ represent hydrogen or a lower alkyl group;
It represents an integer of 6-8. ), And a dicarboxylic acid and / or a derivative thereof and yokuinin or yokuinin extract, which is excellent in treating and improving spots, freckles, acne, keratosis, athlete's foot and the like. have, and to a skin external agent capable long-term continuous administration having improved skin irritation.

[0002]

BACKGROUND OF THE INVENTION stains, freckles, acne, keratosis, drugs and to treat and improve the skin diseases such as athlete's foot, called the whitening cosmetics, cosmetic, etc. allowed to prevent and improve the melanin deposition of skin skin Many external preparations are commercially available.

[0003] There are various compounds as active ingredients of such external preparations for skin, and one of them is, for example,
There are known dicarboxylic acids of suberic acid, azelaic acid and sebacic acid and derivatives thereof.

[0004] For example, ROOC- (CH2) dicarboxylic acids of n = 5 to 11 represented by the general formula n-COOR and /
Or a derivative thereof, in JP-A-53-130433, it has a therapeutic effect of the dye excessive skin disease or skin pigmentation excess diseases, also in JP-A-61-85307, the
Stains, freckles, acne, pigmentation, have effect of improving color such as black is disclosed.

However, among the above compounds, as the number of carbon atoms in the methylene chain is increased, there is a tendency for percutaneous absorption becomes poor of the above compounds, there may not effectively exhibit efficacy in vivo.

Further, compounds numbers less carbon methylene chain, strong skin irritation, therefore, there is a problem that it is difficult to continuously administered for a long period of time.

[0007] On the other hand, Coix is, the grass family (Graminea
e) belongs to Adlay (Coix lachryma-jobiLinnevar ma)
-Yuen Stapf) is a seed excluding the seed coat, and is known to have an effect of improving water metabolism, an anti-inflammatory and analgesic effect, and the like.

Japanese Patent Application Laid-Open No. 10-36279 discloses an attempt to incorporate an extract such as yoquinin or an extract thereof into an external preparation for skin. Specifically, an extract obtained by extracting yoquinin with a solvent such as water has a fibroblast growth promoting action, and is used for skin diseases such as eczema and rough skin, and for the purpose of promoting the growth of skin and dermis. prevention etc., have been disclosed to be effective in the treatment.

However, yoquinin or yoquinin extract is converted into the following formula (1)

Embedded image (Wherein, R _1, R ₂ represents hydrogen or a lower alkyl radical, n
Represents an integer of 6 to 8. ) And / or a derivative thereof to have an excellent synergistic effect on the treatment of spots, freckles, acne, keratosis, athlete's foot, etc., and by using them together, the formula not known at all about what can improve the skin irritation with the compound of formula (1).

[0010]

The object of the present invention is to solve the above is a stain, freckles, have acne, keratoses, excellent effects for treatment and improvement of such athlete's foot, and since less skin irritation, long for a period to provide a continuous administrable external preparation for skin.

[0011]

Means for Solving the Problems The present inventors have conducted various studies to achieve the above object, and as a result, the following formula (1)

Embedded image (Wherein, R _1, R ₂ represents hydrogen or a lower alkyl radical, n
Represents an integer of 6 to 8. The present inventors have found that a skin external preparation characterized by containing a dicarboxylic acid and / or a derivative thereof represented by the formula (1)) and yoquinin or a yoquinin extract is suitable for the purpose of the present invention, and completed the present invention.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

The following formula (1) used in the present invention:

Embedded image (Wherein R ₁ and R ₂ represent hydrogen or a lower alkyl group;
It represents an integer of 6-8. Examples of the dicarboxylic acid represented by ()) include suberic acid, azelaic acid and sebacic acid.

Examples of the dicarboxylic acid derivatives include the above ester compounds. A lower alkyl group refers to a linear or branched alkyl group having 1 to 4 carbon atoms, and specifically, a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, a sec- Butyl group or tert
- and butyl group.

The compound of the formula (1) can be used alone or in combination of two or more if necessary. The amount is 1 wt% to 25 wt% with respect to the skin external composition, and preferably from 4 wt% to 20 wt%. When the content is less than 1% by weight, a sufficient effect is not exhibited.
If the content is 5% by weight or more, it is not desirable because the effect corresponding to the content is not obtained and the preparation is difficult.

[0016] Equation 2% by weight as the concentration of compound (1)
Or more, more preferably it is desirable to 4% by weight or more. By a large amount of the compound of formula (1) in the formulation, improvement in the effect can be expected, moreover According to the present invention, since does not produce skin irritation problems than usual amounts of the formula ( The compound of 1) can be blended.

[0017] The Yokuinin used in the present invention is obtained by drying or pulverizing Yokuinin as it is, and the Yokuinin extract is obtained by extracting Yokuinin with an extraction solvent.

[0018] Coix of extraction, water as an extraction solvent,
Ethanol, anhydrous ethanol, 1,3-butylene glycol, propylene glycol, hexylene glycol,
Acetone or a mixed solvent of two or more of these can be used, but an extract of water is particularly preferable. Extracted extract may be used in concentration as it is, or necessary.

It is desirable to add 0.1% to 50% by weight, more preferably 1% to 20% by weight, as a crude drug, of the yokunin extract in the skin preparation for external use of the present invention. Coix extract may not express sufficient effect is 0.1 wt% or less of the formulation, be blended 50% by weight or more, there is a possibility that the effect is saturated.

The dimethyl isopropyl azulene used in the present invention includes aznol ointment (manufactured by Nippon Shinyaku Co., Ltd.) containing dimethyl isopropyl azulene as it is or containing 0.033% dimethyl isopropyl azulene.

[0021] As the dimethyl isopropyl azulene in the skin external preparation of the present invention 25% ～98.9 wt%, more preferably it is desirable to blend 60 wt% to 95 wt%.

The external preparation for skin of the present invention can be used as it is as an external preparation, but if necessary, any component usually used for the production of pharmaceuticals or cosmetics may be appropriately added within a range not to impair the effects of the present invention. You can also. For example, water, oil, surfactant, Nebazai, resins, physiologically active ingredients, preservatives, buffering agents, pH adjusting agents and the like.

Specifically, the dosage form of the external preparation for skin of the present invention includes ointments, lotions, O / W creams, W / O
Examples include creams, gels, sprays and patches.

[0024] As the oil, normally include volatile and non-volatile oil and a solvent and a resin used in the skin external preparation, it is possible to use a liquid, paste, any of the solid at room temperature. Examples of oils include, for example, cetyl alcohol,
Higher alcohols such as isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, and octyldodecanol; fatty acids such as isostearic acid, undecylenic acid, and oleic acid; polyhydric alcohols such as glycerin, sorbitol, ethylene glycol, propylene glycol, and polyethylene glycol; and myristin Myristyl acid,
Esters such as hexyl laurate, decyl oleate, isopropyl myristate, hexyldecyl dimethyloctanoate, glyceryl monostearate, diethyl phthalate, ethylene glycol monostearate, octyl oxystearate, liquid paraffin, petrolatum, squalane, etc. Hydrocarbons, lanolin, reduced lanolin, waxes such as carnauba wax, mink oil, cocoa butter, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, oils and fats such as olive oil, ethylene / α-olefin / co-oligomers, etc. It is.

Examples of other types of oils include dimethylpolysiloxane, methylhydrogenpolysiloxane, methylphenylpolysiloxane, polyether-modified organopolysiloxane, fluoroalkyl.
Polyoxyalkylene co-modified organopolysiloxane,
Alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, fluorine-modified organopolysiloxane, amodimethicone, amino-modified organopolysiloxane, silicone compound such as silicone gel, silicone RTV rubber, perfluoropolyether, pitch fluoride, fluorocarbon, fluoroalcohol fluorine compounds and the like.

Examples of the solvent include purified water, cyclic silicone, ethanol, light liquid isoparaffin, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, branched volatile Silicone, next-generation chlorofluorocarbon and the like can be mentioned.

As examples of the surfactant, for example, an anionic surfactant, a cationic surfactant, a nonionic surfactant, and an amphoteric surfactant can be used. More specifically, fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, alkyl amide phosphates, alkyloylalkyl taurine salts, N- acylamino acid salts, sulfosuccinic acid salts,
Anionic surfactants such as perfluoroalkyl phosphoric acid esters, alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, bromide stearyltrimethylammonium, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, bromide Nonionic surfactants such as cationic surfactants such as behenyltrimethylammonium, alkanolamide laurate, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE fatty acid ester, polyether-modified silicone, carboxybetaine type,
Amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type,
Amidoamine type and other amphoteric surfactants are exemplified. In addition, natural surfactants such as saponins and sugar surfactants can also be used.

[0028] Nebazai, examples of the resin, sodium polyacrylate, cellulose ether, calcium alginate, carboxyvinyl polymer, ethylene / acrylic acid copolymers, vinylpyrrolidone polymers, vinyl alcohol / vinyl pyrrolidone copolymer, nitrogen Substituted acrylamide polymers, polyacrylamide, cationic polymers such as cationized guar gum, dimethylacrylammonium polymer, acrylic acid methacrylate acrylic copolymer, POE / POP copolymer, polyvinyl alcohol, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high-methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, Toragakantoga , Alginic acid, albumin, casein, curdlan, gellan gum, dextran, cellulose, polyethyleneimine, highly polymerized polyethylene glycol, cationized silicone polymer, synthetic latex, acryl silicone, trimethylsiloxy silicate,
Fluorinated silicone resins and the like can be mentioned.

Examples of the physiologically active ingredient include substances which give some physiological activity to the skin when applied to the skin. Examples include biopolymers, moisturizing components, anti-inflammatory agents, vitamins, antioxidants, cell activators, blood circulation promoters, wound healing agents, and the like. Among them, natural plant extract components,
A seaweed extract component and a crude drug component are particularly preferred.

Examples of these components include Ashitaba extract, Avocado extract, Amacha extract, Althea extract, Arnica extract, Aloe extract, Apricot extract, Apricot kernel extract, Ginkgo extract, Fennel extract, Turmeric extract, Oolong tea extract, Eijitsu Extracts, Echinashi leaf extract, oak extract, oak extract, spinach extract, barley extract, hypericum extract, scotch extract, Dutch mustard extract, orange extract, seawater dried product, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk , Chamomile extract, carrot extract, sagebrush extract, licorice extract, calcade extract, syllium extract, kiwi extract, kina extract, cucumber extract, guanosine,
Gardenia extract, Kumazasa extract, Clara extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract, Mulberry extract, Gentian extract,
Black tea extract, yeast extract, burdock extract, rice bran extract, rice germ oil, comfrey extract, collagen,
Cowberry extract, Saishin extract, Psychoextract, Saitai extract, Salvia extract, Sabonso extract, Sasa extract, Hawthorn extract, Sansho extract, Shiitake extract, Jio extract, Shikon extract, Perilla extract, Shinanoki extract, Shimotsukeiso extract, Peony extract, Shobu root extract , Birch extract, horsetail extract, vegetative extract, hawthorn extract,
Western elderberry extract, Achillea millefolium extract, Common mint extract, Sage extract, Genus mallow extract, Senkyu extract, Assembly extract, Soybean extract, Tissou extract, Thyme extract, Tea extract, Clove extract, Chigaya extract, Chimpanzee extract, Touki extract, Calendula extract, Tonin extract , Spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, nobara extract, hibiscus extract, Bacmondou extract, lotus extract, parsley extract, honey, hamamelis extract, pallietaria extract, lyeme extract, bisabolol, loquat extract, Coltsfoot extract, fukinotou extract, kukuroyou extract, butcher bloom extract, grape extract, propolis, loofah extract Safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, marronie extract, mugwort extract, mukuroji extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, yukinoshita extract, yuzu extract, mugwort extract, lavender extract, apple extract , Lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract and the like.

Also, biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, sodium lactate, urea, sodium pyrrolidonecarboxylate, Moisturizing ingredients such as betaine and whey, anti-inflammatory agents such as ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, azulene, hydrocortisone, vitamin A, vitamin B2, vitamin B6
Vitamins such as vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide and vitamin C ester; antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, saponins, α-hydroxy acids, β Cell activators such as -hydroxy acids, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, and wound healing agents such as retinol and retinol derivatives.

The external preparation for skin of the present invention has an effect on various skin diseases, and is used as a therapeutic agent for liver spots, rough skin, eczema, keratosis, sparrow eggs, pigmentation due to burns, acne, etc. Can be used. It can also be used as a whitening cosmetic or the like for the purpose of suppressing and improving melanin deposition.

It should be further noted that the external preparation for skin of the present invention also has an antifungal action and a hair-growth action.
It can also be used as a therapeutic agent for athlete's foot or a hair growth promoter.

[0034]

EFFECT OF THE INVENTION The skin external preparation of the present invention (an ointment containing azelaic acid and yoquinin extract) showed a remarkable effect as compared with the skin external preparation of the comparative example not containing yoquinine extract. Further, the external preparation for skin of the comparative example, five of 2
In all cases, the administration had to be discontinued due to skin irritation. On the other hand, it was confirmed that the skin external preparation of the present invention did not have administration discontinuation and the side effects were reduced. (See Table 1). In addition, the external preparation of the present invention is effective for inflammatory acute diseases such as irritations, acne, burns, and eczema in a short period of time, and is also effective for chronic diseases such as atopic dermatitis and pigmentation. Was done. In particular athlete's foot, for tinea pedis it was remarkably effective (see Table 2-5).

Accordingly, the present invention provides a skin external preparation which has an excellent effect as compared with a conventional skin external preparation containing a compound of the formula (1), and has improved skin irritation and can be administered continuously for a long period of time. Is provided.

Hereinafter, the present invention will be described in detail with reference to test examples.

[0037] The ointment of Test Example 1 Example 1 and Comparative Example, five (Man Two woman three) were tested for efficacy of ointments against a panel of. In the test, a fixed portion where pigmentation was observed was determined in two places for each panelist, and an appropriate amount of each ointment was applied to the same site three times daily for two weeks. Skin irritation occurs during the test, if the predicate is determined to difficult test was discontinued at that point. Improvement of pigmentation compared to before coating after completion of the test period, confirms the effect of Example 1
And the effect of the ointment of the comparative example was compared. Table 1 shows the results.
Shown in

Test Example 2 The ointment of Example 1 was applied to 24 to 10- to 70-year-old monitors with liver spot, sperm egg spot, pigmentation, acne, and keratosis diseases. It was applied to the affected area for a day. The results are shown in Table 2. Test Example 3 The ointment of Example 3 was applied to the affected area for 2 to 180 days on 13 monitors, aged 1 to 70, who had diseases such as contact dermatitis, eczema, athlete's foot, acne, and burns. Table 3 shows the results. Ointments Test Example 4 Example 4, lacerations, skin roughness, against ten monitors 54 aged 15 with skin diseases such as octopus,
It was applied to the affected area for 15 to 54 days. Table 4 shows the results. Test Example 5 The ointment of Example 5 was applied to erythema, octopus and eczema
24 to 48 for 3 monitors from 4 to 48 years old
Days was applied to the affected area. The results are shown in Table 5.

[0039]

The present invention will be specifically described below with reference to examples and comparative examples.

Prior to the examples, the method for producing yoquinin extract used in the present invention will be described first. After pulverizing 1 kg of yokunin, 2 L of water is added and extracted for 60 minutes. At this time, about 1 L of the extract is obtained. (Thus, Coix extract the original crude drugs weight basis at a concentration of 1 g / mL.) Also, azelaic acid commercially available products (chemical for,
(Manufactured by Wako Pure Chemical Industries, Ltd.).

(Example 1) Ointment A 50 ml of aquenine extract was added to and suspended in 50 g of azelaic acid, and an aznol ointment (an ointment containing 0.033% dimethylisopropylazulene) was added little by little to emulsify to make a total amount of 500 g. to give the ointment of the present invention.

[0042] (Example 2) The lotion azelaic acid 10g was dissolved in ethanol for disinfection 100 mL, added Coix extract 50 mL, to a total volume of 500mL by adding further purified water to obtain a lotion of the present invention.

[0043] (Example 3) was suspended added Coix extract 60mL azelaic acid 100 g, and emulsified by adding small portions Azunoru ointment (0.033% dimethyl isopropyl azulene the ointment containing), a total volume of 500 g, the An ointment of the invention was obtained.

(Example 4) 60 ml of an extract of yoquinin was added to and suspended in 100 g of sebacic acid, and aznol ointment (an ointment containing 0.033% dimethylisopropylazulene) was added little by little to emulsify the mixture to make the total amount 500 g. An ointment of the invention was obtained.

[0045] (Example 5) diethyl sebacate 50 g,
To 50 g of sebacic acid was added and suspended 60 mL of the okinine extract, and an aznol ointment (an ointment containing 0.033% dimethylisopropylazulene) was added little by little to emulsify to make a total amount of 500 g, thereby obtaining an ointment of the present invention.

(Comparative Example) An ointment of Comparative Example was obtained in the same manner as in Example 1 except that the yoquinin extract was not used.

[0047]

[Table 1]

[0048]

[Table 2]

[0049]

[Table 3]

[0050]

[Table 4]

[0051]

[Table 5]

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/00 101 A61P 17/00 101 17/10 17/10 17/12 17/12 17/16 17 / 16

Claims (9)

[Claims] 1. The following formula (1) (Wherein, R _1, R ₂ represents hydrogen or a lower alkyl radical, n
Represents an integer of 6 to 8. A skin external preparation comprising the dicarboxylic acid represented by the formula (1) and / or a derivative thereof, and yoquinin or a yoquinin extract. Wherein azelaic acid and / or skin external agent characterized by containing the derivative and Yokuininekisu. 3. An external preparation for skin, comprising sebacic acid and / or a derivative thereof and yoquinin extract. 4. Azelaic acid and / or a derivative thereof
Skin external agent characterized in that it contains 20 wt% and Yokuininekisu 0.1 to 50 wt%. 5. sebacic acid and / or its derivative 1-2
An external preparation for skin, comprising 0% by weight and 0.1-50% by weight of yoquinin extract. 6. The external preparation for skin according to claim 3, wherein the derivative of sebacic acid is diethyl sebacate. 7. The external preparation for skin according to claim 1, further comprising dimethylisopropylazulene. 8. The external preparation for skin according to claim 1, wherein the external preparation for skin is an external preparation for treating athlete's foot. 9. dosage form ointment external preparation for skin, lotions, O / W cream, W / O creams, gels, according to claim 1 which is spray or patch of the external preparation for skin.