JPH0826961A - Skin external preparation composition - Google Patents

Abstract

(57) [Summary] [Structure] A skin external preparation composition containing one or more compounds selected from xanthine derivatives, β-adrenergic stimulants, α ₂ -adrenergic inhibitors, and bipyridine derivatives and a cationized polymer. . [Effect] The external preparation composition for skin of the present invention imparts a sufficient moist feeling to the skin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation composition excellent in moisturizing feeling of the skin.

[0002]

2. Description of the Related Art Conventionally, xanthine derivatives, β-adrenergic stimulants, α ₂ -adrenergic inhibitors and bipyridine derivatives have been used as a topical drug having a slimming action or an anti-cellulitis action by being mixed with a massage agent or the like. Came.

[0003]

However, the above-mentioned xanthine derivative, β-adrenergic stimulant, α ₂ -adrenergic inhibitor and bipyridine derivative have a slimming effect and an anti-cellulitis effect, but have a sufficient moist feeling on the skin. However, there is a problem that the external feeling agent containing this is uncomfortable when applied to the skin. Therefore, a skin external preparation composition excellent in moisturizing feeling of the skin has been desired.

[0004]

[Means for Solving the Problems] Under such circumstances, as a result of intensive investigations by the present inventors, one selected from xanthine derivatives, β-adrenergic stimulants, α ₂ -adrenergic inhibitors, and bipyridine derivatives 1 If a cationized polymer is mixed with one or more compounds,
The present invention has been completed by finding that an external preparation for skin having excellent moist feeling on the skin after use can be obtained.

That is, the present invention provides a xanthine derivative,
It is intended to provide a skin external preparation composition containing one or more compounds selected from β-adrenergic stimulants, α ₂ adrenergic inhibitors, and bipyridine derivatives and a cationized polymer.

The xanthine derivative used in the present invention is not particularly limited, but for example, the following general formula (1):

[0007]

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[In the formula, R ¹ represents a methyl group or a hydrogen atom, and R ² represents a hydrogen atom, a hydroxy group having 1 to 2 carbon atoms or an alkanoyl group having 2 to 10 carbon atoms, which may be substituted. ~ 12 alkyl groups are shown. ] The compound or its salt represented by these is mentioned.

Examples of such xanthine derivatives include xanthine, aminophylline, theophylline, choline theophylline, caffeine, theobromine, oxtriphylline, diprophylline and proxyphylline. These may be used alone or in combination of two or more. In the present invention, it is preferable to use one or more selected from the group consisting of aminophylline, theophylline and caffeine.

The content of the xanthine derivative in the composition is preferably 0.005% by weight (hereinafter referred to simply as "%") or more, and particularly preferably 0.01 to 10%. In addition, as these xanthine derivatives, those that are substantially purely isolated from plants such as synthetic or tea leaves can be used.

The β-adrenergic stimulant used in the present invention is not particularly limited, but isoproterenol, epinephrine, norepinephrine, dobutamine, dopamine, butopamine, salbutamol, terbutaline, isoethalin, protoxylol, fenoterol, Metaproterenol, chlorprenaline, hexoprenaline, trimethoquinol, procaterol hydrochloride, prenalterol, forskolin, disodium (R,
R) -5- [2-[[2- (3-chlorophenyl) -2
-Hydroxyethyl] -amino] propyl] -1,3-
Benzodioxole-2,2-dicarboxylate,
(R ^* , R ^* )-4- [2-({2-[(3-chlorophenyl) -2-hydroxyethyl] amino} propyl) phenyl] phenoxyacetic acid, {2-hydroxy-5- [2
-({2-hydroxy-3- [4- (1-methyl-4-
Trifluoromethyl) -1H-imidazol-2-yl] phenoxy} propyl) amino] ethoxy} -benzamide monomethanesulfonate, erythro-DL-
Examples thereof include 1- (7-methylindan-4-yloxy) -3-isopropylaminobutan-2-ol, and pharmaceutically acceptable salts thereof. Examples of the pharmaceutically acceptable salt include pharmaceutically acceptable acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts and the like. In the present invention, isoproterenol,
It is preferable to use one or more selected from the group consisting of dobutamine, salbutamol, and pharmacologically acceptable salts thereof. In this case, the salt is preferably a hydrochloride or a sulfate.

The blending amount of the β-adrenergic stimulant is preferably 0.005% or more in the total amount of the composition, and particularly preferably 0.01 to 20%.

The α ₂ adrenergic inhibitor used in the present invention is not particularly limited, but yohimbine, phentolamine, phenoxybenzamine, trazoline, ergotamine, ergotoxin, dihydroergotamine, ergomethrin, methylergomethrin, dihydro. Examples thereof include ergotoxin, lauorcin, piperoxane, and pharmacologically acceptable salts thereof. Examples of the pharmacologically acceptable salt include those similar to the above. In the present invention, yohimbine, phentolamine,
It is preferable to use one or more selected from the group consisting of ergotamine and a pharmacologically acceptable salt thereof, and in this case, the salt is preferably a mesylate salt or a tartrate salt.

The blending amount of the α ₂ adrenergic inhibitor is
The total amount of the composition is preferably 0.005% or more,
It is particularly desirable to set it to 0.01 to 20%.

The bipyridine derivative used in the present invention is not particularly limited, but examples thereof include compounds represented by the following general formula (2), and pharmacologically acceptable salts thereof.

[0016]

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(In the formula, R is a hydrogen atom, a methyl group or an ethyl group.
Shows an alkyl group such as a chloro group and Q is NH. ₂, NC, H₂NC
Indicates O and the like. ) Such bipyridine derivatives include amrinone and mirin.
Lurinone, 5-cyano- [3,4'-bipyridine] -6
(1H) -one, 5-carbamyl- [3,4'-bipyri
Gin] -6 (1H) -one, and pharmacologically acceptable thereof
And the like. As a pharmacologically acceptable salt
Are the same as those mentioned above. In the present invention
Amrinone, milrinone, and their pharmacologically acceptable
One or more selected from the group consisting of contained salts
It is preferable to use.

The blending amount of the bipyridine derivative is preferably 0.005% or more, especially 0.0
It is desirable to be 1 to 20%.

The cationized polymer used in the present invention is not particularly limited, but includes cationized cellulose such as diethylaminated ethyl cellulose, diisopropylaminated ethyl cellulose, dimethylaminated ethyl cellulose, cationized starch, cationized dextran and cationized cellulose. Examples thereof include dextrin, cationized vinylpyrrolidone polymer and cationized chitosan, and these can be used alone or in combination of two or more. Of these, cationized cellulose and cationized dextran are particularly preferable in the present invention.

From the viewpoint of moisturizing the skin, it is preferable that the amount of the cationized polymer is 0.1 to 10%, especially 0.05 to 5%, based on the total amount of the composition.

In addition, the skin external preparation composition of the present invention contains an oily component, a surfactant, a humectant, a polymer compound, an ultraviolet absorber and an antioxidant which are used in various preparations for external medicines and cosmetics. Various raw materials such as metal ion sequestering agents, drugs, preservatives, vitamins, pigments, and fragrances can be added.

Examples of the oily component include fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, essential oils, silicone oils and the like.

Examples of fats and oils are soybean oil, nuka oil,
Jojoba oil, avocado oil, almond oil, olive oil, cacao oil, sesame oil, persic oil, castor oil, coconut oil, mink oil, natural fats and oils such as beef tallow and lard, and hardened oils obtained by hydrogenating these natural fats and oils. And synthetic triglycerides such as myristic acid glyceride and 2-ethylhexanoic acid triglyceride. Examples of waxes include carnauba wax, whale wax, beeswax, and lanolin. Examples of the hydrocarbons include liquid paraffin, petrolatum, paraffin microcrystalline wax, ceresin, squalane, blistane and the like. Examples of the higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid and isostearic acid. Examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol and 2-hexyldecanol. As the esters, cetyl octanoate, triglyceride octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, octyldodecyl myristate,
Isopropyl palmitate, isopropyl adipate,
Examples thereof include butyl stearate, decyl oleate, cholesterol isostearate, and POE sorbit fatty acid ester. Examples of essential oils are peppermint oil, jasmine oil, pepper brain oil, cypress oil, spruce oil, ryu oil, turpentine oil, cinnamon oil, bergamot oil, mandarin oil, chive oil, pine oil, lavender oil, bay oil, clove oil. ,
Hiba oil, rose oil, eucalyptus oil, lemon oil, thyme oil, peppermint oil, rose oil, sage oil, menthol, cineole, eugenol, citral, citronellal,
Examples include borneol, linalool, geraniol, camphor, thymol, spilanthol, pinene, limonene, and terpene compounds. Examples of silicone oils include dimethylpolysiloxane. These oily components described above can be used alone or in combination of two or more. In the present invention, of these, myristic acid glyceride, 2-ethylhexanoic acid triglyceride, lanolin, liquid paraffin, petrolatum, paraffin microcrystalline wax, squalane, lauric acid, myristic acid, palmitic acid, linoleic acid, linolenic acid, isostearic acid , Cetyl alcohol, stearyl alcohol, oleyl alcohol, cholesterol,
Cetyl octanoate, triglyceride octanoate, isopropyl myristyrene, octyldodecyl myristate, cholesterol isostearate, POE sorbit fatty acid ester, peppermint oil, spruce oil, cinnamon oil, rose oil, menthol, cineole, eugenol, citral, citronellal, It is preferable to use geraniol, pinene, limonene, dimethylpolysiloxane.

The content of the oily component in the external preparation for skin can be appropriately selected according to the dosage form (form) of the external preparation for skin, and is usually 0.1 to 95% in the total amount of the composition.
Can be

As the surfactant, any of anionic, cationic, amphoteric, nonionic, natural and synthetic surfactants can be used, but in consideration of skin irritation, a nonionic one is used. It is preferable.

Examples of the nonionic surfactant include glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, tetraoleic acid polyoxyethylene sorbit, polyoxyethylene alkyl ether, polyoxyethylene. Examples thereof include polyoxypropylene glycol, polyoxyethylene polyoxypropylene alkyl ether, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, and alkyl glycoside.

Other various raw materials include carbonates such as sodium hydrogen carbonate, sodium carbonate and calcium carbonate; organic acids such as succinic acid, glutaric acid and fumaric acid; boric acid, metasilicic acid and silicic acid anhydride. Inorganic acids; fennel, chamomile, ginkgo, oyster, cinnamon, safflower, peony, ginger, iris, senkyu, touki, chimpi, sojutsu, valerian, juniper, spruce, peppermint, carrot, yellow ginseng, yellow # 4, yellow Blue 1
No., Yellow No. 202, etc., tar dyes specified in the Ordinance of the Ministry of Health and Welfare, dyes of Appendices I and II, chlorophyll, riboflavin,
Pigments such as natural pigments recognized as food additives such as crocin, safflower, anthraquinone; vitamins such as vitamin A, vitamin C, vitamin D, vitamin E; sulfur, yunohana, mineral sand, mica powder, neutral Examples include white clay, rice bran, bactericides, preservatives, and other necessary components for formulation.

The external preparation for skin of the present invention can be produced by adding the above-mentioned optional components to the above-mentioned essential components as necessary. The blending amount of these optional components is 0 to 99 in the formulation.
It is blended in the range of%.

Further, the skin external preparation composition of the present invention prepared as described above is added with an appropriate amount of water in the range of 0.01 to 90% to increase the stability of the preparation or to emulsify the preparation. It can also have a different form.

The dosage form of the external preparation for skin of the present invention is not particularly limited, and various dosage forms such as creams, gels, ointments, solutions, pastes, poultices and plasters can be used. it can. When the external preparation for skin of the present invention is used as a bath agent, it can be made into various dosage forms such as powder, granules, tablets, and liquids in the same manner as known bath agents.

The bath agent composition is used by putting it in a bath when taking a bath, and the amount used once is a xanthine derivative, a β adrenergic stimulant, an α ₂ adrenergic inhibitor, It is preferable that the concentration of the bipyridine derivative in the bath water is 0.01 to 200 ppm.
If the concentration is less than 0.01 ppm, the moisturizing feeling of the skin cannot be imparted, and if it exceeds 200 ppm, the effect of imparting the moisturizing feeling of the skin is not further improved.

[0032]

The external preparation composition for skin of the present invention gives a sufficient moisturizing feeling to the skin.

[0033]

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Examples 1 to 4 and Comparative Examples 1 and 2 Gel type external preparations for skin having the compositions shown in Table 1 were prepared by a conventional method, and the moist feeling of the skin was examined by the following test method. The results are shown in Table 1.

Moisturization of the skin: About 4 g of the external preparation composition for skin shown in Table 1 is applied around the thigh of each subject (n = 5). The moist feeling of the coated part after 1 hour was judged according to the following criteria and shown as the average point.

5 points: Very moist. 4 points: Moist well. 3 points: Moist. 2 points: Somewhat moist. 1 point: Do not moisturize.

[0037]

[Table 1]

From Table 1, the skin external preparation compositions of Examples 1 to 4 containing the xanthine derivative and the cationized polymer were the same as the skin external preparation compositions of Comparative Examples 1 to 2 containing no xanthine derivative or the cationized polymer. In comparison, it can be seen that the moist feeling of the skin is excellent.

Examples 5 to 8 and Comparative Examples 3 to 4 Gel-like external preparations for skin having the compositions shown in Table 2 were prepared by a conventional method, and the same test method as in Example 1 was used to give the skin a moist feeling. Examined. Table 2 shows the results.

[0040]

[Table 2]

From Table 2, the skin external preparation compositions of Examples 5 to 8 in which the β-adrenergic stimulant and the cationized polymer were blended were the same as those of Comparative Examples 3 to 4 in which the β-adrenergic stimulant or the cationized polymer was not blended. It can be seen that the skin moisturizing feel is superior to that of the external skin preparation composition.

Examples 9 to 12 and Comparative Examples 5 to 6 W / O cream-like external preparations for the skin having the compositions shown in Table 3 were prepared by a conventional method, and the same test method as in Example 1 was applied to the skin. I examined the moist feeling. The results are shown in Table 3.

[0043]

[Table 3]

[0044] From Table 3, the skin external composition of Examples 9-12 were blended alpha ₂ adrenergic inhibitors and cationic polymers are comparative examples not blended alpha ₂ adrenergic inhibitors or cationic polymer 5 It can be seen that the skin moisturizing feel is superior to that of the skin external preparation composition of No. 6.

Examples 13 to 15 and Comparative Examples 7 to 8 Oily gel type external preparations for skin having the compositions shown in Table 4 were prepared by a conventional method, and the moist feeling of the skin was measured by the same test method as in Example 1. I checked. The results are shown in Table 4.

[0046]

[Table 4]

From Table 4, the skin external preparation compositions of Examples 13 to 15 containing the bipyridine derivative and the cationized polymer were the same as the skin external preparation compositions of Comparative Examples 7 to 8 containing no bipyridine derivative or the cationized polymer. In comparison, it can be seen that the moist feeling of the skin is excellent.

Examples 16 to 19 and Comparative Examples 9 to 10 Powdery external preparations for skin (bath preparation compositions) having the compositions shown in Table 5 were prepared by a conventional method, and the skin was moistened by the following test method. And the warmth of the body was examined. The results are shown in Table 5.

Moisturizing sensation of skin: The bath agent composition of the amount used per one time shown in Table 5 is put into a bathtub filled with 150 l of hot water at 40 ° C. After this was dissolved in hot water, the hot water was thoroughly stirred, each subject (n = 5) was allowed to bathe for 5 minutes, and the moist feeling of the skin was judged according to the following criteria and shown as the average point.

5 points: Very moist. 4 points: Moist well. 3 points: Moist. 2 points: Somewhat moist. 1 point: equivalent to Sarayu.

[0051]

[Table 5]

From Table 5, the bath agent compositions of Examples 16 to 19 in which the xanthine derivative, the β-adrenergic stimulant, the α ₂ -adrenergic inhibitor, or the bipyridine derivative and the cationized polymer were blended, were prepared from these compounds or cations. It can be seen that the moisturizing feel of the skin is excellent as compared with the bath agent compositions of Comparative Examples 9 to 10 in which the modified polymer is not blended.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location C07D 213/22 473/06

Claims (5)

[Claims] 1. A skin external preparation composition containing one or more compounds selected from a xanthine derivative, a β-adrenergic stimulant, an α ₂ -adrenergic inhibitor, and a bipyridine derivative, and a cationized polymer. 2. The external preparation composition for skin according to claim 1, wherein the xanthine derivative is selected from the group consisting of aminophylline, theophylline and caffeine. 3. The β-adrenergic stimulant is selected from the group consisting of isoproterenol, dobutamine, salbutamol, and pharmacologically acceptable salts thereof.
The external preparation composition for skin according to the above. 4. The skin external preparation composition according to claim 1, wherein the α ₂ adrenergic inhibitor is selected from the group consisting of yohimbine, phentolamine, ergotamine, and pharmacologically acceptable salts thereof. 5. The skin external preparation composition according to claim 1, wherein the bipyridine derivative is selected from the group consisting of amrinone, milrinone, and pharmacologically acceptable salts thereof.