JP2004075579A - Antipruritic agent for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe antipruritic agent effective for local skin pruritus associated with atopic dermatitis, asteatotic eczema, contact dermatitis and insect bite and sting and also having anti-inflammatory effect. <P>SOLUTION: The antipruritic agent for external use contains an L-3-O-1-22C alkylascorbic acid as the active ingredient. <P>COPYRIGHT: (C)2004,JPO

Description

製法　ａ）〜ｈ）までを混合し、均一に溶解する。
【００１６】
【実施例２】

製法　ａ）およびｇ）をエタノールｄ）に溶解し、残りを加え精製水ｈ）に溶解する。得られたゲル基剤を支持体である不織布に伸展させシート状パップを得る。
【００１７】
【実施例３】

製法　油性成分（Ａ）を７０℃に加熱混合する。水溶性成分（Ｂ）を混合し溶解させた後、７０℃に加熱し、（Ａ）成分を混和してホモミキサーにて乳化させる。室温にまで冷却して容器に充填し、クリームを得る。
【００１８】
【試験例１】
１０匹のＩＣＲ系雌マウス（日本クレア）の背部皮膚を剃毛し、実施例１の水溶液系ローション剤５０μＬを５匹のマウスに塗布した。塗布３０分後にＣｏｍｐｏｕｎｄ４８／８０（Ｓｉｇｍａ）１０μｇを剃毛部に皮内投与し、皮内投与直後から１５分間の掻破行動の発現回数を観察記録した。実施例１のローション剤処方から３−Ｏ−エチルアスコルビン酸のみを配合しないローションを作成して比較例１とし、実施例１のローションを塗した群と同様に５匹のマウスに塗布し、以下同様に処置した。
【００１９】
試験の結果を表１に示す。
【表１】掻破行動発現回数測定結果

【００２０】
表に示したとおり、実施例１は比較例に比べ明らかに掻破行動が抑制されており、実施例１の鎮痒効果が確認された。
【００２１】
【発明の効果】
以上詳述したように、本発明により優れた鎮痒効果を示す外用鎮痒剤を提供することが出来た。[0001]
[Industrial applications]
The present invention relates to an external antipruritic agent, and more particularly, to an external antipruritic agent effective for topical skin pruritus associated with atopic dermatitis, sebum deficiency eczema, contact dermatitis, insect bites and the like.
[0002]
[Prior art]
In recent years, diseases accompanied by itchy skin, such as atopic dermatitis, have increased. The causes of these diseases include air pollution such as an increase in nitrogen oxides contained in exhaust gas from diesel engines, the use of air conditioners throughout the year, and various lifestyle changes based on excessive cleanliness. ing. In addition to atopic dermatitis, not only skin diseases such as urticaria and contact dermatitis, but also visceral diseases such as liver injury and renal injury may be accompanied by itching of the skin. The causes of itching are quite varied. Numerous substances such as histamine, kinins, prostaglandins, leukotrienes, various proteases, and lymphokines are known as substances that cause itch. Of these, histamine has been recognized as the pruritus-inducing substance since the oldest, and in many cases, other stimulants are also considered to act secondary to mast cells to release histamine, thereby causing secondary itch. ing. Therefore, although antihistamines have been frequently used for the treatment of pruritus, it has a central side effect such as drowsiness as a side effect, and it cannot be said that the effect is sufficient.
[0003]
On the other hand, cyclooxygenase inhibitors such as indomethacin, ketoprofen and piroxicam are widely used for inflammatory diseases, but have little effect on dermatitis accompanied by itch. In addition, steroids are used as a first-line drug as an external preparation for atopic dermatitis due to their excellent anti-inflammatory effect, but their effect on itch itself is low, and side effects due to continuous use are also problematic. .
[0004]
[Problems to be solved by the invention]
The present invention is effective against topical skin pruritus associated with atopic dermatitis, sebum deficiency eczema, contact dermatitis, insect bites, etc. under such circumstances, and has an anti-inflammatory effect, It is intended to provide a safe external antipruritic agent.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to develop an external antipruritic agent having the above-mentioned preferable properties, and as a result, have found that a drug containing an L-ascorbic acid derivative as an active ingredient has an excellent antipruritic effect. The present invention has been completed based on the findings.
[0006]
That is, the present invention provides an external antipruritic agent characterized by containing an L-ascorbic acid derivative represented by the following formula (1), wherein R is an alkyl group having 1 to 22 carbon atoms. is there.
[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
The L-ascorbic acid derivative represented by Chemical formula 1 is a known ascorbic acid derivative which generally has an antioxidant effect, and has been found to have a carcinogenesis-suppressing effect, a cancer metastasis preventing effect, a whitening effect, and the like. WO 91/03471 describes an inhibitory effect on organ damage based on an inhibitory activity on lipid peroxidation, and WO 00/09121 describes an anti-inflammatory and analgesic effect on stiff shoulders, muscle pain, joint pain and the like. It has been shown to be excellent in safety, stability and transdermal absorbability.
[0008]
The alkyl group having 1 to 22 carbon atoms represented by R in Chemical Formula 1 may be linear, branched, or cyclic, and examples thereof include a methyl group, an ethyl group, an n-propyl group, and an isopropyl group. N-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, behenyl, cyclopropyl, Examples thereof include a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclooctyl group.
[0009]
The L-ascorbic acid derivative represented by Chemical Formula 1 can be easily produced by, for example, a known method described in JP-A-8-134,055.
[0010]
In the topical antipruritic agent of the present invention, one kind of the L-ascorbic acid derivative represented by the above formula 1 may be used, or two or more kinds may be used in combination. L-3-O-ethylascorbic acid where R is an ethyl group is preferred.
[0011]
The content of the L-ascorbic acid derivative in the topical antipruritic agent of the present invention is appropriately selected according to the form of the composition, but is generally 0.001 to 50.0% by weight based on the total amount of the composition. Selected by range. If the amount is less than 0.001% by weight, it is difficult to obtain an antipruritic effect, and if it exceeds 50.0% by weight, no improvement in the effect corresponding to the increase is observed, which is not preferable. Considering the antipruritic effect and economy, the content of the L-ascorbic acid derivative is preferably in the range of 0.05 to 10.0% by weight.
[0012]
The dosage form of the external antipruritic agent of the present invention can be used without being limited to the dosage form as long as it is used for the outer skin of cosmetics, quasi-drugs, pharmaceuticals and the like. That is, a wide range of forms such as aqueous lotions, solubilizing lotions, suspension lotions, water-oil separation type lotions, emulsions, packs, pasta, pups, sticks, ointments, plasters, liniments and tapes. Possible.
[0013]
The antipruritic agent of the present invention may optionally contain, in addition to the active ingredient L-ascorbic acid derivative, other components used in cosmetics, quasi-drugs, and pharmaceuticals as needed within a range that achieves the object of the present invention. You can do it. For example, powder components such as titanium dioxide, mica, allantoinchlorohydroxyaluminum, krillhydroxyaluminum, calamine, talc, silicone, nylon, cellulose, avocado oil, corn oil, olive oil, rapeseed oil, evening primrose oil, castor oil, sunflower oil, tea Real oil, rice bran oil, jojoba oil, cacao oil, coconut oil, squalane, tallow, lard, mokuro, beeswax, candelilla wax, carnauba wax, whale wax, lanolin, silicone oil, fusso oil, liquid paraffin, cecilane, vaseline, Oils such as polyoxyethylene oleyl alcohol ether, glycerin ethylhexanoate, pentaerythritol ethylhexanoate, cetyl ethylhexanoate, glyceryl monooleate, caprylic alcohol, lauryl alcohol, and millis Alcohols, higher alcohols such as cetyl alcohol, higher fatty acids such as capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, lanolin fatty acid, linoleic acid, linolenic acid, polyethylene glycol, glycerin, sorbitol, xylitol, Moisturizing agents such as maltitol, lactic acid, urea, hyaluronic acid, NMF (natural moisturizing factor), pyrrolidone carboxylic acid, and ceramide; thickening of methyl cellulose, ethyl cellulose, gum arabic, alginic acid, carboxyvinyl polymer, polyvinyl alcohol, montmorillonite, laponite, etc. Agents, organic solvents such as ethanol, butylhydroxytoluene, tocopherol, antioxidants such as phytic acid, ferulic acid, and edetic acid, benzoic acid, salicylic acid, alkyl parahydroxybenzoate. Ter (ethylparaben, butylparaben, etc.), antimicrobial preservatives such as hexachlorophene, lower organic acids used as skin nutritional components of α-hydroxy acids such as lactic acid, tartaric acid, citric acid, glycolic acid and salts thereof, alanine; arginine, glutamine, cysteine, serine, amino acids histidine, adenine, guanine, nucleic acids such as uracil, retinol palmitate or vitamin a and other derivatives, beta-carotene and derivatives thereof, vitamin B ₂ and its derivatives, vitamin of B ₆ and derivatives thereof, vitamin B ₁₂ and its derivatives, niacin and derivatives thereof, tocopherol and derivatives thereof, .gamma.-oryzanol and derivatives thereof, vitamin D and derivatives thereof, vitamin H, pantothenic acid, pantethine, pantothenyl Vitamins such as alcohols, ascorbic acid and other derivatives not specified in the scope of the present invention (ascorbic acid phosphate and salts thereof, ascorbic acid glycosides, ascorbic acid higher fatty acid esters, etc.), allantoin, glycyrrhetinic acid and derivatives thereof , Kojic acid and its derivatives, glabridine and its derivatives, hinokitiol, mucidin, bisabolol, eucalyptrol, thymol, inositol, panthenyl ethyl ether, saponins (such as saikosaponin, hepimasaponin, muclodisaponin), royal jelly, ethinyl estradiol, cepharanthin , Placenta extract, photosensitizer, tranexamic acid, azulene and derivatives thereof, and ubiquinones skin nourishment and skin medicinal ingredients, hawthorn, eyeー, marronnier, fennel, orange, lemon, avocado, kiwi, peach, cucumber, eggplant, tomato, carrot, yukinoshita, loofah, sage, thyme, mint, birch, spruce, touki, lily, mugwort, chamomile, strawberry, grape, Pineapple, apple, ashitaba, banana, kelp, seaweed, alge colloid, arnica, lettuce, cabbage, grapefruit, mango, papaya, lychee, etc. Alcohols, solids extracted with aqueous alcohol, etc., semi-solid and liquid extracts of plants not defined in the scope of the present invention, chitin / chitosan, milk protein, silk, animal extracts such as tosaka extract were used as raw materials. Pressed, dried, pulverized, extracted and other products And decomposed products, sodium lauryl sulfate, polyoxyethylene lauryl sulfate triethanolamine, anionic surfactants such as dioctyl sulfosuccinate, and higher alcohol phosphates, and positive surfactants such as benzethonium chloride, cetylpyridinium chloride, and benzalkonium chloride. Ionic surfactant, glycerin higher fatty acid ester, sorbitan higher fatty acid ester (Span ^™ ), polyoxyethylene polyhydric alcohol fatty acid ester (Tween ^™ ), sucrose fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether Lactoferrin, edetic acid and derivatives thereof or metal sequestering agents such as salts thereof, and fragrances and the like can be blended in optional proportions.
[0014]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples. The present invention is not limited to the embodiments.
[0015]
Embodiment 1

Processes a) to h) are mixed and uniformly dissolved.
[0016]
Embodiment 2

Production methods a) and g) are dissolved in ethanol d), the remainder is added and dissolved in purified water h). The obtained gel base is spread on a nonwoven fabric as a support to obtain a sheet-like pulp.
[0017]
Embodiment 3

Production method The oil component (A) is heated and mixed at 70 ° C. After mixing and dissolving the water-soluble component (B), the mixture is heated to 70 ° C., and the component (A) is mixed and emulsified by a homomixer. Cool to room temperature and fill container to obtain cream.
[0018]
[Test Example 1]
The back skin of 10 ICR female mice (CLEA Japan) was shaved, and 50 μL of the aqueous lotion of Example 1 was applied to 5 mice. Thirty minutes after the application, 10 μg of Compound 48/80 (Sigma) was intradermally administered to the shaved part, and the number of times of occurrence of the scratching behavior for 15 minutes immediately after the intradermal administration was recorded. A lotion not containing only 3-O-ethylascorbic acid was prepared from the lotion formulation of Example 1 to prepare Comparative Example 1, and applied to 5 mice in the same manner as the group to which the lotion of Example 1 was applied. Treated similarly.
[0019]
Table 1 shows the test results.
[Table 1] Measurement results of the number of occurrences of scratching behavior

[0020]
As shown in the table, the scratching behavior of Example 1 was clearly suppressed as compared with the comparative example, and the antipruritic effect of Example 1 was confirmed.
[0021]
【The invention's effect】
As described above in detail, an external antipruritic agent having an excellent antipruritic effect was provided by the present invention.

Claims (2)

General formula

(In the formula, R is an alkyl group having 1 to 22 carbon atoms.)
An antipruritic agent for external use, comprising an L-ascorbic acid derivative represented by the formula: An antipruritic agent for external use, which comprises 3-O-ethylascorbic acid wherein R in Chemical Formula 1 is an ethyl group.