JPH09124500A - Therapeutic agent for atopic dermatitis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent useful for treating dermal symptoms in an atopic disease, comprising a specific crude medicine having inhibitory action on physiological activities of sphingosylphosphorylcholine as an active ingredient. SOLUTION: This therapeutic agent for atopic dermatitis comprises one or more of essences of crude medicines selected from Paenoia suffruticosa Andrews, Panax ginseng C.A.Meyer, Cervus(Cervus) elaphus L. var. xanthopygus Milne-Edwards, Mallotus japonicus (Thunb. ex L.f.) Muell.Arg., Uncaria sinensis (OLIV.) Havil and Civet cat as an active ingredient. The essence of the crude medicine suppresses rise in calcium ion concentration in a cell by sphingosylphosphorylcholine. The content of the essence in the therapeutic agent is 0.00001 to 5wt.% calculated as a dried solid content.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for atopic dermatitis, and more specifically, to atopic skin containing a herbal medicine extract that suppresses an increase in intracellular calcium ion concentration due to sphingosylphosphorylcholine (SPC) as an active ingredient. It relates to a therapeutic agent for inflammation.

[0002]

BACKGROUND OF THE INVENTION Atopic dermatitis is an eczema skin disease with strong itching that develops in people with atopic constitution. It causes symptoms such as itching, inflammation, dyskeratosis, impaired barrier ability, and dry skin. Show. In recent years, changes in living environment, westernization of eating habits,
The number of people suffering from atopic dermatitis is rapidly increasing due to the improvement of the housing environment, the increase of stress, etc., and 10-20% or more of infants now have symptoms. Most atopic dermatitis develops from infants and shows a tendency of improvement with growth, but in recent years, adult-type and intractable atopic dermatitis has rapidly increased, and has become a big problem. Atopic dermatitis, atopic dermatitis, means "strange" or "out of place" in Greek, and as the name implies, the actual situation has not yet been clarified.

For this reason, most of the treatments currently performed are symptomatic treatments, and in medical external treatments, steroid agents such as corticosteroids are mainly applied. However, since steroids have side effects due to long-term use, the use of steroids requires careful attention under the guidance of a doctor. Therefore, a safe external preparation with few side effects is desired.

On the other hand, in the stratum corneum of atopic patients, there is a mechanism different from that of healthy people in the pathway of metabolizing ceramide from sphingomyelin, so that sphingosylphosphorylcholine (SPC) is produced, and SPC produces atopic skin symptoms. Have been suggested to deteriorate [9th
3rd Annual Meeting of the Japanese Dermatological Association / Academic Conference (Abstracts)].

[0005]

Therefore, an object of the present invention is to provide a therapeutic agent for atopic dermatitis which suppresses the physiological activity of SPC produced in atopic dermatitis.

[0006]

In view of such circumstances, the present inventor has diligently studied, and as a result, extracts of button piper, ginseng, locust, red mulberry, red ginkgo and civet have an action of suppressing the physiological activity of SPC, It was found that the use of this can improve / treat various symptoms of atopic dermatitis, and completed the present invention.

[0007] That is, the present invention provides a therapeutic agent for atopic dermatitis containing, as an active ingredient, one or more kinds of crude drug extracts selected from sea urchins, ginseng, locust, red megalois, pearl millet and civet. .

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The physiological activity of SPC is an action of promoting an increase in intracellular calcium ion concentration in human epidermal keratinocytes, and this increase in calcium ion leads to aggravation of atopic dermatitis. The active ingredients of the agent for treating atopic dermatitis of the present invention, such as Botanpi, Kojin, Rokujou, Akamegasiwa, Kotoko and Civet, suppress the elevation of intracellular calcium ion concentration by SPC and improve atopic dermatitis symptoms.・ It is a cure.

Among the herbal extracts used in the present invention, civet is preferably used as a tincture, and the other is preferably used as an extract.

[0010] Button pipi extract is a button (Paenoia suff
ruticosa Andrews) root bark dried (crude drug) with water or ethanol, butanol, propylene glycol,
It can be obtained by extraction with a solvent in which one or more water-soluble organic solvents such as 1,3-butylene glycol are mixed, or a solvent in which these solvents are combined with water. The amount of the solvent used in the extraction is preferably 1 to 20 times the weight of the crude drug. In the present invention, the obtained extract may be used as it is or after being concentrated, or the extract may be used as a dried dry powder.

Ginseng extract is a ginseng (Pana ginseng)
x ginseng CAMeyer) obtained by steaming roots of x ginseng CAMeyer) in the same manner as above, and may be used as an extract or a dry powder of the extract.

[0012] Rokujou extract is a Mansua deer (Cervus (Cervus) elaphus L. var. Xanthopygus MILNE-ED
WARDS] and / or Manshu deer [Cervus (Sika) nippo
n TEMMINCK var. mantchuricus SWINHOE] male non-keratinized or slightly keratinized larvae obtained by extracting dried ones in the same manner as above, and even when used as an extract, a dry powder of the extract is obtained. You may use.

The red wrinkle extract is a red wrinkle [Ma
Llotus japonicus (Thunb.ex Lf) Muell.Arg.] bark is obtained by extracting in the same manner as above, and may be used as an extract or a dry powder of the extract.

[0014] As the extract of Ginkgo biloba, dried spiny spines with a part of stems and branches of Uncaria sinensis (OLIV.) HAVIL and / or U. rhynchophylla (MIQ.) JACKSON are used. It may be obtained by extraction in the same manner as above, and may be used as an extract or a dry powder of the extract.

Civet tincture is a civet (Civet)
It is obtained by dissolving the sacral gland secretion of cat) in the same solvent as above. The amount of solvent used is 1 to 30
It is preferable to make the weight times.

These crude drug extracts may be used alone or in combination of two or more, and the compounding amount thereof is 0.00001 to 5% by weight (hereinafter simply referred to as "dry solid content" in the therapeutic agent for atopic dermatitis of the present invention. %)), 0.0
It is particularly preferably set to 0001 to 1%.

The atopic dermatitis therapeutic agent of the present invention may optionally contain various optional substances used in cosmetics, quasi drugs, pharmaceuticals, etc., in addition to the above-mentioned essential components, as long as the effects of the present invention are not impaired. The components can be blended appropriately.
Examples of such optional ingredients include purified water, oily ingredients, moisturizers, thickeners, preservatives, emulsifiers, other medicinal ingredients,
Examples include powders, fragrances, emulsion stabilizers, pH adjusters and the like.

Examples of the oily component include soybean oil, bran oil, jojoba oil, avocado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, lard, synthetic diglyceride. Fats and oils such as synthetic triglyceride; waxes such as carnauba wax and lanolin; higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid and isostearic acid Higher alcohols such as lauryl alcohol, lanolin alcohol, cholesterol and 2-hexyldecanol; silicone oils such as dimethylpolysiloxane and various modified silicones. Examples of moisturizing agents include sorbitol, xylitol, glycerin, maltitol, 1,3-butylene glycol, 1,
4-butylene glycol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, polyoxypropylene fatty acid ester, polyethylene glycol and the like can be mentioned. Examples of the thickener include water-soluble polymer compounds such as carboxyvinyl polymer, carboxymethyl cellulose, polyvinyl alcohol, carrageenan and gelatin;
Examples of the electrolyte include sodium chloride and potassium chloride. Examples of preservatives include urea, methylparaben, ethylparaben, butylparaben, sodium benzoate and the like. As the emulsifier, any nonionic, cationic, anionic, amphoteric natural or synthetic emulsifier can be used. As the nonionic surfactant,
For example, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, fatty acid monoglyceride, sucrose fatty acid ester, higher fatty acid alkanolamide, etc. Examples of the surface active agent include quaternary ammonium salts. Any of the quaternary ammonium salts is preferably used as long as it is usually used in a composition for the body, and those containing a branched quaternary ammonium salt described in JP-A No. 61-267505 are particularly preferable. . Examples of the anionic surfactant include a linear alkylbenzene sulfonate, a branched alkylbenzene sulfonate, an alkyl sulfate, an alkenyl sulfate, an alkyl ether carboxylate or an alkenyl ether carboxylate to which ethylene oxide and / or propylene oxide is added. Acid salts, α-sulfo fatty acid esters, amino acid type surfactants, phosphoric acid ester type surfactants, taurine type surfactants, amide ether sulfate type surfactants, and the like, and amphoteric surfactants include sulfonic acid. Examples thereof include amphoteric amphoteric surfactants and betaine amphoteric surfactants. Examples of the powder include talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc white, mica, titanium mica, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, iron oxide, ultramarine blue and the like. To be

The therapeutic agent for atopic dermatitis of the present invention is preferably used as an external preparation for skin in terms of safety and convenience. The form of the external preparation for skin can be arbitrarily selected according to the symptoms, purpose and the like, and can be, for example, a bath agent, cream, lotion, emulsion or the like.

The therapeutic agent for atopic dermatitis of the present invention includes not only pharmaceuticals but also quasi-drugs and cosmetics as long as they are expected to improve or cure various symptoms of atopic dermatitis. Needless to say.

[0021]

EFFECTS OF THE INVENTION The therapeutic agent for atopic dermatitis of the present invention improves various skin symptoms that develop in atopic diseases.

[0022]

The present invention will be described below with reference to examples.
The present invention is not limited to these examples.

Production Example 1 Production of Botanpi Extract: 670 g of dried root bark of Button was finely chopped and water was added to
After performing extraction with stirring occasionally at ℃, press-separated and filtered to obtain 100 g of peony extract (solid content 2.1.
%).

Production Example 2 Production of red ginseng extract: 1000 g of dried root of Panax ginseng was steamed, dried and chopped, 30% ethanol was added, and extraction was performed at 50 ° C. with occasional stirring, followed by squeeze separation and drying. Thus, 100 g of ginseng extract (solid content 2.4%) was obtained.

Production Example 3 Production of Rokujou Extract: Ethanol was added to 1430 g of dried larvae of Manchurian red deer, and the mixture was extracted at 50 ° C. with occasional stirring.
100 g of Rokujo extract by filtration (solid content 0.7%)
I got

Production Example 4 Production of Red-spotted wrinkle extract: 400 g of dried bark of Red-spotted wrinkle was shredded with water, extracted at 50 ° C. with occasional stirring, squeezed and separated, and filtered to obtain 100 g of red-spotted wrinkle extract.
(Solid content 1.5%) was obtained.

Production Example 5 Production of a butterfly extract:
Water was added to finely chopped 1600 g of dried hook spines (with stems and branches) of Scutellaria japonicum, and the mixture was extracted at 50 ° C. with occasional stirring, followed by squeeze separation and filtration to obtain 100 g of Scutellaria baicalensis extract (solid content 1. 8%).

Production Example 6 Production of Civet tincture: 5 g of the glandular secretion of civet cat was dissolved in 95 g of ethanol,
100 g of civet tincture was obtained.

Test Example 1 Inhibition of intracellular calcium ion concentration increase by SPC: Crude drug extracts obtained in Production Examples 1 to 6 and other test substances shown in Table 1 and Fura-2 / AM (intracellular calcium fluorescence indicator) SPC was added to human keratinocytes cultured for 1 hour in a culture medium containing Dojindo Laboratories. At this time, the fluorescence intensity ratio to the intracellular 340 nm / 380 nm two-wavelength excitation light was measured by ARUGUS-200 / CA (Hamamatsu Photonics KK).
Manufactured), and an increase in intracellular calcium ion concentration was observed. As a control, Fura-2 /
It was confirmed that the intracellular calcium ion concentration was increased when SPC was added to human keratinocytes cultured for 1 hour in a culture medium containing only AM.

[0030]

[Table 1]

From the above results, it is clear that the red wrinkles, red ginseng, civet, red cormorant, white pearl oyster, and red loach suppress the increase in calcium ion concentration in SPC.

Test Example 2 Effect on atopic dermatitis: To see the improving effect on atopic dermatitis,
Thirty volunteers with atopic skin symptoms were divided into two groups, and 20g each of bath agents A and B shown below was used to
I had a bath once a day. The improvement rate was based on the improvement (somewhat better) of the symptoms reported by the volunteer after 4 weeks.

[0033]

[Table 2]

(Production method) The oily component is heated and dissolved at 70 ° C.,
After cooling to room temperature with stirring, the water layer component was added,
A transparent liquid bath agent was prepared.

[0035]

[Table 3]

From the above results, it is clear that the bathing agent containing the ginseng extract is effective in improving atopic dermatitis.

Example 2 An oily component was heated and dissolved at 70 ° C., cooled to room temperature with stirring, and then an aqueous layer component was added to prepare a transparent liquid bath agent having the following composition.

[0038]

[Table 4]

Example 3 An oily component was dissolved by heating at 70 ° C., an aqueous component heated at 60 ° C. was added with stirring to emulsify, and the emulsion was cooled to room temperature with stirring to prepare a cream having the following composition. did.

[0040]

[Table 5]

Example 4 An oily component was dissolved by heating at 70 ° C., an aqueous component heated at 60 ° C. was added with stirring to emulsify, and the emulsion was cooled to room temperature with stirring to prepare a cream having the following composition. did.

[0042]

[Table 6]

Example 5 The ingredients were mixed by heating at 70 ° C. with stirring, and after the system became uniform, the mixture was cooled to room temperature with further stirring to prepare a lotion having the following composition.

[0044]

[Table 7]

Example 6 An oily component was dissolved by heating at 70 ° C., an aqueous component heated at 60 ° C. was added with stirring to emulsify, and the emulsion was cooled to room temperature with stirring to prepare an emulsion having the following composition. did.

[0046]

[Table 8]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 7/00 A61K 7/00 W 7/48 7/48 35/32 35/32 35/55 35 / 55 (72) Inventor, Kazuhiko Higuchi, 2606, Akabane, Kai-cho, Haga-gun, Tochigi Prefecture, Kao Institute of Stock Companies (72) Inventor, Genji Imokawa, 2606, Akabane, Kai-cho, Haga-gun, Tochigi Prefecture (72) Inventor, Kao Corporation Yukihiro Yada 2-1-3 Fumika, Sumida-ku, Tokyo Kao Institute of Stock Research

Claims (2)

[Claims] 1. A therapeutic agent for atopic dermatitis, which comprises, as an active ingredient, one or more crude drug extracts selected from botanpi, ginseng, oak dwarf, red wrinkle, red ginkgo and civet. 2. The therapeutic agent for atopic dermatitis according to claim 1, wherein the dosage form is a skin external preparation.