JPH08301779A - External preparation for atopic dermatitis - Google Patents

Abstract

PURPOSE: To obtain an external preparation excellent in safety, having a moisture-retaining effect and an antiinflammatory effect, excellent in an antipruritic effect, and having suitability as the external preparation for the atopic dermatitis. CONSTITUTION: This external preparation for the atopic dermatitis contains the extract of one or more kinds of plants selected from the group of Tilia Europaea L., Melissa officinalis L., Trigonella foenumgraecum L., Borago officinalis L., Paris polyphylla Smith var. chinensis Franch., Pyrola japonica Kenze, Clerodendron cyrtophyllum Turcz, Pinellia cordata N. B. Br., and Clinopodium chinense (Benth.) O. Ktze., as an active ingredient.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an external preparation for atopic dermatitis containing an extract of a specific plant as an active ingredient, and more specifically, linden, lemon balm, fenugreek, borage, soukyu, deer. An atopy that has a moisturizing effect and an anti-inflammatory effect, and an antipruritic effect, with an active ingredient of an extract of one or more plants selected from the group consisting of hoof grass, large green leaves, drip pearl syrup, and kale rape. External preparation for dermatitis.

[0002]

BACKGROUND OF THE INVENTION Atopic dermatitis is a chronic skin disease whose cause has not yet been clarified, and it is thought that people who easily dry their skin or who have skin vulnerable to external stimuli are prone to it. Has been. In recent years, the number of people suffering from this disease is increasing, and the effective treatment method has not been found yet. The symptoms are characterized by papules, erythema, thickening and lichenification in childhood, and in adolescence:
Thickening and lichenification accompanied by erythema and desquamation are both accompanied by pruritus. The scratches caused by this itch sensation cause dermatitis and the symptoms worsen. This itching sensation is considered to be one of the causes of the intractable atopic dermatitis, and its improvement and treatment have been tried.

Antihistamine agents, antiallergic agents, antiinflammatory agents, steroid agents and the like are known as agents for improving or treating atopic dermatitis, but they are not always satisfactory in terms of pharmacological effects and side effects. There wasn't. For example, antihistamines and antiallergic agents
It has an antipruritic effect but lacks persistence and anti-inflammatory effect, and after administration, symptoms such as fatigue and drowsiness may appear, which may interfere with daily life, so long-term continuous use for chronic pruritus is difficult Met. On the other hand, although steroids have a high pharmacological effect, they have very strong side effects peculiar to the drugs, and it is necessary to give sufficient consideration to their use, and at the same time, long-term continuous use is also difficult.

[0004] In addition, for the purpose of suppressing the itching sensation, attempts have been made to apply agents for suppressing sweating, and preparations for the purpose of moisturizing such as urea ointment, but the action is temporary, and especially scratching is performed. There was no sufficient effect on the symptoms associated with the subsequent inflammation. Furthermore, in recent years, studies have been conducted on the use of natural materials for atopic dermatitis, mainly for the purpose of reducing side effects, although the effect is mild regardless of internal or external application. For example,
Japanese Unexamined Patent Publication No. 6-166629 discloses an atopic dermatitis improving agent in which Daisaikoto and Tokishakuyakusan are mixed, and Japanese Unexamined Patent Publication No. 6-329547 includes a mugwort extract and horse oil. An external preparation effective for atopic dermatitis is disclosed. However, none of these is sufficient in terms of their effects.

[0005]

DISCLOSURE OF THE INVENTION The object of the present invention is to radically solve the above-mentioned conventional drawbacks, and to treat atopic dermatitis which has a moisturizing effect and an anti-inflammatory effect and an excellent antipruritic effect. -To provide improved external preparations with high safety.

[0006]

Means for Solving the Problems Atopic dermatitis is a kind of chronic pruritic skin disease, and scratches caused by this pruritic sensation certainly cause inflammation in the part and exacerbate the inflammation. The present inventor, in order to suppress the itching sensation, if there is an external preparation having both a moisturizing effect and an effect of suppressing skin inflammation, it is possible to improve atopic dermatitis, and it is natural. Focusing on herbs and Chinese herbs among ingredients, as a result of trial and error in order to achieve the above purpose, as a result of trial and error, linden, lemon balm, fenugreek, borage, sow cucumber, deer hoof, large green leaves, drops of water droplets and feng wanna The present invention has been completed on the basis of the new finding that the extract of No. 1 has excellent moisturizing effect and anti-inflammatory effect, and further suppresses the itching sensation of the skin. That is, according to the present invention, Linden, lemon balm, fenugreek, borage, sow cucumber,
A safe and extremely highly effective external preparation for atopic dermatitis containing an extract of one or more plants selected from the group consisting of deer hoof, large green leaves, drip pearls, and wind rape. Provided.

[0007]

DETAILED DESCRIPTION OF THE INVENTION The lindane used in the present invention is a plant of the family Lindenaceae, Tilia Europaea L.
It is used for flavoring food and drinks and herbal tea. As the extract, one obtained by extracting the whole linden grass with water and / or alcohol and further removing ethanol by adding ethanol is preferably used.

Lemon balm is a plant belonging to the Labiatae family, Melissa officinalis L.
It is used for flavoring food and drinks and herbal tea. As the extract, one obtained by extracting whole lemon balm with one kind or a mixture of water, alcohol, 1,3-butylene glycol, glycerin, propylene glycol and the like and filtering it is preferably used.

Fenugreek is a fenugreek plant (Trigonel).
la foenumgraecum L.) and is used as a raw material for curry powder and sauce. As the extract, one obtained by extracting fenugreek seeds and / or leaves with water, alcohol, an organic solvent or the like is preferably used. It is also possible to use a fraction obtained by purifying the obtained extract with an adsorbent such as activated carbon and an ion exchange resin.

Borage officinalis L. is a plant of the family Musaceae, and its leaves are edible. As the extract, one obtained by extracting the whole borage of borage with water, alcohol, organic solvent and the like is preferably used. It is also possible to use a fraction obtained by purifying the obtained extract using ultrafiltration and a reverse osmosis membrane.

Soukyu is a plant of the family Liliaceae
It is the rhizome of (Paris polyphylla Smith var.chinensis Franch.) And is also used as a herbal medicine. As the extract, the one obtained by extracting the soybean cucumber with one kind or a mixture of water, alcohol, 1,3-butylene glycol, glycerin, propylene glycol and the like and filtering it is preferably used.

[0012] Deer hoof is a whole plant of Pyrola japonica Klenze, which is a plant belonging to the family Glycyrrhizaceae, and is also used as a herbal medicine. As the extract, one obtained by extracting the whole grass of Strawberry with water, alcohol, organic solvent and the like is preferably used. It is also possible to use a fraction obtained by purifying the obtained extract using ultrafiltration, a reverse osmosis membrane, and an adsorbent such as an ion exchange resin.

The large green leaves are branches and leaves of Cleodendron cyrtophyllum Turcz, which is a plant belonging to the family Vaticanaceae.
It is also used as a herbal medicine. As the extract,
A large green leaf extracted with water, alcohol, an organic solvent, or the like is preferably used. The obtained extract is ultrafiltered,
It is also possible to use a fraction purified using an adsorbent such as activated carbon and an ion exchange resin.

Droplet pearl is a plant of the family Araceae, which is a leaf of the heart and leaves in the summer (Pi
nellia cordata NBBr.) tuber and is also used as a herbal medicine. As the extract, a fraction obtained by extracting drip water beads with water and / or alcohol and further removing ethanol by adding ethanol is preferably used.

Furinsai is a whole plant of the mint plant, Clinopodium chinense (Benth.) O.Ktze., Which is also used as a herbal medicine. The extract is
The one obtained by extracting the Chinese quince vegetable with water, alcohol, an organic solvent or the like is preferably used. It is also possible to use a fraction obtained by purifying the obtained extract with an adsorbent such as activated carbon and an ion exchange resin.

The external preparation for skin of the present invention is produced by mixing these plant extracts as an active ingredient into a known dosage form that is acceptable for skin application, and the amount thereof is a treatment method, a concentration degree, and Although it varies somewhat depending on the form of the formulation to be blended, it is usually preferable to add about 0.001 to 20% by weight, particularly 0.05 to 5% by weight of the extract or its treatment solution.

Further, it is possible to enhance the effect by using in combination with a drug which has been conventionally used for atopic dermatitis. In that case, it is necessary to appropriately adjust the compounding amount. In this case, the amount of the conventional drug can be reduced according to the symptom, and the side effect can be reduced.

As described above, the external preparation for atopic dermatitis of the present invention is not particularly limited as long as it is suitable for skin application, and examples thereof include poultices, plasters, pastes, creams, ointments and aerosols. It is widely used in known forms such as agents, emulsions, lotions, emulsions, essences, packs, gels, powders, foundations, sun cares and bath salts.

In the case of preparing the external preparation for skin of the present invention, various known active ingredients which are usually used, for example, carpronium chloride, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinic acid amide, benzyl nicotinate, and shaw are shown. Peripheral vasodilators such as tincture, capsicum tincture, camphor, menthol, cooling agents such as peppermint oil, hinokitiol, benzalkonium chloride, antibacterial agents such as undecylenic acid, adrenocortical hormone,
Anti-inflammatory agents such as ε-aminocaproic acid, lysozyme chloride, glycyrrhizin and allantoin, whitening agents such as kojic acid, ascorbic acid and arbutin, cembly extract, garlic extract, carrot extract, sardine extract, rosemary extract, aloe extract, loofah extract , Ginkgo biloba extract, elderberry extract, purple root extract, liver extract, placenta extract, lactic acid bacterium culture extract, and other extracts derived from animals, plants, and microorganisms, etc. are added as appropriate according to the purpose at the time of use. can do. Further, in addition to the active ingredient and the surfactant, base components such as oils and fats, known moisturizers, thickeners, preservatives, antioxidants, ultraviolet absorbers / scattering agents, chelating agents, if necessary. Various additives such as pH adjusters, fragrances, and colorants can be used in combination.

[0020]

[Examples] Next, examples of the present invention will be described with reference to production examples of the above-mentioned plant extract and test examples for showing the effects thereof, but these do not limit the present invention at all.

<Production Example 1> Dried whole linden grass was crushed, 90 g of the crushed product was added with 1 kg of water, and the mixture was extracted with stirring at room temperature for 3 hours. Then, the mixture was left standing at 5 ° C. for 3 days and then filtered, and an appropriate amount of ethanol was further added and filtered. Water was added to the obtained filtrate to adjust it to obtain about 5 kg of 10% ethanol extract.

<Production Example 2> Whole dried lemon balm grass was finely chopped, 200 g of the chopped 10 kg of 30% 1,3-butylene glycol aqueous solution (w / w) was added, and the mixture was stirred at room temperature for 2 hours. Extracted. This extract was filtered to obtain about 9 kg of extract.

<Production Example 3> Dried fenugreek seeds were crushed, 1 kg of water was added to 200 g of this crushed product, and the mixture was extracted with stirring at room temperature for 24 hours. Then, it was left at 5 ° C. for 10 days and filtered. Synthetic adsorbent HP21 was added to this filtrate, and after stirring for 1 hour, synthetic adsorbent HP21 was removed to obtain about 900 g of an extract.

<Production Example 4> Whole dried borage plant was crushed, and 50 g of this crushed product was mixed with 50% ethanol aqueous solution (w /
w) 1 kg was added, and the mixture was extracted with stirring at room temperature overnight. After that, filtration was performed to obtain about 900 g of the extract.

<Production Example 5> Dried succulents were chopped, 200 g of the chopped chopped product was added with 10 kg of a 30% 1,3-butylene glycol aqueous solution (w / w), and the mixture was extracted with stirring at room temperature for 20 hours. This extract was filtered to obtain about 9 kg of extract.

<Production Example 6> Dried hoofed grass was crushed, 40 g of this crushed product was added with 1 kg of 10% ethanol (w / w), and the mixture was stirred and extracted at room temperature for 2 hours. Then, the filtrate was filtered and the reverse osmosis membrane (NTR-74 manufactured by Nitto Electric Industry Co., Ltd.) was used.
10) Treatment was performed to obtain 800 g of a permeated liquid.

<Production Example 7> Dried large green leaves were pulverized, 200 g of the pulverized product was added with 1 kg of 10% aqueous ethanol solution (w / w), and the mixture was extracted with stirring at 50 ° C for 2 hours. After cooling, filtration was performed, and the filtrate was ultrafiltered to obtain about 800 g of a permeated liquid.

<Production Example 8> Dried water droplets were crushed, 200 g of this crushed product was added with 1 kg of purified water, and the mixture was extracted with stirring at room temperature for 2 hours. After filtration, the filtrate is 50% aqueous ethanol (w /
w) was added in an appropriate amount so that the mixture was allowed to stand at 5 ° C. for 1 hour and then filtered to obtain about 1.8 kg of an extract.

<Production Example 9> Dried bean sprouts were crushed, 100 g of the crushed product was added with 1 kg of a 10% aqueous ethanol solution (w / w), and the mixture was extracted with stirring at room temperature for 24 hours. After filtration, the synthetic adsorbent SP850 was added to the filtrate, stirred for 1 hour and then removed to obtain about 900 g of an extract.

[0030]

[Test example]

<Test Example 1> Moisture retention test by impedance meter High frequency impedance meter (manufactured by IBS: MODEL IB
-355) was used to examine the moisturizing properties of the extract of the present invention using purified water as a control. Test sample: (1) Control: purified water (2) Control: 10% ethanol (3) Control: 50% ethanol (4) Control: 30% 1,3-butylene glycol (5) Production Example 1 (Linden 10 % Ethanol extract) (6) Production example 2 (30% 1,3-butylene glycol extract of lemon balm) (7) Production example 3 (water extract of fenugreek) (8) Production example 4 (50% ethanol of borage) Extraction liquid) (9) Production example 5 (30% 1,3-butylene glycol extract liquid of Soukyu) (10) Production example 6 (10% ethanol extract liquid of Deerfoot grass) (11) Production example 7 (Large green leaves) (10% ethanol extract) (12) Production example 8 (50% ethanol extract of drip bead) (13) Production example 9 (10% ethanol extract of kale)

(Measurement method) A sample is applied to the inside of the human forearm.
(2 cm x 2 cm), 30 seconds later, quickly wipe gently with gauze,
Conductivity of the skin every 5 minutes
Measured to the minute. (Measurement conditions: measurement room temperature 20 ° C, humidity 60%, number of measurements n =
Ten).

(Measurement Results) As shown in Table 1, the plant extract was found to have high moisturizing properties.

<Test Example 2> Anti-inflammatory effect of guinea pig (Test method) A sample was applied to Hartley white guinea pig twice, 1 hour before and 30 minutes before UV irradiation.
It was wiped off with Kimwipe and then washed. Then, using two UVB lamps, the direction of the guinea pig was changed, and UV irradiation was performed every 2 minutes for a total of 4 minutes (UV amount: 305 nm 0.980).
mW / cm, 365nm 0.420mW / cm). Immediately after the ultraviolet irradiation, the sample was applied 3 hours and 6 hours after the irradiation, and the measurement was performed by the naked eye and a color difference meter 6 hours and 24 hours after the ultraviolet irradiation. As a placebo, 30 of 1,3-butylene glycol
% (W / w) aqueous solution was used.

The criteria for judgment are as follows. The visual evaluation was performed in the following 5 steps. 4: Altitude, 3: Medium, 2: Mild, 1: Minor, 0: None Erythema degree by a color difference meter was calculated from the following formula. Erythema degree (a value) = (a value after irradiation, average of 3 times measurement)-(a value before irradiation, average of 3 times measurement) Sample adjustment: 1,3-butylene glycol at a final concentration of 30
% (W / w) formulation was adjusted.

(Measurement Results) Table 2 shows the results of visual judgment.
Table 3 shows the determination results obtained by a color difference meter. In the test, 8 guinea pigs were used per group, and the average value was entered in the table. By both judgments, the plant extract showed an erythema suppressing effect.

[0036]

[0037]

Test Example 3 Treatment / Amelioration Effect on Atopic Dermatitis in Humans (Test Method) 15 males and females aged 2 to 40 years old with atopic dermatitis (refractory symptoms accompanied by inflammation) were observed. A test was conducted on the subject. The cream of Formulation Example 1 described below (representative example) was applied to the eczema site of the hand three times a day.

(Observation Items and Observation Dates) At the start of application, 1 week, 2 weeks, 3 weeks, and 4 weeks later, itching and skin findings as subjective symptoms (erythema, papules, moistening, lichenification,
The degree of the total amount of desquamation) was judged according to the following 5 grades. 4: Advanced, 3: Moderate, 2: Mild, 1: Minor, 0: None The usefulness is extremely useful (+++), quite useful (++), useful from the improvement level of each item and the subject's interview. (+), Invalid (-)
It was determined.

(Results) The results are shown in Table 4.

As is clear from the above results, the clinical test results of 15 patients were extremely useful in 6 (40%), fairly useful in 5 (33%), useful in 4 (27%), and ineffective in 0. First name (0
%), Proving the remarkable effect of the external preparation for skin of the present invention. No side effects were observed during the test period, demonstrating high safety.

The formulation examples of the present invention are shown below. In the formulation examples, "appropriate amount" means a value at which the total formulation becomes 100% by weight.

<Formulation Example> Formulation Example 1 Cream (% by weight) A Monostearic acid 2.0 Polyethylene glycol (40.EO) Self-emulsifying glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Liquid paraffin 10.0 Glyceryl trioctanoate 10.0 B Glycerin 5.0 Ethyl paraben 0.1 Plant extract of Production Example 0.5 Purified water Appropriate amount A component belonging to A is dissolved by heating. Separately, the components belonging to B are melted by heating. After adding B to A, stirring and emulsifying, cooling was performed to produce a cream.

Formulation Example 2 Emulsion (wt%) A Polyoxyethylene sorbitan monostearate (20.EO) 1.0 Polyoxyethylene sorbitate monostearate (60.EO) 0.5 Glycerin monostearate 1.0 Stearic acid 0.5 Behenyl alcohol 0.5 Avocado oil 4.0 Glyceryl trioctanoate 4.0 1,3-Butylene glycol 5.0 Plant extract of Production Example 1.0 Methylparaben 0.2 Purified water Appropriate amount Components of A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. After adding B to A, stirring and emulsifying, it was cooled to produce an emulsion.

Formulation 3 Lotion (wt%) Polyoxyethylene hydrogenated castor oil (60.EO) 8.0 Ethanol 15.0 Plant extract of Preparation 9 0.1 Ethylparaben 0.1 Citric acid 0.1 Sodium citrate 0.3 1,3-Butylene glycol 4.0 Disodium edetate 0.01 Purified water Appropriate amount The above components were mixed, stirred uniformly and dissolved to produce a lotion.

Formulation Example 4 Cream pack (wt%) A Veam 5.0 Squalane 2.0 Propylene glycol 5.0 Plant extract liquid of Production Example 2.0 Plant extract liquid of Production Example 2.0 Vitamin B12 0.05 Purified water Amount B Zinc oxide 10.0 C Ethanol 5.0 A The ingredients belonging to (3) are mixed, stirred to swell, and B is added little by little. C was gradually added to this and kneaded until a paste was formed to produce a cream pack.

Formulation Example 5 Essence (% by weight) Glycerin 20.0 Ethanol 1.0 Plant extract of Production Example 4 0.3 Purified water Appropriate amount The above components were mixed, uniformly stirred and dissolved to produce an essence.

Formulation Example 6 Hydrophilic ointment (% by weight) A Polyoxyethylene cetyl ether 2.0 Glyceryl monostearate 10.0 Liquid paraffin 10.0 Vaseline 4.0 Cetanol 5.0 B Propylene glycol 10.0 Methylparaben 0.1 Plant extract of Production Example 1.0 Purified water qs A The ingredients belonging to are dissolved by heating. Separately, the components belonging to B are dissolved by heating. After adding B to A, stirring and emulsifying, it was cooled to produce a hydrophilic ointment.

Formulation Example 7 Aerosol (wt%) A Kojic acid 2.0 Plant extract of Production Example 2.0 Benzyl nicotinate 0.01 Vitamin E acetate 0.05 Cetanol 1.2 Propylene glycol 4.0 Ethanol 8.0 Purified water Appropriate amount B LPG 7.0 A component belonging to A The mixture was uniformly mixed and dissolved, placed in an aerosol container, and B was filled in the container by an ordinary method to produce an aerosol agent.

Formulation Example 8 Patch (% by weight) A Polyacrylic acid 30.0 Sorbitan monooleate 1.0 Purified water Appropriate amount B Polysodium acrylate 7.0 Aluminum chloride 0.3 Plant extract of Production Example 0.05 Concentrated glycerin 20.0 Titanium oxide 1.0 A The ingredients that belong to it are dissolved by heating. Separately, the ingredients belonging to B were dissolved by heating, stirred and mixed to produce a poultice.

Formulation Example 9 Bath agent (liquid type) (wt%) Sorbitan monostearate 4.0 Carboxyvinyl polymer 0.1 Methyl paraoxybenzoate 0.1 Propylene glycol 20.0 Ethanol 5.0 Fragrance Rice higa oil 2.0 Touki extract 5.0 Plant extraction of Production Example 6 Liquid 3.0 Purified water Appropriate amount After mixing the above components to make them uniform, they were filtered to produce a liquid type bath agent.

Formulation Example 10 Bath agent (granular type) (wt%) A Sodium chloride 5.0 Sodium sulfate 40.0 Sodium sesquicarbonate 10.0 Sodium hydrogencarbonate 26.0 Dextrin (excipient for granulation) 10.0 Lavender oil 1.0 Mint oil 1.0 Perfume Trace yellow No. 205 Trace amount Plant extract of Production Example 5.0 B Aqueous sodium carboxymethylcellulose solution 2.0 A The ingredients belonging to A are thoroughly mixed with a powder mixer. Add B to A and mix thoroughly to make a suitable granulator (eg cylindrical granulator)
The granules were granulated to prepare a granule type bath agent.

It was confirmed that each of the external preparations of Formulation Examples 1 to 10 is a preparation having an effect satisfying the object of the present invention.

[0054]

EFFECTS OF THE INVENTION According to the present invention, an extract of one or more plants selected from the group consisting of linden, lemon balm, fenugreek, borage, borage, deer hoof, large green leaves, drip syrup, and azalea. A safe external preparation for atopic dermatitis containing is provided, the external preparation is excellent in moisturizing effect, anti-inflammatory effect, and further in antipruritic effect, and is useful as an external preparation for atopic dermatitis. is there.

Claims (1)

[Claims] 1. An extract of one or more kinds of plants selected from the group consisting of linden, lemon balm, fenugreek, borage, borage, deer hoof, large green leaves, drip bead, and feng walnut as an active ingredient. An external preparation for atopic dermatitis characterized by: