JP4974475B2 - Composition for prevention and / or treatment of pruritus containing acacia bark-derived material - Google Patents

Description

  The present invention relates to a composition for preventing and / or treating pruritus derived from a tree belonging to the genus Acacia, and uses of this composition as a food, animal feed, medicine and quasi-drug.

Pruritus, or itching, is very unpleasant and can interfere with daily life. Pruritus is a variety of skin diseases such as atopic dermatitis, senile dermatitis, hives, eczema, insect bites, dry skin, and rash, kidney disease, diabetes, collagen disease, old age, and hot and cold irritation Caused by a cause. There may be a vicious circle in which the symptom is further exacerbated by scratching the pruritic site or a stronger itch is produced.
For example, atopic dermatitis is known to be easily exacerbated by external stimuli such as sweating, scratching, and friction, and itching is the most important therapeutic target.
Therefore, in order to treat the skin diseases as described above, it is important to first perform a treatment for suppressing itching.

  Various treatments for internal use and external treatments are known as treatment methods for pruritus. For example, in oral therapy, antihistamines such as diphenhydramine, chlorpheniramine maleate, mequitazine, ketotifen, azelastine, oxatomide, terfenadine, and epinastine, and antiallergic agents such as tranilast and suplatast are used. In topical therapy, moisturizers such as petrolatum, urea and heparin, antihistamines such as diphenhydramine and chlorpheniramine maleate, steroids such as dexamethasone and hydrocortisone, antipruritics such as crotamiton, and local anesthetics such as dibucaine and lidocaine are used. Is done.

Acacia is known to be able to use tannin extracted from acacia honey and its bark as a tanning agent and adhesive for wood, and recently, it has a selective inhibitory effect of COX-2 on the extract of the genus Acacia ( Patent Document 1) discloses that the bark of the genus Acacia has a whitening effect (Patent Document 3) due to an active oxygen scavenging effect (Patent Document 2) and a tyrosinase activity inhibitory effect. However, it has not been known that an acacia bark or a polyphenol derived from a bark has an antipruritic effect.
JP-T-2004-532811 JP 2004-352639 A Japanese Patent Laid-Open No. 10-025238

  The present invention provides a highly safe composition for preventing and / or treating pruritus.

As a result of intensive studies to solve the above problems, the present inventors have found that an acacia bark-derived material has an itching effect and completed the present invention.
That is, the present invention relates to a composition for preventing and / or treating pruritus, which contains an acacia bark-derived material.

The composition of the present invention exhibits an antipruritic effect or an antipruritic effect, prevents the onset of pruritus, and cures or reduces pruritus, and thus can be used for the prevention and / or treatment of pruritus.
In addition, the composition of the present invention is less likely to cause side effects even when taken for a long time, and has high safety.

The Acacia bark-derived product that can be used in the present invention is not particularly limited as long as it is obtained from the bark of a tree belonging to the genus Acacia (hereinafter referred to as “Acacia” or “Acacia genus”), For example, acacia bark debris, powder and suspensions thereof, extracts such as acacia bark extract, concentrated extract, and extract powder, and purified products obtained by purifying the extract include Can be mentioned. An extract of acacia bark, particularly acacia bark polyphenol, is preferred in order to obtain an excellent anti-pruritic effect.
In the present invention, only one kind of these Acacia bark-derived materials may be used, or two or more kinds thereof may be used in combination.

The acacia that can be used in the present invention is not particularly limited as long as it is a tree belonging to the genus Acacia, but the scientific name: Acacia mearnsii De Wild. (Bartle), scientific name: Acacia mangium Willd. (Generic name Acacia mangium), scientific name: Acacia dealbata Link., Scientific name: Acacia decurrens Willd., And scientific name: Acacia pycnantha Benth. Acacia mearnsii De Wild. And Acacia mangium Willd. Are particularly preferable.
In the present invention, only one kind of these Acacia barks may be used, or two or more kinds thereof may be used in combination.

The bark of the genus Acacia is usually obtained by cutting only a bark after harvesting it as a tree, and then collecting and drying it. Preferably, the bark is further dried in the sun.
Acacia bark consists of an outer skin and a slightly fibrous endothelium, and when dried to a moisture content of about 20% or less, it is easily pulverized with a pulverizer such as a hammer mill. In the present invention, as the acacia bark, both the inner skin and the outer skin of the acacia may be used together, or only one of them may be used.

The acacia bark strips can be obtained by pulverizing the acacia bark to an appropriate size according to a conventional method.
The powder of the acacia bark can be obtained by pulverizing the acacia bark by a conventional method, and a powder having a particle size of 100 μm or less, particularly 50 to 70 μm is particularly preferable. In the powder fractionation, the bark dried to a moisture content of 20% or less is pulverized to an appropriate size, for example, a particle size of 1.6 mm or less, and the obtained powder is classified with a vibration sieve or the like to obtain the required powder. Obtainable.

The acacia bark extract can be obtained by extracting the acacia bark according to a conventional method. In order to obtain an acacia bark extract having an excellent anti-pruritic effect, it is preferable to extract the acacia bark with alcohol or a polar solvent.
Ethanol can be used as such an alcohol, and water can be used as a polar solvent, and these solvents can be used alone or in combination of two or more as required. In particular, in order to obtain an excellent anti-pruritic effect, a mixed solvent of water and an alcohol such as ethyl alcohol is preferable.
Furthermore, the extraction operation may be performed multiple times with the same or different solvents.
In order to obtain an extract having an excellent anti-pruritic effect, an extract obtained by further extracting an extract from water or hot water from acacia bark with ethanol may be used.

Extraction is carried out by adding a solvent to acacia bark strips or powder and stirring as necessary, but the temperature, time, or solid-liquid ratio is not particularly limited. When water is used as the solvent, it may be extracted with hot water. The obtained extract may be freeze-dried or spray-dried as it is, or may be freeze-dried or spray-dried after concentration under reduced pressure. The obtained extract can be in various forms such as an extract, a solution, a powder, a concentrated solution, and a paste, and can be widely used as needed.
Furthermore, the Acacia bark extract of the present invention obtained in these forms can be used as it is for the prevention or treatment of pruritus, and further purified as necessary, and the purified product should also be used as an anti-pruritus active ingredient. Can do.

In the present invention, components contained in the bark of the genus Acacia are also exemplified as the acacia bark-derived material. Examples of such components include acacia bark polyphenols. In particular, acacia bark polyphenol is a preferred component because it exhibits an excellent anti-itching effect.
The acacia bark polyphenol of the present invention means a kind of condensed tannin which is a polymer of flavanols having flavan-3-ol as a basic skeleton. Here, such a condensed tannin preferably has a molecular weight of 500 to 3,000. The acacia bark polyphenol used in the present invention can be obtained by hot water extraction of the acacia bark powder and the like.
Acacia bark polyphenol products include registered trademarks of MIMOSA Central Co-operative Ltd. Examples include MIMOSA AL POWDER, MIMOSA CR POWDER, and GOLDEN MIMOSA POWDER.

  The composition of the present invention may be an acacia bark-derived material such as an acacia bark, an extract thereof, a purified product thereof, or an acacia bark polyphenol itself, but other substances having an anti-pruritic effect such as , Antihistamines such as crotamine, antiallergic agents, turmeric, ginseng, KW lactic acid bacteria, maca, or mugwort lotion. In particular, it is preferable to contain an antihistamine, an antiallergic agent, turmeric, ginseng, or KW lactic acid bacteria in that an excellent antipruritic effect due to a synergistic effect is obtained.

  The composition of the present invention may be an acacia bark-derived material, for example, an acacia bark, an extract thereof, a purified product thereof, or an acacia bark polyphenol itself, but as long as the effects of the present invention are not impaired, It may contain additives, ingredients generally used in pharmaceuticals and foods, and other preparations, sweeteners, acidulants, thickeners, fragrances, pigments, emulsifiers, and the like.

The composition of the present invention can be used for prevention or treatment of pruritus. Examples of such pruritus include eczema, dermatitis, urticaria, prurigo nodularis, and pruritus associated with skin diseases such as pruritus. In detail, atopic dermatitis, contact dermatitis, housewife eczema, hand eczema, diaper dermatitis, seborrheic dermatitis, senile pruritus, rash, rash, senile xerosis, sebum-deficient eczema, Examples include cutaneous pruritus, skin pruritus associated with skin diseases such as tinea rotata, foot ringworm, and blepharitis associated with hay fever. The composition of the present invention is also useful for notalgia paresthetica, itching due to hemodialysis for the treatment of renal failure, and psoriasis with itching.
In particular, the composition of the present invention is suitable for pruritus caused by immune abnormalities such as allergies, such as urticaria, atopic dermatitis, contact dermatitis, blepharitis associated with hay fever, especially atopic dermatitis and hay fever. Useful for accompanying blepharitis.
In the present invention, treatment includes elimination of pruritus, reduction of symptoms, healing, suppression of exacerbation, and the like.

The intake amount of the composition according to the present invention is not particularly limited, but can be appropriately selected according to the dosage form and the age, weight and symptoms of the intake person or intake animal such as the user or patient. For example, the amount of the active ingredient is 0.005 to 1 g, preferably 0.005 to 0.5 g, more preferably 0.005 to 0.1 g in terms of the amount of acacia bark polyphenol per 1 kg of the body weight of the ingestor or ingestion animal per day. Ingestion is desirable because it provides an excellent anti-pruritic effect.
The intake period can be arbitrarily determined according to the age and symptoms of the intake person or animal.

  The composition according to the present invention can be used as a food or animal feed, for example, as a health food, a functional food, a health supplement, a specific health food, a beauty food, and a nutritional supplement (supplement). These foods and animal feeds may be in the form of, for example, drinking water such as tea and juice; and ice cream, jelly, candy, chocolate, chewing gum and the like. Moreover, the form of a liquid agent, a powder agent, a granule, a capsule, or a tablet may be sufficient. Here, animals for animal feed include all animals that require prevention or treatment of pruritus, including pet animals, livestock animals, and animals raised in zoos.

  The composition according to the present invention can be used as a medicine or a quasi-drug. These drugs or quasi drugs can be administered orally, for example, in the form of powders, tablets, coated tablets, dragees, hard or soft gelatin capsules, solutions, emulsions or suspensions, for example in the form of suppositories. For example, in the form of an ointment, cream, gel, or solution, and may be administered parenterally, either locally or transdermally.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to Production Examples, Test Examples, and Formulation Examples, but the present invention is not limited thereto. In particular, the embodiment shows the acacia bark of the present invention without dividing the bark into the outer skin and the endothelium, but the outer skin can be used separately from the inner skin.
In the following production examples and test examples, each acacia of the present invention is indicated by a number shown in parentheses after each scientific name. For example, an acacia with the scientific name: Acacia mearnsii De Wild. 1 is written.
Scientific name: Acacia mearnsii De Wild. (No. 1), Scientific name: Acacia mangium Willd. (No. 2), Scientific name: Acacia dealbata Link. (No. 3), Scientific name: Acacia decurrens Willd. (No. 4), Scientific name : Acacia pycnantha Benth. (No. 5).

Production example 1 of Acacia bark powder
Acacia No. 1 bark was dried to a moisture content of 20% or less, and the dried bark was pulverized into a powder of 1.6 mm or less (10 mesh sieve (Tyler) passed) with a hammer mill (Raymond), and then further sieved. The fine powder of 63 micrometers or less (under 250 mesh sieve) was obtained.
Similarly, the remaining four Acacia No. 2 to 5 bark were pulverized to obtain a fine powder of 63 μm or less. Although there were some differences in the yield of the fine powder that passed through the 250 mesh sieve depending on the type, the desired fine powder was obtained.

Production example 2 of Acacia bark extract
Each Acacia No. of the present invention. Each bark of 1 to 5 is dried to a moisture content of 20% or less, and the dried bark is pulverized to a powder of 1.6 mm or less with a hammer mill, and then 5 times the amount of hot water is added to 100 g of the dry crushed bark. After boiling, the mixture was extracted for 15 minutes and filtered using a 10 to 20 μm filter. The obtained filtrate was spray-dried with a spray dryer to obtain 40 g of bark extract.
Hereinafter, each bark extract is acacia no. 1-5 hot water extract.

Production Example 3 of Acacia Bark Extract
The acacia bark of the present invention was dried to a moisture content of 20% or less, and the dried bark was pulverized to a powder of 1.6 mm or less with a hammer mill, and then 5 times the amount of ethanol was added to 100 g of the dry crushed bark, Extraction was carried out for 15 minutes while boiling and refluxing, followed by filtration using a 10-20 μm filter. After evaporating ethanol from the obtained filtrate, the concentrate was spray-dried with a closed spray dryer to obtain 40 g of a bark extract (hereinafter referred to as Acacia No. 1 ethanol extract).
Acacia No. 1 to 5 ethanol extracts were obtained.

Production Example 4 of Acacia Bark Extract
Three times the amount of ethanol was added to 10 g of the Acacia hot water extract obtained in Production Example 2, and the mixture was boiled and refluxed for 15 minutes, and filtered using a 10 to 20 μm filter. Ethanol was evaporated from the obtained filtrate, and water was added thereto, followed by freeze-drying to obtain 9 g of an extract (hereinafter referred to as an Acacia No. 1 hot water extract ethanol fraction).
Acacia No. 1 to 5 hot water extract ethanol fractions were obtained.

Test Example 1 Skin Pruritus Behavior Suppression Test (1) Preparation of Test Feed Acacia No. 1 described in Production Example 2 above. 1 Weigh out the required amount of hot water extract and mix it with regular feed (trade name: Labo MR Stock, Powder, Nippon Agricultural Industrial Co., Ltd.). 1 Test feed 1 containing 1.5% hot water extract was prepared. The test feed was prepared at a frequency of at least once a week during the test period, and the obtained test feed was stored in a cool and dark place.

(2) Animals used ddY mice (4-5 weeks old, body weight of about 20 g, male, purchased from Japan SLC) were used. After feeding the above-mentioned normal feed and carrying out preliminary breeding for 7 days including quarantine, mice in which no abnormalities were observed in the general state were used in the following tests.

(3) Test schedule Each of the above mice was divided into three groups of normal feed group, compound-treated group, and test feed group 1 by the stratified continuous randomization method using body weight as an index, respectively. Allocated. From the next day after grouping, the normal feed group and the compound treatment group were allowed to freely ingest the normal feed, and the test feed 1 group was allowed to freely ingest the test feed 1 respectively. In each group, tap water was freely consumed.
The mice in each group were placed in a cage made of polycarbonate in a breeding environment set at a temperature of 22 ± 3 ° C., a humidity of 50 ± 20%, an illumination time of 8:00:00 to 20:00, and a ventilation rate of 10-17 times / hour. 182W × 260D × 128Hmm).
On the 28th day (4 weeks), 35th day (5 weeks), and 42nd day (6 weeks) after the start of feed intake, the pruritus behavior of the mice was measured.

(4) Measuring method
Compound 48/80 (manufactured by Sigma) was dissolved in physiological saline to a concentration of 0.125 mg / ml, and 0.5 mg / kg (20 μg / animal) was added to each mouse in the compound treatment group and test feed group 1 The dorsal skin was administered subcutaneously. Next, the mice were individually placed in a plastic container, and video recording of the pruritus behavior of the mice for 30 minutes after the administration of Compound 48/80 was performed.
The number of mouse scratching actions was counted from the video footage taken. That is, the above pruritus behavior includes scratching of the back of the neck by the left and right hind limbs (hereinafter referred to as “scratch”), grooming of the head by the forelimbs (hereinafter referred to as “grooming”), and licking the back from the abdomen (hereinafter referred to as “grooming”). , "Licking behavior"), and the number of each was counted as the cumulative number of every 5 minutes.

(5) Statistical processing The cumulative number of each pruritus behavior obtained above was collected for each group, and the average value ± standard error was calculated.
The cumulative number of pruritus behaviors is tested for equal variances by the Bartlett method, and in the case of equal variances (P> 0.05), further comparison is made by one-way analysis of variance (ANOVA), and ANOVA is significant In other cases (P ≦ 0.05), the average values were further compared by the Tukey method. In the case of unequal variance by the Bartlett method (P ≦ 0.05), comparison is made by the Kruskal-Wallis H test, and only when significant (P ≦ 0.05), the average is further calculated by the Tukey method. A comparison of values was made.
The risk factors for the Bartlett method, one-way analysis of variance, Kruskal-Wallis H test, and Tukey method were 5% and 1%, respectively.

(6) Test results Table 1 shows the results of counting the cumulative number of each pruritic behavior.
When the normal feed group and the compound treatment group were compared, an increase in the number of scratches was observed in the compound treatment group.
When the test feed group and the compound treatment group were compared, a decrease in the number of scratches was observed in the test feed group. In addition, the number of grooming at the 5th and 6th weeks also decreased in the test feed group. Furthermore, the number of licking actions also decreased in the test feed group 1 and was statistically significantly reduced especially at the 5th week.
From the above results, it was confirmed that the pruritus behavior of the mice was suppressed by ingestion of the test feed 1, and it was shown that the acacia bark is effective against skin pruritus.

Test Example 2 Acute toxicity test (oral administration)
An oral acute toxicity test using mice was performed according to OECD (Guidelines for the Testing of Chemicals 401, 1987).
For ICR male and female mice, specimens of 9 doses each with a tolerance of 500 mg / kg, up to 7,000 mg / kg for males and 6,500 mg / kg for females (Acacia No. 1 hot water extract of Production Example 2 above) Was orally administered to male and female mice once. As the specimen, the product of the present invention was suspended in pure water. As a result, the LD50 value was 4,468 mg / kg for males and 3,594 mg / kg for females, and no death was observed at a dose of 3,000 mg / kg.
The above test was conducted using the Acacia No. of Production Example 2. Similar results were obtained with 2-5 hot water extracts. Thereby, it turned out that the composition of this invention is excellent in safety | security.

Test Example 3 Mutagenicity Test A mutagenicity test was conducted according to Ministry of Labor Notification No. 77 (September 1, 1988).
Using the Escherichia coli WP2 uvrA strain and the Salmonella typhimurium TA strain 4 strains, a reverse mutation test including metabolic activation was conducted at a dose of 156 to 5,000 μg / plate (Acacia No. 1 to 5 hot water of Production Example 2). Extract). As a result, no increase in the number of revertant colonies was observed for any of the strains. It was concluded that mutagenicity of 1-5 hot water extracts was negative, and it was found to be excellent in safety.

Formulation Example 1 Preparation of internal use Using the acacia bark hot water extract ethanol fraction of Production Example 4, an internal preparation was prepared with the composition shown below.
Extract fraction of Production Example 4 1.0 (% by weight)
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
Total 100.0

Formulation Example 2 Preparation of Pet Food Using the acacia bark hot water extract of Production Example 2, a pet food was prepared with the composition shown below.
Extract of Production Example 2 1.0 (% by weight)
Oatmeal 88.0
Starch 5.0
Salt 2.5
Whole egg 3.0
Seasoning 0.5
Total 100.0

Formulation Example 3 Preparation of Tablet (Confectionery) Using the ethanol fraction of Acacia bark hot water extract of Production Example 4, tablets (confectionery) were prepared with the composition shown below.
Extract fraction of Production Example 4 1.0 (% by weight)
Citric acid 1.0
Nonfat dry milk 15.0
Sucrose ester 1.0
Flavor 0.5
Powdered sugar 20.0
Lactose 61.5
Total 100.0

According to the present invention, a composition for preventing and / or treating pruritus can be obtained.
More specifically, the composition of the present invention is useful for the prevention and / or treatment of pruritus in allergic diseases.
These compositions can be used for pharmaceuticals or quasi drugs, foods such as health foods, health supplements, foods for specified health, or dietary supplements, or animal feed.

Claims (5)

Scientific name:. Acacia mearnsii De Wild, scientific name:. Acacia mangium Willd, scientific name: Acacia dealbata Link, scientific name:.. Acacia decurrens Willd, and scientific name: containing Acacia pycnantha Benth bark of genus Acacia selected from the group consisting of. A prophylactic and / or therapeutic agent for pruritus, characterized by comprising: Bark of genus Acacia is an extract of the bark of the genus Acacia, prophylactic and / or therapeutic agent for pruritus according to claim 1, wherein. The agent for preventing and / or treating pruritus according to claim 1, wherein the bark derived from Acacia is an acacia bark polyphenol.   The agent for preventing and / or treating pruritus according to any one of claims 1 to 3, which is for oral intake. Acacia spp scientific name:. Acacia mearnsii De Wild is, the prevention and / or therapeutic agent for pruritus according to any one of claims 1 to 4.