JPH1036276A - Antiallergic agent and antiallergic cosmetic material and food containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject drug which can display antiallergic effect caused by inhibiting liberation of chemical mediator from mast cells and basophils by using a specific crude drug and a plant extract as an active ingredient. SOLUTION: This drug contains one or more kinds of crud drugs selected from Gambir, Zanthoxylum fruit, Clove bud, Rose fruit, Sanguisorba, Eriobotrya leaf, Chinchona and Saxifraga as active ingredients. This drug is additionally containable an extract of plant of the genus Betula Platyphylla and an extract of grape fruit as active ingredients. As solvents for extracting these crude drugs and plants, one or more kinds of solvents among water, ethanol, 1.3- butylene glycol, propylene glycol, glycerol and diglycerol are preferable. By this drug, the liberation of histamine, serotonin and leukotriene is inhibited and a variety of symptoms caused by allergic reaction are also suppressed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an allergic reaction caused by suppressing the release of chemical mediators such as histamine, serotonin and leukotriene released from mast cells and / or basophils. The present invention relates to drugs for preventing or treating diseases, cosmetics and foods containing these as active ingredients.

[0002]

2. Description of the Related Art Chemical mediators such as histamine, serotonin, and leukotriene are released from mast cells and basophils by allergen inflammation stimulation, resulting in increased vascular permeability, smooth muscle contraction, increased mucus secretion, and enhanced immune cell migration. Allergic reaction occurs.

Therefore, antihistamines such as histamine receptor inhibitors and histamine antagonists have been used as therapeutic agents for inflammation due to allergic reactions. However, antihistamines composed of chemically synthesized products themselves include:
There has been a problem that side effects such as drowsiness and dizziness and fatigue occur easily.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a highly safe antiallergic agent which does not cause the above-mentioned side effects.

[0005]

Means for Solving the Problems As a means for solving the above-mentioned problems, the present inventors have widely screened substances having an anti-allergic effect from natural products, and as a result, it has been found that specific crude drugs and plant extracts contain mast cells and plant extracts. The present inventors have found that they have an antiallergic action based on the action of inhibiting the release of chemical mediators from basophils, and have completed the present invention.

That is, the antiallergic agent of the present invention comprises one or more crude drugs selected from Asenyaku, Sansho, Choshi, Yomi, Jiyu, Loquat leaf, Nina, Tiger ear grass and a plant of the genus Birch. The extract and grape extract are based on the action of inhibiting the release of chemical mediators such as histamine, serotonin and leukotriene from mast cells and / or basophils.

Asenyaku (Asenyaku), a kind of crude drug used in the present invention, is known as an astringent antistatic drug, and is a genus Rubiaceae Gambir ( Uncaria gambir Kurz.) And its congener plant, Uncaria acidida ( Uncaria acid
a Roxb.), Uncaria berna
ysii Muell.), Uncaria d' Asoneura ( Uncaria d)
asyoneura Korth.), Uncaria lanosa ( Uncaria la)
nosa Wall.) and other leaves and shoots. In addition, the water of the lumber or bark of the same herbal medicine, peg asen- drug ( Acasia catechu Willd., Acasia suma Kurz., Pineace burmanica Kunz. Extract) also provides an anti-allergic effect based on the same chemical mediator release inhibitory action as Asenyaku.

[0008] Next, the Japanese pepper is Zantrum salmon ( Zant
hoxylum piperitum DC.) and its congener plants, and has long been used as a stomachic. As a congener plant, Asakusan show ( Zanthoxylum piperi)
um DC. forma inerme Makino), Yamasa sakurazanzan ( Zanthoxylum piperium DC. forma brevispinosumMa)
kino), pepper ( Zanthoxylum bungeanum Sieb.et Zu)
cc.), dog shark ( Zanthoxylum schinifolium Si)
eb.et Zucc.), Zanthoxylum avicenn
ae DC., Zanthoxylum simulans Hance, Zanthoxylum pl
anispinum Sieb.et Zucc.).

[0009] The clove is Syzygium a
romaticum L., Eugenia caryophyllata Thunb., Eugeni
a aromatica Baill. non Berg.), which has long been used as a stomachic and has a therapeutic effect on dermatitis has also been disclosed (JP-A-5-246874).

[0010] The fruit of the rose family Rosa multiflora
a Thunb., Rosa polvantha Sieb.etZucc.var.genuina N
akai) or a related plant thereof, which has been used for a long time as a diuretic antidote and has a hyaluronidase-inactivating effect (JP-A-2-11520). Closely related plants include Terihanoibara ( Rosa wichura)
iana Creign var.anpullicarpa Honda), Fujiibara ( Rosa fujisanensis Makino), Yamahamanas ( Rosa da )
vurica Pallas, Rosa willdenowii Sprengel) and the like.

[0011] Chinire is, Rosaceae Burnet (Sanguisorba
officinalis L., Sanguisorba tenuifolia Fisch et Li
nk, Sanguisorba applanata , Sanguisorba alpina ) roots and rhizomes, which have long been used as hemostatic astringents. Waremokou has a hyaluronidase inactivating effect (JP-A-2-11520) and an anti-plasmin effect (JP-A-1
-61415) is already known.

Loquat leaves are Eriobotrya japon
ica ) leaf, which has long been used as a diuretic and cooling agent.

[0013] kina is, Rubiaceae Cinchona pubescens (Cinchona
succirubra Pavon et Klotzsch, Cinchona pubescens
Vahl.) Or the bark of its congener, and has been used as a stomachic for a long time. As a congener of the red linden, Cinchona calysata W
edd.), Bolivian linden ( Cinchona ledgeriana ),
Cinchona officinalis
L.), Cinchona pitayensis
Wedd.), Cinchona maritima ,
Remijia-Pedunkurata (Remijia pedunculata Tria
na), Remijia-Purujeana (Remijia purdieana)
And the like.

The tiger ear grass is Saxifragaceae ( Saxi).
fraga stolonifera Meerburg, Saxfraga sarmentosa
L.), which has long been used as an antipyretic and antidote, and is also known to have a whitening effect (Japanese Patent Laid-Open No.
139951).

As the birch plants of the birch family, birch ( Betula platyphylla Sukatchev var. Japonic)
a Hara), Betula birch ( Betula ermanii Cham.), Giant birch ( Betula globispica Shirai), Yaegawa birch ( Betula davurica Pall.), Betula birch ( Betula )
maximowicziana Regel.), Azusa ( Betula grossa Sie)
var. ulmifolia), white birch ( Betu )
la pendula Roth.) and the like. Birch birch plants are more preferred examples of birch, birch birch and white birch, of which birch is particularly preferred. The extraction site for obtaining the extract is not particularly limited, but roots, rhizomes, heartwood, bark, leaves and the like are preferable. Among them, extracts from bark are particularly preferred from the viewpoint of antiallergic action.

Extraction sites for obtaining grape ( Vitis venifera L.) extracts are preferably fruits, pericarp, and leaves, and among them, extracts from leaves are particularly preferred in terms of effect.

As a solvent for obtaining these crude drugs and plant extracts, one or more selected from water, ethanol, 1,3-butylene glycol, propylene glycol, glycerin and diglycerin are preferred, but they are used. Depending on the type of crude drug and the plant, more preferable solvents are limited. The most preferred extraction solvent for extracting the active ingredient from Asenyaku, Yomi, Jiyu, Loquat leaf, Nina, Tiger ear plant, Birch plant and grape is selected from water, ethanol and 1,3-butylene glycol. One or two or more of them, more preferably a 50% by weight aqueous solution of ethanol or a 50% aqueous solution of 1,3-butylene glycol. Further, when extracting the active ingredient from cloves and Japanese pepper, ethanol and / or water are preferred, and the most preferred extraction solvent is a 50% by weight aqueous ethanol solution. As an extraction solvent for extracting an active ingredient from a birch plant and a grape, one or more selected from water, 1,3-butylene glycol, ethanol, and polyethylene glycol are preferable, and 50%, An aqueous solution of 3-butylene glycol is most preferred.

The ratio of the plant to the solvent at the time of extraction is not particularly limited.
It is preferably 0 times by weight, especially 5 to 100 times by weight in terms of extraction operation and efficiency. The extraction temperature is conveniently in the range of room temperature to normal pressure and below the boiling point of the solvent. The extraction time varies depending on the extraction temperature and the like, but is preferably in the range of 2 hours to 2 weeks.

The plant extract thus obtained can be used as such as the extract, or can be blended after deodorizing and purifying operations as long as the antiallergic effect is not lost. It may be used, and further, a fraction may be obtained by column chromatography or the like. Further, these extracts, deodorized, purified, and fractionated products can be dried by removing the solvent therefrom, and further provided in the form of a solution solubilized in a solvent such as alcohol or in the form of an emulsion. can do.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION The antiallergic agent according to the present invention comprises:
It can be added to and blended with foods, pharmaceuticals, cosmetics, etc. In foods, it can be added to oils and fats products, emulsified products, soft drinks and the like. Pharmaceuticals can be added to oral preparations, external preparations, injections, inhalants, nasal drops, eye drops, etc. Depending on the method of use, tablets, liquids, injections, ointments, creams, lotions, aerosols , Suppositories and the like. In addition, excipients, bases, emulsifiers, stabilizers, dissolution aids, flavoring agents,
Preservatives, fragrances, coloring agents, coating agents and the like can be appropriately compounded. As cosmetics, lotions, emulsions,
It can be added to creams, etc.
A humectant, an ultraviolet absorber, a water-soluble polymer, an antioxidant, a surfactant, a sequestering agent, an antibacterial preservative, and the like can be added. The effect can be further enhanced by using it together with other anti-inflammatory and anti-allergic cosmetic ingredients such as glycyrrhizic acids, water-soluble azulene, diphenhydramine hydrochloride, dl-α-tocopherol and its derivatives, vitamins B ₂ and B _6. it can.

[0021] The dosage of the plant extract used as a medicament varies greatly depending on the kind of plant used, the degree of purification, the age and symptoms of the patient, etc., but in general, the dry weight in the case of oral administration. Range from 5 to 500 mg / day. When blended in foods and cosmetics, the concentration is preferably in the range of 0.001 to 5% by weight in view of the effect and the scent and color tone when added. Further, in formulating, one kind of plant extract may be used,
A synergistic effect can be expected by using a mixture of two or more plant extracts.

[0022]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The features of the present invention will be described in detail with reference to embodiments.

Prior to the description of the examples, a method for preparing the plant extract used in each example will be described. 100 g of the dried product from a specific part of the plant was immersed in 1000 g of a solvent at room temperature for 7 days, and the supernatant was filtered. Table 1 shows the extraction site and solvent for each plant.

[0024]

[Table 1]

The histamine release inhibitory effects of the crude drugs and plant extracts of Examples 1 to 10 were determined using an antiallergic test method using histamine released from rat-derived basophil leukemia cells (RBL-2H3) as an index. evaluated.

Add RBL-2H3 to a 48-well plate
Cells were seeded at a density of 10 ⁵ cells / well, cultured for 24 hours (carbon dioxide 5%, 37 ° C.), and then released with a solvent (117).
mM, NaCl, 5.4 mM, KCl, 2.0 mM, Ca
_{Cl 2, 0.8mM, MgSO 4,} 5.6mM, D- glucose, 25m, N-2- hydroxyethylpiperazine--N'-2-ethanesulfonic acid buffer and 1 mg / m
1, a solution containing bovine serum albumin, pH 7.7) 500
After washing twice with μl, the reaction solution was added and the cells were cultured at 37 ° C. for 60 minutes. 100 μl of the extracellular solution was taken out, and the remaining solution was removed by suction. Then, 0.2% Triton X-10
0 was added at 300 μl / well, and after 20 minutes, 100 μl of cell lysate (intracellular solution) was taken out. An unreacted reaction solution was also taken out of the extracellular solution and the intracellular solution by 100 μl each and used as a control. Table 2 shows the composition of the reaction solution.

[0027]

[Table 2]

The amount of histamine as a chemical mediator in the extracellular fluid, intracellular fluid and control thus obtained was determined by a post-column method using a high performance liquid chromatograph (immune experiment operation method). 2. Shunsuke Migita, Susumu Konda, Yusuke Honjo, Toshiyuki Hamaoka, edited by Nankodo, 1995, 1037 Base). The histamine release rate and the histamine release inhibition rate were calculated using Equations 1 and 2. Table 3 shows the histamine release inhibition rates of Examples 1 to 10.

[0029]

(Equation 1) In Formula 1, A represents the amount of histamine in the intracellular fluid, Bin and Bout represent the amount of histamine in the control intracellular fluid and extracellular fluid, and C represents the amount of histamine in the extracellular fluid.

[0030]

(Equation 2) In Formula 2, D represents the histamine release rate at the time of sample addition, E represents the histamine release rate in the positive control, and F represents the histamine release rate in the negative control.

[0031]

[Table 3]

As shown in Table 3, it is clear that the crude drugs and plant extracts of Examples 1 to 10 suppress histamine release.

Examples 11 to 20 Water-in-oil ointment (1) Beeswax 3.0 (% by weight) (2) Hydrogenated lanolin 8.0 (3) Squalane 34.0 (4) Solid paraffin 2.0 (5) ) Microcrystalline wax 9.0 (6) White petrolatum 5.0 (7) Hexyldecyl adipate 12.8 (8) Sorbitan sesquioleate 3.5 (9) Polyoxyethylene (50) hydrogenated castor oil 1.0 (10) Glycerin 10.0 (11) Purified water 10.0 (12) Ethanol 1.0 (13) Crude drug and plant extract 0.5 of Examples 1 to 10 (14) Methyl paraoxybenzoate 0.2 Production method After heating the oil phase components (1) to (9) and the aqueous phase components (10) to (11) to 75 ° C. to mix and homogenize, add the water phase to the oil phase and emulsify. After cooling, the mixture obtained by mixing (12) to (14) at 40 ° C. and homogenizing is kneaded.

The water-in-oil ointments of Examples 11 to 20
30-year-old woman with atopic dermatitis
It was applied to the face continuously for 2 weeks, and the results shown in Table 4 were obtained.
At the same time, an ointment containing no plant extract was prepared. During the period of use, use of another antiallergic agent such as an antihistamine was stopped.

[0035]

[Table 4]

Examples 11 to 20 containing the crude drug and the plant extract according to the present invention were all effective in improving the symptoms of atopic dermatitis, and none of the patients worsened during the application period. On the other hand, in Comparative Example 1 in which the crude drug and the plant extract were not mixed, none of the patients showed a remarkable effect, and conversely, there were four patients who became worse.

Example 21 Oil-in-water Emulsion (1) Beeswax 0.5 (% by weight) (2) Vaseline 2.0 (3) Squalane 5.0 (4) Sorbitan sesquioleate 0.8 (5) ) Sucrose fatty acid ester 1.2 (6) 1,3-butylene glycol 10.0 (7) Glycerin 5.0 (8) Purified water 55.0 (9) Sodium carboxymethyl cellulose 20.0 (1% by weight aqueous solution) (10) Extract of Example 2 0.3 (11) Extract of Example 3 0.2 Production method: Oil phase components (1) to (4) and aqueous phase components (5) to (8) After heating to 75 ° C. to homogenize the mixture, the oil phase is added to the aqueous phase and pre-emulsified while stirring, and the component (9) heated to 70 ° C. is added, followed by emulsification with a homomixer. Cool to 40 ° C, add components (10) and (11) and mix.

Example 21 Oil-in-water emulsion (1) Polyoxyethylene (40) hydrogenated castor oil 1.0 (% by weight) (2) Glycerin 10.0 (3) 1,3-butylene glycol 5.0 (4) ) Methyl paraoxybenzoate 0.3 (5) Purified water 51.3 (6) Squalane 10.0 (7) Glyceryl monostearate 1.0 (8) Carboxyvinyl polymer (1% by weight aqueous solution) 15.0 (9 ) Sodium hydroxide (1% by weight aqueous solution) 6.0 (10) Extract of Example 4 0.2 (11) Extract of Example 5 0.1 (12) Extract of Example 6 0.1 Preparation method : The aqueous phase of (1) to (5) and the oil phase components of (6) and (7) were each heated to 75 ° C. and mixed and homogenized, and then the oil phase was added to the aqueous phase and pre-emulsified while stirring. Further, after adding the component (8) heated to 70 ° C., the mixture is emulsified by a homomixer. After cooling, at 40 ° C., the component (9) was added and mixed,
The components (10) to (12) are added and mixed.

Example 22 Lotion (1) Methyl parahydroxybenzoate 0.2 (% by weight) (2) Ethanol 5.0 (3) Glycerin 10.0 (4) Extract of Example 7 0.5 (5) Purified water 84.3 Production method; After dissolving (1) in (2), (3) to (5) were sequentially added to make the solution uniform.

Example 23 Lotion (1) Extract of Example 8 0.5 (% by weight) (2) 1,3-butylene glycol 25.0 (3) Polyoxyethylene (50) hydrogenated castor oil 0 (4) Purified water 73.5 Production method; Components (1) to (4) are mixed, dissolved and homogenized.

Example 24 Water-in-oil emulsion (1) Beeswax 2.0 (% by weight) (2) Microcrystalline wax 1.0 (3) Lanolin 2.0 (4) Liquid paraffin 30.0 (5) Stearin Aluminum acrylate 0.2 (6) Sorbitan sesquioleate 4.0 (7) Sucrose fatty acid ester 1.0 (8) Glycerin 20.0 (9) Methyl parahydroxybenzoate 0.5 (10) Purified water 38.8 (11) Extract 0.5 of Example 9 Production method: The oil phase of (1) to (6) and the aqueous phase of (7) to (11) were each heated to 75 ° C. to mix and homogenize. Add the aqueous phase to the phase and emulsify.

Example 25 Oil-in-water emulsified cream (1) Beeswax 6.0 (% by weight) (2) Cetyl alcohol 5.0 (3) Hydrogenated lanolin 8.0 (4) Squalane 30.0 (5) Stearin Monoglyceryl acid 4.0 (6) Sorbitan sesquioleate 2.0 (7) Polyoxyethylene (50) hydrogenated castor oil 2.0 (8) Purified water 32.2 (9) Methyl paraoxybenzoate 0.3 ( 10) Glycerin 5.0 (11) Ethanol 5.0 (12) Extract 0.5 of Example 10 Preparation method: The oil phase of (1) to (7) and the component of (8) were 75 each.
After heating to ℃ to make the mixture uniform, the oil phase is added to (8) and emulsified. After cooling, the components (9) to (12) are dissolved and homogenized at 40 ° C. and added.

Example 26 Candy (1) White sugar 60.0 (% by weight) (2) Ginger syrup 39.5 (3) Extract of Example 3 0.1 (4) Extract of Example 10 0.3 ( 5) Fragrance 0.1 Production method: (1) and (2) were mixed by heating, cooled, and cooled to 70%.
The components (3) to (5) are added at ℃, and the mixture is homogenized and molded.

Example 27 Tablets The Acacia catechu extract obtained in Example 1 was concentrated to dryness under reduced pressure.
A dried product was obtained. The dried product (150 g) was mixed with the same amount of lactose and magnesium stearate (5 g) to produce a tablet having a diameter of 10 mm and a weight of 300 mg with a tableting machine. The tablets were taken by 20 hay fever patients for two weeks a day for two weeks. Tablets containing only lactose and magnesium stearate, which did not contain the Acacia catechu extract, were simultaneously prepared, and taken as Comparative Example 2 by 20 hay fever patients. During the administration period, the use of other allergic drugs such as antihistamines was discontinued. A questionnaire was given on the 3rd, 7th, and 14th days after the administration, and the antiallergic effect was evaluated. At the start of the evaluation, all subjects were allergic to hay fever and complained of itchy eyes, excessive nasal discharge, and sneezing.

[0045]

[Table 5]

As shown in Table 5, administration of the tablet of Example 27 reduced symptoms such as itchy eyes and excessive nasal discharge. In addition, the effect was shown to be remarkable by continuous use for one week or more. On the other hand, in Comparative Example 2 in which the extract of Aseniya was not added, none of the patients had significantly improved symptoms, and 5-7 patients had worsened symptoms.
People. In addition, none of the patients who used Example 27 complained of side effects such as causing drowsiness and dizziness and causing fatigue.

[0047]

As described in detail above, 1 is selected from Asenyaku, Sansho, Choshi, Yomi, Jiyu, Loquatha, Nina, and Tiger eargrass.
An antiallergic agent containing one or more kinds of crude drugs, extracts of birch plants, and grape extracts as active ingredients, can be obtained from mast cells and / or basophils, by using histamine, serotonin,
It has the effect of suppressing the release of chemical mediators such as leukotriene, and has the effect of suppressing symptoms such as itching of the skin and mucous membranes, excessive nasal discharge and sneezing due to allergic reactions.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location A23L 1/221 A23L 1/221 C 1/30 1/30 B A61K 7/00 A61K 7/00 K W 7/48 7/48

Claims (9)

[Claims] (1) An antiallergic agent comprising one or more crude drugs selected from the group consisting of Asenyaku, Sansho, Choshi, Yomi, Jiyu, Loquat, Nina, and Tiger eargrass as active ingredients. 2. An antiallergic agent comprising an extract of a plant of the genus Birch as an active ingredient. 3. An antiallergic agent comprising a grape extract as an active ingredient. 4. Mast cells and / or basophils containing as an active ingredient one or more crude drugs selected from the group consisting of Asenyaku, Sansho, Choshi, Yomi, Jiyu, Loquat, Nina and Tiger ear grass. Of release of chemical mediators from water. 5. An agent for inhibiting the release of chemical mediators from mast cells and / or basophils, comprising an extract of a plant of the genus Birch as an active ingredient. 6. An agent for suppressing the release of chemical mediators from mast cells and / or basophils, comprising a grape extract as an active ingredient. 7. The method of claim 1, wherein the chemical mediator is histamine,
The chemical mediator release inhibitor according to any one of claims 4 to 6, which is one or more selected from serotonin and leukotriene. 8. An antiallergic cosmetic comprising the antiallergic agent according to claim 1 as an active ingredient. 9. An antiallergic food containing the antiallergic agent according to claim 1 as an active ingredient.