JPH1017493A - Antiinflammatory or antiallergic external preparation for skin containing calcium ion sequestering agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an external preparation having no adverse effect and capable of preventing cutaneous allergy due to hair dying agent by including a medicine preventing or reducing inflow of calcium ion into a mast cell at the first stage of inflammation. SOLUTION: This medicine contains a calcium ion sequestering agent as an active ingredient. It is preferable that the sequestering agent has a bi- or polyfunctional basic acid group. Phosphate group, sulfate group, carbonate group, etc., can be exemplified as the basic acid group. It is preferable that the medicine contains 0.01-10.0% one or two or more kinds of the sequestering agents. In addition, for example, ethylenediamine tetraacetic acid, diethylenetriamine pentaacetic acid, triamine acetate, etc., or metal salts thereof can be exemplified as the sequestering agent. Thus, the medicine effective in treatment of allergic diseases or reduction of skin sensitizing potential due to an oxidation dyeing agent containing paraphenylendiamin, etc., as a main agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an anti-inflammatory skin preparation or an anti-allergic skin preparation for reducing or suppressing allergy and the resulting inflammatory reaction.

[0002]

2. Description of the Related Art In recent years, allergic diseases such as allergic rhinitis and atopic dermatitis have greatly increased. As a method for treating these, an external preparation including administration of adrenocortical hormone, a histamine receptor antagonist and the like is used.
On the other hand, in the beauty industry, oxidized hair dyes containing paraphenylenediamine or the like as a main component are mainstream, although there is no skin sensitization, and there is no useful hair dye instead of this, At present, it must be used in consideration of the dangers of water.

[0003]

In general, any drug used for treating allergic diseases such as allergic rhinitis and atopic dermatitis has strong side effects and is not suitable for daily use. In the case of corticosteroids, when long-term continuous use is stopped, a skin reaction called rebound occurs. Further, currently used skin external preparations are originally applied after the onset of dermatitis, and are not intended to prevent allergic diseases. In addition, in the case of the hair dye described in the previous section, there is no alternative hair dye, and at present, a method of further reducing skin sensitization is desired, and it is desirable to prevent skin allergy due to the hair dye. . It is an object of the present invention to provide an anti-inflammatory skin external preparation or an anti-allergic skin external preparation which has no side effects against such diseases.

[0004]

[Means for Solving the Problems] The allergic inflammatory response is caused by the calcium ion (Ca ⁺⁺⁾ from outside the cell when the antigen binds to two IgE antibodies bound on mast cells and basophils in such a manner as to bind the antigen. ) Flows into the cells, and the calcium ions activate the enzymes in the cells, resulting in the release of inflammatory mediators such as histamine outside the cells. Therefore, the present invention provides an anti-inflammatory skin external preparation or an anti-allergic agent comprising a calcium sequestering agent (chelating agent) for preventing or reducing the influx of calcium ions into mast cells, which is the first step of inflammation. It relates to a skin external preparation. More specifically, the present invention relates to an external preparation for skin containing a calcium sequestering agent wherein the calcium sequestering agent has a divalent or higher basic acid, and as a basic acid group of the calcium sequestering agent. Represents a phosphoric acid group, a sulfuric acid group, a carbonic acid group or the like, and a hydroxyl group, an N group, an NH group,
It may contain an NH ₂ group.

[0005] The present invention is also provided as an external preparation for skin containing 0.01 to 1.0% of one or more of the above calcium sequestering agents. The external preparation for skin is applied to any of cosmetics, quasi-drugs, and pharmaceuticals. Further, after treating the hair with the oxidative hair dye, one or more of the calcium sequestering agents are used in an amount of 0.01 to 2%.
It is provided as a skin external preparation containing 1.0%.

The compounds of the present invention include substantially the following calcium sequestering agents: ethylenediaminetetraacetic acid and its metal salts, diethylenetriaminepentaacetic acid and its metal salts, amine triacetate and its metal salts, triacetate. Ethylenetetraamine hexaacetic acid and its metal salts, tripolyphosphoric acid and its metal salts, trimetaphosphoric acid and its metal salts, tetrametaphosphoric acid and its metal salts, hydroxyethanediphosphonic acid and its metal salts, phytic acid and its metal salts, etc. Yes, metal salts include monovalent alkali metals such as sodium and potassium.

[0007]

EXAMPLES The anti-inflammatory or anti-allergic skin external preparation of the present invention will be described in more detail including the following examples. 1: Evaluation as an anti-inflammatory or anti-allergic skin external preparation containing a calcium sequestering agent A skin sensitization test was conducted with 10 guinea pigs using paraphenylenediamine, which is a hair dye raw material, as an allergen. The anti-inflammatory or anti-allergic properties of the calcium sequestering agents of the present invention were tested. [Guine pig skin sensitization test with paraphenylenediamine] The Ishihara method was used as a contact sensitization test method. This method comprises a sensitization induction phase in which a sensitizer is repeatedly applied to the skin of a guinea pig, and a challenge administration phase after a 2-week non-treatment period. test. As a sensitizing inducer, 0. Using 1% paraphenylenediamine (hereinafter PPDA), 0.1% ethylenediaminetetraacetic acid (hereinafter EDTA), 0.1% phytic acid (hereinafter PA) as a calcium sequestering agent
Or 0.1% hydroxyethanediphosphonic acid (hereinafter H
EP) was converted into an aqueous solution as needed to prepare a sample. Table 1 shows the list.

[0008]

[Table 1]

The results are shown in Tables 2 and 3. The antiallergic property was evaluated by the sensitization rate after 48 hours. The sensitization rate was described as the number of sensitizations out of 10 animals, with the reaction of clear erythema or higher as a sensitization example.

[0010]

[Table 2]

[0011] Anti-inflammatory properties were evaluated by the average score 48 hours after the inflammatory response. The inflammatory response was scored according to the Ishihara method.

[0012]

[Table 3]

As a result of the test, the sensitization rate of paraphenylenediamine in the group induced by sensitization with paraphenylenediamine containing no calcium sequestering agent was 60 to 70% for all calcium sequestering agents. The rating of the evoked response was 0.7 to 0.75. The rating of the evoked reaction by the mixture of paraphenylenediamine and ethylenediaminetetraacetic acid in the same group was 0.4, which was a remarkable decrease. This result indicates that allergic inflammation is reduced even in animals that have acquired skin allergy by the combined use of ethylenediaminetetraacetic acid.
Furthermore, the sensitization rate of paraphenylenediamine in the group sensitized with a mixture of paraphenylenediamine and ethylenediaminetetraacetic acid is 10%, which is significantly lower than the sensitization rate of the previous group. This result indicates that ethylenediaminetetraacetic acid clearly suppressed the skin sensitization of paraphenylenediamine. The rating of the evoked reaction by the mixed solution of paraphenylenediamine and ethylenediaminetetraacetic acid in the same group was 0.0, and the apparent sensitization rate was 0.
%Became. This is presumably because the anti-inflammatory effect was further exerted on the evoked response of the animal whose sensitization was reduced to 10%.
Therefore, ethylenediaminetetraacetic acid acting as a calcium sequestering agent can be evaluated as having anti-inflammatory and anti-allergic properties, and can reduce or suppress the sensitization of allergens such as paraphenylenediamine.

Next, phytic acid and hydroxyethanediphosphonic acid were subjected to the same test to evaluate their anti-inflammatory or anti-allergic properties. As a result, similarly to ethylenediaminetetraacetic acid, anti-inflammatory and anti-allergic properties were confirmed, and it was found that the calcium sequestering agent could reduce or suppress inflammation and allergy.

Human anti-inflammatory or anti-allergic properties were evaluated using a patch test. In the test, allergens of each subject were evaluated in Example 1 and its base, Example 2
And a sample kneaded with the base or Example 3 and the base were evaluated according to Japanese standards after patching for 48 hours and one day after removing the patch bond. Examples are described in Table 4.

[0016]

[Table 4]

As a result, in all of the eight cases, the samples in which the above three kinds of calcium sequestering agents were mixed with the allergen showed lower scores than the original allergen reaction scores in the pasted samples. These results indicate that human allergic dermatitis also acts as an anti-inflammatory or anti-allergic skin external preparation. The results are shown in Table 5.

[0018]

[Table 5]

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[Procedure amendment]

[Submission date] September 30, 1996

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0005

[Correction method] Change

[Correction contents]

The present invention also relates to a method for preparing one or more of the above calcium sequestering agents from 0.01 to
It is provided as a skin external preparation containing 10.0 % by weight .
The external preparation for skin is applied to any of cosmetics, quasi-drugs, and pharmaceuticals. Further, after treatment of hair with an oxidative hair dye, it is provided as an external preparation for skin containing 0.01 to 10.0 % by weight of one or more calcium sequestering agents.

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location C09K 3/00 108 C09K 3/00 108E

Claims (2)

[Claims] 1. An anti-inflammatory external skin preparation containing a sequestering agent for calcium. 2. An external preparation for skin for reducing or preventing allergic dermatitis, comprising a sequestering agent for calcium.