JPH08157321A - Cosmetic - Google Patents

Abstract

PURPOSE: To obtain a cosmetic comprising histamine H1 -antagonist(s) or salt(s) thereof, having inhibitory action on the decomposition of hyarulonic acid, thus effective for remedying the chapped skin and dried skin. CONSTITUTION: This cosmetic contains at least one kind of histamine H1 - antagonist or salt thereof, having inhibitory action on the decomposition of hyarulonic acid important for skin dampishness and firmness, therefore, can remedy chapped or dried skin. The histamine H1 -antagonist is esp. pref. chlorpheniramine, pyrilamine, diphenhydramine, tripelennamine, brompheniramine, cyclizine, or promethazine. The salt thereof is e.g. a hydrochloride, hydrobromide, sulfate, acetate, fumarate, maleate, tartrate. This cosmetic can take such a form as gel, cream, spray, cataplasm, lotion, pack, milky lotion, or powder.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a cosmetic composition which inhibits the decomposition of hyaluronic acid and is effective for rough and dry skin.

[0002]

2. Description of the Related Art Hyaluronic acid is used to retain water in cell spaces, retain cells based on the formation of a jelly-like matrix in tissues, maintain skin lubricity and flexibility, and exert external forces such as mechanical damage. It has many functions such as resistance to bacteria and prevention of bacterial infection (BIO INDUSTR
Y, vol. 8, p. 346, 1991). It is said that hyaluronic acid in the skin decreases with age, resulting in aging such as wrinkles and roughness.

Therefore, it is considered that by inhibiting the decomposition of hyaluronic acid, the lubricity and flexibility of the skin are maintained and the skin is prevented from becoming rough or the skin is dried.

Therefore, for the purpose of inhibiting the degradation of hyaluronic acid, various cosmetics have been proposed which use an active inhibitory component of hyaluronidase which degrades hyaluronic acid. However, in recent years, it has been reported that conventionally known hyaluronidase does not exist in human skin fibroblasts (BBA, 172, 70, 1990). Therefore, it is considered that cosmetics using a hyaluronidase activity-inhibiting ingredient cannot be expected to have a hyaluronic acid decomposition inhibiting effect.

[0005]

Therefore, it is an object of the present invention to use hyaluronidase using the evaluation method using human skin-derived cells developed by the present inventor, without using the conventional evaluation method using hyaluronidase. It is an object of the present invention to provide a cosmetic composition which is effective for physiologically deteriorated skin due to acid decomposition, that is, rough skin and dry skin.

[0006]

The above object is achieved by a cosmetic composition containing a histamine H ₁ -antagonist or a salt thereof.

The structure of the present invention will be described below in detail.

The histamine H ₁ -antagonist used in the present invention is not particularly limited, and examples thereof include ethanolamine-type diphenhydramine, ethylenediamine-type pyrilamine, triprenamine, alkylamine-type chlorpheniramine, brompheniramine, and piperazine-type. Examples thereof include cyclidine and phenothiazine type promethazine.

The salt of histamine H ₁ -antagonist is not particularly limited, but particularly pharmaceutically acceptable inorganic acid salts such as hydrochloride, hydrobromide, sulfate and phosphate, and acetate. , Fumarate, maleate, tartrate, citrate, p-toluenesulfonate, and other organic acid salts.

These histamine H ₁ -antagonists or salts thereof can be used alone or in combination of two or more.

The amount of the histamine H ₁ -antagonist or salt thereof used in the present invention varies depending on the object of application and cannot be specified unconditionally, but 0.001 to 0.5% by weight based on 100 as the total amount of cosmetics. % (Hereinafter abbreviated as%) is preferable, and 0.01 to 0.1 is particularly preferable.
%.

The excipient or auxiliary agent used in the cosmetic of the present invention may be appropriately selected from those generally used for the same purpose according to the dosage form, and is not particularly limited. , For example, hydrocarbons such as petrolatum and squalane, higher alcohols such as stearyl alcohol, lower fatty acid lower alkyl esters such as isopropyl myristate, animal oils and fats such as lanolinic acid, polyhydric alcohols such as glycerin and propylene glycol, glycerin fatty acid esters , Polyethylene glycol monostearate,
Surfactants such as polyethylene alkyl ether phosphate,
Preservatives such as methyl paraoxybenzoate and butyl paraoxybenzoate, waxes, resins, various fragrances, various pigments, various inorganic salts such as sodium citrate, sodium carbonate, lactic acid, various acids, water, and ethanol. .

The cosmetics of the present invention may be in the form of liquids, solids or semisolids, preferably gels, creams, sprays, patches, lotions, packs, emulsions, powders and the like. .

[0014]

EXAMPLES Hereinafter, more detailed description will be given with reference to test examples, comparative examples and examples. Prior to the test example, a test method for inhibiting the degradation of hyaluronic acid will be shown. In addition, the compounding amounts in Tables 2 to 5 are
Indicates weight percent.

(1) Method for preparing MEM medium Minimum Essential Medium
(Dainippon Pharmaceutical Co., Ltd., 10-101) 10.6 g each with a final concentration of 1% (V / V) Non Essentia
l Amino Acid (Dainippon Pharmaceutical Co., 16-81
0) 1 mM sodium pyruvate (manufactured by Dainippon Pharmaceutical Co., Ltd., 1
6-820), 1.2% (W / V) sodium hydrogencarbonate and distilled water were added to make 1 liter, and then carbon dioxide gas was blown to bring the pH to about 7 (hereinafter abbreviated as MEM medium).

(2) Inactivation of fetal bovine serum (FBS) FBS (manufactured by Irvine Scientific)
Heat treatment was performed at 6 ° C. for 30 minutes.

(3) Method for Preparing Polymer Tritium Hyaluronic Acid for Cell Addition Normal human fibroblast cell line [Detroit 551 strain (ATCC
CCL 110)] cell number was adjusted to 2 × 10 ⁵ cells / ml with MEM medium containing 10% (V / V) inactivated FBS, 50 ml was put in a 225 cm ² flask and cultured for 3 days to be confluent. And then tritiated glucosamine (Ameri), the precursor of hyaluronic acid.
can Radiolabeled Chemical
s Inc. Was added to the culture system (10 μCi / ml), and the mixture was further cultured for 3 days. Then, tritiated hyaluronic acid was added to the culture solution by the method of Underhill et al. (J. Cell Biology, 82, 475 (19).
79)) and further, high molecular weight tritium hyaluronic acid (specific radioactivity, 0.1 μCi / μg) having a molecular weight of 1,000,000 or more was prepared by a gel filtration column. This was used as polymer tritium hyaluronic acid for addition to the cell culture system.

(4) Test Method for Degradation and Degradation Inhibition of Hyaluronic Acid Normal human fibroblast cell line [Detroit 551 strain (ATCC
CCL 110)], the cell number is 1.5 × 10 ⁵ cells / m 2 in MEM medium containing 10% (V / V) inactivated FBS.
Adjust to 1 and 0.8 on a 12-well plate (Falcon)
ml seeds, 95% (V / V) air-5% (V / V
V) Incubation at 37 ° C. for 3 days in an atmosphere of carbon dioxide gas,
Further, the medium was replaced with only the MEM medium, and the cells were cultured for 1 day. Then, the polymer containing tritium hyaluronan (1
4000 DPM / ml) MEM medium was prepared, the medium was exchanged, and the cells were cultured for 3 days. When the medium was replaced, histamine and various antagonist preparation solutions were added so that the final concentration was 10 μM.

(5) Evaluation method of hyaluronic acid decomposition and inhibition of hyaluronic acid decomposition After the completion of the culture, the culture solution was recovered and heat-treated at 100 ° C. for 5 minutes, and 1 ml of the medium was added to a Sepharose CL-2B column (internal diameter: 1 cm , 60 cm in length) and gel filtration was performed under the following conditions. Flow rate: 0.6 ml / min Fraction: 4 ml / 1 Fraction Total number: 25 Furthermore, 26 fractions 10 to 25 in which hyaluronic acid having a molecular weight of 100,000 or less is eluted are collected, and [ ³ H] radioactivity is measured to measure low molecular weight. The amount of converted hyaluronic acid was determined. further,
The hyaluronic acid decomposition rate and the hyaluronic acid decomposition rate and the decomposition inhibition rate were determined by the equations 1 and 2.

[0020]

[Formula 1] Degradation rate of hyaluronic acid (%) = B / A x 100 A = Degradation amount of hyaluronic acid by addition of histamine B = Degradation amount of hyaluronic acid by addition of histamine + antagonist

[0021]

[Equation 2] Degradation inhibition rate (%) = (1-B / A) × 100 A = Amount of hyaluronic acid decomposed by adding histamine B = Amount of hyaluronic acid decomposed by adding histamine + antagonist

Test Examples 1 to 3, Comparative Examples 1 to 2 Histamine H ₁ -Chlorpheniramine, pyrilamine and diphenhydramine as antagonists were used at a concentration of 10 μM.
Glycyrrhizin (inflammation, 4) which is an inhibitor of a bovine testis-derived hyaluronidase conventionally known as Comparative Example 2 is prepared by using an aqueous solution (Test Examples 1 to 3) prepared as follows, and purified water as Comparative Example 1. Volume 4, Issue 437 (198
The test was carried out by the methods (1) to (5) described above using an aqueous solution in which the concentration of 4)) was adjusted to 10 μM.

[0023]

[Table 1]

As shown in Table 1, all of the antagonists chlorpheniramine, pyrilamine and diphenhydramine (Test Examples 1 to 3) inhibited the degradation of hyaluronic acid, but they were inhibitors of Comparative Example 1 and hyaluronidase. Glycyrrhizin (Comparative Example 2) showed no effect.

From these results, the histamine H ₁ -antagonist is effective as a hyaluronic acid decomposition inhibitor. Further, the histamine H ₁ -antagonist used in the present invention is considered to be effective in improving the skin in which hyaluronic acid decomposition is accelerated.

Next, examples of the present invention will be described.

Examples 1 to 4 (Cream) Creams were prepared with the compositions shown below.

[0028]

[Table 2]

Preparation method: The component (A) was uniformly mixed and dissolved at 80 ° C., and then the component (B) was mixed and dissolved (mixed solution I). Separately from this, the component (D) was uniformly mixed and dissolved at 80 ° C., and then the component (C) was mixed and dissolved therein (mixed liquid II). Next, the mixed solution II was gradually added to the mixed solution I and cooled to 30 ° C. with sufficient stirring to obtain a cream.

Examples 5 to 8 (lotion) Lotions were prepared with the compositions shown below.

[0031]

[Table 3]

Preparation Method: Each component was mixed and dissolved to prepare a lotion.

Examples 9 to 12 (gel) Gels were prepared with the compositions shown below.

[0034]

[Table 4]

Preparation method: (A) was swollen with a part of purified water (D), the component (C) was dissolved with the remaining purified water (D), and then both were uniformly mixed (mixed solution I). ). Ingredient (B)
Were mixed and dissolved uniformly (mixture II). The mixed solution II was added to the mixed solution I and dispersed to obtain a gel.

Examples 13 to 16 (hair tonic) Gels were prepared with the compositions shown below.

[0037]

[Table 5]

Preparation method: After the perfume was dissolved with the perfume-solubilizing agent, it was added to ethanol while stirring at room temperature and dissolved, and the component (B) was sequentially added and dissolved (mixed solution I). The component (C) was dissolved and added to the mixed solution I with stirring to make the mixture uniform, and then filtered to obtain a hair tonic.

[0039]

INDUSTRIAL APPLICABILITY As described above, it is apparent that the present invention can provide a cosmetic composition capable of suppressing the degradation of hyaluronic acid, which is important for moisturizing the skin, and improving rough and dry skin.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location A61K 31/44 ADS 31/495 31/54 45/00 AEM (72) Inventor Shintaro Inoue Odawara, Kanagawa 5-3 28, Kotobuki-cho, Kanebo Biotechnology Research Institute

Claims (2)

[Claims] 1. A cosmetic comprising a histamine H ₁ -antagonist or a salt thereof. 2. The histamine H ₁ -antagonist is one or more selected from chlorpheniramine, pyrilamine, diphenhydramine triprenamine, brompheniramine, cyclidine, promethazine, and the like. Cosmetics.