JPH09241296A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use, capable of raising affinity for skin of escinol for suppressing production of pigment cell activator and improving effectiveness of escinol, excellent in safety and feeling in use, by blending escinol (salt) with a phospholipid. SOLUTION: An escinol of the formula (R<1> is H or a hydroxyl group; R<2> is a pyranose residue) or its salt is mixed with one or more phospholipid such as cholesterol or β-sitosterol, further a polyhydric alcohol such as glycerol, an oil component such as a higher fatty acid, an organic acid such as citric acid, an alkali such as triethanolamine, a surfactant, powder, a colorant, an antiseptic fungicide, a resin, a pH adjustor, an antioxidant, an ultraviolet light absorber, a chelating agent, a thickening agent, a humectant, an alcohol, water, a perfume, etc., and pharmaceutically manufactured to give the objective skin preparation for external use, capable of raising affinity for skin of the escinol for suppressing production of pigment cell activator and the action of the activator and permeating into the inner layer of skin and excellent in safety and feeling in use.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation having excellent skin affinity. More specifically, a skin external preparation containing one or more phospholipids, escinol or a salt thereof and cholesterol in order to enhance the skin affinity of escinol and to permeate escinol to the dermis to improve its effectiveness. The present invention relates to a skin external preparation containing, escinol or a salt thereof and a skin external preparation containing β-sitosterolol.

[0002]

2. Description of the Related Art The surface of the skin is called the stratum corneum of the skin, and since it originally has a physiological function as a barrier to prevent the invasion of foreign substances from the outside of the body, it is simply a base conventionally used for external preparations. Sufficient skin permeability cannot be obtained only by incorporating the drug into the agent. In order to improve this,
Various types of percutaneous absorption enhancers have been proposed, and they are generally incorporated in the base of external preparations. As the transdermal absorption enhancer, for example, ionic surfactants such as sodium dodecyl sulfate are used, but these destroy the horny layer of the skin and cause irritation such as erythema and scales on the skin. It is hard to say that this is enough. On the other hand, the present inventors have already found that escinol, which is a triterpenoid saponin obtained by alkaline decomposition of escin in extracts of horse chestnut seeds to remove an acyl group, has an excellent whitening effect. (Japanese Patent Application No. 6-179544, Japanese Patent Application No. 7-
58149).

In view of the above problems, the inventors of the present invention have made escinol excellent in skin affinity, permeated escinol to the dermis to improve its effectiveness, and are satisfactory in safety and usability in the external preparation for skin. As a result of intensive research to develop escinol, excellent skin permeability of escinol can be obtained by using one or more phospholipids, cholesterol, or β-sitostelerol and escinol or a salt thereof. The present invention has been completed and the present invention has been completed.

[0004]

That is, claim 1 of the present invention is characterized by containing escinol or a salt thereof represented by the following general formula 2 and one or more phospholipids. It is an external preparation for skin.

Embedded image (In the formula, R ¹ represents a hydrogen atom or a hydroxyl group, and R ² represents a pyranose residue.)

A second aspect of the present invention is an external preparation for skin characterized by containing escinol represented by the general formula 2 and cholesterol. A third aspect of the present invention is an external preparation for skin, characterized by containing escinol represented by the general formula 2 and β-sitostelerol.

The structure of the present invention will be described in detail below. As the phospholipid, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, lysophosphatidylcholine,
Examples thereof include lysophosphatidylserine, lysophosphatidylinositol, lysophosphatidylethanolamine, lecithin, lysolecithin, egg yolk phospholipid, soybean phospholipid and the like. One or two or more types are arbitrarily selected from these.

Phospholipids, cholesterol and β-sitosterolol used in the present invention are 0.001 in the skin external preparation.
-10 wt% is preferable, and more preferably 0.001-
5% by weight.

The escinol or its salt used in the present invention has an action of suppressing the production of pigment cell activating factor and its action in the skin, and as a result, suppresses abnormal proliferation of pigment cells. It is also known to have significantly lower cytotoxicity than escin (Folia Histchemica et Cytchem
ica 16:69, 1978). Such escinol or a salt thereof can be obtained by alkali-decomposing an extract or escin from plants such as horse chestnut seeds. For example, escin is dissolved in a sodium methylate / methanol solution, heated to reflux, and returned to room temperature. After neutralizing with a strongly acidic resin, the resin is removed by filtration and concentrated. This is fractionated and purified by gel chromatography such as Wako Gel C200 column. Alternatively, it is recrystallized after heating under reflux. The escinol thus obtained is represented by the general formula 2
One or more compounds of the above.

As the escinol of the above general formula 2,
R ¹ is a hydroxyl group, R ² is β-D-glucopyranose; R ¹
Is a hydroxyl group, R ² is β-D-xylopyranose, R ¹ is a hydrogen atom, and R ² is β-D-galactopyranose (M.YOSIKAWA et.al. Chem. Bull. 42 (6 )13
57-1359 (1994)). Examples of the escinol salt include alkaline earth metal salts such as sodium salt and potassium salt, basic amino acids or alkanolamines, and esters thereof, and specifically, escinol sodium salt, escinol potassium salt. , Escinol ammonium salt and the like.

The amount of escinol or its salt to be blended in the cosmetic composition of the present invention can be appropriately selected according to its use form, purpose of use, method of use, dosage form and the like, but is not particularly limited, but in general, , 0.001 for all cosmetics
-20% by weight, preferably 0.1-7% by weight. If the content is less than 0.001% by weight, the effects such as tend to be poor, and conversely, if the content is more than 20% by weight, an increase in the effects cannot be expected substantially and it is difficult to compound into cosmetics. Tends to become.

The external preparation for skin according to the present invention may have any dosage form, for example, a solubilization system such as lotion, an emulsion system such as emulsion or cream, or an ointment or dispersion liquid.

The external preparation for skin according to the present invention may contain, in addition to the above-mentioned essential components, components that are generally contained in pharmaceuticals, quasi drugs, cosmetics and the like. These components include polyhydric alcohols such as glycerin and propylene glycol, oils such as liquid paraffin, squalane, higher fatty acids and higher alcohols, organic acids such as citric acid and lactic acid, alkalis such as caustic soda and triethanolamine, and cationic agents. Surfactants, amphoteric surfactants, nonionic surfactants, powders, pigments, dyes, antiseptic and antifungal agents, resins, pH adjusters, antioxidants, ultraviolet absorbers, chelating agents, thickeners, moisturizers , Alcohol, water, fragrances and the like.

[0013]

EXAMPLES The present invention will be specifically described below with reference to examples and test examples, but the present invention is not limited thereto. The compounding amount is% by weight.

(Drug Permeability Test) A drug permeability test was conducted on the product of the present invention. Examples 1 to 5 Drug samples having the following compositions were prepared. (1) Escinol 0.1% (2) Phospholipid, Cholesterol, β-Cytosterolol (described in Table 1) 0.1 (3) Ethanol 20.0 (4) Purified water Residual (Production method) (1), After dissolving (2) in (3) (4)
Was added and mixed to prepare a sample.

[0015]

[Table 1] ──────────────────────────────────── Phospholipid Cholesterol, β-Cytosterolol ─ ────────────────────────────────── Example 1 Phosphatidylcholine ─── Example 2 Phosphatidylcholine Cholesterol Example 3 Soybean Phospholipid ── Example 4 Soybean phospholipid β-cytosterolol Example 5 ─── Cholesterol Comparative example 1 ─── ─── ──────────────────── ──────────────────

Comparative Example 1 (1) Escinol 0.1% (2) Ethanol 20.0 (3) Purified water Residue (Production method)

Test Example In order to evaluate the effect of phospholipid for promoting the percutaneous absorption of escinol, in vitro using the excised skin of hairless mice,
A drug permeability test was carried out using a ro diffusion cell. As the diffusion cell device, a vertical membrane type two-chamber cell with a diffusion area of 2 cm ² was used.
The entire skin layer on the back of a male hairless mouse aged 15 weeks was excised and attached to a diffusion cell. Put 2 ml of the drug sample in the cell chamber on the drug sample side and 2 ml of phosphate buffered saline (pH 7.2) in the cell chamber on the receptor side, and keep the whole cell at 32 ° C in a thermostat while gently stirring both phases. It was After 24 hours, the receptor liquid was sampled and the amount of the drug that had permeated to the receptor side was quantified by high performance liquid chromatography. The results were expressed as drug permeability (%).

[0018]

[Table 2]

As is clear from Table 2, the percutaneous absorption enhancer of the present invention is excellent in the skin permeation promoting effect of escinol.

Example 6 Cream A. Cetanol 4.0% Vaseline 5.0 Liquid paraffin 8.0 Squalane 5.0 Isopropyl myristate 3.0 POE (25) cetyl ether 2.0 β-Cytosterolol 0.1 Glyceryl monostearate 2.0 Preservative Appropriate amount B. Escinol 0.5 Glycerin 5.0 Propylene glycol 5.0 Purified water Amount based on 100 as a whole (Production method) A component is heated to 70 ° C. and dissolved. After the component B is dissolved by heating at 70 ° C., A is added therein and emulsified. After that, heat exchange is performed to obtain a cream.

Comparative Example 2 Cream A. Cetanol 4.0% Vaseline 5.0 Liquid paraffin 8.0 Squalane 5.0 Isopropyl myristate 3.0 POE (25) cetyl ether 2.0 Glyceryl monostearate 2.0 Preservative Suitable amount B. Escinol 0.5 Glycerin 5.0 Propylene glycol 5.0 Purified water Amount based on 100 as a whole (Production method) According to Example 6.

(Whitening Effect Test) With respect to the creams prepared in Examples 7, 6 and Comparative Example 2, one sample cream was prepared for 20 subjects per group, suffering from darkness, stains, freckles, etc. It was applied to the face every day for a month, and its whitening effect was examined. The criteria for judgment are "pigmentation is almost inconspicuous" (score 2), "very thin", (score 1), "slightly thin" (score 0.5), no change (score 0 The average score was calculated for each base.

[0023]

[Table 3] ─────────────────────── Base average score after 3 months ──────────────── ──────── Example 7 1.5 Comparative Example 2 0.9 ───────────────────────

As is apparent from Table 3, the creams of Examples have excellent whitening effect.

Example 8 Emulsion A. Cetanol 1.5% Stearic acid 1.0 Palmitic acid 1.2 Lanolin 3.0 Squalane 4.0 Olive oil 2.0 Oleyloylate 2.0 Dimethylpolysiloxane (6cs) 3.0 Glyceryl monooleate 2.0 POE (50 ) Oleyl ether 1.0 Preservative proper amount Perfume proper amount B. Propylene glycol 5.0 Glycerin 2.0 PEG1500 2.0 Caustic potassium 0.08 Cholesterol 0.5 Carboxyvinyl polymer 0.15 Ethanol 3.0 Purified water Amount based on 100 C.I. Escinol 5.0 (Manufacturing method) The component of A is heated at 70 degreeC and melt | dissolved. After the component B is dissolved by heating at 70 ° C., A is added therein and emulsified. C is added to the mixture to uniformly mix it, and then heat exchange is performed to obtain an emulsion.

Example 9 Lotion Escinol 0.1% Phosphatidylcholine 0.01 Ethanol 9.0 POE (20) oleyl ether 1.0 Preservative Suitable amount Perfume Suitable amount Purified water 100 parts of the above components Then get lotion.

The skin external preparations obtained in Examples 8 and 9 were:
The effect was recognized in the whitening effect test conducted in Example 7.

[0028]

The external preparation for skin according to the present invention is an external preparation for skin which has an excellent effect of promoting percutaneous absorption of escinol or a salt thereof, and has a good safety and a feeling in use.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 31/70 ADS A61K 31/70 ADS 35/78 35/78 C 47/24 47/24 E 47 / 28 47/28 E

Claims (3)

[Claims] 1. A skin external preparation containing escinol represented by the following general formula 1 or a salt thereof and one or more phospholipids. Embedded image (In the formula, R ¹ represents a hydrogen atom or a hydroxyl group, and R ² represents a pyranose residue.) 2. An external skin preparation containing escinol represented by the general formula 1 and cholesterol. 3. Escinol represented by the general formula 1 and β-
A skin external preparation characterized by containing sitosterolol.