JP2005170918A - Skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use effectively improving rustle, dryness and roughness of the skin without having an association with type IV allergy reaction. <P>SOLUTION: This skin care preparation improves the turnover function of the skin by using a specific 5-membered triterpenoic acid, especially barbinervic acid as an active ingredient. Thereby, it is expected to improve the rustle, dryness and roughness of the skin. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a skin external preparation that exhibits excellent effects in improving rough skin, rough skin, and improved skin dryness by promoting epikeratinization by a specific pentacyclic triterpenic acid, salt or derivative thereof.

  The epidermal stratum corneum has a function of protecting the skin from harmful substances invading from the outside world, and has a protective action on the skin because a weakly acidic fat film is formed by sebum. The epidermal stratum corneum is formed as a stratum corneum by the differentiation of epidermal keratinocytes, and the old stratum corneum is peeled off. This series of turnover processes is usually repeated at regular intervals. However, internal and external factors such as aging, desiccation, ultraviolet light, and stress cause abnormally increased epidermal keratinocyte proliferation and turnover. An error occurs in the function. In skin where normal turnover has not been performed, abnormalities have also occurred in the differentiation of epidermal keratinocytes that should occur during the turnover process, and NMF and ceramide are skin moisturizing factors produced by normal differentiation. It causes abnormalities in the production of intercellular keratinous lipids, and the skin's original function is lost, causing problems such as skin roughness, dryness, and rough skin. In particular, in recent years, stimuli such as atmospheric dryness, ultraviolet rays, and stress enhance the proliferation of epidermal keratinocytes, and the angle caused by immature keratinocytes due to the absence of keratinization of normal epidermal keratinocytes. Deterioration of the layer barrier function is often the cause of skin roughness, dryness and rough skin.

  Conventionally, skin external preparations, cosmetics, and the like containing various moisturizing agents have been mainly used as means for improving the skin roughness, dryness and roughness caused by abnormal skin turnover. However, these are intended to improve the feel of the skin by temporarily providing moisture to the skin, and do not improve the turnover function by controlling the proliferation and differentiation of the epidermal keratinocytes themselves. It was not effective in improving the roughness, dryness and rough skin.

  The main object of the present invention is to provide an external preparation for skin, which is effectively unaffected by type IV allergic reaction and effectively improves skin roughness, dryness and rough skin.

  As a result of intensive research on ingredients for providing an external preparation for skin that effectively improves skin roughness, dryness, and rough skin, which is not related to type IV allergic reaction, the present inventor has obtained specific pentacyclic triterpenic acid. In particular, it has been found that barbinervic acid improves the skin turnover function and improves skin roughness, dryness, and rough skin, and the present invention has been completed.

That is, the external preparation for skin of the present invention has an action of promoting keratinization of the epidermis, and therefore improves the skin turnover function. Therefore, it is not related to type IV allergic reaction, and improves skin roughness, dryness, and rough skin. It is effective for.

The present invention is described in detail below.
The present invention will be specifically described below.
Active ingredient of the external preparation for skin of the present invention The external preparation for skin of the present invention contains, as an active ingredient, formula 1:

The pentacyclic triterpenic acid represented by these is contained. The pentacyclic triterpenic acid may be contained in the form of a salt or a derivative thereof. Examples of the salt include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts, magnesium salts and aluminum salts; and various organic amines. Examples of the derivative include an acetyl derivative in which a hydroxyl group is acetylated.

  Examples of the pentacyclic triterpenic acid represented by the formula 1 include barbinervic acid, rotundic acid, and rotogenic acid. Among these, in particular, Formula 2:

Barbinerbic acid represented by the formula is suitable in that it has a more excellent skin roughness, dryness, and rough skin improving action.

  The pentacyclic triterpenic acid of the present invention can be obtained by synthesis, extraction / purification from plants, and extraction / purification from callus cultures of plants. Of these, it is particularly desirable to extract and purify from plants. For example, an extract obtained by extracting a plant such as persimmon, leopard or black beetle with a lower alcohol such as methanol, ethanol or butanol, a polyhydric alcohol such as propylene glycol or 1,3-butylene glycol, acetone, or a water mixture thereof. This extract can be concentrated and purified. Of these, extraction with ethanol or water / ethanol is particularly preferred in practice.

  The plant may be used for extraction as it is after being collected, but it is usually subjected to extraction after pretreatment according to a commonly used method. Concentration can be performed according to a conventional method, and after concentration, an extract powder can be obtained by commonly used means such as freeze drying, spray drying, granulation drying and the like. Further, the extract and the extract powder are obtained from the pentacyclic triterpenic acid of the present invention by a conventional separation and fractionation method such as liquid-liquid distribution using various solvents, recrystallization, gel filtration, chromatography and the like. A crude product having an increased content can be obtained. Furthermore, the pentacyclic triterpenic acid represented by Formula 1 or Formula 2 can be isolated by repeating the above operation.

  The pentacyclic triterpenic acid represented by Formula 1 or Formula 2 of the present invention is not particularly limited as long as they are contained, and may be used as a plant extract containing them. it can. When used as a plant extract, the content of the pentacyclic triterpenic acid represented by the formula 1 or formula 2 is increased to 20% or more to obtain a skin external preparation having more excellent drying and roughening action. This is preferable.

The skin external preparation of the present invention comprises the above-described pentacyclic triterpenic acid represented by formula 1 or formula 2, for example, pentacyclic triterpenic acid represented by formula 1 or formula 2 is appropriately used. It is obtained by mixing with a carrier.
The content of the pentacyclic triterpenic acid represented by Formula 1 or Formula 2 in the external preparation for skin is not particularly limited as long as the desired effect is obtained, but is preferably about 0.001 to 5% by weight, particularly Preferably, it is about 0.01 to 3 weight%.

  The external preparation for skin of the present invention can be prepared by various conventional preparations such as an aqueous solution system, a solubilization system, an emulsification system, a powder system, an oil liquid system, a gel system, and an ointment system. The external preparation for skin of the present invention is a component generally used within the range not impairing the effects of the present invention, if necessary, in addition to the above components, such as oil and fat components, surfactants, polyhydric alcohols, and ultraviolet absorbers. And UV scattering agents, thickeners, antioxidants, fragrances, colorants, vitamins and photosensitizers, cell activators, hyaluronic acid, PCA-Na, amino acids and other moisturizers, linoleic acid, γ-linolenic acid, sphingo Lipids, ceramides, sugar ceramides and the like can be blended.

  Next, the present invention will be described in more detail using examples. Needless to say, the present invention is not limited to these examples, and unless otherwise specified, [%] indicates [% by weight].

Experimental Example 1: Differentiation-promoting test for keratinocytes As keratinocytes, SV40-transformed human keratinocytes whose proliferation was established as cultured cells were used. The cells were seeded in a 6-well plastic plate and cultured in Dulbecco's modified Eagles minimal nutrient medium (DMEM) containing 10% fetal calf serum for 1 day at 37 ° C. in a 5% carbon dioxide atmosphere. After 24 hours, the culture solution was removed, the medium was added again, a test substance diluted solvent (DMSO) was added (control), and the test substance was added to 10 μM, followed by culturing for 3 days. After culturing, the cells were detached with trypsin, dissolved in 1% SDS / 20 mM DTT solution, and then heat-treated at 100 ° C. for 5 minutes. The insolubilized cells after heat treatment were counted and used as the number of cornified envelopes. Cornified envelope is not formed in immature epidermal keratinocytes, but is an insoluble protein that is formed in the cells with differentiation, and by measuring the amount of cornitized envelope formation, epidermal keratinocytes You can know the degree of differentiation. The results are shown in Table 1 as the differentiation induction rate after calculating the amount of the cornified envelope when the control is 1.00.

  As is clear from the results shown in Table 1 above, barbinerbic acid, rotundic acid, and rotungenic acid are the same cornified fluorides as those added with 1.2 mM calcium chloride, which is said to induce differentiation of epidermal cells so far. An envelope formation effect (differentiation induction effect) was observed. In particular, barbinerbic acid was found to have a strong differentiation-inducing effect.

Experimental Example 2: Antiproliferative effect on keratinocytes The cells used were keratinocytes (SV40 transformed human keratinocytes) used in Experimental Example 1. The cells were seeded in a 6-well plastic plate and cultured in Dulbecco's modified Eagles minimal nutrient medium (DMEM) containing 10% fetal calf serum for 1 day at 37 ° C. in a 5% carbon dioxide atmosphere. After 24 hours, the culture solution was removed, the medium was added again, a test substance diluted solvent (DMSO) was added (control), and the test substance was added to 10 μM, followed by culturing for 3 days. The cells were detached with trypsin, stained with trypan blue, and the number of stained cells was counted. The total number of cells was calculated based on the measured values, and the results of calculating the ratio of the number of viable cells when the control was 1.00 are shown in Table 1.

  As is clear from the results shown in Table 1, it has been clarified that barbinerbic acid, rotundic acid, and rotungenic acid inhibit the proliferation of epidermal cells. In particular, a strong effect on barbinerbic acid was observed.

Next, the prevention of skin damage due to ultraviolet rays, which is not related to type IV allergic reaction, was examined.
Experimental Example 3: Skin Roughness Inhibition Effect due to UV Damage A group of 5 hairless mice (hos: HR-1, 8-10 weeks old, female) was irradiated with 480 mJ / cm ² of ultraviolet rays (UV-B) on the back skin. From immediately after irradiation, the test solution was applied in a uniform manner at a rate of 200 μl / day. Application of the test solution was continued for 6 days. The stratum corneum moisture content was measured using Skicon 200 (manufactured by IBS) as an index of rough skin before ultraviolet irradiation and on the seventh day from the irradiation date. Table 2 shows the stratum corneum moisture content on the seventh day when the stratum corneum moisture content before ultraviolet irradiation is 1.00, as the degree of improvement in skin roughness.

  As is apparent from the results shown in Table 2, it was recognized that barbinerbic acid, rotundic acid, and rotungenic acid had a higher effect of improving skin roughness induced by ultraviolet rays than control. The effect was higher than that of glycyrrhizic acid used as a comparative example.

Formulation examples 1 to 5 of the present invention are shown below. These can be produced according to conventional methods.
Formulation Example 1: Emulsion preparation for skin Ingredients Amount (%)
Total 100.0
Olive oil 10.0
Squalane 8.0
Barbinervic acid 0.2
Stearic acid 3.0
Cetanol 3.0
Lipophilic glyceryl monostearate 3.0
Butyl paraoxybenzoate 0.3
Glycerin 20.0
Polyglyceryl monostearate 3.0
Methyl paraoxybenzoate 0.1
Potassium hydroxide 0.4
Purified water balance Total 100.0

Formulation Example 2: Solubilized preparation for scalp Ingredients Amount (%)
Rotundic acid 0.1
2-Ethylhexyl paradimethylbenzoate 0.3
l-Menthol 0.1
Salicylic acid 0.1
Polyoxyethylene hydrogenated castor oil (40E.O) 0.7
Photosensitive element 301 0.001
Fragrance 0.2
Ethanol 50.0
Glycerin 15.0
dl-Pyrrolidonecarboxylate solution 3.0
Dipotassium glycyrrhizinate 0.2
Pyridoxine hydrochloride 0.2
Purified water balance Total 100.0

Formulation Example 3: Low-viscosity emulsion preparation for skin Ingredients Amount (%)
Sorbitan isostearate 2.0
Lipophilic glyceryl monostearate 1.0
Barbinerbic acid 0.1
Stearic acid 0.5
D-pantothenyl alcohol 0.5
Olive oil 4.0
Isopropyl palmitate 4.0
dl-α-tocopherol 0.1
Propyl paraoxybenzoate 0.1
Glycerin 15.0
Xanthan gum 0.2
Methylparaben 0.2
Fragrance 0.2
Purified water balance Total 100.0

Formulation Example 4: Solubilized skin preparation Ingredients Amount (%)
Barbinervic acid 0.05
Polyoxyethylene hydrogenated castor oil 0.6
Ethanol 8.0
Methyl paraoxybenzoate 0.1
Glycerin 10.0
dl-Pyrrolidonecarboxylate aqueous solution 2.0
Sodium citrate 0.07
Citric acid 0.03
L-Arginine 0.1
Dipotassium glycyrrhizinate 0.1
1,3-butylene glycol 5.0
Fragrance 0.1
Purified water balance Total 100.0

Formulation Example 5: Skin ointment Ingredient Amount (%)
Diphenhydramine 1.0
Rotungenic acid 3.0
White ointment 40.0
Cetanol 18.0
Sorbitan sesquioleate 5.0
Lauro Macrogol 0.5
Ethyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
Purified water balance Total 100.0

Claims (4)

Formula 1:

A skin external preparation characterized by containing a pentacyclic triterpenic acid represented by the formula: A skin external preparation for improving rough skin, comprising a pentacyclic triterpenic acid represented by formula 1 or a salt or derivative thereof. The external preparation for skin according to claim 1 or 2, wherein the pentacyclic triterpenic acid represented by the formula 1, a salt or a derivative thereof has an action of promoting epidermal keratinization. The pentacyclic triterpenic acid is represented by the formula 2:

The skin external preparation of any one of Claims 1, 2, and 3 which is pentacyclic triterpenic acid represented by these.