JPS62132810A - Cosmetic - Google Patents

Abstract

PURPOSE:A cosmetic having improving hair growing effects, remedying effects on acne, free from side effects, stable in an acidic range, containing a specific 4-androstene-3,17-dione-17-cylic ethylene ketal derivative. CONSTITUTION:A safe cosmetic having hair growing effects and acne effects, stable even in an acidic range, free from unfavorable side effects such as hormone, etc., containing preferably 0.0001-2wt%, especially 0.0001-0.2wt% in cosmetic of a compound shown by the formula (R1 is H or methyl; R2 is methyl, ethyl or propyl) which has improved stability of 4-androstene-3,17-dione-17-cyclic ethylene ketal having inhibitory effects on reductase activity and inhibitory effects on bonding between 5alpha-DHT and receptor protein without suppressing the above-mentioned effects.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a cosmetic that does not have undesirable side effects such as hormonal effects and has excellent hair-nourishing effects and acne treatment effects.

[Prior Art] Physiological symptoms such as baldness, hair loss, seborrhea, and acne are said to be due to increased stimulation of male hormones due to excessive accumulation of male hormones. The main reason for this androgenic activity in these target organs is that testosterone
An enzyme named α-reductase (hereinafter abbreviated as reductase).

) reduced by 5α-dihydrotestosterone (
Hereinafter, it will be abbreviated as 5α-DHT. ) is becoming well known. In other words, testosterone (male hormone) produced by the glands and adrenal glands travels through the bloodstream to the sebaceous glands, where it is converted into 5α-DHT, a more powerful male hormone, by reductase in the sebaceous gland cells. . This 5
α-DHT binds to intracellular receptors and acts on the nucleus to promote the proliferation of sebaceous gland cells, while acting on hair matrix cells to suppress their cell division and hinder hair growth.

Therefore, symptoms such as baldness, hair loss, seborrhea, and acne are caused by inhibition of reductase activity and 5α-DHT.
It is thought that this can be reduced or prevented by inhibiting the binding between the receptor protein and the receptor protein, and several substances have been discovered based on this viewpoint.

However, although these substances have a high inhibition rate of reductase activity, they may have undesirable side effects or may inhibit 5α-DHT.
It has the disadvantage that the rate of inhibition of binding between the protein and the receptor protein is very low.

Therefore, even if these were put to practical use, the hair growth effect and acne treatment effect could not be said to be good and were not satisfactory.

[Problems to be Solved by the Invention] In view of the above circumstances, the present inventors have developed a method that does not have undesirable side effects such as hormonal effects, is safe, has an inhibitory effect on reductase activity, and has a binding effect between 5α-DHT and receptor protein. We searched for a substance that has both an inhibitory effect and conducted research to obtain a cosmetic containing this substance that has excellent hair-nurturing and acne-therapeutic effects.
, 17-thion-17-cyclic ethylene ketal was found to be able to achieve the above object, and a patent application was filed earlier (Japanese Patent Application Laid-Open No. 136505/1983).
Publication No.).

However, the above-mentioned cyclic ethylene ketal has a problem in stability in an acidic region, and has the disadvantage that its use is limited to a neutral or alkaline region. As a result of further research and improvement on this point, the present inventors found that a specific 4-androstene-3,17-sion-17-cyclic nitylenic derivative is stable even in an acidic region and has a hair-nourishing effect. The present inventors have discovered that it also has a therapeutic effect on acne, and have completed the present invention.

[Means for Solving the Problems] That is, the present invention provides a 4- 1. A cosmetic containing one or more kinds of androstene-3,17-sion-17-cyclic nitylenic derivatives.

Hereinafter, the configuration of the present invention will be explained in detail.

The 4-androstene-3°17-thion-17-cyclic nitylenic derivative used in the present invention is a compound represented by the above general formula.

These 4-androstene-3,17-sion-17-
The amount of the cyclic nitylenic derivative incorporated in the cosmetic of the present invention is preferably 0.0001 to 2% by weight, particularly preferably 1 to 0.2% by weight of O,0OQ.

If the amount is less than 0.0001% by weight, the hair nourishing effect may not be exhibited. Also, the higher the amount of the compound, the greater the hair-nourishing effect.
Considering the occurrence of unexpected side effects when used in large amounts, the amount is preferably 2% by weight or less.

The cosmetic according to the present invention includes the above-mentioned 4-androstene-3.
, 17-thion-17-cyclic nitylenic derivatives, as well as skin peripheral vasodilators such as carpronium chloride, minoxidil, spironolactone, vitamin B
6-hydrochloride, cephalanthine (Tamasa Kidzurafuji extract), D-camphor, DL-camphor, DL-α-tocopherol, iodized garlic extract, DL-α-tocopherol lyluinate, Jasmine japonica extract, inositol hexanicotinic acid ester , vitamin E1 dextran sodium sulfate, nicotinic acid, DL-α-tocopherol nicotinate, butoxyethyl nicotinate, γ-oryzanol, benzyl nicotinate, methyl nicotinate, nonanoic acid hanylylamide, DL-α-succinate
Tocopherol-/L/, vinegar MDL-α-tocopherol,
Capsicum tincture, cantharis tincture, ginger tincture, etc., or also additives commonly used in hair nourishing agents, such as hinokitiol, hexachlorophene, phenol, benzalkonium chloride, cetylpyridinium chloride, undecylenic acid, trichlorocarbanilide and bithionol. antibacterial agents such as, cooling agents such as menthol, drugs such as salicylic acid, zinc and its derivatives, lactic acid and its alkyl esters, olive oil, squalane,
Oils such as liquid paraffin, isopropyl myristate, higher fatty acids, higher alcohols, etc., surfactants,
Fragrance, antioxidant, ultraviolet absorber, pigment, ethanol,
Water, a humectant, a thickener, and the like can be appropriately added within a range that does not impair the effects of the present invention.

The hair tonic of the present invention may be in any form as long as it can be applied to the outer skin, such as liquid, milky lotion, or ointment.

Next, regarding the stability of the 4-androstene-3゜17-thion-17-cyclic ethylene tar derivative used in the present invention in an acidic region, the effect of inhibiting reductase activity, and the effect of inhibiting the binding between receptor protein and 5α-DHT. Let me explain with an example.

- Separate the raw buffer (*l) and sample (*2) for 0.5 d each,
Mix and leave in a constant temperature bath at 25°C. The presence of a decomposition product (4-androstene-3,17-dione) was appropriately confirmed by silica gel thin layer chromatography (*3).

*1: Buffer solution 1/IOM secondary sodium citrate aqueous solution 6.0-11
A buffer solution (pH 5.98 at 20° C.) consisting of a mixture of 4.0-4.0% of aqueous solution of IJum/ION hydroxide.

*2: Sample 4-androstene-3,17-thion-17-cyclic ethylene tar and the compound of the present invention (shown in Table 1)
0.1% (W/V) 99.5% ethanol (reagent grade) solution.

*3 Nijiri gel thin layer chromatography Pre-Co
ated TLCplate 5ilica Get
60 F254 used. After developing with a 2/8 mixture of ethyl acetate and benzene, color was developed with iodine.

The results are shown in Table 1. The stability was evaluated based on the following criteria.

O: No decomposition products observed.

Δ: Slight presence of decomposition products is observed.

x: Most of it exists as a decomposition product.

(The following is a blank space) Table 1 As is clear from Table 1, the stability of the compound of the present invention is 4.
-Androstene-3,17-sion-17-cyclic ethylenetal is significantly improved, and it can be seen that it can be used even in a weakly acidic region.

5α-Reduc-ze Method of Takayasu Ago (Journal of the Western Japan Dermatological Society, Vol. 43, No. 12)
15-1217, 1981), the amount of testosterone reduced by reductase was measured using the sebaceous glands on the back of hamsters. The sample concentration used in the experiment was 10' molar concentration, and the inhibition rate was determined from the obtained data using the following equation.

Inhibition rate (%) = ((c - t) /c) X100
C: Reduced amount of testosterone in control t: Reduced amount of testosterone when sample was added Table 2 g-6 ±A'-JTak of protein and 5α-DHT
The method of ayasu et al. (Arch+Dermato1.R
es, 264.50-51.1979), the amount of binding between the receptor protein and 5α-DHT was measured. The sample concentration used in the experiment was 10-' molar. The inhibition rate was determined from the obtained data using the following formula.

The results are shown in Table 3.

Inhibition rate (%) = (c-t/c) 2 and Table 3, the 4-androstene-3,17-sion-17-cyclic ethylene ketal derivative of the present invention is the compound 4-androstene-3゜17 described in JP-A-60-136505. -Sion-17-cyclic ethylene ketal in terms of the inhibitory effect on reductase activity and the inhibitory effect on receptor protein and 5α-DHT, and can be said to be a substance that achieves the object of the present invention.

[Example] Next, the present invention will be explained in more detail by giving examples. The present invention is not limited thereby.

The blending amount is in weight%.

First, an example as a hair nourishing agent will be described, but first, a test method will be explained.

L (judged by the change in the number of hair removals during hair washing before and after using the 旌敦り巴 sample. There were 10 subjects for each example. The measurement time was 4 months, and the first 2 months were when no sample was applied. The second half of the period was the period of sample application.

During this period, the hair was washed every two days and the pulled hair was collected, and the number of hairs for one week was counted. The number of hairs pulled out for each period is indicated by the average value obtained by summarizing the data of the number of hairs pulled out for a total of 8 times during the 2 months without sample application and the data on the number of hairs pulled out for a total of 8 times during the 2 months with hair tonic application. The number of hairs pulled per session was expressed in the form of ±α. The unit is a book. The effectiveness was determined based on the difference between the average values for each period as shown below.

++: The number of hair-pulled trees decreased by 70 or more, and a remarkable effect was observed.

+: The number of hair-pulled trees decreased by 40 or more, and a considerable effect was recognized.

±: The number of hairs removed was reduced by 10 or more, and it could be said that there was a slight effect.

1: The number of hairs removed was less than 10, and it could not be said that there was an effect.

(Margin below) Table 4 Add 4-androstene-3,17-sion-17-cyclic-1°2'-brobylenekecool and hydrogenated castor oil E040 mole adduct to 95% ethanol, stir and dissolve. Ion-exchanged water was added and mixed to obtain the transparent liquid cosmetic of Example 1.

Example 2.3 Comparative Example 1 was also produced in the same manner as Example 1.

Table 5 shows the results of measuring the hair growth effect.

The cosmetic containing the compound of the present invention contains 4-androstene-3
, 17-cyone-17-cyclonitylene ketyl-containing cosmetics.

Table 5 Table 5 Furthermore, the therapeutic effect on acne will be explained in detail by giving Examples and Comparative Examples. Ingredients are in weight percent.

As a sample, a lotion type cosmetic obtained by the following formulation and manufacturing method was used.

4-androstene-3,17-sion-17-cyclic-2”3゛-ethylenekecool 0.25g,
Polyoxyethylene (60 mol) Effect Castor Oil 2. o
g, glycerin 10.0 g, dipropylene glycol 10, Og, 1.3-butylene glycol 5. Og,
and 5.0 g of polyethylene glycol 1500
Heat and dissolve at 0°C. To this were added and mixed 10.0 g of cetyl isooctanoate, 5.0 g of squalane, and 1.3 g of methylparaben heated and melted at <60°C, and treated with a homomixer to form a gel. Next, 0.3g of carboxyvinyl polymer and 0.03g of sodium hexametaphosphate dissolved in 11.0g of ion-exchanged water were added to this gel, and after dispersing with a homomixer, 0.12g of potassium hydroxide was ion-exchanged. 40.0g water
A lotion-type cosmetic was obtained by adding and mixing the solution and emulsifying it with a homomixer. In Comparative Example 2, a similar cosmetic was obtained using 4-androstene-3,17-dione-1-cycloethylene ketal.

(Target for use) The group consisted of 20 men and women between the ages of 15 and 32.

(How to use) After thoroughly washing your face with cosmetic soap, apply the above lotion type cosmetics 1 to 3 times a day only on the skin eruption.
I applied it twice.

(Observation items and observation ports) Observe the three symptoms of acne, papules, and pus, and rate the severity of each finding as severe (4), moderate (3), mild (2), slight (1), respectively. The evaluation was divided into 5 stages: In addition, the severity of sitting vulgaris was divided into three levels: severe, moderate, and mild based on the severity of these three symptoms.

Follow-up observation was performed before treatment, 1 week, 2 weeks, 3 weeks, and 4 weeks after treatment.

(General improvement level) The degree of improvement compared to before use was significantly improved (+++),
The symptoms were divided into five stages: fairly relieved (++), somewhat relieved (+), unchanged (±), and worsened (-).

(Usefulness) Based on the overall degree of improvement, it was judged as extremely useful (+++), quite useful (++), somewhat useful (+), and ineffective (±).

The results are shown in Table 6 (Comparative Example 2) and Table 7 (Example 4).

(Left below) As is clear from the test results, 4-androstene-
3,17-Sion-17-Cyclic -2'3゛-
The cosmetics according to the present invention containing butylentental also have a therapeutic effect on 4-androstene-3,1.
It was proven that the product is equivalent to a cosmetic containing 7-cyone-17-cyclic nithale lentil.

Example 5 Polyoxyethylene (8 mol) in 55.0 g of ethanol
Oleyl alcohol ether 2.0g, 4-androstene-3,17-sion-17-cyclic-1゛2゛-propylene ketal 0.05g hinokitiol 0
．． After adding 0.5 g of perfume and dye to the solution and dissolving them, 42.499 g of ion-exchanged water was added to solubilize to obtain a cosmetic.

When this cosmetic was subjected to practical use tests similar to those in Examples 1 to 3, it was confirmed that the cosmetic had an excellent hair-nourishing effect.

Example 6 4-androstene-3,17-dione-17-cyclic-l'2'-butylene ketal 0.5 g, polyoxyethylene (60 mol) hydrogenated castor oil 2. og, glycerin 10.0g, dipropylene glycol 10,
Og, 1. 3-Butylene glycol5. Og and 5
．． 0 g of polyethylene glycol 1500 at 60°C.
Dissolve by heating (Part A). cetylisooctanony)
10.0g, squalane 5.0g, petrolatum 2.0g
.

and 2.0 g of propylparaben are heated and melted at 60°C (Part B). Carboxyvinyl polymer 1% aqueous solution 3
0.0 g and 0.03 g of sodium hexametaphosphate are dissolved in 8.35 g of ion exchange water (0 parts).

Part A and Part B are mixed at 60°C and treated with a homomixer to form a gel. Add 5.0 g of ion-exchanged water to this and disperse with a homomixer. Next, add 0 parts to this, and finally add an aqueous solution of 0.12 g of caustic potash dissolved in 5.0 g of ion-exchanged water, emulsify with a homomixer, and O/W.
A milky lotion type cosmetic was obtained.

As a result of conducting the same test as in Example 4 for this cosmetic, it was confirmed that it has a therapeutic effect on acne.

Example 7 Liquid paraffin 5.0g, cetostearyl alcohol 5
．． Heating 5g, petrolatum 5.5g, glyceryl monostearate 3.0g, polyoxyethylene (20molny 2-octyl dodecyl ether 3.0g, vitamin E acetate 0.05g, propylparaben 0.3g and fragrance 0.05g) Dissolve and mix.To this, 4-androstene-3,17-sion-17-cyclic-
2°3°-butylene lenticule 0.5g, glycerin 7.
0g, dipropylene glycol 20. Og.

5.0g polyethylene glycol 4000. Sodium hexametaphosphate 0.005 g and ion exchange water 45
．． 095 g of the heated and dissolved mixture was added and emulsified using a homomixer to obtain a creamy cosmetic.

The obtained cosmetic had excellent hair growth and acne treatment effects.

[Effects of the Invention] The cosmetic composition of the present invention has excellent hair nourishing effects and acne treatment effects, and also has good stability.

Claims (1)

[Claims] 4 represented by the following general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 represents hydrogen or a methyl group, and R_2 represents a methyl group, ethyl group, or propyl group.) - A cosmetic containing one or more kinds of androstene-3,17-dione-17-cyclic ethylene ketal derivatives.