JPS62205010A - Hair tonic - Google Patents

Abstract

PURPOSE:An excellent hair tonic, containing a specific steroid derivative, e.g. a 4-estren-3-one-17beta-ethoxy derivative, etc., and [benzo-1,2,4-thiadiazine]-1-dioxide derivative and capable of exhibiting synergistic effect. CONSTITUTION:A hair tonic containing 0.0001-0.2wt% steroid derivative, e.g. a 4-estren-3-one-17beta-ethoxy derivative expressed by formula I [R1 is H or CH3; R2 is -CH2OH, -CH2OCOX (X is alkyl or phenyl), -CH2Y (Y is halogen), etc.], etc., and 0.01-6wt% [benzo-1,2,4-thiadiazine]-1-dioxide derivative expressed by formula II (R1 is Cl, CF3 or -SO2NH2; R2 is H, Cl or -SO2NH2; R3 is H, alkyl, etc.; R4 is H or CH3). The hair tonic may be blended with normally used additives and in any form of liquid, milky lotion, ointment, etc.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a hair nourishing agent having excellent hair nourishing effects.

[Conventional technology]

Physiological symptoms such as male-pattern baldness and seborrhea are said to be due to increased stimulation of androgen due to excessive accumulation of androgen, but recently it has been reported that this androgenic activity in organs such as hair roots and sebaceous glands has been increased. The main body is 5α-dihydrotestosterone (hereinafter abbreviated as 5α-DHT), which is produced by reducing testosterone (male hormone) in these target organs by an enzyme called testosterone-5α-reductase (hereinafter abbreviated as reductase). This is becoming well known. That is, testosterone produced in the rays 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 5α-
DHT binds to intracellular receptors and acts on the nucleus to promote the proliferation of sebaceous cells, while DHT itself exits the sebaceous cells and enters the bloodstream, acting on hair matrix cells and stimulating the growth of hair in the hair bulb. It is said to suppress the division of mother cells, impede hair growth, and promote hair pulling and hair loss.

[Problem that the invention seeks to solve]

Therefore, it is thought that symptoms such as male pattern baldness and hair loss can be reduced or prevented by inhibiting reductase activity and the binding of 5α-D HT to receptor proteins. Based on this viewpoint, substances such as chlormadinone acetate, oleic acid, and linoleic acid have been discovered so far. however,
Although these substances have a high inhibition rate of reductase activity, they may have unfavorable side effects, or have a very low rate of inhibition of binding between 5α-D HT and fertility proteins, so they have no substantial hair growth effect. It had the disadvantage of being inferior.

[Means for solving problems]

In view of the above, the present inventors sought to find a substance that is safe, does not have undesirable side effects such as hormonal effects, and has both an inhibitory effect on reductase activity and an inhibitory effect on the binding between 5α-D HT and receptor protein. As a result of extensive research in order to obtain a hair nourishing agent with excellent hair nourishing effects by blending this, we discovered that the above purpose could be achieved by blending a specific steroid derivative, and we filed a patent application earlier. (Japanese Patent Application Laid-Open No. 60-54310,
JP-A-60-81121, JP-A-59-184114
, JP-A-60-81122, JP-A-60-13650
5. Japanese Patent Publication No. 60-67411, Patent Application No. 60-27394
8).

Furthermore, as a result of research by the present inventors,
811 as a hair growth promoter [
The present inventors have discovered that when a benzo-1,2,4-thiadiazine-1-dioxide derivative is blended with the above-mentioned specific steroid derivative, the effects thereof are synergistically increased, leading to the completion of the present invention.

(The following is a blank space) That is, the present invention is a hair nourishing product characterized by containing at least one selected from the group (a) below and at least one selected from the group (b) below. be.

(a)■ 4-estrene- represented by the following general formula (1)
3-one-1 β-ethoxy derivative or 4-androsten-3-one-17β-ethoxy derivative.

(Left below) (In the formula, R1 represents H, -CI+3, and R2 represents -CH2
0H1-CH20COX (wherein X represents an alkyl group having 1 to 5 carbon atoms or a phenyl group), -CH2Y (however, Y represents F, CI, Br, or I), -CI2
CN, -COOX (where X is the same as above), (2) A 4-androstene-3,17-sion-17-cyclic nitylenic derivative represented by the following general formula (2).

R, R2 (blank below) ■4-Androsten-3-one-17β-carboxylic acid alkyl ester.

(2) 4-Nistrene-3-one-17β-carboxylic acid and its alkyl ester.

■4-Nistrene-3.17-Sion-17-cyclic ethylene ketanol.

(b) [benzo-1,2°4-thiadiazine-1-dioxide derivative represented by the following general formula (3).

(Left below) (Formula V R1 represents CI, -CF3, -502NlI2, and R2 represents ILCI, -502Nl12. However, R1 and R2 cannot both be CI at the same time, or both cannot be -5o2Ni12 at the same time. ), Riri is I (.

Alkyl group having 1 to 3 carbon atoms, -C11,2CI, -C
IICI2, -CCI ko, -COOH,-
Cf12 0+1, -CIl20503 H, -CH2
CH(C113) 2, ClI2 5-CI2 CF3
, - (C112) 4 C113, Cl12 S
-Cf12C1l-'C112, -C112-S -C
112-C113, -CH(C113>CIl (
[benzo-1,2,4-thiadiazine]-1-dioxide derivative represented by the general formula (3) is diazoxide (7-dioxide), which has been known as a hypertension treatment agent. Chloro-3-methyl-2H-1,2,4-benzothiadiazine-1,1-dioxide; In general formula (3), R1=
C1,, R2=HSR3=CH3, R4-H compound)
The occurrence of hirsutism as a side effect of
Pediatrics), 71, (4), 494~
505.1967), it was applied as a hair growth promoter and a patent application was filed.

However, the effect of promoting hair growth and hair growth is very weak when used in small amounts, and when used in large quantities to obtain the effect, side effects such as hyperglycemia occur, so it is not recommended for use as a hair growth and hair growth promotion*F. It has the following drawbacks.

By using this product in combination with the above-mentioned specific steroid derivatives, the present inventors have created a hair nourishing agent that has no side effects and has excellent hair growth and hair nourishing effects.

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

Specifically describing the compounds of general formula (1) and general formula (2) used by the present invention, 17β-(2-hydroxyethoxy)-4-estren-3-one, 17β-(2
-hydroxyethoxy)-4-estren-3-one acetate, 17β-(2-hydroxyethoxy)-4-
Estren-3-one butyrate, 17β-(2-hydroxyethoxy)-4-estren-3-one p-)luenesulfonate, 17β-(2-hydroxyethoxy)-4-estren-3-one methanesulfo*- 1-
217β-(2-chloroethoxy)-4-estrene-
3-one, 17β-(2-iodoethoxy)-4-estren-3-one, 17β-carboxymethoxy-4-
Estren-3-one, 17β-carboxymethoxy-
4-estren-3-one methyl ester, 17β-(
2-cyanoethoxy)-4-estren-3-one, 1
7β-(2-piperidinoethoxy)=4-estrene-
3-one, 17β-(2-((tetrahydrobilan-2-yl)oxy)ethoxy)-4-estren-3-one, 17β-(
2-hydroxyethoxy)-4-androstene-3-
17β-(2-hydroxyethoxy)-4-androsten-3-one acetate, 17β-(2-hydroxyethoxy)-4-androsten-3-one butyrate, 17β-(2-hydroxyethoxy)4-one Androsten-3-one P-)luenesulfonate,
17β-(2-hydroxyethoxy)-4-androsten-3-one methanesulfonate, 17β-(2-
chloroethoxy)-4-androsten-3-one, 1
7β-(2-iodoethoxy)-4-androstene-
3-one, 17β-carboxymethoxy-4-androsten-3-one, 17β-carboxymethoxy-4-
Androsten-3-one-methyl ester, 17β-
(2-cyanoethoxy)-4-androsten-3-one, 17β-(2-piperidinoethoxy)-4-androsten-3-one, 17β-(2-((tetrahydropyran-2-yl) oxy)ethoxy2-4-androstene=3-one, 4-androstene-3,17-dione-1 fucyclink-1°,2°-propylene ketal, 4-androstene-3,17-dione-17
-cyclic-2', 3'-butylene ketal, 4
-estren-3-one-17β-carboxylic acid methyl ester, 4-androsten-3-one-17β-carboxylic acid methyl ester, and the like.

The blending amount is o,ooot~2% by weight in the hair nourishment of the present invention.
is desirable. Particularly preferred is o,ooot to 0.2% by weight.

If the amount is less than o,ooot% by weight, the hair nourishing effect may not be exhibited. In addition, the higher the amount, 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.

Further, [benzo-1゜2.
Examples of the 4-thiadiazine)-1-dioxide derivatives include 7-chloro-3-methyl-2H-1゜2.4-benzothiadiazine-1,1-dioxide, 7-chloro-3
-Hydroxymethyl-2H-1,2,4-benzothiadiazine-1,1-dioxide, 7-chloro-3-carboxyl-2H-1,2,4-benzothiadiazine-1
, 1-dioxide, and the like.

The blending amount is 0.001 to 10% by weight in the hair nourishment of the present invention.
is preferred, particularly preferably 0.01 to 6% by weight.

If the amount is less than 0.001%, the hair nourishing effect may not be exhibited. In addition, the higher the amount, the greater the hair growth effect, but considering the occurrence of side effects when used in large amounts,
It is preferably 0% by weight or less.

In addition to the above-mentioned steroid derivatives and benzo-1,2,4-thiadiazine-1-dioxide derivatives, the hair care product of the present invention contains additives commonly used in hair care products, such as hinokitiol, hexachlorophene, and phenol. , antibacterial agents such as benzalkonium chloride, cetylpyridinium chloride, undecylenic acid, trichlorocarbanilide and bithionol, 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, and higher alcohols, other surfactants, fragrances, antioxidants, ultraviolet absorbers, pigments, ethanol, water, humectants, thickeners, etc. can enhance the effects of the present invention. It can be blended as appropriate within a range that does not cause any damage.

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.

The hair tonic according to the present invention contains the above-mentioned steroid derivatives and expands the peripheral blood vessels of the scalp to promote an increase in blood flow [benzo-1,2
, 4-thiadiazine-1-dioxide derivatives to exert a synergistic hair-nourishing effect.

〔Example〕

Next, the present invention will be explained in more detail with reference to Examples. The present invention is not limited thereby. The blending amount is in weight%.

Prior to the examples, the test method will be explained.

Hair growth effect measurement method Judgment was made based on the change in the number of strands of hair removed during hair washing before and after using the sample. There were 10 subjects in each of seven groups, Examples 1 to 6 and Comparative Example 1. The measurement period is 4 months, and the first two
The first month was the period when no sample was applied, and the second half of the second month was the period when the sample was applied. 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. To display the number of hairs pulled out for each period, data on the number of hairs pulled out 8 times in 2 months without sample application and data on the number of hairs pulled out 8 times in 2 months with hair tonic applied are summarized for each period, and the average is calculated. Value ±
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 hairs pulled was reduced by 70 or more, indicating a significant effect.

+: The number of hairs pulled was reduced by 40 or more, indicating a considerable effect.

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

-The reduction in the number of two-haired trees was less than 10, so it cannot be said that it is effective.

(Margin below) Example 1, Comparative Example 1.2 *EO: Abbreviation for polyoxyethylene, same hereinafter.

(Left below) (Production method) 4-androsten-3-one-1 in 95% ethanol
7β-carboxylic acid methyl ester, 7-chloro-3-methyl-28-1,2,4-benzothiadiazine-1,1
- Dioxa, ido and hydrogenated castor oil EO (40 mol)
The adduct was added, stirred and dissolved, and then ion-exchanged water was added and mixed to obtain a transparent liquid hair nourishment of Example 1. Comparative Example 1.2 was also obtained in the same manner as Example 1.

(Below the margins) (Results) (Below the margins) All of the above results are 4-androstene-3-one-
17β-carboxylic acid methyl ester and 7-chloro-3-
Methyl-2)i-1,2,4-benzothiadiazine-1
, 1-dioxide according to the present invention is a hair tonic containing conventionally known 4-androsten-3-one-17β-carboxylic acid methyl ester and 7-chloro-3-
Methyl-2H-1,2,4-benzothiadiazine-1,
This shows that the hair nourishing effect is synergistically superior to that of the hair nourishing agent containing 1-dioxide.

Example 2 (Phase A) 4-estren-3-one-17β-carboxylic acid ethyl ester 2.07-chloro-3-hydroxymethyl-211-1,2,4-benzothiadiazine-■,1-di Oxide 3.0 Eo (60 mol) Hydrogenated castor oil 2.0 Glycerin
7.0 dipropylene glycol
8.・11-cho 3-butylene glycol
5.0 polyethylene glycol 1500
5.0 (Phase B) Cetyl isooccinate 10.0 Squalane 5.0 Vaseline
2.0 Propylparaben
2.0 (C phase) Carboxyvinyl polymer 1% aqueous solution 30.0 Sodium hexametaphosphate 0.03 Ion exchange water 8.95 (D phase) Ion exchange water 4.5 (E phase) Caustic potash 0.12 Ion exchange water 5.0 (l!! Production method) Phase A and phase B are heated and dissolved at 60°C, mixed and treated with a homomixer to form a gel. Phase D is gradually added to this and dispersed using a homomixer.

Next, the dissolved phase C was added to the paste, and finally the dissolved phase E was added and emulsified with a homomixer to obtain an O/W emulsion type hair nourishment.

When this hair nourishing agent was subjected to a practical use test in the same manner as in Example 1, it was confirmed that its hair nourishing effect was excellent.

Example 3 (human face) 4-androstene-3,17-thion-17-cyclic nichilene kecool 0.27-chloro-
3-Carboxyl-2+1-1.2.4~Benzothiadiazine-■,1-dioxide 2.0 Liquid paraffin 5.0 Cetostearyl alcohol 5.1 Glyceryl monostearate 3.0 EO (20 mol) -2 -Octyl dodecyl ether 3.
0 Propyl paraben 0.3 Fragrance 0.1 (B phase) Glycerin 8.O Dipropylene glycol 20.0 Polyethylene glycol 4000 5.0 Sodium hexametaphosphate o, oos Ion exchange water
48.295 (Production method) Phase A and phase B were respectively heated and dissolved, mixed, and emulsified with a homomixer to obtain an ointment-like hair nourishing agent.

When this hair nourishing agent was subjected to a practical use test in the same manner as in Example 2, it was confirmed that its hair nourishing effect was excellent.

Example 4 Ethanol 55. O17
β-(2-hydroxyethoxy)-4-androsten-3-one 0.00017-chloro-3
-Methyl- 211-1,2,4-benzothiadiazine-1,1-dioxide 0.01 EO (8 mol) Oleyl alcohol ether 2.0 Hinokitiol 0.05 Fragrance
0.1 dye
0.0899 ion exchange water
42.75 (Production method) Ethanol with EO (8 mol) oleyl alcohol ether, 17β-(2-hydroxyethoxy)-4-androsten-3-one, 7-chloro-3-methyl-21m
-1,2,4-benzothiadiazine-1,1-dioxide and hinokitiol were added thereto, perfume and dye were added and dissolved, and then ion-exchanged water was added to solubilize to obtain a hair nourishing agent.

Example 5 0.2 g of 17β-(2-hydroxyethoxy)-4-estren-3-one acetate, ? -Kuroro 3-
Methyl-211-1.2.4-benzothiadiazine-1
, 1-dioxide 0.001g, liquid paraffin 5
．． 0g, cetostearyl alcohol 5.5g, petrolatum 5.5g, glyceryl monostearate 3.0g 5EO
(20 mol)-2-octyldodecyl ether 3.0g
, 0.2 g of propylparaben and 0.1 g of fragrance are heated and melted and mixed. Add 7.0g of glycerin and 20.0g of dipropylene glycol to this.

5.0 g of polyethylene glycol 4000, 0.005 g of sodium hexametaphosphate and 45.0 g of ion exchange water.
494 g of the hot melt mixture was added and emulsified using a homomixer to obtain a cream-like hair nourishing agent.

The obtained hair nourishing agent showed an excellent hair nourishing effect.

〔Effect of the invention〕

The hair growth agent of the present invention has an excellent hair growth effect, is locally effective, has no systemic side effects, and is a highly safe hair growth agent with little skin irritation.

Patent applicant: Shiseido Co., Ltd. Procedural Procedures No. 11 (spontaneous) April 30, 1985 Director General of the Patent Office Michibe Uga 1, Indication of the case 1986 Patent Application No. 46771 2, Name of the invention Hair tonic 3. Relationship with the case of the person making the amendments I will correct it accordingly.

(2) Insert the following sentence after 2) in the general formula on page 9 of the specification.

[(In the formula, R1 represents Hl-C1(3, R2 represents Hl-
Represents CH3, -C2H5, -c3H7. )'' (Attachment) 2. Claims Claims A food product characterized by containing at least one member selected from the group (a) below and at least one member selected from the group (b) below. Hair fee.

(a) ■ 4-estrene- represented by the following general formula ill
3-one-17β-ethoxy derivative or 4-androsten-3-one-17β-ethoxy derivative.

(Left below) (In the formula, R1 represents ■], -CIl3, and R2 represents -CI
l20i+, -CIl20COX (X is 1 carbon number
~5 represents an alkyl group or a phenyl group. ), -CH2
Y (however, Y represents F, CI, mouth r, E), -
C112CN, -C00X (X is the same as above)
, ■ 4-androstene represented by the following general formula (2)
3,17-Sion-17-Cyclic Nethylene Kecool Derivative.

R, R2 (blank below) ■4-Androsten-3-one-17β-carboxylic acid alkyl ester.

(2) 4-Nistrene-3-one-17β-carboxylic acid and its alkyl ester.

■4-Nistrene-3.17-Sion-17-cyclic ethylene ketanol.

(b) [benzo-1,24
-thiadiazine]-1-dioxide derivative.

(In the formula, R8 represents C1, -CF3, -5o2N112, and R2 represents I(, Ct, -50,2NIl, 2. However, RI and R2 may both be CI at the same time. Or both may be -502Nl+2 at the same time. )
, R3 is! (, alkyl group having 1 to 3 carbon atoms, -CIl
, 2 CI.

-CIICI2, -CCI3, -COOII, -C1
12011, -C1120S03 Hl ClI2 C
Il (CIl3) 2, ClI2 S Cl1
2 CF3, (CIl2) 4 Cll3, -C
lI2- S -CIl2- CII= C112, C
lI2 S C112C113, C1l (C11
3) CIl (CIl3) C112CH3,
that's all

Claims (1)

[Scope of Claims] A hair nourishing agent comprising at least one selected from the group (a) below and at least one selected from the group (b) below. (a) [1] A 4-estren-3-one-17β-ethoxy derivative or a 4-androsten-3-one-17β-ethoxy derivative represented by the following general formula (1). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) {In the formula, R_1 represents H, -CH_3, and R_2 represents -C
H_2OH, -CH_2OCOX (however, X is a carbon number of 1 to
5 represents an alkyl group or a phenyl group. ), -CH_2
Y (however, Y represents F, Cl, Br, I), -CH
_2CN, -COOX (X is the same as above), -CH
_2OSO_2C_6H_4CH_3, -CH_2OS
O_2CH_3, ▲There are mathematical formulas, chemical formulas, tables, etc.▼,
▲Represents mathematical formulas, chemical formulas, tables, etc.▼. } [2] 4-androstene-3,17-dione-17-cyclic ethylene ketal derivative represented by the following general formula (2). ▲Contains mathematical formulas, chemical formulas, tables, etc.▼(2) [3] 4-Androsten-3-one-17β-carboxylic acid alkyl ester. [4] 4-estren-3-one-17β-carboxylic acid and its alkyl ester. [5] 4-estrene-3,17-dione-17-cyclic ethylene ketanol. (b) [benzo-1,2,
4-thiadiazine]-1-dioxide derivative. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(3) (In the formula, R_1 is Cl, -CF_3, -SO_2NH_2
, R_2 represents H, Cl, -SO_2NH_2 (however, R_1 and R_2 are not both Cl or -SO_2NH_2 at the same time), R_3 is H, an alkyl group having 1 to 3 carbon atoms, −
CH_2Cl, -CHCl_2, -CCl_3, -CO
OH, -CH_2OH, -CH_2OSO_3H, -C
H_2CH(CH_3)_2, -CH_2-S-CH_
2CF_3, -(CH_2)_4CH_3, -CH_2
-S-CH_2-CH=CH_2, -CH_2-S-C
H_2-CH_3, -CH_(CH_3)CH(CH_3)CH_2CH_
3. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ Mathematical formulas, chemical formulas,
There are tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ Mathematical formulas, chemical formulas,
It represents ▼, and R_4 represents H, -CH_3. )