JPH0585917A - New hair growing agent composition - Google Patents

Abstract

PURPOSE:To obtain a hair growing agent composition containing probucol and free from irritation of skin. CONSTITUTION:A hair growing agent composition containing (A) 0.1-20W/V% 4,4'-isopropylidenedithio-bis(2,6-di-tert. butyl phenol (probucol) of the formula, (B) 0.01-10W/V% at least one kind of ghycyrrhetic acid, glycyrrhizic acid or alkali salt thereof, (C) 0.01-20W/V% at least one kind of tocopherol or acetic ester thereof, nicotinic acid ester, succinic acid ester and/or calcium salt thereof, (D) 20-80W/V% ethanol or isopropyl alcohol, (E) 0.1-20% fatty acid ester and (F) 0.1-20W/V% polyhydric alcohol. The composition is remarkably improved in irritation of skin, because an mount of an alcohol used as a base for dissolving probucol is reduced in the composition.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel hair nourishing composition. More specifically, the present invention relates to a chemical substance,
4,4'-isopropylidenedithio-bis (2,6-di-t-butyl-phenol) (generic name: probucol)
And a hair nourishing composition having an excellent hair nourishing effect.

[0002]

BACKGROUND ART In recent years, it has been proposed that an imbalance of sex hormones caused by an excess of male hormones is the cause of male pattern baldness, and based on this, many hair nourishing agents containing androgen inhibitor have been released. ing. Also, β-glycyrrhetinic acid as a substance having a 5α-reductase inhibitory activity, carpronium chloride as a substance having a skin vasodilator effect by cholinergic action, or a substance having a blood circulation promoting action of senburi system, garlic system, capsicum tincture system, Although substances such as Korean carrots and the mechanism of action are not clear, various hair nourishing agents containing mini sasaniki are commercially available.

However, in these conventional hair nourishing agents, the undesirable side effects of the contained substances and the substantial
It cannot be said to be satisfactory because the hair nourishing effect is not always obtained. Further, conventionally, a hair nourishing agent containing a follicular hormone, ethinyl estradiol, has been sold, and in recent years, a hair nourishing agent containing pentadecanoic acid triglyceride has also been commercially available. Among these, those having a hair-growth effect confirmed by a biological test such as the double-blind comparison method between groups are hair nourishing agents containing pentadecanoic acid triglyceride.

The present inventors previously provided a hair nourishing composition containing probucol (see JP-A-3-135908). This probucol has the following structural formula and is available from Dow Chemical Company of the United States. It is a researched and developed medicinal substance that has the effect of specifically lowering serum lipids, especially serum total cholesterol, and shows a stable lowering effect during long-term use, as well as a regression effect on xanthoma. ..

[0005]

[Chemical 1]

[0006] It has been confirmed by animal experiments that this chemical substance has an effect of suppressing atherogenesis of arteriosclerosis and a regression effect, and an effect of reducing the onset of coronary heart disease (CHD) in humans. On the other hand, _{LD 50} of this chemical, male and female mice (15~19g) and Wist
ar rats (about 200 g) were used to prepare PB (solvent: 0.
5% hydroxypropylmethylcellulose) was investigated by oral administration, and as a result,> 528 in all animals.
It is 0 mg / kg, and it is recognized that the safety is extremely high.

The inventors of the present invention conducted a number of experiments on the safety of the hair nourishing composition containing the chemical substance probucol provided previously, and found that skin irritation was observed in 10 to 30% of the subjects. Since it was confirmed that it occurred, further investigation of this cause revealed the following facts.

[0008] That is, probucol itself has no skin irritation. However, regarding its solubility, acetone, chloroform, dimethylformamide, carbon disulfide, ether, carbon tetrachloride, organic compounds such as methanol and ethanol, etc. Easily soluble in solvent, but almost insoluble in water. Therefore, in order to stably dissolve probucol, it must be prepared by using an extremely large amount of an organic solvent (alcohol) as a base of the hair nourishing agent,
It has been found that the organic solvent used in a large amount is the main cause of increasing the skin irritation of the hair nourishing agent. After all, the present inventors kept the concentration of probucol required to achieve the desired effect, minimized the amount of the organic solvent (alcohol) used as the base material, and added other components such as glycyrrhetinic acid and tocopherols. It was found that the skin irritation was remarkably improved by containing a fatty acid ester and a polyhydric alcohol as a part of the base together with the inclusion of The present invention has been made based on such findings.

[0009]

DISCLOSURE OF THE INVENTION The novel hair nourishing composition according to the present invention comprises:
Based on the total amount of the composition, probucol is 0.1 to 20 W /
V%, preferably 1 to 5 W / V% so as to be contained, and 0.01 to 10 W / V% of glycyrrhetinic acid or glycyrrhizic acid or one or more of these alkali salts, tocopherol Alternatively, one or more of acetic acid ester, nicotinic acid ester, succinic acid ester and / or calcium salt thereof is contained in an amount of 0.01 to 20 W / V%, and ethanol or isopropyl alcohol is added in an amount of 20 to 80 W / V.
%, 0.1 to 20 W / V% of fatty acid ester, and 0.1 to 20 W / V% of polyhydric alcohol.

The hair nourishing composition according to the present invention can be prepared into a dosage form such as a hairnic, a hair lotion and a hair cream according to a conventional method.

As the base of ethanol or isopropyl alcohol of the hair nourishing composition according to the present invention, ethanol and / or anhydrous ethanol or isopropyl alcohol of the Japanese Pharmacopoeia are used. In the case of ethanol, geraniol-modified alcohol, 8 Modified alcohols such as acetylated sucrose modified alcohol, linalool modified alcohol, diethylphthalate modified alcohol, linalyl acetate modified alcohol, and perfume modified alcohol can also be used. Examples of the fatty acid ester include isopropyl myristate, medium-chain fatty acid triglyceride, octadodecyl myristate, triacetin, and the like, and examples of the polyhydric alcohol include concentrated glycerin (content of 98% or more) propylene glycol, 1,3-
Butylene glycol, D-sorbitol (content 97% or more) macrogol (200 to 20000) and the like can be mentioned.

The hair nourishing composition of the present invention further comprises, in addition to the above-mentioned components, a preservative such as paraoxybenzoic acid ester and sodium benzoate, a flavoring agent such as 1-menthol, a tar dye, and copper. Coloring agents such as chlorophyll and photosensitive dyes can be appropriately added.

Experimental and test examples are shown below. A test solution was prepared based on the formulation described in each of the following examples.

Comparative Example 1 (Comparative Control Solution) Isopropyl myristate 10 g Absolute ethanol is added to make 100 ml.

Comparative Example 2 (1 W / V% Probucol) Probucol 1 g Isopropyl myristate 10 g Absolute ethanol is added to make 100 ml.

Comparative Example 3 (Comparative Control Solution) Glycyrrhetinic acid 0.1 g Acetic acid-dl-α-tocopherol 0.2 g l-menthol 0.1 g Methyl paraoxybenzoate 0.1 g Propyl paraoxybenzoate 0.02 g Isopropyl myristate 2 g Propylene glycol 8 g Absolute ethanol 60 g Purified water is added to make 100 ml.

Example 1 (Test liquid) Probucol 1 g Glycyrrhetinic acid 0.1 g Acetic acid-dl-α-tocopherol 0.2 g l-Menthol 0.1 g Methyl paraoxybenzoate 0.1 g Propyl paraoxybenzoate 0.02 g Isopropyl myristate 2 g Propylene glycol 8 g Absolute ethanol 60 g Purified water is added to make 100 ml.

Using each of these test solutions, the following experiments (tests) 1 and 2 were conducted. 1. Skin Irritation Test (1) Samples Comparative Example 1, Comparative Example 2, Comparative Example 3, Example 1

(2) Test method Application time: 24 hours Application site: Inside of upper arm (either left or right) Adhesive bandage: Adhesive bandage for patch test (Torii Pharmaceutical Co., Ltd.) Application amount: 20 μl Number of subjects: 24 (13 males) , 11 women) Judgment method: Observation was carried out 24 hours after application and 24 hours after peeling according to the following criteria. (Reference: Journal of Cosmetics and Cosmetics Vol. 8 2
Issue P. 109-P. 119 (1984)).

(3) Results The test results are shown in Table 1, and the symbols of the judgment items in Table 1 have the following meanings. Skin reaction −: No reaction ±: Light erythema

[0021]

[Table 1]

2. Clinical test (1) Specimen Comparative Example 3 and Example 1

(2) Test method Period of use: 4 weeks Subject: Male aged 23 to 49 years 15 for the sample of Comparative Example 3 21 for the sample of Example 1 Method of use: as follows. 1) Count the number of hair loss when washing hair before use. This operation is performed 3 times (once a day for 3 days). 2) Next, for 4 weeks, apply an appropriate amount of the sample to the head once a day. 3) After the test, count the number of hair loss when washing hair as before use. 3 times (once a day for 3 days). Analysis method: t-test 1) Difference in the number of hair loss before and after use in the test of Example 1. 2) Difference in the number of hair loss before and after use in the test of Comparative Example 3. 3) Comparison between the difference in the number of hair loss before and after using the sample of Example 1 and the difference before and after using the sample of Comparative Example 3 in each individual.

(3) Results The results of the clinical test are shown in Table 2.

[Table 2] 1) Difference before and after use of the sample of Example 1 (21 cases) The amount of hair loss after use was significantly higher than before use (P <0.0.
5) It was decreasing. 2) Difference before and after use of the sample of Comparative Example 3 (15 cases) No difference was observed before and after the amount of hair loss. 3) In each individual, in comparison of difference between before and after use of each sample of Example 1 and Comparative Example 3, Example 1 was compared.
It was observed that the amount of hair loss in the use of the sample of No. 2 was significantly reduced as compared with the use of the sample of Comparative Example 3, and a significant difference (P <0.05) was observed between them. 4) From the results of this clinical test, the amount of hair loss was clearly decreased (about 13% decrease) by using the sample of Example 1.
Further, in the sample of Comparative Example 3, no change was observed in the number of hair loss. 5) Others: In some cases, by using the sample of Example 1 for 4 consecutive weeks, the number of downy hairs in the hair loss decreased and the hair on the hairline increased.

[0025]

As is clear from the results of the skin irritation test and the clinical test described above, the probucol-containing hair nourishing composition according to the present invention has very little skin irritation and is excellent in human hair nourishing effect. It is highly useful.

Claims (1)

[Claims] 1. A hair nourishing composition comprising the following components (A) to (F). (A) 4,4'-isopropylidenedithio-bis (2,6-di-t-butyl-phenol) 0.1-2
0 W / V% (B) Glycyrrhetinic acid, glycyrrhizinic acid, or one or more of these alkali salts 0.01 to 10 W
/ V% (C) One or more of tocopherol, its acetate ester, nicotinate ester, succinate ester and calcium salt 0.01 to 20 W / V% (D) Ethanol or isopropanol 20 to 8
0 W / V% (E) Fatty acid ester 0.1-20 W / V% (F) Polyhydric alcohol 0.1-20 W / V%