JP3168273B2 - New hair restoration composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel hair restorer composition. More specifically, the invention relates to chemicals,
4,4'-isopropylidenedithio-bis (2,6-di-t-butyl-phenol) (generic name: probucol)
And a hair restoration composition having an excellent hair restoration effect.

[0002]

2. Description of the Related Art In recent years, it has been argued that the imbalance of sex hormones caused by an excess of androgen is the cause of male pattern baldness. ing. Also, β-glycyrrhetinic acid as a substance having a 5α-reductase inhibitory activity, carpronium chloride as a substance having a cutaneous vasodilatory action by cholinergic action, or assemblages, garlics, capsicum tinctures as substances having a blood circulation promoting action. Although the substance and the mechanism of action of Korean carrots and the like are not clear, various hair restorations containing mini Sasanishiki are commercially available.

[0003] However, in these conventional hair restorers, there are undesirable side effects of the contained substances,
It cannot be said that it is satisfactory because the hair growth effect is not always obtained. Further, conventionally, a hair restorer containing ethynylestradiol, which is an estrogen, has been sold. In recent years, a hair restorer containing pentadecanoic acid triglyceride has been commercially available. Among these, those which have been shown to have a hair-growing effect by a biological test such as a double-blind comparison method between groups are hair-growth compositions containing pentadecanoic acid triglyceride.

The present inventors have previously provided a hair restorer composition containing probucol (see Japanese Patent Application Laid-Open No. 3-135908). This probucol has the following structural formula and is available from Dow Chemical Company in the United States. A drug substance developed and researched that specifically reduces serum lipids, especially serum total cholesterol, and has a stable lowering effect and a regression effect of xanthomas during long-term use. .

[0005]

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[0006] Animal experiments have shown that this chemical has an effect of inhibiting atherosclerosis and regression of arteriosclerosis, 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) using PB (solvent: 0.
5% hydroxypropyl methylcellulose) was determined to be> 528 in all animals.
0 mg / kg, which indicates that the safety is extremely high.

The present inventors have conducted a number of experiments on the safety of a hair restoration composition containing the chemical substance probucol provided above, and found that skin irritation occurred in 10 to 30% of the subjects. Since the occurrence was recognized, further investigation of the cause revealed the following fact.

That is, although probucol itself has no skin irritation at all, its solubility is determined with respect to organic compounds such as acetone, chloroform, dimethylformamide, carbon disulfide, ether, carbon tetrachloride, methanol and ethanol. It is easily soluble in solvents but hardly soluble in water. Therefore, in order to stably dissolve probucol, it must be prepared using an extremely large amount of an organic solvent (alcohol) as a base for hair restoration.
It has been found that the organic solvent used in a large amount is the largest cause for increasing the skin irritation of the hair growth agent. After all, the present inventors have reduced the amount of the organic solvent (alcohol) used as a base material as much as possible while maintaining the concentration of probucol necessary for achieving the desired effect, and reduced other components such as glycyrrhetinic acid and tocopherols. And the combined use of a fatty acid ester and a polyhydric alcohol as a part of the base succeeded in remarkably improving skin irritation. The present invention has been made based on such findings.

[0009]

DISCLOSURE OF THE INVENTION The novel hair restorer composition according to the present invention comprises:
Based on the total amount of the composition, probucol was 0.1 to 20 W /
V, preferably 1 to 5 W / V%, and 0.01 to 10 W / V% of glycyrrhetinic acid or glycyrrhizic acid, or one or more of these alkali salts, tocopherol. Or one or more of acetate, nicotinate, succinate and / or a calcium salt thereof containing 0.01 to 20 W / V%, and ethanol or isopropyl alcohol containing 20 to 80 W / V.
%, Preferably 20 to 60 W / V%, fatty acid ester of 0.1 to 20 W / V%, polyhydric alcohol of 0.1 to 20 W
/ V%.

The hair restorer composition according to the present invention can be prepared in the form of a hair tonic, a hair lotion, a hair cream or the like according to a conventional method.

Ethanol and / or anhydrous ethanol or isopropyl alcohol of the Japanese Pharmacopoeia are used as ethanol or isopropyl alcohol as a base of the hair restoration composition according to the present invention. In the case of ethanol, geraniol-denatured alcohol, 8 -Denatured alcohols such as acetylated sucrose denatured alcohol, linalool denatured alcohol, diethyl phthalate denatured alcohol, linalool acetate denatured alcohol, and fragrance denatured 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. Examples of the polyhydric alcohol include concentrated glycerin (content 98% or more) propylene glycol, 1,3-
Butylene glycol, D-sorbitol (content 97% or more) macrogol (200 to 20,000) and the like.

[0012] In addition to the above components, the hair restorative composition of the present invention further comprises preservatives such as paraoxybenzoate and sodium benzoate, flavors such as 1-menthol, tar dyes, copper and the like. Coloring agents such as chlorophyll, photosensitive dyes and the like can be appropriately compounded.

The following are experimental examples and test examples. Test solutions were prepared based on the formulations described in the following examples.

Comparative Example 1 (Comparative Control Solution) 10 g of isopropyl myristate Absolute ethanol was added to make 100 ml.

Comparative Example 2 (1 W / V% probucol) Probucol 1 g Isopropyl myristate 10 g Absolute ethanol was 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 parahydroxybenzoate 0.1 g Propyl parahydroxybenzoate 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 1-Menthol 0.1 g Methyl parahydroxybenzoate 0.1 g Propyl parahydroxybenzoate 0.02 g Isopropyl myristate 2 g Propylene glycol 8 g Absolute ethanol 60 g Purified water is added to make 100 ml.

Using these test solutions, the following experiments (tests) 1 and 2 were carried out. 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: Upper arm (can be left or right) Adhesive patch: Adhesive patch for patch test (Torii Pharmaceutical Co., Ltd.) Application amount: 20 μl Number of subjects: 24 (13 males) Evaluation method: Observed according to the following criteria 24 hours after application and 24 hours after peeling. (Reference: Cosmetic Society Journal, Vol. 8, No. 2)
No. P. 109-P. 119 (1984)).

(3) Results The test results described above are shown in Table 1. The symbols of the judgment items in Table 1 have the following meanings. Skin reaction-: No reaction ±: Mild erythema

[0021]

[Table 1]

2. Clinical tests (1) Specimens Comparative Example 3, Example 1

(2) Test method Duration of use: 4 weeks Subject: male aged 23 to 49 15 persons for the sample of Comparative Example 3 21 persons for the sample of Example 1 Usage: as follows. 1) Count the number of hair loss during hair washing before use. This operation is performed three times (once a day for three days). 2) Next, apply an appropriate amount of the sample to the head once a day for 4 weeks. 3) After the test, count the number of hair loss during hair washing 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) For each individual, a comparison between the difference in the number of hair loss before and after the use of the sample of Example 1 and the difference before and after the use of the sample of Comparative Example 3.

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

[Table 2] 1) Difference between before and after use of the sample of Example 1 (21 cases) The amount of hair loss after use was significantly (P <0.0) compared to that before use.
5) It was decreasing. 2) Difference between before and after use of the sample of Comparative Example 3 (15 cases) No difference was observed between the amount of hair loss and before and after use. 3) In each individual, in the comparison of the difference between each sample of Example 1 and Comparative Example 3 before and after the use, the results of Example 1 and Comparative Example 3 were compared.
It was found that the amount of hair loss in the use of the sample of Comparative Example 3 was significantly reduced as compared with the case of using 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 reduced by the use of the sample of Example 1 (about 13% reduction),
In the sample of Comparative Example 3, no change was observed in the number of hair loss. 5) Others: An example in which the number of downy hairs in hair loss and a number of hairs in hairline increased due to continuous use of the sample of Example 1 for 4 weeks was observed.

[0025]

As apparent from the results of the above-mentioned skin irritation test and clinical test, the probucol-containing hair restoration composition of the present invention has extremely low skin irritation and excellent hair growth effect in humans. And are highly useful.

Claims (2)

(57) [Claims] 1. A hair restoration composition comprising the following components (A) to (F): (A) 4,4'-isopropylidenedithio-bis (2,
6-di-t-butyl-phenol) 0.1-20 W /
V% (B) One or two or more of glycyrrhetinic acid, glycyrrhizic acid or an alkali salt thereof 0.01 to 10 W
/ V% (C) one or more of tocopherol, its acetate, nicotinate, succinate 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 to 20 W / V% (F) Polyhydric alcohol 0.1 to 20 W / V% 2. The hair restoration composition according to claim 1, wherein (D) ethanol or isopropanol is 20 to 60 W / V%.