JPS63284125A - Testosterone 5alpha-reductase inhibitor - Google Patents

Abstract

PURPOSE:To obtain the titled inhibitor useful for the remedy of male alopecia and oligotrichosis, drugs, cosmetics, etc., by using eugenol as an active component. CONSTITUTION:Eugenol existing in CHOJI (bud of Syzygium aromatica) is used as an active component among various components originated from animals or vegetables. The role or acting mechanism of testosterone 5alpha-reductase inhibitor in living body is the reduction of testosterone which is a major male hormone with testosterone 5alpha-reductase to keep excess state of dihydrotestosterone, which induces alopecia. Eugenol has testosterone 5alpha-reductase inhibition action and can ameliorate the symptom of alopecia. Since the reductase participates in the development of pimples as well as alopecia, the present inhibitor is expected to be applicable to this field.

Description

DETAILED DESCRIPTION OF THE INVENTION Objects of the Invention The present invention relates to testosterone 5α-reductase inhibitors.

"Industrial Application Field" Testosterone 5α-reductase inhibitor according to the present invention (hereinafter referred to simply as Ts-red inhibitor for convenience)
It can be taken as a single dose or used externally, and is used in the prescription of pharmaceuticals, quasi-drugs, and cosmetics, and is useful for the treatment of male-pattern baldness and hair loss.

"Prior Art" Research on Ts-radii harmful agents has recently been published, for example, as shown below.

The role or mechanism of action of Ts-red inhibitors in the body is 1.For example, from the perspective of the relationship with male pattern baldness and baldness, testosterone, the main male hormone, is activated by testosterone 5α-reductase (hereinafter referred to as For convenience, it is simply abbreviated as Ts-red.) and the result.

The condition caused by excess dihydrotestosterone produced continues. Then, by this.

It is known to induce hair loss.

Therefore, there are substances that can suppress the production of dihydrotestosterone from testosterone.
It is believed that these symptoms can be improved, and development of Ts-red inhibitors is progressing.

In addition to the above-mentioned hair loss mechanism, it is also said to be involved in the onset of acne (old 1 vulgaris); for example, when the production of dihydrotestosterone increases, the sebum secretion ability decreases,
For this reason, Ts-rad inhibitors can be used to treat seborrheic alopecia, seborrheic pityriasis, seborrheic eczema, seborrheic pruritus, etc. by suppressing acne or sebum secretion. Applications are being considered.

“Publications regarding known Ts-radii harmful agents” (1)
J.R. Hemilton: American Jarth
Ofanatomi JR Volume 71 451 (1942) (2) Atsuchi & Kanou: Biochemical and Bio 749kk 91-Chiko Mini Kesic
Volume 41 04 (1970) (3) Masumi Inaba: Mainichi If 74-60 November issue (4) Masumi Inaba: Fragrance Journal No. 14-18, 58 (1!83) (5) 9x (Ikert, H, U, & Rai k”
Anne, J.D.: Journal Off Clinical Endocrinology 9, Anne F. Mekubowism Volume 38, 88
1 (1174) (6) Koshokai Magazine Vol. l t413.2 Plo
t ~107 Yasuo Asada (1985) (7) Published Patent Publication: 1983-193689 (8)
Published Patent Publication: No. 1981-081122 (9) Public Patent Publication: No. 126218 (Sho 60-126218) (lO) Public Patent Publication: No. 146829 (1988) (11) Public Patent Publication: w
B60-028925 (12) Published Patent Publication Ig: 1977
No. 0-064910 (13) Published Patent Publication: 1986-1
No. 42908 "Problems to be Solved by the Invention" The present invention aims to contribute to the fields of application to pharmaceuticals, quasi-drugs, and cosmetics as described above, and aims to solve novel Ts.
-Involved in the development of a substance that can be a radiI harmful agent.

(b) Structure of the invention The present invention is characterized by containing eugenol.

It is a Ts-red inhibitor.

"Means for Solving the r Problem" The present inventors 1! ＋・Regarding the effective use of plant-derived ingredients, we have conducted research and development on extracts and isolated ingredients containing eugenol, and as shown below, we have developed effective Ts-ra
succeeded in developing a harmful agent.

"Experimental Example 1" Extracted from the liver of SD male rats (7 weeks old). Using testosterone 5α-reductase.

It was measured under the following reaction system conditions.

(Reaction system) Testosterone 3.0 #LM and propylene glycol 1
Dissolve in 0 drops of Tris-MCI buffer (pH 7, 2)
Add 5 ml of NADPH5[1 testosterone 5α-reductase solution, and then add 1 ml of NADPH5[1 testosterone 5α-reductase solution, and heat at 37°C.
After 30 minutes of reaction, add dichloromethane to stop the reaction and extract with a total volume of 50ml of dichloromethane to obtain a dichloromethane layer.Next, dichloromethane is distilled off under reduced pressure, and the reaction amount is determined by gas chromatography. Measure.

Incidentally, the specimen (substance obtained in the example) is added to the reaction system after the dropping of testosterone.

(G, C: Force 9 AOV-17. Column length 2ffi Force Ram temperature 250°C, FID) Table 1 Inhibitory activity of testosterone 5α-reductase inhibitors (Notes on Table 1) Harm rate: Control Assuming that the reaction rate is 100% (inhibition rate 0%), calculate the reaction amount with the lfl harmful substance added to determine the inhibition rate. The formula is as shown below.

a: Control (peak area of testosterone) b = Control (peak area of dehydrotestosterone, anthrostanediol) a' = Peak area of testosterone (addition of III harmful substance) b/ , Peak area of dehydrotestosterone, anthrostanediol (inhibition) Furthermore, since dehydrotestosterone is further metabolized to produce anthrostanediol, the peak area (amount) of the 5α-reductase metabolite also includes anthrostanediol.
It has been included.

(Experimental Results) Based on the above Experimental Example 1, we screened for those showing harmful effects of Ts-redll, and the herbal medicines that were finally marked were listed as Syzygiu.
m aromaticum Merrill @
The buds of T. Parry (Myrtaceae) were collected just before flowering.

The main active substance contained in the extract obtained from the clove is eugenol, and this is Ts-r*
It turned out to be a substance that could be a dll harmful agent.

Therefore, we conducted a study on cloves based on various extraction solvents that are compatible with them. For example, according to the method shown in Example 1, the obtained extract contains eugenol and has excellent Ts.
-redlJl It was discovered that it could be a harmful agent.

"Example 1" A method for extracting a solution that can be a Ts-r+edll harmful agent from cloves is to crush cloves and then add 5 parts of 30 v/v% ethanol or ethanol to 1 part of clove powder. After soaking at room temperature, filtration is performed, and the filtrate is further frozen (-20°C to -10°C) and then filtered again to use the clove extract as a Ts-red inhibitor.

Furthermore, instead of ethanol, methanol, acetone,
Extracts obtained using ethyl acetate etc. also have T s −r
It can be used as a sd II inhibitor.

"Example 2" Crush cloves and use 1 part clove ends.

Various organic solvents that are immiscible with water (e.g., n-hexane,
After adding 10 parts of benzene, chloroform, ether, etc., and immersing the mixture at room temperature, it is filtered and the organic solvent is distilled off to obtain a maggot extract (oil).

"Example 3" After crushing cloves, steam distilling the clove powder,
A maggot oil (essential oil) containing 70 to 85% eugenol is obtained.

"Experimental Example 2" Eugenol was determined by gas chromatography using clove extracts obtained by extraction with various organic solvents.9
As a result, the following results were achieved.

(Gas chromatography measurement conditions) Column: 0V-17 column Length: 2. Om Column temperature: 120°C Inlet temperature = 200°C Carrier gas: Nitrogen flow rate: 30 ml/sin detection
Output: FID As shown in Table 2, the extracts of Chimuji obtained by various solvent extractions differ slightly depending on the extraction solvent.
Contains eugenol. Example 1 mentioned above
A more concentrated solution of the extract can also be used.

"Example 3" The following sample was prepared and administered to male volunteers aged 25 to 55 with male pattern baldness (young baldness) (men with hair loss from the forehead) by local application and rubbing. During the 1 period, use of other hair growth agents was discontinued.

(Preparation concentration of sample) Eugenol O and Ig were dissolved in 100 ml of ethanol solution to prepare a sample.

``Results'' The administration period was 6 months, and the application time was approximately twice in the morning and evening, and the sample was thoroughly applied and rubbed only on the hair loss area. .

The results are shown in Table 4.

When considering the results, we found that no side effects were observed during the period.

Of course, for bald young men, there is a noticeable hair growth effect, but the hair growth state is mainly down to down hair. Also, in terms of age, it had little effect on baldness after the age of about 50.

"Table 4" Hair growth test (effect on young baldness) (commentary to Table 4) X/Y (Z) (c) Effects of the invention The present invention seeks active ingredients from a wide variety of animal and plant-derived ingredients found in natural products, and the eugenol contained in Chizen maggot is a novel Ts-red inhibitor. This made it possible to use it as a drug.

As shown in Table 1, for eugenol or unconcentrated clove fluid containing eugenol, Ts-red
is completely inhibited, and no dihydrotestosterone is produced.On the other hand, isoeugenol, an isomer of eugenol, has a slight inhibitory effect, but
-It is unsuitable for use as a red inhibitor.

Furthermore, in Table 181, we compared various conventionally known drugs used in hair tonics or hair styling products, and found that methyleugenol, vanillin, phenol, pyrogallol, resorcinol, and squalane have almost no inhibitory effect. Rather, results were obtained that seemed to promote the production of dihydrotestosterone.

In addition, other plant-derived components (extracts) containing eugenol include the essential oil in the bark of Cinnamon camphor tree (Lauraceae), the essential oil in the trunk and bark of Nerkentus tree (Lauraceae), or Ravansais aron+atic
There is a product called Madagascar clove extracted from various parts of aGmal (Laurinaceae), and extracts of these are also considered to be effective when used as Ts-rad inhibitors.

Claims (1)

[Claims] (1) Testosterone 5α-reductase inhibitor characterized by containing eugenol