JPH0418026A - Testosterone 5 alpha-reductase inhibitor - Google Patents

Abstract

PURPOSE:To obtain testosterone 5 alpha-reductase inhibitor free from side effects, applicable to cosmetic for producing and nourishing hair and for pimple, drugs, etc., containing an extract of specific herb as an active ingredient. CONSTITUTION:Dried powder of one or more herbs selected from Salvia officinalis L., Humulus lupulus L., Rosmarinus officinalis L., Hypericum erectum Thunb., Mentha piperita L., Arnica montana L. Arnica nontana L, and Thynus vulgaris L. is immersed in 99.5% or 50% ethanol in a ratio of 1g/10ml, allowed to stand for one week and then filtered to give extracted solutions. The extracted solutions have excellent inhibitory action on testosterone 5 alpha-reductase and inhibitory action of sebum formation. Consequently, each of the extracted solutions as an active ingredient is blended with a hair tonic, a hair growing agent or a hair cosmetic, a skin external preparation for treating pimple or skin cosmetic and used.

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention provides testosterone 5α, which can be applied to cosmetics and pharmaceuticals for hair growth/nourishment and acne, and has no side effects.
-Relating to reductase inhibitors.

<Prior Art> Male pattern baldness, alopecia, O leakage, acne (acne vulgaris), etc. are said to be caused by an excess of male hormones.

In particular, it is known that the main body of this androgen activity in organs such as hair roots and sebaceous glands is 5α-dihydrotestosterone (CDHT), which is produced by reducing testosterone to νV by testosterone 5α-reductase (TSR) in these target organs. It is being In other words, testosterone (
Male hormones) reach the sebaceous glands through the bloodstream and
Converted to DHT by TSR in l\1 gland cells.

This DHT binds to intracellular receptors and acts on the nucleus to promote the proliferation of sebaceous gland cells, while also acting on hair matrix cells to suppress their cell division and impede hair growth. There is.

Traditionally, treatments for male pattern baldness, alopecia, acne, etc.
Substances with female hormone effects, such as estradiol, and substances with anti-androgen effects, such as cybrothyrone acetate5, have been used.5 Substances with strong oxidizing power (such as ClO2) have been used. Furthermore, focusing on the above-mentioned mechanism of action of testosterone, research on substances that inhibit TSR activity is also progressing.

<11g that the invention seeks to solve> However, hormones and oxidizing agents have problems in terms of side effects and safety, and they cannot be incorporated into cosmetics or can only be used under the supervision of a doctor. In addition, the substances that have been reported to inhibit TSR activity may not have sufficient action or efficacy, may not be safe enough, or may be expensive. For many years, we have been screening medicinal herbal extracts that have no side effects or safety issues and can be incorporated into cosmetics. We have also found that the application of specific medicinal herbal extracts is effective in solving the above problems.

i.e. 99,5% or 50″ of medicinal herbal ri powder
They were immersed in L ethanol at a ratio of 1 g to 8 ml, allowed to stand for one week, filtered, and the filtrate was separated to study TSR activity. As a result, sage (Salvia officin)
alisL, ), hop (Hu tIlu 1 u
s 4 L, ), Rosemary (Rosmarin)
us officinalis (), Hypericum perforatum (ijz: erectum Thunj,), Not\Tsuka (10-tha), Chamomile (
Matricariach for dogs,), Arnica (^
-...μu nta. ! L.).

It was found that ethanol extracts of thyme (Tsuji 1 nL) were effective.

<Effect> Table 1 shows the TSR activity inhibition and protein denaturation rates of the above medicinal herb extracts.

9,0 of rat liver homogenate as TSR solution.
00xg supernatant (S-9) was used. First, dissolve 3 μm of testosterone in 10 drops of propylene glycol.
Tris-HC1 buffer (pH 7,2) 5 ml
Add. To this, ~ADP)l 5mg, S-
91ml, add 0.5r+1 of Mibi herbal extract, 37ml
After incubation for 30 min at °C, dichloromethane 5
0ml was added to stop the reaction, the dichloromethane layer was separated and dried under reduced pressure, and then subjected to gas chromatography (GC).
The reaction products DHT, anthrostanediol, etc. were detected and quantified (GC conditions: column; ULBON
HR-1, carrier gas; He 20ml/l1l
in, column temperature: 200°C), by comparing the amount of the reaction product when the TSR activity-inhibiting herbal extract was not added (control) and the amount of the reaction product when the herbal extract was added.

On the other hand, the protein denaturation rate was determined by adding 1 ml of medicinal herbal extract to 9 ml of 0.15 M sodium sulfate/0.05 M phosphate buffer (pH 7.0) containing 0.02% ovalbumin, stirring for 5 minutes, and then removing the membrane. Filter with a filter and perform high performance liquid chromatography (column: TSK-g
el G-30005W).

For each herbal extract No. 1 to 8, either the 99.5% or 50χ ethanol extract has a high TSR.
S activity inhibition rate was calculated. Although these protein denaturation rates were slightly higher in the 99.5% ethanol extract of rosemary (No. 3) and the 50% ethanol extract of Hypericum perforatum (No. 4), they were generally low values. . Therefore, these medicinal herb extracts exhibited a high TSR activity inhibiting effect, and this effect was not due to denaturation of the enzyme protein.

Although linden extract No. 9 has a high inhibition rate of TSRS activity, the protein denaturation rate is as high as 92.21%, and it seems to have an inhibitory effect due to denaturation of enzyme protein, which is not preferable for our purposes.

No significant TSR activity inhibition effect was observed for each herbal extract No. 1 (1-15).

Note that no influence of ethanol was observed in this measurement system.

Furthermore, the above eight medicinal herbal extracts contain +Il of sebaceous glands.
There are some substances that exhibit the effect of suppressing I biosynthesis. That is, in organ culture of the auricular skin of 10-week-old golden gnomes, inhibition of FiI biosynthesis was observed. For organ culture, after exfoliating the inner skin and removing the cartilage from a piece of Ham's ear skin (6 mm diameter), [! 4C] - 4.4 μCi of sodium acetate and 20 μC of sample solution] were added to 2 ml of culture solution (Eagle MEM medium containing 10% FMS with penicillin, streptomycin, fungizone, and L-glutamine added) so that the epidermis side was facing up. It was floated at 37°C for 6 hours. As a control, the other auricular skin was cultured in a culture solution to which only a solvent was added instead of the sample solution.

After culturing, the dermis was washed with physiological saline, placed in 2N NaBr solution, and allowed to stand at 37°C for 1 hour. The dermis and epidermis were separated, and the resulting dermal sheet was placed in chloroform:methanol (2:l)
The inhibition rate of lipid biosynthesis was extracted in 2 ml for 12 hours. The inhibition rate of uptake of 4C]-sodium acetate was determined and the results are shown in FIG.

Hop (Hul!1ulus 7 L) extract and rosemary (Rosmarinus officina)
lis L.), remarkable inhibition of uptake was observed in the extract. These inhibition rates were 46.21% and 19%, respectively.
．． The inhibition rate was 89%, which was higher than that of pyridoxine hydrochloride, a vitamin that is generally said to inhibit lipid biosynthesis.

This inhibitory effect on lipid biosynthesis is likely to be mediated by inhibition of TSR activity.

In addition, it is generally known that in biosynthesis experiments using 4Cl-labeled substance incorporation in culture systems, the promotion or inhibition of biosynthesis due to hormonal action does not appear until 12 hours or more have passed after culture (v.

Wheatly and J, Br1nd
; J, Invest, Der+natol
.

76293-296.1981). Therefore, the above-mentioned effects are not mediated by hormonal effects, and there is no need to worry about serious side effects.
alisL, 3, hop (f(umulus
□ L, ), Rosemary (Rosmarinu)
s officinalis L,), Hypericum perforatum (Ltanachi"erectu+n Thunb,), Ros-tha pj2erjja L,), Chamomile (F+atricaria value ζF-9 x 11 d),
), arnica (＾unjca yuritsuyu L,), thyme (■
The ethanol extract of □hx=u≦7L, ) is T
5 showing SR inhibiting effect and sebum production suppressing effect, therefore,
One or more of these can be selected as a TSR inhibitor and incorporated into hair nourishing/growth agents or hair cosmetics, or external skin preparations for treating acne or skin cosmetics. At that time, since the above effects are not due to protein denaturation or hormonal effects,
It is possible to provide safe cosmetics and the like that are free from LT and side effects.

[Brief explanation of drawings]

I! Figure 1 shows the inhibition rate of lipid biosynthesis. 4C]-sodium acetate uptake inhibition. Patent applicant Noevir Co., Ltd.

Claims (1)

[Claims] Sage (￥Salvia￥￥officinalis￥
L. ), hops (￥Humulus￥￥lupulus
￥L. ), rosemary (￥Ros￥-￥marinu
s￥￥officinalis￥L. ), Hypericum perforatum (\Hy\-\pericum\\erectum\\
Thunb￥. ), Menthapiper
ita￥L. ), chamomile (￥Matricaria￥
￥chamomi-lla￥L. ), arnica (￥Ar
nica￥￥montana￥L. ), Time (\Th
ymus￥￥vulgaris￥L. ) A testosterone 5α-reductase inhibitor consisting of one or more kinds selected from the ethanol extracts of.