JP3260918B2 - Triterpene acid derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a triterpene acid derivative having an antiandrogenic action and an antiandrogen containing the compound.

[0002]

2. Description of the Related Art As a substance having a triterpenoid structure related to the compound of the present invention, kadsulact is known.
one A [phytochemistry magazine (Phytoche
misry), Vol. 29, pp. 3358-3359, 19
1990], anweweizic acid [Canadian Journal of Chemistry (Cana)
dia Journal of Chemistr
y), 66, 414-415, 1988], ka
dsuric acid [Chemistry Letter Magazine (C
Chemistry Letters), 1307-13
10, p. 1976]. In addition, as the compound derived from Sanekazura, the above kadsuric
acid, and kadsurin [Tetrahedron Letter
s), 4257-4260, 1973] , kads.
urarin (ibid.) , δ-elemenol [Tetrahedron L.
et al., 2899-2901, 1968].
Etc. are known. However, none of them has any known antiandrogenic action.

[0003] The antiandrogenic action is an action of reducing the male hormone activity of testosterone, which is 5α.
Inhibiting the binding of dihydrotestosterone (5α-DHT) to the androgen receptor; an enzyme that reduces testosterone to 5α-DHT (testosterone 5α-
Reductase), and the like. Compounds having such an anti-androgen action are caused by diseases of hair such as androgenetic alopecia and hirsutism; diseases such as prostatic hypertrophy and prostate tumor; and enhanced sebum secretion functions such as acne vulgaris and seborrhea. Is effective in the treatment and prevention of androgen-dependent diseases such as dermatological diseases [Endocrinology and Metabolism Clinics of North America (Endocrinolog)
y and Metabolism Clinics o
f North America), Volume 20, 894-
909, 1991, Trends in Pharma.
macological Sciences), 10
Volume 491-495, 1989].

[0004] The biological activities related to the extract of Saneka quail include hair growth activity (Japanese Patent Application Laid-Open No. 4-1121) and testosterone 5α-reductase inhibitory activity (Japanese Patent Application Laid-Open No. 5-1736) .
5) is known, but all are crude extracts, and the activity of the isolated compound is not known.

[0005]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a novel triterpene acid derivative having an antiandrogen action, particularly an action of inhibiting the binding of 5α-DHT to an androgen receptor, and an antiandrogen containing the compound. Is to provide.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies on the search for novel compounds using the inhibition of binding to the androgen receptor as an index, and as a result, have found that Sanekazura (scientific name: Kadzu)
The above activity was found in a compound obtained from rape japonica, also known as vine perennial. As a result of isolating and purifying this substance, the compound represented by the formula (I)

[0007]

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(Wherein, X represents —O— or a single bond;
R represents hydrogen or hydroxy). Hereinafter, the compound represented by the formula (I) is referred to as compound (I). Hereinafter, specific structural formulas and physicochemical properties of compound (I) are shown. The physicochemical data was measured with the following equipment.

Mass spectrum: Hitachi M-80B mass spectrometer Ultraviolet absorption spectrum: Shimadzu Corporation UV-2200 spectrophotometer Red absorption spectrum: JEOL JIR-RFX3001 Infrared spectrophotometer Nuclear magnetic resonance spectrum: Bruker AM500 Nuclear magnetism Resonance device JEOL JNM-400 Nuclear magnetic resonance device Melting point: Yanagimoto Seisakusho Micro melting point measuring device Optical rotation: JASCO DIP-370 type digital polarimeter Sugar analysis: Dionex BioLC (Column: CarboPac PA1) Compound 1

[0010]

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Properties: colorless powder Melting point: 89.0-92.0 ° C. Molecular weight: 632 Molecular formula: C ₃₆ H ₅₆ O ₉ Specific rotation: [α] _D ²⁵ = + 13.1 ° (c = 1.07, methanol) Infrared absorption spectrum ( KBr method): νcm ^-1 : 3419,2929,1726,1643,1458,1446,1373,1194,1113,1101,1070,754 Ultraviolet absorption spectrum: only showing terminal absorption High-resolution mass spectrometry: [MH ] ^-: Found 631.3813 calculated _{(C 36 H 55 O 9)} 631.3846

Nuclear magnetic resonance spectrum (in CD ₃ OD): ¹ H (4
00MHz) δ ppm: 0.69 (1H), 0.70 (1H), 0.76 (1H), 0.93 (3H,
d), 0.97 (3H, s), 1.03 (3H, s), 1.14 (1H), 1.17 (1H), 1.18 (1
H), 1.35 (1H), 1.36 (2H), 1.37 (1H), 1.39 (3H, s), 1.45 (1H),
1.48 (1H), 1.48 (3H, s), 1.57 (1H), 1.60 (1H), 1.65 (1H), 1.7
2 (2H), 1.75 (1H), 1.82 (1H), 1.92 (3H, d), 1.97 (1H), 2.10 (1H
H), 2.14 (1H), 2.46 (1H), 2.55 (1H), 2.64 (1H), 2.76 (1H), 3.
34 (1H), 3.40 (2H), 3.43 (1H), 3.68 (1H), 3.85 (1H), 5.57 (1
H), 6.10 (1H) ¹³ C (100MHz) δ ppm: 18.7 (q), 19.0 (q), 20.0 (q), 20.7
(q), 23.6 (q), 24.3 (s), 26.6 (t), 27.2 (t), 27.8 (t), 28.2
(t), 28.4 (s), 29.3 (t), 30.4 (t), 31.37 (q), 31.43 (t), 34.2
(t), 35.8 (t), 36.8 (t), 37.0 (t), 37.4 (d), 46.2 (s), 50.0
(s), 50.3 (d), 51.2 (d), 53.7 (d), 62.5 (t), 71.3 (d), 74.1
(d), 78.3 (d), 78.9 (d), 89.4 (s), 95.6 (d), 127.4 (s), 147.3
(d), 167.8 (s), 178.5 (s)

Thin layer chromatography: Rf 0.47
(Purplish red color) color former 5% sulfuric acid ethanol silica gel thin layer (HPTLC RP-18F254 Art13724 Merck) Developing solvent: 95% methanol sugar: HPLC retention time after hydrolysis coincides compound D- glucose preparation 2

[0014]

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Properties: colorless powder Melting point: 127.0-130.0 ° C. Molecular weight: 648 Molecular formula: C ₃₆ H ₅₆ O ₁₀ Specific rotation: [α] _D ³⁰ = + 0.92 ° (c = 0.97, methanol) Infrared absorption spectrum ( KBr method): νcm ^-1 : 3431,2935,1734,1716,1695,1113,1070,754 Ultraviolet absorption spectrum: only showing terminal absorption High-resolution mass spectrometry: [MH] ^- : measured value 647.3763 calculated value _{(C 36 H 55 O 10)} 647.3795

Nuclear magnetic resonance spectrum (in CD ₃ OD): ¹ H (5
00MHz) δ ppm: 0.66 (1H), 0.93 (3H, d), 0.99 (3H, d), 1.07
(3H, s), 1.11 (1H), 1.16 (1H), 1.18 (1H), 1.35 (1H), 1.37 (1H
H), 1.38 (2H), 1.45 (1H), 1.47 (1H), 1.56 (3H, s), 1.57 (1H),
1.58 (1H), 1.65 (2H), 1.71 (3H, s), 1.73 (2H), 1.92 (3H, d),
1.96 (1H), 1.97 (1H), 2.12 (1H), 2.18 (1H), 2.47 (1H), 2.56
(1H), 2.58 (1H), 2.87 (1H), 3.36 (1H), 3.40 (1H), 3.41 (1H),
3.43 (1H), 3.69 (1H), 3.86 (1H), 4.21 (1H), 5.57 (1H), 6.10
(1H) ¹³ C (125 MHz) δ ppm: 18.7 (q), 19.2 (q), 20.3 (q), 20.6
(q), 24.0 (s), 25.5 (q), 27.3 (s), 27.8 (t), 28.1 (t), 29.3
(t), 30.3 (q), 31.3 (t), 32.0 (t), 34.26 (t), 34.33 (t), 36.0
(t), 36.8 (t), 37.0 (t), 37.4 (d), 40.4 (d), 46.4 (s), 49.4
(s), 53.8 (d), 53.9 (d), 62.5 (t), 66.9 (d), 71.2 (d), 74.1
(d), 78.2 (d), 78.9 (d), 90.0 (s), 95.6 (d), 127.3 (s), 147.2
(d), 167.3 (s), 178.9 (s)

Thin layer chromatography: Rf 0.63
(Purplish red color) color former 5% sulfuric acid ethanol silica gel thin layer (HPTLC RP-18F254 Art13724 Merck) Developing solvent: 95% methanol sugar: HPLC retention time after hydrolysis coincides compound D- glucose preparation 3

[0018]

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Properties: colorless powder Melting point: 115.0-116.0 ° C. Molecular weight: 632 Molecular formula: C ₃₆ H ₅₆ O ₉ Specific rotation: [α] _D ²⁵ = −0.39 ° (c = 1.33, methanol) Infrared absorption spectrum (KBr) Method): νcm ^-1 : 3431,2929,1697,1639,1461,1381,1113,1070,756 Ultraviolet absorption spectrum: only showing terminal absorption High-resolution mass spectrometry: [MH] ^- : measured value 631.3813 value _{(C 36 H 55 O 9)} 631.3846

Nuclear magnetic resonance spectrum (in CD ₃ OD): ¹ H (4
00MHz) δ ppm: 0.71 (1H), 0.94 (3H, d), 0.97 (3H, s), 1.11
(3H, s), 1.15 (1H), 1.15 (3H, s), 1.18 (1H), 1.30 (1H), 1.36
(1H), 1.37 (1H), 1.39 (1H), 1.41 (1H), 1.43 (1H), 1.43 (3H,
s), 1.46 (1H), 1.51 (1H), 1.52 (1H), 1.59 (1H), 1.68 (1H), 1.
72 (1H), 1.77 (1H), 1.78 (1H), 1.93 (3H, d), 1.97 (1H), 2.15
(1H), 2.16 (1H), 2.18 (1H), 2.47 (1H), 2.56 (1H), 2.86 (1H),
3.38 (1H), 3.40 (2H), 3.45 (1H), 3.68 (1H), 3.85 (1H), 4.21
(1H), 5.58 (1H), 6.18 (1H) ¹³ C (100 MHz) δ ppm: 18.8 (q), 19.4 (q), 20.3 (q), 20.7
(q), 21.6 (q), 21.8 (s), 23.2 (q), 25.1 (s), 27.4 (t), 27.9
(t), 29.4 (t), 33.0 (t), 34.3 (t), 35.6 (t), 35.6 (t), 36.9
(t), 37.0 (t), 37.5 (d), 38.1 (t), 41.0 (t), 46.9 (s), 49.5
(s), 51.5 (d), 52.1 (s), 53.9 (d), 62.5 (t), 68.0 (d), 71.3
(d), 74.1 (d), 78.3 (d), 78.9 (d), 95.6 (d), 127.4 (s), 147.4
(d), 167.8 (s), 219.0 (s)

Thin layer chromatography: Rf 0.56
(Reddish purple) Coloring agent: 5% sulfuric acid ethanol Silica gel thin layer (HPTLC RP-18F254 Art13724 manufactured by Merck) Developing solvent: 95% methanol Sugar chain: HPLC retention time after hydrolysis matches D-glucose standard

Next, the method for producing the compound (I) will be described. Leaves or whole plants of Sanekazura or its congeners
Extraction is performed with an alcohol such as methanol, ethanol, propanol and butanol, a hydrophilic solvent such as acetone, or a mixed solvent of these hydrophilic solvents and water. Further, if necessary, the residue obtained by removing the solvent from the extract, methanol, ethanol, alcohol such as propanol, butanol, a hydrophilic solvent such as acetone or a mixed solvent of these hydrophilic solvents and water, diethyl ether, An extract containing compound (I) can be obtained by extracting with an organic solvent such as ethyl acetate, chloroform or benzene alone or in combination.

Using the extract as a carrier, Diaion H
Porous polymers such as P-20 (registered trademark; manufactured by Mitsubishi Kasei), Sephadex such as Sephadex LH-20 (registered trademark; manufactured by Pharmacia LKB Biotechnology), normal phase silica gel, reverse phase silica gel, polyamide, It is subjected to column chromatography or preparative high-performance liquid chromatography using activated carbon or cellulose, etc., and thin-layer chromatography (developing solvent: 95% methanol, coloring agent: 5% ethanol sulfate) or androgen receptor binding inhibitory activity (described later) Compound (I) can be obtained by fractional purification while confirming the target component in (see Test Examples). At this time, it is desirable that the column chromatography operation using each carrier is appropriately combined and repeated. Further, if necessary, it can be purified by a recrystallization operation.

Next, the antiandrogenic action of the compound (I) will be described with reference to test examples. Test Example: Androgen Receptor Binding Inhibiting Activity This test was performed in the Journal of Steroid Biochemistry (Journal of Steroid).
Biochemistry), 19, 1141-11
Performed according to the method described on page 46 (1983).

A) Preparation of androgen receptor solution Male Syrian hamster was castrated, and 16 hours later, sebaceous glands were excised and 10 mM Tris-HCl buffer (pH 7.0).
4), 1.5 mM ethylenediaminetetraacetic acid (EDT
A) 1 mM-dithiothreitol (DTT), 10 m
And homogenized the sebaceous glands with a solution of 5 to 20 times volume containing M-Na ₂ MoO ₄ and 10% (V / V) glycerol. Then, this was 33,000 rpm,
After centrifugation at 0 to 4 ° C. for 1 hour, the obtained supernatant was used as an androgen receptor solution.

B) Measurement of androgen receptor binding inhibitory activity 1 nM [ ³ H] R1881 (methyltrienolone, 8
6.0 Ci / nmol), 1 μM triamcinolone acetonide, a mixed solution of the receptor solution and the specimen sample prepared in the above item a) (150 μl in total volume) were incubated at 0 ° C. for 16 hours, and then 0.5% activated carbon and 0.05
500 μl of a solution containing dextran T-70 in%
And left at 0 ° C. for 10 minutes, then 3000 r
The supernatant was obtained by centrifugation at pm for 10 minutes. 300 μl of this supernatant
After collecting and mixing with a liquid scintillation cocktail, [ ³ H] R to the receptor was determined using a liquid scintillator.
The specific binding amount of 1881 was measured, and the obtained data was introduced into the following equation to determine the inhibitory activity as the inhibition rate, and the 50% inhibitory concentration (IC ₅₀ ) was calculated from the inhibition rate.

Inhibition rate (%) = [(cs) / c] × 100 c: receptor protein when no sample is added and [ ³ H]
Specific binding amount to R1881 s: Receptor protein and [ ³ H] R when sample sample was added
Amount of specific binding to 1881 The results are shown in Table 1.

[0028]

[Table 1]

As is clear from the table, the compound (I) is
It showed a marked androgen receptor binding inhibitory effect. Next, the dosage form and dosage of the composition containing compound (I) will be described. The method of administering the composition containing the compound (I) can be any of oral administration, parenteral administration, and external application to the skin, and is not particularly limited, and includes application to the scalp as a hair growth cosmetic. .

The dosage form of the antiandrogen according to the present invention is not particularly limited, and may be tablets, powders, fine granules, granules,
Capsules, injections, oral liquids, suppositories, dermatological agents (linites, lotions, external creams or ointments) and the like. Pharmaceutical compositions can be prepared by uniformly mixing an effective amount of compound (I) as an active ingredient with a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers include, for example, sorbitol, lactose, glucose, dextrin, starch, lactose, light silicic anhydride,
Magnesium aluminate metasilicate, magnesium stearate, polyvinyl alcohol, fatty acid ester, glycerin, polyethylene glycol, sesame oil, p-hydroxybenzoic acid ester, strawberry flavor and the like are used.

The dosage varies depending on factors such as the type, symptom, dosage form, age of the patient and the like of the disease. For adults, Compound (I), which is the active ingredient, is administered in an amount of 0.1 mg orally.
002 to 25 mg / day, 0.005 to 25 mg for suppositories
It is appropriate to administer the drug in 1 to 4 divided doses / day. Further, in the agent for dermis, compound (I) is used in an amount of 0.00001-
A formulation containing 0.1% by weight was prepared.
It is preferable to administer by applying several times a day. For parenteral administration, it is appropriate to prepare a preparation for injection or the like in an amount of 0.001 to 10 mg / day and to administer it in 1 to 4 divided doses. Also, dosages outside these limits can be used, if desired.

Compound (I) can also be used as a cosmetic ingredient. In that case, various components generally used in cosmetics, that is, fats and oils, hydrocarbons, waxes, fatty acids, synthetic esters, alcohols, surfactants, thickeners, humectants, preservatives, fragrances, pigments , A drug, water, and the like. The dosage form of the cosmetic is optional,
For example, dosage forms such as a solubilizing system, an emulsifying system, and a dispersing system can be used. The cosmetic product in the present invention may be in the form of skin care products such as tonics, hair creams, mousses, shampoos, rinses, conditioners, scalp treatments, and makeup products such as lipsticks and foundations.

Examples of the present invention and reference examples will be described below.

[0034]

【Example】

Example 1 5.0 kg of dried leaves of Sanekazura was added to 200 L of methanol.
Then, the mixture was extracted with stirring at room temperature for 16 hours, and then the solvent of the extract was distilled off under reduced pressure to obtain a methanol extract. This extract was extracted with 62 L of 60% methanol-containing water [representing a methanol concentration of 60 (V / V)%], and the solvent of the obtained extract was distilled off under reduced pressure. Suspended, diethyl ether 50
Extracted with L. The diethyl ether layer was evaporated to dryness to obtain 61.2 g of an ether fraction.

The ether fraction was subjected to silica gel (manufactured by Yatron) column chromatography to give chloroform,
It was eluted sequentially with a chloroform-methanol mixed solvent and then methanol. Among the obtained fractions, the fractions eluted with a solvent having a mixture ratio of chloroform: methanol of 15: 1, 10: 1 and 5: 1 were combined and further subjected to silica gel chromatography. The mixing ratio of chloroform-methanol used as a developing solvent is 20: 1,
The fractions eluted with the 15: 1 and 10: 1 solvents were combined, and the mixture was subjected to reversed phase silica gel (ODS type, manufactured by Fuji Devison Chemical Co., Ltd.) column chromatography twice repeatedly (as a developing solvent, , Methanol-water mixed solvent, methanol), fraction A eluted with 75% methanol-containing water, 108 mg, 80%
Fraction B eluted with methanol-containing water, 260 mg, 8
Fraction C eluted with 5% methanol-containing water, 233 mg
I got

213 mg of fraction C was added to Sephadex LH
This was subjected to -20 (Pharmacia) column chromatography, and eluted with 75% methanol-containing water. The obtained fraction having androgen receptor binding inhibitory activity is fractionated by high performance liquid chromatography [a column: COSMOSIL 10C18]
(Nacalai Tesque 50 mm ID x 250 mm, 10 µm gel), developing solvent: water containing 81% methanol, and b column: Deverosil ODS-5 (Nomura Chemical, 20 mm ID x 2)
50 mm, 5 μm gel) and developing solvent: water: methanol: acetonitrile = 26: 40: 34] to give 1,13.5 mg of compound.

Example 2 82 mg of the fraction A obtained in Example 1 was subjected to Sephadex LH-20 (Pharmacia) column chromatography, and eluted with 75% methanol-containing water. The obtained fraction having androgen receptor binding inhibitory activity was fractionated by high performance liquid chromatography [a column: COSMOSIL 1
0C18 (Nacalai Tesque's 20 mm ID x 250 mm, 10 µm gel), developing solvent: water: methanol: acetonitrile = 3
2:40:28, and b column: Deverosil ODS-5
(Manufactured by Nomura Chemical Co., Ltd., 20 mm ID × 250 mm, 5 μm gel), developing solvent: water: methanol: acetonitrile = 33: 4
0:27] to give Compounds 2,2
0.5 mg was obtained.

Example 3 Fraction B (199 mg) obtained in Example 1 was subjected to Sephadex LH-20 (Pharmacia) column chromatography, and eluted with water containing 75% methanol. The obtained fraction having androgen receptor binding inhibitory activity is fractionated by high performance liquid chromatography [a column: COSMOSIL
10C18 (Nacalai Tesque 20mmID x 250mm, 10μm
Gel), developing solvent: water containing 79% methanol, and b
Column: Deverosil ODS-5 (Nomura Chemical, 20 mm ID ×
250 mm, 5 μm gel), developing solvent: water: methanol: acetonitrile = 26: 40: 34] to obtain 3,16.4 mg of compound.

Example 4 (Liniment) Formulation: Compound 1 0.025 mg Tragant 50 g Glycerin 30 ml Ethanol 100 ml Purified water 1000 ml Ethanol 100 ml was collected in a mortar.
025 mg was added and dissolved, and Tragant 50 was added thereto.
g was added and mixed. Next, 30 ml of glycerin was added and mixed, and further mixed while adding 500 ml of purified water to form a paste. Thereafter, purified water was further added to make the total amount 1000 ml and mixed to produce a liniment.

Example 5 (Lotion) Formulation: Compound 2 0.1 mg Hydroxypropylcellulose 1 g Polyethylene glycol 400 10 ml Ethanol 10 ml Purified water Remaining total amount 100 ml Compound 2, 0.1 mg was dissolved in ethanol 10 ml, and polyethylene glycol 400, 10 ml Was added and mixed well. After adding 1 g of hydroxypropylcellulose and mixing, purified water was added to make the total amount 100 ml, and then the mixture was treated with a vacuum homogenizer to produce a lotion.

Example 6 (Hair Liquid) Formulation: Composition for Formulation (Reference Example) 1 mg Vitamin E acetate 0.1 g Pantothenyl alcohol 0.5 g Ethanol 40 ml 1,3-butylene glycol 1 ml Perfume Appropriate amount Purified water Remaining amount 100 ml Above The hair liquid was manufactured according to the conventional method.

Example 7 (Tonic for Hair) Formulation: Composition for Preparation (Reference Example) 1 mg Denatured alcohol 58 ml 1-Menthol 0.1 g 1,3-butylene glycol 1 ml Polyoxyethylene hydrogenated castor oil (60EO) 1 g Perfume Appropriate amount Purified water Remaining amount 100 ml A tonic for hair was manufactured according to the above-mentioned formulation by a conventional method.

Example 8 (External cream or ointment) Formulation: Formulation composition (Reference example) 3 g Diethyl sebacate 8 g Beeswax 5 g Sodium polyoxyethylene oleyl ether phosphate 6 g Sodium benzoate 0.5 g Vaseline balance 100 g With the above formulation, a cream or ointment for external use was produced by a conventional method.

Example 9 (suppository) A suppository was produced by molding according to the above-mentioned formulation by a conventional method.

Example 10 (Powder) A powder was prepared according to the above-mentioned formulation by a conventional method.

Example 11 (granules) Granules were produced according to the above-mentioned formulation by a conventional method.

Example 12 (Tablets, coated tablets and sugar-coated tablets) Formulation: Composition for pharmaceutical preparation (Reference example) 3 mg Microcrystalline cellulose 40 mg Lactose 69.5 mg Corn starch 40 mg Magnesium stearate 7.5 mg 160 mg per tablet

Tablets were prepared according to the above-mentioned formula by a conventional method. On the other hand, a part of the tablets thus obtained was converted into a water-soluble coated tablet by a conventional method using the following coating formulation (weight ratio). Water-soluble coating coating formulation: hydroxypropyl cellulose 4 polyethylene glycol 6000 1 titanium oxide 0.3 talc 0.5 purified water 94.2

Further, a part of the above tablets were made into sugar-coated tablets by a conventional method using the following sub-coating formulation and coloring formulation (weight ratio). Sub-coating formula: Sucrose 40.5 Gelatin 0.5 Gum arabic 1.4 Precipitated calcium carbonate 22 Talc 15.6 Purified water 20 Coloring formula: Sucrose 7 Titanium oxide 50 Lake pigment 39.5 Purified water 3.5

Example 14 (Hard capsule) To 3 mg of the composition for formulation, 121 mg of lactose and 50 mg of corn starch were added and mixed, and an aqueous solution of 16 mg of hydroxypropylcellulose was added and kneaded.
Next, granules were produced by an ordinary method using an extrusion granulator. The granules were filled into hard gelatin capsules to produce hard capsules.

Reference Example (Pharmaceutical Composition) A compound (3, 2 mg) was dissolved in ethanol (100 ml).
To this, 10 mg of dextrin was added and mixed well to obtain a uniform product, which was then dried to obtain a pharmaceutical composition.

[0052]

According to the present invention, there is provided a novel triterpene acid derivative having an antiandrogenic action and an antiandrogen containing the compound.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61P 17/08 A61P 17/08 17/14 17/14 35/00 35/00 43/00 111 43/00 111 (72) Invention Tetsuhiko Suzuki 1-77 Ono-cho, Kasugai-shi, Aichi (72) Inventor Seiko Oishi 1-17, Tenjin-cho, Inuyama-shi, Aichi (72) Inventor Kunio Yagi 2-21, Nishisato-cho, Meito-ku, Nagoya-shi, Aichi (72) Invention Person Mayumi Yoshida 9-18 Isobe, Sagamihara City, Kanagawa Prefecture (72) Inventor Shingo Kakita 3-9-10 Nakamachi, Machida City, Tokyo (72) Inventor Yoshiharu Yokoo 3010-34, Ushikucho, Ushiku City, Ibaraki Prefecture (72) Inventor Nobuyoshi Honda 549-56 Nedo, Abiko City, Chiba Prefecture (72) Inventor Toshio Tatano 2297-6 Ooka, Numazu City, Shizuoka Prefecture (56) References JP-A-4-1121 (JP, A) JP-A-5-17365 (JP) , A) (58) Field surveyed (Int. Cl. ⁷ , DB name) C07H 13/04 A61K 7/00-7/50 A61K 31/7024 CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A compound of the formula (I) (Wherein, X represents -O- or a single bond, and X is -O-
In some cases, R represents hydrogen or hydroxy and X is a single bond
Wherein R represents hydroxy ) or a pharmaceutically acceptable salt thereof. 2. The compound of formula (I) ( Wherein, X represents -O- or a single bond, and X represents -O-
In some cases, R represents hydrogen or hydroxy and X is a single bond
Wherein R represents hydroxy ), or a pharmaceutically acceptable salt thereof. 3. A cosmetic comprising the triterpene acid derivative according to claim 1. 4. A hair growth cosmetic containing the triterpene acid derivative according to claim 1.