JP2015074614A - 5α-REDUCTASE INHIBITOR - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel therapeutic agent useful for prevention and/or treatment of object diseases containing Fucus vesiculosus rhizoid or extract thereof as an active ingredient by resolving the mechanism of hair restoration and growth effects of the Fucus vesiculosus rhizoid by the extract thereof, while considering a high concentration extraction of an activity fraction of the Fucus vesiculosus rhizoid.SOLUTION: The invention provides 5α-reductase inhibitor containing Fucus vesiculosus rhizoid and extract thereof as an active ingredient.

Description

  The present invention relates to a 5α reductase inhibitor containing a kombu temporary root or an extract thereof as an active ingredient. In addition, the present invention relates to a pharmaceutical composition for preventing and / or treating skin diseases and / or prostate diseases, which contains a kombu temporary root or an extract thereof as an active ingredient.

  In recent years, highly safe natural materials have attracted attention in the food field for the purpose of improving male pattern baldness. And the oral composition which has the hair-growth and hair-growth effect using the cultured kombu temporary root part is reported (patent document 1). However, the mechanism of the hair growth and hair growth effect of the kombu temporary root has not yet been elucidated.

  Various mechanisms have been reported to promote hair-growth and hair-growth effects.For example, it acts directly on the hair to grow thicker and increase the overall density, or it acts on the hair matrix cells of the hair root. It is considered to activate hair matrix cells by promoting blood circulation and nutritional supplementation, etc., but there are a variety of mechanisms, and it is also possible that their actions are intricately entangled. There wasn't. In particular, in the case of kombu temporary root, it is not a single compound but a natural material itself, and it is not clear what the active ingredient is, and even a high concentration extract of the active fraction by the extraction operation can be obtained. Until then, there were no reports, and it was expected that the mechanism would be difficult to elucidate.

Japanese Patent No. 4985763

  The present invention examines high concentration extraction of the active fraction of the kombu temporary root, elucidates the mechanism of hair growth and hair growth effect of the kombu temporary root by the extract, and makes the kombu temporary root or its extract an active ingredient It is an object of the present invention to provide a therapeutic agent useful for the prevention and / or treatment of a new target disease.

  As a result of intensive studies to solve the above problems, the present inventors have succeeded in efficiently extracting the active fraction of the kombu temporary root, and found that the extract of the active fraction inhibits 5α reductase. . Furthermore, the present inventors have found out that the organic solvent extract has an excellent inhibitory effect on 5α-reductase type I and type II, among the extracts of the kombu temporary root part. Even in skin diseases involving 5α reductase type I (for example, acne) and / or prostate diseases involving 5α reductase type II (for example, prostatic hypertrophy), the kombu temporary root or its extract exhibits a therapeutic effect. As a result, the present invention was completed.

That is, the present invention
[1] A 5α reductase inhibitor containing a kombu temporary root or an extract thereof as an active ingredient;
[2] The 5α reductase inhibitor according to [1] above, wherein the 5α reductase is type I or type II;
[3] The 5α reductase inhibitor according to [1] or [2] above, wherein the extract is a water extract or an organic solvent extract;
[4] The 5α reductase inhibitor according to the above [3], wherein the organic solvent contains ethanol, chloroform, benzene, ethyl acetate and / or n-hexane;
[5] A pharmaceutical composition for preventing and / or treating a skin disease and / or a prostate disease, which comprises a kombu temporary root or an extract thereof as an active ingredient;
[6] The pharmaceutical composition according to the above [5], wherein the skin disease is acne;
[7] The pharmaceutical composition according to the above [5], wherein the prostate disease is benign prostatic hyperplasia; and [8] a method for preparing a kombu temporary root extract, wherein the kombu temporary root is extracted using a solvent, A method is provided comprising filtering and then concentrating the filtrate.

The present invention also provides
[9] A method for inhibiting 5α reductase, comprising administering to a patient in need of treatment a therapeutically effective amount of a kombu temporary root or an extract thereof;
[10] Use of kombu temporary root or an extract thereof for producing a 5α reductase inhibitor; and [11] A pharmaceutical composition containing kombu temporary root or an extract thereof for use in inhibiting 5α reductase. Is to provide.

  Furthermore, the present invention relates to the drug, the pharmaceutical composition, the method, and the method according to the above [1] to [11], which use a kombu temporary root or an extract thereof, for the prevention and / or treatment of a disease caused by the action of 5α reductase. Provide use.

According to the present invention, the temporary root of a kombu or an extract thereof effectively inhibits 5α reductase, thereby exhibiting an excellent therapeutic effect on skin diseases such as acne and / or prostate diseases such as prostatic hypertrophy. Can be expected to do. Since the present invention uses a kumbu temporary root portion or an extract thereof, which is a natural material, a therapeutic effect with few side effects can be expected.
Moreover, it can be anticipated that the therapeutic effect of male pattern baldness due to hair growth and hair growth by the kombu temporary root itself can be effectively improved by using the extract of the kombu temporary root.

  The 5α reductase inhibitor of the present invention comprises a kombu temporary root or an extract thereof as an active ingredient.

  The “comb temporary root portion” used in the present specification refers to a portion that mainly includes the temporary root portion of the kombu and may include a petiole, and is a portion that was previously not used for food and discarded. Ordinary kombu products are manufactured from the portion excluding the tip and the lower end of the leaf-like body, and the lower end of the leaf-like body is used as a root kelp. The kind of the comb used in the present invention may be a natural comb or a cultured comb. Such combs include, but are not limited to, macomb, honey comb, resilive, and the like.

  The “comb temporary root extract” used in the present specification is obtained by extracting from a kombu temporary root part using various solvents. Examples of such extraction methods include, but are not limited to, hot water extraction method, boiling extraction method, immersion extraction method, shaking extraction method, Soxhlet extraction method, steam distillation method and the like. In one preferred embodiment, the kombu temporary root extract is a water extract or an organic solvent extract. In one more preferred embodiment, the kombu temporary root extract is an organic solvent extract.

  Extraction solvents include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, chloroform, etc.), ethers (ethyl ether, tetrahydrofuran, propyl) Ether, etc.), but is not limited thereto. Preferred are water and organic solvents such as lower alcohols, esters and hydrocarbons, and particularly preferred are ethanol, chloroform, benzene, ethyl acetate and / or n-hexane. These solvents may be used singly or in combination of two or more, and the organic solvent may contain water.

  10-1000 mL is preferable with respect to 10 g of kombu temporary root parts (dry mass conversion), and, as for the usage-amount of an extraction solvent, 20-500 mL is more preferable.

  The extraction temperature may be appropriately determined depending on each solvent, but is preferably 10 to 100 ° C, more preferably 20 to 80 ° C. When extraction temperature is less than 10 degreeC, there exists a tendency of extraction failure, and when it exceeds 100 degreeC, there exists a tendency for an extract to decompose | disassemble.

  The extraction time may be appropriately determined depending on each solvent, but is preferably 1 minute to 96 hours, and more preferably 5 minutes to 24 hours. If the extraction time is less than 1 minute, there is a tendency for poor extraction, and if it exceeds 96 hours, there is a tendency that a higher extraction rate can no longer be desired.

  The extract may be used as it is, or may be used after concentration, dilution and filtration treatment, decolorization with activated carbon, deodorization treatment, or the like, if necessary. Further, the extracted solution may be subjected to treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

  As a method for preparing the extract of the kombu temporary root part, 10 to 1000 mL, preferably 20 to 500 mL of a solvent is added to 10 g of the kombu temporary root part, extracted at 20 to 80 ° C. for 5 minutes to 24 hours, filtered, The method of concentrating a filtrate is mentioned.

  The 5α reductase inhibitor of the present invention only needs to contain the kombu temporary root part or an extract thereof as an active ingredient, and further includes excipients and the like as long as the 5α reductase inhibitory effect by the kombu temporary root part or an extract thereof is not hindered. May be included. Therefore, the ratio of the kombu temporary root portion or the extract thereof in the 5α reductase inhibitor of the present invention is not particularly limited. Or the 5 (alpha) reductase inhibitor of this invention may consist only of a kombu temporary root part or its extract.

5α reductase (5α-SR) is an enzyme that uses NADPH as a coenzyme and reduces steroids having a 4-en-3-one structure such as testosterone, progesterone, and cortisol to 5α-form 3-ketosteroids. (See DW Russell, JD Wilson, Steroid 5α-reductase: Two genes / two enzymes, Annu. Rev. Biochem. 63, 25 (1994)). For 5α reductase, type I (5α-SR1, optimum pH is 7.0, K _m = 1-5 μM) and type II (5α-SR2, optimum pH is 5.5, K _m = 4-50 nM) There are two types of isozymes, and usually the former is mainly expressed in the liver and the latter is mainly expressed in the prostate.
5α reductase metabolizes testosterone to 5α-dihydrotestosterone (5α-DHT), which is an active androgen receptor having high affinity by the reduction reaction, by chemical reduction (Chemical Formula 1). 5α reductase has been reported to function as an enzyme that regulates the action of male hormones (R. Ge, DO Hardy, JF Catterall and MP Hardy, Opposing Changes in 3α-Hydroxysteroid Dehydrogenase: Oxidative and reductive activities in rat leydig cells during pubertal development. Biol. Reproduct., 60, 855 (1999)), and 5α-DHT exhibits various physiological actions such as sperm formation and sexual differentiation through binding to the androgen receptor. It has been reported to function as an aversion factor for prostate diseases such as prostatic hypertrophy and prostate cancer, acne and androgenetic alopecia (DW Russell, JD Wilson, Steroid 5α-reductase: Two genes / two enzymes, Annu. Rev Biochem. 63, 25 (1994); R. Ge, DO Hardy, JF Catterall and MP Hardy, Opposing Changes in 3α-Hydroxysteroid Dehydrogenase: Oxidative and reductive activities in rat leydig cells during pubertal development.Biol. Reproduct., 60, 855 (1999); JD Wil son, The pathogenesis of benign prostatic hyperplasia, Am. J. Med., 68, 745 (1980); DJ Tindall and RSRittmaster, The rationale for inhibiting 5α-reductase isoenzymes in the prevention and treatment of prostate cancer, J. Urology, 179 , 1235 (2008); Journal of the Japan Cosmetic Science Society, 21 (3), 200-202 (1997)). Therefore, 5α-reductase involved in the production of 5α-DHT is a substance that is suggested to be associated with skin diseases and / or prostate diseases, particularly those that are deeply involved in the development and / or progression of acne and benign prostatic hyperplasia. It is. Therefore, the konbu temporary root part and its extract, which have been found to inhibit 5α reductase, are useful as active ingredients in pharmaceutical compositions with few side effects for the prevention and / or treatment of skin and / or prostate diseases. It is.

  Therefore, in one embodiment, the present invention provides a pharmaceutical composition for preventing and / or treating skin diseases and / or prostate diseases, which contains a kombu temporary root or an extract thereof as an active ingredient.

  As used herein, “disease caused by the action of 5α reductase” includes, for example, skin diseases, prostate diseases and the like.

  Examples of “skin diseases” as used herein include acne, proliferative and inflammatory skin diseases, psoriasis, cancer, epidermitis, alopecia, skin atrophy, steroid-induced skin atrophy, dermatitis, atopic dermatitis , Seborrheic dermatitis, contact dermatitis, urticaria, psychogenic pruritus, eczema and the like, but are not limited thereto. Acne is preferable as the skin disease in the present invention.

  Examples of “prostate disease” as used herein include, but are not limited to, benign prostatic hyperplasia, prostate cancer, and the like. Prostatic hypertrophy is preferred as the prostate disease in the present invention.

  As used herein, “treatment” of skin disease or prostate disease also includes preventing the progression of symptoms in a patient already suffering from skin disease or prostate disease.

  The amount of the kombu temporary root portion or extract thereof to be contained as an active ingredient in the pharmaceutical composition of the present invention can be appropriately selected according to the intended dosage form and the like, but it is 1 to 98 mass based on the total composition. %, Preferably about 2 to 95% by weight, more preferably about 3 to 90% by weight.

  The dosage form of the present invention can be appropriately selected and prepared according to the physical condition, health condition, etc. of the subject. For example, tablets (orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets), capsules, granules (effervescent granules), powders, oral solutions (elixirs, suspensions, emulsions, limonades) , Syrup (syrup preparation), oral jelly, oral tablet (troche, sublingual tablet, buccal tablet, adhesive tablet, gum), oral spray, oral semisolid preparation, mouthwash, injection (Infusion, implantable injection, continuous injection), dialysis agent (peritoneal dialysis agent, hemodialysis agent), inhalant (inhalation powder, inhalation solution, inhalation aerosol), suppository, rectal half Solid preparations, enema preparations, eye drops, eye ointments, ear drops, nasal drops (nasal powders, nasal drops), vaginal tablets, vaginal suppositories, external solid preparations (external powders), external liquids (Liniment, lotion), spray (external aerosol, pump spray), soft , Creams, gels, patches (tape, cataplasms), and the like.

  The administration method of the present invention is not limited, but is oral, intraarterial, intravenous, intravenous infusion, continuous infusion, subcutaneous, intramuscular, intradermal, intraarticular, intraperitoneal, intracapsular, air Intraductal, intrapulmonary, intracapsular, intrathoracic, intracardiac, intrauterine, intraoral, buccal, sublingual, inhalation, dental, intracerebral, intraocular, conjunctival, intranasal, otic, intrarectal, intravaginal, Examples include aeration, local, whole body, intravesical, intraurethral, local injection, meninges, intrathecal, subarachnoid, epidural, intramedullary, intratendon sheath, nerve trunk, implantation and the like.

  The pharmaceutical composition of the present invention is a known method for other pharmaceutically active ingredients and additives as long as it does not interfere with the preventive and / or therapeutic effects of skin diseases and / or prostate diseases caused by the root of the kombu or its extract. May be blended as appropriate.

  Additives to be blended in the pharmaceutical composition of the present invention are not limited, but include crude drugs, natural products, stabilizers, surfactants, improvers, plasticizers, lubricants, capsule films, Solubilizers, reducing agents, buffering agents, sweeteners, bases, volatilization aids, adsorbents, flavoring agents, synergists, binders, suspending agents, antioxidants, brighteners, efficacy enhancers, coatings Agent, skin, support, sustaining agent, wetting agent, wetting conditioner, filler, antifoaming agent, cooling agent, feeding accelerator, adhesive agent, enhancer, chewing agent, flavoring agent / fragrance, Coloring agent, sugar-coating agent, isotonic agent, softener, emulsifier, combustion agent, adhesive agent, adhesion enhancer, thickener, thickener, flame retardant, exothermic agent, foaming agent, pH adjuster, Skin protectant, excipient, floater, dispersant, propellant, disintegrant, disintegration aid, fragrance, rust inhibitor, moisture barrier, controlled release film, antiseptic, preservative, soothing agent, attractant , Solubilizer, solubilizing agents, solvents, release agents, flow agents and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention still in detail, this invention is not limited to these Examples.

(Example 1)
Preparation of Kombu temporary root extract 100 g of Kombu temporary root powder (trade name: Ganashi powder, manufactured by Kaigen Pharma Co., Ltd.) was extracted under conditions of 25 ° C. and 24 hours using 800 ml of various solvents, and then a glass filter. (G3, manufactured by Sansho Co., Ltd.) and the filtrate was concentrated under reduced pressure, and then the amount (g) and the extract shown in Table 1 were obtained.

(Example 2)
1. Inhibitory effect on 5α reductase type I Preparation of rat liver microsome fraction A 10-week-old Jcl: Wistar male rat was decapitated and exsanguinated under ether anesthesia, and the liver was removed. The excised liver was shredded, 3 volumes of 1.15% KCl and 0.1 mM EDTA-containing 3 mM Tris-HCl buffer (pH: 7.4) were added, and a Potter-Elvehjem type homogenizer (ASONE stock) was cooled with ice. 25% homogenate was prepared using Subsequently, the 25% homogenate was centrifuged at 9,000 g for 20 minutes at 4 ° C., and the resulting supernatant was further centrifuged for 60 minutes at 105,000 g at 4 ° C., and the resulting precipitate was treated with 10 mM phosphate buffer ( A microsomal fraction that was suspended in pH: 7.4) and was rich in 5α-reductase type I was prepared. The protein concentration was quantified by the bicinchoninic acid method (PKSmithm et al., Measurement of protein using bicinchoninic acid. Anal. Biochem., 150, 76, 1985).

2. Measurement of inhibitory effect on 5α-reductase type I in incubation experiment Incubation experiment was conducted by using the kombu temporary root powder and the extract of kombu temporary root, and the inhibitory effect on 5α reductase type I was measured.
Each sample (100 μg) is added to a substrate with testosterone (138.7 μmol / l), 200 μl of 40 mM phosphate buffer (pH: 7.0) containing 0.3 M sucrose and 1 mM dithiothreitol is added, and the final concentration of NADPH Was added to a concentration of 1 mM, a rat liver microsome fraction (100 μl, protein amount less than 40 μg) was added as an enzyme source, and the mixture was incubated at 37 ° C. for 30 minutes. After completion of the incubation, an internal standard substance was added under ice-cooling, subjected to Bond Elut-C18 (manufactured by Agilent Technologies), washed with purified water (5 ml) and 50% methanol (5 ml), and then 90% methanol (5 ml). After the solvent was distilled off under reduced pressure, heptafluorobutyric anhydride (50 μl) was added and heated at 30 ° C. for 10 minutes. After evaporating the reaction solution under reduced pressure, n-hexane / ethyl acetate (3: 1, 500 μl) was added, applied to a silica gel column (30 × 8 mm), and eluted with n-hexane / ethyl acetate (3: 1, 5 ml). . The solvent was distilled off under reduced pressure, then dissolved in 30 μl of acetone, and 1 μl thereof was injected into a gas chromatograph (Agilent Technologies 6890N, manufactured by Agilent Technologies) equipped with a flame ionization detector.

<Measurement conditions for gas chromatography>
The column used was a non-polar dimethylpolysiloxane-based capillary column (DB-1, 30 mx 0.25 mm id, manufactured by Agilent Technologies). The column temperature was held at 170 ° C. for 3 minutes, then the temperature was increased to 220 ° C. at a rate of 5 ° C./minute, and then programmed to 300 ° C. at a rate of 3 ° C./minute. Helium was used as the carrier gas, and the flow rate was adjusted so that the linear velocity was 39 cm / sec.

  The inhibition rate is obtained from the following inhibition rate calculation formula by calculating the decrease in the reaction rate when each sample is added with the reaction rate (control) when no sample is added being 100% (inhibition rate 0%). It was. Since testosterone is metabolized to dihydrotestosterone and further metabolized to produce androstanediol, the peak area (amount) of the 5α-reductase type I metabolite includes androstanediol.

Inhibition rate (%) = 100 − [(a ′ + b ′ / c ′) × 100] / (a + b / c)
a ′: peak area of dihydrotestosterone (sample addition)
b ′: androstanediol peak area (sample addition)
c ′: Peak area of internal standard substance (sample addition)
a: Peak area of dihydrotestosterone (control)
b: Peak area of androstanediol (control)
c: Peak area of internal standard (control)

It was confirmed that the konbu temporary root part or an extract thereof, which is an active ingredient of the 5α reductase inhibitor of the present invention, has an inhibitory effect on 5α reductase type I. The results are shown in Table 2 (data are average values).

  The inhibition rate for 5α-reductase type I of kombu temporary root powder and its water extract was 31.6% and 37.9%, respectively, but the inhibition rate was significantly increased by extracting with organic solvent. did. From the above results, it is recognized that the kombu temporary root and its extract have an inhibitory effect on 5α-reductase type I, and in particular, the organic solvent extract has an excellent inhibitory effect on 5α-reductase type I.

(Example 3)
1. Inhibitory effect on 5α reductase type II Preparation of rat prostate microsomal fraction 10-week-old Jcl: Wistar male rats were decapitated and exsanguinated under ether anesthesia, and the prostate was removed. The excised prostate is shredded, 3 volumes of 0.3 M sucrose and 1 mM dithiothreitol-containing 40 mM phosphate buffer (pH: 6.5) are added, and a Potter-Elvehjem type homogenizer (manufactured by ASONE CORPORATION) is cooled with ice. ) Was used to prepare a 25% homogenate. Subsequently, the homogenate was centrifuged at 1,500 g for 20 minutes at 4 ° C., and the resulting supernatant was further centrifuged for 60 minutes at 105,000 g at 4 ° C., and the resulting precipitate was treated with 0.3 M sucrose and 1 mM dithiothreitol. A microsomal fraction in which 5α reductase type II was abundant was prepared by suspending in a 40 mM phosphate buffer (pH: 7.5). The protein concentration was quantified by the bicinchoninic acid method (PKSmithm et al., Measurement of protein using bicinchoninic acid. Anal. Biochem., 150, 76, 1985).

2. Measurement of Inhibitory Effect on 5α Reductase Type II in Incubation Experiment An incubation experiment was carried out by the following method using the kombu temporary root powder and the extract of the kombu temporary root, and the inhibitory effect on 5α reductase type II was measured.
Each sample (100 μg) is added to a substrate with testosterone (138.7 μmol / l), 200 μl of 40 mM phosphate buffer (pH: 5.5) containing 0.3 M sucrose and 1 mM dithiothreitol is added, and the final concentration of NADPH Was added to a concentration of 1 mM, a rat prostate microsome fraction (100 μl, protein amount less than 1.2 mg) was added as an enzyme source, and the mixture was incubated at 37 ° C. for 60 minutes. After completion of the incubation, an internal standard substance was added under ice cooling, attached to Bond Elut-C18 (manufactured by Agilent Technologies), washed with purified water (5 ml) and 50% methanol (5 ml), and washed with 90% methanol (5 ml). ). After the solvent was distilled off under reduced pressure, heptafluorobutyric anhydride (50 μl) was added and heated at 30 ° C. for 10 minutes. After evaporating the reaction solution under reduced pressure, n-hexane / ethyl acetate (3: 1, 500 μl) was added, applied to a silica gel column (30 × 8 mm), and n-hexane / ethyl acetate (3: 1, 5 ml). Eluted. After the solvent was distilled off under reduced pressure, it was dissolved in 30 μl of acetone, and 1 μl thereof was injected into a gas chromatograph and measured. The measurement conditions for gas chromatography are the same as the above <measurement conditions for gas chromatography>.
The inhibition rate is obtained from the above inhibition rate calculation formula by calculating the decrease in the reaction rate when each sample is added with the reaction rate (control) when no sample is added being 100% (inhibition rate 0%). It was. The peak area (amount) of the 5α reductase type II metabolite includes androstanediol.

It was confirmed that the konbu temporary root part or an extract thereof, which is an active ingredient of the 5α reductase inhibitor of the present invention, has an inhibitory effect on 5α reductase type II. The results are shown in Table 3 (data are average values).

  From the above results, when using the kombu temporary root powder as a sample, the inhibition rate for 5α-reductase type II was 0.1%, showing almost no inhibitory effect, but the organic solvent extract showed an excellent inhibitory effect. It is done. It is considered that the inhibitory effect of the kombu temporary root powder may be suppressed by the action of components other than the inhibitory component of 5α reductase type II contained in the powder under the conditions of this experiment. Since the organic solvent extract of kombu temporary root powder has an excellent inhibitory effect, it is clear that the 5 k reductase type II inhibitory component is contained in the kombu temporary root powder. Accordingly, it is recognized that the kombu temporary root powder itself has an inhibitory effect on 5α-reductase type II, and in particular, the organic solvent extract is recognized to have an excellent inhibitory effect on 5α-reductase type II.

Claims (8)

  A 5α-reductase inhibitor containing a kombu temporary root or an extract thereof as an active ingredient.   The 5α reductase inhibitor according to claim 1, wherein the 5α reductase is type I or type II.   The 5α reductase inhibitor according to claim 1 or 2, wherein the extract is a water extract or an organic solvent extract.   The 5α reductase inhibitor according to claim 3, wherein the organic solvent contains ethanol, chloroform, benzene, ethyl acetate and / or n-hexane.   A pharmaceutical composition for preventing and / or treating a skin disease and / or a prostate disease, comprising a knot temporary root or an extract thereof as an active ingredient.   The pharmaceutical composition according to claim 5, wherein the skin disease is acne.   6. The pharmaceutical composition according to claim 5, wherein the prostate disease is benign prostatic hyperplasia.   A method for preparing a kombu temporary root extract, the method comprising extracting the kombu temporary root with a solvent, filtering, and then concentrating the filtrate.