KR20120053248A - New use of tanshnone iia - Google Patents

Abstract

PURPOSE: A composition containing tanshinone IIA is provided to effectively suppress androgen and prostate specific antigen. CONSTITUTION: A composition for anti-androgen contains tanshinone IIA as an active ingredient. The composition is used for preventing or treating alopecia, acne, prostate cancer, or prostatitis. The tanshinone IIA is extracted from roots or rhizome of Salvia miltiorrhiza GGE. The composition is a pharmaceutical or food composition. A composition for suppressing prostate specific antigen contains tanshinone IIA as an active ingredient. A composition for preventing or treating alopecia, acne, prostate cancer, or prostatitis contains tanshinone IIA as an active ingredient.

Description

New use of tanshnone IIA

FIELD OF THE INVENTION The present invention relates to novel uses of tanshinone IIA, and more particularly to antiandrogen use or prostate specific antigen inhibition use of tanshinone IIA.

The anti-androgen drug refers to a drug that inhibits the expression of the androgen receptor, and means a drug that inhibits the androgen action. Androgens are male hormones and have a pharmacological mechanism via androgenic receptor (AR), a protein transcription factor that interacts with specific regions of DNA. Therefore, androgens can inhibit androgen action by inhibiting the expression of androgen receptors. Accordingly, the anti-androgen drug can treat, improve or prevent androgen-related diseases or conditions, and as the androgen-related diseases or conditions, prostate cancer, prostatitis, hair loss, acne, oily skin, female hirsutism and the like are known.

In addition, prostate-specific antigen inhibitors are drugs that inhibit prostate-specific antigens by inhibiting the expression of prostate specific antigens, and diseases such as prostate cancer and prostatitis affected by prostate-specific antigens by inhibiting prostate-specific antigens. Or to treat, ameliorate or prevent a condition or the like.

On the other hand, tanshinone ⅡA is not known in relation to anti-androgen use, prostate, especially antigen suppression use.

One problem to be solved by the present invention is to provide a composition for anti-androgens.

In addition, the problem to be solved by the present invention is to provide a composition for inhibiting prostate specific antigen.

In addition, another problem to be solved by the present invention is to provide a composition for the treatment, amelioration or prevention of at least one selected from alopecia, acne, female hirsutism, prostate cancer or prostatitis.

The present invention provides an anti-androgen use of tanshinone IIA, prostate-specific antigen suppression and hair loss, acne, female hirsutism, prostate cancer or prostatitis.

In the present invention, the tanshinone IIA is an IUPAC name of 1,6,6-trimethyl-7,8,9,9b-tetrahydro-3bH-naphtho [1,2-g] [1] benzofuran-10, 11-dione, which can be represented by the following formula (I):

Formula I

The tanshinone ⅡA may be extracted or purchased from the root or rhizome of Salvia miltiorrhiza GGE.

The present invention provides a composition for anti-androgens containing tanshinone IIA as an active ingredient.

The composition may be for the treatment, amelioration or prevention of one or more hair loss, acne, female hirsutism, prostate cancer, or prostatitis. (Homornal therapy for Acne: Semin Cutan Med Surg. 2008 Sep; 27 (3): 188-96 An An alternative pharmacological approach to the detection of anti-androgenic drugs for acne therapy.:Br J Dermatol. 1985 Mar; 112 (3): 329-37.). The treatment, amelioration or prevention may be due to antiandrogen effects.

The anti-androgen may be due to the action of reducing androgen receptor expression.

The composition may be a pharmaceutical composition or a food composition. The pharmaceutical composition may be for the treatment or prevention of one or more hair loss, acne, female hirsutism, prostate cancer, or prostatitis, wherein the food composition is one or more improvement selected from hair loss, acne, female hirsutism, prostate cancer, or prostatitis Or prophylactic.

The present invention also provides a composition for inhibiting prostate specific antigen, comprising tanshinone IIA as an active ingredient.

The extract is not limited thereto, but may be one or more solvents selected from water and alcohols having 1 to 4 carbon atoms, and the solvent may be preferably methanol.

The composition may be for treatment, amelioration or prevention of one or more selected from prostate cancer or prostatitis. The treatment, amelioration or prevention may be due to the prostate specific antigen inhibitory effect.

The composition may be a pharmaceutical composition or a food composition. The pharmaceutical composition may be for the treatment or prevention of one or more selected from prostate cancer, or prostatitis, the food composition may be for the improvement or prevention of one or more selected from prostate cancer, or prostatitis.

The present invention also provides a composition for the treatment, amelioration or prevention of at least one selected from alopecia, acne, female hirsutism, prostate cancer, or prostatitis containing tanshinone IIA as an active ingredient. The treatment, improvement or prevention of the alopecia, acne, female hirsutism, prostate cancer, or prostatitis may be due to anti-androgen effects. In addition, the treatment, improvement or prevention of the prostate cancer, or prostatitis may be due to the anti-androgen effect and / or prostate specific antigen inhibitory effect.

The composition may be a pharmaceutical composition or a food composition. The pharmaceutical composition may be for the treatment or prevention of one or more hair loss, acne, female hirsutism, prostate cancer, or prostatitis, wherein the food composition is one or more improvement selected from hair loss, acne, female hirsutism, prostate cancer, or prostatitis Or prophylactic.

The composition of the present invention may be formulated to include one or more pharmaceutically and / or food acceptable carriers in addition to the active ingredient for administration.

Pharmaceutically and / or food-acceptably acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, as necessary. Other conventional additives, such as antioxidants, buffers, bacteriostatics, can be added. Diluents, dispersants, surfactants, solvents, disintegrants, sweeteners, binders, coatings, swelling agents, lubricants, lubricants or flavoring agents may additionally be added. Furthermore, it may be preferably formulated according to each disease or component by any suitable method in the art or using methods disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.

Formulation forms of the pharmaceutical compositions of the present invention include granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions and sustained release formulations of the active compounds, and the like. This can be

The composition or active ingredient of the present invention may be administered in a conventional manner through intravenous, intraarterial, intraperitoneal, intramuscular, sternum, transdermal, nasal, inhalation, topical, rectal, oral, intraocular or intradermal routes, etc. Can be administered.

In the composition of the present invention, the dosage of the active ingredient can be adjusted within the range of 30mg ~ 150mg per day on the basis of 60kg body weight, can be administered once or divided into several times a day. However, the optimum dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health of the patient It may be adjusted according to various factors including the condition, sex and diet, time of administration, route of administration and the rate of secretion of the composition, the duration of treatment, and the drugs used simultaneously.

The food composition of the present invention may be a health functional food, prepared according to a conventional method, and may be encapsulated after drying with a carrier or formulated in the form of other tablets, granules, powders, beverages, porridge, etc. In addition to one can be produced in all food forms.

The content of the active ingredient in the composition of the present invention may be contained in an amount of 0.08-15% by weight based on the total weight of the composition.

In addition, the present invention is an anti-androgen method comprising a step of administering an active ingredient in a composition of the present invention to a mammal including a human, a method for inhibiting prostate specific antigen and hair loss, acne, female hirsutism, prostate cancer or prostatitis Provided one or more treatments, ameliorations or prophylaxis selected.

The matters mentioned in the uses, compositions and methods of the present invention apply equally unless they contradict each other.

The composition of the present invention is effective for anti-androgen, prostate-specific antigen suppression, and is effective for treating, ameliorating or preventing at least one selected from alopecia, acne, female hirsutism, prostate cancer or prostatitis.

Figure 1 shows the Western blot results confirming the change in the expression level of prostate specific antigen and androgen receptor in the model cells treated with tanshinone ⅡA.
Figure 2 is a graph showing the change in the proportion of prostate specific antigen in accordance with the treatment with tanshinone ⅡA in model cells.

Examples and preparation examples are provided to aid the understanding of the present invention. The following examples and preparations are merely provided to more easily understand the present invention, but the contents of the present invention are not limited by the examples and preparations.

<Example 1> Confirmation of the prostate specific antigen inhibitory effect and anti-androgen effect of tanshinone ⅡA

1-1. Western Blot Method

LNCaP cells expressing androgen receptors were used to confirm the anti-androgen and prostate specific antigen inhibitory effects of tanshinone IIA. Since the LNCaP cells express androgen effects such as expressing androgen receptors, the LNCaP cells were used as a model for confirming that tanshinone IIA exhibited an anti-androgen effect.

In order to confirm the prostate-specific antigen inhibitory effect and anti-androgen effect of tanshinone ⅡA, experiments were performed using the Western blot method in the following manner. Specifically, ⁵ × 10 ⁵ LNCaP cell lines (ATCC, CRL-1740, USA) were plated in a cell culture medium in a T25 culture bottle, and after 24 hours, the groups were divided into groups as shown in FIG. Aldrich, 3uM), androgen inducer Mibolerone (Steraloids Inc, 0.1nM) and / or androgen receptor inhibitor Casodex (Daewoong Pharmaceutical, 40uM) were treated. Each sample was used by dissolving in DMSO (Dimethyl surfoxide). After 24 hours, the cells were collected, and then the cells were collected and separated from the RIPA aqueous solution (50 mM Tris-HCl, pH 7.4, 300). Add mM NaCl, 0.5% Triton X-100, 0.1% SDS, 5 mM EDTA, protease inhibitor cocktail), and leave it on ice for 30 minutes, and process the protein at 14000g for 30 minutes using a centrifuge to separate the protein. Protein quantitation was performed by the Bradford method. Protein quantification was performed using a protein quantification kit (Bio-Rad, Hercules, CA, USA), and the method was performed according to the experimental instructions provided in the kit. 50 ug concentration of the quantified protein was subjected to electrophoresis on SDS-PAGE gel, and the protein spread on the gel was transferred to PVDF membranes (Amersham Biosciences, Piscataway, NJ). Subsequently, it was soaked in 5% nonfat dry milk for 1 hour to remove non-specific proteins from the membrane surface and the primary antibody {AR (BD Phamingen, cat # 554225), PSA (DAKO, cat # A0562), beta-actin ( Sigma Aldrich)} were diluted 1: 1000 and 1: 2000, respectively, and treated at 4 ° C. for one day. Subsequently, the secondary antibody (HRPconjugated secondary antibody-ABD Serotec) is treated at room temperature for 1 hour, and then, using the ECL system kit (Amersham ECL ™ Western Blotting Detection Reagents, # RPN2106), the PSA ( Protein expression of prostate-specific antigen (AR) and android receptor (AR) was confirmed. Untreated cells were used as a control.

 The results are shown in Fig. 1 is a Western blot result confirming the change in the expression level of prostate specific antigen and androgen receptor in the LNCaP cell line with or without tanshinone ⅡA treatment. In FIG. 1,-means untreated sample, and + means processed sample. In addition, AR is the androgen receptor, β-actin is for comparison with the sample sample shows the same amount of protein. PSA stands for prostate specific antigen.

As a result, the group treated with androgen inducer Mibolerone showed more expression of AR and PSA than the control group without the sample, and casodex, known as AR inhibitor, reduced both AR and PSA. Tanshinonone IIA Treatment significantly reduced AR and PSA expressions than casodex despite the lower concentration than casodex.

As shown in Figure 1, tanshinone IIA can be seen that the anti-androgen effect by the prostate specific antigen inhibitory effect and androgen receptor expression inhibition. It is also effective in prostate cancer and prostatitis, which can be prevented, treated or improved by the effect of inhibiting prostate-specific antigens, and prostate cancer, prostatitis, hair loss, acne, and hirsutism in women It can be seen that it is effective in the back.

1-2. In vitro experiment using prostate specific antigen measurement kit

In order to confirm the prostate specific antigen inhibitory effect of tanshinone ⅡA, experiments were performed using the Prostate Specific Antigen Kit in the following manner. Specifically, ⁵ × 10 ⁵ LNCaP cells were plated in 6 well cell culture medium, and after 24 hours, the group was divided into groups as shown in FIG. , 0.1 nM) and / or an androgen receptor inhibitor Casodex (Daewoong Pharmaceutical, 40 uM). Each sample was dissolved in DMSO and used for 24 hours after the cells treated with each sample were collected using the PSA kit (Alpco, cat #. 25-PSAHU-E01). Intracellular / extracellular PSA was measured according to the instructions given in the kit. The same was done for the cells to which the sample was not treated to serve as a control.

The results are shown in Fig. FIG. 2 is a graph showing percentages of PSA in and out of cells compared to the control group when treated with tanshinone ⅡA in a prostate cancer cell line. In FIG. 2, − denotes untreated sample and + denotes treated sample. *** means p <0.001 obtained through statistical significance test.

As shown in Figure 2, it can be seen that the ratio of prostate specific antigen in the tanshinone ⅡA is significantly reduced compared to the control, and showed a comparable effect even at low concentrations compared to casodex.

Therefore, tanshinone ⅡA is effective in inhibiting prostate-specific antigen, and can be seen to be effective in prostate cancer, prostatitis, etc., which can be prevented, treated or improved by the effect of inhibiting prostate-specific antigen.

Preparation Example 1 Preparation of Pharmaceutical Composition

45 mg of tanshinone IIA of Example 1-1, 100 mg of corn starch, 100 mg of lactose, and 2 mg of magnesium stearate were filled into gelatin capsules to prepare a capsule.

Preparation Example 2 Preparation of Food Composition

The remaining amount of water was added to tanshinone ⅡA (4 wt%), liquid fructose (0.5 wt%), oligosaccharide (2 wt%), sugar (2 wt%), and salt (0.5 wt%) of Example 1-1. After adjusting, homogeneously blended and sterilized to prepare a health drink.

Claims (9)

An anti-androgen composition containing tanshinone ⅡA as an active ingredient. The composition of claim 1 for the treatment, amelioration or prevention of at least one selected from alopecia, acne, female hirsutism, prostate cancer or prostatitis. The composition of claim 1, wherein the anti-androgen is by androgen receptor expression reducing action. The composition of claim 1, wherein the composition is a pharmaceutical composition or a food composition. A composition for inhibiting prostate specific antigen, comprising tanshinone ⅡA as an active ingredient. The composition of claim 5 for the treatment, amelioration or prevention of at least one selected from prostate cancer or prostatitis. The composition of claim 5, wherein the composition is a pharmaceutical composition or a food composition. A composition for treating, improving or preventing at least one of hair loss, acne, female hirsutism, prostate cancer, or prostatitis, containing tanshinone ⅡA as an active ingredient. The composition of claim 8, wherein the composition is a pharmaceutical composition or a food composition.

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