JP5143993B2 - Estrogen-like active agent - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention includes premenstrual syndrome and / or coronary artery disease and osteoporosis in adult women by administering an effective amount of an estrogen-like active agent containing an extract of Ganoderma lucidum and the active agent The present invention relates to a method for suppressing symptoms of menopause and / or postmenopausal disorders, or symptoms of prostate cancer and hypertrophy of adult men.
[0002]
[Prior art]
[Patent Document 1]
JP 2003-012533 A [Patent Document 2]
Japanese Patent Laid-Open No. 2001-122871
Estrogen is a steroidal estrus hormone, and many substances are known not only naturally but also synthetically. Estrogens present in humans are produced mainly by the ovary and play an important role in the development of female secondary sexual characteristics, endometrial proliferation, regulation of sexual function, regulation of bone metabolism, regulation of lipid metabolism, and the like. Therefore, the pre-menopausal, post-menopausal, and post-menopausal estrogen content of women with decreased ovarian function is reduced, and symptoms of premenstrual syndrome, menopause and / or post-menopausal disorders such as autonomic ataxia, menopause Various symptoms and diseases such as disability, decreased sexual function, coronary heart disease, and osteoporosis are caused. In order to prevent and treat these symptoms and diseases, estrogen replacement therapy is performed.
[0004]
Various substances having estrogenic activity derived from plants are known. For example, Patent Document 1 describes that a dried ground fruit extract of a plant carrot can directly interact with an estrogen receptor to alleviate the above symptoms. Patent Document 2 discloses that deoxymiroesterol extracted from the root of Pueraria mirifica, a leguminous genus plant, has strong estrogenic activity and is effective in treating various symptoms and diseases dependent on estrogen. Have been described.
[0005]
On the other hand, a number of medicinal effects have been passed down to Mannentake (Reishi), and it is known that there are substances that have various physiological effects, in addition to being known as a mushroom particularly effective against cancer. However, it has not yet been known that Mannentake extract has estrogenic activity.
[0006]
[Problems to be solved by the invention]
It is an object of the present invention to provide an extract of garlic mushroom (reishi) having estrogenic activity.
[0007]
[Means for Solving the Problems]
As a result of various studies on the medicinal and physiological effects of an extract of Ganoderma lucidum, the present inventors have found that the extract is derived from human breast cancer, which is known to proliferate in an estrogen-dependent manner. The present invention was completed by finding that the cells proliferate remarkably when used in MCF-7 cells.
That is, the present invention is an estrogen-like active agent characterized by containing an extract of Ganoderma lucidum.
[0008]
The estrogen-like active agent according to the present invention is a disease / symptom caused by a decrease in estrogen content in the body, for example, symptoms of menopausal and / or postmenopausal disorders including premenstrual syndrome and / or coronary heart disease and osteoporosis in women, It has therapeutic and preventive effects on men's prostate cancer and benign prostatic hyperplasia.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
The estrogen-like active agent of the present invention is an extract of Ganoderma lucidum, commonly referred to as ganoderma.
Ganoderma lucidum (Ganoderma lucidum) used in the present invention is a basidiomycete belonging to the genus Sarnia mushroom family, and has been called Ganoderma or turfgrass in China, and has been called Ganoderma or Saiwaitake in Japan. It is a mushroom of the genus Ganoderma in the Ganoderma taceae belonging to the eyes (Ganoderma tales).
[0010]
For the extraction of banyan mushroom used in the present invention, an organic solvent such as methanol, n-hexane, ethanol, ether, ethyl acetate or water is used, and an organic solvent extraction method and a Soxhlet extractor which are extracted by impregnation with water are used. The Soxhlet extraction method by heating and reflux using can be applied, but is not limited to these methods.
[0011]
For example, the methanol extraction method is a method in which fruit bodies of Ganoderma lucidum are ground, added with methanol, allowed to stand at room temperature for one day, an extract is taken out, and methanol is further added to the residue for extraction. An extract can be prepared by performing this operation three times in total and concentrating and drying the resulting extract together.
In the extraction process of the present invention, decolorization and deodorization treatment with activated carbon or the like may be performed, or heat sterilization may be performed.
[0012]
The estrogen-like active agent according to the present invention may contain additives such as a pharmaceutically acceptable carrier. Specifically, various organic or inorganic carrier substances commonly used as pharmaceutical materials are used. Excipients, lubricants, binders, disintegrants, thickeners in solid preparations; solvents, dispersants, dissolution agents in liquid preparations It is added as an adjuvant, suspending agent, tonicity agent, buffering agent, soothing agent and the like. If necessary, additives such as preservatives, antioxidants, colorants, sweeteners and the like can be used.
[0013]
Preferable examples of the excipient include lactose, sucrose, D-mannitol, starch, crystalline cellulose, light anhydrous silicic acid and the like. Preferable examples of the lubricant include magnesium stearate, calcium stearate, talc, colloidal silica and the like.
Preferable examples of the binder include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone and the like. Preferable examples of the disintegrant include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, carboxymethyl starch sodium and the like.
[0014]
Preferable examples of the thickener include natural gums, cellulose derivatives, acrylic acid polymers and the like.
Preferable examples of the solvent include water for injection, alcohol, propylene glycol, mark gol, sesame oil, corn oil and the like.
Preferable examples of the dispersant include Tween 80, HCO 60, polyethylene glycol, carboxymethyl cellulose, sodium alginate and the like.
Preferable examples of the solubilizer include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.
[0015]
Suitable examples of the suspending agent include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and xericerin monostearate; for example, polyvinyl alcohol, Examples thereof include hydrophilic polymers such as polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.
Preferable examples of the isotonic agent include sodium chloride, glycerin, D-mannitol and the like.
Preferable examples of the buffer include buffer solutions such as phosphate, acetate, carbonate and citrate.
[0016]
Preferable examples of the soothing agent include benzyl alcohol.
Preferable examples of the preservative include paraoxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.
Preferable examples of the antioxidant include sulfite and ascorbic acid.
[0017]
The estrogenic active agent of the present invention is, for example, oral administration of tablets, capsules, granules, drinks, etc., administration by systemic routes such as intravenous infusion or injection, or parenteral administration such as intramuscular injection, Enteral administration or local administration may be used. Specific examples of the pharmaceutical preparation are shown below.
(1) Tablets, powders, granules, capsules: The pharmaceutical composition of the present invention is compression-molded by adding, for example, an excipient, a disintegrant, a binder or a lubricant, and then, if necessary, It can be produced by coating for masking, enteric or persistent purposes.
[0018]
(2) Injection: The inhibitor of the present invention is dissolved in a vegetable oil such as olive oil, sesame oil, cottonseed oil, corn oil, propylene glycol, etc. as an aqueous injection together with a dispersing agent, preservative, tonicity agent, etc. It can be produced by suspending or emulsifying and molding it as an oily injection.
(3) External preparation: produced by making the inhibitor of the present invention into a solid, semi-solid or liquid composition. For example, the solid composition can be produced by using the inhibitor as it is, or by adding and mixing an excipient, a thickener and the like into a powder form.
The liquid composition is almost the same as in the case of an injection, and is produced by making it an oily or aqueous suspension. The semi-solid composition is preferably an aqueous or oily gel or ointment. In addition, any of these compositions may contain a buffering agent, a preservative, and the like.
[0019]
(4) Suppository: manufactured by making the inhibitor of the present invention into an oily or aqueous solid, semi-solid or liquid composition. Examples of the oily base used in such a composition include glycerides of higher fatty acids (for example, cocoa butter, vitepsols), intermediate fatty acids (for example, miglyols), or vegetable oils (for example, sesame oil, soybean oil, Cottonseed oil, etc.). Examples of the aqueous gel base include natural gums, cellulose derivatives, vinyl polymers, and acrylic acid polymers.
[0020]
The estrogen-like active agent of the present invention is generally administered at a daily dose of 1.0 mg to 100 mg per kg of body weight, and is administered in one to several divided doses. The pharmaceutically effective amount and administration method or administration means, treatment The period depends on the pathological state of the target patient and animal.
[0021]
Since the extract from Ganoderma lucidum according to the present invention has estrogenic activity, diseases and symptoms caused by decreased estrogen content in mammals, particularly humans, such as premenstrual syndrome in women And / or a therapeutic / preventive effect on symptoms of menopausal and / or postmenopausal disorders, including coronary artery disease, osteoporosis, lipid metabolism abnormality, menopause, and decreased sexual function. In addition, it has therapeutic and preventive effects on male prostate cancer, benign prostatic hyperplasia, alopecia and the like.
[0022]
【Example】
Example 1
10 g of fruit bodies of Ganoderma lucidum were pulverized to obtain mannentake powder, which was suspended in 250 ml of methanol and immersed overnight at room temperature with occasional stirring. This was filtered to obtain an extract. The filtration residue was newly suspended in 250 ml of methanol and the above extraction was repeated. This operation was performed three times, and the extract was collected and concentrated with an evaporator to dryness to obtain 1.8 g of mannentake extract. A part of this was dissolved in dimethyl sulfoxide (DMSO) to obtain a nanentake extract DMSO solution having a predetermined concentration.
On the other hand, human breast cancer-derived MCF-7 cells were precultured in phenol-red-free RPMI 1640 supplemented with 10% FBS (fetal bovine serum) in a 90 mm diameter culture dish. After removing the medium and washing twice with FBS, the cells were detached and collected with 0.2% tripsin / FBS, adjusted to 4 × 10 ⁴ cells / ml with the medium, and seeded on a 24 well plate at 1 ml / well. . After culturing for 24 hours, the medium was replaced with a medium without addition of serum. After further culturing for 24 hours, the medium was replaced with 1% cFBS (charcol-treated FBS) PRF RPMI1640. At the same time as the medium exchange, the Mannen extract DMSO solution was added to the medium so that the concentration of the extract was 0.01 to 10 ppm (w / v). Further, after culturing for 5 days (medium exchange once every two days), the number of cells was measured using a hemocytometer to evaluate cell proliferation. Moreover, 17β-estradiol (E2), which is an estrogen, was used as positive control.
The measurement was repeated three times, and the average value is shown in FIG. In FIG. 1, E2 used as positive control promoted cell growth up to 175% of control. On the other hand, the garlic mushroom extract showed a lower activity than control at 10 ppm, suggesting cytotoxicity, but promoted cell growth at 0.01-1 ppm. In particular, at 0.1 ppm, an activity comparable to that of E2 was observed, indicating an estrogenic activity.
[0023]
【Effect of the invention】
The estrogen-like active agent containing the garlic mushroom extract according to the present invention is a disease or symptom caused by a decrease in the estrogen content in a mammal, particularly a human body, such as premenstrual syndrome and / or coronary disease in women. It has a therapeutic / preventive effect on symptoms of menopause and / or postmenopausal disorders including osteoporosis, abnormal lipid metabolism, climacteric disorder, decreased sexual function and the like. In addition, it has therapeutic and preventive effects on male prostate cancer, benign prostatic hyperplasia, alopecia and the like.
[Brief description of the drawings]
BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a diagram showing the effect of garlic mushroom extract on cell proliferation of MCF-7 cells.

Claims (3)

An estrogen-like active agent comprising an extract of Ganoderma lucidum. Premenstrual syndrome adult women, estrogenicity agent according to claim 1 for the treatment and prevention least one disease or symptoms are selected from the group consisting of menopausal disorders and postmenopausal disorders.   The estrogen-like active agent according to claim 2, wherein the menopausal disorder or postmenopausal disorder includes at least one selected from the group consisting of coronary artery disease, osteoporosis, abnormal lipid metabolism, climacteric disorder and decreased sexual function.

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