JP7335730B2 - Female hormone booster - Google Patents

Description

TECHNICAL FIELD The present invention relates to an agent for increasing the level of female hormones in blood.

Menopause in women is defined as the permanent cessation of menstruation due to loss of ovarian function, and the period of about five years before and after menopause is called menopause. Menopause is, so to speak, a period of transition from maturity to old age, and is an extremely important period for women as a preparatory period for the coming old age. However, during menopause, along with the rapid decrease in female hormones, autonomic imbalance symptoms such as hot flashes and sweating, and menopausal symptoms such as mental symptoms such as fatigue, depression, and insomnia appear. Disabling symptoms (menopausal disorder) may also occur (Non-Patent Document 1).

Hormone replacement therapy (HRT) is a therapeutic method for relieving various symptoms associated with a rapid decrease in female hormones. Dosage forms for HRT include oral and transdermal drugs. Since HRT is a treatment that directly replenishes female hormones, it has side effects such as nausea and bleeding. In addition, oral medicines may put a burden on the stomach and liver, so they cannot be applied to people with gastrointestinal problems or people with weak livers. It cannot be applied to weak people. However, the efficacy of HRT is so high that it has become the treatment of choice for menopausal symptoms.

On the other hand, Kampo medicine has been based on the concept of oriental medicine since ancient times, and is a drug that mainly aims to improve the constitution and adjust the whole body. sometimes used. Tokishakuyakusan, kamishoyosan, and keishibukuryogan are known as such Kampo medicines (Non-Patent Documents 2, 3, and 4).

Showa Gakushikai Journal, Vol. 77, No. 4, 2017, pp. 367-373 “Kampo preparation Osugi Toki-Shakuyaku Sanyo extract T tablets” Pharmaceutical interview form, created in January 2019 (1st edition) “Kampo preparation Tsumura Kamishoyosan extract granules (medical use)” Pharmaceutical interview form, March 2018 (revised 8th edition) “Kampo preparation Tsumura Keishibukuryogan extract granules (medical use)” pharmaceutical interview form, November 2014 (revised 3rd edition)

There are various types and degrees of symptoms due to a decrease in female hormones, and there are many voices requesting improvement even if symptoms do not lead to menopausal disorders. In addition, for menopausal disorders who find it difficult to apply HRT due to its side effects, or for those who are hesitant about using chemically synthesized HRT and are unable to take treatment, other methods of increasing female hormone levels are desired. .

Kampo medicines are preferable because they have few side effects and can be applied to a wide range of subjects, and because they use natural crude drugs, they are easily accepted. Certain effects are recognized for specific symptoms. However, it is considered that the effects of these Kampo medicines do not reach the effects of a direct approach to the disorder factor, such as HRT, which improves symptoms by increasing female hormones in the blood.

Accordingly, an object of the present invention is to provide a new agent for increasing female hormones.

The present inventors have found that both daisaikoto and bouokito, which are Chinese medicines containing ginger and taisou, can increase female hormones. The present invention has been completed through further studies based on such findings.

That is, the present invention provides inventions in the following aspects.
Section 1. A female hormone increasing agent containing Chinese medicine including ginger and taisou.
Section 2. Item 2. The female hormone increasing agent according to Item 1, wherein the Chinese medicine is Daisaikoto and/or Boukito.
Item 3. Item 3. The female hormone increasing agent according to Item 1 or 2, which increases blood estradiol level.
Section 4. Item 4. The female hormone increasing agent according to any one of Items 1 to 3, which is in the form of tablet, granule, or film.

INDUSTRIAL APPLICABILITY According to the present invention, since a new agent that increases female hormones is provided, various symptoms caused by decreased female hormones can be expected to be improved.

Ovariectomized mice that took the female hormone increasing agent of the present invention (Daisaikoto group, Boukito group), ovariectomized mice that took Bofutsushosan (Bofutsushosan group), and non-ovariectomized mice Blood estradiol levels (pg/ml) in mice (control group) are shown.

The female hormone increasing agent of the present invention is characterized by containing Chinese herbs including ginger and turmeric.

[Kampo medicine containing Ginger and Taisou]
Ginger (Ginger) is a dried rhizome of Zingiberaceae (Zingiberaceae), sometimes with the pericarp removed.・It is used in prescriptions for the purpose of removing diarrhea, coughing, etc.

Taisou (large jujube) is the dried fruit of jujube (Zizyphus jujuba Miller var. inermis Rehder) belonging to the buckthorn family (Rhamnaceae). It is used for this purpose by being compounded in a medicinal formula.

Chinese medicines containing ginger and taisou are not particularly limited, and examples thereof include Kakkonto, Daisaikoto, Untanto, Boukito, Keishikajutsubuto, Hochuekkito, and the like. These herbal medicines may be used singly or in combination of two or more. Among these Kampo medicines, Daisaikoto and Boukito are exemplified, and Daisaikoto is more preferable, from the viewpoint of obtaining a more excellent estrogen-enhancing effect.

Daisaikoto is preferably a herbal prescription listed in the “New OTC Kampo Prescription Guide” (supervised by Yukihiro Goda and Takashi Hakamzuka, edited by the Japan Kampo Medicines Association, published by Jiho Co., Ltd.). It is a mixed crude drug consisting of pheasant, peony, ginger, taisou, and rhubarb. In addition, Daisaikoto contains mixed crude drugs ( Kampo prescriptions) are included.

In the present invention, as Daisaikoto, the mixed crude drugs themselves may be used, or an extract extracted from the mixed crude drugs may be used. It is preferred to use an extract of koyu. The Daisaikoto extract may be either a liquid extract such as a soft extract or a solid dry extract powder.

The liquid extract of Daisaikoto can be obtained by subjecting the crude drug mixture according to the Daisaikoto prescription to extraction treatment, and then concentrating the obtained extract as necessary. Also, the dried extract powder of Daisaikoto can be obtained by drying the liquid extract.

In the production of the Daisaikoto extract, the extraction solvent used in the extraction treatment is not particularly limited, and examples thereof include water and hydrous ethanol. The extraction treatment of Daisaikoto is not particularly limited, but for example, after extraction with an extraction solvent of about 20 times the total weight (converted to dry weight) of the crude drugs contained in Daisaikoto, 1/2 A method of concentrating to volume and removing solids to obtain a liquid extract of Daisaikoto can be mentioned. By subjecting this liquid extract to a drying treatment, a dry extract powder of Daisaikoto can be obtained. The drying treatment is not particularly limited, and a known method may be used. For example, a spray drying method, or adding an appropriate adsorbent (e.g., silicic anhydride, starch, etc.) to a soft extract with an increased extract concentration. A method of using an adsorbent powder and the like can be mentioned.

When using an extract as Daisaikoto in the present invention, the extract prepared by the method described above may be used, or a commercially available product may be used. For example, Daisaikoto dry extract powder includes Daisaikoto dry extract AM, Daisaikoto dry extract SN, Daisaikoto dry extract powder (all manufactured by Nippon Powder Co., Ltd.), and Daisaikoto dry extract F. , and Daisaikoto Dried Extract-F (both manufactured by Alps Yakuhin Kogyo Co., Ltd.) are known as commercial products and can be obtained commercially.

Boukito is preferably prescribed in Chinese medicine as described in the "New OTC Kampo Prescription Guide" (supervised by Yukihiro Goda and Takashi Hakamzuka, edited by the Japan Kampo Medicines Association, published by Jiho Co., Ltd.). It is a mixed crude drug consisting of jutsu, ginger, taisou, and licorice. In addition, as stipulated in the "Basic Policy for Handling Kampo Preparations" stipulated by the Kampo Crude Drug Research Committee, Bogiobukito contains mixtures described in letters related to Kampo medicines that are currently in frequent use. Herbal medicines (Kampo prescriptions) are included.

In the present invention, the mixed herbal medicine itself may be used as the anti-obukito, or an extract extracted from the mixed crude drug may be used. , it is preferable to use the extract of Bogioto. The extract of Boukito may be either a liquid extract such as a soft extract or a solid dry extract powder.

The liquid extract of Boukito can be obtained by extracting the mixed herbal medicine according to the prescription of Boukito and concentrating the resulting extract if necessary. In addition, the dry extract powder of Bogito can be obtained by drying the liquid extract.

The extraction solvent used in the extraction process in the production of the Bogioto extract is not particularly limited, and examples thereof include water and hydrous ethanol. The extraction treatment of Boukito is not particularly limited, but for example, after extraction with an extraction solvent of about 20 times the total weight (converted to dry weight) of crude drugs contained in Boukito , concentration to 1/2 volume, solid content is removed, and a method of obtaining a liquid extract of Daisaikoto can be mentioned. In addition, by subjecting this liquid extract to a drying treatment, the dried extract powder of Bogioto can be obtained. The drying treatment is not particularly limited, and a known method may be used. For example, a spray drying method, or adding an appropriate adsorbent (e.g., silicic anhydride, starch, etc.) to a soft extract with an increased extract concentration. A method of using an adsorbent powder and the like can be mentioned.

In the present invention, when an extract is used as Bogioto, the extract prepared by the method described above may be used, or a commercially available product may be used. For example, as the dried extract powder of Boukito, Boukito dry extract A and Boukito dry extract AZ (both manufactured by Nippon Powder Co., Ltd.), and Boukito extract powder and Boukito Dried Extract-F (both manufactured by Alps Yakuhin Kogyo Co., Ltd.) and the like are known as commercial products, and can be obtained commercially.

In the female hormone increasing agent of the present invention, the content of ginger and turmeric is not particularly limited as long as the effect of the present invention is exhibited. , 5 to 95 parts by weight, preferably 25 to 65 parts by weight.

In addition, in the female hormone increasing agent of the present invention, the ratio of ginger and turmeric is not particularly limited as long as the effect of the present invention is exhibited. parts by weight, preferably 2 to 4 parts by weight, more preferably 2.5 to 3.5 parts by weight.

In the female hormone increasing agent of the present invention, the content of Chinese medicine containing ginger and turmeric is not particularly limited as long as the effect of the present invention is exhibited, but is usually 5 to 80% by weight, preferably 5 to 80% by weight in terms of dry extract powder. 10 to 70% by weight, more preferably 20 to 60% by weight, still more preferably 30 to 50% by weight. In the present invention, the term "converted amount of dried herb extract powder" refers to the amount of dried herb extract itself when using dried herb extract powder, and the residue obtained by removing the solvent when liquid extract of herb is used. It is the amount converted to quantity. In addition, when the dry herbal extract powder contains an additive such as an adsorbent added at the time of production, the amount excludes the additive.

[Other ingredients]
The female hormone increasing agent of the present invention may contain other pharmacological ingredients in addition to the aforementioned herbal medicines, if necessary. The types of such pharmacological ingredients are not particularly limited, but for example, antacids, stomachic agents, digestive agents, antiflatulents, antispasmodics, mucous membrane repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, and antiphlogistic agents. Enzymatic agents, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drugs, crude drug extract powders, vitamins, menthols and the like. These pharmacological ingredients may be used singly or in combination of two or more. In addition, the content of these pharmacological ingredients may be appropriately set from known ones according to the type of the pharmacological ingredient to be used.

The female hormone increasing agent of the present invention may contain pharmaceutically acceptable bases, additives and the like as necessary in order to prepare a desired dosage form. Examples of such bases and additives include excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, agents, suspending agents, adhesives, coating agents, brightening agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps , lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, corrigents, fragrances, powders, thickeners, pigments, chelating agents and the like. These bases and additives may be used singly or in combination of two or more. Moreover, the contents of these bases and additives may be appropriately set from known ones according to the types of additive components to be used, dosage forms, and the like.

[Dosage form]
The dosage form of the female hormone increasing agent of the present invention is not particularly limited, and may be tablets, granules, powders, pills, capsules, films, liquids (drinks), and the like. Among these dosage forms, tablets, granules, and films are preferred from the viewpoint of ease of administration. These dosage forms can be prepared using pharmaceutically acceptable base materials and additives, and the types and blending amounts of the base materials and additives are also known in the field of formulation technology.

When the female hormone increasing agent of the present invention is provided as a tablet, the tablet may be either a gastric-soluble tablet (ordinary tablet) or an enteric-coated tablet. It may be coated with a film coating base or the like.

[Use]
The female hormone increasing agent of the present invention is applied for increasing blood hormone level, preferably for increasing blood estradiol level. Specifically, the agent for increasing female hormones of the present invention is used for the purpose of increasing female hormones that have decreased, or slowing down or suppressing female hormone decreases. Therefore, the agent for increasing estrogen of the present invention is applied to women whose estrogen levels are declining, especially to women who are aware of various symptoms associated with estrogen depletion. Specific applications include menopausal women with menopausal symptoms or menopausal disorders, women with early ovarian insufficiency after oophorectomy or after chemotherapy, and women after hysterectomy.

[Dosage and usage]
The female hormone increasing agent of the present invention is administered orally. The dosage of the female hormone increasing agent of the present invention is appropriately set according to the degree of decrease in female hormones, age, etc. For example, the daily intake is 0.00 in terms of the amount of raw herbal medicine of ginger. 4 to 2.0 g, preferably 0.5 to 1.5 g, more preferably 0.5 to 0.7 g, and 1.5 to 4.0 g, preferably 1.5 to 3 g, more preferably 1.7 to 1.9 g.

When the Chinese medicine used in the female hormone increasing agent of the present invention is Daisaikoto, more specific examples of the daily intake amount include 0.6 g ginger, 1.8 g taiso, 3.6 g of rhubarb, 1.8 g of peony, 1.2 g of pheasant, 2.4 g of hange, 1.8 g of Scutellaria root, and 0.6 g of rhubarb. When the herbal medicine used in the female hormone increasing agent of the present invention is Bogioto, a more specific example of the daily intake is 1 g of ginger, 3 g of Taiso, and 5 g of bowie in terms of crude drug equivalents. , Byakujutsu (or sojutsu) 3g, Chinese mugwort 5g, and licorice 1.5g.

In addition, the daily intake is 400 to 10000 mg, preferably 1300 to 6000 mg, in terms of dried extract powder of Chinese medicine, and 1700 to 5800 mg is particularly preferable when the Chinese medicine is Daisaikoto, and the Chinese medicine is Bao Huang. 1,300 to 4,800 mg is particularly preferred for hot water. The dosing timing is not particularly limited, and may be before, after or between meals, preferably before or between meals.

EXAMPLES The present invention will be specifically described below by way of examples, but the present invention is not limited to these examples.

1. Preparation of extract powder (1) Daisaikoto extract powder As crude drugs, ginger 0.6 (parts by weight, the same applies hereinafter), turmeric 1.8, rhododendron 3.6, peony 1.8, pheasant 1.2, hange 2.4, 1.8 of scutellaria root and 0.6 of rhubarb, minced, extracted with 20 times the weight of water at about 100°C for 1 hour, centrifuged to obtain an extract, and reduced pressure. The extract was concentrated under a vacuum and dried using a spray dryer to obtain Daisaikoto extract powder. Drying with a spray dryer was performed by dropping the extract into an atomizer rotating at 10000 rpm and supplying hot air at 150°C.

(2) Boukito extract powder As crude drugs, 1 ginger (parts by weight, the same shall apply hereinafter), 3 sage, 5 bowies, 3 byakujutsu, 5 Astragalus, and 1.5 licorice were used, and these were chopped. After that, it is extracted at about 100° C. for 1 hour using 20 times its weight of water, centrifuged to obtain an extract, concentrated under reduced pressure and dried using a spray dryer to obtain Bogioto extract powder. Ta. Drying with a spray dryer was performed by dropping the extract into an atomizer rotating at 10000 rpm and supplying hot air at 150°C.

(3) Bofutsushosan extract powder As crude drugs, bellflower 1.67 (parts by weight, the same shall apply hereinafter), byakujutsu 1.67, licorice 1.67, Scutellaria root 1.67, gypsum 1.67, rhubarb 1.25, Angelica 1.0, Peony 1.0, Cnidium 1.0, Sanshishi 1.0, Forsythia 1.0, Mentha 1.0, Lily 1.0, Bohu 1.0, Ephedra 1.0, Ginger 0.33 , 2.5 parts of casseki, and 1.25 parts of bosho. After chopping these, they were extracted at about 100°C for 1 hour using 20 times the weight of water, centrifuged to obtain an extract, and concentrated under reduced pressure. and dried using a spray dryer to obtain Bofutsushosan extract powder. Drying with a spray dryer was performed by dropping the extract into an atomizer rotating at 10000 rpm and supplying hot air at 150°C.

2. Experimental Method Mice (C57BL/6J mice, 6 weeks old, female) underwent bilateral oophorectomy to reproduce menopause, and a recovery period of 17 days was provided after the operation. After that, they were divided into a control group, a Daisaikoto group, a Boukito group, and a Bofutsushosan group. The bofutsuseisan powder was fed to the bofutsuseisan group, and the bofutsuseisan powder to the bofutsuseisan group. were fed with feed containing 2% by weight of Blood was collected after feeding for 7 weeks, and the average estradiol amount in each group was derived. The results are shown in FIG.

As shown in Figure 1, in the mice administered the Daisaikoto extract and the Boukito extract (Daisaikoto group and Boukito group), blood estradiol increased compared with the non-administered mice (control group). significantly increased in volume. On the other hand, in mice administered with the Bofutsushosan extract (Bofutsushosan group), the amount of estradiol in the blood was hardly increased compared to the non-administered mice (control group). Since Daisaikoto and Bookito are both Chinese medicines containing ginger and turmeric, and Bofutsushosan is a Chinese medicine that does not contain such common ingredients, Administration was shown to increase female hormones.

Claims (4)

An orally administered female hormone increasing agent containing Boukito extract . A female hormone increasing agent containing Daisaikoto extract and used for menopausal disorders. The female hormone increasing agent according to claim 1 or 2, which increases the amount of blood estradiol. The female hormone increasing agent according to any one of claims 1 to 3, wherein the dosage form is tablet, granule, or film.