JP2020114820A - Estrogen-like agent - Google Patents
Estrogen-like agent Download PDFInfo
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- JP2020114820A JP2020114820A JP2020036002A JP2020036002A JP2020114820A JP 2020114820 A JP2020114820 A JP 2020114820A JP 2020036002 A JP2020036002 A JP 2020036002A JP 2020036002 A JP2020036002 A JP 2020036002A JP 2020114820 A JP2020114820 A JP 2020114820A
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- extract
- female hormone
- licorice
- rhubarb
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Abstract
Description
本発明は、女性ホルモン様作用を奏する剤に関する。 The present invention relates to agents that exert a female hormone-like action.
エストロゲンは、コレステロールから合成されるステロイドホルモンの一種であり、卵胞ホルモンまたは女性ホルモンとも呼ばれている。エストロゲン受容体は、古典的なリガンド活性化転写因子の一つであり、女性ホルモンは、この受容体を介して、生殖、骨生理等の様々な機能に対する生理作用を発揮する。 Estrogen is a kind of steroid hormone synthesized from cholesterol and is also called estrogen or female hormone. The estrogen receptor is one of the classical ligand-activated transcription factors, and female hormones exert physiological actions on various functions such as reproduction and bone physiology through this receptor.
女性ホルモンが欠乏すると、その影響によって、更年期障害、骨粗鬆症等の症状を引き起こす。これらの症状を緩和させるための治療法として、ホルモン補充療法(HRT)が盛んに行われている。しかしながら、HRTは大量の女性ホルモンを人為的に補充する治療法であるため、有効性が高い一方で体への負荷も大きく、投与の調整が非常に難しい。 When a female hormone is deficient, its effects cause symptoms such as menopause and osteoporosis. Hormone replacement therapy (HRT) is actively used as a treatment for alleviating these symptoms. However, since HRT is a therapeutic method for artificially replenishing a large amount of female hormones, it is highly effective, but also has a large load on the body, and its administration is extremely difficult to adjust.
そこで、近年、植物由来のイソフラボン類が、女性ホルモン様作用を奏する成分として注目されている。このような女性ホルモン様作用は、イソフラボン類の化学構造がエストロゲンの化学構造と類似していることに起因すると考えられている。中でも、大豆に含まれるイソフラボンに由来するエクオールは、エストロゲン活性が高いことが知られており(非特許文献1及び2)、脚光を浴びている。また、生薬のカンゾウにはリクイリチン等のイソフラボン類が含まれており、生薬のオウギにはホルモノネチン、オノニン等のイソフラボン類が含まれていることが知られている。 Therefore, in recent years, plant-derived isoflavones have attracted attention as a component that exerts a female hormone-like action. It is believed that such a female hormone-like action is due to the chemical structure of isoflavones being similar to that of estrogen. Among them, equol derived from isoflavone contained in soybean is known to have high estrogen activity (Non-Patent Documents 1 and 2) and is in the spotlight. It is known that licorice, a herbal medicine, contains isoflavones such as liquiritin, and Ougi, a herbal medicine, contains isoflavones such as formononetin and ononine.
大豆由来のエクオールには女性ホルモンの減少による症状に対する効果が期待されているものの、大豆アレルギーの人には適用できない。従って、女性ホルモン様作用が期待できる植物由来成分について、更なる選択肢が望まれる。カンゾウ等の一部の生薬にはイソフラボン類が含まれているものの、その女性ホルモン様作用は十分とはいえない。 Soy-derived equol is expected to be effective against symptoms caused by decreased female hormones, but it cannot be applied to people with soy allergies. Therefore, further options are desired for plant-derived components that are expected to have female hormone-like actions. Although some crude drugs such as licorice contain isoflavones, their female hormone-like action is not sufficient.
そこで、本発明は、女性ホルモン様作用を奏する新たな剤を提供することを目的とする。 Then, an object of the present invention is to provide a new agent exhibiting a female hormone-like action.
本発明者は、鋭意検討の結果、カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとを組み合わせることによって、予想外の顕著な女性ホルモン様作用が奏されることを見出した。本発明は、かかる知見に基づいて、更に検討を重ねることにより完成したものである。 As a result of diligent studies, the present inventor has found that the combination of the licorice extract with the Ougi extract and/or the rhubarb extract and the Scutellariae extract produces an unexpected and remarkable female hormone-like action. The present invention has been completed by further studies based on such findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項1. カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとを含有する、女性ホルモン様作用剤。
項2. カンゾウエキスと、オウギエキスとを含有する、項1に記載の女性ホルモン様作用剤。
項3. 防已黄耆湯エキス及び/又は当帰飲子エキスを含有する、項1又は2に記載の女性ホルモン様作用剤。
項4. カンゾウエキスと、ダイオウエキス及びオウゴンエキスとを含有する、項1に記載の女性ホルモン様作用剤。
項5. 防風通聖散エキスを含有する、項1又は4に記載の女性ホルモン様作用剤。
That is, the present invention provides the inventions of the following modes.
Item 1. A female hormone-like agent, comprising a licorice extract, and an orchid extract and/or a rhubarb extract and an oriental extract.
Item 2. Item 2. The female hormone-like agent according to Item 1, which contains a licorice extract and an Ougi extract.
Item 3. Item 3. The female hormone-like agent according to Item 1 or 2, which contains an extract of Boi-Ogi-to and/or an extract of Toki-inko.
Item 4. Item 2. The female hormone-like agent according to Item 1, which contains a licorice extract and a rhubarb extract and a sardine extract.
Item 5. Item 5. The female hormone-like agent according to Item 1 or 4, which contains an extract of Bofutsushosan.
本発明によれば、女性ホルモン様作用を奏する新たな剤が提供されるため、女性ホルモンの減少による諸症状の改善が期待できる。 According to the present invention, since a new agent that exerts a female hormone-like action is provided, improvement of various symptoms due to a decrease in female hormone can be expected.
本発明の女性ホルモン様作用剤は、カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとを含有することを特徴とする。 The female hormone-like agent according to the present invention is characterized by containing a licorice extract, an Astragalus membranaceus extract and/or a rhubarb extract and an Astragalus membranaceus extract.
カンゾウエキスは、単独では弱い女性ホルモン様作用しか示さない。また、オウギエキスも単独では弱い女性ホルモン様作用しか示さない。ダイオウエキス及びオウゴンエキスには、イソフラボン類が含まれていることや女性ホルモン様作用があることは知られていないが、本発明で実施した試験においては、いずれも単独で弱い女性ホルモン様作用を示すことが見出された。これら生薬エキスのうち、カンゾウエキスとオウギエキスとの組み合わせは、女性ホルモン様作用を相乗的に増強する。一方、ダイオウエキス及びオウゴンエキスについて新たに見出された女性ホルモン様作用により、これらの生薬エキスをカンゾウエキスと組み合わせることで、カンゾウエキス単独に比べて増強された女性ホルモン様作用が奏される。 Licorice extract by itself exhibits only weak female hormone-like effects. In addition, Ougi extract alone exhibits only a weak female hormone-like action. The rhubarb extract and sardine extract are not known to contain isoflavones and have a female hormone-like action, but in the tests carried out by the present invention, both have a weak female hormone-like action. It was found to show. Among these herbal extracts, the combination of licorice extract and sugi extract synergistically enhances female hormone-like action. On the other hand, due to the newly discovered female hormone-like action of rhubarb extract and sardine extract, by combining these crude drug extracts with licorice extract, an enhanced female hormone-like action is exhibited as compared with licorice extract alone.
本発明の女性ホルモン様作用剤に含まれるカンゾウエキス、オウギエキス、ダイオウエキス、オウゴンエキスは、それぞれ、単味エキス(カンゾウ単味エキス、オウギ単味エキス、ダイオウ単味エキス、オウゴン単味エキス)であってもよいし、漢方エキス(カンゾウ、オウギ、ダイオウ、オウゴンからなる群から選択される2種以上を含む混合生薬のエキス、若しくは、カンゾウ、オウギ、ダイオウ、オウゴンからなる群から選択される1種以上と、カンゾウ、オウギ、ダイオウ、オウゴン以外の生薬から選択される1種以上との混合生薬のエキス)を構成するエキスであってもよい。 The licorice extract, sugi extract, rhubarb extract and sorghum extract contained in the female hormone-like agent of the present invention are, respectively, simple extracts (liquorice simple extract, sorghum simple extract, rhubarb simple extract, sorghum simple extract). May be present, or herbal extract (extract of mixed crude drug containing two or more kinds selected from the group consisting of liquorice, sugi, rhubarb, and swordfish), or selected from the group consisting of licorice, sugi, rhubarb, and swordfish 1 Extract of a mixed herb of at least one species and at least one species selected from herbs other than licorice, sugi, rhubarb, and sardine).
本発明の女性ホルモン様作用剤に含まれるカンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスの具体的態様としては、生薬の単味エキスの混合物、漢方エキス、一の漢方エキスと他の漢方エキスとの混合物、単味エキスと漢方エキスとの混合物等が挙げられる。生薬の単味エキスの混合物の例としては、カンゾウの単味エキスと、オウギの単味エキス並びに/若しくはダイオウの単味エキス及びオウゴンの単味エキスとの混合物が挙げられる。漢方エキスの例としては、カンゾウと、オウギ並びに/若しくはダイオウ及びオウゴンとを含む混合生薬のエキスが挙げられる。一の漢方エキスと他の漢方エキスとの混合物としては、カンゾウ、オウギ、ダイオウ、及びオウゴンからなる群から選択される少なくとも1種を含む一の混合生薬のエキスと、カンゾウ、オウギ、ダイオウ、及びオウゴンからなる群から選択される少なくとも他の1種を含む他の混合生薬のエキスとを含む混合物が挙げられる。単味エキスと生薬混合物のエキスとの混合物としては、カンゾウ、オウギ、ダイオウ、及びオウゴンからなる群から選択される少なくとも1種の単味エキスと、カンゾウ、オウギ、ダイオウ、及びオウゴンからなる群から選択される少なくとも他の1種を含む混合生薬のエキスとを含む混合物等が挙げられる。 Specific embodiments of the licorice extract and the rye extract and/or the rhubarb extract and the sorghum extract contained in the female hormone-like agent of the present invention include a mixture of plain extracts of crude drug, Chinese herbal extract, one Chinese herbal extract and other Chinese herbs. Examples thereof include a mixture with an extract and a mixture of a plain extract and a Chinese herb extract. An example of a mixture of crude extract of crude drug is a mixture of a simple extract of licorice and a simple extract of sugi and/or a simple extract of rhubarb and a simple extract of sorghum. Examples of the herbal extracts include extracts of mixed crude drugs containing licorice and sugi and/or rhubarb and sardine. As a mixture of one Chinese herbal extract and another Chinese herbal extract, a mixed herbal extract containing at least one selected from the group consisting of liquorice, rye, rhubarb, and sorghum, and liquorice, astragalus, rhubarb, and And a mixture containing an extract of another mixed herbal medicine containing at least one other selected from the group consisting of Auregon. The mixture of the plain extract and the extract of the herbal medicine includes at least one plain extract selected from the group consisting of liquorice, sugi, rhubarb, and swordfish, and the group consisting of liquorice, sugi, rhubarb, and sardine. Examples thereof include a mixture containing an extract of a mixed crude drug containing at least one other selected drug.
また、本発明において用いられる上記の生薬エキスの形態としては、軟エキス等の液状のエキス、及び固形状の乾燥エキス末のいずれであってもよい。 The crude drug extract used in the present invention may be in the form of a liquid extract such as a soft extract or a solid dry extract powder.
カンゾウ(甘草)は、マメ科(Leguminosae)のGlycyrrhiza uralensis Fischer又は Glycyrrhiza glabra Linneの根及びストロンで、ときには周皮を除いたもの(皮去りカンゾウ)であり、生薬(日本薬局方)として主に去痰薬、胃潰瘍薬などの用途に使用される。カンゾウの市販品としては、日本粉末薬品株式会社、高砂薬業株式会社、株式会社栃本天海堂等から商業的に入手可能である。カンゾウの単味エキスは、カンゾウエキスとして、医薬部外品原料規格に記載されており、公知である。カンゾウエキスの市販品としては、例えば、丸善製薬株式会社、日本粉末薬品株式会社、アルプス薬品工業株式会社等から商業的に入手可能である。 Licorice (licorice) is the root and stront of Glycyrrrhiza uralensis Fischer or Glycyrrrhiza glabra Linne of the leguminous family (Leguminosae), and sometimes it is a herb medicine that has been removed from the pericarp (the licorice herb), which is a local herb medicine and is a crude drug. Used for medicine, gastric ulcer drug, etc. Commercially available licorice is commercially available from Nippon Powder Chemicals Co., Ltd., Takasago Pharmaceutical Co., Ltd., Tochimoto Tenkaido Co., Ltd., etc. A simple extract of licorice is known as a licorice extract, which is described in the standard for quasi drug raw materials. Commercially available licorice extract is commercially available from Maruzen Pharmaceutical Co., Ltd., Nippon Powder Chemical Co., Ltd., Alps Pharmaceutical Co., Ltd., etc.
オウギ(黄耆)は、マメ科(Leguminosae)のキバナオウギ Astragalus membranaceus Bunge又は Astragalus mongholicus Bungeの根であり、生薬(日本薬局方)として、血圧降下、利尿などの用途に使用される。オウギの市販品は、高砂薬業株式会社、株式会社栃本天海堂等から商業的に入手可能である。オウギの単味エキスの市販品は、例えば、日本粉末薬品株式会社、アルプス薬品工業株式会社等から商業的に入手可能である。 Ougi is a root of Astragalus membranaceus Bunge or Astragalus mongolicus Bunge of the leguminous family (Leguminosae), and is used as a crude drug (Japanese Pharmacopoeia) for use in blood pressure reduction, diuresis and the like. Commercial products of Ougi are commercially available from Takasago Pharmaceutical Co., Ltd., Tochimoto Tenkaido Co., Ltd., etc. Commercially available plain extract of Astragalus membranaceus is commercially available from, for example, Nippon Powder Chemical Co., Ltd., Alps Chemical Co., Ltd., and the like.
ダイオウ(大黄)は、タデ科(Polygonaceae)のRheum palmatum L., Rheum tanguticum Maximowicz, Rheum officinale Baillon, Rheum coreanum Nakai又はそれらの種間雑種の通例、根茎であり、生薬(日本薬局方)として主に健胃薬や瀉下薬の用途に使用される。ダイオウの市販品は、三和生薬株式会社、株式会社栃本天海堂等から商業的に入手可能である。ダイオウの単味エキスの市販品は、例えば、アルプス薬品工業株式会社等から商業的に入手可能である。 Rheum palmatum L. of the Polygonaceae family is used as a rhubarb. , Rheum tanguticum Maximowicz, Rheum officinale Bailron, Rheum coreanum Nakai or their interspecific hybrids, which are rhizomes, and are mainly used as gastric medicines and laxatives as a crude drug (Japanese Pharmacopoeia). Commercial products of rhubarb are commercially available from Sanwa Seiyaku Co., Ltd., Tochimoto Tenkaido Co., Ltd., etc. Commercial products of the simple extract of Rhubarb communis are commercially available from, for example, Alps Pharmaceutical Co., Ltd.
オウゴン(黄ごん)は、シソ科(Labiatae)のコガネバナ Scutellaria baicalensis Georgiの周皮を除いた根であり、生薬(日本薬局方)として主に抗炎症薬、抗アレルギー薬、抗菌・抗真菌薬の用途に使用される。オウゴンの市販品は、高砂薬業株式会社、株式会社栃本天海堂等から商業的に入手可能である。オウゴンの単味エキスは、オウゴンエキスとして、医薬部外品原料規格に記載されており、公知である。オウゴンエキスの市販品は、例えば、一丸ファルコス株式会社等から商業的に入手可能である。 Ougon is a root excluding the pericardium of Scutellaria baicalensis Georgi of the Labiatae family, Scutellaria baicalensis. Used for. A commercial product of Ougon is commercially available from Takasago Pharmaceutical Co., Ltd., Tochimoto Tenkaido Co., Ltd., etc. The plain extract of Scutellaria baicalensis is described in the standard for quasi-drug raw materials as Scutellaria extract and is well known. A commercial product of Scutellaria baicalensis extract is commercially available from, for example, Ichimaru Falcos Co., Ltd.
また、上記の生薬の単味エキスについては、市販品を用いる他、上記の植物の部位を、水又は含水エタノール、好ましくは水を抽出溶媒として抽出処理し、得られた抽出液を必要に応じて濃縮することでエキス液として得てもよいし、エキス液を乾燥処理することでエキス末として得てもよい。また、生薬の単味エキスの乾燥処理としても、特に限定されず、公知の方法、例えば、スプレードライ法や、エキス液の濃度を高めた軟エキスに対して適当な吸着剤(例えば無水ケイ酸、デンプン等)を加えて吸着末とする方法等が挙げられる。 Further, for the plain extract of the above crude drug, in addition to using a commercially available product, the plant part is subjected to an extraction treatment with water or hydrous ethanol, preferably water as an extraction solvent, and the obtained extract is used as necessary. May be concentrated to obtain an extract, or may be dried to obtain an extract powder. Also, the drying treatment of the crude extract of crude drug is not particularly limited, and a known method, for example, a spray drying method, or an adsorbent suitable for a soft extract having an increased concentration of the extract solution (for example, silicic acid anhydride) is used. , Starch, etc.) to obtain an adsorption powder.
本発明の女性ホルモン様作用剤の具体的な例においては、カンゾウエキスと、オウギエキスとを含む。更に、カンゾウエキス及びオウギエキスは、より一層優れた女性ホルモン様作用を得る観点から、漢方エキスを構成するエキスであることが好ましい。このような漢方エキスとしては、好ましくはカンゾウ及びオウギを含む混合生薬のエキスが挙げられる。このような漢方エキスとしては特に限定されず、例えば、防已黄耆湯エキス、当帰飲子エキス、加味帰脾湯エキス、帰脾湯エキス、黄耆建中湯エキス、帰耆建中湯エキス、桂枝加黄耆湯エキス、十全大補湯エキス、清暑益気湯エキス、清心蓮子飲エキス、当帰湯エキス、人参養栄湯エキス、補中益気湯エキス、麗沢通気湯エキス、麗沢通気湯加辛夷エキス、大防風湯エキス等が挙げられる。これらの漢方エキスは、1種を単独で用いてもよいし、複数種を組み合わせて用いてもよい。これらの漢方エキスの中でも、より一層優れた女性ホルモン様作用を得る観点から、好ましくは、防已黄耆湯エキス及び当帰飲子エキスが挙げられる。 Specific examples of the female hormone-like agent of the present invention include licorice extract and sugi extract. Further, licorice extract and sugi extract are preferably the extracts that constitute Kampo extract, from the viewpoint of obtaining a more excellent female hormone-like action. Such herbal extracts preferably include mixed crude drug extracts containing licorice and rye. Such Kampo extract is not particularly limited and includes, for example, Hoi-Oki-to extract, Toki-inko extract, Kami-Ki-to extract, Khi-to extract, O-Kikenchu-to extract, Kiki-Kenchu-to extract, Keishikagekiyuto extract, Juzentaihoto extract, Seisekikikito extract, Seishinrenkoin extract, Tokiyuto extract, Ninjinyoeito extract, Hochuekkito extract, Reisawatsutoyu extract, Reisawa Kentou hot spring extract, Daihofu hot water extract and the like can be mentioned. These Kampo extracts may be used alone or in combination of two or more. Among these Kampo extracts, from the viewpoint of obtaining a more excellent female hormone-like action, preferred are Hoi-Ogi-to extract and Toki-inko extract.
本発明の女性ホルモン様作用剤の具体的な他の例においては、カンゾウエキスと、ダイオウエキス及びオウゴンエキスとを含む。更に、カンゾウエキス、ダイオウエキス及びオウゴンエキスは、より一層優れた女性ホルモン様作用を得る観点から、漢方エキスを構成するエキスであることが好ましい。このような漢方エキスとしては、防風通聖散エキス、乙字湯エキス、柴胡加竜骨牡蛎湯エキス、潤腸湯エキス、女神散エキス、加味解毒湯エキス等が挙げられる。これらの漢方エキスは、1種を単独で用いてもよいし、複数種を組み合わせて用いてもよい。これらの漢方エキスの中でも、より一層優れた女性ホルモン様作用を得る観点から、より好ましくは、防風通聖散エキスが挙げられる。 Other specific examples of the female hormone-like agent of the present invention include licorice extract, rhubarb extract and sardine extract. Furthermore, the licorice extract, rhubarb extract and sardine extract are preferably the extracts constituting the Chinese herb extract from the viewpoint of obtaining a more excellent female hormone-like action. Examples of such Kampo extract include Bofutsushosan extract, Otsuji-to extract, Saiko-karyukotsu-boi-to extract, Jun-en-to extract, Megami-san extract, Kami-doku-to extract and the like. These Kampo extracts may be used alone or in combination of two or more. Among these Kampo extracts, from the viewpoint of obtaining a more excellent female hormone-like action, more preferably, Bofutsushosansan extract.
防已黄耆湯を構成する生薬は、「一般用漢方処方の手引き」(厚生省薬務局監修、日薬連漢方専門委員会編集、薬業時報社発行)、「第十七改正日本薬局方」、「一般用漢方製剤製造販売承認基準」(厚生労働省医薬・生活衛生局施行)によれば、ボウイ、オウギ、ビャクジュツ(ソウジュツも可)、ショウキョウ、タイソウ、及びカンゾウである。また、防已黄耆湯には、漢方生薬調査会により定められた「漢方製剤の基本的取扱い方針」に規定されるように、現在繁用されている漢方関係の書簡に記載されている混合生薬(漢方処方)が包含される。 The herbal medicines that compose Hoi-Ogi-to are "General Chinese Medicine Prescription Guide" (supervised by the Ministry of Health, Labor and Welfare, edited by the Japan Pharmacopoeia Special Committee, published by The Pharmaceutical Industry Bulletin), "The 17th Amended Japanese Pharmacopoeia" According to the “Standards for the manufacture and sale of Kampo formulations for general use” (Enforced by the Ministry of Health, Labor and Welfare's Pharmaceutical and Living Health Bureau), they are Bowie, Ougi, Sandalwood (also available), Ginseng, Thalis and licorice. In addition, as for the Bosai-Ogi-to, it is mixed in the currently used traditional Chinese medicine-related letters, as specified in the "Basic policy for the treatment of traditional Chinese medicines" established by the Study Committee for Traditional Chinese Medicine. Herbal medicines (Chinese herbal prescription) are included.
防已黄耆湯エキスの市販品は、防已黄耆湯乾燥エキスA及び防已黄耆湯乾燥エキスAZ(いずれも日本粉末株式会社製)、並びに防已黄耆湯エキス末及び防已黄耆湯乾燥エキス−F(いずれもアルプス薬品工業株式会社製)等が商業的に入手可能である。 Commercially available products of Hoi-Oki-to extract are Ho-i-Oki-to dried extract A and O-O-Goi-to dried extract AZ (both manufactured by Nippon Powder Co., Ltd.), and O-Iki-to extract powder and I-Oh. Soybean paste dried extract-F (all manufactured by Alps Chemical Co., Ltd.) and the like are commercially available.
当帰飲子の構成生薬は、「一般用漢方処方の手引き」(厚生省薬務局監修、日薬連漢方専門委員会編集、薬業時報社発行)、「一般用漢方製剤製造販売承認基準」(厚生労働省医薬・生活衛生局施行)によれば、トウキ、シャクヤク、センキュウ、シツリシ、ボウフウ、ジオウ、ケイガイ、オウギ、カシュウ、カンゾウである。 The composition of herbal medicines of Toki-inko is "Handbook of Kampo prescription for over-the-counter" (supervised by the Ministry of Health and Welfare, edited by the Japan Pharmacopoeia Special Committee, published by Yakuhin Jikkan Co., Ltd.), "Criteria for manufacturing and marketing over-the-counter Kampo formulations" According to the Ministry of Health, Labor and Welfare's Pharmaceutical and Life Sanitation Bureau enforcement, they are Japanese persimmon, peony, senkyu, shirushi, bow hu, dio, kayigai, sugi, kashu, and kanzo.
当帰飲子エキスの市販品は、当帰飲子エキス細粒(松浦薬業株式会社)等が商業的に入手可能である。 As a commercial product of Toki-inko extract, Toki-inko extract fine granules (Matsuura Pharmaceutical Co., Ltd.) and the like are commercially available.
防風通聖散の構成生薬は、「一般用漢方処方の手引き」(厚生省薬務局監修、日薬連漢方専門委員会編集、薬業時報社発行)、「第十七改正日本薬局方」、「一般用漢方製剤製造販売承認基準」(厚生労働省医薬・生活衛生局施行)によれば、トウキ、シャクヤク、センキュウ、サンシシ、レンギョウ、ハッカ、ショウキョウ、ケイガイ、ボウフウ、マオウ、ダイオウ、ボウショウ、ビャクジュツ、キキョウ、オウゴン、カンゾウ、セッコウ、及びカッセキである。また、防風通聖散の構成生薬は、上記生薬のうちビャクジュツを含まないもの(例えば「経験漢方処方分量集」、大塚敬節・矢数道明監集、医道の日本社発行)、オウゴンを含まないもの(例えば「続漢方あれこれ」大阪読売新聞社編、浪速社発行)、ボウフウの代わりにハマボウフウを含むもの、ビャクジュツの代わりにソウジュツを含むものであってもよい。 The constituent crude drugs of Bofutsushosan are "Handbook of Kampo prescription for general use" (supervised by the Ministry of Health and Welfare of the Pharmaceutical Affairs Bureau, edited by the Special Committee for Kampo Medicines of the Nichiyakuren, published by Pharmaceutical Industry Bulletin), "The 17th Amended Japanese Pharmacopoeia", According to the “Standards for Manufacturing and Marketing Approval of General Chinese Medicines” (Enforced by the Ministry of Health, Labor and Welfare, Pharmaceutical and Life Sanitation Bureau), Japanese persimmon, peony, senkyu, sanshishi, forsythia, peppermint, ginger, ginger, pearl oyster, mahou, rhubarb, pearl oyster, pearl oyster, pearl syrup , Kyokyo, swordfish, licorice, gypsum, and kaseki. In addition, the constituent crude drugs of Bofutsushosan include the ones that do not contain juniper soybeans among the above-mentioned crude drugs (for example, "Experience Kampo prescription volume collection", Otsuka Keisetsu/Yazawa Michiaki Supervisor, Ido Japanese Company), and Ougon. It may be one that does not exist (for example, "Sequential Chinese medicine about this" edited by Osaka Yomiuri Shimbun, published by Naniwasha), one that includes Hamabofu instead of Bowfu, and one that includes Sojutsu instead of jerk.
防風通聖散エキスの市販品は、「風通聖散乾燥エキスA、防風通聖散乾燥エキスAM、防風通聖散乾燥エキスE、及び防風通聖散乾燥エキスEM(いずれも日本粉末株式会社製)、並びに防風通聖散料乾燥エキス−C、及び防風通聖散料乾燥エキス−F(いずれもアルプス薬品工業株式会社製)等が商業的に入手可能である。 Commercially available products of Koufutsushosan dry extract are "Koutsushosan dried extract A, Koutsushosan dried extract AM, Koutsushosan dried extract E, and Koutsushosan dried extract EM (all of which are Nippon Powder Co., Ltd. Commercially available), and the wind-proof Tsusho powder dry extract-C, the wind-proof Tsusho powder dry extract-F (all are Alps Yakuhin Kogyo Co., Ltd.), etc. are commercially available.
また、上記の漢方エキスについては、市販品を用いる他、上記の漢方の構成生薬の混合物を、水又は含水エタノール、好ましくは水を抽出溶媒として抽出処理し、得られた抽出液を必要に応じて濃縮することによりエキス液として得てもよいし、エキス液を乾燥処理することでエキス末として得てもよい。また、漢方エキスの乾燥処理としても、特に限定されず、公知の方法、例えば、スプレードライ法や、エキス液の濃度を高めた軟エキスに対して適当な吸着剤(例えば無水ケイ酸、デンプン等)を加えて吸着末とする方法等が挙げられる。 In addition, as the above-mentioned Kampo extract, in addition to using a commercially available product, a mixture of the above-mentioned Kampo herbal constituents is subjected to an extraction treatment with water or hydrous ethanol, preferably water as an extraction solvent, and the obtained extract is used as necessary. It may be obtained as an extract solution by concentrating the extract solution, or may be obtained as an extract powder by subjecting the extract solution to a drying treatment. Also, the drying treatment of the Chinese herb extract is not particularly limited, and a known method, for example, a spray drying method, or an adsorbent suitable for a soft extract having an increased concentration of the extract solution (eg, silicic acid anhydride, starch, etc.) ) Is added to obtain an adsorption powder.
本発明の女性ホルモン様作用剤において、カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとの含有量としては、本発明の効果を奏する限り特に限定されないが、女性ホルモン様作用剤100重量部当たりの原生薬換算量として、カンゾウエキスの含有量が、0.1〜10000重量部、好ましくは1〜1000重量部;オウギエキスの含有量が、0.1〜10000重量部、好ましくは1〜1000重量部;ダイオウエキスの含有量が、0.1〜10000重量部、好ましくは1〜1000重量部;オウゴンエキスの含有量が、0.1〜10000重量部、好ましくは1〜1000重量部が挙げられる。 In the female hormone-like acting agent of the present invention, the content of licorice extract and Ougi extract and/or rhubarb extract and Scutellaria extract are not particularly limited as long as the effects of the present invention are exhibited, but the female hormone-like agent 100 parts by weight The amount of licorice extract is 0.1 to 10000 parts by weight, preferably 1 to 1000 parts by weight; Parts by weight; content of rhubarb extract is 0.1 to 10000 parts by weight, preferably 1 to 1000 parts by weight; content of rhubarb extract is 0.1 to 10000 parts by weight, preferably 1 to 1000 parts by weight. To be
また、本発明の女性ホルモン様作用剤において、カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとの比率としては、本発明の効果を奏する限り特に限定されないが、例えば、カンゾウエキスの原生薬換算量1重量部に対する原生薬換算量として、オウギエキスが0.1〜100重量部、好ましくは0.5〜10重量部、より好ましくは0.7〜8重量部;ダイオウエキスが0.05〜100重量部、好ましくは0.09〜10重量部、より好ましくは0.09〜1重量部;オウゴンエキスが0.1〜100重量部、好ましくは0.3〜10、より好ましくは0.5〜2重量部が挙げられる。 Further, in the female hormone-like agent of the present invention, the ratio of licorice extract and sugi extract and/or rhubarb extract and sardine extract are not particularly limited as long as the effects of the present invention are exhibited, and, for example, a crude drug of licorice extract As a crude drug equivalent to a converted amount of 1 part by weight, 0.1 to 100 parts by weight of cypress extract, preferably 0.5 to 10 parts by weight, more preferably 0.7 to 8 parts by weight; 100 parts by weight, preferably 0.09 to 10 parts by weight, more preferably 0.09 to 1 parts by weight; 0.1 to 100 parts by weight of sardine extract, preferably 0.3 to 10 and more preferably 0.5. Up to 2 parts by weight.
本発明の女性ホルモン様作用剤に含まれる、カンゾウエキスと、オウギエキス並びに/若しくはダイオウエキス及びオウゴンエキスとの総量としては、本発明の効果を奏する限り特に限定されないが、乾燥エキス末量換算で、通常1〜100重量%、好ましくは5〜90重量%、より好ましくは10〜80重量%、更に好ましくは20〜60重量%が挙げられる。なお、本発明において、乾燥エキス末量換算とは、乾燥エキス末を使用する場合にはそれ自体の量であり、液状のエキスを使用する場合には、溶媒を除去した残量に換算した量である。また、乾燥エキス末が、製造時に添加される吸着剤等の添加剤を含む場合は、当該添加剤を除いた量である。 Included in the female hormone-like agent of the present invention, licorice extract, and the total amount of sugi extract and/or rhubarb extract and sardine extract are not particularly limited as long as the effects of the present invention are exhibited, but in terms of dry extract powder amount, The amount is usually 1 to 100% by weight, preferably 5 to 90% by weight, more preferably 10 to 80% by weight, and further preferably 20 to 60% by weight. Incidentally, in the present invention, the dry extract powder amount conversion is the amount of the dry extract powder itself when used, when the liquid extract is used, the amount converted to the residual amount after removing the solvent Is. When the dry extract powder contains an additive such as an adsorbent added at the time of production, the amount is the amount excluding the additive.
[他の含有成分]
本発明の女性ホルモン様作用剤は、前述の生薬エキスの他に、必要に応じて、他の薬理成分を含んでいてもよい。このような薬理成分の種類については、特に限定されないが、例えば、制酸剤、健胃剤、消化剤、整腸剤、鎮痙剤、粘膜修復剤、抗炎症剤、収れん剤、鎮吐剤、鎮咳剤、去痰剤、消炎酵素剤、鎮静催眠剤、抗ヒスタミン剤、カフェイン類、強心利尿剤、抗菌剤、血管収縮剤、血管拡張剤、局所麻酔剤、生薬末、生薬エキス、ビタミン類、メントール類等が挙げられる。これらの薬理成分は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。また、これらの薬理成分の含有量については、使用する薬理成分の種類等に応じて公知のものから適宜設定すればよい。
[Other ingredients]
The female hormone-like agent of the present invention may contain other pharmacological components, if necessary, in addition to the above-mentioned crude drug extract. The type of such a pharmacological component is not particularly limited, and examples thereof include antacids, stomachic agents, digestive agents, intestinal agents, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, and antiphlogistics. Enzymes, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, powdered crude drugs, crude drug extracts, vitamins, menthols and the like. These pharmacological components may be used alone or in combination of two or more. The contents of these pharmacological components may be appropriately set from known ones according to the kind of the pharmacological components used and the like.
本発明の女性ホルモン様作用剤には、所望の剤型に調製するために、必要に応じて、薬学的に許容される基剤や添加剤等が含まれていてもよい。このような基剤及び添加剤としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、等張化剤、可塑剤、分散剤、乳化剤、溶解補助剤、湿潤化剤、安定化剤、懸濁化剤、粘着剤、コーティング剤、光沢化剤、水、油脂類、ロウ類、炭化水素類、脂肪酸類、高級アルコール類、エステル類、水溶性高分子、界面活性剤、金属石鹸、低級アルコール類、多価アルコール、pH調整剤、緩衝剤、酸化防止剤、紫外線防止剤、防腐剤、矯味剤、香料、粉体、増粘剤、色素、キレート剤等が挙げられる。これらの基剤や添加剤は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。また、これらの基剤や添加剤の含有量については、使用する添加成分の種類や剤型等に応じて公知のものから適宜設定すればよい。 The female hormone-like agent of the present invention may optionally contain a pharmaceutically acceptable base or additive 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, brighteners, water, oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps , Lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, perfumes, powders, thickeners, dyes, chelating agents and the like. These bases and additives may be used alone or in combination of two or more. Further, the contents of these bases and additives may be appropriately set from known ones according to the type and dosage form of the additive components used.
[剤型]
本発明の女性ホルモン様作用剤の剤型については、特に制限されず、錠剤、顆粒剤、散剤、丸剤、カプセル剤、フィルム剤、液剤(ドリンク剤)等のいずれであってもよい。これらの剤型の中でも、服用簡易性等の観点から、好ましくは錠剤、顆粒剤、フィルム剤が挙げられる。これらの剤型は、薬学的に許容される基材や添加剤を用いて調製することができ、当該基材や添加剤の種類や配合量についても、製剤技術の分野で公知である。
[Formulation]
The dosage form of the female hormone-like agent of the present invention is not particularly limited and may be any of tablets, granules, powders, pills, capsules, films, liquids (drinks) and the like. Among these dosage forms, tablets, granules and films are preferable from the viewpoint of ease of administration and the like. 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 pharmaceutical technology.
本発明の女性ホルモン様作用剤を錠剤として提供する場合、当該錠剤は、胃溶性錠剤(通常錠剤)又は腸溶性錠剤のいずれであってもよく、また、必要に応じて、糖衣基剤、水溶性フィルムコーティング基剤等でコーティングがなされていてもよい。 When the female hormone-like agent of the present invention is provided as a tablet, the tablet may be either a gastric-soluble tablet (normal tablet) or an enteric-coated tablet, and if necessary, a sugar-coated base, a water-soluble tablet. It may be coated with a film-forming film base.
[用途]
本発明の女性ホルモン様作用剤は、エストロゲン受容体への結合活性を有するため、女性ホルモンとエストロゲン受容体との結合により発現する生理的及び病態生理学的な作用を期待する用途に適用される。具体的には、本発明の女性ホルモン様作用剤は、女性ホルモンの減少により生じる症状の予防又は改善に用いられ、そのような症状としては、更年期症状、更年期障害、骨粗鬆症、体調の揺らぎ、月経痛、肌質又は髪質(コラーゲン及び/又はエラスチンの保持能)の低下等が挙げられる。従って、本発明の女性ホルモン増加剤は、女性ホルモンが減少している女性、特に、女性ホルモンの減少により生じる症状を自覚する女性に対して適用される。具体的な適用対象としては、40歳以上の女性、更年期の女性、卵巣摘出手術後又は化学療法後等の早期卵巣不全の女性、子宮摘出手術後の女性、老年期の女性等が挙げられる。
[Use]
Since the female hormone-like agent of the present invention has a binding activity to the estrogen receptor, it is applied to applications where physiological and pathophysiological actions expressed by the binding of the female hormone and the estrogen receptor are expected. Specifically, the female hormone-like agent of the present invention is used for the prevention or amelioration of symptoms caused by a decrease in female hormone, and such symptoms include menopausal symptoms, menopausal disorders, osteoporosis, physical condition fluctuation, and menstruation. Examples include pain, deterioration of skin quality or hair quality (ability to retain collagen and/or elastin). Therefore, the female hormone-increasing agent of the present invention is applied to a woman having a decreased female hormone, particularly to a woman who is aware of the symptoms caused by the decreased female hormone. Specific applications include women over 40 years old, menopausal women, women with early ovarian insufficiency after ovariectomy surgery or chemotherapy, women after hysterectomy surgery, old age women and the like.
[用量・用法]
本発明の女性ホルモン様作用剤は、経口投与によって投与される。本発明の女性ホルモン様作用剤の投与量については、女性ホルモンの減少の程度、年齢等に応じて適宜設定されるが、例えば、1日当たりの摂取量として、カンゾウエキスの原生薬換算量で0.01〜50g、好ましくは0.1〜10gが挙げられ、オウギエキスの原生薬換算量で0.01〜50g、好ましくは0.1〜10gが挙げられ、ダイオウエキスの原生薬換算量で0.01〜50g、好ましくは0.1〜10gが挙げられ、オウゴンエキスの原生薬換算量で0.01〜50g、好ましくは0.1〜10gが挙げられる。
[Dose/Usage]
The female hormone-like agent of the present invention is administered by oral administration. The dose of the female hormone-like agent according to the present invention is appropriately set according to the degree of reduction of female hormone, age, etc., but for example, the daily intake is 0 in terms of the amount of licorice extract as a crude drug. 0.01 to 50 g, preferably 0.1 to 10 g, and 0.01 to 50 g, preferably 0.1 to 10 g, as a crude drug equivalent of Astragalus membranaceus extract, and 0.1 to 10 g as a crude drug equivalent of rhubarb extract. 01 to 50 g, preferably 0.1 to 10 g, and 0.01 to 50 g, preferably 0.1 to 10 g, in terms of the amount of the crude drug extracted from the drug substance is used.
また、本発明の女性ホルモン様作用剤の投与量としては、生薬エキス総量の乾燥エキス末換算量で、400〜10000mg、好ましくは1300〜7000mgが挙げられ、防已黄耆湯エキスについては1300〜4800mg、当帰飲子エキスについては1300〜5000mg、防風通聖散エキスについては1600〜6000mgが挙げられる。服用タイミングについては特に制限されず、食前、食後、又は食間のいずれであってもよいが、好ましくは食前又は食間が挙げられる。 The dose of the female hormone-like agent of the present invention is 400 to 10000 mg, preferably 1300 to 7000 mg, in terms of dry extract powder based on the total amount of herbal medicine extract, and 1300 to 1000 for Hoi-igi-to extract. 4,800 mg, 1300-5000 mg for Toki-inko extract, and 1600-6000 mg for Bofutsushosan extract. The timing of administration is not particularly limited and may be before meal, after meal, or between meals, but preferably before meal or between meals.
以下、本発明を実施例により具体的に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.
1.エキス末の調製
(1)生薬単味エキス
原料生薬として、カンゾウ、オウギ、ダイオウ、オウゴン、ボウイ、ビャクジュツ、ショウキョウ、タイソウをそれぞれ100g用意し、これらを刻んだ後、15倍量の水を加えて約100℃で1時間抽出し、遠心分離して抽出液を得、減圧下で濃縮して凍結乾燥を行い、カンゾウ単味エキス末15.7g、オウギ単味エキス末21.0g、ダイオウ単味エキス末16.3g、オウゴン単味エキス末29.8g、ボウイエキス単味末3.4g、ビャクジュツ単味エキス末8.6g、ショウキョウ単味エキス末4g、タイソウ単味エキス末38.3gを得た。
1. Preparation of extract powder (1) Crude drug plain extract As raw material crude drug, prepare 100 g of licorice, ougi, rhubarb, sorghum, bowie, sandalwood, ginger, turmeric, and add 15 times amount of water after chopping them. Extract at 100°C for 1 hour, centrifuge to obtain an extract, concentrate under reduced pressure, and lyophilize. Taste extract powder 16.3 g, Scutellariae neat extract powder 29.8 g, Bowie extract single powder powder 3.4 g, White pearl syrup simple powder powder extract 8.6 g, Ginger sardine ground powder powder end product 4 g, Taiso sweet ground powder powder end product 38.3 g Got
(2)防已黄耆湯エキス
原料生薬として、ショウキョウ1(重量部、以下同じ)、タイソウ3、ボウイ5、ビャクジュツ3、オウギ5、カンゾウ1.5の割合で用い、これらを刻んだ後、総量100gを、水15倍重量を用いて約100℃で1時間抽出し、遠心分離して抽出液を得、減圧下で濃縮して凍結乾燥を行い、防已黄耆湯エキス末20.3gを得た。
(2) Bosai-Ogito extract As raw material herb medicine, Ginger 1 (parts by weight, the same applies below), Tassius 3, Bowie 5, Sandalwood 3, Ougi 5, Licorice 1.5 are used in a ratio of The total amount of 100 g was extracted with 15 times the weight of water at about 100° C. for 1 hour, centrifuged to obtain an extract solution, concentrated under reduced pressure and freeze-dried to obtain 20% of the powder of the anti-Kiyakuto extract. 3 g was obtained.
(3)当帰飲子エキス
原料生薬として、トウキ2.5(重量部、以下同じ)、シャクヤク1.5、センキュウ1.5、シツリシ1.5、ボウフウ1.5、ジオウ2.0、ケイガイ0.75、オウギ0.75、カシュウ1.0、カンゾウ0.5の割合で用い、これらを刻んだ後、総量100gを、水15倍重量を用いて約100℃で1時間抽出し、遠心分離して抽出液を得、減圧下で濃縮して凍結乾燥を行い、当帰飲子エキス末18.3gを得た。
(3) Toki-inko extract As a raw material for herbal medicine, Touki 2.5 (part by weight, the same applies below), Peony 1.5, Senkyu 1.5, Shiritsushi 1.5, Bowfu 1.5, Dioe 2.0, Kaigai 0.75, Astragalus 0.75, Kash 1.0, and Licorice 0.5, and after chopping them, a total amount of 100 g was extracted with 15 times weight of water at about 100° C. for 1 hour and centrifuged. The extract was separated to obtain an extract, which was concentrated under reduced pressure and freeze-dried to obtain 18.3 g of Toki-inshi extract powder.
(4)防風通聖散エキス
原料生薬として、キキョウ1.67(重量部、以下同じ)、ビャクジュツ1.67、カンゾウ1.67、オウゴン1.67、セッコウ1.67、ダイオウ1.25、トウキ1.0、シャクヤク1.0、センキュウ1.0、サンシシ1.0、レンギョウ1.0、ハッカ1.0、ケイガイ1.0、ボウフウ1.0、マオウ1.0、ショウキョウ0.33、カッセキ2.5、ボウショウ1.25の割合で用い、これらを刻んだ後、総量100gを、水15倍重量を用いて約100℃で1時間抽出し、遠心分離して抽出液を得、減圧下で濃縮して凍結乾燥を行い、防風通聖散エキス24.1gを得た。
(4) Bofutsushosansan extract As raw material crude drug, kyoto 1.67 (part by weight, the same applies below), juniper gland 1.67, licorice 1.67, sardine 1.67, gypsum 1.67, rhubarb 1.25, touki. 1.0, Peonies 1.0, Senkyu 1.0, Sanshishi 1.0, Forsythia 1.0, Mint 1.0, Kaigai 1.0, Bowfu 1.0, Maou 1.0, Ginger 0.33, Use Kaseki 2.5 and Bowsho 1.25 in proportions, and after chopping them, 100 g of total amount is extracted with 15 times weight of water at about 100° C. for 1 hour and centrifuged to obtain an extract, which is depressurized. The extract was concentrated under the following conditions and freeze-dried to obtain 24.1 g of the wind-proof Tsusho-san extract.
2.試験方法
50U/mlのペニシリン、50mg/mlのストレプトマイシン、3%のウシ胎児血清(FBS)、及び0.5mMのL−グルタミンを含むフェノールレッド非添加DMEM培地を準備した。ヒト乳癌由来のMCF7細胞(株式会社ケー・エー・シー)を準備した。MCF7細胞は、エストロゲン依存的に増殖能が向上する癌細胞であり、MCF7細胞の増殖性は、エストロゲン様作用の検出系として利用されている。
2. Test method A phenol red-free DMEM medium containing 50 U/ml penicillin, 50 mg/ml streptomycin, 3% fetal bovine serum (FBS), and 0.5 mM L-glutamine was prepared. Human breast cancer-derived MCF7 cells (KAC Co., Ltd.) were prepared. MCF7 cells are cancer cells whose proliferative ability is improved in an estrogen-dependent manner, and the proliferative ability of MCF7 cells is used as a detection system for estrogen-like actions.
実験用培地で4×104cells/mlに調整したMCF7細胞懸濁液を、96ウェルプレートのウェルに50μl/ウェルとなるように播種した。次いで、上記の生薬単味エキス末又は漢方エキス末を、1ウェル当たりの各エキス末の終濃度が表1に示す量(単位:μg/mL)となるよう、エキス末と0.2体積%DMSOを含む培地50μlを各ウェルに添加した。また、MCF7細胞懸濁液50μlを播種したウェルに、エキス末を含まない、0.2体積%DMSOを含む培地50μlを添加したものをコントロールとした。ウェルプレートを、37℃、CO2存在下に供し、48時間培養を行った。 An MCF7 cell suspension adjusted to 4×10 4 cells/ml with an experimental medium was seeded in a well of a 96-well plate at 50 μl/well. Then, 0.2% by volume of the above crude herbal extract powder or Chinese herb extract powder was added so that the final concentration of each extract powder per well would be the amount shown in Table 1 (unit: μg/mL). 50 μl of medium containing DMSO was added to each well. Further, a well in which 50 μl of the MCF7 cell suspension was seeded was added with 50 μl of a medium containing 0.2% by volume DMSO without the extract powder as a control. The well plate was subjected to 37° C. in the presence of CO 2 and cultured for 48 hours.
培養後、細胞増殖/細胞毒性アッセイキット(商品名「Cell Counting kit−8」、株式会社同仁科学研究所)を用いて、450nmの吸光度(細胞数に対応)を計測した。測定した450nmの吸光度の値を用いて、下記算出式に従って、細胞増殖促進率を計算した。本試験はn=6で実施し、得られた細胞増殖促進率の平均値を、女性ホルモン様作用の評価値として得た。結果を表1に示す。 After culturing, the absorbance at 450 nm (corresponding to the number of cells) was measured using a cell proliferation/cytotoxicity assay kit (trade name "Cell Counting kit-8", Dojindo Laboratories Inc.). Using the measured absorbance value at 450 nm, the cell growth promoting rate was calculated according to the following calculation formula. This test was performed with n=6, and the average value of the obtained cell growth promoting rates was obtained as the evaluation value of the female hormone-like action. The results are shown in Table 1.
3.結果
比較例1〜3に示すように、イソフラボンが含まれることが知られているカンゾウ及びオウギの単味エキスには、女性ホルモン様作用が確認されたが、その程度は弱いものであった。また、イソフラボンの含有の如何について知られていない、ボウイ、ビャクジュツ、ショウキョウ、タイソウ、ダイオウ、オウゴンの単味エキスのうち、比較例3〜7に示すように、ボウイ、ビャクジュツ、ショウキョウ、タイソウの単味エキスには女性ホルモン様作用は見られなかったが、参考例1、2に示すように、ダイオウ、オウゴンの単味エキスには、弱い女性ホルモン様作用が示唆された。そして、実施例5に示されるように、カンゾウの単味エキスに、女性ホルモン様作用が知られていなかったダイオウ、オウゴンの単味エキスを組み合わせることで、予想外の顕著な女性ホルモン様作用が認められた。なお、実施例5に示されるように、単独で女性ホルモン様作用が認められたエキスの組み合わせで顕著な女性ホルモン様作用が認められたものの、その程度としては、カンゾウ、ダイオウ、オウゴン(比較例1、参考例1、参考例2)の相加効果を下回った一方で、実施例1及び2に示されるように、カンゾウ単味エキスとオウギ単味エキスとの組み合わせでは、女性ホルモン様作用は相乗的に増強された格別顕著なものであった。さらに、実施例3、4、6に示されるように、単独で女性ホルモン様作用が認められたエキスの組み合わせを含む漢方エキス(実施例3の防已黄耆湯エキス及び実施例4の当帰飲子エキスは、カンゾウ及びオウギを含む混合生薬のエキスであり、実施例6の防風通聖散エキスは、カンゾウ、ダイオウ及びオウゴンを含む混合生薬のエキスである。)では、さらに顕著な女性ホルモン様作用が認められた。
3. Results As shown in Comparative Examples 1 to 3, a simple extract of licorice and sugi which is known to contain isoflavone was confirmed to have a female hormone-like action, but its degree was weak. In addition, among the plain extracts of bowie, sandalwood, ginger, ginseng, pearl millet, rhubarb, and sardine, which are not known about the content of isoflavones, as shown in Comparative Examples 3 to 7, bowie, sandalnut, ginger, pearl millet. No hormonal effect was observed in the plain extract of No. 2, but as shown in Reference Examples 1 and 2, a weak female hormonal effect was suggested in the plain extract of Rheum palmatum and Rhubarb. Then, as shown in Example 5, by combining the simple extract of licorice with the simple extract of rhubarb, which has not been known to have a female-hormone-like action, an unexpected remarkable female-hormone-like action was obtained. Admitted. As shown in Example 5, a significant female hormone-like effect was observed in the combination of the extracts which had a female hormone-like effect alone, but the extent of the increase was as follows: licorice, rhubarb, augon (comparative example). 1 and Reference Example 1 and Reference Example 2) were less than the additive effect, but as shown in Examples 1 and 2, the combination of the licorice simple extract and the simple sugi extract showed no female hormone-like action. It was a particularly remarkable synergistically enhanced one. Furthermore, as shown in Examples 3, 4, and 6, Kampo extract containing a combination of extracts which were observed to have female hormone-like actions alone (the Hoi-Ogito extract of Example 3 and the apocalypse of Example 4). The ginkgo syrup extract is an extract of a mixed crude drug containing licorice and sugi, and the Bofutsushosan extract of Example 6 is an extract of a mixed crude drug containing licorice, rhubarb and sardine.) A similar effect was observed.
Claims (5)
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