JP2009035527A - Androgen receptor-binding inhibitor composed of animal placenta extract - Google Patents
Androgen receptor-binding inhibitor composed of animal placenta extract Download PDFInfo
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- JP2009035527A JP2009035527A JP2007220363A JP2007220363A JP2009035527A JP 2009035527 A JP2009035527 A JP 2009035527A JP 2007220363 A JP2007220363 A JP 2007220363A JP 2007220363 A JP2007220363 A JP 2007220363A JP 2009035527 A JP2009035527 A JP 2009035527A
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Abstract
Description
本発明は、アンドロゲン受容体結合阻害剤、抗男性ホルモン剤、養毛化粧料に関する。具体的に言うと、テストステロンがテストステロン５α−リダクターゼの作用を受け活性型５α−ジヒドロテストステロン（活性型５α−ＤＨＴ）に還元されると、５α−ＤＨＴが細胞内の受容体と結合し転写を介して性の分化や性徴の発現といった強いアンドロゲンの生理作用を発現する。加齢にしたがい、男性では男性ホルモンのバランスの乱れから、前立腺肥大症、前立腺癌、男性型禿頭、多毛症、などの男性ホルモン亢進に由来する疾患が増加している。
本発明は５α−ＤＨＴが、アンドロゲン受容体への結合を阻害する作用を有する動物胎盤抽出物よりなる新規な抗男性ホルモン剤及びアンドロゲン受容体結合阻害剤を利用した養毛化粧料に関する。The present invention relates to an androgen receptor binding inhibitor, an anti-androgen agent, and a hair nourishing cosmetic. Specifically, when testosterone is reduced to active 5α-dihydrotestosterone (active 5α-DHT) by the action of testosterone 5α-reductase, 5α-DHT binds to an intracellular receptor and mediates transcription. It expresses strong androgen physiological actions such as sex differentiation and sexual characteristics. As males age, male hormones are out of balance, leading to an increase in male hormones such as benign prostatic hyperplasia, prostate cancer, androgenetic baldness, and hirsutism.
The present invention relates to a novel anti-androgen agent comprising an animal placenta extract having an action of 5α-DHT inhibiting binding to androgen receptor and a hair nourishing cosmetic using an androgen receptor binding inhibitor.
多くのステロイドホルモンは産生臓器から分泌された分子型で受容体と結合してその作用を発現するが、アンドロゲンと総称される男性ホルモンの場合、たとえばテストステロンは標的臓器の細胞内に入ってテストステロン５α−レダクターゼにより５α−ジヒドロテストステロン（５α−ＤＨＴ）に還元されてから受容体と結合し、としての作用を発現する。 Many steroid hormones are expressed in the form of molecules secreted from the production organ and bind to receptors to express their effects. In the case of male hormones collectively called androgens, for example, testosterone enters the cells of the target organ and enters testosterone 5α. -It is reduced to 5α-dihydrotestosterone (5α-DHT) by reductase, and then binds to the receptor to express its action.
アンドロゲンは重要なホルモンであるが、それが過度に作用すると、前立腺肥大症、前立腺癌、男性型禿頭、多毛症などを誘発する。そこで、従来から、これらの症状を改善するために過剰のアンドロゲンの作用を抑制する方法、具体的には、テストステロンを活性型５α−ＤＨＴに還元するテストステロン５α−レダクターゼの作用を阻害することにより活性な５α−ＤＨＴを生じるのを抑制する方法と、テストステロンから生じた５α−ＤＨＴが受容体と結合するのを阻害することによりアンドロゲン活性を発現させない方法とが検討され、その結果シプロテロンアセテート、オキセンドロン、酢酸クロルマジノン等の有効性が確認された。 Androgen is an important hormone, but when it works excessively, it causes prostatic hypertrophy, prostate cancer, androgenetic baldness, hirsutism, etc. Therefore, conventionally, in order to improve these symptoms, a method of suppressing the action of excess androgen, specifically, by inhibiting the action of testosterone 5α-reductase which reduces testosterone to active 5α-DHT A method for suppressing the generation of 5α-DHT, and a method for inhibiting the binding of 5α-DHT generated from testosterone to the receptor to prevent the development of androgenic activity. As a result, cyproterone acetate and oxendron The effectiveness of chlormadinone acetate was confirmed.
しかしながら、これらはステロイドホルモン誘導体であるため、ホルモン様作用等の好ましくない副作用を有するという欠点があった。 However, since these are steroid hormone derivatives, they have the disadvantage of having undesirable side effects such as hormone-like effects.
本発明の目的は、テストステロン５α−レダクターゼにより活性化された５α−ＤＨＴのアンドロゲン受容体結合阻害作用を有する新規な動物胎盤抽出物を見いだし、安全な抗男性ホルモン剤を提供すると共に、予防のための養毛化粧料を提供することにある。 An object of the present invention is to find a novel animal placenta extract having an androgen receptor binding inhibitory action of 5α-DHT activated by testosterone 5α-reductase, to provide a safe anti-androgen agent, and for prevention It is to provide hair nourishing cosmetics.
本発明に係るアンドロゲン受容体結合阻害剤は動物胎盤抽出物よりなることを特徴としている。 The androgen receptor binding inhibitor according to the present invention is characterized by comprising an animal placenta extract.
以下に、本発明について更に詳細に説明すると、本発明に係るアンドロゲン阻害剤は、動物の胎盤酵素等で抽出したエキスからなるものであって、活性化された５α−ＤＨＴをアンドロゲン受容体に結合するのを阻害するものである。
本発明においては、使用できる胎盤は豚、馬、などの哺乳類を主に使用するが、この限りではない。Hereinafter, the present invention will be described in more detail. The androgen inhibitor according to the present invention comprises an extract extracted with an animal placenta enzyme or the like, and binds activated 5α-DHT to an androgen receptor. It is an obstacle to doing.
In the present invention, the placenta that can be used mainly includes mammals such as pigs and horses, but is not limited thereto.
また、胎盤抽出物は、一般的な製剤化による公知の方法により単独で、あるいは適当な助剤を用いて、内服液剤、内服固形剤、注射剤、座剤等各種製剤化され、化粧料、医薬部外品、医薬品等の構成成分として広く利用することができる。
養毛化粧料としては、例えば、ヘアトニック、ヘアクリーム、ヘアリキッド、ヘアローション、ヘアシャンプー、ヘアリンス等、任意の剤形が可能である。In addition, the placenta extract is formulated into various preparations such as a liquid preparation for internal use, a solid preparation for internal use, an injection, and a suppository by a known method based on a general formulation, or using an appropriate auxiliary agent. It can be widely used as a constituent of quasi-drugs and pharmaceuticals.
As the hair nourishing cosmetic, any dosage form such as hair tonic, hair cream, hair liquid, hair lotion, hair shampoo, hair rinse and the like is possible.
製剤中における胎盤抽出物の配合量は、適宜、使用目的、性別、症状等を考慮して検討すればよいが、胎盤抽出物の量として約０．００５〜７０重量％である。 The blending amount of the placenta extract in the preparation may be appropriately examined in consideration of the purpose of use, sex, symptoms, etc., but the amount of the placenta extract is about 0.005 to 70% by weight.
以下、本発明に係る実施例を示し、本発明について更に詳細に説明する。Examples of the present invention will be described below, and the present invention will be described in more detail.
アンドロゲン受容体結合阻害作用の試験実施例１による胎盤抽出物について、下記の試験法によりアンドロゲン受容体結合阻害作用を試験した。 Test of Androgen Receptor Binding Inhibitory Action The placenta extract according to Example 1 was tested for the androgen receptor binding inhibitory action by the following test method.
東北大学加齢医学研究所付属医用細胞資源センターより供与頂いたアンドロゲン依存性ヒト前立腺癌細胞株ＬＮＣａＰ．ＦＧＣ（ＴＫＧ０６０３）を、１０％ＦＣＳ含有ＲＰＭＩ−１６４０培地（以下前培養培地）を用いて１．０×１０４ｃｅｌｌｓ／ｍＬの細胞密度にて１２穴マイクロプレートに播種、３７℃、５％Ｃ０２−９５％ａｉｒの下で７２ｈｒ培養した。前培養培地を吸引除去後、内因性の５α−ＤＨＴを除くため活性炭処理したＦＣＳを０．５％含むＲＰＭＩ１６４０培地（アッセイ培地）を１ｍＬ加え、２４時間後、アッセイ培地を吸引除去した。これに、アッセイ培地と２５０ｎＭのＤＨＴを添加したアッセイ培地を用いて、凍結乾燥した胎盤エキスを溶解し１ｍＬ加え、７２ｈｒ培養を行った。
培養終了後にアッセイ培地０．５ｍＬにＷＳＴ（同仁化学）２０μＬの割合で加えた培地０．５ｍＬ加えて３７℃３ｈｒ培養を行った。生じた水溶性ホルマザンを４５０ｎｍの吸光度をマイクロプレートリーダーで測定した。An androgen-dependent human prostate cancer cell line, LNCaP., Provided by the Institute for Aging Medicine, Tohoku University. FGC (TKG0603) was seeded in a 12-well microplate using RPMI-1640 medium (hereinafter referred to as preculture medium) containing 10% FCS at a cell density of 1.0 × 10 4 cells / mL, 37 ° C., 5% C02. -Cultured for 72 hr under -95% air. After removing the preculture medium by aspiration, 1 mL of RPMI1640 medium (assay medium) containing 0.5% of FCS treated with activated carbon to remove endogenous 5α-DHT was added, and after 24 hours, the assay medium was removed by aspiration. Using this assay medium and assay medium supplemented with 250 nM DHT, 1 mL of lyophilized placenta extract was dissolved and added, and cultured for 72 hr.
After completion of the culture, 0.5 mL of the medium added at a ratio of 20 μL of WST (Dojindo Chemical) to 0.5 mL of the assay medium was added and cultured at 37 ° C. for 3 hours. The resulting water-soluble formazan was measured for absorbance at 450 nm with a microplate reader.
抗アンドロゲン作用を示す結合阻害率を次式により算出した。
結合阻害率（％）＝｛１−（Ｃ−Ｄ）／（Ａ−Ｂ）｝×１００
但し、Ａ：ＤＨＴ添加、試料無添加の場合の吸光度Ｂ：ＤＨＴ無添加、試料無添加の場合の吸光度Ｃ：ＤＨＴ添加、試料添加の場合の吸光度Ｄ：ＤＨＴ無添加、試料添加の場合の吸光度The binding inhibition rate showing antiandrogenic activity was calculated by the following formula.
Binding inhibition rate (%) = {1− (C−D) / (A−B)} × 100
However, A: Absorbance when DHT is added and sample is not added B: Absorbance when DHT is not added and sample is not added C: Absorbance when DHT is added and sample is added D: Absorbance when DHT is not added and sample is added
図１、図２より、胎盤抽出物が濃度依存的にアンドロゲン結合阻害作用を有することが確認された。1 and 2, it was confirmed that the placenta extract has an androgen binding inhibitory effect in a concentration-dependent manner.
本発明は、副作用が少なく新規なアンドロゲン受容体結合阻害剤を提供することができる。この阻害剤により、抗男性ホルモン剤として、前立腺肥大症、前立腺癌、男性型禿頭、多毛症などの改善あるいは予防に大きく貢献できる。The present invention can provide a novel androgen receptor binding inhibitor with few side effects. This inhibitor can greatly contribute to the improvement or prevention of prostatic hypertrophy, prostate cancer, androgenetic baldness, hirsutism, etc. as an anti-androgenic agent.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2015526469A (en) * | 2012-08-20 | 2015-09-10 | ボリス, マルコシアンMarkosian, Boris | Placental vaccination therapy for cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2015526469A (en) * | 2012-08-20 | 2015-09-10 | ボリス, マルコシアンMarkosian, Boris | Placental vaccination therapy for cancer |
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