JP4630597B2 - Environmental hormone excretion promoter - Google Patents
Environmental hormone excretion promoter Download PDFInfo
- Publication number
- JP4630597B2 JP4630597B2 JP2004228362A JP2004228362A JP4630597B2 JP 4630597 B2 JP4630597 B2 JP 4630597B2 JP 2004228362 A JP2004228362 A JP 2004228362A JP 2004228362 A JP2004228362 A JP 2004228362A JP 4630597 B2 JP4630597 B2 JP 4630597B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- environmental hormone
- excretion promoter
- hormone excretion
- promoter according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Description
本発明は、体内に蓄積している環境ホルモンまたは摂取した食物中の環境ホルモンの排泄を促進することができる化合物を有効成分とする環境ホルモン排泄促進剤に関する。 The present invention relates to an environmental hormone excretion promoter comprising as an active ingredient a compound capable of promoting the excretion of environmental hormones accumulated in the body or ingested environmental hormones.
環境に排出された化学物質や天然由来の植物エストロジェンの中には、ヒトや動物の内分泌作用を撹乱させる物質が存在し、ヒトの生殖機能阻害や悪性腫瘍など生体の健康に影響を与える可能性があることがわかってきた。これらの物質は、生物またはその子孫に対して、内分泌作用を変化させることによって健康に有害な影響を生じる外因性の物質、つまり環境ホルモン(ホルモン様作用物質)と呼ばれている。環境ホルモンとしては、焼却施設等から排出されるダイオキシン類、電気機器や印刷インク類に使用されているポリ塩化ビフェニル類(PCB類)、食器、玩具や医療器具などの樹脂製品から溶出していると指摘されているビスフェノールA、フタル酸エステル類、ノニルフェノールなどの樹脂原料や可塑剤、あるいは、DDTをはじめとする殺虫剤および除草剤、トリブチルスズなどの防腐剤が知られている。これら環境ホルモンは、他の一般毒性とは異なり微量で、しかも、胚や胎児に大きな影響を及ぼすと指摘されている。 Chemical substances emitted into the environment and naturally occurring phytoestrogens contain substances that disrupt the endocrine action of humans and animals, which may affect human health such as human reproductive function inhibition and malignant tumors. I know that there is. These substances are called exogenous substances that cause harmful effects on health by changing the endocrine action on an organism or its progeny, that is, environmental hormones (hormone-like substances). Environmental hormones are eluted from dioxins discharged from incineration facilities, polychlorinated biphenyls (PCBs) used in electrical equipment and printing inks, resin products such as tableware, toys and medical equipment. Resin raw materials and plasticizers such as bisphenol A, phthalates, and nonylphenol, insecticides and herbicides such as DDT, and preservatives such as tributyltin are known. These environmental hormones have been pointed out to have a trace amount unlike other general toxicities and to have a great effect on embryos and fetuses.
例えば、環境ホルモンの曝露に関して、ワニにおける生殖器へのDDTの影響、魚類における雌雄同体へのノニルフェノールやトリブチルスズなどの影響、ヒトにおける出生時の性比や、乳幼児期及び小児期の神経発達及び認識発達へのPCB類やダイオキシン類の影響などが報告されている。これらの曝露は食物の摂取及び食物連鎖が主な経路であり、例えば、ヒトの場合、ダイオキシン類が食物を経由して、小腸で吸収され、代謝されずに肝臓や脂肪組織などに蓄積される。一部のダイオキシン類は血液から消化管壁を通じて消化管腔に排泄されるが、ほとんどが再吸収され、糞中に排泄されるのは微量である。また、女性の場合、母乳中にもダイオキシン類が検出され、経産婦よりも初産婦の方が、さらに年齢が高いほど、ダイオキシン類の濃度が高く、授乳に伴う乳児へのダイオキシン類の移行が懸念されている。 For example, regarding exposure to environmental hormones, the effects of DDT on genitals in crocodiles, the effects of nonylphenol and tributyltin on hermaphrodites in fish, sex ratios at birth in humans, and neurodevelopment and cognitive development in infancy and childhood The effects of PCBs and dioxins have been reported. These exposures are mainly through food intake and the food chain. For example, in humans, dioxins are absorbed in the small intestine via food and accumulate in the liver and adipose tissue without being metabolized. . Some dioxins are excreted from the blood through the gastrointestinal tract into the digestive tract cavity, but most of them are reabsorbed and excreted in the faeces. In the case of women, dioxins are also detected in breast milk, and the concentration of dioxins is higher in the first-born mothers than in the parous women, and there is concern about the transfer of dioxins to infants accompanying breastfeeding. Has been.
したがって、生体は、一般環境下で、食物などを通して環境ホルモンにより汚染される可能性があるため、体内に蓄積された環境ホルモンを少しでも多く体外へ排出することが強く望まれている。例えば、高濃度の摂取で中毒症を引き起こしたPCB類やポリ塩化ジベンゾフラン(PCDF)に対する排泄促進に関して、ラットにおける前記有害成分の糞中排泄量、または排泄促進剤への前記有害成分のin vitroでの吸着率(pH5〜pH8緩衝液中での吸着率)を評価することにより、流動パラフィン、スクワランまたは薬用炭に排泄促進効果があることが確認されていた(非特許文献1参照)。最近では、ダイオキシン類に対して、PCB類の排泄促進剤へのin vitroでの吸着率(水中での吸着率)とラットからのPCB類の糞中排泄率に正の相関が確認され、米ぬか等の食物繊維に排泄促進効果があることが確認されている(非特許文献2)。 Therefore, since a living body may be contaminated by environmental hormones through food or the like in a general environment, it is strongly desired to discharge as much environmental hormones accumulated in the body as possible. For example, regarding the promotion of excretion of PCBs and polychlorinated dibenzofurans (PCDF) that caused poisoning due to high intake, the amount of the harmful component excreted in the rat in rats, or the harmful component in the excretion enhancer in vitro It was confirmed that liquid paraffin, squalane or medicinal charcoal has an excretion promoting effect by evaluating the adsorption rate (adsorption rate in pH 5 to pH 8 buffer solution) (see Non-Patent Document 1). Recently, for dioxins, a positive correlation was confirmed between the in vitro adsorption rate of PCBs to the excretion promoter (adsorption rate in water) and the excretion rate of PCBs from rats in the feces, and rice bran It has been confirmed that dietary fibers such as have an excretion promoting effect (Non-patent Document 2).
さらに、クロロフィリンなどのポルフィリン構造をもつ環状化合物(例えば、非特許文献3参照)及びそれらを含む抹茶(非特許文献4参照)、クロレラ及びスピルリナ(非特許文献5参照)、緑色野菜(非特許文献6参照)にダイオキシン類の排泄促進効果が確認された。さらには、新規なダイオキシン類体外排出促進物質として、食物繊維とポルフィリン誘導体を結合させた銅クロロフィリン結合型キトサン(非特許文献7参照)や、マンネンタケの熱水抽出物を含有したダイオキシン類排出作用促進剤が見出されている(特許文献1参照)。
しかしながら、従来の環境ホルモン排泄促進剤では、依然、十分な改善効果は認められてはいなかった。そこで、本発明の目的は、ダイオキシン類など生体内に蓄積された環境ホルモンや食物を経口摂取した際に食物中に含まれる環境ホルモンを消化管内で吸着し、生体外へ少量でも効率よく排出させ、かつ生体に対して安全性が高い環境ホルモン排出促進剤を提供することにある。 However, conventional environmental hormone excretion promoters have not yet been sufficiently improved. Therefore, an object of the present invention is to adsorb environmental hormones contained in food such as dioxins or foods in the digestive tract when they are ingested orally, and efficiently excrete them in small amounts outside the body. Another object of the present invention is to provide an environmental hormone excretion promoter that is highly safe for living bodies.
本発明者らは、上記の課題について検討を行った結果、予想外にも、医薬品の経口製剤のコーティング剤やコーティング基材の補助剤として用いられる化合物が、消化管内でダイオキシン類などの環境ホルモンを吸着しやすく、環境ホルモンを体外に効率よく排出できる環境ホルモン排泄促進剤に適した化合物であることを見出し、本発明を完成するに至った。すなわち、本発明は、(1)合成高分子、セルロース誘導体、天然高分子及び高級脂肪酸誘導体からなる群から選ばれる少なくとも1種の化合物を有効成分とする環境ホルモン排泄促進剤である。(2)前記化合物が、水不溶性であり、かつ皮膜形成能を有することを特徴とする前記(1)に記載の環境ホルモン排泄促進剤である。(3)前記化合物が粒子状、薄層状、繊維状、多孔質状、中空状及び綿状の群から選ばれる形状である前記(1)または前記(2)記載の環境ホルモン排泄促進剤である。また、(4)前記化合物を担体にコーティングしてなる前記(1)または前記(2)記載の環境ホルモン排泄促進剤である。(5)前記化合物をマイクロカプセルの壁物質として使用してなる前記(1)または前記(2)記載の環境ホルモン排泄促進剤である。(6)前記マイクロカプセルの芯物質が環境ホルモンを溶解し、かつ可食性の油状物質であることを特徴とする前記(5)記載の環境ホルモン排泄促進剤である。(7)前記合成高分子が、ポリビニルアセタールジエチルアミノアセテート、アミノアルキルメタクリレートコポリマー、メタアクリル酸コポリマー及びジメチルポリシロキサンからなる群から選ばれる少なくとも1種である前記(1)ないし前記(6)の何れかに記載の環境ホルモン排泄促進剤である。(8)前記合成高分子が、ポリビニルアセタールジエチルアミノアセテートである前記(1)ないし前記(7)の何れかに記載の環境ホルモン排泄促進剤である。(9)前記セルロース誘導体が、エチルセルロース及び/またはメチルセルロースである前記(1)ないし前記(6)の何れかに記載の環境ホルモン排泄促進剤である。(10)前記天然高分子が、セラックである前記(1)ないし前記(6)の何れかに記載の環境ホルモン排泄促進剤である。(11)前記高級脂肪酸誘導体が、ステアリン酸金属塩及び/またはエステルガムである前記(1)ないし前記(6)の何れかに記載の環境ホルモン排泄促進剤である。(12)前記(1)ないし前記(11)の何れかに記載の環境ホルモン排泄促進剤を含有する経口組成物である。 As a result of studying the above problems, the present inventors have unexpectedly discovered that a compound used as a coating agent for an oral pharmaceutical preparation or an auxiliary agent for a coating base is an environmental hormone such as dioxins in the digestive tract. It has been found that the compound is suitable for an environmental hormone excretion promoting agent that can easily adsorb environmental hormones and can efficiently excrete environmental hormones outside the body, and the present invention has been completed. That is, the present invention is (1) an environmental hormone excretion promoter comprising as an active ingredient at least one compound selected from the group consisting of synthetic polymers, cellulose derivatives, natural polymers, and higher fatty acid derivatives. (2) The environmental hormone excretion promoter according to (1), wherein the compound is insoluble in water and has a film-forming ability. (3) The environmental hormone excretion promoter according to (1) or (2) above, wherein the compound has a shape selected from the group consisting of particles, thin layers, fibers, porous, hollow and cotton. . (4) The environmental hormone excretion promoter according to (1) or (2) above, wherein the compound is coated on a carrier. (5) The environmental hormone excretion promoter according to (1) or (2) above, wherein the compound is used as a wall material for microcapsules. (6) The environmental hormone excretion promoter according to (5), wherein the core substance of the microcapsule is an edible oily substance that dissolves environmental hormones. (7) Any of (1) to (6), wherein the synthetic polymer is at least one selected from the group consisting of polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, and dimethylpolysiloxane. Is an environmental hormone excretion promoter. (8) The environmental hormone excretion promoter according to any one of (1) to (7), wherein the synthetic polymer is polyvinyl acetal diethylaminoacetate. (9) The environmental hormone excretion promoter according to any one of (1) to (6), wherein the cellulose derivative is ethyl cellulose and / or methyl cellulose. (10) The environmental hormone excretion promoter according to any one of (1) to (6), wherein the natural polymer is shellac. (11) The environmental hormone excretion promoter according to any one of (1) to (6), wherein the higher fatty acid derivative is stearic acid metal salt and / or ester gum. (12) An oral composition containing the environmental hormone excretion promoter according to any one of (1) to (11).
本発明の環境ホルモン排泄促進剤は、経口投与することによって、前記排泄促進剤中の前記化合物に体内循環により消化管腔に存在する環境ホルモンを効率よく吸着させることにより、消化管への環境ホルモンの再吸収を抑制し、体外への排泄を促進することができる。また、食事の際に、同時に、または、その前後に、本発明の環境ホルモン排泄促進剤を摂取することにより、食物中の環境ホルモンが消化管に吸収される前に、消化管において前記排泄促進剤中の前記化合物に環境ホルモンを効率よく吸着させ排出を促進することができる。これにより、体内での環境ホルモンの蓄積を低減させ、ヒトや動物の生殖機能、後継世代への負荷を大きく軽減できる。さらに、これらの排泄促進剤は、従来の環境ホルモン排泄促進剤よりも吸着率が高いので、少量の投与でも、効率よく環境ホルモンを吸着することができるため、コンプライアンス上、負荷が少なく継続服用でき、その結果、生体内の環境ホルモンの蓄積を抑制できる。 The environmental hormone excretion enhancer of the present invention is obtained by orally administering the environmental hormone present in the gastrointestinal tract through the systemic circulation to the compound in the excretion enhancer, thereby allowing the environmental hormone to enter the digestive tract. Can be suppressed, and excretion outside the body can be promoted. In addition, by taking the environmental hormone excretion promoter of the present invention at the same time or before and after the meal, the excretion promotion in the digestive tract is performed before the environmental hormone in food is absorbed into the digestive tract. It is possible to efficiently adsorb environmental hormones to the compound in the agent to promote excretion. Thereby, accumulation of environmental hormones in the body can be reduced, and the load on the reproductive function of humans and animals and the successor generation can be greatly reduced. Furthermore, since these excretion promoters have higher adsorption rates than conventional environmental hormone excretion promoters, they can be adsorbed efficiently even with a small amount of administration. As a result, accumulation of environmental hormones in the living body can be suppressed.
本発明において、合成高分子は、重縮合、重付加、付加縮合、開環重合または付加重合などにより1種類の低分子化合物(モノマー)または2種類以上のモノマーが繰り返し結合した化合物や、これらの合成高分子をさらにエーテル化やエステル化させた誘導体などである。例えば、医薬品の経口製剤のコーティング剤やコーティング補助剤として利用されている化合物であり、アミノアルキルメタクリレートコポリマーE(商品名オイドラギッドE、ロームファーム社)、アミノアルキルメタクリレートコポリマーRS(商品名オイドラギッドRS、ロームファーム社)及び乾燥メタクリル酸コポリマーLD(商品名オイドラギッドL100−55、ロームファーム社)、メタクリル酸コポリマーL(商品名オイドラギッドL、ロームファーム社)などのアクリル酸系/メタクリル酸系高分子、ポリビニルアセタールジエチルアミノアセテート(商品名AEA三共:三共株式会社、以下AEAとする)などのポリビニル系高分子、クロスポビドン、コポリビドンなどのポリビニルピロリドン系高分子、ジメチルポリシロキサンやジメチルポリシロキサン・二酸化ケイ素混合物(シリコーン樹脂)などのシリコーン、ポリイソブチレンなどのゴム類が挙げられるが、これらに限定されるものではない。本発明の合成高分子は、好ましくは、水に不溶性の化合物であり、皮膜形成能を有していることが望ましい。本発明において、水に不溶性の化合物とは、日本薬局方または米国薬局方での溶解性に関する記載に準じて、ほとんど溶けない、極めて溶けにくい、溶けにくい、やや溶けにくい性状を示す化合物を示す。また、水に不溶性の化合物とは水を加えるとき膨潤する化合物も含む。また、被膜形成能を有する化合物とは、核となる物質の表面に付着、被覆もしくは積層する性質、あるいはカプセルの壁物質の基材となる性質を有する化合物である。 In the present invention, the synthetic polymer is composed of one kind of low molecular weight compound (monomer) or two or more kinds of monomers repeatedly bonded by polycondensation, polyaddition, addition condensation, ring-opening polymerization or addition polymerization, Derivatives obtained by further etherifying or esterifying synthetic polymers. For example, it is a compound that is used as a coating agent or a coating auxiliary agent for oral pharmaceutical preparations, such as aminoalkyl methacrylate copolymer E (trade name Eudragit E, Rohm Farm), aminoalkyl methacrylate copolymer RS (trade name Eudragit RS, ROHM). Acrylic / methacrylic acid polymers, polyvinyl acetal, such as methacrylic acid copolymer LD (trade name Eudragit L100-55, Rohm Farm), methacrylic acid copolymer L (trade name Eudragit L, Rohm Farm) Polyvinyl polymers such as diethylaminoacetate (trade name AEA Sankyo: Sankyo Corporation, hereinafter referred to as AEA), polyvinylpyrrolidone polymers such as crospovidone and copolyvidone, Silicones such as siloxane and dimethyl polysiloxane silicon dioxide mixture (silicone resin), rubber such as polyisobutylene, and the like, but not limited thereto. The synthetic polymer of the present invention is preferably a compound insoluble in water and desirably has a film forming ability. In the present invention, the water-insoluble compound refers to a compound that exhibits almost insoluble, extremely insoluble, insoluble, or slightly insoluble properties according to the description of solubility in the Japanese Pharmacopoeia or the US Pharmacopoeia. Further, the water-insoluble compound includes a compound that swells when water is added. Further, the compound having a film forming ability is a compound having a property of adhering to, coating or laminating on the surface of a substance serving as a nucleus, or a property of becoming a base material of a capsule wall material.
本発明において、セルロース誘導体は、天然のセルロースを用いて、エーテル化やエステル化などにより得ることができる。例えば、医薬品の経口製剤のコーティング剤として利用されている化合物であり、メチルセルロース(MC)、ヒドロキシプロピルメチルセルロース(HPMC)、ヒドロキシプロピルセルロース(HPC)、エチルセルロース(EC)、酢酸セルロース、ピロキシリン(NC)、酢酸フタル酸セルロース(CAP)、フタル酸ヒドロキシプロピルメチルセルロース(HPMCP)、ヒドロキシプロピルメチルセルロースアセテート・サクシネート(HPMCAS)、カルボキシメチルエチルセルロース(CMEC)、カルボキシメチルセルロース・カルシウム、カルボキシメチルセルロース、クロスカルメロースナトリウム(架橋CMC−Na)、低置換度カルボキシメチルセルロース・ナトリウム(L−CMA−Na)、低置換度ヒドロキシプロピルセルロース(L−HPC)、セルロースアセテートジブチルアミノハイドロキシプロピルエーテル(CABP)などが挙げられるが、これらに限定されるものではない。セルロース誘導体は、好ましくは、水に不溶性であり、皮膜形成能を有している。 In the present invention, the cellulose derivative can be obtained by etherification or esterification using natural cellulose. For example, compounds that are used as coating agents for oral pharmaceutical preparations, such as methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), ethylcellulose (EC), cellulose acetate, piroxylin (NC), Cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), carboxymethylethylcellulose (CMEC), carboxymethylcellulose calcium, carboxymethylcellulose, croscarmellose sodium (crosslinked CMC- Na), low-substituted carboxymethylcellulose sodium (L-CMA-Na), low-substituted hydro Shi cellulose (L-HPC), but like cellulose acetate dibutyl amino hydroxy propyl ether (CABP), not limited thereto. The cellulose derivative is preferably insoluble in water and has a film-forming ability.
本発明において、天然高分子は、医薬品添加物や食品添加物として利用できる高分子が望ましい。例えば、医薬品の経口製剤のコーティング剤として利用されている化合物であり、セラック、テルペン樹脂などの天然樹脂、ゼラチン、コラーゲンなどのタンパク質などが挙げられるが、これらに限定されるものではない。天然樹脂やタンパク質は、好ましくは、水に不溶性であり、皮膜形成能を有している。 In the present invention, the natural polymer is preferably a polymer that can be used as a pharmaceutical additive or food additive. For example, it is a compound that is used as a coating agent for oral pharmaceutical preparations, and examples thereof include natural resins such as shellac and terpene resins, proteins such as gelatin and collagen, but are not limited thereto. Natural resins and proteins are preferably insoluble in water and have film-forming ability.
本発明において、高級脂肪酸誘導体では、常温で固体または半固体状態であり、水に不溶性であり、皮膜形成能を有していることが望ましい。例えば、医薬品の経口製剤のコーティング剤として利用されている化合物であり、高級脂肪酸、高級アルコールとの脂肪酸エステル、グリセリン脂肪酸エステル(トリグリセライド含む)、脂肪酸金属塩などが挙げられる。高級脂肪酸としては、ステアリン酸、パルミチン酸、ミリスチン酸、カルミン酸(コチニール)、フェルラ酸、アビエチン酸(ロジンの主成分)など、グリセリン脂肪酸エステルでは、モノステアリン酸グリセリン、アセチルグリセリン脂肪酸エステルなど、高級アルコールとの脂肪酸エステルでは、カルナウバロウ、硬化油など、グリセリン脂肪酸エステルでは、アセチルグリセリン脂肪酸エステル、エステルガム(ロジンエステル)、オクチルドデシルトリグリセリド、カカオ脂、カスターワックス、高級脂肪酸金属塩では、ステアリン酸マグネシウム、ステアリン酸アルミニウム、ステアリン酸カルシウムなどが挙げられるが、これらに限定されるものではない。 In the present invention, it is desirable that the higher fatty acid derivative is in a solid or semi-solid state at room temperature, is insoluble in water, and has a film-forming ability. For example, it is a compound used as a coating agent for oral pharmaceutical preparations, and examples thereof include higher fatty acids, fatty acid esters with higher alcohols, glycerin fatty acid esters (including triglycerides), and fatty acid metal salts. Higher fatty acids include stearic acid, palmitic acid, myristic acid, carminic acid (cochineal), ferulic acid, abietic acid (main component of rosin), and glycerin fatty acid esters such as glyceryl monostearate and acetylglycerin fatty acid ester. In fatty acid ester with alcohol, carnauba wax, hardened oil, etc., in glycerin fatty acid ester, acetyl glycerin fatty acid ester, ester gum (rosin ester), octyldodecyl triglyceride, cocoa butter, castor wax, higher fatty acid metal salt, magnesium stearate, Examples thereof include, but are not limited to, aluminum stearate and calcium stearate.
本発明の環境ホルモン排泄促進剤の有効成分に用いられる化合物は、経口投与して、そのまま単独で、または前記化合物を2種類以上混合して、環境ホルモン排泄促進剤として用いることができる。本発明の環境ホルモン排泄促進剤の有効成分である合成高分子、セルロース誘導体、天然高分子及び/または高級脂肪酸誘導体は、消化管内で環境ホルモンを効率よく吸着する環境ホルモン吸着剤である。さらに、これらの化合物は、環境ホルモンを吸着したまま消化管に吸収されることなく排泄される化合物である。前記化合物は、好ましくは水に不溶性であり、さらに好ましくは、環境ホルモンが体内循環される小腸または大腸の環境下(pH5〜pH8)で不溶性の化合物である。以上より、本発明の環境ホルモン排泄促進剤の有効成分に適した化合物は、水に不溶性であり、かつ皮膜形成能を有しており、たとえば、合成高分子では、ポリビニルアセタールジエチルアミノアセテート、オイドラギッドE、オイドラギッドL100−55、セルロース誘導体ではEC、MC、天然高分子ではセラック、高級脂肪酸誘導体では、ステアリン酸マグネシウム、エステルガム(ロジンエステル)が良い。さらに、このましくは、pH5〜8で水に不溶性であるAEA、オイドラギッドE、EC、MC、エステルガムである。 The compound used as the active ingredient of the environmental hormone excretion enhancer of the present invention can be used as an environmental hormone excretion enhancer by oral administration, as it is, or by mixing two or more of the above compounds. The synthetic polymer, cellulose derivative, natural polymer and / or higher fatty acid derivative, which are the active ingredients of the environmental hormone excretion promoter of the present invention, are environmental hormone adsorbents that efficiently adsorb environmental hormones in the digestive tract. Furthermore, these compounds are excreted without being absorbed into the digestive tract while adsorbing environmental hormones. The compound is preferably insoluble in water, and more preferably insoluble in the environment of the small or large intestine (pH 5 to pH 8) in which environmental hormones are circulated in the body. From the above, the compound suitable as the active ingredient of the environmental hormone excretion promoter of the present invention is insoluble in water and has a film-forming ability. For example, in the case of synthetic polymers, polyvinyl acetal diethylaminoacetate, Eudragit E Eudragit L100-55, EC and MC for cellulose derivatives, shellac for natural polymers, magnesium stearate and ester gum (rosin ester) for higher fatty acid derivatives. Furthermore, this is preferably AEA, Eudragit E, EC, MC, ester gum which is insoluble in water at pH 5-8.
本発明において、環境ホルモン排泄促進剤の有効成分である化合物は、経口投与できる形態であれば特に限定されず、供給された原料をそのまま用いることもできるが、消化管中で環境ホルモンを効率よく吸着できる形状や形態が好ましい。例えば、粉砕機などにより解砕したり、水、エタノール、アセトンなどの溶媒を用いてスプレードライ、凍結乾燥などの処理により、さらに粒子状、薄層状、繊維状、多孔質状、綿状などの形状にして用いることができる。これらの形状にすることにより、比表面積が大きくなり、前記化合物への環境ホルモンの吸着率を高め、排泄促進を効率よくすることができる。 In the present invention, the compound that is the active ingredient of the environmental hormone excretion promoter is not particularly limited as long as it can be administered orally, and the supplied raw material can be used as it is, but the environmental hormone can be efficiently used in the digestive tract. A shape or form that can be adsorbed is preferred. For example, it can be crushed by a pulverizer or sprayed with a solvent such as water, ethanol, acetone, etc., and freeze-dried, etc. to further form particles, thin layers, fibers, porous, cotton, etc. It can be used in a shape. By adopting these shapes, the specific surface area is increased, the adsorption rate of environmental hormones to the compound can be increased, and excretion can be promoted efficiently.
さらに、本発明の環境ホルモン排泄促進剤の有効成分である化合物は、比表面積の大きい担体の表面に付着、積層または被覆できるような性質を有する化合物であり、例えば、経口医薬製剤のコーティング剤やコーティング基材の補助剤として利用される化合物が好適である。例えば、本発明の化合物は、ラテックス、薬用炭、樹脂、寒天、ワックスなどの担体や、その他の多孔質状、中空状もしくは繊維状の担体などに、必要に応じて、クエン酸トリエチル、ポリエチレングリコール、アセチル化モノグリセリド、トリアセチン、ヒマシ油などの可塑剤やアルコールや塩化メチレンなどの溶媒とともにコーティングして用いることもできる。前記化合物は一種または二種以上を混合して使用してもよいし、層状に重ねて使用しても良い。さらに、目的に応じてコーティングを重ねても良い。例えば、本発明の化合物を胃酸などから保護するために、耐酸性コーティングしても良い。 Furthermore, the compound which is an active ingredient of the environmental hormone excretion promoter of the present invention is a compound having such a property that it can be attached, laminated or coated on the surface of a carrier having a large specific surface area. Compounds that are used as adjuvants for coating substrates are preferred. For example, the compound of the present invention can be applied to a carrier such as latex, medicinal charcoal, resin, agar, wax, or other porous, hollow or fibrous carrier, if necessary, triethyl citrate, polyethylene glycol. It can also be used by coating with a plasticizer such as acetylated monoglyceride, triacetin, castor oil, or a solvent such as alcohol or methylene chloride. The compounds may be used alone or in combination of two or more, or may be used in layers. Furthermore, you may accumulate a coating according to the objective. For example, an acid resistant coating may be applied to protect the compound of the present invention from gastric acid and the like.
さらに、本発明の環境ホルモン排泄促進剤の有効成分である化合物は、芯物質を内包化しうるカプセルの壁物質として使用することができる。つまり、本発明の化合物は、マイクロカプセル等の形態にして使用しても良い。ここで、壁物質は、環境ホルモン排泄促進剤であれば特に限定されるものではないが、ポリビニルアセタールジエチルアミノアセテート、オイドラギッドE、エチルセルロース、メチルセルロース、ロジンエステルなどが好ましい。カプセルの壁物質には、さらに、壁物質とは異なる化合物で、目的に応じてコーティングを施しても良い。例えば、壁物質を胃酸などから保護するために、耐酸性コーティングしても良い。また、芯物質は、特に限定されるものではないが、例えば、固体状物質としては、澱粉類、無機塩類、糖類など、半固体状物質としては、モノグリセライド、ワセリンなどのワックス類、また、液状物質としては、ビタミンA、D、E、Kなどの脂溶性ビタミン類、動物油、植物油、鉱物油、合成油などを用いることができる。さらに、芯物質として、壁物質とは異なる本発明の環境ホルモン排泄促進剤の有効成分である化合物を併用しても良い。芯物質は、環境ホルモン物質を溶解することができ、可食性の油状物質が好ましい。 Furthermore, the compound which is an active ingredient of the environmental hormone excretion promoter of the present invention can be used as a capsule wall material capable of encapsulating a core material. That is, the compound of the present invention may be used in the form of a microcapsule or the like. Here, the wall material is not particularly limited as long as it is an environmental hormone excretion promoter, but polyvinyl acetal diethylaminoacetate, Eudragit E, ethylcellulose, methylcellulose, rosin ester and the like are preferable. The wall material of the capsule may be further coated with a compound different from the wall material depending on the purpose. For example, an acid resistant coating may be used to protect the wall material from stomach acid and the like. Further, the core substance is not particularly limited. For example, as a solid substance, starches, inorganic salts, saccharides and the like, as a semi-solid substance, waxes such as monoglyceride and petrolatum, and liquid As the substance, fat-soluble vitamins such as vitamins A, D, E, and K, animal oils, vegetable oils, mineral oils, synthetic oils, and the like can be used. Furthermore, a compound that is an active ingredient of the environmental hormone excretion promoter of the present invention, which is different from the wall material, may be used in combination as the core material. The core substance is preferably an edible oily substance that can dissolve environmental hormone substances.
本発明において、環境ホルモン排泄促進剤の有効成分に用いられる化合物は、各種添加物とともに製剤化し、服用しやすい経口組成物としても提供できる。もちろん、本発明の化合物は、供給された原料のまま本発明の経口組成物に配合しても良いが、粒子状や繊維状等の形状に加工した化合物、または本発明の化合物をコーティングした担体、あるいは本発明の化合物を壁物質とするマイクロカプセルを経口組成物として配合しても良い。ここで、本発明の経口組成物は、医薬品の製剤として一般に用いられる散剤、顆粒剤、カプセル剤、錠剤、懸濁剤、ゼリー剤などが挙げられるが、これに限定するものではない。さらに、チョコレート、ビスケット、飲料水など前記化合物または前記化合物を用いた担体やマイクロカプセルを含む食品の形態でも有用である。好ましくは、本発明の化合物が小腸または大腸で効率よく作用できるように、化合物、または化合物の担体やカプセル等の形態が、胃液から保護されるような腸溶性コーティングが施された経口組成物である。 In the present invention, the compound used as the active ingredient of the environmental hormone excretion promoter can be formulated with various additives and provided as an oral composition that is easy to take. Of course, the compound of the present invention may be blended in the oral composition of the present invention with the supplied raw material, but the compound processed into a shape such as particles or fibers, or a carrier coated with the compound of the present invention Alternatively, microcapsules containing the compound of the present invention as a wall substance may be blended as an oral composition. Here, examples of the oral composition of the present invention include, but are not limited to, powders, granules, capsules, tablets, suspensions, and jelly agents that are generally used as pharmaceutical preparations. Furthermore, it is also useful in the form of foods including the above compounds such as chocolate, biscuits and drinking water, or carriers and microcapsules using the above compounds. Preferably, the composition of the present invention is an oral composition provided with an enteric coating so that the form of the compound or a carrier of the compound or a capsule is protected from gastric juice so that the compound of the present invention can efficiently act in the small intestine or large intestine. is there.
本発明の経口組成物における添加物として、賦形剤、結合剤、崩壊剤、滑沢剤、矯味剤、甘味剤、懸濁剤、乳化剤、着香剤、着色剤、抗酸化剤、ゲル化剤、安定化剤、pH調整剤、防腐剤、保存剤などが挙げられる。賦型剤としては、乳糖、D−マンニトール、トウモロコシデンプン、バレイショデンプン、結晶セルロース、軽質無水ケイ酸、無水リン酸カルシウム、沈降炭酸カルシウム、ケイ酸カルシウム、カカオ脂、流動パラフィン、大豆油、オリブ油、中鎖脂肪酸トリグリセライド、グリセリン、プロピレングリコールなど、結合剤として、ポリビニルピロリドン、デキストリン、ヒドロキシプロピルメチルセルロース、メチルセルロース、ポリビニルアルコール、カルボキシメチルセルロースナトリウム、部分α化デンプン、α化デンプン、アルギン酸ナトリウム、プルラン、アラビアゴム末など、崩壊剤として、低置換度ヒドロキシプロピルセルロース、カルメロース、カルボキシメチルスターチナトリウム、クロスポビドンなど、滑沢剤として、ショ糖脂肪酸エステル、ステアリン酸マグネシウム、フマル酸ステアリルナトリウム、タルクなど、矯味剤として、クエン酸、アスコルビン酸、酒石酸、リンゴ酸、グルタミン酸ナトリウム、5'−イノシン酸ナトリウム、甘味剤としては、ぶどう糖、果糖、蔗糖、エリスリトール、マルチトール、トレハロース、ソルビトール、キシリトール、アスパルテーム、アセスルファムカリウム、サッカリンナトリウム、グリチルリチン二カリウムなど、懸濁剤または乳化剤として、レシチン、ショ糖脂肪酸エステル、ポリグリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、ポリソルベート、ポリオキシエチレン・ポリオキシプロピレン共重合物など、香料として、メントール、はっか油、レモン油、オレンジ油など、着色剤として、酸化チタン、三二酸化鉄、黄色三二酸化鉄、銅クロロフィリンナトリウムなど、抗酸化剤として、アスコルビン酸ナトリウム、L−システイン、亜硫酸ナトリウム、天然ビタミンEなど、ゲル化剤として、カラギーナン、ペクチン、アルギン酸ナトリウム、グァーガム、ローカストビーンガム、キサンタンガム、カルボキシビニルポリマー、カルボキシメチルセルロース、ゼラチンなど、安定化剤として、ポリリン酸ナトリウム、メタリン酸ナトリウムなど、pH調整剤として、クエン酸、クエン酸ナトリウム、塩酸、水酸化ナトリウム、リン酸水素二ナトリウムなど、防腐剤または保存剤として、ソルビン酸、安息香酸塩、パラベンなどを用いることができるが、これらに限定されるものではない。 As additives in the oral composition of the present invention, excipients, binders, disintegrants, lubricants, flavoring agents, sweeteners, suspending agents, emulsifiers, flavoring agents, coloring agents, antioxidants, gelation Agents, stabilizers, pH adjusters, preservatives, preservatives and the like. As an excipient, lactose, D-mannitol, corn starch, potato starch, crystalline cellulose, light anhydrous silicic acid, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, cocoa butter, liquid paraffin, soybean oil, olive oil, medium Chain fatty acid triglyceride, glycerin, propylene glycol, etc., binders such as polyvinylpyrrolidone, dextrin, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sodium carboxymethylcellulose, partially pregelatinized starch, pregelatinized starch, sodium alginate, pullulan, gum arabic powder, etc. As a disintegrator, as a lubricant, such as low-substituted hydroxypropylcellulose, carmellose, sodium carboxymethyl starch, crospovidone, Sucrose fatty acid ester, magnesium stearate, sodium stearyl fumarate, talc, etc., as a corrigent, citric acid, ascorbic acid, tartaric acid, malic acid, sodium glutamate, 5′-inosinate, sweeteners, glucose, fructose , Sucrose, erythritol, maltitol, trehalose, sorbitol, xylitol, aspartame, acesulfame potassium, saccharin sodium, glycyrrhizin dipotassium, etc. Oil, polysorbate, polyoxyethylene / polyoxypropylene copolymer, etc. As a fragrance, menthol, brackish oil, lemon oil, orange oil, etc. Titanium oxide, iron sesquioxide, yellow iron sesquioxide, copper chlorophyllin sodium, etc., as antioxidants, sodium ascorbate, L-cysteine, sodium sulfite, natural vitamin E, etc., gelling agents, carrageenan, pectin, sodium alginate, Guar gum, locust bean gum, xanthan gum, carboxyvinyl polymer, carboxymethylcellulose, gelatin, etc., as stabilizer, sodium polyphosphate, sodium metaphosphate, etc., pH adjuster, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, As a preservative or preservative such as disodium hydrogen phosphate, sorbic acid, benzoate, paraben and the like can be used, but are not limited thereto.
本発明の対象となる環境ホルモンは、WHOや各国政府の環境や健康に関する機関において定義されている物質や、そこで公表されている環境ホルモンとして疑われる化学物質も含まれる。野生生物において雄性化または個体数の減少、雌雄同体、ペニスの矮小化などの影響が確認された有機スズ化合物、ノニルフェノール、有機塩素系農薬、あるいはヒトの生殖機能や新生児や乳児の発達などへの影響が報告されたPCB類やダイオキシン類、あるいは、in vitro実験や動物実験などによりエストロゲン作用が報告されているベンゾ(a)ピレン(3.4−ベンゾピレン)、フタル酸エステル類、ビスフェノールA、ベンゾフェノンなどの物質である。 The environmental hormones that are the subject of the present invention include substances that are defined by WHO and governmental agencies related to the environment and health, and chemical substances that are suspected as environmental hormones published there. Organotin compounds, nonylphenol, organochlorine pesticides that have been confirmed to be affected by masculinization or decrease in population, hermaphrodite, penile dwarfing in wildlife, or effects on human reproductive function or development of newborns and infants PCBs and dioxins that have been reported, or benzo (a) pyrene (3.4-benzopyrene), phthalates, bisphenol A, benzophenone, etc., which have been reported to have estrogenic effects by in vitro and animal experiments, etc. It is a substance.
特に、有機塩素系化合物は、廃棄物処理に伴う非意図的に生成される環境汚染物質や農薬などであり、食物連鎖により生物濃縮やヒトの日常生活で摂取する食物から体内へ取り込まれていることが確認されていることから、本発明の対象となる。有機塩素系化合物は、例えば、ポリ塩化ジベンゾパラジオキシン(PCDD)、ポリ塩化ジベンゾフラン(PCDF)またはコプラナポリ塩化ビフェニル(コプラナーPCB)のダイオキシン類や、二塩化ビフェニル、六塩化ビフェニルなどのPCB類、ヘキサブロモビフェニル、デカブロモビフェニルなどのポリ臭化ビフェニ−ル類(PBB類)などである。 In particular, chlorinated organic compounds are unintentionally produced environmental pollutants and pesticides associated with waste treatment, and are taken into the body from food that is consumed in the daily life of human beings through bioconcentration through the food chain. This is the subject of the present invention. Organochlorine compounds include, for example, polychlorinated dibenzoparadoxine (PCDD), polychlorinated dibenzofuran (PCDF) or coplana polychlorinated biphenyl (coplanar PCB) dioxins, PCBs such as biphenyl dichloride and biphenyl hexachloride, hexabromo And polybrominated biphenyls (PBBs) such as biphenyl and decabromobiphenyl.
以下に、試験例および実施例を示し、本発明の詳細を述べる。ただし、これに限定されるものではない。 The test examples and examples are shown below and the details of the present invention are described. However, it is not limited to this.
(試験例1)
本発明において環境ホルモン排泄促進作用を有する化合物は、環境ホルモンを物理的または化学的に吸着できる性質を有する必要がある。非特許文献3においても、PCB類(またはPCDF、PCDDのいずれもモデル化合物としても良い)の食物繊維へのin vitro吸着率とラットからのPCB糞中排泄率には正の相関が確認されている。したがって、in vitroで環境ホルモンが吸着することが確認できれば、環境ホルモン排泄促進作用を有する化合物として利用できる。本試験では、環境ホルモンのモデル物質として、ダイオキシン類の基本構造を有するジベンゾフラン(DF)を用いた。
(Test Example 1)
In the present invention, the compound having an action of promoting environmental hormone excretion needs to have a property capable of physically or chemically adsorbing environmental hormone. Also in Non-Patent Document 3, a positive correlation was confirmed between the in vitro adsorption rate of PCBs (or both PCDF and PCDD may be used as model compounds) to dietary fiber and the excretion rate of PCB feces from rats. Yes. Therefore, if it can be confirmed that environmental hormones are adsorbed in vitro, it can be used as a compound having an action of promoting environmental hormone excretion. In this test, dibenzofuran (DF) having a basic structure of dioxins was used as a model substance for environmental hormones.
被験物質40mgに水2mLを添加して湿潤させ、さらに、4μg/mLのDFメタノール溶液2mLを添加し、37℃30分間インキュベートした後、3000rpmで15分間遠心分離した。この上澄液2mLに、2%硫酸ナトリウム水溶液2mL及びn−ヘキサン4mLを加え、30分間振とう抽出した。n−ヘキサン層は、硫酸で1回洗浄した後、ガスクロマトグラフで未吸着のDFを定量した(n=3)。ガスクロマトグラフ法で評価を行うにあたり、DFの検量線(ピーク面積とDF濃度)の直線性を確認したところ、相関係数は、0.9999であった。対照とした米ぬか繊維(非特許文献2記載)以外の被験物質は、供給された原料をそのまま用いた。米ぬか繊維は、米ぬか5gにアセトン20gを添加して、5分間スターラーで撹拌後、ろ紙で濾過した。その後、減圧下、70℃で4時間乾燥した。 2 mL of water was added to 40 mg of the test substance to be moistened, 2 mL of 4 μg / mL DF methanol solution was added, and the mixture was incubated at 37 ° C. for 30 minutes, and then centrifuged at 3000 rpm for 15 minutes. To 2 mL of this supernatant, 2 mL of 2% aqueous sodium sulfate solution and 4 mL of n-hexane were added, and the mixture was extracted by shaking for 30 minutes. The n-hexane layer was washed once with sulfuric acid, and then unadsorbed DF was quantified by gas chromatography (n = 3). When the linearity of the DF calibration curve (peak area and DF concentration) was confirmed in the evaluation by the gas chromatographic method, the correlation coefficient was 0.9999. As the test substance other than the rice bran fiber (described in Non-Patent Document 2) as a control, the supplied raw material was used as it was. The rice bran fiber was filtered with a filter paper after adding 20 g of acetone to 5 g of rice bran and stirring with a stirrer for 5 minutes. Then, it dried at 70 degreeC under pressure reduction for 4 hours.
試験結果を表1に吸着率(%)及び標準偏差(S.D.)を示す。本試験の結果、合成高分子、天然高分子及び高級脂肪酸誘導体から選ばれる化合物にDFの吸着作用を有することが確認された。特に、中性からアルカリ性で水に不溶性の合成高分子であるAEA、EC、オイドラギッドL100−50、オイドラギッドEの順で高い吸着率を認めた。また、エステルガム、ステアリン酸マグネシウム、ジメチルポリシロキサンやセラックも比較的高い吸着率を示した。特に、AEAやECは、対照の米ぬか繊維よりも高い吸着率を示した。以上より、これらの化合物は、体内で環境ホルモンを吸着できる環境ホルモン吸着剤として、さらに環境ホルモンを体外に排出できる環境ホルモン排泄促進剤として有用であることが確認された。 The test results are shown in Table 1 for the adsorption rate (%) and standard deviation (S.D.). As a result of this test, it was confirmed that a compound selected from a synthetic polymer, a natural polymer and a higher fatty acid derivative has a DF adsorption action. In particular, a high adsorption rate was observed in the order of neutral, alkaline, water-insoluble synthetic polymer AEA, EC, Eudragit L100-50, Eudragit E. Ester gum, magnesium stearate, dimethylpolysiloxane and shellac also showed a relatively high adsorption rate. In particular, AEA and EC showed higher adsorption rates than the control rice bran fiber. From these results, it was confirmed that these compounds are useful as environmental hormone adsorbents capable of adsorbing environmental hormones in the body, and as environmental hormone excretion promoters capable of excreting environmental hormones outside the body.
(実施例1)
AEA10g及びクエン酸10gを200mlの水に溶解した。この溶液中に酢酸トコフェロール10gを加えポリトロンを用いて乳化し、酢酸トコフェロールのエマルジョンを得た。これとは別に、あらかじめメグルミン10gを100mlの水に溶解したメグルミン溶液を調製した。酢酸トコフェロールのエマルジョン溶液を室温下スターラーで攪拌しながら、ペリスタポンプでメグルミン溶液を徐々に加え、マイクロカプセルを得た。その後、このマイクロカプセルを300メッシュの篩を用いて濾過し、水で洗浄した後、五酸化リンを装填したデシケーター中で真空乾燥し、酢酸トコフェロールを内包した約100〜500μmの球状マイクロカプセル(以下、MC−AEAとする)を得た。
Example 1
10 g AEA and 10 g citric acid were dissolved in 200 ml water. 10 g of tocopherol acetate was added to this solution and emulsified using polytron to obtain an emulsion of tocopherol acetate. Separately, a meglumine solution in which 10 g of meglumine was previously dissolved in 100 ml of water was prepared. While stirring the emulsion solution of tocopherol acetate with a stirrer at room temperature, the meglumine solution was gradually added with a peristaltic pump to obtain microcapsules. Thereafter, the microcapsules were filtered using a 300-mesh sieve, washed with water, vacuum-dried in a desiccator charged with phosphorus pentoxide, and approximately 100 to 500 μm spherical microcapsules (hereinafter referred to as “tocopherol acetate”). MC-AEA).
(実施例2)
AEA100g及びクエン酸30gを水1000mLに溶解した後、スプレードライヤーで、110〜130℃で乾燥し、綿状のポリビニールアセタールジエチルアミノアセテートのスプレードライ品(以下、SD−AEAとする)を得た。
(Example 2)
100 g of AEA and 30 g of citric acid were dissolved in 1000 mL of water, and then dried at 110 to 130 ° C. with a spray dryer to obtain a spray-dried product of cotton-like polyvinyl acetal diethylaminoacetate (hereinafter referred to as SD-AEA).
(試験例2)
実施例1のMC−AEA、実施例2のSD−AEA、AEA(供給された原料)に対するDFの吸着率を評価した。対照として、試験例1の米ぬか繊維を用いた。試験法は、試験例1に準じ、被験物質40mgに、20μg/mLの10%DFメタノール溶液4mLを添加し、37℃30分間インキュベートした後、3000rpmで15分間遠心分離した。この上澄液2mLに、2%硫酸ナトリウム水溶液2mL及びn−ヘキサン4mLを加え、30分間振とう抽出した。n−ヘキサン層は、硫酸で1回洗浄した後、ガスクロマトグラフ法を用いて未吸着のDFを定量した(n=3)。ガスクロマトグラフ法で評価を行うにあたり、DFの検量線(ピーク面積とDF濃度)の直線性を確認したところ、相関係数は、0.9999であった。
(Test Example 2)
The adsorption rate of DF with respect to MC-AEA of Example 1, SD-AEA of Example 2, and AEA (supplied raw material) was evaluated. As a control, the rice bran fiber of Test Example 1 was used. The test method was the same as in Test Example 1. To 40 mg of the test substance, 4 mL of 20 μg / mL 10% DF methanol solution was added, incubated at 37 ° C. for 30 minutes, and then centrifuged at 3000 rpm for 15 minutes. To 2 mL of this supernatant, 2 mL of 2% aqueous sodium sulfate solution and 4 mL of n-hexane were added, and the mixture was extracted by shaking for 30 minutes. The n-hexane layer was washed once with sulfuric acid, and then unadsorbed DF was quantified using a gas chromatographic method (n = 3). When the linearity of the DF calibration curve (peak area and DF concentration) was confirmed in the evaluation by the gas chromatographic method, the correlation coefficient was 0.9999.
試験結果を表2に示す。本試験の結果、本発明の化合物をマイクロカプセル化、あるいはスプレードライ加工することにより、DFの吸着率を著しく高めることが判明した。以上より、本発明の化合物は、カプセル化、繊維化、微細化などの製剤化が可能であり、従来の排泄促進剤と比べて、環境ホルモン物質を効率よく吸着し、かつ体外へ排泄させることができることが明らかとなった。 The test results are shown in Table 2. As a result of this test, it was found that the DF adsorption rate was remarkably increased by microencapsulating or spray-drying the compound of the present invention. As described above, the compound of the present invention can be formulated into capsules, fibers, and refined, and can adsorb environmental hormone substances efficiently and excrete them outside the body as compared with conventional excretion promoters. It became clear that it was possible.
Claims (11)
前記化合物はポリビニルアセタールジエチルアミノアセテート、アミノアルキルメタクリレートコポリマー、メタクリル酸コポリマー、ジメチルポリシロキサン、ポリ酢酸ビニル、エチルセルロース、メチルセルロース及びセラックからなる群から選ばれる化合物であり、
前記環境ホルモンはダイオキシン類、ポリ塩化ビフェニル類及びポリ臭化ビフェニル類からなる群から選ばれる、環境ホルモン排泄促進剤。 Synthetic polymer, a environmental hormone excretion promoter comprising as an active ingredient at least one compound selected from cellulose derivatives and natural high content child or Ranaru group,
The compound is a compound selected from the group consisting of polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, dimethylpolysiloxane, polyvinyl acetate, ethyl cellulose, methyl cellulose and shellac.
The environmental hormone excretion promoter selected from the group consisting of dioxins, polychlorinated biphenyls and polybrominated biphenyls .
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JPS63287543A (en) * | 1987-05-19 | 1988-11-24 | Eisai Co Ltd | Production of microcapsule |
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