JP2009269895A - Drug-induced liver disorder inhibitory composition - Google Patents

Drug-induced liver disorder inhibitory composition Download PDF

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JP2009269895A
JP2009269895A JP2008140140A JP2008140140A JP2009269895A JP 2009269895 A JP2009269895 A JP 2009269895A JP 2008140140 A JP2008140140 A JP 2008140140A JP 2008140140 A JP2008140140 A JP 2008140140A JP 2009269895 A JP2009269895 A JP 2009269895A
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drug
induced liver
composition
bitter gourd
liver injury
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Kazuyoshi Yazawa
一良 矢澤
Tomoyuki Susa
智之 諏佐
Ayumi Takasu
亜由美 高須
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Shonan Inst For Medical & Prev
Shonan Institute for Medical and Preventive Science
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Shonan Institute for Medical and Preventive Science
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition having a drug-induced liver disorder inhibitory action, and as a result, to provide foods, beverages, medicines or feeds containing the composition. <P>SOLUTION: This drug-induced liver disorder inhibitory composition is characterized by containing the components of seeds of a balsam pear (Momordica charantia), and the foods, beverages, medicines or feeds containing the same composition are also provided. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

本発明はゴーヤ種子の成分を含有することを特徴とした薬物性肝障害抑制組成物に関する。
本発明における薬物性肝障害抑制組成物とは、薬物性肝障害の予防、薬物性肝障害の進行・進展の防止、及び/または薬物性肝障害患者における肝臓の機能の改善のため、更には肝臓の機能を正常に維持するために、ヒト若しくはヒト以外の動物に与えられる医薬品(動物用治療薬も含む)用、飲食品用、及び飼料用の組成物を意味する。
The present invention relates to a drug-induced liver injury-suppressing composition comprising a bitter gourd seed component.
The drug-induced liver injury-suppressing composition in the present invention refers to prevention of drug-induced liver injury, prevention of progression and progression of drug-induced liver injury, and / or improvement of liver function in patients with drug-induced liver injury, It means compositions for pharmaceuticals (including animal therapeutics), foods and drinks, and feeds given to humans or non-human animals in order to maintain normal liver function.

薬物性肝障害は、薬物療法を継続する過程において発現する副作用である。薬剤使用の頻度や、薬剤の種類が増加する近年、本疾患は増加してきている。薬物性肝障害はアレルギー性と中毒性の2つの発生機序に分けられる。肝機能改善剤としては、肝保護作用、利胆作用、抗酸化作用を有する薬剤が考えられ、ウルソデオキシコール酸、アミノエチルスルホ酸などが使用されているが、臨床上、薬効や副作用の点において十分に満足できる薬剤は未だなく、効果が高く副作用の少ない肝機能改善剤が望まれている。また、肝機能を改善する食品としては、ウコン、シリマリンなどが使用されている。Drug-induced liver injury is a side effect that develops in the course of continuing drug therapy. In recent years when the frequency of drug use and the types of drugs have increased, this disease has increased. Drug-induced liver injury can be divided into two developmental mechanisms, allergic and toxic. As liver function improving agents, drugs with liver protective action, biliary action and antioxidant action are considered, and ursodeoxycholic acid, aminoethyl sulfonic acid, etc. are used, but in terms of clinical efficacy and side effects However, there is still no drug that can be satisfactorily satisfied, and a liver function improving agent that is highly effective and has few side effects is desired. In addition, turmeric, silymarin and the like are used as foods for improving liver function.

ゴーヤ(学名 Momordica charantia L.)は別名ニガウリともよばれるウリ科の植物で、インドを中心とした熱帯アジア原産であり、日本では沖縄県や南九州で多く栽培されている。ゴーヤ通常可食部(果実)には細胞傷害防御・修復作用、アルコール脱水素酵素促進作用、発癌予防作用、血糖値低下作用、脂質代謝改善作用、育毛作用、美白作用、消臭作用があるといわれている。しかしゴーヤ種子において肝機能改善に有効であるという報告は全くない。Bitter gourd (Scientific name Momorica charantia L.) is a cucurbitaceae plant also known as bitter gourd and is native to tropical Asia centering on India and is cultivated in Japan in Okinawa and southern Kyushu. The bitter gourd normal edible part (fruit) has cytotoxicity protection / restoration effect, alcohol dehydrogenase promotion effect, carcinogenesis prevention effect, blood sugar level lowering effect, lipid metabolism improving effect, hair growth effect, whitening effect, deodorizing effect It is said. However, there is no report that bitter gourd seed is effective in improving liver function.

本発明が解決しようとする課題は肝機能改善作用を有する組成物を提供し、ひいては該組成物を含有する飲食品又は医薬品または飼料を提供することにある。The problem to be solved by the present invention is to provide a composition having an effect of improving liver function, and to provide a food, drink, medicine or feed containing the composition.

上記課題を解決すべく研究を重ねた結果、ゴーヤ種子が四塩化炭素誘導薬物性肝障害モデルマウスにおいて薬物性肝障害を抑制することを見出した。すなわち、本発明は、以下の構成を有する。
(1)ゴーヤ種子の成分を含有することを特徴とする薬物性肝障害抑制組成物
(2)上記の成分がゴーヤ種子のメタノール抽出物である(1)に記載の薬物性肝障害抑制組成物
(3)上記(1)または(2)に記載の薬物性肝障害抑制組成物を含む飲食品または医薬品または飼料
As a result of repeated studies to solve the above-mentioned problems, it was found that bitter gourd seeds suppress drug-induced liver injury in a carbon tetrachloride-induced drug-induced liver injury model mouse. That is, the present invention has the following configuration.
(1) A drug-induced liver injury-suppressing composition comprising a bitter gourd seed component (2) The drug-induced liver injury-suppressing composition according to (1), wherein the component is a methanol extract of bitter gourd seed (3) Food / beverage products or pharmaceuticals or feeds containing the drug-induced liver injury-suppressing composition according to (1) or (2)

本発明により、ゴーヤ種子の成分を含有することを特徴とする薬物性肝障害抑制組成物、及び該組成物を含有する飲食品または医薬品または飼料を提供することができる。According to the present invention, it is possible to provide a drug-induced liver injury-suppressing composition containing a bitter gourd seed component, and a food, drink, medicine or feed containing the composition.

本発明に関わる「ゴーヤ種子」は(英名 Bitter melon 、学名 Momordica charantia)をさす。“Goya seed” relating to the present invention refers to (English name: Bitter melon, scientific name: Modica charantia).

本発明に関わるゴーヤ種子は生のまま使用することができ、乾燥もしくは乾燥後粉砕した粉末としても使用することができる。また、熱水抽出、エタノール、または酢酸エチル等有機溶媒で抽出した抽出物としても使用できる。The bitter gourd seed according to the present invention can be used as it is, and can also be used as a dried or pulverized powder after drying. It can also be used as an extract extracted with an organic solvent such as hot water extraction, ethanol, or ethyl acetate.

本発明に関わる薬物性肝障害抑制剤を製造するには、上記の方法で製造したゴーヤ種子粉末もしくは抽出物を用いることができ、常法に従って公知の医薬用無毒性担保と組み合わせて製剤化すればよい。本発明に関わる抗骨粗鬆症剤は、種々の剤型での投与が可能であり、例えば、経口投与剤としては錠剤、顆粒剤、散剤、カプセル剤、ソフトカプセル剤等の固形剤、溶液剤、懸濁剤、乳剤等の液剤、凍結乾燥製剤等が挙げられ、非経口投与剤としては、注射剤のほか、坐剤、噴射剤、経皮吸収剤等が挙げられ、これらの製剤は製剤上の常套手段により調整することができる。上記の医薬用無毒性担保としては、例えば、グルコース、乳糖、ショ糖、澱粉、マンニトール、デキストリン、脂肪酸グリセリド、ポリエチレングリコール、ヒドロキシエチルデンプン、エチレングリコール、ポリオキシエチレンソルビタン脂肪酸エステル、アミノ酸、アルブミン、水、生理食塩水等が挙げられる。また、必要に応じて安定化剤、滑剤、湿潤剤、乳化剤、結合剤等の慣用の添加剤を適宜添加することができる。本発明に関わる抗骨粗鬆症剤においてモモタマナ粉末もしくは抽出物の投与量は、患者の年齢、体重、症状、疾患の程度、投与スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり0.01〜10g/体重程度とされ、一日数回に分けて投与してもよい。
動物においても同様に製剤化すればよい。動物の年齢、体重、症状、疾患の程度、投与スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日あたり0.01〜10g/kg体重程度とされ、一日数回に分けて投与してもよい。
In order to produce the drug-induced hepatic disorder inhibitor according to the present invention, bitter gourd seed powder or extract produced by the above method can be used and formulated in combination with a known non-toxic pharmaceutical guarantee according to a conventional method. That's fine. The anti-osteoporosis agent according to the present invention can be administered in various dosage forms. For example, as oral administration agents, solid agents such as tablets, granules, powders, capsules, soft capsules, solutions, suspensions Liquids such as suppositories and emulsions, lyophilized preparations, and the like, and parenteral administration agents include suppositories, propellants, transdermal absorption agents, etc., in addition to injections. It can be adjusted by means. Examples of the non-toxic collateral for pharmaceutical use include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, albumin, water And physiological saline. In addition, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, binders and the like can be appropriately added as necessary. In the anti-osteoporosis agent according to the present invention, the dosage of momotamana powder or extract is appropriately selected and determined according to the patient's age, weight, symptoms, degree of disease, administration schedule, formulation form, etc. The dose is about 0.01 to 10 g / body weight and may be administered in several divided doses a day.
A similar formulation may be used for animals. It is appropriately selected and determined according to the age, body weight, symptom, degree of disease, administration schedule, formulation form, etc. of the animal. For example, it is about 0.01 to 10 g / kg body weight per day and divided into several times a day. May be administered.

また、本発明に関わるゴーヤ種子は、食経験も豊富なことから安全性が高いと考えられ、薬物性肝障害抑制作用を目的として、機能性食品としても摂取することができる。本発明に関わるゴーヤ種子の成分を含有することを特徴とする機能性食品は、特定保健用食品、栄養機能性食品、又は健康食品として位置づけることができる。機能性食品としては、例えば、ゴーヤ種子の抽出物に適当な助剤を添加した後、慣用の手段を用いて、食用に適した形態、例えば、顆粒状、粒状、錠剤、カプセル剤、ペースト状等に形成したものを用いることができる。この機能性食品はそのまま食用に供してもよく、また種々の食品、例えばハム、ソーセージ、かまぼこ、ちくわ、パン、バター、粉乳、菓子などに添加して使用したり、水、酒類、果汁、牛乳、清涼飲料水等の飲物に添加して使用したりしてもよい。かかる食品の形態における本発明のゴーヤ種子の成分摂取量は、対象の年齢、体重、症状、摂取スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり0.01〜10g/kg体重程度とされる。
動物においても同様に、例えばゴーヤ種子の抽出物に適当な助剤を添加した後、慣用の手段を用いて、食用に適した形態、顆粒状、粒状、錠剤、カプセル剤、ペースト状等に形成したものを用いることができる。また、飼料およびペットフードに添加して使用したり、水などの飲料水に添加してもよい。かかる食品の形態における本発明のゴーヤ種子の成分摂取量は、動物の年齢、体重、症状、摂取スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり0.01〜10g/kg体重程度とされる。
In addition, bitter gourd seeds according to the present invention are considered to be highly safe because of their rich dietary experience, and can be taken as a functional food for the purpose of suppressing drug-induced liver injury. A functional food characterized by containing components of bitter gourd seeds according to the present invention can be positioned as a food for specified health use, a nutritional functional food, or a health food. As a functional food, for example, after adding an appropriate auxiliary agent to an extract of bitter gourd seeds, a form suitable for consumption, for example, granular, granular, tablet, capsule, paste, using conventional means What was formed in etc. can be used. This functional food may be used for food as it is, and added to various foods such as ham, sausage, kamaboko, chikuwa, bread, butter, powdered milk, confectionery, etc., water, alcoholic beverages, fruit juice, milk It may be used by adding to drinks such as soft drinks. The ingredient intake of bitter gourd seeds of the present invention in the form of such food is appropriately selected and determined according to the age, weight, symptoms, intake schedule, formulation form, etc. of the subject. For example, 0.01 to 10 g / day About kg body weight.
Similarly, in animals, for example, after adding a suitable auxiliary agent to an extract of bitter gourd seeds, it is formed into a form suitable for food, granules, granules, tablets, capsules, pastes, etc. using conventional means. Can be used. Moreover, you may add and use for feed and pet food, or may add to drinking water, such as water. The ingredient intake of bitter gourd seeds of the present invention in the form of such food is appropriately selected and determined according to the age, weight, symptoms, intake schedule, formulation form, etc. of the animal. For example, 0.01 to 10 g / day About kg body weight.

以下に本発明をより詳細に説明する為に実施例を挙げるが、本発明はこれらによって何ら限定されるものではない。Examples are given below to describe the present invention in more detail, but the present invention is not limited by these.

実施例 ゴーヤ種子の薬物性肝障害抑制効果
四塩化炭素は、ヒト薬物性肝障害によく似た症状が得られることから急性肝障害モデルとして汎用されている。そこでゴーヤ種子の薬物性肝障害に対する効果を調べるために以下の実験を行った。
7週齢のddY系雌性マウスを実験動物として用い、24時間絶食後0.6%四塩化炭素を強制経口投与して肝障害を誘導した。ゴーヤ種子をミルで破砕後メタノール抽出したエキス1000mg/kg体重は、0.6%四塩化炭素投与の1時間前と24時間前に強制経口投与した。0.6%四塩化炭素投与後、20時間後に尾採血を行い肝障害のマーカーである血清AST・ALT活性値の測定を行った。コントロール群はゴーヤ種子抽出物の代わりに蒸留水を投与した。コントロール群と比較してサンプル併用群において血清AST・ALT活性の有意な抑制がみられた場合に、肝機能改善作用があると判断される。表1に各群の血清AST活性値±標準誤差(IU/L)と血清ALT活性値±標準誤差(IU/L)を示した。各群の四塩化炭素投与群に対する有意差の検定は、Student’st−testにより行った。四塩化炭素投与群と比較して危険率0.5%で有意差があり、表1中において###で示す。
Examples Inhibitory effect of bitter gourd seeds on drug-induced liver injury Carbon tetrachloride is widely used as an acute liver injury model because it provides symptoms similar to those of human drug-induced liver injury. Therefore, the following experiment was conducted to examine the effect of bitter gourd seeds on drug-induced liver injury.
Seven-week-old female ddY mice were used as experimental animals. After fasting for 24 hours, 0.6% carbon tetrachloride was forcibly administered orally to induce liver damage. 1000 mg / kg body weight of extract extracted from methanol after crushing bitter gourd seeds with a mill was forcibly administered orally 1 hour and 24 hours before administration of 0.6% carbon tetrachloride. Tail blood was collected 20 hours after administration of 0.6% carbon tetrachloride, and the serum AST / ALT activity value, which is a marker of liver damage, was measured. In the control group, distilled water was administered instead of bitter gourd seed extract. When significant suppression of serum AST / ALT activity is observed in the sample combination group as compared with the control group, it is determined that there is an effect of improving liver function. Table 1 shows the serum AST activity value ± standard error (IU / L) and the serum ALT activity value ± standard error (IU / L) of each group. The test of the significant difference of each group with respect to the carbon tetrachloride administration group was performed by Student'st-test. Compared with the carbon tetrachloride administration group, there is a significant difference at a risk rate of 0.5%, which is indicated by ## in Table 1.

Figure 2009269895
Figure 2009269895

この結果から、ゴーヤ種子メタノール抽出物が薬物性肝障害に有効であることが判明した。From these results, it was found that bitter gourd seed methanol extract is effective for drug-induced liver injury.

産業上の利用の可能性Industrial applicability

本発明により、ゴーヤ種子の成分を含有することを特徴とする薬物性肝障害抑制効果組成物及び該組成物を含有する飲食品または医薬品または飼料を提供することが可能となった。INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a drug-induced liver injury-suppressing composition that contains bitter gourd seed components, and a food or drink, a pharmaceutical product, or a feed containing the composition.

Claims (3)

ゴーヤ種子の成分を含有することを特徴とする薬物性肝障害抑制組成物。A composition for suppressing drug-induced liver injury, comprising a bitter gourd seed component. 上記の成分がゴーヤ種子メタノール抽出物である請求請1に記載の薬物性肝障害抑制組成物。The composition for suppressing drug-induced liver injury according to claim 1, wherein the ingredient is bitter gourd seed methanol extract. 請求項1又は2に記載の薬物性肝障害抑制組成物を含有する飲食物又は医薬品又は飼料。A food, beverage, medicine or feed comprising the composition for suppressing drug-induced liver injury according to claim 1 or 2.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012062294A (en) * 2010-09-17 2012-03-29 National Institute Of Advanced Industrial Science & Technology Agent for shortening hair growth telogen

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012062294A (en) * 2010-09-17 2012-03-29 National Institute Of Advanced Industrial Science & Technology Agent for shortening hair growth telogen

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