JPWO2007111306A1 - Lipid metabolism improver - Google Patents

Lipid metabolism improver Download PDF

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JPWO2007111306A1
JPWO2007111306A1 JP2008507493A JP2008507493A JPWO2007111306A1 JP WO2007111306 A1 JPWO2007111306 A1 JP WO2007111306A1 JP 2008507493 A JP2008507493 A JP 2008507493A JP 2008507493 A JP2008507493 A JP 2008507493A JP WO2007111306 A1 JPWO2007111306 A1 JP WO2007111306A1
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匡央 佐藤
匡央 佐藤
勝己 今泉
勝己 今泉
敬 大久保
敬 大久保
行生 尾崎
行生 尾崎
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Abstract

本発明は、カックロールを含む、食品又は医薬組成物を提供する。バングラディシュ原産のカックロール(Kakrol)青果は、ニガウリに似ている。本発明の食品又は医薬品組成物は、脂質代謝に関連した疾患又は状態に、高脂血症(原発性(家族性、散発性)、二次性、高コレステロール血症、高LDL-コレステロール血症を含む。)、動脈硬化、虚血性心疾患(狭心症、心筋梗塞を含む。)、脳血管障害(脳梗塞、脳出血を含む。)、又は生活習慣病の処置のために有用である。本発明の食品又は医薬組成物は、脂質の吸収を阻害する。The present invention provides a food or pharmaceutical composition comprising kaklol. Kakrol fruit and vegetables native to Bangladesh is similar to bitter gourd. The food or pharmaceutical composition of the present invention can be used to treat hyperlipidemia (primary (familial, sporadic), secondary, hypercholesterolemia, high LDL-cholesterolemia in diseases or conditions related to lipid metabolism. ), Arteriosclerosis, ischemic heart disease (including angina pectoris, myocardial infarction), cerebrovascular disorder (including cerebral infarction, cerebral hemorrhage), or lifestyle-related diseases. The food or pharmaceutical composition of the present invention inhibits lipid absorption.

Description

本発明は、ウリ科の植物であるカックロールに関する。より詳細には、本発明は、カックロールの脂質代謝改善剤としての新たな機能に関する。本発明は食品及び医薬品の分野で有用である。   The present invention relates to a cucumber which is a plant of the Cucurbitaceae family. More specifically, the present invention relates to a new function of Kaklol as a lipid metabolism improving agent. The present invention is useful in the food and pharmaceutical fields.

ニガウリの果肉や種子は南アジアにおいて、伝統的に薬効のある植物として糖尿病治療に利用されている。近年の研究により、血清及び肝臓中のTGを減少させ、脂肪肝を予防する作用があるという報告がある(非特許文献1、2)。さらに、作用機構は未解明であるが、糖尿病改善作用が認められてきている(非特許文献3、特許文献1)。このように、ニガウリは糖尿病や高脂血症の改善など、様々な高機能性が認められている有用な野菜である。   Bittern and seeds are traditionally used in South Asia as a medicinal plant for the treatment of diabetes. Recent studies have reported that serum and liver TGs are decreased to prevent fatty liver (Non-patent Documents 1 and 2). Furthermore, although the mechanism of action is not yet elucidated, an action for improving diabetes has been recognized (Non-patent Document 3, Patent Document 1). Thus, bitter gourd is a useful vegetable with various high functions such as diabetes and improvement of hyperlipidemia.

一方、カックロール(Kakrol、Momordica dioica Roxb.)は、バングラディシュ周辺で雨季に収穫される野菜である。ニガウリと同様ウリ科に属し、ニガウリに類似した形をしているが、ニガウリほどには苦味がない。カックロールについては、これまで、栽培法、単為結実、組織培養カルスからの植物体再生、及び形態学上・生理学上の特徴等の面から研究されてきた(非特許文献4〜7)。On the other hand, kakrol (Kakrol, Momordica dioica Roxb.) Is a vegetable harvested in the rainy season around Bangladesh. Like bitter gourd, it belongs to the Cucurbitaceae family and has a similar shape to bitter gourd but not as bitter as bitter gourd. So far, cucumber has been studied from the aspects of cultivation method, parthenocarpy, plant regeneration from tissue culture callus, and morphological and physiological characteristics (Non-Patent Documents 4 to 7).

さらにカックロールはビタミン高含有であることが知られているが、多くの機能性について検討の余地がある。
特開平11-59692(特許第3261090号) Gamarallage V. K. Senanayake, et al., J. Nutr. Sci. Vitaminol., 50 253-257, 2004 Gamarallage V. K. Senanayake, et al., J. Ethnoparmacology,91 257-262, 2004 Dhanasekar S., et al., Biol. Pharm. Bull., 28(6) 978-983, 2005 Mohammad Ali, et al., Scientia Horticulturae, 47 335-343, 1991 Mohammad Nazmul Islam Mnik, et al., J. Fac. Agr., Kyushu Univ., 45(2) 459-463, 2001 Shaila Arifa Nabi, et al., J. Fac. Agr., Kyushu Univ., 46(2) 303-309, 2002 Mohammad Golam Rasul, et al., J. Fac. Agr., Kyushu Univ., 49(1) 1-11, 2004
In addition, kaklol is known to have a high vitamin content, but there is room for studying many functionalities.
JP 11-59692 (Patent No. 3261090) Gamarallage VK Senanayake, et al., J. Nutr. Sci. Vitaminol., 50 253-257, 2004 Gamarallage VK Senanayake, et al., J. Ethnoparmacology, 91 257-262, 2004 Dhanasekar S., et al., Biol. Pharm. Bull., 28 (6) 978-983, 2005 Mohammad Ali, et al., Scientia Horticulturae, 47 335-343, 1991 Mohammad Nazmul Islam Mnik, et al., J. Fac. Agr., Kyushu Univ., 45 (2) 459-463, 2001 Shaila Arifa Nabi, et al., J. Fac. Agr., Kyushu Univ., 46 (2) 303-309, 2002 Mohammad Golam Rasul, et al., J. Fac. Agr., Kyushu Univ., 49 (1) 1-11, 2004

本発明者らは、SDラットにおいて、カックロール粉末を3%含む食餌を与えた際の脂質代謝に及ぼす影響について検討した。その結果、カックロールを含む食事を与えた群が、コントロール群に比較して、脂質代謝に関連した指標において有意な改善が見られること、また糞中への脂肪酸排泄量が有意に高いことを発見し、本発明を完成した。   The present inventors examined the influence of a diet containing 3% kakrol powder on lipid metabolism in SD rats. As a result, it was confirmed that the group fed a diet containing kaklol showed a significant improvement in the index related to lipid metabolism and that the amount of fatty acid excreted in feces was significantly higher than the control group. Discovered and completed the present invention.

本発明は、すなわち、カックロール、及び食品又は医薬として許容可能な添加物を含む、食品又は医薬組成物を提供する。   The present invention provides a food or pharmaceutical composition that includes a cucumber and a food or pharmaceutically acceptable additive.

カックロール(kakrol、学名:Momordica dioica Roxb.)は、ニガウリと同じウリ科モモルディカ属の植物である。カックロールは、蔓性多年草、雌雄異株であり、地下部に塊根を作る(図1〜4参照)。インド亜大陸ベンガル地方原産といわれており、高温多湿気候に適し、栽培は容易である。バングラデシュ国では雨季の重要な野菜となっている。果実はレモン型で、小突起に覆われ、1個の重さは50〜100gであり、ニガウリのような苦みを全く持たない。Kakrol (scientific name: Momordica dioica Roxb.) Is a plant belonging to the genus Momordica , the same cucurbitaceae as Nigauri. Kakroll is a vine perennial, sexually different strain, and forms tuberous roots in the basement (see Figures 1-4). It is said to be native to the Bengal region of the Indian subcontinent, suitable for hot and humid climates, and easy to grow. In Bangladesh it is an important vegetable during the rainy season. The fruit is lemon-shaped, covered with small protrusions, each weighing 50-100 g, and has no bitter taste like bitter gourd.

本発明の食品又は医薬組成物に、カックロールを用いる場合、栽培法、形態学上・生理学上の特徴によらず、あらゆる品種を用いることができる。カックロールの栽培法及び形態学上・生理学上の特徴に関しては、当業者は、上述の非特許文献4〜7等を参照することができる。   When kakroll is used in the food or pharmaceutical composition of the present invention, any variety can be used regardless of the cultivation method, morphological and physiological characteristics. With respect to the cultivation method and morphological / physiological characteristics of kakroll, those skilled in the art can refer to the above-mentioned Non-Patent Documents 4 to 7 and the like.

本明細書で「カックロール」というときは、特別な場合を除き、カックロールの植物体の全体又は一部を指し、これには、カックロール果実(食するのに適した段階の果実(青果)を指して「カックロール」ということもある。)、果肉、皮、種子、葉、茎、根、花、蕾が含まれる。本発明の食品又は医薬組成物の原料として、果実が適している。果実は、果皮及び種子を除くことなく、そのまま用いてもよい。カックロールの食するのに適した果実の段階(青果)では種子はまだ柔らかく、果肉とともに食することができる。必要に応じ、果肉、皮若しくは種子を、単独又は組み合わせて用いてもよい。   In this specification, the term “cuck roll” refers to the whole or a part of a plant body of a cuck roll, unless otherwise specified, and includes a cuck roll fruit (a fruit at a stage suitable for eating (fruits and vegetables). ) Refers to “kuck roll”.), Including pulp, skin, seeds, leaves, stems, roots, flowers, and buds. Fruit is suitable as a raw material for the food or pharmaceutical composition of the present invention. The fruit may be used as it is without removing the skin and seeds. At the fruit stage (fruit and vegetables) suitable for eating kakroll, the seeds are still soft and can be eaten with the pulp. If necessary, pulp, skin or seed may be used alone or in combination.

本明細書で「カックロール」というときは、特別な場合を除き、加工の有無、程度を問わず、カックロールを原料とした抽出物、抽出物残滓、分画物、単離物、濃縮物、加工物、乾燥物を含む。   In the present specification, “kuck roll” refers to an extract, an extract residue, a fraction, an isolate, and a concentrate obtained from kak roll, regardless of whether or not processed, unless otherwise specified. Including processed and dried products.

乾燥物には、凍結乾燥物の粉末が含まれる。抽出物には、水又は水系溶媒による抽出物、メタノール、エタノール、ヘキサン、アセトン等の有機溶媒による抽出物が含まれる。   The dried product includes a lyophilized product powder. The extract includes an extract with water or an aqueous solvent, and an extract with an organic solvent such as methanol, ethanol, hexane, and acetone.

本発明の食品又は医薬組成物には、青果を乾燥物にして用いることができる。   In the food or pharmaceutical composition of the present invention, fruits and vegetables can be used as a dried product.

本発明の食品又は医薬組成物は、脂質代謝に関連した疾患又は状態を処置するために有用である。より特定すると、血清脂質濃度又は肝臓脂質濃度に関連した疾患又は状態を処置するために有用である。血清脂質及び肝臓脂質には、コレステロール(遊離型、エステル型)、トリアシルグリセロール(TG)(トリグリセリド、中性脂肪ということもある。)、リン脂質(PL)、非エステル型脂肪酸が含まれる。本発明の食品又は医薬組成物は、特に、血清中の総コレステロール濃度、肝臓中のコレステロール濃度、トリアシルグリセロール(TG)濃度、及び/又はリン脂質(PL)濃度を低減させるのに効果がある。本発明の食品又は医薬組成物は、より具体的には、高脂血症(原発性(家族性、散発性)、二次性を含む。高コレステロール血症、高中性脂肪血症、高コレステロール高中性脂肪血症を含む。)、動脈硬化、虚血性心疾患(狭心症、心筋梗塞)、脳血管障害(脳梗塞、脳出血)、脂肪肝、糖尿病、肥満、生活習慣病(糖尿病、脳卒中、心臓病、高脂血症、高血圧、肥満)を処置するために有用である。なお、本発明者らの検討によると、9〜18週齢の雌雄アポE欠損マウスでの評価においては、カックロール青果の乾燥物を摂取した群が、血清中の血清中のチオバルビツール酸反応物(TBARS)濃度がコントロール群と比較して低くなった(実施例4参照)ことから、本発明の医薬又は食品組成物は、酸化ストレスに関連した疾患又は状態(例えば動脈硬化)を処置するために、特に有用であると考えられる。   The food or pharmaceutical composition of the present invention is useful for treating diseases or conditions associated with lipid metabolism. More particularly, it is useful for treating diseases or conditions associated with serum lipid levels or liver lipid levels. Serum lipids and liver lipids include cholesterol (free type and ester type), triacylglycerol (TG) (triglyceride, sometimes referred to as neutral fat), phospholipid (PL), and non-ester type fatty acid. The food or pharmaceutical composition of the present invention is particularly effective for reducing serum total cholesterol concentration, liver cholesterol concentration, triacylglycerol (TG) concentration, and / or phospholipid (PL) concentration. . More specifically, the food or pharmaceutical composition of the present invention includes hyperlipidemia (primary (familial, sporadic), secondary. Hypercholesterolemia, hypertriglyceridemia, high cholesterol Including hypertriglyceridemia), arteriosclerosis, ischemic heart disease (angina, myocardial infarction), cerebrovascular disorder (cerebral infarction, cerebral hemorrhage), fatty liver, diabetes, obesity, lifestyle-related diseases (diabetes, stroke) , Heart disease, hyperlipidemia, hypertension, obesity). According to the study by the present inventors, in the evaluation in 9-18 week-old male and female apo E-deficient mice, the group ingested dried kakrol fruit and vegetables was thiobarbituric acid in the serum. Since the reactant (TBARS) concentration was lower than that in the control group (see Example 4), the pharmaceutical or food composition of the present invention treated a disease or condition related to oxidative stress (eg, arteriosclerosis). Is considered to be particularly useful.

本発明者らの検討によると、5週齢の雄SDラットでの評価においては、カックロール青果の乾燥物を摂取した群は、血清中の総コレステロール濃度が、コントロール群に比較して低くなり、特にLDL-コレステロール及びVLDL-コレステロールがかなり低下したと考察された(実施例3参照)。また、9〜18週齢の雌雄アポE欠損マウスでの評価においては、カックロール青果の乾燥物を摂取した群は、血清中の総コレステロール濃度、VLDL及びLDL濃度がコントロール群と比較して有意に低かったが、HDL濃度は群間に有意差は見られなかった(実施例4参照)。したがって、本発明の医薬又は食品組成物は、特に、高コレステロール血症及び/又は高LDL-コレステロール血症を処置するために有用である。   According to the study by the present inventors, in the evaluation with 5-week-old male SD rats, the group that ingested dried kakrol fruit and vegetables had a lower serum total cholesterol concentration than the control group. In particular, it was considered that LDL-cholesterol and VLDL-cholesterol were significantly reduced (see Example 3). In the evaluation of 9-18 week old male and female apo E deficient mice, the group that ingested dried kakrol fruit and vegetables had significant serum total cholesterol, VLDL and LDL concentrations compared to the control group. However, the HDL concentration was not significantly different between the groups (see Example 4). Therefore, the pharmaceutical or food composition of the present invention is particularly useful for treating hypercholesterolemia and / or hyper LDL-cholesterolemia.

また、本発明者らの検討によると、5週齢の雄SDラットでの評価においては、カックロール青果の乾燥物を摂取した群には、食効率、肝臓重量、膵臓重量、血清アミラーゼ活性においてコントロール群に比較して高いとの実験結果が得られた(実施例3参照)。食効率が高いことは、エネルギー代謝の効率化が行われていることを指し、また、肝臓重量の増加は脂肪肝ではなく、代謝亢進の可能性を示唆する。さらに、膵臓重量の増加は、消化酵素、インシュリン、グルカゴンなどの血糖調節作用が効率的に行える可能性を有し、血清アミラーゼは、膵臓重量の増加に伴って増加していることから、膵臓の活発な活動を意味する。したがって、本発明の食品又は医薬組成物は、このようなカックロールの作用により改善される疾患又は状態の処置にも有用である。   In addition, according to the study by the present inventors, in the evaluation with 5-week-old male SD rats, the group that ingested the dried kakrol fruit and vegetables had a diet efficiency, liver weight, pancreas weight, serum amylase activity. The experimental result was higher than that of the control group (see Example 3). A high dietary efficiency means that energy metabolism has been made more efficient, and an increase in liver weight suggests the possibility of hypermetabolism rather than fatty liver. Furthermore, the increase in pancreatic weight has the potential to efficiently perform blood glucose regulating effects such as digestive enzymes, insulin, and glucagon, and serum amylase increases with the increase in pancreatic weight. Means active activity. Therefore, the food or pharmaceutical composition of the present invention is also useful for the treatment of diseases or conditions that are ameliorated by the action of such kakrol.

さらに本発明者らの検討によると、7週齢の雄SDラットでの評価においては、カックロール青果の乾燥物を摂取した群の糞中への脂肪酸排泄量は、コントロール群と比較して有意に高かった(実施例4参照)。したがって、本発明の医薬又は食品組成物は、食餌由来の脂質の吸収を阻害する作用があり、そのようなカックロールの作用により改善される疾患又は状態の処置にも有用である。なお、本明細書において、生体内での吸収に関連して「脂質」というときは、特別な場合を除き、単純脂質(例えば油脂;油脂は、脂肪酸とグリセリンから成る3価のエステルであり、トリグリセリド(TG)ということもある。)、複合脂質(例えばリン脂質、糖脂質)、コレステロールを含む。単純脂質と複合脂質には、構成成分として不飽和脂肪酸又は飽和脂肪酸が含まれる。脂質の吸収阻害は、通常、排泄又は吸収された脂肪酸量を測定することにより、評価することができる。   Furthermore, according to the study by the present inventors, in the evaluation in 7-week-old male SD rats, the amount of fatty acid excreted in the feces of the group ingested dried kakrol fruit and vegetables was significantly higher than that in the control group. (See Example 4). Therefore, the pharmaceutical or food composition of the present invention has an action of inhibiting the absorption of diet-derived lipids, and is also useful for the treatment of diseases or conditions that are ameliorated by the action of such kakrol. In the present specification, the term “lipid” in relation to absorption in a living body, except for special cases, is a simple lipid (for example, fat and oil; fat is a trivalent ester composed of a fatty acid and glycerin, Triglyceride (TG)), complex lipids (eg phospholipids, glycolipids), and cholesterol. Simple lipids and complex lipids contain unsaturated fatty acids or saturated fatty acids as constituents. Inhibition of lipid absorption can usually be evaluated by measuring the amount of fatty acid excreted or absorbed.

本明細書において、疾患又は状態を「処置(する)」というときは、特別な場合を除き、対象となる疾患もしくは状態を、予防もしくは治療すること、軽度に抑えること、又は進行を抑えることを意味する。「処置」には、根本的な治療が含まれ、また長期的な予防及び/又は治療とが含まれる。   In the present specification, when a disease or condition is referred to as “treating”, except for special cases, prevention or treatment, mild suppression, or suppression of progression of the target disease or condition. means. “Treatment” includes fundamental therapy and includes long-term prevention and / or therapy.

本発明の食品組成物は、飲料の形態であるものも含む。本発明の食品組成物は、栄養機能食品、特定保健用食品、健康食品、栄養補助食品、ドリンク剤、ジュース、濃縮ジュース等とすることができる。食品組成物はまた、乾燥品、加工品(例えば、漬け物。塩漬、しょうゆ漬、みそ漬、ぬかみそ漬、粕漬、麹漬、調味漬、酢漬)、エキスの形態とすることもでき、以下で説明する医薬組成物である場合に準じて、エキス、濃縮物等を含むカプセル剤、錠剤、丸剤、タブレット、散剤、顆粒剤等の形態とすることもできる。食品組成物として摂取するカックロールの量は、以下で説明する医薬組成物である場合に準じて、適宜とすることができる。   The food composition of the present invention includes those in the form of beverages. The food composition of the present invention may be a nutritional functional food, a food for specified health use, a health food, a nutritional supplement, a drink, a juice, a concentrated juice, or the like. The food composition can also be in the form of a dried product, a processed product (eg pickled, salted, soy sauce, miso pickled, nuka miso pickled, pickled, pickled, seasoned, pickled), extract, According to the case where it is a pharmaceutical composition demonstrated below, it can also be set as forms, such as a capsule containing an extract and a concentrate, a tablet, a pill, a tablet, a powder, a granule. The amount of kaklol taken as a food composition can be appropriately determined according to the case of a pharmaceutical composition described below.

本発明の食品組成物は、食品として許容可能な種々の添加物、例えば甘味料、着色料、保存料、酸化防止剤、香料、酸味料、調味料、防かび剤(防ばい剤)、pH調整剤、栄養強化剤、乳化剤、増粘剤、安定剤、ゲル化剤、糊剤、発色剤、漂白剤を含んでもよい。   The food composition of the present invention contains various food-acceptable additives such as sweeteners, colorants, preservatives, antioxidants, flavors, acidulants, seasonings, fungicides (antifungal agents), pH. It may contain a regulator, a nutrient enhancer, an emulsifier, a thickener, a stabilizer, a gelling agent, a paste, a color former, and a bleaching agent.

本発明の組成物を医薬組成物とする場合、有効成分であるカックロールの量、投与期間、間隔は、目的、症状、対象者の年齢、体重等に応じて適宜とすることができる。治療の目的では、例えば、臨床上有効量を、数週間〜数ヶ月の間、継続して投与することができる。より具体的には、成人患者に対して、一日当たり、青果の乾燥物(実施例参照)として 10g〜1000g(好ましくは25g〜500g、より好ましくは50g〜250g)に相当する量を、単回又は複数回(例えば3回)に分割して投与することができる。このような量の1/10〜1/1(例えば1/3)を一単位剤形中に含むように設計された製剤は、本発明の好ましい態様の一つである。   When the composition of the present invention is used as a pharmaceutical composition, the amount, administration period, and interval of the active ingredient kakrol can be appropriately determined according to the purpose, symptoms, subject's age, weight, and the like. For therapeutic purposes, for example, a clinically effective amount can be administered continuously for weeks to months. More specifically, an amount equivalent to 10 g to 1000 g (preferably 25 g to 500 g, more preferably 50 g to 250 g) as a dried product of fruits and vegetables per day is given to an adult patient once a day. Or it can divide and administer several times (for example, 3 times). Formulations designed to contain such amounts of 1/10 to 1/1 (eg, 1/3) in a unit dosage form are one of the preferred embodiments of the present invention.

また、健康維持及び/又は発症予防等の目的では、より少ない量での投与が効果的である場合がある。より具体的には、成人である対象者に対して、一日当たり、青果の乾燥物(実施例参照)として 1g〜100g(好ましくは2.5g〜50g、より好ましくは5g〜25g)に相当する量を、単回又は複数回に分割して投与することができる。このような量の1/10〜1/1を一単位剤形中に含むように設計された製剤もまた、本発明の好ましい態様の一つである。   In addition, for the purpose of maintaining health and / or preventing onset, administration in a smaller amount may be effective. More specifically, for an adult subject, the amount corresponding to 1 g to 100 g (preferably 2.5 g to 50 g, more preferably 5 g to 25 g) per day as a dried product of fruits and vegetables (see Examples) Can be administered in a single dose or divided into multiple doses. A formulation designed to contain such an amount of 1/10 to 1/1 in one unit dosage form is also a preferred embodiment of the present invention.

青果の乾燥物に相当する量は、当業者であれば、本明細書の実施例等を参考にして、青果全体、青果の抽出物、抽出物残滓、分画物、単離物、濃縮物もしくは加工物、又は青果の一部(例えば、果肉、皮、種子)、その乾燥物、抽出物、抽出物残滓、分画物、単離物、濃縮物もしくは加工物等について、それぞれ求めることができる。   For those skilled in the art, the amount corresponding to the dried product of fruits and vegetables can be obtained by referring to the examples and the like of the present specification, and the whole fruits and vegetables, extracts of fruits and vegetables, extract residues, fractions, isolates and concentrates. Alternatively, a processed product, or a part of a fruit or vegetable (for example, pulp, skin, seed), a dried product, an extract, an extract residue, a fraction, an isolate, a concentrate, or a processed product may be obtained. it can.

投与経路、剤形も適宜設計することができ、例えば、全身的な投与のため、又は局所投与のために製剤化することができ、内服剤、外用剤、固形剤、液状製剤、散剤、顆粒剤、カプセル剤、錠剤、丸剤、タブレット、エキス剤、軟膏剤、硬膏剤、ハップ剤、ローション剤、リニメント剤、又は坐剤とすることができる。また、除放化製剤、放出制御型製剤とすることもできる。製剤化は、従来の方法にしたがって行うことができる。   The administration route and dosage form can also be designed as appropriate. For example, it can be formulated for systemic administration or topical administration, and is used as an internal preparation, external preparation, solid preparation, liquid preparation, powder, granule Agent, capsule, tablet, pill, tablet, extract, ointment, plaster, haptic, lotion, liniment, or suppository. Moreover, it can also be set as a sustained release formulation and a controlled release formulation. Formulation can be performed according to conventional methods.

本発明の医薬組成物は、医薬として許容できる種々の添加物、例えば、附形剤、結合剤、崩壊剤、滑沢剤、コーティング剤、懸濁化剤、乳化剤、安定剤、保存剤、緩衝剤を含んでもよい。   The pharmaceutical composition of the present invention comprises various pharmaceutically acceptable additives such as excipients, binders, disintegrants, lubricants, coating agents, suspending agents, emulsifiers, stabilizers, preservatives, buffers. An agent may be included.

本発明の食品又は医薬組成物は、他の食事療法(脂肪制限、糖質・アルコール制限、食物繊維を多く摂取する等。)、薬物療法(コレスチラミン、ニコチン酸、メバロチン等の抗コレステロール剤の投薬。)、運動療法と併用して用いることができる。   The food or pharmaceutical composition of the present invention can be used for other diet therapy (fat restriction, sugar / alcohol restriction, high intake of dietary fiber, etc.), drug therapy (anticholesterol drugs such as cholestyramine, nicotinic acid, and mevalotin). Medication), can be used in combination with exercise therapy.

本発明の組成物には、その具体的な用途(例えば、生活習慣病予防のため、体質改善のため、長期的な治療のため、等。)、及び/又はその具体的な用い方(例えば、量、回数、継続的に使用すべき旨、期間、等。)を表示することができる。   The composition of the present invention has a specific use thereof (for example, prevention of lifestyle-related diseases, improvement of constitution, long-term treatment, etc.) and / or a specific usage thereof (for example, , Amount, number of times, continuous use, period, etc.) can be displayed.

本発明はまた、カックロールを摂取させることにより脂質代謝を改善する、ヒト又は非ヒト動物における脂質代謝に関連した疾患又は状態の処置方法、カックロールを含む、脂質代謝改善剤、及びカックロールを脂質代謝改善のために用いるための指針(例えば、具体的な用途、及び/又はその具体的な用い方に関する情報、そのような情報を記載した書面)を含む、製品も提供する。また、カックロールを摂取させることを含む、脂質吸収の阻害方法、カックロールを含む、脂質吸収阻害剤も提供する。   The present invention also provides a method for treating a disease or condition related to lipid metabolism in a human or non-human animal, which improves lipid metabolism by ingesting kakrol, a lipid metabolism improving agent containing kakrol, and kaklol. Also provided is a product that includes guidelines for use to improve lipid metabolism (eg, information about specific uses and / or specific uses thereof, a document describing such information). Moreover, the lipid absorption inhibitor including the method of inhibiting lipid absorption including ingesting kkroll and kkroll is also provided.

図1は、カックロール全体の写真である。FIG. 1 is a photograph of the entire crawl. 図2は、カックロール果実の写真である。FIG. 2 is a photograph of cucumber fruit. 図3は、カックロール果実の写真である。FIG. 3 is a photograph of cucumber fruit. 図4は、カックロール塊根の写真である。FIG. 4 is a photograph of the cock roll tuberous root.

〔実施例1:成分比較等〕
九州大学内で栽培したカックロールの青果について、成分及び脂肪酸組成を比較した。対照として、ニガウリ(佐土原3号)を用いた。
[Example 1: Component comparison, etc.]
Ingredients and fatty acid compositions were compared for the fruits and vegetables of Kakroll grown in Kyushu University. As a control, bitter gourd (Sadohara No. 3) was used.

カックロール及びニガウリの成分を下表に示した。   The ingredients of cucumber and bitter gourd are shown in the table below.

Figure 2007111306
また、脂肪酸組成を下表に示した。
Figure 2007111306
The fatty acid composition is shown in the table below.

Figure 2007111306
測定は、Folch法(クロロホルム/メタノール=2:1)で抽出後、けん化し、脂肪酸画分をガスクロマトグラフィーで行った。
Figure 2007111306
The measurement was performed by the Folch method (chloroform / methanol = 2: 1), saponified, and the fatty acid fraction was subjected to gas chromatography.

ニガウリに比べてカックロールは、脂質量が少ない(カロリーが低い)割には-tocopherol(ビタミンE)量が多く、また、血清コレステロール低下作用の強いリノール酸が多く含まれていた。なお、カックロールのコレステロール低下作用について後述するが、含有量からすると、このリノール酸が効いてコレステロールを下げているのではない。   Compared to bitter gourd, Kakroll has a low amount of lipid (low calories), but it contains a large amount of -tocopherol (vitamin E) and a large amount of linoleic acid, which has a strong serum cholesterol lowering effect. In addition, although the cholesterol lowering effect | action of kakrol is mentioned later, from the content, this linoleic acid is effective and does not lower cholesterol.

〔実施例2:凍結乾燥粉末の調製〕
カックロール青果を3cm角に切り凍結乾燥し、ミキサーで粉砕した。青果1004gから、淡緑色の粉末131.3gを得た。得られた乾燥物は、苦みはなく、キュウリの味に似ており、青臭い匂いを有した。これを以下の実施例で用いた。
[Example 2: Preparation of freeze-dried powder]
The cucumber fruits and vegetables were cut into 3 cm squares, freeze-dried, and pulverized with a mixer. From 1004 g of fruits and vegetables, 131.3 g of pale green powder was obtained. The resulting dried product had no bitterness, resembled the taste of cucumber, and had a blue smell. This was used in the following examples.

〔実施例3:脂質代謝に与える影響の評価〕
方法:
5週齢の雄SDラットを市販の固形食で1週間予備飼育後、体重により2群に分け、1群6匹とした。AIN-76(米国国立栄養研究所(American Institute of Nutrition, AIN))組成に準じ、5%コーン油を含むコントロール食(コントロール群)、及び5%のコーン油と3%のkakrol凍結乾燥粉末(実施例2)を含むカックロール食(カックロール群)を、摂食量を調節しながら与え、2週間飼育した。
[Example 3: Evaluation of influence on lipid metabolism]
Method:
Five weeks old male SD rats were preliminarily raised on a commercially available solid diet for 1 week, and then divided into 2 groups according to body weight, so that 6 rats per group were obtained. According to AIN-76 (American Institute of Nutrition, AIN) composition, a control diet containing 5% corn oil (control group), and 5% corn oil and 3% kakrol lyophilized powder ( A kakroll meal (cuck roll group) containing Example 2) was fed while adjusting the amount of food intake, and was bred for 2 weeks.

食餌組成を下表に示した。   The diet composition is shown in the table below.

Figure 2007111306
絶食をさせずに断頭により屠殺後、肝臓、膵臓、白色脂肪組織(睾丸周辺、腸間膜周辺、腹膜後腔周辺)及び筋肉を摘出した。肝臓脂質は化学法(コレステロール:Sperry S., J. Biol. Chem., 187, 97-106, 1950, トリグリセリド:Fletcher S., Clin. Chim. Acta. 22, 393-397, 1968, リン脂質:Rouser S., Lipids, 1, 85-86, 1966)により測定し、血清脂質は酵素法キット(コレステロール:デターミナーTC555、協和メディクス、HDL分画試薬:簡易DCM 測定法, トリグリセリド:トリグリセライドE-テストワコー、和光純薬工業)、血清グルコースは酵素法キット(グルコースC-II-テストワコー、和光純薬工業)を用いて測定した。血清アミラーゼ濃度はキット(アミラーゼテストワコー、和光純薬工業)を用いて測定した。また、肝臓の脂肪酸合成系・脂肪酸酸化系の酵素活性を測定した。
Figure 2007111306
After being killed by decapitation without fasting, the liver, pancreas, white adipose tissue (around the testicles, around the mesentery, around the retroperitoneum) and muscles were removed. Liver lipids are chemically treated (cholesterol: Sperry S., J. Biol. Chem., 187, 97-106, 1950, triglycerides: Fletcher S., Clin. Chim. Acta. 22, 393-397, 1968, phospholipids: Rouser S., Lipids, 1, 85-86, 1966). Serum lipids are measured by enzyme method kit (cholesterol: Determiner TC555, Kyowa Medics, HDL fractionation reagent: simple DCM assay, triglyceride: triglyceride E-test Wako. , Wako Pure Chemical Industries, Ltd.) and serum glucose were measured using an enzyme method kit (glucose C-II-Test Wako, Wako Pure Chemical Industries). Serum amylase concentration was measured using a kit (Amylase Test Wako, Wako Pure Chemical Industries). Moreover, the enzyme activity of the fatty acid synthesis system and fatty acid oxidation system of the liver was measured.

結果:
結果を下表に示した。
result:
The results are shown in the table below.

Figure 2007111306
Figure 2007111306

Figure 2007111306
Figure 2007111306

Figure 2007111306
Figure 2007111306

Figure 2007111306
体重増加量、終体重、摂食量及び脂肪組織重量に群間に有意差は見られなかったが、食効率、肝臓重量及び膵臓重量はControl群と比較してKakrol群が有意に増加した。また、相対筋重量は有意に減少した。
Figure 2007111306
There were no significant differences among the groups in body weight gain, final body weight, food intake, and adipose tissue weight, but food efficiency, liver weight, and pancreas weight were significantly increased in the Kakrol group compared to the Control group. In addition, the relative muscle weight was significantly reduced.

Figure 2007111306
血清中のGOT活性は群間に有意差は見られなかったが、血清中のアミラーゼ活性はControl群と比較してKakrol群が有意に増加した。
Figure 2007111306
There was no significant difference in serum GOT activity between groups, but amylase activity in serum was significantly increased in the Kakrol group compared to the Control group.

Figure 2007111306
Figure 2007111306

Figure 2007111306
血清中の総コレステロール濃度、HDL-コレステロール濃度はControl群と比較してKakrol群が有意に減少した。HDL-コレステロール濃度の低下が総コレステロール濃度の低下に比較して少ないことから、LDL-コレステロール+VLDL-コレステロールがかなり低下したと考えられる。
Figure 2007111306
Serum total cholesterol and HDL-cholesterol concentrations were significantly decreased in the Kakrol group compared to the Control group. Since the decrease in HDL-cholesterol concentration is small compared to the decrease in total cholesterol concentration, LDL-cholesterol + VLDL-cholesterol is considered to have decreased considerably.

また、肝臓中のコレステロール濃度、トリアシルグリセロール(TG)濃度及びリン脂質(PL)濃度は、Control群と比較してKakrol群が有意に減少した。なお、血清TG濃度及び血清グルコース濃度においては、群間に有意差は見られなかった。  In addition, the cholesterol concentration, triacylglycerol (TG) concentration, and phospholipid (PL) concentration in the liver were significantly decreased in the Kakrol group as compared to the Control group. In the serum TG concentration and serum glucose concentration, no significant difference was observed between the groups.

Figure 2007111306
FAS、Malic Enzyme及びG6PDH活性は群間に有意差は見られなかった。また、CPT活性も群間に有意差は見られなかった。一方、ACO活性は、Control群と比較してKakrol群が有意に減少した。
Figure 2007111306
FAS, Malic Enzyme and G6PDH activities were not significantly different between groups. In addition, there was no significant difference in CPT activity between groups. On the other hand, the ACO activity was significantly decreased in the Kakrol group compared to the Control group.

考察:
Kakrolには血清コレステロール濃度の低下作用があり、肝臓脂質の低下作用を示す物質が含まれていることが示唆された。食品成分で同様の作用が見られるものとしては、大豆タンパク質が挙げられるが、その際の食餌中の大豆タンパク質の割合は20%である。3%カックロール食における本実施例での結果は従来の食品成分からは予想できない顕著なものであるといえる。
Discussion:
It was suggested that Kakrol has an effect of lowering serum cholesterol concentration and contains a substance showing an action of lowering liver lipids. Examples of food components that have the same effect include soy protein, and the proportion of soy protein in the diet at that time is 20%. It can be said that the result in the present Example in a 3% cucumber meal is remarkable which cannot be predicted from conventional food ingredients.

〔実施例4:脂質代謝に与える影響の評価〕
SDラット又はアポE欠損マウスにカックロール凍結乾燥粉末を摂取させ、カックロールが脂質代謝に及ぼす影響と、その作用機構について検討した。
[Example 4: Evaluation of influence on lipid metabolism]
SD rats or apoE-deficient mice were ingested with Kakrol lyophilized powder, and the effects of Kakrol on lipid metabolism and the mechanism of action were examined.

方法:
[実験1 糞中への脂肪酸排泄量の測定]
AIN-76組成に準じて5%コーン油を含む食餌(Control群)と5%コーン油及び3%カックロール凍結乾燥粉末を含む食餌(Kakrol群)、5%コーン油及び3%ニガウリ凍結乾燥粉末を含む食餌(Bitter gourd群)を与えた7週齢の雄SDラットの糞を3日間回収し、滴定により脂肪酸量を測定した。
Method:
[Experiment 1 Measurement of Fatty Acid Excretion in Feces]
A diet containing 5% corn oil according to AIN-76 composition (Control group), a diet containing 5% corn oil and 3% Kakrol lyophilized powder (Kakrol group), 5% corn oil and 3% bittern lyophilized powder The feces of 7-week-old male SD rats fed with diet containing Bitter (Bitter gourd group) were collected for 3 days and the amount of fatty acid was measured by titration.

[実験2 アポE欠損マウスにおける脂質代謝の評価]
9〜18週齢の雌雄アポE欠損マウス29匹を市販固形食で1週間予備飼育した後、AIN-76組成に準じ、10%ラードを含むControl食(Control群、雄雌8匹)及び10%ラードと3%のカックロール凍結乾燥粉末を含むカックロール食(Kakrol群、雄6匹、雌7匹)をPair feedingで9週間飼育した。
[Experiment 2: Evaluation of lipid metabolism in apoE-deficient mice]
After 29 weeks of male and female apo E deficient mice aged 9-18 weeks were pre-bred on a commercial solid diet for 1 week, according to AIN-76 composition, a control diet containing 10% lard (Control group, 8 males and 10 females) and 10 A Kakroll diet (Kakrol group, 6 males, 7 females) containing% lard and 3% Kakroll freeze-dried powder was bred for 9 weeks by Pair feeding.

食餌組成を下表に示した。   The diet composition is shown in the table below.

Figure 2007111306
6時間絶食させた後、動脈採血により屠殺し、肝臓、心臓、白色脂肪組織(睾丸・卵巣周辺、腸間膜周辺、腹膜後腔・腎周辺、皮下)及び大動脈を摘出した。肝臓脂質は化学法により測定し、血清脂質は酵素法キットを用いて測定した(実施例3参照)。血清中のチオバルビツール酸反応物(TBARS)は化学法により測定した。
Figure 2007111306
After fasting for 6 hours, the blood was sacrificed by arterial blood sampling, and the liver, heart, white adipose tissue (around testicle / ovary, mesentery, retroperitoneal cavity / around kidney, subcutaneous) and aorta were removed. Liver lipids were measured by chemical methods, and serum lipids were measured using an enzymatic method kit (see Example 3). Serum thiobarbituric acid reactant (TBARS) was measured by chemical method.

結果:
[実験1 糞中への脂肪酸排泄量の測定]
result:
[Experiment 1 Measurement of Fatty Acid Excretion in Feces]

Figure 2007111306
糞中への脂肪酸排泄量は、Control群及びBitter gourd群と比較してKakrol群で有意に高かった。
Figure 2007111306
The amount of fatty acid excreted in feces was significantly higher in the Kakrol group than in the Control group and the Bitter gourd group.

[実験2 アポE欠損マウスにおける脂質代謝の評価]     [Experiment 2: Evaluation of lipid metabolism in apoE-deficient mice]

Figure 2007111306
初体重、終体重、体重増加量、摂食量及び体重あたりの肝臓重量は群間に有意差は見られなかったが、食効率はControl群と比較してKakrol群で有意に低かった。
Figure 2007111306
The initial body weight, the final body weight, the weight gain, the amount of food intake, and the liver weight per body weight were not significantly different among the groups, but the food efficiency was significantly lower in the Kakrol group than in the Control group.

Figure 2007111306
総脂肪重量、腸間膜及び皮下脂肪組織重量はControl群と比較してKakrol群で有意に低かった。また、腹膜後腔及び腎周辺、睾丸・卵巣周辺の脂肪組織重量は群間に有意差は見られなかった。
Figure 2007111306
Total fat weight, mesentery and subcutaneous adipose tissue weight were significantly lower in Kakrol group compared to Control group. In addition, there was no significant difference between the groups in the weight of adipose tissue around the retroperitoneal cavity, around the kidney, and around the testicle / ovary.

Figure 2007111306
血清中の総Chol濃度、VLDL及びLDL濃度はControl群と比較してKakrol群で有意に低かったが、HDL濃度は群間に有意差は見られなかった。一方、肝臓中の総Chol濃度、TG濃度は群間に有意差は見られなかったが、リン脂質はControl群と比較してKakrol群で有意に低かった。
Figure 2007111306
The serum total Chol concentration, VLDL and LDL concentrations were significantly lower in the Kakrol group compared to the Control group, but HDL concentrations were not significantly different between the groups. On the other hand, the total Chol concentration and TG concentration in the liver were not significantly different between the groups, but phospholipids were significantly lower in the Kakrol group than in the Control group.

Figure 2007111306
血清中のTBARS濃度はControl群と比較してKakrol群で有意に低かった。
Figure 2007111306
Serum TBARS concentration was significantly lower in the Kakrol group compared to the Control group.

考察:
カックロールの肝臓脂質及び血清コレステロール濃度低下作用は、TGの吸収を抑制することに起因していると示唆された。よって今後はカックロールの脂質吸収阻害の機構を明らかにするため、小腸吸収細胞での脂質の輸送に及ぼす影響を検討する。また今回飼育したアポE欠損マウスの大動脈切片を作成し、カックロールが動脈硬化症の進展に及ぼす影響も評価する予定である。
Discussion:
It was suggested that the action of Kakrol to lower liver lipid and serum cholesterol levels was due to suppression of TG absorption. Therefore, in order to clarify the mechanism of Kakroll's lipid absorption inhibition, we will investigate the effects on lipid transport in small intestinal absorption cells. In addition, we plan to make aortic sections of apoE-deficient mice raised this time and evaluate the effect of cuckroll on the progression of arteriosclerosis.

Claims (10)

カックロール、及び食品又は医薬として許容可能な添加物を含む、食品又は医薬組成物。   A food or pharmaceutical composition comprising cucumber and a food or pharmaceutically acceptable additive. 脂質代謝に関連した疾患又は状態を処置するための、請求項1に記載の食品又は医薬組成物。   2. The food or pharmaceutical composition according to claim 1, for treating a disease or condition associated with lipid metabolism. 疾患又は状態が、高脂血症(原発性(家族性、散発性)、二次性を含む。また、高コレステロール血症を含む。)、脂肪肝、動脈硬化、虚血性心疾患(狭心症、心筋梗塞を含む。)、脳血管障害(脳梗塞、脳出血を含む。)又は生活習慣病である、請求項2に記載の食品又は医薬組成物。   The disease or condition is hyperlipidemia (including primary (familial, sporadic), secondary, and hypercholesterolemia), fatty liver, arteriosclerosis, ischemic heart disease (anginal) 3. The food or pharmaceutical composition according to claim 2, wherein the food or pharmaceutical composition is a cerebrovascular disorder (including cerebral infarction or cerebral hemorrhage) or a lifestyle-related disease. カックロールが、カックロール青果、その乾燥物、抽出物、分画物、単離物、もしくは濃縮物又はそれらのいずれかの加工物である、請求項1〜3のいずれか1項に記載の食品又は医薬医薬組成物。   The roll of kak roll is a roll of kak roll, a dried product, an extract, a fraction, an isolate, or a concentrate or any processed product thereof. A food or pharmaceutical composition. カックロールを摂取させることにより脂質代謝を改善する、脂質代謝に関連した疾患又は状態の処置方法。   A method for treating a disease or condition related to lipid metabolism, wherein lipid metabolism is improved by ingesting kakrol. カックロールを含む、脂質代謝改善剤。   An agent for improving lipid metabolism, including kaklol. カックロール、及びカックロールを脂質代謝改善のために用いるための指針を含む、製品。   A product comprising kakrol and guidelines for using kakrol for improving lipid metabolism. カックロールを、青果の乾燥物として 10g〜1000g(好ましくは25g〜500g、より好ましくは50g〜250g)に相当する量で含む、請求項4に記載の食品又は医薬組成物。 5. The food or pharmaceutical composition according to claim 4, comprising kak roll in an amount corresponding to 10 g to 1000 g (preferably 25 g to 500 g, more preferably 50 g to 250 g) as a dried product of fruits and vegetables. カックロールを摂取させることを含む、脂質吸収の阻害方法。   A method for inhibiting lipid absorption, comprising ingesting cocolol. カックロールを含む、脂質吸収阻害剤。   Lipid absorption inhibitors, including cocolol.
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