JP2004323469A - Medicinal composition and food for prevention and treatment of type ii diabetes - Google Patents
Medicinal composition and food for prevention and treatment of type ii diabetes Download PDFInfo
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- JP2004323469A JP2004323469A JP2003123434A JP2003123434A JP2004323469A JP 2004323469 A JP2004323469 A JP 2004323469A JP 2003123434 A JP2003123434 A JP 2003123434A JP 2003123434 A JP2003123434 A JP 2003123434A JP 2004323469 A JP2004323469 A JP 2004323469A
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Abstract
Description
【０００１】
【発明の属する技術分野】
本発明は、通常の食事を取りながら毎日簡単に摂取できる、酵素処理により１個から複数個のグルコースを付加したフラボノイド類を含有するＩＩ型糖尿病の予防、治療用の医薬組成物および健康食品に関する。
【０００２】
【従来の技術】
１９９７年の厚生省による糖尿病実態調査によると、日本の糖尿病患者は推計で６９０万人、糖尿病を疑われる「予備軍」を含めると１３７０万人、国民の約１０％にも達する。さらに糖尿病患者の９０％がＩＩ型糖尿病に罹患しているといわれる。ＩＩ型糖尿病は肥満等が原因となって血糖低下ホルモンであるインスリンが作用しにくくなって発症する糖尿病である。ＩＩ型糖尿病の治療法は一般に食事、運動療法を基本としている。そこで毎日の食事をしながら摂取できるＩＩ型糖尿病の予防用の食品や予防用、治療用の医薬品が望まれる。ＩＩ型糖尿病の治療効果をもつ薬剤については種々のものが既に報告されているが、前駆脂肪細胞が脂肪細胞へ分化するのを促進する働きによる治療効果を持つピオグリタゾン（ｐｉｏｇｌｉｔａｚｏｎｅ）が一例として挙げられる。しかし、これらの治療効果の高い合成の医療用医薬品は長期にわたって使用すると人体に対して有害な副作用を引き起こす可能性があった。そのため、長期にわたって使用しても人体に有害な副作用を生じさせない天然物由来のもので治療効果を持つものの開発が待ち望まれている。前駆脂肪細胞が脂肪細胞へ分化するのを促進する働きによりＩＩ型糖尿病の治療効果をもつ天然物としては、柑橘類等の植物抽出物があり、その有効成分は、ヘスペリジンやナリンジンといったフラバノンであったとされている（特許文献１）。しかしながら、これらの物質は吸収性が低く有効な効果を得るためには多量に摂取する必要があった。
【０００３】
天然物由来のフラボノイド類は、配糖体の形で含まれているのが一般的である。なかでもケルセチンやナリンジン、ヘスペリジンなど糖質部をルチノースとするものが多く、これらの配糖体は、小腸では吸収されず、大腸内の細菌によって糖とアグリコンに分解され、大腸から吸収されると考えられていた。従って、フラボノイドの吸収性を高めるためには、配糖体の形ではなくアグリコンとして摂取するのが有効とされていた（特許文献２）。しかるに本発明者らは上記の結果とは逆に糖質部をルチノースとするヘスペリジンなどのフラボノイドの配糖体にさらに糖を付加し、分岐した糖鎖をもった配糖体を糖尿病マウスに投与し、糖尿病症状を改善することを発見し、本発明を完成させた。
【０００４】
【特許文献１】
特開平１１−１７１７６６号公報
【０００５】
【特許文献２】
特開平２０００−２８１６７３号公報
【０００６】
【発明が解決しようとする課題】
本発明の目的は安全であり、かつ毎日の食事をしながら容易に摂取でき、有効成分の吸収性が高いＩＩ型糖尿病予防用の食品および、予防用、治療用の医薬組成物を提供することにある。
【０００７】
【課題を解決するための手段】
上記目的を達成するための本発明の技術的手段を以下に示す。
天然物、特に植物組織から抽出して得られる、糖質部位にルチノースをもつフラボノイド配糖体に糖転移酵素により、グルコースをさらに１個から複数個付加させることにより、分岐した糖鎖をもつ配糖体が得られる。これらの配糖体は、大腸からだけでなく胃や小腸からも吸収されるようになり、吸収性が著しく高まった。本発明品は、これらの吸収性が高まったフラボノイド類を有効成分として含有する食品または医薬組成物である。
【０００８】
これらの発明品は液状品、粉末品、顆粒品、錠剤品とすることができる。添加量は０．０５％から９０％が望ましい。好ましくは１％〜５０％、より好ましくは１％〜１０％、さらに好ましくは１％〜５％添加することが望ましい。
【０００９】
本発明の有効成分を含有する飲食物および医薬品は、健康飲食物および医薬品とすることができる。また、本物質は飼料に添加することができ、家畜、ペットなどの糖尿病予防や治療などに用いることができる。本発明品の例としては、有効成分を含有する和菓子、洋菓子、氷菓、飲料、スプレッド、ペースト、調味料、漬物、瓶缶詰、畜肉加工品、魚肉・水産加工品、乳・卵加工品、野菜加工品、果実加工品、穀類加工品など、ほとんどすべての飲食物および医薬品に利用することができる。本発明品の有効成分は、添加する食品に制約をもつものではないが、糖尿病患者が食するものとして、特に嗜好品においては食後の血糖値の上昇が緩やかなものに添加するのが好ましいと考えられる。
【００１０】
【実施例】
以下に本発明の実施例を示す。
【００１１】
（実施例１）
本発明品の有効成分の吸収量測定試験
６週齢のオスのｄｄＹ マウスを１６時間絶食後、５０ｍｇ／ｍｌのヘスペリジン懸濁液または酵素処理により糖を付加したヘスペリジン（以下酵素処理ヘスペリジンと呼ぶ）溶液をゾンデ針を用いて、１個体あたり２００μｌ（ヘスペレチンとして４ｍｇ）経口投与した。経口投与前、投与後１５分、３０分、１時間、２時間、４時間、６時間、９時間、１２時間後毎に心臓より採血。
血漿に分離し、血漿中の濃度をアグリコンであるヘスペレチン濃度として測定した。測定結果を図１に示す。これより、酵素処理ヘスペリジンのほうがヘスペリジンに比べより多く吸収されており、少量の摂取で効果を発揮することができることがわかる。
【００１２】
（実施例２）
本発明品の糖尿病に対する効果の試験
本試験において、食餌中に添加することにより、ＩＩ型糖尿病のモデル動物であるＫＫＡｙマウスに投与して血糖値の改善効果を検討した。
【００１３】
飼育条件として、４週齢のＫＫＡｙマウスを購入し、１週間の予備飼育後、体重、血糖値を測定した。それぞれが均一となるようにマウスを２群に分けた。１群を対照群、もう１群を試験食群とした。試験食群は被験物質として酵素処理して糖を付加したヘスペリジンを１％摂取するように餌に配合した。１群５匹ずつプラスチック製の飼育ケージに入れ、餌、水は自由摂取させた。体重、摂餌量、飲水量を毎日測定した。
【００１４】
実験飼料の調製としては、表１の配合のごとく飼料を調製した。
【００１５】
【表１】
（実施例３）
実施例１および２の条件で飼育したマウスを飼料摂取開始後８週後に糖負荷試験を実施した。１５時間絶食させた後、グルコースを１ｇ／ｋｇ体重となるように経口投与した。投与前、投与後３０、６０、１２０、１８０分に尾より採血し、小型血糖測定器グルテストを用い、酵素電極法により血糖値を測定した。表２に試験結果を示す。
【００１７】
【表２】
（実施例４）
実験方法３
【００１９】
飼育方法および測定項目
ＩＩ型糖尿病モデルマウスであるＫＫＡｙ（♀，４週齢）を用い、１週間の予備飼育後、体重、血糖値を測定した。それぞれの平均が等しくなるように群分けを行った。対照群には餌としてＣＥ−２（日本クレア（株））を与え、試験群には、被験物質として酵素処理ヘスペリジンを１％配合したＣＥ−２を与えた。餌、水は自由摂取させ、２〜３日毎に体重、摂餌量、飲水量を記録した。また、１週間ごとに血糖値を測定し記録した。表３に飼育結果を、図３に血糖値の測定結果を示す。
【００２０】
【表３】
上記実施例の結果、酵素処理によりグルコースを付加したフラボノイドは血糖値の改善効果を示すことがわかった。
【００２２】
本発明品の有効成分を表４の配合に従い、アイスクリームに添加した。通常のアイスクリームと変わらず、風味良好なアイスクリームが得られた。
【００２３】
【表４】
【発明の効果】
本発明により、ＩＩ型糖尿病の予防、治療に効果的で通常の食事をしながら簡単に摂取でき、副作用の面からも安全な医薬組成物および食品が提供される。
【００２５】
【図面の簡単な説明】
【図１】吸収量測定結果である。 ＨｓｐＧｎは酵素処理ヘスペリジンをＨｓｐはヘスペリジンをそれぞれ意味する。
【図２】表３の結果をグラフ化したものである。
【図３】実施例４における血糖値測定結果である[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a pharmaceutical composition and health food for the prevention and treatment of type II diabetes containing flavonoids added with one to a plurality of glucoses by enzyme treatment, which can be easily ingested daily while taking a normal meal. .
[0002]
[Prior art]
According to a 1997 survey of diabetes by the Ministry of Health and Welfare, there are an estimated 6.9 million diabetic patients in Japan, 13.7 million including the “reserve army” suspected of diabetes, or about 10% of the population. Furthermore, 90% of diabetic patients are said to suffer from type II diabetes. Type II diabetes is diabetes that develops because obesity or the like causes insulin that is a hypoglycemic hormone to be less effective. Treatment of type II diabetes is generally based on diet and exercise therapy. Therefore, foods for preventing type II diabetes that can be ingested while eating daily, and pharmaceuticals for prevention and treatment are desired. Various drugs have already been reported as therapeutic agents for type II diabetes, and an example is pioglitazone that has a therapeutic effect by promoting the differentiation of preadipocytes into adipocytes. . However, these highly therapeutic synthetic ethical drugs may cause harmful side effects when used for a long time. Therefore, there is a long-awaited development of a natural product derived from a natural product that does not cause harmful side effects to the human body even when used over a long period of time and has a therapeutic effect. Natural products that have a therapeutic effect on type II diabetes by promoting the differentiation of preadipocytes into adipocytes include plant extracts such as citrus fruits, and their active ingredients were flavanones such as hesperidin and naringin. (Patent Document 1). However, these substances are low in absorption and need to be ingested in large quantities to obtain an effective effect.
[0003]
Naturally derived flavonoids are generally contained in the form of glycosides. In particular, glucosine, such as quercetin, naringin, and hesperidin, have many saccharides as the rutinose, and these glycosides are not absorbed in the small intestine, but are decomposed into sugars and aglycones by bacteria in the large intestine. It was thought. Therefore, in order to increase the absorbability of flavonoids, it has been considered effective to take in as aglycone rather than in the form of glycoside (Patent Document 2). However, contrary to the above results, the present inventors further added a saccharide to a flavonoid glycoside such as hesperidin having a carbohydrate moiety as rutinose, and administered the glycoside having a branched sugar chain to a diabetic mouse. The present invention was completed by discovering that the symptoms of diabetes were improved.
[0004]
[Patent Document 1]
Japanese Patent Laid-Open No. 11-171766
[Patent Document 2]
Japanese Patent Laid-Open No. 2000-281673 [0006]
[Problems to be solved by the invention]
An object of the present invention is to provide a food for prevention of type II diabetes and a pharmaceutical composition for prevention and treatment, which is safe and can be easily ingested while eating daily, and has high absorbability of active ingredients. It is in.
[0007]
[Means for Solving the Problems]
The technical means of the present invention for achieving the above object will be described below.
A flavonoid glycoside having lutinose at the carbohydrate site obtained by extraction from natural products, particularly plant tissues, is added with one or more glucoses by glycosyltransferase to provide a branched sugar chain. Glycosides are obtained. These glycosides are absorbed not only from the large intestine but also from the stomach and small intestine, and the absorbability is remarkably increased. The product of the present invention is a food or pharmaceutical composition containing these enhanced flavonoids as active ingredients.
[0008]
These invention products can be liquid products, powder products, granule products, and tablet products. The addition amount is desirably 0.05% to 90%. It is desirable to add 1% to 50%, more preferably 1% to 10%, and still more preferably 1% to 5%.
[0009]
Foods and beverages and pharmaceuticals containing the active ingredients of the present invention can be healthy foods and beverages and pharmaceuticals. Moreover, this substance can be added to feed and can be used for the prevention and treatment of diabetes in livestock, pets and the like. Examples of the present invention products include Japanese confectionery, Western confectionery, ice confectionery, beverages, spreads, pastes, seasonings, pickles, canned bottles, processed meat products, processed fish / fishery products, processed milk / egg products, vegetables It can be used for almost all foods and beverages, such as processed products, processed fruit products, and processed cereal products. The active ingredient of the product of the present invention is not limited to the food to be added, but it is preferable to add it to those with a gradual increase in blood glucose level after meals, particularly in luxury products, as eaten by diabetic patients. Conceivable.
[0010]
【Example】
Examples of the present invention are shown below.
[0011]
(Example 1)
Absorption measurement test of active ingredient of the present invention A 6-week-old male ddY mouse is fasted for 16 hours and then hesperidin added with a sugar by 50 mg / ml hesperidin suspension or enzyme treatment (hereinafter referred to as enzyme-treated hesperidin) The solution was orally administered with a sonde needle at 200 μl per individual (4 mg as hesperetin). Blood was collected from the heart before oral administration and every 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 9 hours and 12 hours after administration.
After separating into plasma, the concentration in plasma was measured as the concentration of hesperetin, an aglycone. The measurement results are shown in FIG. This shows that enzyme-treated hesperidin is absorbed more than hesperidin and can be effective with a small amount of ingestion.
[0012]
(Example 2)
Test of the effect of the product of the present invention on diabetes In this test, the effect of improving blood glucose level was examined by adding it to the diet to KKAy mice, which are model animals for type II diabetes.
[0013]
As the breeding conditions, 4 week old KKAy mice were purchased, and after preliminary breeding for 1 week, body weight and blood glucose level were measured. The mice were divided into two groups so that each was uniform. One group was a control group and the other group was a test meal group. The test food group was blended into the diet so as to ingest 1% of hesperidin with an enzyme-treated and added sugar as a test substance. Each group contained 5 animals in a plastic cage and allowed food and water to be freely consumed. Body weight, food intake and water consumption were measured daily.
[0014]
As the preparation of the experimental feed, the feed was prepared as shown in Table 1.
[0015]
[Table 1]
(Example 3)
A glucose tolerance test was performed 8 weeks after the start of feed intake of the mice bred under the conditions of Examples 1 and 2. After fasting for 15 hours, glucose was orally administered to 1 g / kg body weight. Blood samples were collected from the tail before administration and 30, 60, 120, and 180 minutes after administration, and blood glucose levels were measured by the enzyme electrode method using a small blood glucose meter Glutest. Table 2 shows the test results.
[0017]
[Table 2]
Example 4
Experimental method 3
[0019]
Breeding method and measurement items Using KKAy (♀, 4 weeks old) which is a type II diabetes model mouse, body weight and blood glucose level were measured after preliminary breeding for 1 week. Grouping was performed so that the average of each was equal. The control group was given CE-2 (Nippon Claire Co., Ltd.) as a food, and the test group was given CE-2 containing 1% enzyme-treated hesperidin as the test substance. Food and water were freely consumed, and body weight, food intake, and water consumption were recorded every 2-3 days. In addition, blood glucose levels were measured and recorded every week. Table 3 shows the results of breeding, and FIG. 3 shows the results of blood glucose measurement.
[0020]
[Table 3]
As a result of the above Examples, it was found that flavonoids added with glucose by enzyme treatment showed an effect of improving blood glucose level.
[0022]
The active ingredient of the product of the present invention was added to ice cream according to the formulation shown in Table 4. An ice cream having a good flavor was obtained without changing from a normal ice cream.
[0023]
[Table 4]
【The invention's effect】
INDUSTRIAL APPLICABILITY According to the present invention, there are provided a pharmaceutical composition and a food that are effective for prevention and treatment of type II diabetes, can be easily taken while eating a normal meal, and are safe in terms of side effects.
[0025]
[Brief description of the drawings]
FIG. 1 is an absorption measurement result. HspGn means enzyme-treated hesperidin, and Hsp means hesperidin.
FIG. 2 is a graph of the results in Table 3.
FIG. 3 shows blood glucose level measurement results in Example 4
Claims (8)
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| JP2003123434A JP2004323469A (en) | 2003-04-28 | 2003-04-28 | Medicinal composition and food for prevention and treatment of type ii diabetes |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2004096198A1 (en) * | 2003-05-02 | 2006-07-13 | タカラバイオ株式会社 | Therapeutic agent |
| JP2007223914A (en) * | 2006-02-21 | 2007-09-06 | Unitika Ltd | Oral administration formulation |
| JP2007314446A (en) * | 2006-05-24 | 2007-12-06 | Kao Corp | AMPK activator |
| JP2009538342A (en) * | 2006-05-26 | 2009-11-05 | ネステク ソシエテ アノニム | Method for using touchi extract and nutritional composition |
| JP2018080204A (en) * | 2011-08-01 | 2018-05-24 | 株式会社林原 | CRYSTAL OF α-GLUCOSYL HESPERIDIN AND USE THEREOF |
-
2003
- 2003-04-28 JP JP2003123434A patent/JP2004323469A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2004096198A1 (en) * | 2003-05-02 | 2006-07-13 | タカラバイオ株式会社 | Therapeutic agent |
| JP2007223914A (en) * | 2006-02-21 | 2007-09-06 | Unitika Ltd | Oral administration formulation |
| JP2007314446A (en) * | 2006-05-24 | 2007-12-06 | Kao Corp | AMPK activator |
| JP2009538342A (en) * | 2006-05-26 | 2009-11-05 | ネステク ソシエテ アノニム | Method for using touchi extract and nutritional composition |
| US8815312B2 (en) | 2006-05-26 | 2014-08-26 | Nestec S.A. | Methods of use and nutritional compositions of Touchi Extract |
| JP2018080204A (en) * | 2011-08-01 | 2018-05-24 | 株式会社林原 | CRYSTAL OF α-GLUCOSYL HESPERIDIN AND USE THEREOF |
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