JPH10279496A - Preventive and therapeutic agent for diabetes from rice - Google Patents

Preventive and therapeutic agent for diabetes from rice

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Publication number
JPH10279496A
JPH10279496A JP9120057A JP12005797A JPH10279496A JP H10279496 A JPH10279496 A JP H10279496A JP 9120057 A JP9120057 A JP 9120057A JP 12005797 A JP12005797 A JP 12005797A JP H10279496 A JPH10279496 A JP H10279496A
Authority
JP
Japan
Prior art keywords
rice
enzyme
diabetes
fermentation
therapeutic agent
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.)
Granted
Application number
JP9120057A
Other languages
Japanese (ja)
Other versions
JP4838920B2 (en
Inventor
Takashi Tokuyama
孝 徳山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Soken Co Ltd
Original Assignee
Soken Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Soken Co Ltd filed Critical Soken Co Ltd
Priority to JP12005797A priority Critical patent/JP4838920B2/en
Publication of JPH10279496A publication Critical patent/JPH10279496A/en
Application granted granted Critical
Publication of JP4838920B2 publication Critical patent/JP4838920B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Abstract

PROBLEM TO BE SOLVED: To obtain a preventive and therapeutic agent for diabetes from rice which is safe, inexpensive, readily processable and has no fear of adverse effects at all even by regular use for a long period of time. SOLUTION: This preventive and a therapeutic agent for diabetes comprises an extract of rice with any of an acid, an alkali and an organic solvent, a treated solution obtained by treating rice with one or more enzymes of a protease, a cellulolytic enzyme, a lipolytic enzyme and an amylolytic enzyme and a koji and an extract of rice with water under an acidic or an alkali condition. The preventive and the therapeutic agent are obtained by incorporating rice, germinated rice or rice white bran with water, an acid, an alkali or an organic solvent in an amount of 1-100 times as much as that of rice, treating the mixture with one or more enzymes of a protease, a cellulolytic enzyme, a lipolytic enzyme and an amylolytic enzyme and a koji, heating the mixture to 40 deg.C to the boiling temperature and then carrying out alcohol fermentation, lactic acid fermentation, acetic acid fermentation or yeast aerated fermentation.

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【0001】[0001]

【産業上の利用分野】本発明は、米を用いることによ
り、インスリン感受性を上昇させ、糖・脂質代謝活性を
促進する、糖尿病予防・治療剤に関するものである。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a prophylactic / therapeutic agent for diabetes, which enhances insulin sensitivity and promotes glucose / lipid metabolic activity by using rice.

【0002】[0002]

【従来の技術】飽食の時代といわれる現代、カロリーの
摂取過剰が、肥満・糖尿病・高脂血症・動脈硬化症等様
々な疾患を生み、罹病率は増加の一途をたどっている。
また、発病するには至らなくとも、その予備軍といえる
人がそれ以上存在すると言われている。糖尿病には、イ
ンスリン依存型糖尿病(I型糖尿病)とインスリン非依
存型糖尿病(II型糖尿病)の2タイプがあるが、全体
の90%は後者のタイプである。インスリン非依存型糖
尿病は、過栄養によるインスリンの作用不足、例えば組
織におけるインスリン感受性低下、インスリン抵抗性及
び、それらの症状は、インスリン需要を増加させるた
め、インスリン分泌を担う膵臓に負担がかかりやがてイ
ンスリン分泌不足もきたすことによる、糖・脂質代謝の
異常が原因といわれている。インスリン非依存型糖尿病
は薬物による治療より、まずは食事療法、運動療法でコ
ントロールすることが基本とされている。しかし、その
ように自己管理がなされていても必ずしも代謝異常が是
正されるとは限らず、薬に依存しがちである。ところ
が、薬剤には、投与による副作用や使用量、使用期限に
制限の問題がある。また、これらは単一化された物質の
混合によるものがほとんどであるため、単一物質の副作
用、さらには長期に亘る服用により起こる安全性の面か
らも問題になっている。即ち、糖・脂質代謝異常に起因
する疾患に対して有効で安全な予防・治療剤は未だ開発
されていないのが現状である。
2. Description of the Related Art In the modern age of satiety, excessive intake of calories produces various diseases such as obesity, diabetes, hyperlipidemia, and arteriosclerosis, and the morbidity is steadily increasing.
It is said that even if they do not get sick, there are more people who can be said to be a reserve army. There are two types of diabetes, insulin-dependent diabetes mellitus (type I diabetes) and non-insulin-dependent diabetes mellitus (type II diabetes), with 90% of the latter being the latter type. Non-insulin-dependent diabetes mellitus is an inadequate action of insulin due to overnutrition, such as decreased insulin sensitivity in tissues, insulin resistance, and their symptoms, which increase insulin demand, and eventually burden the pancreas responsible for insulin secretion. It is said that abnormalities in glucose and lipid metabolism due to insufficient secretion are caused. Non-insulin-dependent diabetes mellitus is basically controlled by diet therapy and exercise therapy rather than drug treatment. However, such self-management does not always correct metabolic abnormalities and tends to depend on drugs. However, the drug has problems of side effects due to administration, the amount to be used, and restrictions on the expiration date. In addition, since most of these substances are obtained by mixing unified substances, there is a problem in terms of side effects of the single substance and safety caused by taking the substance for a long time. That is, at present, an effective and safe preventive / therapeutic agent for a disease caused by abnormal sugar / lipid metabolism has not yet been developed.

【0003】一方、米は主食以外に、清酒、焼酎、みり
ん、酢、麹などとして用途開発され、古くから生活に欠
かせないものとなっている。このほかには、美容的用途
として糠袋が知られている。これらは米を単なる主食で
あると見るか、またはせいぜい澱粉源としてしか見てい
なかったということによるものであると思われる。ま
た、糠袋にしても、皮膚によいとされ、慣例的にそのま
ま使用されてきたのみであり、有効成分という概念もな
ければ、その有効成分を利用するという考え方も全くな
かったのである。
On the other hand, rice has been developed for use as sake, shochu, mirin, vinegar, koji and the like in addition to the staple food, and has been indispensable to daily life since ancient times. In addition, bran bags are known for cosmetic use. These may be due to the fact that rice was viewed as a staple food only, or at best, as a source of starch. In addition, even though the bran bag is good for the skin, it has only been conventionally used as it is, and there was no concept of an active ingredient, and there was no idea of using the active ingredient at all.

【0004】[0004]

【発明が解決しようとする課題】薬物を使った糖尿病治
療は、常に人体に対する副作用を伴う危険性がある。糖
尿病薬である経口血糖降下剤の使用や、インスリン注射
は、作用が強すぎると重度の低血糖症を起こすことが知
られている。また、糖尿病予防は、食事に気をつけるこ
とや運動を取り入れる以外、効果的な方法はなっかた。
このような背景から、副作用が全くなく、しかも予防・
治療剤として、長期にわたって常用しても充分に安全な
糖尿病予防・治療剤が要求されている。本発明は、安全
で安価であり、常用しても全く安全な米からの糖尿病予
防・治療剤を提供することを目的としている。
There is a risk that the treatment of diabetes using a drug is always accompanied by side effects on the human body. It is known that the use of an oral antihyperglycemic agent, which is a diabetes drug, and insulin injection cause severe hypoglycemia if the action is too strong. Also, there has been no effective way to prevent diabetes other than taking care of food and exercising.
Against this background, there are no side effects,
As a therapeutic agent, a preventive / therapeutic agent for diabetes which is sufficiently safe even when used regularly for a long time is required. An object of the present invention is to provide an agent for preventing and treating diabetes from rice that is safe, inexpensive, and completely safe even when used regularly.

【0005】[0005]

【課題を解決するための手段】発明者らは、動植物合和
すの観点から、主食である米を中心に種々の植物成分の
研究を進めてきた。その過程で米は今までに予測できな
かった数多くの可能性及び効果があることが判明してき
た。そこで主食として用いられ、安全性が最も高いこと
が実証されている米をテーマとして取り上げ、米の総合
利用研究を行ってきた。その中の1テーマとして、米か
らの糖尿病予防・治療剤について、鋭意研究を重ねてき
たのである。その結果、米には、インスリン感受性を高
め、糖・脂質代謝活性を促進する成分が含まれることが
わかり、本発明の完成に至った。
Means for Solving the Problems The inventors have been studying various plant components, mainly rice, which is a staple food, from the viewpoint of blending animals and plants. In the process, rice has been discovered to have a number of possibilities and effects that could not be predicted before. Therefore, we have taken up the theme of rice, which is used as a staple food and proved to be the safest, and conducted comprehensive research on rice utilization. As one of the themes, he has been conducting diligent research on preventive and therapeutic agents for diabetes from rice. As a result, it was found that rice contains components that increase insulin sensitivity and promote sugar / lipid metabolism activity, and thus completed the present invention.

【0006】本発明において、米または発芽させた米、
または米白糠に含有されている糖尿病予防・治療効果を
有する成分は未だ解明するには至っていないが米または
発芽させた米、または米白糠を処理したものには、糖尿
病に対する予防・治療効果を示すことが判明した。原料
の米は、ジャポニカ、インディカ米を問わず、うるち米
および餅米等の玄米および白米、白糠を指し、品質、種
類は問わない。また、発芽させた米が使用される。な
お、有効成分は、熱及び光に対して安定であるため、上
記の原料は、浸漬、蒸煮、ばい煎(砂あぶり、網あぶ
り、熱風ばい煎等全てを指す)、蒸煮ばい煎、凍結乾燥
等の表面変性、UV照射等の光変性、パットライス等の
加圧ばい煎、揚げる等の処理をしてもよい。その米およ
び発芽させた米は、そのまま用いても有効であるが、実
用上の面から粉砕して用いるのが好ましい。米および発
芽させた米を粉砕して粉体化するには、粉砕機または精
米機を用い一般的な方法で行えばよい。
[0006] In the present invention, rice or sprouted rice,
Or, the components having the preventive and therapeutic effect of diabetes contained in rice white bran have not been elucidated yet, but rice or germinated rice, or those treated with rice white bran show a preventive and therapeutic effect on diabetes. It has been found. The raw material rice refers to brown rice, white rice, and white bran such as glutinous rice and rice cake, regardless of the quality or type, regardless of japonica or indica rice. Also, sprouted rice is used. In addition, since the active ingredient is stable against heat and light, the above-mentioned raw materials are dipped, steamed, roasted (refer to all kinds of sand roasting, net roasting, hot air roasting, etc.), steamed roasting, and freeze-dried. Surface modification such as UV irradiation, and treatment such as pressurized roasting and frying such as patrice. The rice and the germinated rice are effective as they are, but are preferably ground and used for practical use. In order to pulverize and pulverize the rice and the sprouted rice, a general method using a pulverizer or a rice mill may be used.

【0007】米を発芽させる場合、胚芽のついた米を水
に浸漬あるいは水を噴霧して発芽させる。発芽させる時
の温度は5〜70℃である。ただし、発芽さえすれば、
温度および時間は問わない。また、発芽中に水が腐敗す
る危険性がある場合は、腐敗しないように水を取り替え
るか、何らかの防腐を行うのが好ましい。ここで、発芽
とは、発芽する直前から発芽したものまで全てを指す。
この発芽させた米をよく洗浄して用いる。この時、乾燥
して用いてもよい。
[0007] When germinating rice, the germinated rice is immersed in water or sprayed with water to germinate the rice. The temperature at the time of germination is 5 to 70 ° C. However, as long as it germinates,
The temperature and time do not matter. In addition, when there is a risk of water spoiling during germination, it is preferable to replace the water so as not to spoil or perform some preservation. Here, germination refers to everything from immediately before germination to germination.
The sprouted rice is thoroughly washed and used. At this time, it may be dried before use.

【0008】米を水抽出する場合、抽出温度は、高温が
効率的であるが、低温でも十分に抽出を行うことができ
る。ただし、40℃以下の低温の場合は、pHを酸性あ
るいはアルカリ性にするか、防腐剤あるいはアルコール
を加えて、米が腐敗しないように処理する。抽出時間
は、有効成分さえ抽出できればよく、抽出温度により定
めればよい。また、抽出は、加圧下、常圧下でも、減圧
下で行ってもよい。さらに加水量の有効な範囲は、米に
対して1〜100倍である。効果さえあれば、もっと薄
い濃度で抽出しても良い。ただこの場合は、抽出後濃縮
して有効成分を濃くする必要性が生じる可能性がある。
In the case of extracting rice with water, the extraction temperature is efficient at a high temperature, but sufficient extraction can be performed even at a low temperature. However, in the case of a low temperature of 40 ° C. or less, the pH is made acidic or alkaline, or a preservative or alcohol is added so as to prevent the rice from spoiling. The extraction time only needs to be able to extract the active ingredient, and may be determined according to the extraction temperature. The extraction may be performed under increased pressure, normal pressure, or reduced pressure. Further, the effective range of the amount of water is 1 to 100 times that of rice. If it is effective, it may be extracted at a lower concentration. However, in this case, there is a possibility that it is necessary to concentrate the extract after the extraction to make the active ingredient dense.

【0009】水抽出の場合、最も問題になるのは糊化現
象である。糊状になれば、抽出効率が悪くなるばかりで
なく、実作業においては困難を極める。これを防ぐため
には、アミラーゼを加えて反応させるか、塩酸などで酸
性にして澱粉を切ってやればよく、この方法を用いるこ
とにより、十分に解決でき、実用上も全く問題はない。
抽出物中の有効成分は、酸、アルカリに安定であるた
め、酸分解抽出、あるいはアルカリ分解抽出を行うのも
有効である。この場合、必要により中和、脱塩を行う。
In the case of water extraction, the most problem is the gelatinization phenomenon. If it becomes glue-like, not only does the extraction efficiency deteriorate, but it becomes extremely difficult in actual work. In order to prevent this, the starch may be cut by adding amylase and making it react, or acidifying it with hydrochloric acid or the like. This method can sufficiently solve the problem and has no practical problem at all.
Since the active ingredient in the extract is stable to acids and alkalis, it is effective to perform acid decomposition extraction or alkali decomposition extraction. In this case, neutralization and desalting are performed as necessary.

【0010】有機溶媒で抽出する場合も、米はなるべく
微粉砕または粉体化して抽出することが望ましい。有機
溶媒はアルコール、アセトン、ブタノール、n−ヘキサ
ン、メタノール、エーテル等の一般的な有機溶媒でよい
が、人体に対して有害なものは抽出後、溶媒を完全に除
去する必要がある。
In the case of extraction with an organic solvent, it is desirable that rice is extracted by pulverizing or powdering as much as possible. The organic solvent may be a general organic solvent such as alcohol, acetone, butanol, n-hexane, methanol, ether and the like, but it is necessary to completely remove the solvent harmful to the human body after extraction.

【0011】また、抽出を行うにあたり、澱粉分解酵
素、蛋白分解酵素、脂肪分解酵素、繊維分解酵素を各
々、または2種以上を組み合わせても良い。また、麹を
使用してもよく、この場合使用する麹は、一般に使用さ
れる麹でよく、麹菌の種類および品種を問わない。な
お、上記の酵素反応及び麹は、前記の前記の抽出前、あ
るいは抽出と同時に、または抽出の後に作用させてもよ
い。なお、必要により、酵母による通気発酵、アルコー
ル沈殿、合成吸着剤等を用いて除糖してもよい。
In the extraction, amylolytic enzymes, proteolytic enzymes, lipolytic enzymes and fibrinolytic enzymes may be used alone or in combination of two or more. In addition, koji may be used. In this case, the koji used may be a commonly used koji, regardless of the type and variety of the koji mold. The enzymatic reaction and the koji may be performed before the extraction, simultaneously with the extraction, or after the extraction. If necessary, sugar may be removed using aeration fermentation with yeast, alcohol precipitation, a synthetic adsorbent, or the like.

【0012】本発明においては、上記の各処理を行うと
同時または処理後、アルコール発酵あるいは乳酸発酵、
酢酸発酵等の有機酸発酵を行ってもよい。このアルコー
ル発酵を行う場合、上記のようにして得られた抽出物を
糖化し、そのまま、または圧搾、ろ過して得た液をアル
コール発酵させる。なお、酵素反応とアルコール発酵は
同時に行ってもよい。すなわち、米の加水物に、酵素ま
たは麹、さらに酒母または酵母を添加して、糖化、アル
コール発酵を行う。必要により補糖してアルコール発酵
を行ってもよい。糖化およびアルコール発酵は10〜2
4日間行い、この際、腐敗が心配な場合は、酸を添加す
るか、発酵の阻害にならない適当な防腐を施す。
In the present invention, alcohol fermentation or lactic acid fermentation is carried out simultaneously with or after each of the above treatments.
Organic acid fermentation such as acetic acid fermentation may be performed. When performing this alcohol fermentation, the extract obtained as described above is saccharified, and the liquid obtained by saccharification or by pressing and filtering is subjected to alcohol fermentation. The enzyme reaction and the alcohol fermentation may be performed simultaneously. That is, saccharification and alcohol fermentation are performed by adding enzymes or koji, and further adding sake or yeast to the rice water. If necessary, sugar fermentation may be performed to carry out alcohol fermentation. Saccharification and alcohol fermentation are 10-2
It is carried out for 4 days, and at this time, if putrefaction is a concern, an acid is added or an appropriate preservative which does not inhibit fermentation is applied.

【0013】アルコール発酵、通気発酵を行うと、ベト
ツキがなくなること、濃縮がしやすく有効成分の濃縮が
容易になることなどの利点もある。乳酸発酵を行う場合
は、アルコール発酵の場合と同様で、この場合は、酒母
または酵母の代わりに乳酸菌を添加して乳酸発酵を行
う。乳酸発酵は一般的な常法によって行い、乳酸菌の種
類および乳酸発酵の条件は問わない。次に、酢酸発酵の
場合は、上記のようにして得られた発酵物をそのまま、
あるいは希釈してアルコール4〜5%にした後、酢酸菌
を添加して酢酸発酵を行う。また、アルコールのないも
のは、アルコールを添加して酢酸発酵を行えばよい。酢
酸発酵は一般的な常法によって行い、酢酸菌の種類およ
び酢酸発酵の条件は問わない。
When alcohol fermentation or aeration fermentation is carried out, there are also advantages such as elimination of stickiness, easy concentration, and easy concentration of the active ingredient. Lactic acid fermentation is performed in the same manner as alcohol fermentation. In this case, lactic acid bacteria are added instead of sake brewer or yeast to perform lactic acid fermentation. Lactic acid fermentation is performed by a common method, and the type of lactic acid bacteria and the conditions of lactic acid fermentation are not limited. Next, in the case of acetic acid fermentation, the fermented product obtained as described above is
Alternatively, after diluting to 4 to 5% alcohol, acetic acid bacteria are added to perform acetic acid fermentation. In addition, in the case where there is no alcohol, acetic acid fermentation may be performed by adding alcohol. Acetic acid fermentation is carried out by a general method, and the type of acetic acid bacteria and the conditions of acetic acid fermentation are not limited.

【0014】以上のようにして得られた米の処理物は、
残差を分離することなくそのまま、あるいは圧搾、ろ過
して用いる。また、そのまま用いる時は、殺菌あるいは
除菌して製品にする。また、フリーズドライあるいはス
プレードライ等で乾燥して製品化してもよい。なお、本
発明品を配合する場合は常法に従って剤型化する。本発
明品の糖尿病予防・治療剤としての効果を試験に基づい
て以下に示す。
The processed rice obtained as described above is
Use the residue as it is without separating it, or after pressing and filtering. When used as it is, it is sterilized or disinfected to produce a product. Further, the product may be dried and dried by spray drying or the like. When the product of the present invention is blended, it is made into a dosage form according to a conventional method. The effects of the product of the present invention as an agent for preventing and treating diabetes are shown below based on tests.

【0015】本発明品の糖尿病予防・治療効果は、脂肪
細胞へと分化する性質をもつ、マウス胎仔由来の培養細
胞3T3−L1前駆脂肪細胞(3T3−Swiss a
lbino細胞の亜株)を用いて、糖・脂質代謝活性の
上昇効果として脂肪細胞への分化促進(グリセロール−
3−リン酸デヒドロゲナーゼ活性の上昇、中性脂肪トリ
アシルグリセロール蓄積量の増加)、リポプロテインリ
パーゼ活性上昇、インスリン感受性上昇効果としてグリ
セロール取り込み量を測定した。3T3−L1前駆脂肪
細胞は、分化前の繊維芽脂肪細胞では脂肪細胞に特徴的
な酵素の活性はほとんど検出されず、中性脂肪もみられ
ず、またホルモン感受性も認められない。脂肪細胞へ分
化することにより、糖・脂質代謝に関わる様々な酵素、
グリセロール−3−リン酸デヒドロゲナーゼ、リポプロ
テインリパーゼ、ホルモン感受性リパーゼなどの活性が
上昇し、中性脂肪の蓄積がみられ、インスリン、エピネ
フリン等のホルモンにも感受性をもつようになる。分化
した脂肪細胞は、生体内の成熟脂肪細胞とほとんど同じ
ホルモン感受性を持つことからインスリン作用等の研究
に用いられることも多い。先にも記述したように、イン
スリン非依存型糖尿病は、インスリン感受性の低下から
くるインスリン作用不足、インスリン分泌不足による糖
・脂質代謝活性の低下が原因である。これらの症状は脂
肪細胞の分化が抑制されているために起こる訳ではない
ことは、肥満者に糖尿病発症が起こりやすい事実からみ
ても明きらかである。脂肪細胞は中性脂肪を蓄積する
が、蓄積できる量にも限界があり、それを越えても過剰
に食物を摂取すると脂肪細胞数が増加する。よって、肥
満者は一つ一つの脂肪細胞が肥大化しており、その数も
多いことであろう。しかし、その様にして増加した脂肪
細胞が正常に機能しているとは限らずむしろ、その反対
であることが多い。食事により摂取したカロリーを代謝
するためにはインスリンが必要であるが、それはインス
リンが、細胞へ多量の糖を取り込ませる作用を有するた
めである。肥大化した脂肪細胞はインスリン感受性が鈍
くなりより多くのインスリンを必要とする。また摂取カ
ロリーが多ければ、それだけ多量のインスリンを必要と
する。このような状態が続くと、インスリン分泌臓器で
ある膵臓は疲労し、インスリンを充分に分泌できなくな
り糖尿病が発病する。よって単に脂肪細胞分化を促進す
るだけではなく、正常な代謝活性を有する脂肪細胞の分
化を促進することが、重要である。
[0015] The preventive and therapeutic effects of the product of the present invention on diabetes mellitus are shown by the fact that cultured cells derived from mouse embryos, 3T3-L1 preadipocytes (3T3-Swiss a
lbino cell sub-strain) to promote differentiation into adipocytes (glycerol-
Glycerol uptake was measured as an increase in 3-phosphate dehydrogenase activity, an increase in neutral fat triacylglycerol accumulation), an increase in lipoprotein lipase activity, and an increase in insulin sensitivity. In 3T3-L1 preadipocytes, the activity of enzymes characteristic of adipocytes is hardly detected in fibroblast adipocytes before differentiation, neutral fat is not observed, and hormone sensitivity is not observed. Various enzymes involved in sugar / lipid metabolism by differentiating into fat cells,
The activity of glycerol-3-phosphate dehydrogenase, lipoprotein lipase, hormone-sensitive lipase and the like is increased, the accumulation of neutral fat is observed, and the cells become sensitive to hormones such as insulin and epinephrine. Differentiated adipocytes have almost the same hormonal sensitivity as mature adipocytes in vivo, and are therefore often used for studies on insulin action and the like. As described above, non-insulin-dependent diabetes mellitus is caused by insufficient insulin action due to a decrease in insulin sensitivity and a decrease in glucose / lipid metabolic activity due to insufficient insulin secretion. It is clear from the fact that these symptoms are not caused by suppression of adipocyte differentiation because diabetes is likely to occur in obese people. Fat cells accumulate neutral fat, but the amount that can accumulate is also limited, and even if food is exceeded, excessive intake of food increases the number of fat cells. Therefore, in an obese person, each fat cell is enlarged, and the number of fat cells will be large. However, such increased fat cells are not always functioning normally, but rather the opposite. Insulin is required to metabolize calories ingested through meals, because insulin has the effect of taking up a large amount of sugar into cells. Hypertrophic fat cells become less sensitive to insulin and require more insulin. The more calories you consume, the more insulin you need. If such a state continues, the pancreas, which is an insulin-secreting organ, becomes fatigued, cannot sufficiently secrete insulin, and develops diabetes. Therefore, it is important not only to promote adipocyte differentiation but also to promote the differentiation of adipocytes having normal metabolic activity.

【0016】(実験方法1) 培養方法:3T3−L1前駆脂肪細胞は10%牛胎仔血
清(FBS)を含むDME培地(Dulbecos M
odified Eagle Medium)を用い5
%炭酸ガス、37℃で培養し、2〜3日ごとに培地交換
を行い、コンフルエンスに達した後、分化誘導処理を行
った。即ち、本発明品を培地に添加し、10μg/ml
インスリン共存で培養を行った。なお添加量は、液体の
場合培地1mlあたり33μl(3.3%)、固体の場
合は、生理食塩水で1%溶液とし、培地1mlあたり3
3μl(300μg/ml)添加した。コンフルエンス
に達してから、5回の培地交換を行った後培養を停止
し、グリセロール−3−リン酸デヒドロゲナーゼ(GP
DH)活性及び、細胞内に蓄積した中性脂肪(トリアシ
ルグリセロール:TG)量、リポプロテインリパーゼ活
性、グルコース取り込み量を下記の方法で測定した。培
養は、6ウェルプレートを用い、一群3穴で行った。な
お、コントロールとしてコンフルエンスに達した後も通
常の培地で培養したもの(BASAL)、10μg/m
lインスリンを添加したもの(Insulin)、ポジ
ティブコントロールとして、0.25μMデキサメタゾ
ン、0.5mM3−イソブチル−1−メチルキサンチ
ン、6μg/mlインスリンを添加した培地で、2日間
培養した後、再び通常の培地で培養したもの(DMI)
も測定を行った。
(Experimental method 1) Culture method: 3T3-L1 preadipocytes were prepared from DME medium (Dulbecos M) containing 10% fetal bovine serum (FBS).
5 using modified Eagle Medium.
After culturing at 37 ° C. in% carbon dioxide, the medium was replaced every 2 to 3 days, and after reaching confluence, a differentiation inducing treatment was performed. That is, the product of the present invention was added to the medium, and 10 μg / ml
Culture was performed in the presence of insulin. The addition amount is 33 μl (3.3%) per 1 ml of the culture medium in the case of a liquid, and 1% solution in physiological saline in the case of a solid.
3 μl (300 μg / ml) was added. After reaching confluence, the medium was exchanged five times, and then the culture was stopped and glycerol-3-phosphate dehydrogenase (GP
DH) activity, the amount of neutral fat (triacylglycerol: TG) accumulated in cells, lipoprotein lipase activity, and glucose uptake were measured by the following methods. The culture was performed using a 6-well plate in a group of 3 wells. As a control, those cultured in a normal medium even after reaching confluence (BASAL), 10 μg / m
l) Insulin was added, and as a positive control, the cells were cultured for 2 days in a medium supplemented with 0.25 μM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, and 6 μg / ml insulin, and then returned to a normal medium again. (DMI)
Were also measured.

【0017】(実験方法2) GPDH活性測定方法:培養停止後、細胞を生理食塩水
で2回洗浄し、25mMTrs−HCl 1mMEDT
Abuffer(pH7.4)1mlを加え細胞を剥が
し、氷冷中で超音波処理する。この細胞液を、500r
pm、4℃で10分間遠心分離し、上清と沈殿物以外の
部分を採取しGPDH活性、及びタンパク質測定用試料
とする。GPDH活性は、解糖の代謝中間物ジヒドロキ
シアセトンリン酸からGPDHの作用でNADHによる
還元をうけグリセロール−3−リン酸が形成される反応
でのNADHの減少量を波長340nmの吸光度から求
め、Lowry法によって測定したタンパク質量で割り
付けた値で示した。
(Experimental method 2) GPDH activity measuring method: After stopping the culture, the cells were washed twice with physiological saline, and 25 mM Trs-HCl 1 mM EDT.
1 ml of Abuffer (pH 7.4) is added, the cells are detached, and the cells are sonicated under ice-cooling. This cell solution is transferred to 500r
After centrifugation at 4 ° C. for 10 minutes at pm, a portion other than the supernatant and the precipitate is collected and used as a sample for GPDH activity and protein measurement. The GPDH activity is determined from the absorbance at a wavelength of 340 nm from the absorbance at a wavelength of 340 nm. It was shown as a value divided by the amount of protein measured by the method.

【0018】(実験方法3) TG蓄積量測定方法:培養停止後、細胞を生理食塩水で
2回洗浄し、25mMTrs−HCl 1mM EDT
Abuffer(pH7.4)を加え細胞を剥がし、氷
冷中で超音波処理する。この細胞液にリポプロテインリ
パーゼ、グリセロールキナーゼ、グリセロール−3−リ
ン酸オキシターゼ、ペルオキシターゼ、ATP、4−ア
ミノアンチピリンを加え37℃で 10分間反応させ、
505nmの吸光度を測定する。
(Experimental Method 3) Method for measuring TG accumulation: After the culture was stopped, the cells were washed twice with physiological saline, and 25 mM Trs-HCl 1 mM EDT.
Abuffer (pH 7.4) is added to detach the cells, and the cells are sonicated in ice. Lipoprotein lipase, glycerol kinase, glycerol-3-phosphate oxidase, peroxidase, ATP, and 4-aminoantipyrine were added to the cell solution and reacted at 37 ° C. for 10 minutes.
The absorbance at 505 nm is measured.

【0019】リポプロテインリパーゼ(LPL活性)活
性測定方法:培養停止後、細胞を生理食塩水で2回洗浄
し、50mM NHCl−NHOH 20mg/m
lBSA buffer(pH8.2)を加え細胞を剥
がし、氷冷中で超音波処理する。1500rpm、4℃
で10分間遠心し、その上清、沈殿物以外の部分を採取
し、Hラベルトリオレイン乳化物、ラット血清、0.
2MTrs−HCl3%BSA buffer(pH
8.2)混合物を加え1時間インキュベーションした後
メタノール:クロロホルム:ヘプタン(1.41:1.
25:1:)混液を加え反応を停止し、pH11カリウ
ムbufferを加え強くvortexした後室温で1
500rpm、10分間遠心し、その上清に酢酸適量を
加えた後、シンチレーター(ACS−II)を加え放射
能を測定する。
Method for measuring lipoprotein lipase (LPL activity) activity: After stopping the culture, the cells were washed twice with physiological saline, and 50 mM NH 4 Cl—NH 4 OH 20 mg / m 2.
The cells are detached by adding IBSA buffer (pH 8.2), and sonicated in ice-cooling. 1500 rpm, 4 ° C
In centrifugation for 10 min, the supernatant, the portion other than the precipitate was collected, 3 H label triolein emulsion, rat serum, 0.
2MTrs-HCl 3% BSA buffer (pH
8.2) After adding the mixture and incubating for 1 hour, methanol: chloroform: heptane (1.41: 1.
25: 1 :) The mixture was quenched by adding a mixed solution, pH 11 potassium buffer was added, and the mixture was strongly vortexed.
After centrifugation at 500 rpm for 10 minutes, an appropriate amount of acetic acid is added to the supernatant, and then a scintillator (ACS-II) is added to measure the radioactivity.

【0020】(実験方法4) グルコース取り込み量測定方法:インスリン感受性はグ
ルコース取り込み量によって示した。インスリンによる
糖の取り込みは非常に速やかに起こるため、測定誤差を
考え、直接グルコース量を測定することはせず、そのグ
ルコースによって合成された中性脂肪を抽出して取り込
み量とした。すなわち、培養停止後、細胞を生理食塩水
で2回洗浄し、0.5%Hanks buffer1m
l/wellを加える。1μMインスリン20μL(a
インスリン共存)もしくは、生理食塩水20μL(bイ
ンスリン非共存)を加え、37℃で10分間プレインキ
ュベーションした後、14Cラベルグルコースを50μ
L加え軽く揺する。再び37℃で30間インキュベーシ
ョンした後、先程加えたbuffer等を捨て、アルカ
リ水を加え細胞を剥がす。剥がした細胞に抽出用試薬を
加え、強めにvortexし、さらにHeptanを加
え強めにvortexする。室温で、2000rpm、
5分間遠心し上清をバイヤル瓶にとりトルエンシンチレ
ーターを加え放射能を測定する。
(Experimental Method 4) Method of measuring glucose uptake: Insulin sensitivity was indicated by glucose uptake. Since the uptake of sugar by insulin occurs very quickly, considering the measurement error, the amount of glucose was not directly measured, but the neutral fat synthesized by the glucose was extracted and taken as the amount of uptake. That is, after the culture is stopped, the cells are washed twice with a physiological saline, and the cells are washed with 0.5% Hanks buffer 1m.
Add 1 / well. 20 μL of 1 μM insulin (a
After adding 20 μL of physiological saline (without insulin b) and preincubating at 37 ° C. for 10 minutes, 50 μL of 14 C-labeled glucose was added.
Add L and shake lightly. After incubating again at 37 ° C. for 30 minutes, the buffer and the like added previously are discarded, and alkaline water is added to detach the cells. An extraction reagent is added to the detached cells, vortex is stronger, and Heptan is added, and vortex is stronger. At room temperature, 2000 rpm,
Centrifuge for 5 minutes, take the supernatant into a vial, add toluene scintillator, and measure the radioactivity.

【0021】GPDH活性、TG蓄積量、LPL活性、
グルコース取り込み量測定結果は、表1〜表3に示すと
おりである。
GPDH activity, TG accumulation, LPL activity,
The results of the glucose uptake measurement are shown in Tables 1 to 3.

【0022】[0022]

【表1】 [Table 1]

【0023】[0023]

【表2】 [Table 2]

【0024】[0024]

【表3】 [Table 3]

【0025】本発明品は、脂肪細胞の分化の指標となる
酵素、本実験ではグリセロール−3−リン酸デヒドロゲ
ナーゼの活性を高めトリアシルグリセロール蓄積量を増
加させた。GPDHは、コントロールの無処理群(Ba
sal)は、ほとんど活性が無く、インスリン添加によ
り活性は上昇する。強力な分化促進剤として一般的なデ
キサメタゾン、3−イソブチル−1−メチルキサンチ
ン、インスリンの混合物は、非常に活性を高めたが本発
明品は、それに匹敵するあるいは、それ以上に酵素活性
を高めた。また、トリアシルグリセロール蓄積量もGP
DH活性と同様の傾向を示し、本発明品は、脂肪細胞の
分化を促進した。リポプロテインリパーゼは、脂肪細胞
内ではなく血液中の中性脂肪を分解する酵素であるが、
この様に脂肪細胞は他の組織の代謝に多大な影響を与え
る。本発明品はこの酵素の活性も高めることから、脂肪
組織およびその他の組織の代謝も促進することがわかっ
た。また本発明品は、グルコース取り込み量を上昇させ
るが、取り込み量測定前のインスリン処理により取り込
み量が非常に高まることからインスリン感受性の上昇が
うかがえた。
The product of the present invention increased the activity of glycerol-3-phosphate dehydrogenase and increased the accumulation of triacylglycerol in this experiment. GPDH was a control untreated group (Ba
sal) has almost no activity, and the activity increases with the addition of insulin. A mixture of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin, which are common as potent differentiation promoters, greatly enhanced the activity, but the product of the present invention enhanced the enzyme activity to be equal to or more than that. . In addition, the amount of triacylglycerol accumulated was also GP
It showed the same tendency as DH activity, and the product of the present invention promoted adipocyte differentiation. Lipoprotein lipase is an enzyme that breaks down neutral fat in the blood rather than in fat cells,
Thus, fat cells have a significant effect on the metabolism of other tissues. Since the product of the present invention also increased the activity of this enzyme, it was found that the metabolism of adipose tissue and other tissues was also promoted. In addition, the product of the present invention increases the amount of glucose uptake, and the insulin treatment before the measurement of the amount of uptake significantly increases the amount of uptake, indicating an increase in insulin sensitivity.

【0026】脂肪組織は、エネルギーを中性脂肪として
貯えるエネルギー貯蔵臓器としてのイメージが強いた
め、非活発な臓器と考えられがちであるが、実際は中性
脂肪の合成、分解を行い、又種々の生理活性物質を分泌
する代謝的に活発な臓器である。そして、この脂肪組織
が正常に機能しないと、インスリン抵抗性を示し、組織
における糖の取り込みが低下する糖尿病のように、全身
における代謝が円滑に行われなくなる。脂肪組織はイン
スリンの重要な標的細胞であり、全身でのインスリン作
用が正常に働くためには、正常な脂肪細胞が必要であ
る。本実験で用いた3T3L1前駆脂肪細胞のように、
未分化でGPDH、LPL等の酵素の活性がほとんど検
出されず、またインスリン等のホルモンに対する感受性
を持っていない糖、脂質代謝活性が低い前駆脂肪細胞は
実際の生体内にも多数存在する。チアゾリジン誘導体の
様な糖尿病治療薬が、脂肪細胞への分化促進作用を有す
ることは周知のことであるが、本発明品も同様の作用を
有する。本発明品は代謝活性の低い前駆脂肪細胞を正常
な脂肪細胞へ分化させ、インスリンに対する感受性を高
めることにより、生体内において糖、脂質代謝を活発に
すると考えられる。
Adipose tissue is often considered to be an inactive organ because it has a strong image as an energy storage organ that stores energy as neutral fat, but actually synthesizes and degrades neutral fat, It is a metabolically active organ that secretes bioactive substances. If the adipose tissue does not function properly, metabolism in the whole body cannot be performed smoothly as in diabetes, which exhibits insulin resistance and decreases glucose uptake in the tissue. Adipose tissue is an important target cell of insulin, and normal fat cells are necessary for normal insulin action in the whole body. Like the 3T3L1 preadipocytes used in this experiment,
The activity of enzymes such as GPDH and LPL is hardly detected due to undifferentiation, and a large number of preadipocytes having low sugar and lipid metabolic activity having no sensitivity to hormones such as insulin are present in actual living bodies. It is well known that a therapeutic agent for diabetes such as a thiazolidine derivative has an action of promoting differentiation into adipocytes, but the product of the present invention has a similar action. It is considered that the product of the present invention activates glucose and lipid metabolism in vivo by differentiating preadipocytes having low metabolic activity into normal adipocytes and increasing sensitivity to insulin.

【0027】[0027]

【実施例】【Example】

(実施例1)玄米を粉砕機にかけ、玄米の粉砕物500
gを得た。この粉砕物に澱粉分解酵素10gと水150
0mlを添加した。その後、徐々に温度を上げていき、
5分間煮沸抽出した後、冷却した。その後、圧搾、濾過
し、本発明品1420mlと残渣560gを得た。 (実施例2)白米を粉砕機にかけ、白米の粉砕物500
gを得た。この粉砕物に蛋白分解酵素2g、脂肪分解酵
素2g、繊維分解酵素2g、澱粉分解酵素2gと水15
00mlを加え、50℃で5時間放置し、煮沸後冷却し
た。その後、圧搾、濾過し、本発明品1420mlと残
渣560gを得た。
(Example 1) Brown rice is crushed with a grinder, and the crushed brown rice 500
g was obtained. 10 g of amylolytic enzyme and 150 g of water
0 ml was added. After that, gradually increase the temperature,
After boiling extraction for 5 minutes, the mixture was cooled. Then, it was pressed and filtered to obtain 1420 ml of the product of the present invention and 560 g of residue. (Example 2) Pulverized rice 500 is crushed with a pulverizer,
g was obtained. 2 g of protease, 2 g of lipolytic enzyme, 2 g of fibrinolytic enzyme, 2 g of amylolytic enzyme and 15 g of water
After adding 00 ml, the mixture was left at 50 ° C. for 5 hours, boiled and cooled. Then, it was pressed and filtered to obtain 1420 ml of the product of the present invention and 560 g of residue.

【0028】(実施例3)実施例1と同様にして、米の
抽出物2000gを得た。この抽出物に麹、酵母を添加
し、16日間アルコール発酵した。その後、圧搾、濾過
し、本発明品1880mlと残渣80gを得た。 (実施例4)実施例1で得られた本発明品2000ml
に、糖化酵素2gを加え、15時間反応させた後、煮沸
殺菌した後、37℃まで冷却し、前もって乳酸菌を培養
したスターター200mlを添加後、よく撹伴密封し、
37℃で2日間乳酸発酵を行った。その後、圧搾、濾過
し、本発明品1380mlと残渣590gを得た。
Example 3 In the same manner as in Example 1, 2,000 g of rice extract was obtained. Koji and yeast were added to this extract, and alcohol fermentation was performed for 16 days. Then, it was squeezed and filtered to obtain 1880 ml of the product of the present invention and 80 g of a residue. (Example 4) 2000 ml of the product of the present invention obtained in Example 1
After adding 2 g of saccharifying enzyme and reacting for 15 hours, sterilized by boiling, cooled to 37 ° C., added with 200 ml of a starter in which lactic acid bacteria were previously cultured, sealed well with stirring,
Lactic acid fermentation was performed at 37 ° C. for 2 days. Then, it was pressed and filtered to obtain 1380 ml of the product of the present invention and 590 g of a residue.

【0029】(実施例5)実施例1で得られた本発明品
1000mlに95%エタノール80mlを添加し、2
0日間酢酸発酵を行った。その後、濾過をし、本発明品
990mlを得た。 (実施例6)実施例1で得られた本発明品2000ml
に、糖化酵素3gを加え、15時間反応させた後、酵母
を添加し、24時間通気発酵し、除糖した。その後、濾
過し、本発明品1890mlを得た。
(Example 5) To 1000 ml of the product of the present invention obtained in Example 1, 80 ml of 95% ethanol was added.
Acetic acid fermentation was performed for 0 days. Thereafter, the mixture was filtered to obtain 990 ml of the product of the present invention. (Example 6) 2000 ml of the product of the present invention obtained in Example 1
Then, 3 g of a saccharifying enzyme was added thereto, and the mixture was reacted for 15 hours. Then, yeast was added, and aeration fermentation was performed for 24 hours to remove sugar. Thereafter, the mixture was filtered to obtain 1890 ml of the product of the present invention.

【0030】(実施例7)インディカ米の白米を粉砕機
にかけ、インディカ米の白米の粉砕物500gを得た。
この粉砕物に水1500mlを添加、HClでpHを落
とし、10日間放置した。その後、圧搾、濾過し、本発
明品1200mlと残渣760gを得た。 (実施例8)白糠500gに2N−NaOH1500m
lを添加して5日間放置した。その後、圧搾、濾過し、
清澄液1300mlと残渣700gを得た。この清澄液
を10N−HClで中和して、本発明品1580mlを
得た。
(Example 7) White rice of Indica rice was crushed with a grinder to obtain 500 g of white rice of Indica rice.
1500 ml of water was added to the pulverized product, the pH was lowered with HCl, and the mixture was left for 10 days. Thereafter, the product was pressed and filtered to obtain 1200 ml of the product of the present invention and 760 g of a residue. (Example 8) 2N-NaOH 1500m in 500g of Shiranuka
1 was added and left for 5 days. Then squeeze, filter,
1300 ml of a clarified liquid and 700 g of a residue were obtained. The clarified solution was neutralized with 10N-HCl to obtain 1580 ml of the product of the present invention.

【0031】(実施例9)もち米の白米を粉砕機にか
け、もち米の白米の粉砕物500gを得た。この粉砕物
に40%エタノール1500ml添加して、5日間放置
した。その後、圧搾、濾過し、清澄液1300mlと残
渣650gを得た。この清澄液に水2000mlを添加
し、ロータリーエバポレーターで濃縮し、本発明品15
00mlを得た。 (実施例10)インディカ米500gに澱粉分解酵素1
0gと水1500mlを添加した。その後、徐々に温度
を上げていき、5分間煮沸抽出した後、冷却した。その
後、圧搾、濾過し、本発明品1500mlと残渣470
gを得た。
Example 9 White rice of glutinous rice was crushed with a grinder to obtain 500 g of white rice of glutinous rice. 1500 ml of 40% ethanol was added to the pulverized product, and the mixture was left for 5 days. Then, it was squeezed and filtered to obtain 1300 ml of a clear liquid and 650 g of a residue. 2000 ml of water was added to the clarified solution, and the mixture was concentrated by a rotary evaporator.
00 ml were obtained. Example 10 Starch-degrading enzyme 1 in 500 g of indica rice
0 g and 1500 ml of water were added. Thereafter, the temperature was gradually increased, and after boiling extraction for 5 minutes, the mixture was cooled. Then, it is squeezed and filtered.
g was obtained.

【0032】(実施例11)白糠500gに蛋白分解酵
素2g、脂肪分解酵素2g、繊維分解酵素2g、澱粉分
解酵素2gと水1500mlを加え、50℃で5時間放
置し、煮沸後冷却した。その後、圧搾、濾過し、本発明
品1480mlと残渣500gを得た。 (実施例12)実施例10と同様にして、米の抽出物2
000gを得た。この抽出物に麹、酵母を添加し、16
日間アルコール発酵した。その後、圧搾、濾過し、本発
明品1860mlと残渣80gを得た。
Example 11 To 500 g of white bran were added 2 g of protease, 2 g of lipolytic enzyme, 2 g of fibrinolytic enzyme, 2 g of starch-degrading enzyme and 1500 ml of water, left at 50 ° C. for 5 hours, boiled and cooled. Then, it was squeezed and filtered to obtain 1480 ml of the product of the present invention and 500 g of a residue. (Example 12) In the same manner as in Example 10, rice extract 2
000 g were obtained. Add koji and yeast to this extract and add 16
Alcohol fermented for days. Then, it was squeezed and filtered to obtain 1860 ml of the product of the present invention and 80 g of a residue.

【0033】(実施例13)実施例10で得られた本発
明品2000mlに、糖化酵素2gを加え、15時間反
応させた後、煮沸殺菌した後、37℃まで冷却し、前も
って乳酸菌を培養したスターター200mlを添加後、
よく撹伴密封し、37℃で3日間乳酸発酵を行った。そ
の後、圧搾、濾過し、本発明品1370mlと残渣60
0gを得た。 (実施例14)実施例10で得られた本発明品1000
mlに95%エタノール80mlを添加し、20日間酢
酸発酵を行った。その後、濾過をし、本発明品970m
lを得た。
Example 13 To 2000 ml of the product of the present invention obtained in Example 10, 2 g of saccharifying enzyme was added, reacted for 15 hours, sterilized by boiling, cooled to 37 ° C., and lactic acid bacteria were cultured in advance. After adding 200 ml of starter,
The mixture was sealed well with stirring, and lactic acid fermentation was performed at 37 ° C. for 3 days. Then, it is squeezed and filtered, and 1370 ml of the product of the present invention and residue 60
0 g was obtained. (Example 14) Inventive product 1000 obtained in Example 10
80 ml of 95% ethanol was added to each ml, and acetic acid fermentation was performed for 20 days. Thereafter, the mixture was filtered and the product of the present invention 970m
1 was obtained.

【0034】(実施例15)実施例10で得られた本発
明品2000mlに、糖化酵素1gを加え、15時間反
応させた後、酵母を添加し、24時間通気発酵し、除糖
した。その後、濾過し、本発明品1900mlを得た。 (実施例16)もち米500gに水1500mlを添
加、NaOHでpHを上げ、10日間放置した。その
後、圧搾、濾過し、得られた清澄液を中和して本発明品
1250m1と残渣710gを得た。
(Example 15) To 2000 ml of the product of the present invention obtained in Example 10, 1 g of a saccharifying enzyme was added, and the mixture was reacted for 15 hours. Then, yeast was added, followed by aeration fermentation for 24 hours to remove sugar. Thereafter, the mixture was filtered to obtain 1900 ml of the product of the present invention. (Example 16) 1500 ml of water was added to 500 g of glutinous rice, the pH was increased with NaOH, and the mixture was allowed to stand for 10 days. Thereafter, the resultant was squeezed and filtered, and the obtained clear solution was neutralized to obtain 1250 ml of the product of the present invention and 710 g of a residue.

【0035】(実施例17)ジャポニカ米500gに2
N−HCl1500mlを添加して5日間放置した。そ
の後、圧搾、濾過し、清澄液1350mlと残渣650
gを得た。この清澄液を10N−NaOHで中和して、
本発明品1560mlを得た。 以上の実施例で得た本発明品は、適宜の形態に調整して
試用されるが、本発明品を配合する場合の実施例につい
て、次に記載する。なお、配合例は以下の実施例に限定
されるものではない。
Example 17 2 in 500 g of Japonica rice
1500 ml of N-HCl was added and left for 5 days. Then, it is pressed and filtered, and 1350 ml of the clarified liquid and 650 residues
g was obtained. This clarified solution is neutralized with 10N-NaOH,
1560 ml of the product of the present invention was obtained. The product of the present invention obtained in the above examples is adjusted to an appropriate form and used as a trial. Examples in which the product of the present invention is blended are described below. In addition, the composition examples are not limited to the following examples.

【0036】(実施例18)錠剤 実施例10で得られた本発明品100gをフリーズドラ
イにより乾燥し、20gの乾燥品を得た。この乾燥品1
0gを下記のようにして錠剤を得た。 本発明品 10.0g ポリエチレングリコール6000 10.0g ラウリル硫酸ナトリウム 1.5g コーンスターチ 3.0g 乳糖 25.0g ステアリン酸マグネシウム 0.5g 上記成分を表量した後、ポリエチレングリコール600
0を70〜80℃に加温し、これに本発明品、ラウリル
硫酸ナトリウム、コーンスターチおよび乳糖を加え混合
後、そのまま冷却する。固化した混合物を粉砕機にかけ
造粒する。本顆粒をステアリン酸マグネシウムと混合
後、圧縮打錠して重量250mgの錠剤とする。
Example 18 Tablets 100 g of the product of the present invention obtained in Example 10 was dried by freeze drying to obtain 20 g of a dried product. This dried product 1
0 g was obtained as follows. Invention product 10.0 g Polyethylene glycol 6000 10.0 g Sodium lauryl sulfate 1.5 g Corn starch 3.0 g Lactose 25.0 g Magnesium stearate 0.5 g After weighing the above components, polyethylene glycol 600
0 is heated to 70 to 80 ° C, the product of the present invention, sodium lauryl sulfate, corn starch and lactose are added thereto, mixed, and then cooled as it is. The solidified mixture is granulated in a grinder. The granules are mixed with magnesium stearate and then compressed and compressed into tablets weighing 250 mg.

【0037】 (実施例19)清涼飲料 実施例2で得られた本発明品 15.0 %(重量比) 甘草エキス 0.01 % 砂糖 4.0 % 精製水 78.49% レモン果汁 2.5 % 以上の配合材料を常法により混合溶解し、清涼飲料水を
得た。
(Example 19) Soft drink The present invention product obtained in Example 2 15.0% (weight ratio) Licorice extract 0.01% Sugar 4.0% Purified water 78.49% Lemon juice 2.5 % Or more of the blended materials were mixed and dissolved by a conventional method to obtain a soft drink.

【0038】(実施例20)粉体 実施例10で得られた本発明品10 と6Kgのデキス
トリンを混合し、その混合物をスプレードライにより乾
燥し、7Kgの粉体を得た。
Example 20 Powder 10 kg of dextrin according to the present invention obtained in Example 10 and 6 kg of dextrin were mixed, and the mixture was dried by spray drying to obtain 7 kg of powder.

【0039】[0039]

【発明の効果】本発明によれば、食事療法や運動療法、
薬物療法によらず、簡単で安全にインスリン感受性上
昇、糖・脂質代謝活性促進療効果を発揮する糖尿病予防
・治療剤が得られる。米は主食であったため、食以外の
新規な分野での製法、利用用途はほとんど開発されてい
なかった。さらに、米は今まで主食として、またその他
の食品原料として食されてきたものであり、安全性も充
分に実証されているものである。すなわち、本発明は非
常に優れた糖尿病予防・治療剤を見いだしたばかりでな
く、米の新たな利用用途を見いだしたこと、および米の
イメージアップによる消費拡大を図り得ることは極めて
有意義なことである。
According to the present invention, diet therapy, exercise therapy,
A prophylactic / therapeutic agent for diabetes which can easily and safely exhibit insulin sensitivity increase and glucose / lipid metabolic activity promoting effect can be obtained irrespective of drug therapy. Since rice was a staple food, its production methods and uses in new fields other than food were hardly developed. In addition, rice has been eaten as a staple food and other food ingredients, and its safety has been well proven. In other words, it is extremely significant that the present invention not only finds an excellent diabetes preventive / therapeutic agent, but also finds new uses of rice, and can increase consumption by improving the image of rice. .

Claims (13)

【特許請求の範囲】[Claims] 【請求項1】 米の水抽出物、または当該水抽出物の処
理物を含有してなる糖尿病予防・治療剤。
1. An agent for preventing or treating diabetes comprising an aqueous extract of rice or a processed product of the aqueous extract.
【請求項2】 米の水抽出物の処理が、蛋白分解酵素、
繊維分解酵素、脂肪分解酵素、澱粉分解酵素及び麹から
なる群から選ばれる1または2以上の酵素を作用させる
処理である請求項1記載の糖尿病予防・治療剤。
2. The method of claim 1, wherein the treatment of the rice water extract comprises the step of:
The diabetes preventive / therapeutic agent according to claim 1, wherein the agent is treated with one or two or more enzymes selected from the group consisting of a fibrinolytic enzyme, a lipolytic enzyme, a starch-degrading enzyme and koji.
【請求項3】 米の水抽出物の処理が、酸またはアルカ
リ条件下で行われる処理である請求項1記載の糖尿病予
防・治療剤。
3. The preventive / therapeutic agent for diabetes according to claim 1, wherein the treatment of the water extract of rice is a treatment carried out under acid or alkaline conditions.
【請求項4】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の水を加え、蛋白分解酵
素、繊維分解酵素、脂肪分解酵素、澱粉分解酵素及び麹
からなる群から選ばれる1または2以上の酵素を作用さ
せた後、40℃ないし沸騰する温度までその混合物を加
熱することからなる糖尿病予防・治療剤の製法。
4. Rice or germinated rice or rice white bran is added with water in an amount of 1 to 100 times the amount of rice, and comprises a protease, a fibrinolytic enzyme, a lipolytic enzyme, a starch-degrading enzyme, and a koji. A method for producing a diabetic preventive / therapeutic agent comprising heating one or more enzymes selected from the group and then heating the mixture to a temperature of from 40 ° C. to boiling.
【請求項5】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の水を加え、蛋白分解酵
素、繊維分解酵素、脂肪分解酵素、澱粉分解酵素及び麹
からなる群から選ばれる1または2以上の酵素を作用さ
せた後、40℃ないし沸騰する温度までその混合物を加
熱し、ついでアルコール発酵、または乳酸発酵、または
酢酸発酵、または酵母通気発酵を行うことからなる、請
求項4記載の糖尿病予防・治療剤の製法。
5. A rice or sprouted rice or rice white bran is added with water in an amount of 1 to 100 times the amount of rice, and is composed of a protease, a fibrinolytic enzyme, a lipolytic enzyme, a starch-degrading enzyme, and a koji. After the action of one or more enzymes selected from the group, the mixture is heated to 40 ° C. to a boiling temperature, and then alcoholic fermentation, lactic acid fermentation, acetic acid fermentation, or yeast aeration fermentation is performed. A method for producing the agent for preventing or treating diabetes according to claim 4.
【請求項6】 米の酸またはアルカリ抽出物、または当
該酸またはアルカリ抽出物の処理物を含有してなる糖尿
病予防・治療剤。
6. A preventive / therapeutic agent for diabetes comprising an acid or alkali extract of rice or a processed product of the acid or alkali extract.
【請求項7】 米の酸またはアルカリ抽出物の処理が、
蛋白分解酵素、繊維分解酵素、脂肪分解酵素、澱粉分解
酵素及び麹からなる群から選ばれる1または2以上の酵
素を作用させる処理である請求項6記載の糖尿病予防・
治療剤。
7. The treatment of an acid or alkali extract of rice comprises:
7. Diabetes prevention / treatment according to claim 6, wherein the treatment is carried out with one or more enzymes selected from the group consisting of proteolytic enzymes, fibrinolytic enzymes, lipolytic enzymes, amylolytic enzymes and koji.
Therapeutic agent.
【請求項8】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の酸またはアルカリを加
え、蛋白分解酵素、繊維分解酵素、脂肪分解酵素、澱粉
分解酵素及び麹からなる群から選ばれる1または2以上
の酵素を作用させた後、40℃ないし沸騰する温度まで
その混合物を加熱することからなる糖尿病予防・治療剤
の製法。
8. Rice or germinated rice or rice white bran is added with an acid or alkali in an amount of 1 to 100 times the amount of rice to produce a protease, fibrinolytic enzyme, lipolytic enzyme, amylolytic enzyme and koji. A method for producing a prophylactic / therapeutic agent for diabetes, which comprises heating one or more enzymes selected from the group consisting of:
【請求項9】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の酸またはアルカリを加
え、蛋白分解酵素、繊維分解酵素、脂肪分解酵素、澱粉
分解酵素及び麹からなる群から選ばれる1または2以上
の酵素を作用させた後、40℃ないし沸騰する温度まで
その混合物を加熱し、ついでアルコール発酵、または乳
酸発酵、または酢酸発酵、または酵母通気発酵を行うこ
とからなる、請求項8記載の糖尿病予防・治療剤の製
法。
9. Rice or germinated rice or rice white bran is added with an acid or alkali in an amount of 1 to 100 times the amount of rice to produce a protease, a fibrinolytic enzyme, a lipolytic enzyme, an amylolytic enzyme, and a koji. After reacting one or more enzymes selected from the group consisting of: heating the mixture to a temperature of 40 ° C. to boiling, and then performing alcohol fermentation, lactic acid fermentation, acetic acid fermentation, or yeast aeration fermentation. 9. A method for producing the agent for preventing or treating diabetes according to claim 8, comprising:
【請求項10】 米の有機溶媒抽出物、または当該有機
溶媒抽出物の処理物を含有してなる糖尿病予防・治療
剤。
10. A prophylactic / therapeutic agent for diabetes comprising an organic solvent extract of rice or a processed product of the organic solvent extract.
【請求項11】 米の有機溶媒抽出物の処理が、蛋白分
解酵素、繊維分解酵素、脂肪分解酵素、澱粉分解酵素及
び麹からなる群から選ばれる1または2以上の酵素を作
用させる処理である請求項10記載の糖尿病予防・治療
剤。
11. The treatment of the organic solvent extract of rice is treatment with one or more enzymes selected from the group consisting of a protease, a fibrinolytic enzyme, a lipolytic enzyme, a starch degrading enzyme, and a koji. The agent for preventing or treating diabetes according to claim 10.
【請求項12】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の有機溶媒を加え、蛋白分
解酵素、繊維分解酵素、脂肪分解酵素、澱粉分解酵素及
び麹からなる群から選ばれる1または2以上の酵素を作
用させた後、40℃ないし沸騰する温度までその混合物
を加熱することからなる糖尿病予防・治療剤の製法。
12. To rice or sprouted rice or rice white bran, an organic solvent in an amount of 1 to 100 times the amount of rice is added, and a protease, fibrinolytic enzyme, lipolytic enzyme, amylolytic enzyme and koji are added. A method for producing a prophylactic / therapeutic agent for diabetes comprising heating one or more enzymes selected from the group and then heating the mixture to a temperature of from 40 ° C. to boiling.
【請求項13】 米または発芽させた米、または米白糠
に、米の量の1〜100倍量の有機溶媒を加え、蛋白分
解酵素、繊維分解酵素、脂肪分解酵素、澱粉分解酵素及
び麹からなる群から選ばれる1または2以上の酵素を作
用させた後、40℃ないし沸騰する温度までその混合物
を加熱し、ついでアルコール発酵、または乳酸発酵、ま
たは酢酸発酵、または酵母通気発酵を行うことからな
る、請求項12記載の糖尿病予防・治療剤の製法。
13. A method in which rice, germinated rice, or rice white bran is added with an organic solvent in an amount of 1 to 100 times the amount of rice to produce a protease, fibrinolytic enzyme, lipolytic enzyme, amylolytic enzyme, and koji. After allowing one or more enzymes selected from the group to act, heating the mixture to a temperature of 40 ° C. to boiling and then performing alcohol fermentation, or lactic acid fermentation, or acetic acid fermentation, or yeast aeration fermentation. A method for producing a prophylactic / therapeutic agent for diabetes according to claim 12.
JP12005797A 1997-04-02 1997-04-02 Diabetes prevention and treatment from rice Expired - Lifetime JP4838920B2 (en)

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EP1011702A1 (en) * 1997-08-29 2000-06-28 The Ricex Company A method for treating diabetes, hyperglycemia and hypoglycemia
JP2005068132A (en) * 2003-08-06 2005-03-17 Enkaku Iryo Kenkyusho:Kk Adiponectin secretion promoter, and anti-arteriosclerosis agent, anti-obesity agent, antidiabetic mellitus agent, food additive, functional food and feed additive containing adiponectin secretion promoter
JP2006036694A (en) * 2004-07-27 2006-02-09 Nakamurado:Kk Method for producing fermentation prepared liquid of rice bran or the like
JP2006219467A (en) * 2005-02-10 2006-08-24 Oriza Yuka Kk Fat accumulation inhibitor
US7157431B2 (en) 1996-08-09 2007-01-02 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
WO2007004638A1 (en) * 2005-07-04 2007-01-11 Takahito Tokuyama White rice-based organ preservative
JP2008530000A (en) * 2005-02-04 2008-08-07 チュンブク ナショナル ユニヴァーシティ インダストリー アカデミック コーポレイション ファウンデーション Drinking water for diabetics and method for producing the same
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Publication number Priority date Publication date Assignee Title
US7196064B2 (en) * 1996-08-09 2007-03-27 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
US7202220B2 (en) 1996-08-09 2007-04-10 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
US7157431B2 (en) 1996-08-09 2007-01-02 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
US7199104B2 (en) 1996-08-09 2007-04-03 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
EP1011702A4 (en) * 1997-08-29 2004-01-21 Ricex Company A method for treating diabetes, hyperglycemia and hypoglycemia
EP1011702A1 (en) * 1997-08-29 2000-06-28 The Ricex Company A method for treating diabetes, hyperglycemia and hypoglycemia
JP2005068132A (en) * 2003-08-06 2005-03-17 Enkaku Iryo Kenkyusho:Kk Adiponectin secretion promoter, and anti-arteriosclerosis agent, anti-obesity agent, antidiabetic mellitus agent, food additive, functional food and feed additive containing adiponectin secretion promoter
JP2006036694A (en) * 2004-07-27 2006-02-09 Nakamurado:Kk Method for producing fermentation prepared liquid of rice bran or the like
JP2008530000A (en) * 2005-02-04 2008-08-07 チュンブク ナショナル ユニヴァーシティ インダストリー アカデミック コーポレイション ファウンデーション Drinking water for diabetics and method for producing the same
JP2006219467A (en) * 2005-02-10 2006-08-24 Oriza Yuka Kk Fat accumulation inhibitor
WO2007004638A1 (en) * 2005-07-04 2007-01-11 Takahito Tokuyama White rice-based organ preservative
KR101095894B1 (en) 2009-06-11 2011-12-20 박길남 A diabetes pharmaceutical composition and manufacturing process thereof
JP2016063801A (en) * 2014-09-19 2016-04-28 国立大学法人山形大学 Support for cell culture, and cell culture method using the same

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