JP2005089417A - Composition for prevention/treatment of diabetes - Google Patents
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本発明は、マツタケを有効成分として含有する、糖尿病の予防・治療用組成物に関する。 The present invention relates to a composition for preventing / treating diabetes, comprising matsutake as an active ingredient.
肥満及び糖尿病は、過剰カロリーの摂取が主な原因となり、増加の一途をたどっている。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における高血糖の原因として、食後の急峻な血糖上昇に対応し、瞬時に分泌されるべきインスリン早期相の欠如と食後高血糖の持続により誘導される内因性基礎インスリン分泌低下が挙げられる。食後高血糖の是正は経口血糖降下剤、インスリンを用いても困難なことがあり、消化系における糖質の急速な吸収を防ぐ方法が有望である。消化系における糖質の吸収としては、第一段階として唾液中のα−アミラーゼ、第二段階として小腸中のα−グルコシダーゼが関与しており、これらの酵素を阻害することにより、食後の血糖値上昇が抑制され、さらにそれに続くインシュリン値の上昇も抑制されることが明らかにされている。 Obesity and diabetes are continually increasing, mainly due to excessive caloric intake. There are two types of diabetes, insulin-dependent diabetes (type I diabetes) and non-insulin-dependent diabetes (type II diabetes), of which 90% are of the latter type. The cause of hyperglycemia in non-insulin-dependent diabetes mellitus is a lack of an early phase of insulin that should be secreted instantaneously and a decrease in endogenous basal insulin secretion induced by persistence of postprandial hyperglycemia in response to a rapid increase in blood glucose after meals. Can be mentioned. Correction of postprandial hyperglycemia may be difficult even with an oral hypoglycemic agent and insulin, and a method for preventing rapid absorption of carbohydrates in the digestive system is promising. As the absorption of carbohydrates in the digestive system, α-amylase in saliva is involved as the first step, and α-glucosidase in the small intestine is involved as the second step. By inhibiting these enzymes, blood glucose level after meals It has been clarified that the increase is suppressed and the subsequent increase in insulin level is also suppressed.
かかるアミラーゼ活性阻害物質としては、コムギ水抽出物(特許文献1)、ストレプトマイセス属微生物由来のT−76(特許文献2),N−61(特許文献3),X−2(特許文献4),I−1001(特許文献5),AI−B(特許文献6),アミロスタチンA(特許文献7),クラドスポリウム属微生物由来のトマスタチン(特許文献8),グラキスポリエラ属微生物の代謝産物(特許文献9)等が既に開示されている。 Examples of such amylase activity inhibitors include wheat water extract (Patent Document 1), T-76 (Patent Document 2), N-61 (Patent Document 3), and X-2 (Patent Document 4) derived from Streptomyces microorganisms. ), I-1001 (patent document 5), AI-B (patent document 6), amylostatin A (patent document 7), tomatostatin derived from the genus Cladosporium (patent document 8), metabolites of the genus Glachyspoliera (patent document 8) Patent Document 9) and the like have already been disclosed.
また、グルコシダーゼ活性阻害物質としては、エゾイシゲ抽出物(特許文献10),紅景天属植物(特許文献11),アカルボース、エミグリテート、ミグリトール及びボグリボース(特許文献12)等が既に開示されている。 Moreover, as a glucosidase activity inhibitory substance, Ezoi Shige extract (patent document 10), Hongkage genus plant (patent document 11), acarbose, emiglitate, miglitol, voglibose (patent document 12), etc. have already been disclosed.
しかしながら、これまでのアミラーゼ活性阻害物質やグルコシダーゼ活性阻害物質では、安定性,安全性,有効性の全てを満足するものは、未だ得られておいないのが実状である。 However, the actual amylase activity inhibitors and glucosidase activity inhibitors that satisfy all of the stability, safety, and effectiveness have not yet been obtained.
本発明で用いるマツタケ(Tricholoma matsutake (S. Ito et Imai) Singer)は、キシメジ科キシメジ属に属する担子菌類で、特有の香りと歯切れのよさで、茸の王様ともいわれ、汎く食用に供されている。マツタケの含有成分及び有効性に関する研究もなされている。マツタケに含まれる、エルゴステロールはシクロデキストリンと併用して血管新生阻害作用を(特許文献13参照)、β−グルカンは乳酸産生菌の加熱処理菌体と併用して感染抑制効果を(特許文献14参照)、それぞれ発揮することが知られている。また、マツタケが、抗腫瘍効果を発揮することも知られている(特許文献15〜18参照)。しかしながら、これまでマツタケが血糖値上昇抑制効果と、耐糖能改善効果を有することに関しては、全く知られていなかった。 The matsutake ( Tricholoma matsutake (S. Ito et Imai) Singer) used in the present invention is a basidiomycete belonging to the genus Kishimeji, and has a unique aroma and crispness. ing. Studies have been conducted on the ingredients and effectiveness of matsutake. Ergosterol contained in matsutake is used in combination with cyclodextrin to inhibit angiogenesis (see Patent Document 13), and β-glucan is used in combination with heat-treated cells of lactic acid-producing bacteria (Patent Document 14). Each of which is known to perform). It is also known that matsutake exhibits an antitumor effect (see Patent Documents 15 to 18). However, until now, it has not been known at all that matsutake has an effect of suppressing an increase in blood glucose level and an effect of improving glucose tolerance.
そこで本発明においては、血糖値上昇抑制効果と耐糖能改善効果を有する糖尿病予防・改善用組成物を提供することを目的とした。 Accordingly, an object of the present invention is to provide a composition for preventing or improving diabetes having an effect of suppressing an increase in blood glucose level and an effect of improving glucose tolerance.
先に述べた課題を解決するべく種々検討したところ、本発明者らは、マツタケが血糖値上昇抑制効果と耐糖能改善効果を発揮することを見いだし、本発明を完成するに至った。 As a result of various studies to solve the above-mentioned problems, the present inventors have found that matsutake exhibits an effect of suppressing an increase in blood glucose level and an effect of improving glucose tolerance, and has completed the present invention.
本発明の糖尿病予防・改善用組成物は、天然物であるキノコに由来し、安全性が高く、かつ血糖値上昇抑制作用と耐糖能改善作用を有するので、本発明の糖尿病予防・改善用組成物を摂取することにより、糖尿病の予防効果や糖尿病の治療効果が期待できる。 The composition for preventing / ameliorating diabetes according to the present invention is derived from a mushroom, which is a natural product, has high safety, and has an action to suppress an increase in blood glucose level and an action to improve glucose tolerance. Ingesting foods can be expected to prevent diabetes and treat diabetes.
本発明において用いるマツタケは、日本,朝鮮半島,沿海州,サハリン,千島列島に分布するキシメジ科キシメジ属に属するマツタケ(Tricholoma matsutake (S. Ito et Imai) Singer)のほか、近縁種であるオウシュウマツタケ,アメリカマツタケを用いることもできる。 The matsutake used in the present invention includes Tricholoma matsutake (S. Ito et Imai) Singer, which belongs to the genus Xymetidae, which is distributed in Japan, the Korean Peninsula, Primorye, Sakhalin, and Kuril Islands. Hamamatsutake and American matsutake can also be used.
マツタケは、担子菌に属するキノコの一種であり、一般に子実体が食用に供されており、本発明においてもその効果の点から子実体を用いることが好ましい。 Matsutake is a kind of mushroom belonging to the basidiomycete, and generally the fruiting body is used for food. In the present invention, it is preferable to use the fruiting body from the viewpoint of its effect.
マツタケは、子実体をそのまま若しくは乾燥させて用いても良い。またかかる子実体の抽出物を用いることもでき、またエタノールや水等の溶媒を用いて抽出して得られる抽出物を用いることもできる。本発明の糖尿病予防・治療効果の観点から、乾燥物特に凍結乾燥物を用いることが、最も好ましい。 Matsutake may be used as it is or after it is dried. Such fruit body extracts can also be used, and extracts obtained by extraction using a solvent such as ethanol or water can also be used. From the viewpoint of the diabetes preventive / therapeutic effect of the present invention, it is most preferable to use a dried product, particularly a lyophilized product.
実施例1〜3 マツタケ子実体の凍結乾燥粉末の調製
アメリカマツタケ子実体3kg,日本産マツタケ子実体3kg,オウシュウマツタケ子実体3kgを、凍結乾燥機にて処理後、粉砕機にて粉砕し、マツタケ子実体の凍結乾燥粉末を調製した。アメリカマツタケ子実体乾燥物を実施例1、日本産マツタケ子実体乾燥物を実施例2、オウシュウマツタケ子実体乾燥物を実施例3とした。
Examples 1-3 Preparation of freeze-dried powder of Matsutake fruiting body 3 kg of American Matsutake fruiting body, 3 kg of Japanese Matsutake fruiting body, and 3 kg of Satsuma matsutake fruiting body were processed in a freeze dryer and pulverized in a pulverizer. A freeze-dried powder of Matsutake fruiting bodies was prepared. The dried matsutake fruit body of Example 1 was used as Example 1, the dried matsutake fruit body of Japan as Example 2, and the dried dried matsutake fruit body as Example 3.
実施例4〜6 マツタケ子実体の超臨界二酸化炭素抽出物
実施例1〜3のマツタケ子実体乾燥物をそれぞれ超臨界抽出装置に投入し、40℃において25MPaの圧力下で二酸化炭素の超臨界流体を用いて抽出した。4時間後に抽出物を回収し、それぞれ実施例4〜6にかかる超臨界二酸化炭素抽出物を得た。
Examples 4-6 Supercritical carbon dioxide extract of Matsutake fruiting bodies Each of the dried Matsutake fruiting bodies of Examples 1-3 was put into a supercritical extraction apparatus, and a supercritical fluid of carbon dioxide under a pressure of 25 MPa at 40 ° C. Extracted using. The extract was recovered after 4 hours, and supercritical carbon dioxide extracts according to Examples 4 to 6 were obtained.
実施例7〜9 マツタケ子実体の熱水抽出物
実施例1〜3のマツタケ子実体乾燥物各1kgに水を20L加え90℃にて20分間抽出した。その後抽出液をろ過してろ液を回収し、それぞれ実施例7〜9にかかる熱水抽出物を得た。
Examples 7 to 9 Hot water extract of Matsutake fruit bodies 20 kg of water was added to each 1 kg of dried Matsutake fruit bodies of Examples 1 to 3 and extracted at 90 ° C for 20 minutes. Thereafter, the extract was filtered to collect the filtrate, and hot water extracts according to Examples 7 to 9 were obtained.
実施例10〜12 マツタケ子実体のエタノール抽出物
実施例1〜3のマツタケ子実体乾燥物各1kgに50容量%エタノール水溶液を20L加え室温にて撹拌しながら2時間抽出した。その後抽出液をろ過してろ液を回収し、それぞれ実施例10〜12にかかるエタノール抽出物を得た。
Examples 10-12 Ethanol extract of Matsutake fruiting bodies 20 L of 50 vol% ethanol aqueous solution was added to each 1 kg of dried Matsutake fruiting bodies of Examples 1-3, and the mixture was extracted for 2 hours while stirring at room temperature. Thereafter, the extract was filtered to collect the filtrate, and ethanol extracts according to Examples 10 to 12 were obtained.
1型糖尿病に対する効果
1型糖尿病モデル動物の一種であるストレプトゾトシン(STZ)糖尿病モデルラットを用いて、マツタケの糖尿病予防・改善効果を次のようにして調べた。約4週齢の雄のSDラットに65mg/kgのストレプトゾトシンを腹腔内に投与し、糖尿病を誘発させた。1週間後に高血糖,尿糖,多食,多飲を示したラットについて以下の実験に供した。作製したSTZ糖尿病モデルラット10匹を1群とし、基本食としてラット用固形飼料(日本チャールズリバー社製CRF−1)を投与した基本食群と、基本食に5重量%となるように上記実施例1〜3記載のマツタケ子実体乾燥物を混合した実施例1〜3混合食群とに群分けした。これらを室温23℃,12時間明暗サイクルにて飼料と水を自由に摂取できる環境で4週間飼育した。飼育開始から1週間毎に20時間絶食後のラット尾静脈から採血し、血糖値を測定した。さらに、0,2,4週目ではブドウ糖負荷試験を行った。すなわち、20時間の絶食後、2g/kgのブドウ糖をゾンデを用いて経口投与した。ブドウ糖投与前(0時間)、投与0時間後,0.5時間後,1時間後,1.5時間後,2時間後にそれぞれ尾静脈から採血し血糖値を測定し平均値を算出した。試験期間中の空腹時血糖値の変化を表1に、ブドウ糖負荷試験の結果を表2〜4にそれぞれ示す。
Effect on Type 1 Diabetes Using a streptozotocin (STZ) diabetic model rat, which is a type 1 diabetic model animal, the effect of matsutake mellitus on diabetes was examined as follows. About 4 weeks old male SD rats were given 65 mg / kg streptozotocin intraperitoneally to induce diabetes. One week later, rats that showed hyperglycemia, urine sugar, multiple meals, and multiple drinks were subjected to the following experiment. A group consisting of 10 STZ diabetic model rats prepared, and a basic diet group administered with a solid feed for rats (CRF-1 manufactured by Charles River Japan) as a basic diet, and the above-described implementation so that the basic diet is 5% by weight It divided into the Example 1-3 mixed food group which mixed the matsutake fruit body dried material of Examples 1-3. These were bred for 4 weeks in an environment where food and water could be freely ingested at room temperature of 23 ° C. and 12 hours light / dark cycle. Blood was collected from the rat tail vein after fasting for 20 hours every week from the start of the breeding, and the blood glucose level was measured. Furthermore, a glucose tolerance test was performed at 0, 2, and 4 weeks. That is, after fasting for 20 hours, 2 g / kg of glucose was orally administered using a sonde. Blood samples were collected from the tail vein before glucose administration (0 hours), 0 hours, 0.5 hours, 1 hour, 1.5 hours, and 2 hours after administration, and blood glucose levels were measured to calculate average values. Table 1 shows the changes in fasting blood glucose levels during the test period, and Tables 2 to 4 show the results of the glucose tolerance test.
表1からわかるように、基本食群と比較して実施例混合食群では,空腹時血糖値の上昇が抑えられる傾向にあることが示された。また、糖負荷試験の結果では、表2に示したとおり試験開始時には基本食群と実施例混合食群に差は認められなかったが、表3,表4に示した飼育2週目及び4週目では、ブドウ糖投与直後の血糖値の上昇が抑えられ、さらに血糖値の回復も早くなっていた。従って、基本食群と比較して実施例混合食群では、耐糖能が改善されていた。以上のことからマツタケには1型糖尿病の予防・改善効果があることが示された。 As can be seen from Table 1, it was shown that the increase in fasting blood glucose level tended to be suppressed in the example mixed diet group as compared with the basic diet group. Moreover, in the result of the glucose tolerance test, as shown in Table 2, there was no difference between the basic food group and the example mixed food group at the start of the test. In the week, the increase in blood glucose level immediately after glucose administration was suppressed, and the recovery of blood glucose level was accelerated. Therefore, compared with the basic food group, the glucose tolerance was improved in the Example mixed food group. From the above, it was shown that matsutake has an effect of preventing and improving type 1 diabetes.
2型糖尿病に対する効果
2型糖尿病モデル動物の1種であるKKAY糖尿病モデルマウスを用い1型糖尿病と同様にマツタケの効果を次のようにして調べた。約4週齢のKKAY/Ta Jclマウスを1週間予備飼育した後、10匹を一群として基本食群と実施齢混合食群に群分けして試験を開始した。マウスはケージに個別に入れて室温23℃、12時間明暗サイクルにて飼料と水を自由に摂取できる環境で飼育した。飼育開始から1週間毎に、5時間絶食後のマウス眼底からキャピラリー採血管を用いて採血し、血糖値を測定した。さらに、飼育開始から36日後にブドウ糖負荷試験を行った。すなわち、20時間絶食した後、2g/kgのブドウ糖をゾンデを用いて経口投与した。ブドウ糖投与前(0時間),投与後0.5時間,1時間,1.5時,2時間後に眼底から採血し血糖値を測定し平均値を算出した。試験期間中の血糖値の変化を表5に、糖負荷試験の結果を表6に示す。
Effect on type 2 diabetes Using the KKA Y diabetes model mouse, which is one of type 2 diabetes model animals, the effect of matsutake was examined in the same manner as in type 1 diabetes. About 4 weeks old KKA Y / Ta Jcl mice were preliminarily raised for 1 week, and 10 animals were grouped into a basic diet group and a working age mixed diet group, and the test was started. Mice were individually housed in cages and reared in an environment where food and water could be freely ingested in a light / dark cycle at room temperature of 23 ° C. for 12 hours. Every week from the start of breeding, blood was collected from the fundus of the mouse after fasting for 5 hours using a capillary blood collection tube, and the blood glucose level was measured. Furthermore, a glucose tolerance test was performed 36 days after the start of the breeding. That is, after fasting for 20 hours, 2 g / kg of glucose was orally administered using a sonde. Before glucose administration (0 hour), 0.5 hours, 1 hour, 1.5 hours, and 2 hours after administration, blood was collected from the fundus oculi, blood glucose level was measured, and an average value was calculated. Table 5 shows changes in blood glucose level during the test period, and Table 6 shows the results of the glucose tolerance test.
表5,表6に示したとおり、基本食群と比較して実施例混合食群では、ブドウ糖投与直後の血糖値上昇が抑制され、さらに血糖値の回復も早いことが確認された。以上のことから,マツタケは2型糖尿病の予防・改善効果を有することが示された。 As shown in Tables 5 and 6, it was confirmed that in the example mixed diet group, the increase in blood glucose level immediately after glucose administration was suppressed and the recovery of blood glucose level was quicker than that in the basic diet group. From the above, it was shown that matsutake has a preventive / ameliorating effect on type 2 diabetes.
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JP2005225801A (en) * | 2004-02-12 | 2005-08-25 | Kureha Chem Ind Co Ltd | New therapeutic agent against diabetes and food |
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JP2000159682A (en) * | 1998-09-17 | 2000-06-13 | Kozo Niwa | Method of strengthening antitumor activity of crude drug, composition containing crude drug for strengthening antitumor activity, method of evaluating antitumor effectivity treated by crude drug and method of evaluating antitumor effectivity of crud drug |
CN1429576A (en) * | 2001-12-31 | 2003-07-16 | 钱师良 | Edible fungus formula for treating hypertension and diabetes and its preparation method |
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JP2000159682A (en) * | 1998-09-17 | 2000-06-13 | Kozo Niwa | Method of strengthening antitumor activity of crude drug, composition containing crude drug for strengthening antitumor activity, method of evaluating antitumor effectivity treated by crude drug and method of evaluating antitumor effectivity of crud drug |
CN1429576A (en) * | 2001-12-31 | 2003-07-16 | 钱师良 | Edible fungus formula for treating hypertension and diabetes and its preparation method |
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JP2005225801A (en) * | 2004-02-12 | 2005-08-25 | Kureha Chem Ind Co Ltd | New therapeutic agent against diabetes and food |
JP4587441B2 (en) * | 2004-02-12 | 2010-11-24 | 株式会社クレハ | Novel diabetes treatment and food |
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