JP4864064B2 - 抗糖尿病作用を有するペプチドおよびその用途 - Google Patents
抗糖尿病作用を有するペプチドおよびその用途 Download PDFInfo
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- JP4864064B2 JP4864064B2 JP2008280031A JP2008280031A JP4864064B2 JP 4864064 B2 JP4864064 B2 JP 4864064B2 JP 2008280031 A JP2008280031 A JP 2008280031A JP 2008280031 A JP2008280031 A JP 2008280031A JP 4864064 B2 JP4864064 B2 JP 4864064B2
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Description
最新医学大辞典、p.1211、1988年、医歯薬出版 新しい糖尿病治療薬、90〜99頁、(1994)、医薬ジャーナル社 JOSLIN’S DIABETES MELLITUS 13Th Edition 521-522
(I-1)Leu-Ser-Glu-Leuで示されるアミノ酸配列からなるペプチド。
(II-1)(I)に記載するペプチドを有効成分とする医薬組成物、食品組成物または飼料組成物。
(II-2)(I)に記載するペプチドを有効成分とする血糖値上昇抑制用組成物。
(II-3)(I)に記載するペプチドを有効成分とするインスリン分泌亢進用組成物。
(II-4)(I)に記載するペプチドを有効成分とする、高血糖に起因する疾患の予防または治療用組成物。
(II-5)高血糖に起因する疾患が、糖尿病、並びに糖尿病アシドーシス、糖尿病性黄色腫、糖尿病性筋萎縮症、糖尿病性ケトーシス、糖尿病性昏睡、糖尿病性胃障害、糖尿性壊疽、糖尿病性潰瘍、糖尿病性合併症、糖尿病性下痢症、糖尿病性細小血管症、糖尿病性子宮体硬化症、糖尿病性心筋症、糖尿病性ニューロパシー、糖尿病性腎症、糖尿病性水疱、糖尿病性白内障、糖尿病性皮膚障害、糖尿病性浮腫性硬化症、糖尿病性網膜症、糖尿病性リポイド類壊死症、糖尿病性血流障害等の糖尿病の合併症である(II-4)に記載する組成物。
(II-6)高血糖に起因する疾患が、II型糖尿病またはその合併症である(II-4)に記載する組成物。
本発明は、Leu-Ser-Glu-Leuのアミノ酸配列からなるテトラペプチド(以下、「ペプチドLSEL」、または「本発明のペプチド」ともいう)を提供する。当該ペプチドは、人為的に高血糖状態にした正常マウスおよび糖尿病モデルマウスに対して行った実験例(後述)で示すように、経口投与および非経口投与によって、血糖値上昇抑制作用およびインスリン分泌亢進作用を発揮する。すなわち、当該ペプチドは、血糖値上昇抑制作用およびインスリン分泌亢進作用を有する生理活性ペプチドである。
本発明の医薬組成物は、上記ペプチドLSELを有効成分として含有することを特徴とする。
本発明の食品組成物は、前述するペプチドLSELを有効成分として含有することを特徴とする。
本発明の飼料組成物は、ペプチドLSELを有効成分として含有することを特徴とする。
アミノ酸配列Leu-Ser-Glu-Leu(配列番号1)からなるペプチド(ペプチドLSEL)を、定法の液相法に従って合成した(Shanghai C-Strong社(上海,中国)に製造委託)。得られたペプチドについて、液相自動エドマン分解法(装置:アプライドバイオシステムズ製Procise HT, Protein Sequencing System)によりアミノ酸配列を分析したところ、上記アミノ酸配列からなるテトラペプチドであることが確認された。
調製例1で調製したペプチドLSELをグルコース負荷正常マウスに経口投与または皮下投与して、当該ペプチドの上記マウスの血糖値に及ぼす影響を調べた。試験には、7週齢の雄性ICRマウス(日本エスエルシー)を用いた。
調製例1で調製したペプチドLSELをグルコース負荷KK-Ayマウスに経口投与して、当該ペプチドの上記マウスの血糖値に及ぼす影響を調べた。試験には、9週齢の雄性2型糖尿病モデルKK-Ayマウス(日本クレア)を用いた。
調製例1で調製したペプチドLSELを、スクロース負荷正常マウスに経口投与して、当該ペプチドの上記マウスの血糖値に及ぼす影響を調べた。試験には7週齢の雄性ICRマウス(日本エスエルシー)を用いた。
調製例1で調製したペプチドLSELを、グルコース負荷正常マウスに経口投与して、当該ペプチドの上記マウスの血漿インスリン濃度に及ぼす影響を調べた。試験には7週齢の雄性ICRマウス(日本エスエルシー)を用いた。
調製例1で調製したペプチドLSELをマウスに経口投与した場合、2g/kg体重でも全く毒性を発現しなかった。このことから、ペプチドLSEL のLD50は2g/kg体重をはるかに上まわることが判明した。
緑茶8kgを80℃の熱水300Lに入れ、同温度で4分間抽出した。得られた抽出液を冷却後、遠心分離し、清澄な上清を採取してこれを緑茶抽出物とした。この抽出物にビタミンCを0.4kg配合し、さらに調製例1で調製したペプチドLSELを50g添加して、熱水で最終容量が1000Lになるよう調製した。これを85℃以上に加熱し、金属缶に充填して、レトルト殺菌(125℃、5分)して緑茶飲料とした。
下記の全成分を、常法により練合および造粒し、乾燥後打錠して1錠(200mg)中、ペプチドLSELを5重量%(10mg)の割合で含む錠剤を得た。当該錠剤は、ペプチドLSELの薬理作用(血糖値上昇抑制作用、インスリン分泌亢進作用、抗糖尿病作用)を有する医薬製剤またはサプリメントとして提供することができる。
ペプチドLSEL(調製例1) 50mg
ソルビトール 190mg
ショ糖脂肪酸エステル 10mg
合計 250mg。
ビタミン、ミネラル等が配合されたプレミックスに調製例1で調製したペプチドLSELを0.1%の割合で配合し、これを市販のドッグ用飼料に10%の割合で添加し、インスリン分泌亢進作用または血糖値上昇抑制作用を有するドッグフードを調製した。
Claims (7)
- Leu-Ser-Glu-Leuで示されるアミノ酸配列からなるペプチド。
- 請求項1に記載するペプチドを有効成分とする医薬組成物、食品組成物または飼料組成物。
- 請求項1に記載するペプチドを有効成分とする血糖値上昇抑制用組成物。
- 請求項1に記載するペプチドを有効成分とするインスリン分泌亢進用組成物。
- 請求項1に記載するペプチドを有効成分とする、高血糖に起因する疾患の予防または治療用組成物。
- 高血糖に起因する疾患が糖尿病である請求項5に記載する組成物。
- 請求項1に記載するペプチドを有効成分とする、糖尿病合併症の予防用組成物。
Priority Applications (10)
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JP2008280031A JP4864064B2 (ja) | 2008-10-30 | 2008-10-30 | 抗糖尿病作用を有するペプチドおよびその用途 |
US13/123,784 US8691949B2 (en) | 2008-10-30 | 2009-10-28 | Peptide having anti-diabetic activity and use thereof |
KR1020117008996A KR101731252B1 (ko) | 2008-10-30 | 2009-10-28 | 항-당뇨 활성을 갖는 펩티드 및 그것의 용도 |
CA2739712A CA2739712C (en) | 2008-10-30 | 2009-10-28 | Peptide having anti-diabetic activity and use thereof |
CN2009801431064A CN102197044B (zh) | 2008-10-30 | 2009-10-28 | 具有抗糖尿病活性的肽及其用途 |
PCT/JP2009/068504 WO2010050508A1 (ja) | 2008-10-30 | 2009-10-28 | 抗糖尿病作用を有するペプチドおよびその用途 |
AU2009310912A AU2009310912B2 (en) | 2008-10-30 | 2009-10-28 | Peptide having anti-diabetic activity and use thereof |
EP09823618.5A EP2341066B1 (en) | 2008-10-30 | 2009-10-28 | Peptide having anti-diabetic activity and use thereof |
TW098136988A TWI465245B (zh) | 2008-10-30 | 2009-10-30 | Peptides with antidiabetic effect and their use |
HK12102085.8A HK1161280A1 (en) | 2008-10-30 | 2012-02-29 | Peptide having anti-diabetic activity and use thereof |
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JP2008280031A JP4864064B2 (ja) | 2008-10-30 | 2008-10-30 | 抗糖尿病作用を有するペプチドおよびその用途 |
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JP2010105963A JP2010105963A (ja) | 2010-05-13 |
JP4864064B2 true JP4864064B2 (ja) | 2012-01-25 |
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JP2008280031A Active JP4864064B2 (ja) | 2008-10-30 | 2008-10-30 | 抗糖尿病作用を有するペプチドおよびその用途 |
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US (1) | US8691949B2 (ja) |
EP (1) | EP2341066B1 (ja) |
JP (1) | JP4864064B2 (ja) |
KR (1) | KR101731252B1 (ja) |
CN (1) | CN102197044B (ja) |
AU (1) | AU2009310912B2 (ja) |
CA (1) | CA2739712C (ja) |
HK (1) | HK1161280A1 (ja) |
TW (1) | TWI465245B (ja) |
WO (1) | WO2010050508A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9868764B2 (en) | 2013-06-12 | 2018-01-16 | Maruha Nichiro Corporation | Dipeptidyl peptidase-IV (DPPIV), inhibitory peptide compound, composition containing the same, and production method for the same |
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JP4864064B2 (ja) * | 2008-10-30 | 2012-01-25 | エムジーファーマ株式会社 | 抗糖尿病作用を有するペプチドおよびその用途 |
JP2012046432A (ja) * | 2010-08-25 | 2012-03-08 | Takeshi Ogura | カルシウム強化海洋ミネラル複合体を有効成分とする抗ストレス剤及び糖質コルチコイドの分泌抑制剤 |
WO2023098817A1 (en) * | 2021-12-03 | 2023-06-08 | The Hong Kong Polytechnic University | Glucoregulatory compound, composition and uses thereof |
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FR2809733B1 (fr) | 2000-06-02 | 2004-04-30 | Inst Nat Sante Rech Med | Substrat peptidique reconnu par la toxine botulique de type bont/b et son utilisation pour doser et/ou detecter ladite toxine ou des inhibiteurs correspondants |
AUPR595601A0 (en) * | 2001-06-27 | 2001-07-19 | International Diabetes Institute | Hypoglycaemic peptides and methods of use thereof |
JPWO2003030936A1 (ja) * | 2001-10-02 | 2005-01-20 | 住友製薬株式会社 | 生活習慣病又は拒食症治療薬及びそのスクリーニング方法 |
AU2004235872A1 (en) * | 2003-05-09 | 2004-11-18 | Novo Nordisk A/S | Peptides for use in treating obesity |
KR20060026011A (ko) * | 2003-05-09 | 2006-03-22 | 노보 노르디스크 에이/에스 | 비만 치료용 펩티드 |
CN1784423A (zh) * | 2003-05-09 | 2006-06-07 | 诺沃挪第克公司 | 用于治疗肥胖的肽 |
CA2585442A1 (en) * | 2004-11-15 | 2006-05-18 | Mg Pharma Inc. | Protein hydrolysate with antidiabetic effect |
EP2109054A1 (en) * | 2008-04-09 | 2009-10-14 | Biotempt B.V. | Methods for identifying biologically active peptides and predicting their function |
JP4864064B2 (ja) * | 2008-10-30 | 2012-01-25 | エムジーファーマ株式会社 | 抗糖尿病作用を有するペプチドおよびその用途 |
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2008
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2009
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- 2009-10-28 KR KR1020117008996A patent/KR101731252B1/ko active IP Right Grant
- 2009-10-28 US US13/123,784 patent/US8691949B2/en not_active Expired - Fee Related
- 2009-10-28 AU AU2009310912A patent/AU2009310912B2/en not_active Ceased
- 2009-10-28 WO PCT/JP2009/068504 patent/WO2010050508A1/ja active Application Filing
- 2009-10-28 CA CA2739712A patent/CA2739712C/en not_active Expired - Fee Related
- 2009-10-28 EP EP09823618.5A patent/EP2341066B1/en not_active Not-in-force
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9868764B2 (en) | 2013-06-12 | 2018-01-16 | Maruha Nichiro Corporation | Dipeptidyl peptidase-IV (DPPIV), inhibitory peptide compound, composition containing the same, and production method for the same |
US10513538B2 (en) | 2013-06-12 | 2019-12-24 | Maruha Nichiro Corporation | Dipeptidyl peptidase-IV (DPPIV), inhibitory peptide compound, composition containing the same, and production method for the same |
Also Published As
Publication number | Publication date |
---|---|
JP2010105963A (ja) | 2010-05-13 |
HK1161280A1 (en) | 2012-08-24 |
WO2010050508A1 (ja) | 2010-05-06 |
CN102197044A (zh) | 2011-09-21 |
KR20110074989A (ko) | 2011-07-05 |
CA2739712A1 (en) | 2010-05-06 |
US20110201551A1 (en) | 2011-08-18 |
EP2341066B1 (en) | 2015-05-20 |
AU2009310912A1 (en) | 2010-05-06 |
TWI465245B (zh) | 2014-12-21 |
US8691949B2 (en) | 2014-04-08 |
TW201026319A (en) | 2010-07-16 |
AU2009310912B2 (en) | 2014-05-08 |
KR101731252B1 (ko) | 2017-04-28 |
CN102197044B (zh) | 2013-11-27 |
CA2739712C (en) | 2018-05-22 |
EP2341066A4 (en) | 2012-03-21 |
EP2341066A1 (en) | 2011-07-06 |
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