JP5721232B2 - Glucagon-like peptide-1 secretion promoter - Google Patents
Glucagon-like peptide-1 secretion promoter Download PDFInfo
- Publication number
- JP5721232B2 JP5721232B2 JP2011544281A JP2011544281A JP5721232B2 JP 5721232 B2 JP5721232 B2 JP 5721232B2 JP 2011544281 A JP2011544281 A JP 2011544281A JP 2011544281 A JP2011544281 A JP 2011544281A JP 5721232 B2 JP5721232 B2 JP 5721232B2
- Authority
- JP
- Japan
- Prior art keywords
- glp
- potato extract
- secretion
- potato
- fraction
- 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.)
- Expired - Fee Related
Links
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 title claims description 57
- 230000028327 secretion Effects 0.000 title claims description 40
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 title claims description 8
- 102100040918 Pro-glucagon Human genes 0.000 title claims 2
- 244000061456 Solanum tuberosum Species 0.000 claims description 58
- 235000002595 Solanum tuberosum Nutrition 0.000 claims description 58
- 239000000284 extract Substances 0.000 claims description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 53
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 229920003002 synthetic resin Polymers 0.000 claims 1
- 239000000057 synthetic resin Substances 0.000 claims 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 55
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 49
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 24
- 230000001737 promoting effect Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 238000010828 elution Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 9
- 235000013305 food Nutrition 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 238000000605 extraction Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 235000012054 meals Nutrition 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 210000002429 large intestine Anatomy 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000010298 pulverizing process Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010076119 Caseins Proteins 0.000 description 2
- 102000011632 Caseins Human genes 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 101100288498 Mus musculus Large1 gene Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000036186 satiety Effects 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 101000635799 Homo sapiens Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Proteins 0.000 description 1
- 241000976924 Inca Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102100030852 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Human genes 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000448053 Toya Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000002156 adsorbate Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 108010067454 caseinomacropeptide Proteins 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000011899 heat drying method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000021246 κ-casein Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Botany (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Endocrinology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
本発明は、グルカゴン様ペプチド−１分泌促進剤に関する。 The present invention relates to a glucagon-like peptide-1 secretion promoter.
近年、様々な面での環境変化によりメタボリックシンドロームを心配する人々が増えてきている。メタボリックシンドロームは各種疾病のリスクを高めるため、その改善は社会的な課題である。 In recent years, an increasing number of people are worried about metabolic syndrome due to environmental changes in various aspects. Since metabolic syndrome increases the risk of various diseases, its improvement is a social issue.
消化管に散在するＬ細胞から分泌されるホルモンのグルカゴン様ペプチド−１（以下、「ＧＬＰ−１」ともいう）は、食物の刺激による、強力なインスリン分泌促進、満腹中枢の刺激、消化管の蠕動運動抑制などの作用を有することが確認されている。これらのＧＬＰ−１の作用はいずれも、摂食による急激な血糖値の上昇を抑制する効果に関連すると考えられており、糖尿病の治療へのＧＬＰ−１の利用について研究がなされている。また、ＧＬＰ−１は、肥満抑制作用についても注目されている。 Glucagon-like peptide-1 (hereinafter also referred to as “GLP-1”), a hormone secreted from L cells scattered in the digestive tract, is a potent stimulator of insulin secretion by stimulating food, stimulation of the satiety center, It has been confirmed to have effects such as peristaltic movement suppression. All of these actions of GLP-1 are considered to be related to the effect of suppressing a rapid increase in blood glucose level due to feeding, and studies have been conducted on the use of GLP-1 for the treatment of diabetes. GLP-1 is also attracting attention for its obesity-inhibiting action.
したがって、ＧＬＰ−１の抗糖尿病作用または抗肥満作用を利用した治療薬の開発が期待されている。しかし、ＧＬＰ−１は、体内での安定性が非常に低いので、投与法および投与経路の至適化、体内での安定性が高い機能的アナログの探索などが必要である。 Therefore, development of therapeutic agents utilizing the anti-diabetic action or anti-obesity action of GLP-1 is expected. However, since GLP-1 has very low stability in the body, it is necessary to optimize administration methods and administration routes, search for functional analogs having high stability in the body, and the like.
そこで、ＧＬＰ−１を直接投与するのではなく、体内でＧＬＰ−１の分泌を促進させる物質についても研究がなされている。ＧＬＰ−１の分泌促進作用を有するいくつかの天然由来成分が知られている。例えば、特許文献１には、酸カゼインなどにＧＬＰ−１分泌促進作用があることが開示されている。特許文献２には、カゼイングリコマクロペプチド（ＣＧＭＰ）にＧＬＰ−１分泌促進作用があることが開示されている。特許文献３には、κ−カゼインを有効成分として含有するＧＬＰ−１分泌促進剤が開示されている。非特許文献１には、トウモロコシの難消化性タンパク質Ｚｅｉｎをパパインで加水分解して得られるペプチドＺｅｉｎＨに強いＧＬＰ−１分泌促進作用があることが開示されている。
Therefore, research is being conducted on substances that promote GLP-1 secretion in the body, instead of directly administering GLP-1. Several naturally-occurring components having a GLP-1 secretion promoting effect are known. For example,
本発明は、有用なグルカゴン様ペプチド−１分泌促進剤を提供することを目的とする。 An object of the present invention is to provide a useful glucagon-like peptide-1 secretion promoter.
本発明は、ジャガイモ抽出物を含むグルカゴン様ペプチド−１分泌促進剤を提供する。 The present invention provides a glucagon-like peptide-1 secretion promoter containing a potato extract.
本発明によれば、新規なグルカゴン様ペプチド−１分泌促進剤が提供される。このグルカゴン様ペプチド−１分泌促進剤は、糖尿病および肥満の予防および改善に有用であり得、そして医薬品および飲食品に好適に利用され得る。 According to the present invention, a novel glucagon-like peptide-1 secretion promoter is provided. This glucagon-like peptide-1 secretion promoter can be useful for the prevention and improvement of diabetes and obesity, and can be suitably used for pharmaceuticals and foods and drinks.
以下、本発明の実施形態について説明する。なお、本発明は、下記の実施形態に限定して解釈すべきではなく、特許請求の範囲における記載の範囲内で種々の変更が可能である。 Hereinafter, embodiments of the present invention will be described. The present invention should not be construed as being limited to the following embodiments, and various modifications can be made within the scope of the claims.
ジャガイモ抽出物の原料となるジャガイモの品種は特に限定されず、例えば男爵薯、メークイン、キタアカリ、とうや、トヨシロ、インカのめざめ、デジマ、十勝こがねなどを用いることができる。ジャガイモの産地もまた特に限定されないが、北海道産のジャガイモが好ましい。また、生の（例えば、採取２日以内の未加工の）ジャガイモが原料として好ましい。 The potato varieties used as a raw material for the potato extract are not particularly limited, and examples thereof include baron candy, make-in, kitakari, toya, toyoshiro, inca sword, digima, and Tokachi rice. The potato production area is also not particularly limited, but Hokkaido potato is preferred. Raw (e.g., unprocessed potatoes within 2 days of collection) is also preferred as a raw material.
ジャガイモ抽出物の製造方法には特段の制限はなく、通常食品の製造において使用可能な抽出方法、抽出溶媒、製造助剤などを用いることができる。 There is no special restriction | limiting in the manufacturing method of a potato extract, The extraction method, extraction solvent, manufacturing adjuvant, etc. which can be normally used in manufacture of a foodstuff can be used.
一実施形態では、ジャガイモ抽出物は、以下に説明するように調製され得る。まず、ジャガイモの可食部（塊茎）を粉砕し搾汁して得られる液状物に抽出溶媒（酸）を添加してｐＨを酸性に調整し、次いで加熱下で溶媒抽出を行い得る。抽出溶媒として用いられ得る酸としては、一般に、塩酸、酢酸、硫酸、ギ酸、クエン酸、アスコルビン酸などが挙げられる。添加する酸の量または濃度は、ｐＨが一般に２〜５、好ましくは３〜４となるような量または濃度で適宜設定され得る。溶媒抽出は、一般に７０〜９０℃にて１０〜６０分、好ましくは７５〜８５℃にて１０〜２０分で行われ得る。溶媒抽出後、遠心分離、濾過などの適当な分離手段により沈殿物または不溶性画分を除き、上清または可溶性画分を回収し得る。さらに、上記抽出後の沈殿物または不溶性画分について再度同様の抽出処理を行って、上清または可溶性画分を回収することもできる。 In one embodiment, the potato extract can be prepared as described below. First, an extraction solvent (acid) is added to a liquid material obtained by pulverizing and squeezing an edible portion (tuber) of potato, the pH is adjusted to be acidic, and then solvent extraction can be performed under heating. Examples of acids that can be used as the extraction solvent generally include hydrochloric acid, acetic acid, sulfuric acid, formic acid, citric acid, and ascorbic acid. The amount or concentration of the acid to be added can be appropriately set in such an amount or concentration that the pH is generally 2 to 5, preferably 3 to 4. The solvent extraction is generally carried out at 70 to 90 ° C. for 10 to 60 minutes, preferably 75 to 85 ° C. for 10 to 20 minutes. After solvent extraction, the precipitate or insoluble fraction can be removed by an appropriate separation means such as centrifugation or filtration, and the supernatant or soluble fraction can be recovered. Furthermore, the same extraction process can be performed again on the precipitate or insoluble fraction after the extraction, and the supernatant or the soluble fraction can be recovered.
回収された上清または可溶性画分（すなわち、ジャガイモ抽出液）から、膜処理により分子量が１万以上の画分を分離および回収し、続いて、冷却した上記抽出液に苛性ソーダを添加してｐＨを中性またはその付近に調整して、ジャガイモ抽出物を取得し得る。分子量分画のための膜処理としては、限外濾過膜処理、ゲル濾過膜処理が挙げられ、好ましくは限外濾過膜処理である。 From the recovered supernatant or soluble fraction (ie, potato extract), a fraction having a molecular weight of 10,000 or more is separated and recovered by membrane treatment, and then caustic soda is added to the cooled extract to adjust the pH. Can be adjusted to neutral or near to obtain a potato extract. Examples of membrane treatment for molecular weight fractionation include ultrafiltration membrane treatment and gel filtration membrane treatment, with ultrafiltration membrane treatment being preferred.
ジャガイモ抽出物は、さらに、乾燥手段、粉砕手段などの処理に供してもよい。乾燥法としては、公知の任意の方法が用いられ得るが、例えば、風乾法、加熱乾燥法、スプレードライ法、凍結乾燥法などが挙げられる。ジャガイモ抽出物は、例えば、賦型剤（例えば、デキストリン）を添加し、それをスプレードライなどにより乾燥し得る。粉砕法は、例えば、粉砕機や摩砕機を使用して微粉末化または微粒化するなどの手段を含む。 The potato extract may be further subjected to processing such as drying means and pulverizing means. As the drying method, any known method can be used, and examples thereof include an air drying method, a heat drying method, a spray drying method, and a freeze drying method. The potato extract can be dried, for example, by adding an excipient (eg, dextrin) and spray-drying it. The pulverization method includes means such as pulverization or atomization using a pulverizer or an attritor.
ジャガイモ抽出物は、液状または溶媒除去した固形のいずれの形態でも用いられ得る。 The potato extract can be used in either liquid or solvent-removed solid form.
本発明には、株式会社東洋新薬製のジャガイモ抽出物が、好ましく用いられ得る。 In the present invention, a potato extract manufactured by Toyo Shinyaku Co., Ltd. can be preferably used.
ジャガイモ抽出物は、ＧＬＰ−１の分泌を直接的に刺激し、促進し得る。ＧＬＰ−１分泌促進作用は、吸着剤ＨＰ２０に吸着し、８０％（v/v）エタノールにて溶出されるジャガイモ抽出物の成分に起因し得る。本発明によれば、ジャガイモ抽出物をＧＬＰ−１分泌促進剤として使用し得、そしてジャガイモ抽出物を含むＧＬＰ−１分泌促進剤が提供される。 Potato extracts can directly stimulate and promote GLP-1 secretion. The GLP-1 secretion promoting action can be attributed to the components of the potato extract adsorbed on the adsorbent HP20 and eluted with 80% (v / v) ethanol. According to the present invention, a potato extract can be used as a GLP-1 secretion promoter, and a GLP-1 secretion promoter comprising a potato extract is provided.
ＧＬＰ−１は、食物の刺激による、強力なインスリン分泌促進、満腹中枢の刺激、消化管の蠕動運動抑制などの作用を有する。本発明のＧＬＰ−１分泌促進剤は、糖尿病および肥満の予防および改善に有用であり得る。本発明のＧＬＰ−１分泌促進剤は、ＧＬＰ−１分泌の増大によって改善される任意の症状の予防および治療にも有用であり得る。 GLP-1 has effects such as strong insulin secretion promotion, stimulation of the satiety center, suppression of peristaltic movement of the digestive tract by food stimulation. The GLP-1 secretion promoter of the present invention may be useful for the prevention and improvement of diabetes and obesity. The GLP-1 secretion promoter of the present invention may also be useful for the prevention and treatment of any condition that is ameliorated by increased GLP-1 secretion.
本発明のＧＬＰ−１分泌促進剤は、単独で、または種々の栄養成分、賦形剤、増量剤、結合剤、増粘剤、乳化剤、着色料、香料、食品添加物、栄養補助剤、調味料などと混合して、経口投与または摂取用の組成物として調製され得る。 The GLP-1 secretion promoter of the present invention can be used alone or in various nutritional components, excipients, extenders, binders, thickeners, emulsifiers, coloring agents, fragrances, food additives, nutritional supplements, seasonings. It can be mixed with a preparation or the like and prepared as a composition for oral administration or ingestion.
本発明のＧＬＰ−１分泌促進剤の配合量は、配合される製品の種類または剤形、投与または摂取の対象の年齢、性別、体重または状態、投与または摂取の方法、時期または時間などに応じて適宜設定され得る。 The compounding amount of the GLP-1 secretion promoter of the present invention depends on the type or dosage form of the product to be formulated, the age, sex, weight or condition of the subject of administration or ingestion, the method of administration or ingestion, timing or time, etc. Can be set appropriately.
本発明のＧＬＰ−１分泌促進剤の投与量は、例えば、健康食品などの飲食品として摂取する場合には、有効成分として、通常成人１人につき１日１回当たり１０〜２０００ｍｇ、好ましくは１００〜１０００ｍｇ、特に好ましくは３００〜１０００ｍｇであり得る。ＧＬＰ−１分泌促進剤の投与時期は、食前、食間および食後のいずれでもよいが、食事前２時間以内、食事直前または食事直後が好ましい。数回に分けて投与してもよい。 The dose of the GLP-1 secretion promoter of the present invention is, for example, 10 to 2000 mg per adult per day, preferably 100, as an active ingredient when taken as a food or drink such as health food. It can be -1000 mg, particularly preferably 300-1000 mg. The administration time of the GLP-1 secretion promoter may be before meal, between meals or after meal, but is preferably within 2 hours before meal, immediately before meal or immediately after meal. It may be administered in several divided doses.
経口投与または摂取用の組成物は、需要者の嗜好に合わせて、ハードカプセル、ソフトカプセルのようなカプセル剤、錠剤、丸剤などの剤形、または粉末状、顆粒状、飴状などの形状に成形され得る。また、溶液、懸濁液、または乳液のような液状の剤形もしくは形状にも調製され得る。 Compositions for oral administration or ingestion are shaped into capsules such as hard capsules and soft capsules, tablets and pills, or powders, granules, and bowls according to consumer preferences Can be done. It can also be prepared in liquid dosage forms or forms such as solutions, suspensions, or emulsions.
本発明のＧＬＰ−１分泌促進剤は、医薬品、医薬部外品、特定保健用食品、栄養補助食品、その他の飲食品などとして用いる、あるいはこれらに配合して用いることができる。 The GLP-1 secretion promoter of the present invention can be used as a pharmaceutical, a quasi-drug, a food for specified health use, a dietary supplement, or other food or drink, or can be used in combination with these.
経口投与または摂取用の組成物、あるいはその配合製品は、剤形もしくは形状または好みに応じて、そのまま食されても良いし、水、湯、牛乳、豆乳、茶、ジュースなどに溶かして飲んでも良い。 A composition for oral administration or ingestion, or a combination product thereof, may be eaten as it is depending on the dosage form or shape or preference, or it can be taken by dissolving in water, hot water, milk, soy milk, tea, juice, etc. good.
以下、実施例により本発明をより具体的に説明するが、本発明はこれらの実施例により限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited by these Examples.
（実施例１：ジャガイモ抽出物のＧＬＰ−１分泌促進作用）
ＧＬＰ−１分泌試験を以下の手順で行った。まず、マウス大腸由来のＧＬＰ−１産生細胞株ＧＬＵＴａｇ（Dr. Daniel J. Drucker, Mount Sinai Hospital Samuel Lunenfeld Research Institute Banting and Best Diabetes Centre, University of Torontoより提供）を、４８ウェルプレート中で、１０％ウシ胎児血清（ＦＢＳ）を含むダルベッコ改変イーグル培地にて、３７℃、５％ＣＯ２存在下、サブコンフルエントになるまで２〜３日間培養した。続いて、ウェルから培養培地を取り除き、Ｈｅｐｅｓバッファー（140mM NaCl、4.5mM KCl、20mM Hepes、1.2mM CaCl2、1.2mM MgCl2、10mM D-グルコース、0.1% ウシ血清アルブミン(ＢＳＡ)、pH 7.4）にてウェル中で細胞を洗浄した後、Ｈｅｐｅｓバッファーに溶解した試験物質溶液80μlを各ウェルに添加し、３７℃にて６０分間インキュベートした。上清を回収し、８００×ｇで４℃にて５分間、遠心分離して細胞を沈殿させ、その上清70μlを回収し、凍結保存した。凍結保存した上清を適宜解凍し、上清中のＧＬＰ−１濃度を、市販のＥＬＩＳＡキット（矢内原研究所製）を用いて定量した。上清中のＧＬＰ−１濃度（ｎＭ）をＧＬＰ−１産生細胞株ＧＬＵＴａｇからのＧＬＰ−１分泌量とした。(Example 1: GLP-1 secretion promoting effect of potato extract)
The GLP-1 secretion test was performed according to the following procedure. First, a GLP-1-producing cell line GLUTag (provided by Dr. Daniel J. Drucker, Mount Sinai Hospital, Samuel Lunenfeld Research Institute Banting and Best Diabetes Centre, University of Toronto), 10% in a 48-well plate. The cells were cultured in Dulbecco's modified Eagle's medium containing fetal bovine serum (FBS) in the presence of 37 ° C. and 5% CO 2 until they became subconfluent for 2-3 days. Subsequently, the culture medium is removed from the well, and Hepes buffer (140 mM NaCl, 4.5 mM KCl, 20 mM Hepes, 1.2 mM CaCl 2 , 1.2 mM MgCl 2 , 10 mM D-glucose, 0.1% bovine serum albumin (BSA), pH 7.4) After washing the cells in the wells, 80 μl of a test substance solution dissolved in Hepes buffer was added to each well and incubated at 37 ° C. for 60 minutes. The supernatant was collected, centrifuged at 800 × g for 5 minutes at 4 ° C. to precipitate the cells, and 70 μl of the supernatant was collected and stored frozen. The cryopreserved supernatant was appropriately thawed, and the concentration of GLP-1 in the supernatant was quantified using a commercially available ELISA kit (manufactured by Yauchihara Laboratory). The GLP-1 concentration (nM) in the supernatant was defined as the amount of GLP-1 secretion from the GLP-1-producing cell line GLUTag.
試験物質として、以下を用いた：
ジャガイモ抽出物（株式会社東洋新薬製）（２および10mg/ml）；および
ＺｅｉｎＨ（トウモロコシ難消化性タンパク質Ｚｅｉｎのパパイン加水分解物：トウモロコシ由来ゼイン（東京化成工業株式会社製）を脱塩水に懸濁してpH７に調整し、パパイン（アサヒビール株式会社製）を基質に対して０．５質量％で添加して５５℃にて６０分間処理し、煮沸によりパパインを失活させた後、遠心上清を凍結乾燥したもの；２および10mg/ml；陽性コントロールとして使用）。The following were used as test substances:
Potato extract (manufactured by Toyo Shinyaku Co., Ltd.) (2 and 10 mg / ml); After adjusting the pH to 7, papain (manufactured by Asahi Breweries Co., Ltd.) was added at 0.5% by mass with respect to the substrate, treated at 55 ° C. for 60 minutes, and papain was inactivated by boiling. Lyophilized; 2 and 10 mg / ml; used as positive control).
この結果を図１に示す。図１は、ジャガイモ抽出物およびＺｅｉｎＨによるマウス大腸由来のＧＬＰ−１産生細胞株ＧＬＵＴａｇのＧＬＰ−１分泌量を棒グラフにて表した図である。縦軸にＧＬＰ−１分泌量をｎＭ単位で表し、そして横軸では、「Blank」が陰性コントロール区（試験物質添加なし）の結果、「ジャガイモ抽出物」がジャガイモ抽出物処理区（２、10mg/ml）の結果、そして「ＺｅｉｎＨ」がＺｅｉｎＨ処理区（２、10mg/ml）の結果を表す。結果の値は、平均値＋標準誤差である（ｎ＝３〜４）。図中のａ、ｂおよびｃは、ダンカンの多群間有意差検定において、異なるアルファベットを有する記号の表示で、処理群間で有意差があることを示す（Ｐ＜0.05）。 The result is shown in FIG. FIG. 1 is a bar graph showing the amount of GLP-1 secreted from a GLP-1-producing cell line GLUTag derived from a mouse large intestine by potato extract and ZeinH. On the vertical axis, the amount of GLP-1 secretion is expressed in nM. On the horizontal axis, “Blank” is a negative control group (no test substance added), and “potato extract” is a potato extract treated group (2, 10 mg). / Ze), and “ZeinH” represents the result of ZeinH treatment (2, 10 mg / ml). The resulting value is the mean + standard error (n = 3-4). In the figure, a, b, and c are symbols having different alphabets in Duncan's multigroup significance test, indicating that there is a significant difference between treatment groups (P <0.05).
図１に示されるように、ジャガイモ抽出物は、濃度依存的にＧＬＰ−１分泌促進活性を示した。 As shown in FIG. 1, the potato extract exhibited GLP-1 secretion promoting activity in a concentration-dependent manner.
（実施例２：吸着剤ＨＰ２０を用いたカラムクロマトグラフィーによるジャガイモ抽出物の分画物のＧＬＰ−１分泌促進作用）
試験物質として以下を用いたこと以外は、実施例１と同様の試験を行った。(Example 2: GLP-1 secretion promoting effect of fraction of potato extract by column chromatography using adsorbent HP20)
The same test as in Example 1 was performed except that the following were used as test substances.
本実施例において用いた試験物質は、以下の通りである：
ジャガイモ抽出物（10mg/ml）；
ジャガイモ抽出物ＨＰ２０非吸着画分（7.44mg/ml、ジャガイモ抽出物の10mg/ml分に相当；
ジャガイモ抽出物ＨＰ２０吸着−２０％エタノール溶出画分（1.17mg/ml、ジャガイモ抽出物の10mg/ml分に相当）；および
ジャガイモ抽出物ＨＰ２０吸着−８０％エタノール溶出画分（0.45mg/ml、ジャガイモ抽出物の10mg/ml分に相当）。The test substances used in this example are as follows:
Potato extract (10mg / ml);
Potato extract HP20 non-adsorbed fraction (7.44 mg / ml, equivalent to 10 mg / ml of potato extract;
Potato extract HP20 adsorption-20% ethanol elution fraction (1.17 mg / ml, corresponding to 10 mg / ml of potato extract); and Potato extract HP20 adsorption-80% ethanol elution fraction (0.45 mg / ml, potato Equivalent to 10 mg / ml of extract).
上記の試験物質の調製について、以下に説明する。Diaion HP20（三菱化学製）を充填したカラムに、ジャガイモ抽出物を通して吸着させ、純水で洗浄した。次いで、２０％（v/v）エタノールおよび８０％（v/v）エタノールを順次カラムに通して吸着物を溶出させた。カラム吸着操作の際に流出した非吸着液と純水による洗浄で流出した洗浄液とを合わせたもの、２０％（v/v）エタノールによる溶出液、および８０％（v/v）エタノールによる溶出液をそれぞれ濃縮後、凍結乾燥し、ジャガイモ抽出物ＨＰ２０非吸着画分、ジャガイモ抽出物ＨＰ２０吸着−２０％エタノール溶出画分、およびジャガイモ抽出物ＨＰ２０吸着−８０％エタノール溶出画分とした。収率はそれぞれ、分画に用いたジャガイモ抽出物の74.4％、11.7％および4.5％に相当した。 The preparation of the above test substance will be described below. The potato extract was adsorbed through a column packed with Diaion HP20 (Mitsubishi Chemical) and washed with pure water. Subsequently, 20% (v / v) ethanol and 80% (v / v) ethanol were sequentially passed through the column to elute the adsorbate. A combination of the non-adsorbed liquid that flowed out during the column adsorption operation and the cleaning liquid that flowed out by washing with pure water, eluent with 20% (v / v) ethanol, and eluent with 80% (v / v) ethanol The potato extract HP20 non-adsorbed fraction, the potato extract HP20 adsorbed-20% ethanol-eluted fraction, and the potato extract HP20 adsorbed-80% ethanol-eluted fraction were each concentrated and then lyophilized. Yields corresponded to 74.4%, 11.7% and 4.5% of the potato extract used for fractionation, respectively.
この結果を図２に示す。図２は、ジャガイモ抽出物、ジャガイモ抽出物ＨＰ２０非吸着画分、ジャガイモ抽出物ＨＰ２０吸着−２０％エタノール溶出画分、およびジャガイモ抽出物ＨＰ２０吸着−８０％エタノール溶出画分のそれぞれの処理によるマウス大腸由来のＧＬＰ−１産生細胞株ＧＬＵＴａｇのＧＬＰ−１分泌量を棒グラフにて表した図である。縦軸にＧＬＰ−１分泌量をｎＭ単位で表し、そして横軸では、「Blank」が陰性コントロール区（試験物質添加なし）の結果、「ジャガイモ抽出物」がジャガイモ抽出物処理区の結果、「ＨＰ２０非吸着画分」がジャガイモ抽出物ＨＰ２０非吸着画分処理区の結果、「ＨＰ２０吸着−２０％エタノール溶出画分」がジャガイモ抽出物ＨＰ２０吸着−２０％エタノール溶出画分処理区の結果、そして「ＨＰ２０吸着−８０％エタノール溶出画分」がジャガイモ抽出物ＨＰ２０吸着−８０％エタノール溶出画分処理区の結果を示す。結果の値は、平均値＋標準誤差である（ｎ＝３〜４）。図中のａおよびｂは、ダンカンの多群間有意差検定において、異なるアルファベットを有する記号の表示で、処理群の間で有意差があることを示す（Ｐ＜0.05）。 The result is shown in FIG. FIG. 2 shows the mouse large intestine by each treatment of potato extract, potato extract HP20 non-adsorbed fraction, potato extract HP20 adsorbed-20% ethanol elution fraction, and potato extract HP20 adsorbed-80% ethanol eluted fraction. It is the figure which represented the GLP-1 secretion amount of origin GLP-1 producing cell strain GLUTag by the bar graph. On the vertical axis, the amount of GLP-1 secretion is expressed in units of nM, and on the horizontal axis, “Blank” is the result of the negative control group (no test substance added), “potato extract” is the result of the potato extract treatment group, “ “HP20 non-adsorbed fraction” is the result of the potato extract HP20 non-adsorbed fraction treatment group, “HP20 adsorption—20% ethanol elution fraction” is the result of the potato extract HP20 adsorption—20% ethanol elution fraction treatment group, and “HP20 adsorption—80% ethanol elution fraction” indicates the result of the potato extract HP20 adsorption—80% ethanol elution fraction treatment group. The resulting value is the mean + standard error (n = 3-4). In the figure, “a” and “b” indicate that there is a significant difference between the treatment groups by displaying symbols having different alphabets in Duncan's multigroup significance test (P <0.05).
ジャガイモ抽出物ＨＰ２０吸着−８０％エタノール溶出画分処理区では、0.45mg/mlという低い濃度にも関わらず、高いＧＬＰ−１分泌促進活性が見られた。ジャガイモ抽出物ＨＰ２０非吸着画分処理区およびジャガイモ抽出物ＨＰ２０吸着−２０％エタノール溶出画分処理区では、有意なＧＬＰ−１分泌促進効果が見られなかった。 In the potato extract HP20 adsorbed-80% ethanol elution fraction treatment group, a high activity of promoting GLP-1 secretion was seen despite the low concentration of 0.45 mg / ml. In the potato extract HP20 non-adsorbed fraction treatment group and the potato extract HP20 adsorption-20% ethanol elution fraction treatment group, no significant GLP-1 secretion promoting effect was observed.
ジャガイモ抽出物は、そのＧＬＰ−１分泌促進作用に基づき、糖尿病および肥満の予防および改善に有用であり得る。このようなジャガイモ抽出物を含むＧＬＰ−１分泌促進剤は、医薬品および飲食品への広範な利用が可能である。また、本発明の知見は、社会的な課題でもあるメタボリックシンドロームの改善にも役立ち得る。 The potato extract may be useful for the prevention and improvement of diabetes and obesity based on its GLP-1 secretion promoting action. The GLP-1 secretion promoter containing such a potato extract can be widely used for pharmaceuticals and foods and drinks. In addition, the knowledge of the present invention can be useful for improving metabolic syndrome, which is also a social problem.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011544281A JP5721232B2 (en) | 2009-12-04 | 2010-12-02 | Glucagon-like peptide-1 secretion promoter |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009276994 | 2009-12-04 | ||
| JP2009276994 | 2009-12-04 | ||
| PCT/JP2010/071555 WO2011068150A1 (en) | 2009-12-04 | 2010-12-02 | Glucagon-like peptide-1 secretion enhancer |
| JP2011544281A JP5721232B2 (en) | 2009-12-04 | 2010-12-02 | Glucagon-like peptide-1 secretion promoter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO2011068150A1 JPWO2011068150A1 (en) | 2013-04-18 |
| JP5721232B2 true JP5721232B2 (en) | 2015-05-20 |
Family
ID=44114996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011544281A Expired - Fee Related JP5721232B2 (en) | 2009-12-04 | 2010-12-02 | Glucagon-like peptide-1 secretion promoter |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP5721232B2 (en) |
| TW (1) | TW201125573A (en) |
| WO (1) | WO2011068150A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6045845B2 (en) * | 2011-09-02 | 2016-12-14 | 花王株式会社 | GLP-1 secretion promoter |
| JP6447848B2 (en) * | 2017-11-21 | 2019-01-09 | 株式会社東洋新薬 | Anti-glycation composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005336208A (en) * | 1999-07-27 | 2005-12-08 | Kemin Consumer Care Lc | Composition for extending post meal satiety |
| WO2008120813A1 (en) * | 2007-04-03 | 2008-10-09 | Mitsubishi Tanabe Pharma Corporation | Combined use of dipeptidyl peptidase iv inhibitor compound and sweetener |
-
2010
- 2010-12-02 WO PCT/JP2010/071555 patent/WO2011068150A1/en active Application Filing
- 2010-12-02 JP JP2011544281A patent/JP5721232B2/en not_active Expired - Fee Related
- 2010-12-03 TW TW099142029A patent/TW201125573A/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005336208A (en) * | 1999-07-27 | 2005-12-08 | Kemin Consumer Care Lc | Composition for extending post meal satiety |
| WO2008120813A1 (en) * | 2007-04-03 | 2008-10-09 | Mitsubishi Tanabe Pharma Corporation | Combined use of dipeptidyl peptidase iv inhibitor compound and sweetener |
Non-Patent Citations (3)
| Title |
|---|
| JPN6011000338; Ａｃｔａ Ｅｎｄｏｃｒｉｎｏｌｏｇｉｃａ Ｖｏｌ．１２３ Ｎｏ．４, 1990, ｐｐ．４６４-４７０ * |
| JPN6011000340; Ｊ． Ｆｏｏｄ Ｓｃｉ． Ｖｏｌ．３９, 1974, ｐｐ．１０６２-１０６３ * |
| JPN6011000341; 栄養学雑誌 Ｖｏｌ．５３ Ｎｏ．６, 1995, ｐｐ．３６１-３６８ * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2011068150A1 (en) | 2013-04-18 |
| TW201125573A (en) | 2011-08-01 |
| WO2011068150A1 (en) | 2011-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101426513B (en) | Composition containing peptide as active ingredient | |
| JP5916387B2 (en) | Dipeptidyl peptidase-4 inhibitor | |
| KR20170020459A (en) | Glucose metabolism ameliorating agent | |
| JP7291974B2 (en) | Recombinant irisin gene optimized for plant expression and method for producing recombinant irisin protein using the same | |
| US20140072650A1 (en) | Gelatin extract made from skate ray skin and antihypertensive composition having peptide isolated from extract as active ingredient | |
| JPWO2017002786A1 (en) | Composition for promoting GLP-2 secretion | |
| AU2018227125A1 (en) | GLP-1 secretagogue and composition | |
| JP5721232B2 (en) | Glucagon-like peptide-1 secretion promoter | |
| JP2008519758A (en) | Protein hydrolyzate with anti-diabetic activity | |
| JP2018516987A (en) | Pharmaceutical composition or health functional food for prevention and treatment of metabolic disease containing water extract of Aso as active ingredient | |
| JP3691685B2 (en) | Blood sugar level rise inhibitor | |
| CA2681593A1 (en) | Preventive or therapeutic composition for liver disease | |
| JP5872725B1 (en) | Dipeptidyl peptidase IV inhibitory composition derived from bonito | |
| JP5794678B2 (en) | Glucagon-like peptide-1 secretion promoter | |
| JP4673071B2 (en) | Iron-adsorptive polymer substance, iron-containing polymer substance, and production method thereof | |
| KR101443510B1 (en) | Pharmaceutical composition for preventing or treating influenza virus infection diseases comprising extract of Cichorium intybus and preparation method thereof | |
| JP6273440B2 (en) | GLP-1 production promoter, DPPIV inhibitor and glucose absorption inhibitor | |
| JP5674047B2 (en) | Cholecystokinin secretion promoter | |
| JP2002275087A (en) | Antidiabetic medicine and food for preventing diabetes | |
| KR101905009B1 (en) | Polysaccharide fraction isolated from kale with immune-enhancing activity and method for producing the same | |
| TW201639586A (en) | Water-soluble PAUA extract | |
| JP5717433B2 (en) | Bile acid adsorption composition | |
| JP5297867B2 (en) | Anti-fatigue agent or physical fitness improver containing Morohaya extract | |
| KR20230148629A (en) | Peptide Having Activity of Anti-Obesity and Anti-Diabetes and Uses Thereof | |
| JP6418911B2 (en) | GLP-1 secretion promoter |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130329 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140327 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140404 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140327 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140520 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140717 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140717 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140812 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140819 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140909 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141010 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20141014 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150303 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150320 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5721232 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |