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Glp-1 secretagogue

A technology of GLP-1, 1. GLP-1, applied in the field of secretion promoters, can solve the problems of biased inhibition and inconvenience, and achieves a technology that is easy to use, promotes GLP-1 secretion, and has excellent GLP-1 secretion ability. Effect

Pending Publication Date: 2018-06-08
JICHI MEDICAL UNIVERSITY +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs are synthetic drugs and are not cheap. Although they can be taken orally with the daily diet, a doctor's prescription is required.
[0008] Also, these past α -GI agent is an antagonistic disaccharide-decomposing enzyme inhibitor, so its inhibitory effect is biased, and a certain effect cannot always be obtained. In order to solve this problem, a drug is proposed, which is characterized in that it replaces the antagonistic inhibitor , containing non-antagonistic sucrase inhibitors (L-arabinose, D-xylose, and / or D-tagatose) and sucrose as active ingredients or ingested together with sucrose-containing foods (Patent Document 1)
However, this drug is characterized by containing sucrose as an essential active ingredient, and it is necessary to restrict the intake of sucrose for diabetic patients. Therefore, the method of use requires careful attention and is inconvenient.

Method used

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Experimental program
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Effect test

Embodiment 1

[0064] As experimental animals, C57BL / 6J male mice (9-11 weeks old) were used. D-Psicose 1 g / kg was orally administered at 10:00 am to the mice that had been fasted for 16 hours from 18:00 the day before the experiment. The oral administration amount is 10ml / kg. Portal vein blood was collected under isoflurane anesthesia before D-psicose administration and 30 minutes and 60 minutes after the administration. It should be noted that blood coagulation inhibitor (heparin (final concentration 50IU / ml)), peptide decomposition inhibitor (aprotinin (final concentration 500KIU / ml) and vildagliptin (Vildagliptin) were pre-added in the sampling syringe. (final concentration 10 μM)). The collected blood was cooled and centrifuged, and the obtained plasma was stored at -80°C until analysis. Quantitative analysis of active GLP-1, total GLP-1, and total GIP was performed using ELISA kits (manufactured by Millipore, EGLP-35K, EZGLP1T-36K, and EZRMGIP-55K, respectively). In addition, for s...

Embodiment 2

[0067] For C57BL / 6J male mice (9-11 weeks old) who had fasted for 16 hours from 18:00 the day before the experiment, D-psicose 0.3g / kg or 1g / kg, D-psicose at 10:00 am - Each 1 g / kg of tagatose or D-glucose, or physiological saline was administered orally. The oral administration amount is 10ml / kg. Thirty minutes after the administration, blood was collected from the portal vein under isoflurane anesthesia. It should be noted that blood coagulation inhibitor (heparin (final concentration 50IU / ml)), peptide decomposition inhibitor (aprotinin (final concentration 500KIU / ml) and vildagliptin (Vildagliptin) were pre-added in the sampling syringe. (final concentration 10 μM)). The collected blood was cooled and centrifuged, and the plasma was stored at -80°C until analysis. Quantitative analysis of active GLP-1 and total GIP was performed using the kits described above. Furthermore, regarding statistical analysis, one-way analysis of variance (without pairing) was performed, fol...

Embodiment 3

[0070] C57BL / 6J male mice (9-11 weeks old) were preliminarily bred in a separate cage for more than 1 week, and were manipulated by the experimenter to adapt to the feeding and experimental environment. After fasting for 16 hours from 18:00 on the day before the experiment, physiological saline or GLP-1 receptor inhibitor (Exendin-9, Ex-9, 200 nmol / kg) was intraperitoneally administered from 9:45, and immediately thereafter Physiological saline or 1 g / kg of D-psicose was orally administered. The administration volumes for intraperitoneal administration and oral administration were 5 ml / kg and 10 ml / kg, respectively. From 10:00 minutes, the mice were allowed to ingest CE-2 feed (general mouse feed for nutritionally balanced intake, manufactured by CLEA in Japan) freely, and after 0.5 hour, 1 hour, 2 hours, 3 hours and 6 hours, Food intake was measured over time. The amount of food intake was calculated as an energy intake (kcal) of 0 kcal per 1 g of D-psicose administered ora...

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Abstract

An object of the present invention is to provide a GLP-1 secretagogue which is an incretin hormone-related drug relatively inexpensive, excellent in safety, and capable of promoting GLP-1 secretion without containing sucrose as an essential constituent. The object is achieved by a GLP-1 secretagogue characterized by containing D-psicose as an active ingredient.

Description

technical field [0001] The present invention relates to an agent for promoting secretion of GLP-1, which is an incretin hormone, useful for the treatment of impaired glucose tolerance (abnormal glucose tolerance), the prevention of diabetes, and the like. Background technique [0002] Glucagon-like peptide-1 (GLP-1) is a type of incretin hormone that is secreted from the digestive tract by dietary intake and has an action of promoting insulin secretion from the pancreas. GLP-1 is secreted by L cells, one of the endocrine cells of the digestive tract, in response to the influx of nutrients into the lumen of the digestive tract, and is associated with the β GLP-1 receptor binding on the cell surface promotes β Intracellular insulin secretion. GLP-1 inhibits the secretion of glucagon, a hormone that raises blood sugar levels. In addition, the pancreas β Actions such as cell protection and proliferation promotion have also been confirmed in animals. As other effects, there a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7004A61K31/715A61P1/18A61P3/08A61P3/10A61P5/50A61P9/00A61P9/12A61P29/00A61P37/06A61P43/00
CPCA61K31/715A61K31/7004A61P1/18A61P29/00A61P3/08A61P37/06A61P43/00A61P5/50A61P9/00A61P9/12A61P3/10
Inventor 矢田俊彦岩崎有作原博比良彻岸本由香南真知子
Owner JICHI MEDICAL UNIVERSITY
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