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Combination therapy comprising SGLT inhibitor and DPP4 inhibitor

A DPP4 and inhibitor technology, applied in the field of compositions for increasing the concentration of active GLP-1 in mammalian plasma, can solve problems such as reducing the concentration of glucose

Inactive Publication Date: 2014-02-26
MITSUBISHI TANABE PHARMA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, inhibition of SGLT causes excretion of blood glucose into the urine, resulting in lower plasma glucose concentration

Method used

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  • Combination therapy comprising SGLT inhibitor and DPP4 inhibitor
  • Combination therapy comprising SGLT inhibitor and DPP4 inhibitor
  • Combination therapy comprising SGLT inhibitor and DPP4 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0483] Effect of SGLT inhibitors on plasma active GLP-1 concentrations in glucose-treated DPP4-deficient rats

[0484] (a) Animals:

[0485] DPP4-deficient male Fisher rats (purchased from Charles River Japan, Inc.)

[0486] (b) method:

[0487] (b-1) Preparation and administration of test compound

[0488] The test compound was suspended in a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at the dose shown in Table 1, and was orally administered to the test group at a volume of 5 mL / kg. The vehicle control group received oral administration of a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at a volume of 5 mL / kg. Glucose solution (2 g / kg / 5 ml) was orally administered immediately after compound or vehicle administration.

[0489] (b-2) Blood collection process and determination of active GLP-1 concentration in plasma

[0490] Blood was collected from the tail vein of unanesthetized rats immediately before glucose adminis...

Embodiment 2

[0503] Synergistic Effect of SGLT Inhibitor and DPP4 Inhibitor on Concentration of Active GLP-1 in Plasma of Glucose-Treated Normal Rats

[0504] (a) Animals:

[0505] DPP4-positive male Fisher rats (purchased from Japan SLC, Inc.)

[0506] (b) method:

[0507] (b-1) Preparation and administration of test compound

[0508] Each test compound was suspended in a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at the dose shown in Table 2, and was orally administered to the test group at a volume of 5 mL / kg. The vehicle control group received oral administration of a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at a volume of 5 mL / kg. Glucose solution (2 g / kg / 5 ml) was orally administered immediately after compound or vehicle administration.

[0509] (b-2) Blood collection process and determination of active GLP-1 concentration in plasma

[0510] Blood was collected from the tail vein of unanesthetized rats immediately befor...

Embodiment 3

[0525] Effects of SGLT inhibitors and DPP4 inhibitors on plasma active GLP-1 concentrations in glucose-treated diabetic mice

[0526] (a) Animals:

[0527] Male BKS.Cg - +Lepr db / +Lepr db / Jc1 mouse; animal model of type 2 diabetes (purchased from CLEA Japan, Inc.)

[0528] (b) method:

[0529] (b-1) Preparation and administration of test compound

[0530] Each test compound was suspended in a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at the dose shown in Table 3, and was orally administered to the test group at a volume of 5 mL / kg. The vehicle control group received oral administration of a 0.5% carboxymethylcellulose solution containing 0.2% Tween 80 (Tween80) at a volume of 5 mL / kg. Glucose solution (2 g / kg / 5 ml) was orally administered immediately after compound or vehicle administration.

[0531] (b-2) Blood collection process and determination of active GLP-1 concentration in plasma

[0532] Blood was collected from the tail vein of...

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Abstract

The present invention relates to combination therapy comprising a DPP4 inhibitor and an SGLT inhibitor. The combination of the present invention leads to increased plasma GLP-1 level and the combination is useful for prevention or treatment of conditions such as diabetes and diseases related to diabetes.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of January 16, 2009, an application number of 200980102300.8, and an invention title of "Combined Therapy Comprising SGLT Inhibitors and DPP4 Inhibitors". technical field [0002] The present invention relates to a composition and method for increasing the concentration of active GLP-1 in mammalian plasma. The present invention also relates to a composition and method for alleviating a condition by increasing the concentration of active GLP-1 in plasma. Background technique [0003] Glucagon-like peptide-1 (GLP-1) is an incretin hormone released by L-cells in the lower small intestine following food ingestion. GLP-1 has been shown to stimulate insulin secretion from pancreatic β-cells in response to glucose and to increase pancreatic β-cell mass. GLP-1 has also been shown to reduce the rate of gastric emptying and promote feelings of fullness. However, GLP-1 is rapi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/706A61K31/7042A61K31/7056A61K31/496A61K31/4985A61K31/401A61K31/40A61P3/10A61P9/10A61P25/28A61P3/06A61P9/12A61P13/12A61P27/12A61P25/16A61P25/14A61P25/02
CPCA61K31/7008A61K31/401A61K31/7004A61K45/06C07H7/04A61P13/12A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/28A61P27/02A61P27/12A61P3/00A61P3/04A61P3/06A61P43/00A61P5/50A61P9/00A61P9/10A61P9/12A61P3/10A61K2300/00A61K31/40A61K31/496A61K31/4985A61K31/5377A61K31/7034A61K31/7056A61K31/706
Inventor 植田喜一郎荒川健司松下泰明
Owner MITSUBISHI TANABE PHARMA CORP