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
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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
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