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Compositions comprising inhibitors of sodium-glucose cotransporters 1 and 2 and using methods

A dosage form and therapeutic agent technology, applied in the field of compounds and pharmaceutical compositions, can solve problems such as glucose-galactose malabsorption

Inactive Publication Date: 2013-12-18
LEXICON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is apparently based, at least in part, on the fact that, while humans lacking a functional SGLT2 gene appear to live normally except for exhibiting high urinary glucose excretion, humans with mutations in the SGLT1 gene experience glucose-galactose malabsorption

Method used

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  • Compositions comprising inhibitors of sodium-glucose cotransporters 1 and 2 and using methods
  • Compositions comprising inhibitors of sodium-glucose cotransporters 1 and 2 and using methods
  • Compositions comprising inhibitors of sodium-glucose cotransporters 1 and 2 and using methods

Examples

Experimental program
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Embodiment

[0264] In vitro human SGLT2 inhibition assay

[0265] Human sodium / glucose cotransporter type 2 (SGLT2; accession number P31639; GI:400337) was cloned into the pIRESpuro2 vector for mammalian expression (construct: HA-SGLT2-pIRESpuro2).

[0266] HEK293 cells were transfected with the human HA-SGLT2-pIRESpuro2 vector, and a large number of stable cell lines were selected in the presence of 0.5 μg / ml puromycin. Human HA-SGLT2 cells were maintained in DMEM medium containing 10% FBS, 1% GPS and 0.5 μg / ml puromycin.

[0267] HEK293 cells expressing human HA-SGLT2 were seeded in 384-well plates (30,000 cells / well) in DMEM medium containing 10% FBS, 1% GPS, and 0.5 μg / ml puromycin, and then incubated at 37 °C, 5%CO 2 Incubate overnight. Then with uptake buffer (140mM NaCl, 2mM KCl, 1mM CaCl 2 , 1 mM MgCl 2 , 10mM HEPES, 5mM Tris, 1mg / ml bovine serum albumin (BSA), pH7.3) to wash the cells. 20 microliters of uptake buffer with or without test compound was added to the cells. Th...

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Abstract

Pharmaceutical dosage forms useful for improving the cardiovascular and / or metabolic health of patients, particularly those suffering from type 2 diabetes, are disclosed, as well as methods of their manufacture.

Description

[0001] This application claims priority to US Provisional Patent Application No. 61 / 430,027, filed January 5, 2011, which is hereby incorporated by reference in its entirety. technical field [0002] The present invention relates to methods for improving the cardiovascular and / or metabolic health of patients, especially patients with type 2 diabetes, and compounds and pharmaceutical compositions that can be used in said methods. Background technique [0003] Type 2 diabetes mellitus (T2DM) is a disorder characterized by elevated serum glucose. One way serum glucose is lowered in patients with this disease is by inhibiting glucose reabsorption in the kidneys. The kidneys play an important role in the overall control of glucose, as glucose is filtered through the glomeruli at a rate of approximately 8 g / h and is almost completely reabsorbed in the proximal tubule through the sodium-glucose cotransporter (SGLT). Komoroski, B. et al., Clin Pharmacol Ther. 85(5):513-9 (2009)....

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K9/20A61K31/335A61P3/10
CPCA61K9/2054A61K9/2077A61K31/335A61K31/7032A61K31/155A61K31/7034A61P13/12A61P3/00A61P3/04A61P3/06A61P43/00A61P7/00A61P9/00A61P9/10A61P9/12A61P3/10A61K9/0053A61K9/20A61K31/351A61K45/06A61K47/38A61K47/00A61K9/16A61K47/02A61K9/1652A61K9/2009A61K31/7028
Inventor 陈金玲纳瑟尔·N·尼亚姆韦亚基尼斯·K·H·昂格
Owner LEXICON PHARM INC
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