Compositions and methods for treating metabolic diseases

A technology for metabolic diseases and compounds, which is applied in the field of compositions for the treatment of metabolic diseases, and can solve problems such as unapproved SGLT1 inhibitors

CN114450011APending Publication Date: 2022-05-06アヴォリント
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2022-05-06

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Abstract

The invention described herein relates to oral dosage form therapies for the combined treatment of metabolic disorders using SGLT1 and SGLT2 inhibitors. In such dosage forms, SGLT1 is effective in the enteric cavity and either is not absorbed, or is poorly absorbed, while the SGLT2 inhibitor inhibits sugar reabsorption in the kidney by inhibiting SGLT2 activity. Metabolic disorders treated in combination with SGLT1 and SGLT2 oral dosage forms include conditions associated with abnormal liver lipid accumulation, which may also coexist with hyperglycemia. Combination, in particular of SGLT1 and SGLT2 inhibitors, is contemplated herein.
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Description

technical field

[0001] The invention relates to compositions and methods for treating metabolic diseases. Background technology

[0002] People with abnormal lipid accumulation in the liver, such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), nutritional excess fatty liver, diabetes fatty liver, alcoholic fatty liver, toxic fatty liver, and general fatty liver, are increasing year by year. Most importantly, Nash is especially considered a problem because it shows serious symptoms. (Ishii et al., tanaki et al.). In addition, abnormal lipid accumulation in the liver can lead to liver inflammation or liver fiber formation (cirrhosis), which may then develop into more serious diseases, such as liver cancer. (Ishii et al., tanaki et al., Koike et al., UCHIMURA et al.). Therefore, inhibiting lipid accumulation in the liver is very important to avoid and treat liver diseases.

[0003] The treatments used to treat lipid accumulation in the liver are inc...

Examples

Embodiment 1

[0062] Example 1 Combination therapy of mizoglitazone and rimoglitazone.

[0063] Kgt-1681 and kga-3235 were combined to treat normal rats. Kgt-1681 is suspended in 0.1% methylcellulose (MC), and kga-3235 is dissolved in distilled water (DW). Rats (9 weeks old) were divided into the following four groups and treated according to the instructions: vector, 0.1% MC + DW; KGT, kgt-1681 (3mg / kg, 5ml / kg) plus DW; KGA, 0.1% MC plus kga-3235 (0.03mg / kg, 5ml / kg); And composition (Combo), kgt-1681 plus kga-3235 (3 and 0.03 mg / kg, respectively). After fasting for 16 hours, rats were given oral drugs and glucose solution (400g / L, 5ml / kg). Blood was collected from the caudal vein at each sampling point in heparinized and aprotinin treated tubes. Plasma glucose concentration was measured by glucose CII test Wako (Wako pure chemicals, Osaka, Japan). Plasma insulin was determined using an enzyme-linked immunosorbent assay kit (Morinaga Institute of biological science, Inc., Yokohama, ...