Application of compound in preparation of drug for treating type 2 diabetic cardiomyopathy

Abstract

The invention discloses a novel application of iCRT14, and particularly relates to a novel application of iCRT14 in preparation of a drug for treating type 2 diabetic cardiomyopathy. In the research, the inventor of the application finds that: the iCRT14 can reduce the blood sugar of the type 2 diabetic cardiomyopathy, improve myocardial remodeling of the type 2 diabetic cardiomyopathy, improve cardiac contraction and diastolic dysfunction caused by the type 2 diabetic cardiomyopathy and inhibit myocardial cell hypertrophy induced by high glucose and high insulin, and has a good treatment effect on the type 2 diabetic cardiomyopathy. The invention provides a new drug choice for treatment of the type 2 diabetic cardiomyopathy.

Description

technical field

[0001] The invention relates to a new application of a compound in the preparation and treatment of type 2 diabetic cardiomyopathy, especially the new application of iCRT14 in the preparation of a drug for the treatment of type 2 diabetic cardiomyopathy. Background technique

[0002] Diabetes mellitus (DM) is a chronic disease that occurs when the body cannot secrete or not secrete enough insulin or cannot effectively use insulin, resulting in elevated glucose levels in the blood. According to the latest diabetes map statistics released by the International Diabetes Federation, my country currently has 116.4 million diabetic patients (not included in the data of Hong Kong, Macao and Taiwan), ranking first in the world. The incidence of diabetes in adults in mainland China is close to 10%. In 2019 alone, the number of patients who died of diabetes and its complications in my country was 830,000. Among them, the proportion of patients who died under the age of ...

Examples

Embodiment 1

[0028] Example 1 Effect test of the compound (iCRT14) of the present invention in the treatment of type 2 diabetic cardiomyopathy 1. Experimental method

[0029] 1. Construction of animal models of type 2 diabetes

[0030]Select 3-4 week-old C57BL / 6J male mice as the test subjects, after 2 weeks of high-fat diet, intraperitoneally inject STZ (85mg / kg), inject once every other day, fast for 12h before intraperitoneal injection, and avoid light The injection was completed within 30 minutes, and the animal model of type 2 diabetes was constructed, followed by high-fat feeding. The random blood glucose of mice ≥ 16.7mmol / L can be used as a model group for experiments. Mice of the same age and sex are the normal control group (Control group, CON) , mice in the normal control group had normal diet and free access to water.

[0031] 2. Main solution configuration

[0032] (1) iCRT14 suspension injection: Weigh the injection dose, add 20% PEG300 and 80% PBS solution, and mix on a vo...

Embodiment 2

[0099] Embodiment 2 Compound (iCRT14) described in the present invention pharmacokinetic detection test in mice

[0100] At present, the data on the pharmacokinetics of iCRT14 is extremely limited. We established and verified a sensitive and highly selective method to detect the concentration of iCRT14 in mouse plasma for the study of iCRT14 pharmacokinetics.

[0101] In this example, the analyte was protein precipitated with methanol. The LC-ESIMS / MS method uses an Agilent Eclipse Plus C18 column (2.1 mm×50 mm, 1.8 μm), and the mobile phase is methanol-water (containing 0.1% formic acid). The linear range is 2.5~2000ng / mL. This method was used to study the pharmacokinetic characteristics of iCRT14 after intravenous and intraperitoneal administration in mice.

[0102] experimental method:

[0103] 1. 24 C57BL / 6J mice aged 7-8 weeks were randomly divided into two groups: intravenous injection group (Iv) and intraperitoneal injection group (Ip). The injection solution is dis...

technical field

[0001] The invention relates to a new application of a compound in the preparation and treatment of type 2 diabetic cardiomyopathy, especially the new application of iCRT14 in the preparation of a drug for the treatment of type 2 diabetic cardiomyopathy. Background technique

[0002] Diabetes mellitus (DM) is a chronic disease that occurs when the body cannot secrete or not secrete enough insulin or cannot effectively use insulin, resulting in elevated glucose levels in the blood. According to the latest diabetes map statistics released by the International Diabetes Federation, my country currently has 116.4 million diabetic patients (not included in the data of Hong Kong, Macao and Taiwan), ranking first in the world. The incidence of diabetes in adults in mainland China is close to 10%. In 2019 alone, the number of patients who died of diabetes and its complications in my country was 830,000. Among them, the proportion of patients who died under the age of ...

Examples

Embodiment 1

[0028] Example 1 Effect test of the compound (iCRT14) of the present invention in the treatment of type 2 diabetic cardiomyopathy 1. Experimental method

[0029] 1. Construction of animal models of type 2 diabetes

[0030]Select 3-4 week-old C57BL / 6J male mice as the test subjects, after 2 weeks of high-fat diet, intraperitoneally inject STZ (85mg / kg), inject once every other day, fast for 12h before intraperitoneal injection, and avoid light The injection was completed within 30 minutes, and the animal model of type 2 diabetes was constructed, followed by high-fat feeding. The random blood glucose of mice ≥ 16.7mmol / L can be used as a model group for experiments. Mice of the same age and sex are the normal control group (Control group, CON) , mice in the normal control group had normal diet and free access to water.

[0031] 2. Main solution configuration

[0032] (1) iCRT14 suspension injection: Weigh the injection dose, add 20% PEG300 and 80% PBS solution, and mix on a vo...

Embodiment 2

[0099] Embodiment 2 Compound (iCRT14) described in the present invention pharmacokinetic detection test in mice

[0100] At present, the data on the pharmacokinetics of iCRT14 is extremely limited. We established and verified a sensitive and highly selective method to detect the concentration of iCRT14 in mouse plasma for the study of iCRT14 pharmacokinetics.

[0101] In this example, the analyte was protein precipitated with methanol. The LC-ESIMS / MS method uses an Agilent Eclipse Plus C18 column (2.1 mm×50 mm, 1.8 μm), and the mobile phase is methanol-water (containing 0.1% formic acid). The linear range is 2.5~2000ng / mL. This method was used to study the pharmacokinetic characteristics of iCRT14 after intravenous and intraperitoneal administration in mice.

[0102] experimental method:

[0103] 1. 24 C57BL / 6J mice aged 7-8 weeks were randomly divided into two groups: intravenous injection group (Iv) and intraperitoneal injection group (Ip). The injection solution is dis...

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