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Pharmaceutical composition for treating heart failure with preserved ejection fraction and application of pharmaceutical composition

A heart failure and ejection fraction technology, applied in the field of medicine, can solve the problems of reducing myocardial infarction size and increasing the release of vascular endothelial relaxation factors, and achieve the effect of increasing patient compliance, reducing treatment costs, and reducing drug resistance.

Active Publication Date: 2016-07-13
SHANDONG UNIV QILU HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the process of alcohol metabolism. In recent years, it has been reported that ALDH2 has a protective effect in myocardial ischemic postconditioning. By enhancing the expression of ALDH2, it can effectively reduce the size of myocardial infarction and play a role Myocardial protection (the role of mitochondrial acetaldehyde dehydrogenase 2 in myocardial ischemic postconditioning[J]. Chinese Pharmacology Bulletin, 2010,26(8):1088-1092), one of its mechanisms is as An esterase that increases the release of nitric oxide NO, a vascular endothelial relaxation factor, and further improves myocardial blood supply and heart function. However, in the treatment of heart failure with preserved ejection fraction, there has been no literature report on the use of mitochondrial acetaldehyde dehydrogenation The activator of enzyme activity of enzyme 2 is used in combination with nitrate drugs as the main active ingredient of the drug

Method used

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  • Pharmaceutical composition for treating heart failure with preserved ejection fraction and application of pharmaceutical composition
  • Pharmaceutical composition for treating heart failure with preserved ejection fraction and application of pharmaceutical composition
  • Pharmaceutical composition for treating heart failure with preserved ejection fraction and application of pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Fifteen healthy Wistar male rats, weighing 200-220 g. After one week of adaptive feeding of the rats, 3 rats were randomly selected as the sham operation group (the surgical silk thread was passed through the abdominal aorta after laparotomy in the sham operation group, but the abdominal aorta was not ligated), and the remaining 12 rats were treated as follows: Aortic coarctation surgery to establish an animal model of heart failure with preserved ejection fraction: After skin preparation, the rats were anesthetized intraperitoneally with 3% sodium pentobarbital at 2.3ml / kg, made a midline incision under the xiphoid process, and opened the abdominal cavity in layers. Bluntly dissect the abdominal aorta below the branch of the renal artery, place the needle of a No. 9 syringe parallel to the abdominal artery, ligate the abdominal aorta and the needle with No. 4 surgical silk thread, and then withdraw the needle slowly to make the rat abdominal aorta The diameter was redu...

Embodiment 2

[0029] The method is the same as in Example 1, except that the Alda-1 group is given 6 mg / kg of Alda-1 by stomach every day; the combined drug group is given 3 mg / kg of Alda-1 and 15 mg / kg of isosorbide mononitrate by stomach every day .

[0030]The left ventricular systolic pressure and left ventricular end-diastolic pressure were detected by hemodynamics. The statistical results are shown in Table 1. Myocardial hypertrophy index was measured for whole heart mass index and left ventricular mass index, and the statistical results are shown in Table 2.

[0031] It should be noted that the rats in the model control group did not take any treatment measures, and the symptoms of heart failure gradually aggravated, and all died after 5 days. The symptoms of heart failure in rats in the combined drug group were significantly improved, and the concomitant symptoms of rats in the special combined drug group were improved most significantly. In addition, after taking the drug for 10 ...

Embodiment 3

[0040] The method is the same as in Example 1, except that the Alda-1 group is administered intragastrically with 90 mg / kg of Alda-1 every day; the combined drug group is administered with 45 mg / kg of Alda-1 and 15 mg / kg of isosorbide mononitrate .

[0041] The left ventricular systolic pressure and left ventricular end-diastolic pressure were detected by hemodynamics. The statistical results are shown in Table 1. Myocardial hypertrophy index was measured for whole heart mass index and left ventricular mass index, and the statistical results are shown in Table 2.

[0042] It should be noted that the rats in the model control group did not take any treatment measures, the symptoms of heart failure gradually aggravated, and all died after 10 days. The Alda-1 group had no obvious effect on the improvement of the rats' heart failure symptoms. The symptoms of heart failure in the combined drug group were significantly improved, and the concomitant symptoms of heart failure in the ...

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Abstract

The invention discloses a pharmaceutical composition for treating a heart failure with preserved ejection fraction. The pharmaceutical composition comprises two active components: (1) activity factors of mitochondria acetaldehyde dehydrogenase 2 enzymatic activity; and (2) a nitrate medicine. According to the pharmaceutical composition, left ventricular end diastolic pressure is effectively reduced; the symptom of myocardial hypertrophy of a heart failure patient is improved; the heart failure with preserved ejection fraction is treated; meanwhile, the tolerance of the nitrate medicine when the heart failure with preserved ejection fraction is effectively reduced; and the effective dose of each single medicine is reduced, so that the incidence rate of the side effect of the medicine is relatively low; the treatment cost is also reduced; the benefit / cost ratio of treatment is obviously improved; the compliance of a patient is increased; the living quality is obviously improved.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a pharmaceutical composition for treating heart failure with preserved ejection fraction and application thereof. Background technique [0002] Chronic heart failure (referred to as heart failure) is a clinical syndrome in which ventricular filling or ejection ability is impaired due to structural or functional abnormalities of the heart. Its main clinical manifestations are dyspnea, fatigue and fluid retention. Chronic heart failure and its acute episodes are the severe and terminal stages of various heart diseases, and are also one of the leading causes of death in heart disease patients. According to whether the left ventricular ejection fraction (LVEF) is normal, heart failure can be divided into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The prevalence and hospitalization rates of HFpEF have increased si...

Claims

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Application Information

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IPC IPC(8): A61K31/36A61K31/34A61P9/04
CPCA61K31/34A61K31/36A61K2300/00
Inventor 边圆
Owner SHANDONG UNIV QILU HOSPITAL
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