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Use of hydrogen sulfide and its donor sodium hydrosulfide in the production of medicaments

A sodium hydrosulfide, a technology for preparing medicines, applied in the direction of medicine combination, sulfur/selenium/tellurium active ingredients, anti-toxic agents, etc., can solve the problems of ischemic electrocardiogram not obvious, unsatisfactory curative effect, trauma, etc., to achieve Inhibition of transmembrane calcium currents in cardiomyocytes

Inactive Publication Date: 2007-08-08
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These drugs have a certain curative effect, but they cannot control the development of the disease, and also produce side effects such as headache, palpitation, lower limb edema, conduction block, and liver and kidney function damage, and are prone to relapse after stopping the drug.
Currently more advanced methods such as coronary intervention, coronary stent, coronary artery resection, myocardial perforation and coronary artery bypass grafting, some patients have better postoperative effect, but there are still 30% to 50% of patients with postoperative recurrence. narrow
In addition, it is expensive and traumatic, which also makes patients have doubts
The current Chinese patent medicine preparations on the market, such as: Compound Danshen Tablets, Di'ao Xinxuekang Capsules, Compound Danshen Dropping Pills and other Chinese patent medicines, these drugs do not improve the ischemic electrocardiogram obviously, and cannot control the development of coronary heart disease, and the curative effect is still unsatisfactory

Method used

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  • Use of hydrogen sulfide and its donor sodium hydrosulfide in the production of medicaments
  • Use of hydrogen sulfide and its donor sodium hydrosulfide in the production of medicaments
  • Use of hydrogen sulfide and its donor sodium hydrosulfide in the production of medicaments

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1H 2 S and its donor NaHS reduce the size of myocardial infarction and reduce the death rate of myocardial infarction

[0053] Eighty Wistar rats were randomly divided into 3 groups and given NaHS (H 2 S donor) 14 μmol / kg / day or endogenous H 2 S production inhibitor (DL-propargylglycine, PAG,), rats in the control group were given a corresponding volume of placebo saline. One week after administration, under the condition of anesthesia, tracheal intubation and mechanical ventilation, the left anterior descending coronary artery was ligated at about 2 mm from the starting point to cause myocardial infarction. Surviving rats continued to be dosed according to the original plan, and the animals were sacrificed 48 hours later to check the size of myocardial infarction. The area of ​​myocardial infarction was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the area of ​​myocardial infarction was expressed as the percentage of infarct area in...

Embodiment 2

[0054] Example 2.H 2 S and its donor NaHS inhibit myocardial perivascular and myocardial interstitial fibrosis

[0055] As shown in Figure 2-3, the cross-sectional paraffin sections of the middle section of the left ventricle were stained with Sirius red picric acid, and red collagen was visible, which was quantified by Image Measure software. After three months of chronic administration of NaHS, in spontaneously hypertensive rats (spontaneously hypertensiverat, SHR) with daily intraperitoneal injection of 10, 30 and 90 μmol / kg NaHS, pericardial arterioles and myocardial interstitial fibrosis The degree of rats given placebo was significantly less than that of SHR rats given placebo (one-way analysis of variance: P2 In addition to the antihypertensive effect, S has the effect of directly inhibiting the fibrosis around the small blood vessels in the myocardium and the myocardial interstitial fibrosis. Reduced myocardial compliance (reduced myocardial compliance can impair card...

Embodiment 3

[0060] Example 3.H 2 S and its donor NaHS inhibit myocardial arteriolar hypertrophy

[0061] As shown in Figure 4, hematoxylin-eosin staining of the paraffin section of the mid-section of the left ventricle shows the cross-section of the arterioles in the myocardium. The cross-section of the vessel wall and the area of ​​the lumen can be quantified with the Image Measure image processing software. NaHS was injected intraperitoneally at doses of 10, 30 and 90 μmol / kg body weight daily for three months in SHR rats. In the SHR rats treated with 90 μmol / kg / day, the degree of hypertrophy of the arteriolar wall in the myocardium was significantly lower than that in the SHR rat control group given placebo (normal saline) (one-way analysis of variance: P2 In addition to the antihypertensive effect, S has the effect of directly inhibiting the hypertrophy of the wall of small arteries in the myocardium. Reducing the hypertrophy of the small artery wall in the myocardium can reduce the ...

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Abstract

The invention relates to a method for using hydrogen sulfide and relative donator as sodium bisulfide in the drug preparation. The invention uses exogenous hydrogen sulfide and relative donator as sodium bisulfide, via serial animal models and external tests to prove that said hydrogen sulfide and relative donator as sodium bisulfide can be used to treat several cardiovascular diseases, or reduce the active oxygen, accelerate the vessel growth, negative inotropic action, or calcium antagonist. Said cardiovascular diseases comprise myocardial infarction, fibrosis, or the like.

Description

technical field [0001] The invention belongs to the field of medicine and pharmacy, and relates to the application of hydrogen sulfide and its donor sodium hydrosulfide in pharmacy, in particular to the application of hydrogen sulfide and its donor sodium hydrosulfide in the preparation of drugs for treating cardiovascular diseases. Background technique [0002] Hydrogen sulfide (H 2 S) is a metabolite of cysteine ​​in the human body, and it has been reported in the literature that human endogenous H 2 The level of S is about 20-50 μmol / L. There are also reports in the literature that H 2 S can cause the expansion of vascular smooth muscle, so it is considered that H 2 S is a new type of endogenous gas molecule involved in the regulation of cardiovascular activity. Due to hydrogen sulfide (H 2 The content of S) in the body is very low, and it is not easy to be controlled artificially, so its medicinal use has not been reported in the literature so far. [0003] Accordi...

Claims

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Application Information

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IPC IPC(8): A61K33/04A61P9/00A61P9/10A61P9/12A61P3/10A61P39/00
Inventor 朱依纯朱依谆姚泰蔡文杰陈莹孙英刚石英贤姚玲玲黄晓伟丁滢泂
Owner FUDAN UNIV
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