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Application of bisindole maleimide PKC inhibitor in preparation of medicine for treating myocarditis and arrhythmia

A technology of bisindolemaleimide and indolemaleimide, which is applied in the field of bisindolemaleimide PKC inhibitors, can solve the problems of lack of effective treatment drugs, inhibition of arrhythmia and the like

Inactive Publication Date: 2020-08-18
MINJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The antiarrhythmic drugs currently in clinical use are mainly beta-receptor blockers, which play an antiarrhythmic role mainly by blocking various ion channels in cardiomyocytes, but cannot essentially inhibit arrhythmia
For long QRS complex arrhythmias, the prior art has no effective therapeutic drug

Method used

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  • Application of bisindole maleimide PKC inhibitor in preparation of medicine for treating myocarditis and arrhythmia
  • Application of bisindole maleimide PKC inhibitor in preparation of medicine for treating myocarditis and arrhythmia
  • Application of bisindole maleimide PKC inhibitor in preparation of medicine for treating myocarditis and arrhythmia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Inhibitory effect of bisindolemaleimide PKC inhibitors on the prolongation of QRS complexes in the electrocardiogram of EAM rats.

[0030] Establishment of myocarditis animal model (EAM): firstly, pig cardiac myosin was prepared for rat immunization. Take 0.3mol / L KCL solution to dissolve the purified porcine cardiac myosin to a final concentration of 10mg / mL. Take another 2 glass syringes, absorb the same amount of myosin and complete Freund's adjuvant (containing Mycobacterium tuberculosis 10 mg / mL), connect the 2 syringes through the three-way tube, blow and mix about 200 times until It is in the form of chylus and does not disperse when dropped into water, indicating that the antigen has been prepared. Inject 100 μL of the emulsion containing myosin and Mycobacterium tuberculosis into each foot pad of each rat, and the amount of myosin given to each rat is 1 mg. At 2 weeks of EAM, the electrocardiogram of the rats was detected by lead II; at the same tim...

Embodiment 2

[0033] Example 2 Effects of PKC Activators on the QRS Complex of Isolated Hearts

[0034] Take normal rats, after being anesthetized by a small animal anesthesia machine, quickly open the chest, cut the pericardium, take out the heart and place it in 4°C amended Rockwell solution, stop the heart, squeeze out the blood, trim the heart, and intubate the aorta for administration Langendorff perfusion. The electrocardiographic signal is recorded by connecting the recording electrode to the biological signal acquisition and processing system. After repulsion, the rats were stabilized in normal Rockwell's solution for 20 minutes and perfused with 50 μM PMA, while the control group was given modified Rockwell's solution. During the perfusion process, the constant temperature of the perfusate was maintained at 37°C, and oxygen containing 5% CO2 was introduced at the same time. Record the ECG signal, observe the changes of the QRS wave group, and the recorded result is image 3 as s...

Embodiment 3

[0036] Example 3 Inhibitory effect of bisindolemaleimide PKC inhibitors on abnormal morphology and distribution of Cx43 connexin induced by EAM.

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Abstract

The invention belongs to the field of medicines, and discloses an application of a bisindole maleimide PKC inhibitor in preparation of a medicine for preventing or treating myocarditis and arrhythmia.The bisindole maleimide PKC inhibitor disclosed by the invention has high efficiency and low toxicity, and the action mechanism of the bisindole maleimide PKC inhibitor is that the effect of resisting arrhythmia is achieved by inhibiting the extension of an electrocardiogram QRS wave group. In an isolated heart, the bisindole maleimide PKC inhibitor shows good pharmaceutical activity for inhibiting QRS wave group extension, and animal experiments show that the bisindole maleimide PKC inhibitor has a remarkable treatment effect on myocarditis arrhythmia. The PKC inhibitor is proposed for the first time to be used for safely and effectively treating myocarditis arrhythmia, and can be developed into clinical medicines for treating QRS wave group extension type arrhythmia.

Description

technical field [0001] The invention belongs to the application technical field of bisindolemaleimide PKC inhibitors, and specifically relates to the application of bisindolemaleimide PKC inhibitors in the preparation of drugs for treating myocarditis and arrhythmia. Background technique [0002] Arrhythmia is the external manifestation of abnormal conduction of electrical signals in myocardial cells. Malignant arrhythmia can induce sudden cardiac death in patients and seriously endanger the health of patients. In recent years, with the change of lifestyle and the increase of work pressure, the sudden death rate of young and middle-aged people has increased year by year. Pathological biopsy shows that 2-42% of patients died of sudden cardiac death induced by myocarditis. Myocarditis arrhythmia has become the main factor of sudden death in patients. At present, the treatment of myocarditis is mainly to improve the symptoms, and there is no effective treatment drug. How to pre...

Claims

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Application Information

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IPC IPC(8): A61K31/437A61P9/00A61P9/06
CPCA61K31/437A61P9/00A61P9/06
Inventor 钟春莲赵欢戚智卢余盛贾力
Owner MINJIANG UNIV
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