Histone deacetylase inhibitor for preparing medicaments for treating multi-organ damage

A technology of deacetylase and pharmaceutical preparations, applied in the directions of drug combinations, medical preparations containing active ingredients, antidote, etc., can solve the problems of lack of HDACi or coenzyme Q10, etc., and achieve improved cell survival, good therapeutic effect, and improved The effect of cure rate

Active Publication Date: 2014-09-24
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the prior art still lacks the application of HDACi or coenzyme Q10 in the treatment and / or prevention of multiple organ damage, as well as the pharmaceutical preparations of combined drugs with synergistic effects

Method used

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  • Histone deacetylase inhibitor for preparing medicaments for treating multi-organ damage
  • Histone deacetylase inhibitor for preparing medicaments for treating multi-organ damage
  • Histone deacetylase inhibitor for preparing medicaments for treating multi-organ damage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1. The protective effect of HDACi on cell damage

[0053] This example adopts four cell models of sodium disulfite chemical hypoxia, cobalt chloride chemical hypoxia injury, physical hypoxia injury and oxidative stress injury to prove that sodium valproate, chidamide, vorinostat and other HDACi have Protective effects of multiple injured organ tissues (including myocardium, liver and lung), and then explore the possibility of HDACi being used to prepare drugs for the treatment of multiple organ injuries.

[0054] 1.1 Experimental method

[0055] 1.1.1 Cell lines: rat cardiomyocytes H9C2, human normal liver cells HL-7702 and human normal embryonic lung fibroblasts MRC-5.

[0056] 1.1.2 Effect of sodium valproate on cell proliferation: H9C2, HL-7702 and MRC-5 cells were cultured in a 96-well culture plate with Hyclone high-glucose serum medium containing 10% fetal bovine serum. Different concentrations of sodium valproate low-sugar DMEM solution were added to th...

Embodiment 2

[0068] Example 2.HDACi improves the detection of mitochondrial respiratory energy metabolism

[0069] In this example, a cell bioenergy analyzer was used to detect the effect of HDACi on basic metabolism, ATP generation and limit respiration capacity of cardiomyocytes, and to explore the mechanism of HDACi protecting cells by regulating mitochondrial energy metabolism when cells are damaged.

[0070] 2.1 Experimental method:

[0071]Inoculate 10,000 H9C2 rat cardiomyocytes per well in a special culture plate for XF cell bioenergy analyzer, and measure the oxygen consumption rate (OCR) of the cells. Four positions A1, B4, C3, and D6 were reserved in each 24-well microwell plate, and an equal volume of culture medium was placed for background correction. After the cells were attached, an appropriate amount of medium was added to each well, and then the cell culture plate was placed in a carbon dioxide incubator for overnight culture for hydrogen peroxide damage. After the damag...

Embodiment 3

[0076] Example 3. HDACi and coenzyme Q10 prevent and treat multiple organ damage animals

[0077] In this example, the rat model of multiple organ injury caused by acute severe blood loss was used to observe the preventive and therapeutic effects of HDACi alone and the combination of HDACi and coenzyme Q10 on multiple organ injury, and then confirmed that HDACi and coenzyme Q10 were used in the preparation of multiple organ injury Possibility of preventive and curative medicines.

[0078] 3.1 Experimental method

[0079] 3.1.1 Experimental animals: male Wistar rats, 12 in each test group, with an average body weight of 250 g, provided by Beijing Weitong Lihua Experimental Animal Co., Ltd.

[0080] 3.1.2 Experimental equipment and articles: multi-conductor physiological apparatus, constant flow pump BT00-50M, isoflurane, drainage tube, normal saline, sodium valproate, etc.

[0081] 3.1.3 Experimental process:

[0082] The animal model of multiple organ injury caused by acute...

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Abstract

The invention discloses an application of a histone deacetylase inhibitor in preparation of medicaments for treating and / or preventing multi-organ damage, and a medicinal preparation for treating and / or preventing multi-organ damage, wherein the preparation comprises effective treatment amount of the histone deacetylase inhibitor and coenzyme Q10. The medicinal preparation has significant treatment effect on multi-organ damage.

Description

technical field [0001] The invention relates to a medicine for treating and / or preventing multiple organ damage, belonging to the field of emergency medicine. Background technique [0002] Heart failure, acute lung injury, blood loss, burns, cardiovascular and cerebrovascular diseases, severe trauma, drowning, electric shock and other diseases often lead to multiple organ damage. In the early stage of injury, hypoxia, oxidative stress injury, and energy metabolism disorder mainly occurred in important vital organs. If not actively and effectively treated, it will lead to a series of serious consequences, such as ischemia-reperfusion injury, disseminated intravascular coagulation, acute respiratory distress syndrome, resulting in extremely high mortality in the later period. Protecting the survival and function of cells when multiple organs are injured is the key to preventing the progression of the disease and improving the cure rate of the disease. Broad-spectrum cytoprote...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/19A61K31/122A61P3/00A61P9/06A61P7/04A61P9/10A61P9/00A61P11/00A61P9/04A61P17/02A61P39/00
Inventor 于群何跃忠李伟静任素萍王璇琳王春燕贺敏苏丽华张公庆谢楠
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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