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Application of BCL-2 inhibitor and pharmaceutical composition for treating senescence-related skin diseases

A BCL-2 and inhibitor technology, applied in the field of medicine, can solve the problems of expensive biological preparations, poor patient treatment effect, and adverse reactions, etc., and achieve the effect of improving skin inflammation, skin aging, and low price.

Active Publication Date: 2021-06-04
NANCHANG ANTI SENESCENCE BIOLOGICAL & MEDICAL CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of the traditional treatment effects can only reach the short-term clinical curative effect, it is difficult to cure, and most of them are accompanied by adverse reactions of varying degrees; biological targeted therapy has higher efficacy and better safety than traditional therapy, but there are still some patients Ineffective or adverse reactions, in addition, some biological agents are expensive

Method used

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  • Application of BCL-2 inhibitor and pharmaceutical composition for treating senescence-related skin diseases
  • Application of BCL-2 inhibitor and pharmaceutical composition for treating senescence-related skin diseases
  • Application of BCL-2 inhibitor and pharmaceutical composition for treating senescence-related skin diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] 2.5mg / ml BCL-2 Inhibitor Injection

[0087] Prescription Composition:

[0088] The mass percent content is 0.25% BCL-2 inhibitor (ABT-737), 10% DMSO, 40% PEG-300, 5% Tween 80, and the balance is phosphate buffer saline (PBS).

[0089] Preparation:

[0090] Accurately weigh the components according to the prescription amount or accurately measure each component with a pipette gun; take 3 mg of BCL-2 inhibitor ABT-737 powder, add 120 μL DMSO with a pipette gun, and gently blow until ABT-737 is completely dissolved to obtain a yellow Then add 480 μL PEG300, 60 μL Tween 80, and 537 μL PBS to the above solution in sequence, and use a vortexer to vortex the above to mix evenly, and the desired yellow clear solution is obtained.

Embodiment 2

[0092] BCL-2 Inhibitor Gel

[0093] Prescription Composition:

[0094] The mass percentage content is 0.05% BCL-2 inhibitor (ABT-737), 1% DMSO, 0.5% carbomer, and the balance is purified water.

[0095] Preparation:

[0096] Accurately weigh the components according to the prescription or use a pipette gun to accurately measure each component; take 0.5g of carbomer and dissolve it in 98.5g of purified water, stir to dissolve completely, and obtain a translucent solution, and wrap it with plastic wrap in a refrigerator at 4°C Swell overnight; the next day, slowly add triethanolamine under stirring to make the pH value of the matrix 7, and obtain a transparent gel matrix for later use; take 50mg of ABT-737 powder in 1mLDMSO, and gently blow it with a pipette gun to fully dissolve it; ABT-737 The solution was transferred to the spare gel base, stirred well to make it evenly mixed, and a light yellow gel was obtained.

Embodiment 3

[0098] 0mg / ml BCL-2 Inhibitor Injection (Blank Injection)

[0099] Prescription Composition:

[0100] The mass percentage content is 10% DMSO, 40% PEG-300, 5% Tween 80, and the balance is phosphate buffer saline (PBS).

[0101] Preparation:

[0102] Accurately weigh each component according to the prescription amount or use a pipette gun to accurately measure each component; take 120 μL DMSO, add 480 μL PEG300, 60 μL Tween 80 in sequence, and then take 540 μL PBS to the above solution, and use a vortexer to vortex the above to mix evenly , that is, the desired transparent and clear solution.

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Abstract

The invention discloses application of a BCL-2 inhibitor to treatment of senescence-related skin diseases and a pharmaceutical composition for treating the senescence-related skin diseases, and belongs to the technical field of medicines. The research finds that the pharmaceutical composition containing the BCL-2 inhibitor can significantly improve skin erythema, scales and other symptoms of an imiquimod-induced psoriasis mouse model, significantly reduce the skin lesion thickness, and can reduce the expression of senescence-related proteins p16 and p21 and the mRNA expression level of genes p16, p21 and the like at the skin lesion of the psoriasis mouse model, and in addition, the pharmaceutical composition containing the BCL-2 inhibitor can significantly reduce CD4 + T cell infiltration and mRNA expression levels of skin lesion inflammatory factors such as IFN-gamma, IL-17A, IL-22, IL-23 and the like at skin lesion dermis of the psoriasis mouse model. The pharmaceutical composition is superior to a traditional intraperitoneal injection method. Therefore, the BCL-2 inhibitor and the pharmaceutical composition can effectively improve the condition of the psoriasis mouse model, and have the prospect of being developed into drugs for treating psoriasis and the senescence-related skin diseases.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of BCL-2 inhibitors and a pharmaceutical composition for treating aging-related skin diseases. Background technique [0002] Cell senescence refers to the change process in which the cell proliferation and differentiation ability and physiological functions gradually decline as time goes by during the execution of life activities. Senescent cells undergo morphological and metabolic changes, chromatin remodeling, altered gene expression, cell cycle arrest, and secrete the senescence-associated secretory phenotype (SASP). Senescent cells widely exist in aging populations and disease tissues, and studies have found that senescent cells may play a key role in the occurrence and progression of many diseases, such as cancer, Alzheimer's disease, Parkinson's disease, atherosclerosis, heart disease, etc. Vascular dysfunction and inflammatory diseases, etc. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/635A61K45/06A61P17/00A61P17/06A61P17/18A61P17/04A61P17/02A61P35/00
CPCA61K31/635A61K45/06A61P17/00A61P17/06A61P17/18A61P17/04A61P17/02A61P35/00A61K9/0019A61K47/10A61K47/26A61K9/0014A61K47/18A61K47/20A61K2300/00A61K47/60A61K9/06
Inventor 陆前进吴海竞朱欢蒋娇赵明李文群
Owner NANCHANG ANTI SENESCENCE BIOLOGICAL & MEDICAL CO
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