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Herba andrographitis lactone decalin structural modified derivative series I as well as preparation method and application thereof

A technology of andrographolide and decalin, applied in the field of medicine, can solve problems such as lack of effective prevention and treatment methods, and achieve the effects of expanding the range of options, good application and development prospects, and improving myocardial fibrosis.

Pending Publication Date: 2019-05-10
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Statistics show that the 5-year survival rate is less than 50%, and the 10-year survival rate is about 30%. At present, there is still a lack of effective prevention and treatment methods

Method used

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  • Herba andrographitis lactone decalin structural modified derivative series I as well as preparation method and application thereof
  • Herba andrographitis lactone decalin structural modified derivative series I as well as preparation method and application thereof
  • Herba andrographitis lactone decalin structural modified derivative series I as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 Compounds of the present invention inhibit the migration of human hepatic stellate cells LX-2

[0037] Under the stimulation of various inflammatory mediators, growth factors and other cytokines, hepatic stellate cells migrate to the inflammatory site of damaged liver tissue, and then proliferate, activate, and synthesize collagen and other ECM components, which are the key to the occurrence and development of liver fibrosis. Therefore, the anti-hepatic fibrosis effect of the compounds of the present invention was evaluated by the scratch injury method.

[0038] 1) Cell culture and test compounds

[0039] Using human hepatic stellate cell LX-2 (provided by Beijing Beina Chuanglian Institute of Biotechnology), compared with andrographolide, the in vitro anti-hepatic fibrosis effect of the compound of the present invention was studied. LX-2 cells were cultured in RPMI1640 medium containing 10% (V / V) fetal bovine serum, 100 μg / mL streptomycin, and 100 IU / mL penici...

Embodiment 2

[0047] Example 2 The compounds of the present invention inhibit the mesenchymal transition of human type II alveolar epithelial cells A549 induced by TGF-β1

[0048] The type II alveolar epithelial cells existing in the alveoli are stimulated by cytokines such as inflammatory mediators and growth factors, and the cell shape changes from cobblestone-like to spindle-like, completes epithelial-mesenchymal transition (EMT), and has the function of mesenchymal cells. , and then synthesize collagen fibers, and the deposition of a large number of collagen fibers can aggravate the course of interstitial pulmonary fibrosis. Therefore, the morphological observation method was used to evaluate the anti-pulmonary fibrosis effect of the compounds of the present invention.

[0049] 1) Cell culture and drug treatment

[0050] Using human type II alveolar epithelial cells A549, compared with andrographolide, the in vitro anti-pulmonary fibrosis effect of the compounds of the present inventio...

Embodiment 3

[0058] Example 3 The compounds of the present invention inhibit the mesenchymal transition of human proximal tubular epithelial cells HK-2 induced by TGF-β1

[0059] Early studies found that renal tubular epithelial cells can transdifferentiate into fibroblasts and express their marker protein fibroblast-specific protein 1 (FSP1, fibroblast-specific protein 1). one of the important pathogenic mechanisms of Therefore, the anti-renal fibrosis effect of the compounds of the present invention was evaluated by morphological observation after stimulation with TGF-β1.

[0060] 1) Cell culture and test drugs

[0061] Using human proximal tubular epithelial cells HK-2 (provided by the China Center for Type Culture Collection), compared with andrographolide AD, the in vitro anti-renal fibrosis effect of the compounds of the present invention was studied. HK-2 cells were cultured in DMEM-F12 medium containing 10% fetal bovine serum (V / V), 100 μg / mL streptomycin, and 100 IU / mL penicilli...

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Abstract

The invention belongs to the technical field of medicines, and discloses an application of herba andrographitis lactone decalin derivatives in preparing drugs for preventing and treating various tissue and organ fibrosis of human bodies, and relates to herba andrographitis lactone decalin structural modified derivatives. The herba andrographitis lactone decalin structural modified derivative has astructure as shown in general formula I. Experiments show that the compounds can significantly inhibit the migrating activation of hepatic stellate cells, can significantly inhibit the mesenchymal transition of TGF-beta 1 induced human alveolar type-II epithelial cells A549, can significantly inhibit the mesenchymal transition of renal cortex proximal convoluted tubule epithelial cells HK-2, andcan significantly inhibit the migration of Angiotensin II (AngII) induced human heart myofibroblast HCFB. The compounds are used as active ingredients to prepare fibrosis-resisting drugs and are efficient and low in toxicity, and can provide a novel drug way for treating and preventing fibrosis related diseases, thereby enlarging the selection range of clinical medication, and having good application and development prospect. (Shown in the description).

Description

technical field [0001] The invention relates to andrographolide derivatives, a synthesis method and their application as anti-human tissue and organ fibrosis drugs, in particular to andrographolide decalin structure-modified derivatives, belonging to the technical field of medicine. Background technique [0002] Human tissue and organ fibrosis is a chronic disease that occurs mostly in the liver, lung, heart, kidney and other parts. One-third of people worldwide die from tissue fibrosis and the resulting organ failure. Fibrosis is caused by persistent damage to epithelial tissue, which stimulates the over-proliferation of related effector cells, causing the extracellular matrix (ECM). A large amount of deposition, tissue fibrosis occurs, and eventually leads to a disease in which the tissue gradually loses its biological function. Organs with more epithelial tissue composition are more susceptible, so fibrosis is more common in organs such as liver, lung, kidney, and heart....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/58C07D417/06C07D405/06C07D493/10A61P1/16A61P11/00A61P13/12A61P9/00
Inventor 徐海伟戴桂馥张晓沛李博黄瑞彬张贺峰吴健刘梓晗张迪
Owner ZHENGZHOU UNIV
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