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Application of compound in preparation of osteoarthritis therapeutic drug

A technology for osteoarthritis and compounds, applied in the field of medicine, can solve the problems of limited promotion, high cost and time cost, long onset time, etc., and achieve the effects of improving the quality of life, easy dosage, and dosage control

Inactive Publication Date: 2015-09-16
SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

NSAIDs have always been one of the most prescribed drugs in the world. These drugs have obvious gastrointestinal reactions, which further restrict their use. Although COX2 selective inhibitors avoid such problems, they still have certain risks to the cardiovascular system ;Chondroprotective agents such as Weiguli, the cost of daily medication is 30 yuan / day, and the onset time is long (>3 weeks). Because of the high cost and time cost, there are certain restrictions on its promotion

Method used

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  • Application of compound in preparation of osteoarthritis therapeutic drug
  • Application of compound in preparation of osteoarthritis therapeutic drug
  • Application of compound in preparation of osteoarthritis therapeutic drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] 1. Take out the cartilage in the joints of the extremities of the 24-hour-old SD rats, and extract the chondrocytes. Passage the first passage cells for study.

[0027] 2. The cells were divided into 5 groups: control group, IL-1β group (50ng / ml, peprotech company), IP0.1 group [IL-1β+PD0325901 (0.1μM)], IP0.25 group [IL-1β +PD0325901 (0.25μM)], IP0.5 group [IL-1β+PD0325901 (0.5μM)], TNFa group (50ng / ml, peprotech company), TP0.1 group [TNFa+PD0325901 (0.1μM)], TP0 .25 group [TNFa+PD0325901 (0.25 μM)], TP0.5 group [TNFa+PD0325901 (0.5 μM)]. Among them, PD0325901 was purchased from santacruz company. The above drug concentrations and cytokines were added respectively. After 24 hours, the total cell protein was extracted for quantitative protein detection (Western blot method) MMP13 (santacruz company, product number SC-30073), Col2a1 (santacruz company, product number SC-52658) and the content of glycosaminoglycans in the cells.

[0028] 3. Quantitative protein detec...

Embodiment 2

[0031]The femoral heads of SD rats at the age of 2 weeks were taken out (at this time, the femoral heads were not calcified and were all cartilage tissues). Divided into 5 groups: control group (con group), IL-1β group (50ng / ml, peprotech company), IP0.1 group [IL-1β+PD0325901 (0.1μM)], TNFa group (50ng / ml, peprotech company), TP0.1 group [TNFa+PD0325901 (0.1 μM)]. Among them, PD0325901 was purchased from santacruz company. The above drug concentrations and cytokines were added respectively. Change the medium every 48 hours until 96 hours, take out the femoral head, fix with 4% paraformaldehyde for more than 24 hours, carry out decalcification and dehydration, tissue embedding and paraffin sectioning.

[0032] In the femoral head cartilage tissue culture experiment in vitro, it was found that the IL-1β group (50ng / ml, peprotech company) and the TNFa group (50ng / ml, peprotech company) acted on inflammatory factors for 4 days, compared with the control group (con group ) Obvi...

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Abstract

The invention discloses an application of a compound of the structural formula (I) in the preparation of an osteoarthritis therapeutic drug. Experiments prove that the compound of the structural formula (I) can significantly inhibit the expression of MMP13 induced by IL-1beta and TNFalpha, can improve the expression of collagen type II and glycosaminoglycan and is a new approach and means for treating osteoarthritis. The osteoarthritis therapeutic drug is clear in therapeutic target, has single constituent, easily controls the dosage, can be used for therapy of the osteoarthritis and can improve the quality of life of patients suffering from the osteoarthritis. Please see the structural formula (I) in the instructions.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to a new medical application of a compound, in particular to the application of compound PD0325901 in the preparation of medicines for treating osteoarthritis. Background technique [0002] The total incidence of arthritis (osteoarthritis, OA) in my country is about 13%, among which osteoarthritis is the most common, and the incidence increases with age. According to the latest statistics, among people over 60 years old, the incidence of osteoarthritis on X-ray is about 42.8% in women and 21.5% in men, and the incidence of symptomatic osteoarthritis is about 15% in women and 15% in men. About 5.6%. Osteoarthritis has become one of the main causes of functional disability and quality of life decline in middle-aged and elderly people. Due to the development of society, the improvement of medical level, and the increase of life expectancy, China will become a big country with osteoart...

Claims

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Application Information

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IPC IPC(8): A61K31/166A61P29/00A61P19/02
Inventor 丁道芳郑昱新李玲慧宋奕杜国庆庞坚赵咏芳曹月龙詹红生
Owner SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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