Application of epidermal growth factor receptor blocking agent to preparation of medicine for treating osteoarthritis

A technology of epidermal growth factor and receptor blockers, which is applied in the field of application of epidermal growth factor receptor blockers, can solve problems such as cartilage destruction, long-term clinical application, and one-way regulation of osteoarthritis, and achieve relief of osteoarthritis. Arthritis, good clinical efficacy, effect of promoting expression

Inactive Publication Date: 2015-01-07
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Blockers of related signaling pathways such as TGF-β, PI3K-mTOR, Wnt and inflammatory factors are widely used in the treatment of osteoarthritis, but they are only limited to the basic experimental stage, which is far from the final clinical application, even if it can be used in the end Clinically, a huge economic price is also required, and the regulation of these signaling pathways on osteoarthritis is unidirectional, that is, mainly blocking the factors that destroy cartilage

Method used

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  • Application of epidermal growth factor receptor blocking agent to preparation of medicine for treating osteoarthritis
  • Application of epidermal growth factor receptor blocking agent to preparation of medicine for treating osteoarthritis
  • Application of epidermal growth factor receptor blocking agent to preparation of medicine for treating osteoarthritis

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Embodiment 1

[0047] Example 1 Microsphere preparation and characterization detection

[0048] The invention adopts the method of emulsion polymerization to prepare chitosan microspheres: firstly, the chitosan is dissolved with 2% glacial acetic acid aqueous solution to prepare a 0.02 g / ml chitosan solution. Secondly, synthetic emulsification system: Measure 20ml of chitosan solution, add 1mg of gefitinib to it, mix well and set aside, stir in a constant temperature water bath at 40°C, and keep the stirring speed at 800-1000rpm / min during the entire emulsification process. To make the system uniform and form an emulsified system. Then, 5 ml of cross-linking agent glutaraldehyde was added to the emulsification system, kept at 40° C., and stirred for reaction. After the cross-linking reaction is over, let it stand for 30 minutes, remove the upper layer after complete separation, wash the lower layer particles with petroleum ether and isopropanol three times, and then freeze-dry at -109°C to ...

Embodiment 2

[0051] Change gefitinib into erlotinib in embodiment 1, and other operations are the same as embodiment 1, and obtain erlotinib / chitosan microspheres, and the scanning electron microscope sees Figure 4 Shown, sustained release performance see Figure 5 shown.

Embodiment 3

[0052] The application of embodiment 3 gefitinib / chitosan microspheres

[0053] 1. Animal model establishment:

[0054] ① Anesthesia: Calculated at 40 mg / kg, intraperitoneally anesthetized with 1% sodium pentobarbital.

[0055] ② Prepare the mouse knee joint skin in a sterile environment, disinfect it with 2% iodophor, cut an incision about 0.5 cm in size along the medial edge of the patellar ligament, and expose the knee joint layer by layer, and use microsurgical instruments under a microscope The anterior cruciate ligament of the knee was cut off, disinfected immediately, and sutured. In the sham operation group, only the knee joint was exposed and sutured with disinfection.

[0056] 2. Grouping of experimental animals:

[0057] 36 of 40 C57BL / 6J mice were randomly selected for model establishment, and were randomly divided into 6 groups (6 mice in each group): osteoarthritis group, chitosan microsphere group, gefitinib / chitosan group Sugar microsphere low dose group (1...

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Abstract

The invention discloses application of an epidermal growth factor receptor blocking agent to preparation of a medicine for treating osteoarthritis. The epidermal growth factor receptor blocking agent is gefitinib or erlotinib. Gefitinib / chitosan microspheres are favorable in dispersion and smooth in surface, has the drug slow-release performance and mouse articular cavity biocompatibility, can effectively relieve mouse osteoarthritis, promotes the expression of mouse osteoarthritis knee joint collagen II and inhibits the expression of MMP-13; besides, gefitinib is a clinical medicine, is widely used for treating the non-small cell lung cancer, and obtains excellent clinical curative effects, so that the extremely high economic cost and the long research and development period, which are required for medicine research and development, are reduced and shortened respectively; and owing to the dosing way of sustained-release medicine delivery, the local medicine concentration can be improved while corresponding side effects caused by whole-body medicine application are reduced, and a clinical application prospect is achieved.

Description

(1) Technical field [0001] The invention relates to the application of an epidermal growth factor receptor blocking agent, in particular to the application of the epidermal growth factor receptor blocking agent in preparing medicine for treating osteoarthritis. (2) Background technology [0002] Osteoarthritis (OA) is a chronic joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. The disease occurs frequently after middle age. Preliminary surveys in China show that the overall prevalence of osteoarthritis is about 15%, the prevalence of people aged 40 is 10%-17%, and the prevalence of people over 60 is 50%. And among people over the age of 75, 80% have osteoarthritis. The final disability rate of the disease is 53%. Clinically, joint swelling and pain, bone hyperplasia and limited mobility are the most common. The incidence of osteoarthritis has no regional and racial differences. Age, obesity, inflammation, trauma and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5377A61K31/517A61K9/16A61K9/19A61K47/36A61P19/02A61P29/00
CPCA61K31/5377A61K9/5036A61K31/517
Inventor 欧阳宏伟吴岩熊思王俊娟邹晓辉
Owner ZHEJIANG UNIV
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