Making method of aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis

A technology of proteoglycanase and hyaluronic acid is applied in the field of preparation of drugs for the treatment of osteoarthritis. Effect

Inactive Publication Date: 2015-09-30
ZHEJIANG UNIV
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

At present, some studies have focused on small molecule inhibitors that can inhibit ADAMTS-5

Method used

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  • Making method of aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis
  • Making method of aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis
  • Making method of aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis

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Example Embodiment

[0045] Example 1 Preparation and Characterization of Externally Linked Hyaluronic Acid Hydrogel

[0046] The present invention adopts the method of in vitro cross-linking to prepare hyaluronic acid hydrogel: (1) Hyaluronic acid aldehyde modification: 60 mg of hyaluronic acid is first dissolved in 20 ml of double distilled water, and then 218 μl of NaIO4 (10 mg / mL ) was added to the solution and reacted for two hours at room temperature, the reaction equation is shown in figure 1 . Then 0.2 ml of hexanediol was added and stirred for 1 hour to terminate the reaction. After this, the mixture was dialyzed against water for three days. Finally the product was lyophilized and stored at 4°C. The prepared aldehyde-modified hyaluronic acid was detected by infrared spectroscopy. The results of the aldehyde analysis curve showed that the oxidation reaction produced 31.66±0.117% aldehyde groups on each hyaluronic acid unit. These results illustrate that the aldehyde The radical group ...

Example Embodiment

[0050] Example 2

[0051] The mass dosage of the proteoglycanase inhibitor combined with in vitro cross-linked hyaluronic acid hydrogel is 200 μl / Kg body weight, that is, the mass dosage of the proteoglycanase inhibitor is 3 mg / Kg body weight;

[0052] Application of Proteoglycanase Inhibitors Combined with Externally Linked Hyaluronic Acid Hydrogels

[0053] 1. Animal model establishment:

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

[0055] ② Prepare the skin of the rat knee joint in a sterile environment, disinfect it with 2% povidone iodine, make an incision about 1 cm along the medial edge of the patellar ligament, cut the knee joint layer by layer, and cut it under a microscope with microsurgical instruments The anterior cruciate ligament of the knee joint was immediately sterilized and sutured. In the sham operation group, only the knee joint was exposed and sutured with disinfection.

[0056] 2....

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Abstract

The invention discloses a making method of an aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis. The making method comprises the steps of aldehyde group modification on hyaluronic acid, adipic dihydrazide modification on hyaluronic acid and in-vitro cross-linking of hyaluronic acid. The aggrecanases inhibitor combined with in-vitro cross-linked hyaluronic acid hydrogel provided by the invention has properties of sustained releasing drugs, can effectively alleviate rat osteoarthritis, promote expression of proteoglycan of osteoarthritis knees and inhibit expression of degradation products of proteoglycan. According to the making method of the aggrecanases inhibitor combined with the in-vitro cross-linked hyaluronic acid hydrogel and application thereof in drugs for treating osteoarthritis, biological materials and drugs are combined, a tissue engineering method is adopted for treating osteoarthritis, the manner of delivering drugs to articular cavities is utilized, wound caused by treatment of osteoarthritis is reduced, the sustained release drug delivery manner can improve local drug concentration while reducing corresponding side effect caused by systemic administration of drugs.

Description

technical field [0001] The invention relates to the application of a proteoglycanase inhibitor combined with externally linked hyaluronic acid hydrogel, in particular to its application in the preparation of medicines for treating osteoarthritis. Background technique [0002] Osteoarthritis is one of the most common orthopedic diseases. According to statistics, in the West alone, about 12% of the middle-aged and elderly people suffer from different degrees of osteoarthritis. In the United States, there are more than 27 million people suffering from osteoarthritis, and the prevalence rate of people over 60 years old can reach more than 50%. A study by the Center for Disease Control and Prevention of the United States and the Department of Public Health of Harvard University shows that osteoarthritis is One of the five major diseases that cause disability in older adults. Osteoarthritis is characterized by the collapse and necrosis of articular surface cartilage, accompanied ...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K31/427A61P19/02
Inventor 陈鹏飞欧阳宏伟
Owner ZHEJIANG UNIV
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