Injectable temperature-sensitive hydrogel capable of treating osteoarthritis

Abstract

The invention relates to an injectable temperature-sensitive hydrogel capable of treating osteoarthritis. The injectable temperature-sensitive hydrogel comprises collagen, alginate, hyaluronic acid, calcium salt and salt used for forming an alkaline environment, wherein the volume fraction of the hyaluronic acid is not less than 24%. The invention also relates to a pharmaceutical composition which contains the above injectable temperature-sensitive hydrogel capable of treating the osteoarthritis, and a pharmaceutically acceptable carrier. The hydrogel disclosed by the invention has good biocompatibility and degradability. Under a condition that a cross-linking agent is not used, the hydrogel has good injectability, flowability and curing performance, and can effectively protect the cartilago articularis shape and improve the state of the subchondral bone.

Description

technical field

[0001] The present invention relates to osteoarthritis treatment, and more particularly to an injectable temperature-sensitive hydrogel capable of treating osteoarthritis. Background technique

[0002] The subchondral bone is located under the cartilage, mainly including the subchondral cortical endplate, bone trabecular structure, blood vessels and trabecular space structure. The main biological functions are to absorb stress, buffer shock, maintain joint shape, provide nutrition for cartilage and remove metabolites . Subchondral bone and articular cartilage form a tightly combined functional unit called "osteochondral junction", which maintains the balance of the joint environment as a functional whole. The trabeculae of subchondral bone play an important role in shock absorption and support in normal joints, and may also play an important role in the nutrient supply and metabolism of cartilage. The pathological changes of bone marrow lesion (BML) in the ...

Examples

Embodiment 1

[0024] Example 1. Preparation of hydrogel

[0025] 1. Preparation of stock solutions

[0026] 1) Type I collagen stock solution: use HCl with pH=2 to prepare 5 mg / ml type I collagen;

[0027] 2) Sodium alginate stock solution: use ultrapure water to prepare 2.5% w / v sodium alginate;

[0028] 3) Hyaluronic acid stock solution: use ultrapure water to prepare a 10 mg / ml hyaluronic acid solution;

[0029] 4) Calcium pyrophosphate stock solution: use HCl with pH=2 to prepare 2 mg / ml calcium pyrophosphate solution;

[0030] 5) Sodium bicarbonate stock solution: Use ultrapure water to prepare a supersaturated sodium bicarbonate stock solution with a final concentration of 7.4 g / L.

[0031] 2. Preparation of hydrogel (hydrogel)

[0032] a) For every 5 ml of type I collagen stock solution, add 1 ul of calcium pyrophosphate and 10 mg of hydroxyapatite particles;

[0033] b) According to 60 ul NaHCO 3 , 100 ul sodium alginate, 240 ul hyaluronic acid stock solution, and 600 ul colla...

Embodiment 2

[0036] Example 2 Effect of the gel of the present invention on osteoarthritis

[0037] The SD rats were divided into two groups: model group (model) and treatment group (gel-treat). Animals underwent amputation of the anterior cruciate ligament to establish an osteoarthritis model. That is, SD rats were anesthetized and fixed on a platform, and the leg on the side to be operated was bent at 90°. Cut the superficial skin of the knee with a scalpel, and bluntly dissect the subcutaneous fascia, avoiding subcutaneous blood vessels. Cut the vastus medialis muscle from the junction where the vastus medialis muscle forms the patellar ligament, taking care to avoid intramuscular blood vessels in the vastus medialis muscle to avoid bleeding. The patella is then pushed laterally, exposing the knee joint space. The fat pad under the patella was pulled apart with micro-tweezers, and the anterior cruciate ligament was cut. After the wound was sutured, iodine tincture was applied extern...

technical field

[0001] The present invention relates to osteoarthritis treatment, and more particularly to an injectable temperature-sensitive hydrogel capable of treating osteoarthritis. Background technique

[0002] The subchondral bone is located under the cartilage, mainly including the subchondral cortical endplate, bone trabecular structure, blood vessels and trabecular space structure. The main biological functions are to absorb stress, buffer shock, maintain joint shape, provide nutrition for cartilage and remove metabolites . Subchondral bone and articular cartilage form a tightly combined functional unit called "osteochondral junction", which maintains the balance of the joint environment as a functional whole. The trabeculae of subchondral bone play an important role in shock absorption and support in normal joints, and may also play an important role in the nutrient supply and metabolism of cartilage. The pathological changes of bone marrow lesion (BML) in the ...

Examples

Embodiment 1

[0024] Example 1. Preparation of hydrogel

[0025] 1. Preparation of stock solutions

[0026] 1) Type I collagen stock solution: use HCl with pH=2 to prepare 5 mg / ml type I collagen;

[0027] 2) Sodium alginate stock solution: use ultrapure water to prepare 2.5% w / v sodium alginate;

[0028] 3) Hyaluronic acid stock solution: use ultrapure water to prepare a 10 mg / ml hyaluronic acid solution;

[0029] 4) Calcium pyrophosphate stock solution: use HCl with pH=2 to prepare 2 mg / ml calcium pyrophosphate solution;

[0030] 5) Sodium bicarbonate stock solution: Use ultrapure water to prepare a supersaturated sodium bicarbonate stock solution with a final concentration of 7.4 g / L.

[0031] 2. Preparation of hydrogel (hydrogel)

[0032] a) For every 5 ml of type I collagen stock solution, add 1 ul of calcium pyrophosphate and 10 mg of hydroxyapatite particles;

[0033] b) According to 60 ul NaHCO 3 , 100 ul sodium alginate, 240 ul hyaluronic acid stock solution, and 600 ul colla...

Embodiment 2

[0036] Example 2 Effect of the gel of the present invention on osteoarthritis

[0037] The SD rats were divided into two groups: model group (model) and treatment group (gel-treat). Animals underwent amputation of the anterior cruciate ligament to establish an osteoarthritis model. That is, SD rats were anesthetized and fixed on a platform, and the leg on the side to be operated was bent at 90°. Cut the superficial skin of the knee with a scalpel, and bluntly dissect the subcutaneous fascia, avoiding subcutaneous blood vessels. Cut the vastus medialis muscle from the junction where the vastus medialis muscle forms the patellar ligament, taking care to avoid intramuscular blood vessels in the vastus medialis muscle to avoid bleeding. The patella is then pushed laterally, exposing the knee joint space. The fat pad under the patella was pulled apart with micro-tweezers, and the anterior cruciate ligament was cut. After the wound was sutured, iodine tincture was applied extern...

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