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Hydrogel loaded with bone morphogenetic protein, preparation method and application

A hydrogel and protein technology, applied in the fields of pharmaceutical formula, medical science, prosthesis, etc., can solve the problems of poor biocompatibility, immunogenicity, insufficient reaction conditions, cytotoxicity, etc., shorten the molding time and improve the utilization rate, promote the effect of repair

Inactive Publication Date: 2021-03-19
SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing technologies mostly use hydrogels to compound with BMP-2, but the reaction conditions are often not mild enough, or the cross-linked hydrogels will have certain cytotoxicity, and there are problems such as poor biocompatibility or immunogenicity

Method used

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  • Hydrogel loaded with bone morphogenetic protein, preparation method and application
  • Hydrogel loaded with bone morphogenetic protein, preparation method and application
  • Hydrogel loaded with bone morphogenetic protein, preparation method and application

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preparation example Construction

[0035] The invention provides a method for preparing a hydrogel loaded with bone morphogenic protein, comprising: mixing and reacting a cross-linking agent, a water-soluble natural degradable polymer, and bone morphogenic protein in a liquid for injection or an aqueous buffer solution to obtain a bone-loaded gel. A protein hydrogel is formed.

[0036] The bone morphogenic protein includes more than 30 related proteins, such as BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, etc., the bone morphogenic protein described in this application It is one or a mixture of two or more of the 30 related proteins.

[0037] The crosslinking agent is 1,4 butanediol diglycidyl ether, glutaraldehyde, N-hydroxysuccinimide ester, carbodiimide, genipin, cystamine, hexamethylene isodicyanate, azide One or more of nitrogen diphenylphosphine, polyethylene glycol diacrylate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[0038] The water-soluble natural degradable polymer is one o...

Embodiment 1

[0068] (1) Sterilization of raw materials

[0069] The polyglutamate powder with a weight-average molecular weight of 1.5 million Daltons was sterilized by irradiation with gamma-rays at a sterilization dose of 6 kGy.

[0070] (2) Preparation of hydrogel

[0071] The following procedures were performed under sterile conditions.

[0072] Dissolve 0.01 mL of 1,4-butanediol diglycidyl ether in 5 mL of double-distilled water, and add 2.5 mg of BMP-2 protein. Weigh 0.25 g of the sterilized polyglutamate powder with a weight-average molecular weight of 1.5 million Daltons, add it to the above solution, stir evenly, let stand for a while until the bubbles disappear, and keep warm at 37°C for 10 hours.

[0073] The release rate of bone morphogenetic protein in the products prepared by this method was 3.17%, 14.84%, 32.06%, 50.15%, 65.02%, 71.91%, 78.73% respectively on the 2d, 5d, 10d, 15d, 20d, 25d, and 30d; The porosity (area / total area occupied by pores) of the product reaches 9...

Embodiment 2

[0075] (1) Sterilization of raw materials

[0076] Hyaluronic acid with a weight-average molecular weight of 2.5 million Daltons was sterilized by irradiation with gamma-rays, and the sterilization dose was 10 kGy;

[0077] (2) Preparation of hydrogel

[0078] The following procedures were performed under sterile conditions.

[0079] Dissolve 0.05 mL of glutaraldehyde in 5 mL of borate buffer, and add 25 mg of BMP-2. Weigh 1.0 g of the sterilized hyaluronic acid with a weight-average molecular weight of 2.5 million Daltons, add it to the above solution, stir evenly, let it stand still for a while until the bubbles disappear, and keep warm at 60° C. for 2 hours.

[0080] The release rate of the bone morphogenic protein of the product prepared by this method on the 2d, 5d, 10d, 15d, 20d, 25d, and 30d was 2.00%, 13.00%, 30.00%, 48.00%, 63.0%, 70.0%, and 76.0% respectively; The porosity (area / total area occupied by pores) of the product reaches 97%; the cell proliferation rate ...

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Abstract

The invention relates to the field of biological tissue engineering, in particular to hydrogel loaded with bone morphogenetic protein, a preparation method and application. The method comprises the following steps: mixing and reacting a cross-linking agent, a water-soluble natural degradable polymer and bone morphogenetic protein in liquid for injection or a water-based buffer solution to obtain the hydrogel loaded with bone morphogenetic protein. The hydrogel loaded with the bone morphogenetic protein prepared by the method has good biocompatibility and biodegradability, and avoids taking outan implant material in a secondary operation.

Description

technical field [0001] The invention relates to the field of biological tissue engineering, and more specifically relates to a hydrogel loaded with bone morphogenic protein, a preparation method and application. Background technique [0002] Currently, bone injury caused by trauma, infection, tumor or congenital genetic disease is a common orthopedic disease. Bone tissue itself has a certain ability of self-repair and regeneration. However, large-area bone defects need to be treated by external intervention, and its regenerative repair is still a major challenge in clinical medicine. At present, autologous bone transplantation and allogeneic bone transplantation are common methods for treating bone injuries. As the gold standard, autologous bone grafting has the three characteristics of osteoconduction, osteoinduction, and bone regeneration, but the amount of autologous bone is greatly limited, and there are problems such as large trauma, long operation time and high risk f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/075C08L77/04C08L5/08C08L5/02C08L89/00A61L27/52A61L27/50A61L27/54A61L27/26
CPCC08J3/246C08J3/075A61L27/52A61L27/50A61L27/54A61L27/26C08J2377/04C08J2305/08C08J2305/02C08J2489/00A61L2400/06A61L2300/252A61L2300/412A61L2430/02C08L89/00C08L5/00C08L5/08C08L77/04
Inventor 刘飞张秀华孙婷凌沛学陈勉邵华荣刘霞刘英梅郭新艳何小华
Owner SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES