Joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid as well as preparation method and application of joint injection preparation

A hyaluronic acid and peptide-binding technology, which is applied in pharmaceutical formulations, medical science, prostheses, etc., can solve the problems of multiple injections and repeated administration, joint injection preparations and damaged cartilage surfaces cannot be combined, and achieve good resistance Non-specific adsorption properties, effects of overcoming insufficient lubricating properties, good feasibility and practicality

Active Publication Date: 2020-09-25
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] At present, no synthetic collagen-binding peptides have been found to modify hyaluronic acid, and then prepare joint injection preparations for the treatment of cartilage damage, so as to o

Method used

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  • Joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid as well as preparation method and application of joint injection preparation
  • Joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid as well as preparation method and application of joint injection preparation
  • Joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid as well as preparation method and application of joint injection preparation

Examples

Experimental program
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Effect test

Embodiment 1

[0034] 1) Preparation of collagen-binding polypeptide-modified hyaluronic acid:

[0035] Prepare a 10 mmol / L phosphate buffer solution with pH=7.4 with disodium hydrogen phosphate dodecahydrate and potassium dihydrogen phosphate. Dissolve 1.2g of hyaluronic acid (HA) in 120mL of the above phosphate buffer, adjust the pH of the solution to 5 with 1.0mol / L hydrochloric acid, and then add 1-ethyl-(3-dimethylamino Propyl) carbodiimide hydrochloride (1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and hyaluronic acid repeating unit molar ratio is 1:1), after stirring for 20min Collagen-binding polypeptides were added (the molar ratio of collagen-binding polypeptides to hyaluronic acid repeating units was 1:1), the pH of the solution was maintained at 5 with 1 mol / L hydrochloric acid, and the reaction was stirred at 20° C. for 1 hour. The reacted solution was placed in a dialysis bag (MWCO: 8000-14000Da), and dialyzed in an aqueous solution with pH=5.0 for 2 days, and th...

Embodiment 2

[0053] 1) Preparation of collagen-binding polypeptide-modified hyaluronic acid:

[0054] Prepare a 10 mmol / L phosphate buffer solution with pH=7.4 with disodium hydrogen phosphate dodecahydrate and potassium dihydrogen phosphate. Dissolve 1.2g of hyaluronic acid (HA) in 120mL of the above phosphate buffer, adjust the pH of the solution to 5.5 with 1.0mol / L hydrochloric acid, and then add 1-ethyl-(3-dimethylamino Propyl) carbodiimide hydrochloride (1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and hyaluronic acid repeating unit molar ratio is 1:1), after stirring for 25min Collagen-binding polypeptides were added (the molar ratio of collagen-binding polypeptides to hyaluronic acid repeating units was 2:1), the pH of the solution was maintained at 5.5 with 1 mol / L hydrochloric acid, and the reaction was stirred at 25°C for 2 hours. The reacted solution was placed in a dialysis bag (MWCO: 8000-14000Da), and dialyzed in an aqueous solution with pH=5.0 for 2 days, and...

Embodiment 3

[0070] 1) Preparation of collagen-binding polypeptide-modified hyaluronic acid:

[0071] Prepare a 10 mmol / L phosphate buffer solution with pH=7.4 with disodium hydrogen phosphate dodecahydrate and potassium dihydrogen phosphate. Dissolve 1.2g of hyaluronic acid (HA) in 120mL of the above phosphate buffer, adjust the pH of the solution to 6 with 1.0mol / L hydrochloric acid, and then add 1-ethyl-(3-dimethylamino Propyl) carbodiimide hydrochloride (1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and hyaluronic acid repeating unit molar ratio is 1:1), after stirring for 30min Collagen-binding polypeptides were added (the molar ratio of collagen-binding polypeptides to hyaluronic acid repeating units was 3:1), the pH of the solution was maintained at 6 with 1 mol / L hydrochloric acid, and the reaction was stirred at 30°C for 3 hours. The reacted solution was placed in a dialysis bag (MWCO: 8000-14000Da), and dialyzed in an aqueous solution with pH=5.0 for 2 days, and the...

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Abstract

The invention discloses a joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid as well as a preparation method and application of the joint injection preparation.The method comprises the following steps: firstly, designing and synthesizing a polypeptide molecule capable of being combined with collagen, then grafting modified hyaluronic acid through amidationreaction, and then embedding the hyaluronic acid to the surface of a cartilage matrix through the specific recognition binding effect of the collagen binding polypeptide and cartilage surface II typecollagen so as to obtain the joint injection preparation based on collagen binding polypeptide-modified hyaluronic acid. The joint injection preparation not only can specifically bind the hyaluronic acid to the surface of damaged cartilage tissue, but also endows the surface of the damaged cartilage with excellent non-specific adsorption resistance and lubricating property, and can be used for preparing cartilage repair materials, treating osteoarthritis and improving anti-inflammatory factors and lubricating property of the surface of the damaged cartilage; and the joint injection preparationcan also be used as a modified material for improving the friction performance of cartilage repair materials.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and relates to a joint injection preparation, in particular to a joint injection preparation based on collagen-binding polypeptide-modified hyaluronic acid, a preparation method and application thereof. Background technique [0002] Arthritis is one of the most common chronic diseases, and arthritis caused by acute and chronic cartilage tissue damage is recognized as a disabling disease in the world, and its incidence rate accounts for about 30% of patients with arthritis diseases, and its treatment has not yet been overcome world problems. The traditional surgical treatment methods for arthritis caused by acute and chronic cartilage tissue injury mainly include arthroscopic irrigation, microfracture, and arthrodesis. Although some potential drugs are being tested in clinical trials, they can only reduce the suffering of patients in the short term, but cannot fundamentally improve or treat os...

Claims

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Application Information

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IPC IPC(8): A61L27/24A61L27/20A61L27/50
CPCA61L27/20A61L27/24A61L27/50A61L2400/06A61L2400/10A61L2430/06C08L5/08
Inventor 苏荣欣黄仁亮袁慧崔美齐崴
Owner TIANJIN UNIV
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