Preparation and application of a highly biocompatible biodegradable bone filling material

Abstract

The invention belongs to the technical field of biomaterials, and particularly relates to a preparation method and an application of a high-biocompatibility biodegradable bone filling material. The bone filling material is composed of polyurethane urea having phosphorylcholine at the end of a flexible side chain, and polyurethane urea is prepared from a single-ended dihydroxy polyethylene glycol phosphorylcholine compound, double-ended hydroxypolydioxanone and L-lysine diisocyanate-1,4-dibutyl diamine-L-lysine diisocyanate. The phosphorylcholine group located at the end of the flexible polyethylene glycol side chain is easily enriched on the surface of the material in order to greatly improve the hydrophilicity of the material, hinder the deposition of platelets and proteins and avoid theformation of thrombus, so the material has high biocompatibility, solves the problems of low biocompatibility and poor mechanical performances of polyurethane with the side chain simply being polyethylene glycol or phosphorylcholine, especially used a long-term implant material, in the biomedical field, and has widened applications in fields of tissue engineering, drug controlled release, gene therapy and cosmetics.

Description

technical field

[0001] The invention belongs to the technical field of biomaterials, in particular to the field of biocompatibility modification of biomedical polymer materials, in particular to the preparation and application of a highly biocompatible biodegradable bone filling material. Background technique

[0002] With the rapid development of biotechnology, biomedical materials have become a hot spot in the current scientific research field. However, in the clinical application of existing biomedical materials and devices, problems such as infection, blood coagulation, and postoperative tissue hyperplasia exist to varying degrees. These biocompatibility problems have become key factors restricting the clinical application of biomedical materials.

[0003] Phosphorylcholine (PC) is the main component of the outer membrane of biological cells. 4 - (CH 2 ) 2 N + (CH 3 ) 3 Group compounds. Phosphorylcholine is an amphiphilic molecule consisting of a hydrophilic head...

Examples

Embodiment 1

[0075] Preparation of Diisocyanate Chain Extender LBL Containing Urea Structure

[0076] Under dry nitrogen protection and mechanical stirring, add 1,4-butanediamine dropwise to L-lysine diisocyanate (-NCO:-NH 2 =8:1, molar ratio), after reacting at room temperature for 2h, add four times the volume of n-hexane to the reaction product, after stirring evenly, obtain a white solid by suction filtration, wash with n-hexane repeatedly until the filtrate IR detects that there is no -NCO absorption Peak (2270cm -1 ), vacuum-dried to constant weight to obtain white powder LBL.

Embodiment 2

[0078] Under the protection of dry nitrogen, 6.5g (5mmol) terminal dihydroxypolyethylene glycol phosphorylcholine compound (PC-(OH) 2 ,M n =1300) and 60.0g (25mmol) polydioxanone (PPDO, M n =2400) were mixed, N,N-dimethylformamide (DMF) was added to dissolve (0.5g / mL), the temperature of the reaction system was raised to 80°C, and a DMF solution (1.0g / mL) of LBL (30.6mmol) was added dropwise, After the dropwise addition, keep the temperature and continue the reaction for 4.0 hours, lower to room temperature, then add DMF to make a solution with a concentration of about 10%, settle with 8 times the volume of glacial ether, and dry the obtained solid under vacuum at 35°C to obtain high biocompatibility and biodegradability Polyurethane urea;

[0079] Dissolve the polyurethane urea in dioxane, control the mass volume concentration to 60%, stir the solution at 40° C. for 12 hours to obtain a homogeneous solution, put it into a mold (polytetrafluoroethylene) and freeze-dry to obt...

Embodiment 3

[0081] Under the protection of dry nitrogen, 6.5g (5mmol) terminal dihydroxypolyethylene glycol phosphorylcholine compound (PC-(OH) 2 ,M n =1300) and 48.0g (20mmol) polydioxanone (PPDO, M n =2400) were mixed, N,N-dimethylformamide (DMF) was added to dissolve (0.5g / mL), the temperature of the reaction system was raised to 85°C, a DMF solution (1.0g / mL) of LBL (25.8mmol) was added dropwise, After the dropwise addition, keep the temperature and continue the reaction for 3.5 hours, lower to room temperature, then add DMF to make a solution with a concentration of about 10%, settle with 8 times the volume of glacial ether, and dry the obtained solid under vacuum at 35°C to obtain high biocompatibility and biodegradability Polyurethane urea;

[0082] Dissolve the polyurethane urea in dioxane, control the mass volume concentration to 60%, stir the solution at 40° C. for 12 hours to obtain a homogeneous solution, put it into a mold (polytetrafluoroethylene) and freeze-dry to obtain ...

technical field

[0001] The invention belongs to the technical field of biomaterials, in particular to the field of biocompatibility modification of biomedical polymer materials, in particular to the preparation and application of a highly biocompatible biodegradable bone filling material. Background technique

[0002] With the rapid development of biotechnology, biomedical materials have become a hot spot in the current scientific research field. However, in the clinical application of existing biomedical materials and devices, problems such as infection, blood coagulation, and postoperative tissue hyperplasia exist to varying degrees. These biocompatibility problems have become key factors restricting the clinical application of biomedical materials.

[0003] Phosphorylcholine (PC) is the main component of the outer membrane of biological cells. 4 - (CH 2 ) 2 N + (CH 3 ) 3 Group compounds. Phosphorylcholine is an amphiphilic molecule consisting of a hydrophilic head...

Examples

Embodiment 1

[0075] Preparation of Diisocyanate Chain Extender LBL Containing Urea Structure

[0076] Under dry nitrogen protection and mechanical stirring, add 1,4-butanediamine dropwise to L-lysine diisocyanate (-NCO:-NH 2 =8:1, molar ratio), after reacting at room temperature for 2h, add four times the volume of n-hexane to the reaction product, after stirring evenly, obtain a white solid by suction filtration, wash with n-hexane repeatedly until the filtrate IR detects that there is no -NCO absorption Peak (2270cm -1 ), vacuum-dried to constant weight to obtain white powder LBL.

Embodiment 2

[0078] Under the protection of dry nitrogen, 6.5g (5mmol) terminal dihydroxypolyethylene glycol phosphorylcholine compound (PC-(OH) 2 ,M n =1300) and 60.0g (25mmol) polydioxanone (PPDO, M n =2400) were mixed, N,N-dimethylformamide (DMF) was added to dissolve (0.5g / mL), the temperature of the reaction system was raised to 80°C, and a DMF solution (1.0g / mL) of LBL (30.6mmol) was added dropwise, After the dropwise addition, keep the temperature and continue the reaction for 4.0 hours, lower to room temperature, then add DMF to make a solution with a concentration of about 10%, settle with 8 times the volume of glacial ether, and dry the obtained solid under vacuum at 35°C to obtain high biocompatibility and biodegradability Polyurethane urea;

[0079] Dissolve the polyurethane urea in dioxane, control the mass volume concentration to 60%, stir the solution at 40° C. for 12 hours to obtain a homogeneous solution, put it into a mold (polytetrafluoroethylene) and freeze-dry to obt...

Embodiment 3

[0081] Under the protection of dry nitrogen, 6.5g (5mmol) terminal dihydroxypolyethylene glycol phosphorylcholine compound (PC-(OH) 2 ,M n =1300) and 48.0g (20mmol) polydioxanone (PPDO, M n =2400) were mixed, N,N-dimethylformamide (DMF) was added to dissolve (0.5g / mL), the temperature of the reaction system was raised to 85°C, a DMF solution (1.0g / mL) of LBL (25.8mmol) was added dropwise, After the dropwise addition, keep the temperature and continue the reaction for 3.5 hours, lower to room temperature, then add DMF to make a solution with a concentration of about 10%, settle with 8 times the volume of glacial ether, and dry the obtained solid under vacuum at 35°C to obtain high biocompatibility and biodegradability Polyurethane urea;

[0082] Dissolve the polyurethane urea in dioxane, control the mass volume concentration to 60%, stir the solution at 40° C. for 12 hours to obtain a homogeneous solution, put it into a mold (polytetrafluoroethylene) and freeze-dry to obtain ...

Images