Submicron nucleocapsid microsphere material capable of releasing active factors on time and preparation method of submicron nucleocapsid microsphere material

Abstract

The invention relates to a submicron nucleocapsid microsphere material capable of releasing active factors on time and a preparation method of the submicron nucleocapsid microsphere material, and solves the technical problems that a conventional size effect can hardly meet clinical conversion applications based on a bone defect repair with a support material, and the ideal time-sequence cooperation of bone-formation and vessel-formation still cannot be acquired. The submicron nucleocapsid microsphere material is provided with a nuclear layer and a shell layer, wherein the nuclear layer is made of poly-dl-lactic acid, and morphogenetic protein are carried on the poly-dl-lactic acid; the shell layer is made of polylactide-glycolide, and vascular endothelial growth factors are carried on the polylactide-glycolide; the diameter mu of the microsphere material ranges from 0.4 [mu]m to 1.6 [mu]m. The invention provides the preparation method of the submicron nucleocapsid microsphere material capable of releasing the active factors on time, and can be widely used for the preparation field of the repair materials for bone defect and bone deficiency.

Description

technical field

[0001] The invention relates to a surgical repair material and a preparation method thereof, in particular to a submicron core-shell microsphere material for releasing active factors in a timely manner and a preparation method thereof. Background technique

[0002] At present, there are many patients with bone defects and loss caused by diseases, traffic accidents and sports trauma every year in the world, so the demand for bone repair materials for treatment is very large. The progress of social civilization, the development of economy, and the improvement of living standards will inevitably lead to higher and higher requirements for the speed and quality of bone repair. Bionic design is an important step for human beings to learn from nature. There is a spatiotemporal coupling of osteogenesis and angiogenesis in the process of bone regeneration and repair. This process is precisely regulated by a variety of orderly expressed growth factors. It has been pro...

Examples

Embodiment 1

[0026] (1) Weigh 0.4g poly-D,L-lactic acid (PDLLA), add 10mL trifluoroethanol solution to swell at room temperature for 1h, and then stir at 37°C for 24h to form a uniform shell solution of 2% w / v. Weigh 0.2 g of PLGA, add 10 mL of trifluoroethanol solution to swell at room temperature for 1 h, and then stir at 37° C. for 24 h to form a 4% w / v uniform core layer solution.

[0027] (2) Dissolve VEGF and BMP‐2 growth factors in ultrapure water respectively, add VEGF solution to the shell layer solution at a ratio of 10nm / ml, and add BMP‐2 solution to the core layer solution at a ratio of 100nm / ml , respectively stirred for 10 min to form a uniform and stable core and shell solution.

[0028] (3) Inject the core and shell solutions obtained in step (2) into 20mL medical syringes respectively, and place them in a coaxial electrostatic spray device to spray microspheres with a spray voltage of 15kV, a total flow rate of 0.8ml / h, and a core-shell flow rate ratio of 1. : 3, the rece...

Embodiment 2

[0032] (1) Prepare 1% w / v PDLLA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C for 24 hours; prepare 3% w / v PLGA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C 24h.

[0033] (2) Dissolve VEGF and BMP‐2 growth factors in ultrapure water respectively, add VEGF solution to the nuclear layer solution at a ratio of 10nm / ml, and add BMP‐2 solution to the nuclear layer solution at a ratio of 100nm / ml , respectively stirred for 10 min to form a uniform and stable core and core layer solution.

[0034] (3) Inject the core and layer solutions obtained in step (2) into 20mL medical syringes respectively, place them in a coaxial electrostatic spraying device to spray microspheres, the spraying voltage is 15kV, the total flow rate is 0.8ml / h, and the core-shell flow rate ratio is 1: 4. The receiving board distance is 20cm.

[0035] (4) Dry the product obtained in step (3) in a vacuum freeze dryer ...

Embodiment 3

[0038] (1) Prepare 1% w / v PDLLA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C for 24 hours; prepare 3% w / v PLGA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C 24h.

[0039] (2) Dissolve BMP-2 and VEGF growth factors in ultrapure water respectively, add BMP-2 solution to the nuclear layer solution at a ratio of 100nm / ml, and add VEGF solution to the nuclear layer solution at a ratio of 10nm / ml , respectively stirred for 10 min to form a uniform and stable core and core layer solution.

[0040] (3) Inject the core and layer solutions obtained in step (2) into 20mL medical syringes respectively, place them in a coaxial electrostatic spraying device to spray microspheres, the spraying voltage is 15kV, the total flow rate is 0.8ml / h, and the core-shell flow rate ratio is 1: 2.

[0041] (4) Dry the product obtained in step (3) in a vacuum freeze dryer for 24 hours, and store it sealed at -...

technical field

[0001] The invention relates to a surgical repair material and a preparation method thereof, in particular to a submicron core-shell microsphere material for releasing active factors in a timely manner and a preparation method thereof. Background technique

[0002] At present, there are many patients with bone defects and loss caused by diseases, traffic accidents and sports trauma every year in the world, so the demand for bone repair materials for treatment is very large. The progress of social civilization, the development of economy, and the improvement of living standards will inevitably lead to higher and higher requirements for the speed and quality of bone repair. Bionic design is an important step for human beings to learn from nature. There is a spatiotemporal coupling of osteogenesis and angiogenesis in the process of bone regeneration and repair. This process is precisely regulated by a variety of orderly expressed growth factors. It has been pro...

Examples

Embodiment 1

[0026] (1) Weigh 0.4g poly-D,L-lactic acid (PDLLA), add 10mL trifluoroethanol solution to swell at room temperature for 1h, and then stir at 37°C for 24h to form a uniform shell solution of 2% w / v. Weigh 0.2 g of PLGA, add 10 mL of trifluoroethanol solution to swell at room temperature for 1 h, and then stir at 37° C. for 24 h to form a 4% w / v uniform core layer solution.

[0027] (2) Dissolve VEGF and BMP‐2 growth factors in ultrapure water respectively, add VEGF solution to the shell layer solution at a ratio of 10nm / ml, and add BMP‐2 solution to the core layer solution at a ratio of 100nm / ml , respectively stirred for 10 min to form a uniform and stable core and shell solution.

[0028] (3) Inject the core and shell solutions obtained in step (2) into 20mL medical syringes respectively, and place them in a coaxial electrostatic spray device to spray microspheres with a spray voltage of 15kV, a total flow rate of 0.8ml / h, and a core-shell flow rate ratio of 1. : 3, the rece...

Embodiment 2

[0032] (1) Prepare 1% w / v PDLLA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C for 24 hours; prepare 3% w / v PLGA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C 24h.

[0033] (2) Dissolve VEGF and BMP‐2 growth factors in ultrapure water respectively, add VEGF solution to the nuclear layer solution at a ratio of 10nm / ml, and add BMP‐2 solution to the nuclear layer solution at a ratio of 100nm / ml , respectively stirred for 10 min to form a uniform and stable core and core layer solution.

[0034] (3) Inject the core and layer solutions obtained in step (2) into 20mL medical syringes respectively, place them in a coaxial electrostatic spraying device to spray microspheres, the spraying voltage is 15kV, the total flow rate is 0.8ml / h, and the core-shell flow rate ratio is 1: 4. The receiving board distance is 20cm.

[0035] (4) Dry the product obtained in step (3) in a vacuum freeze dryer ...

Embodiment 3

[0038] (1) Prepare 1% w / v PDLLA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C for 24 hours; prepare 3% w / v PLGA trifluoroethanol core layer solution, swell at room temperature for 1 hour, and stir at 37°C 24h.

[0039] (2) Dissolve BMP-2 and VEGF growth factors in ultrapure water respectively, add BMP-2 solution to the nuclear layer solution at a ratio of 100nm / ml, and add VEGF solution to the nuclear layer solution at a ratio of 10nm / ml , respectively stirred for 10 min to form a uniform and stable core and core layer solution.

[0040] (3) Inject the core and layer solutions obtained in step (2) into 20mL medical syringes respectively, place them in a coaxial electrostatic spraying device to spray microspheres, the spraying voltage is 15kV, the total flow rate is 0.8ml / h, and the core-shell flow rate ratio is 1: 2.

[0041] (4) Dry the product obtained in step (3) in a vacuum freeze dryer for 24 hours, and store it sealed at -...

Images