BE1027375B1 - High porosity porous nanohydroxyapatite microsphere and its preparation process - Google Patents

Abstract

The invention provides a porous microsphere of high porosity nanohydroxyapatite and its preparation process. The composite size of the hydroxyapatite microsphere produced by the method of the invention is evenly distributed, with a particle size distribution range of 10-100 μm and a center size of 20-60 μm. Adding the organic phase in the mixing process can effectively improve the stability of the suspension, the produced microsphere size is evenly distributed, and the particle size is larger than the microsphere size obtained by the traditional drying system of spraying, it can be used as a support material in injection; the microsphere has a good shape with large pores which can improve material injection.

Description

DESCRIPTION Porous microsphere of high porosity nanohydroxyapatite and its preparation process Technical field The invention belongs to the technical field of materials and relates in particular to a porous microsphere of high porosity nanohydroxyapatite and its preparation process.

Background Technology Hydroxyapatite has attracted a lot of attention from biomaterials and medical experts because its structure and composition are very similar to human bone tissue. There are many processes for preparing hydroxyapatite microspheres, such as the hydrothermal process, the emulsion crosslinking process, the microwave process, and the spray drying process. Among these, the emulsion crosslinking process is mainly used for the preparation of organic or inorganic composite hydroxyapatite microspheres, but this process has problems such that the microspheres are easy to agglomerate and the crosslinking agent is difficult. to be eliminated completely. The drying process

> BE2019 / 5546 by spraying has the following advantages: simple operation, no need to add toxic reagents and easy industrialization, but it also has shortcomings such as irregular shape of the microspheres and wide particle size distribution. The processes for preparing the porous hydroxyapatite include a chemical foaming process, a blowing agent process, an organic foam impregnation process and an organic matrix process. When the porous hydroxyapatite is prepared by the chemical foaming process, the pore diameter and the void rate of the porous material are difficult to control, and the pores of the obtained porous material are generally closed and the porosity of the pores is poor. The porous hydroxyapatite obtained by the pore-forming agent has a low porosity and a wide pore size distribution. The organic foam impregnation process easily generates microcracks on the biomaterial during drying and sintering, and reduces the strength of the porous hydroxyapatite. The organic template method requires the selection of an appropriate surfactant, which can be toxic and must be removed at elevated temperatures, thereby reducing the biological activity of the porous hydroxyapatite.

Content of the invention

In order to overcome the problems of the existing techniques, the present invention provides a process for preparing porous microspheres of high porosity nanohydroxyapatite, and the preparation process comprises the following steps:

Step 1: Add nanohydroxyapatite powder to the water by formulating a thick hydroxyapatite liquid with a content of 10-40% (w / v),

Step 2: Mix the thick hydroxyapatite liquid, blowing agent and oleic acid, place in the bead mill for 6-24 hours and obtain a uniform suspension;

Step 3: Add the suspension to the organic compound, mix according to the proportion and put in a 30-80 ° C water bath and stir to dissolve;

Step 4: Pass this dissolved uniform suspension to the process of spray drying granulation, get solidified microsphere;

Step 5: Pass the solidified microsphere to high temperature dewaxing treatment, then incinerate under high temperature condition, and obtain high porosity nanohydroxyapatite porous microsphere.

Compared to existing techniques, the invention has the following advantages: the composite size of the hydroxyapatite microsphere produced by the method of the invention is evenly distributed, with a particle size distribution range of 10-100 µm and a central size of 20-60 µm.

Adding the organic phase in the mixing process can effectively improve the stability of the suspension, the produced microsphere size is evenly distributed, and the particle size is larger than the microsphere size obtained by the traditional drying system of spraying, it can be used as a support material in the injection; the microsphere has a good shape with large pores which can improve material injection.

Detailed Operation Embodiment 1 A process for preparing high porosity nano-hydroxyapatite porous microspheres of the present embodiment comprises the following steps: Step 1: Add nanohydroxyapatite powder into water by formulating a thick liquid hydroxyapatite with a content of 10-40% (w / v); Step 2: Mix the thick hydroxyapatite liquid, blowing agent and oleic acid in the appropriate proportion, the weight ratio of thick hydroxyapatite liquid to blowing agent is 80:20. Place in the bead mill for 6-24 hours and obtain a uniform suspension; the porogen is carbon powder.

5 Step 3: Add the suspension to the organic compound, mix according to the appropriate proportion and put in a water bath of 80 ° C and stir to dissolve; The organic compounding agent is a combination of gelatin, gum arabic, chitosan and sodium alginate. The stirring speed of the water bath is 600 rev / min and the dissolution time is 5 hours.

Step 4: Pass this dissolved uniform slurry to the process of spray drying granulation, the spray temperature is 250 ° C, the feed rate is 10ml / min, and the spray pressure is 0.05 MPa , obtain a solidified microsphere; Step 5: Pass the solidified microsphere to high temperature dewaxing treatment, the dewaxing temperature is 800 ° C, the dewaxing treatment time is 120 min; then incinerate under high temperature conditions, the high temperature calcination temperature is 1000 ° C, the calcination time is 120 min; and obtaining a porous microsphere of high porosity nanohydroxyapatite. The high porosity porous nano-hydroxyapatite microspheres prepared according to Embodiment 1 have a size distribution range of 20 to 75 µm, a central particle diameter of 20 to 60 µm and a porosity of 78%.

Embodiment 2 A process for preparing high porosity nano-hydroxyapatite porous microspheres of the present embodiment comprises the following steps: Step 1: Adding nanohydroxyapatite powder to water by formulating a thick liquid of hydroxyapatite with a content of 10-40% (wv); Step 2: Mix the thick hydroxyapatite liquid, blowing agent and oleic acid in the appropriate proportion, the weight ratio of thick hydroxyapatite liquid to blowing agent being 85:15. Place in the bead mill for 6-24 hours and obtain a uniform suspension; the porogen is carbon powder.

Step 3: Add the suspension to the organic compound, mix according to the appropriate proportion and put in a 50 ° C water bath and stir to dissolve; The organic compounding agent is a combination of gelatin, gum arabic, chitosan and sodium alginate. The stirring speed of the water bath is 250 rev / min and the dissolution time is 5 hours.

Step 4: Pass this dissolved uniform slurry to the process of spray drying granulation, the spray temperature is 250 ° C, the feed rate is 10ml / min, and the spray pressure is 0.05 MPa , obtain a solidified microsphere; Step 5: Pass the solidified microsphere to high temperature dewaxing treatment, the dewaxing temperature is 1500 ° C, the dewaxing treatment time is 60 min; then incinerate under high temperature condition, the high temperature calcination temperature is 1000 ° C, the calcination time is 180 min and obtain a porous microsphere of high porosity nanohydroxyapatite. The high porosity porous nano-hydroxyapatite microspheres prepared according to Embodiment 2 have a size distribution range of 60 to 85 µm, a central particle diameter of 20 to 60 µm and a porosity of 78%.

Embodiment 3 A process for preparing high porosity nano-hydroxyapatite porous microspheres of the present embodiment comprises the following steps: Step 1: Add nanohydroxyapatite powder to water by formulating a thick liquid of hydroxyapatite with a content of 10-40% (w / v),

Step 2: Mix the thick hydroxyapatite liquid, blowing agent and oleic acid in the appropriate ratio, the weight ratio of thick hydroxyapatite liquid to blowing agent is 95: 5. Place in the bead mill for 6-24 hours and obtain a uniform suspension; the porogen is carbon powder.

Step 3: Add the suspension to the organic compound, mix according to the appropriate proportion and put in a 50 ° C water bath and stir to dissolve; The organic compounding agent is a combination of gelatin, gum arabic, chitosan and sodium alginate. The stirring speed of the water bath is 250 rev / min and the dissolution time is 5 hours.

Step 4: Pass this dissolved uniform slurry to the process of spray drying granulation, the spray temperature is 250 ° C, the feed rate is 10ml / min, and the spray pressure is 0.1 MPa , obtain a solidified microsphere; Step 5: Pass the solidified microsphere to high temperature dewaxing treatment, the dewaxing temperature is 1500 ° C, the dewaxing treatment time is 60 min; then incinerate under high temperature condition, the high temperature calcination temperature is 1000 ° C, the calcination time is 180 min and obtain a porous microsphere of high porosity nanohydroxyapatite.

The high porosity porous nano-hydroxyapatite microspheres prepared according to Embodiment 2 have a size distribution range of 50 to 85 µm, a central particle diameter of 20 to 60 µm and a porosity of 89%. The high porosity nano-hydroxyapatite porous microspheres prepared according to this embodiment have high porosity, almost complete penetration and moderate mechanical strength.

Claims (5)

CLAIM 1. Process for preparing porous microspheres of high porosity nanohydroxyapatite comprising the following steps: Step 1: Add nanohydroxyapatite powder in water by formulating thick liquid of hydroxyapatite with a content of 10-40% (w / v), Step 2: Mix the thick liquid of hydroxyapatite, blowing agent and oleic acid, place in the bead mill for 6-24 hours and obtain a uniform suspension; Step 3: Add the suspension to the organic compound, mix according to the proportion and put in a 30-80 ° C water bath and stir to dissolve; Step 4: Pass this dissolved uniform suspension to the process of spray drying granulation, get solidified microsphere; Step 5: Pass the solidified microsphere to high temperature dewaxing treatment, then incinerate under high temperature conditions, and obtain a porous microsphere of high porosity nanohydroxyapatite. 2. The method of claim 1, wherein the weight ratio of the thick liquid of hydroxyapatite and the blowing agent is 80-95: 20-5; the organic composite agent is any combination of one or more of the following: gelatin, acacia, chitosan, sodium alginate, polylactic acid, natural cellulose; the blowing agent is any combination of one or more carbon powder, graphite powder, or acetylene blacks; the water bath stirring speed is 200-600 rpm, the dissolution time is 2-5 h; the dewaxing temperature is 800 to 1500 ° C and the dewaxing treatment time is 30 to 120 min. 3. Process according to claim 1, the high temperature calcination temperature is 1000 to 1500 ° C and the calcination time is 45 to 180 min. 4. The method of claim 1, the spray temperature is between 250 and 500 ° C, the feed rate is between 10 and 30 ml / min and the spray pressure is between 0.05 and 0.1. MPa. 5. A high porosity porous nanohydroxyapatite microsphere produced by the process according to any one of claims 1 to 4, said porous microsphere comprising a particle size distribution ranging from 10 to 100 µm, a central particle diameter of 20 to 60 µm and a particle size distribution. porosity of 60 to 90%.