CN102249206A - Selenium-doped hydroxyapatite and preparation method thereof - Google Patents

Abstract

The invention discloses a selenium-doped hydroxyapatite and a preparation method thereof. The selenium-doped hydroxyapatite obtained by the preparation method has an apatite-like structure, and selenium is partially replaced by selenite Position of phosphate and/or hydroxyl groups in hydroxyapatite crystals. The selenium-doped hydroxyapatite has high yield and good dispersibility.

Description

A kind of selenium-doped hydroxyapatite and its preparation method

technical field

The invention belongs to the technical field of biomaterials.

Background technique

Synthetic hydroxyapatite is an excellent hard tissue replacement material with good compatibility with human tissue. It is clinically used in the repair and replacement of human hard tissue, such as artificial bone, dental implant, bone filling material, artificial joint etc., can improve the osteogenic ability of bone implant materials. Also available as orthopedic implants (e.g. saddle nose fillers). In addition, medicinal hydroxyapatite also has some special properties, such as inhibiting the growth of some tumor cells.

Selenium is an important trace element essential to the human body. Trace amounts of selenium have strong antioxidant and anticancer effects. It can also remove free radicals in the body, eliminate toxins in the body, resist oxidation, effectively inhibit the production of lipid peroxides, prevent blood clots, remove cholesterol, and enhance human immune function. In addition, it also has the effect of preventing cardiovascular and cerebrovascular diseases, Keshan disease, Kashin-Beck disease, and arthritis.

In recent years, the research of trace element doping hydroxyapatite has become a hot spot. Further expanding the types and functions of doped trace elements is an important topic for in-depth research and application of hydroxyapatite. At present, some trace elements have been doped into hydroxyapatite, for example, doping strontium element into hydroxyapatite to prepare strontium-containing hydroxyapatite (manufacturing method of nano-doped strontium hydroxyapatite, Patent No.: 200510025590.4), and doping carbonate into hydroxyapatite (synthesis method of nano-hydroxyapatite powder containing carbonate, patent No.: 200410053208), etc. So far, there have been no reports of selenium-doped hydroxyapatite powder materials, and how to combine the application of selenium element with hydroxyapatite is still an unresolved problem.

Contents of the invention

The purpose of the present invention is to solve the above problems and provide a selenium-doped hydroxyapatite and other preparation methods. The selenium-doped hydroxyapatite obtained by the preparation method has high yield and good dispersibility.

The technical scheme adopted in the present invention is:

A selenium-doped hydroxyapatite has an apatite-like structure, and the selenium element partially replaces the phosphate and/or hydroxyl positions in the hydroxyapatite crystal in the form of selenite.

Further, the molar substitution degree of selenium to phosphorus in the selenium-doped hydroxyapatite is 0.1%-10%, that is, the molar ratio of selenium to phosphorus in the selenium-doped hydroxyapatite is 0.1%-10%).

Furthermore, the hydroxyapatite can be controlled to the nanometer level, and its particle size distribution width is 20-60nm, and the length is 80-150nm.

A preparation method of selenium-doped hydroxyapatite, the specific steps of the preparation method are:

(1) When the pH value is 9-10 and the reaction temperature is 80-85°C, add the phosphorus salt solution dropwise to the calcium salt solution to make it react completely, and the molar ratio of the calcium content in the calcium salt to the phosphorus content in the phosphorus salt is The ratio is 10/(6-0.667x);

(2) After the first step reaction is completed for 30 to 40 minutes, a selenite solution with a molar ratio of 0.01mol/L to 0.1mol/L is added dropwise to the reaction solution, so that the molar number of selenium in the solution is equal to that of the step (1) The molar ratio of phosphorus in the phosphorus salt solution is x, and the pH value is controlled to be 10-10.5;

(3) After the addition of selenite is completed, keep the pH value of the reaction, react for 24 hours, and keep the temperature at 75-80°C;

(4) Centrifugal washing with water or dialysis to remove free nitrate and other impurity ions, drying, and finally obtain selenium-doped hydroxyapatite.

A preparation method of nanoscale selenium-doped hydroxyapatite, the specific steps of the preparation method are:

(1) When the pH value is 9-10 and the reaction temperature is 80-85°C, add the phosphorus salt solution dropwise into the calcium salt solution to make it react completely, the molar ratio of the calcium content in the calcium salt to the phosphorus content in the phosphorus salt 10/(6-0.667x), then add dispersant;

(2) After the first step reaction is completed for 30 to 40 minutes, a selenite solution with a molar ratio of 0.01mol/L to 0.1mol/L is added dropwise to the reaction solution, so that the molar number of selenium in the solution is equal to that of the step (1) The molar ratio of phosphorus in the phosphorus salt solution is x, and the pH value is controlled to be 10-10.5;

(3) After the addition of selenite is completed, keep the pH value of the reaction, react for 24 hours, and keep the temperature at 75-80°C;

(4) Centrifugal washing with water or dialysis to remove free nitrate and other impurity ions, and drying to obtain nano-scale selenium-doped hydroxyapatite.

Preferably, the dispersant is sodium polyacrylate.

Preferably, the calcium salt is calcium nitrate.

Preferably, the phosphorus salt is diammonium hydrogen phosphate, ammonium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate.

Preferably, the selenite is sodium selenite.

The present invention has the following advantages:

The product prepared by the invention is a brand-new selenium-doped hydroxyapatite material, and its selenium content is 0.1% to 10%. The selenium-doped hydroxyapatite has high yield and good dispersibility, and its nanoscale particle size can reach 20-150nm. The selenium-doped hydroxyapatite can be used for bone tissue engineering, nano drug loading, controlled release system and the like. At the same time, the whole preparation method has simple process, low cost and environmental friendliness, and is convenient for large-scale production of high-purity selenium-doped hydroxyapatite material.

Description of drawings

The present invention will be described in further detail below in conjunction with the accompanying drawings and embodiments.

Fig. 1 is the hydroxyapatite X-ray diffraction figure of the selenium doped that embodiment 1 to embodiment 4 obtains;

Fig. 2 is the selenium-doped hydroxyapatite infrared spectrogram that embodiment 1 to embodiment 4 obtain;

Fig. 3 is a transmission electron micrograph when the percentage of selenite doped in the selenium-doped hydroxyapatite obtained in Example 1 and the phosphate in the reactant is 0.1%.

Fig. 4 is a transmission electron micrograph when the percentage of selenite doped in the selenium-doped hydroxyapatite obtained in Example 2 and the phosphate in the reactant is 1%.

Fig. 5 is a transmission electron micrograph when the percentage of selenite doped in the selenium-doped hydroxyapatite obtained in Example 3 and the phosphate in the reactant is 5%.

Fig. 6 is a transmission electron micrograph when the percentage of selenite doped in the selenium-doped hydroxyapatite obtained in Example 4 and the phosphate in the reactant is 10%.

FIG. 7 is a graph showing the results of fluorescent probes of selenium-doped hydroxyapatite obtained in Examples 1 to 4. FIG.

Detailed ways

Example 1

Select and analyze pure calcium nitrate, diammonium hydrogen phosphate, and sodium selenite, and synthesize nanoscale hydroxyapatite doped with 0.1% selenium through this preparation method. The specific steps are:

(1) Add 12.398g of analytically pure calcium nitrate into 140ml of distilled water; 4.156g of analytically pure diammonium hydrogen phosphate into 320ml of distilled water, add 0.0083g of analytically pure sodium selenite into 20ml of distilled water, and stir until completely dissolved;

(2) Adjust the pH value of the calcium nitrate solution to 9 with ammonia water, and use a constant temperature magnetic stirrer to raise its temperature to 80°C;

(3) Slowly add the diammonium hydrogen phosphate solution in step (1) to the calcium nitrate solution under the conditions described in step (2), and control the dropping rate so that the dropping process lasts for 30 minutes;

(4) In step (3), when the reaction lasts for 15 minutes, slowly add 3ml of sodium polyacrylate dispersant dropwise to the reaction solution.

(5) 15 minutes after the completion of step (3), add the sodium selenite solution prepared in step (1) dropwise into the reaction vessel, and the dropping process lasts for 10 minutes. During the dropping process, the pH value of the reaction solution was adjusted and maintained at 10 by adding ammonia water dropwise, and the temperature was maintained at 80° C. with a constant temperature magnetic stirrer;

(6) After the reaction in step (4) is completed, keep the pH value of the reaction solution at 10 by dropping ammonia water or nitric acid, keep the temperature at 80°C with a constant temperature magnetic stirrer, and react for 24 hours;

(7) The selenium-doped hydroxyapatite powder obtained in step (6) was dialyzed and washed 5 times with triple distilled water, and dried overnight at 60° C. to obtain the nano-scale selenium-doped hydroxyapatite.

Referring to Fig. 1, Fig. 1 is the X-ray diffraction pattern of the selenium-doped hydroxyapatite, and it can be seen from the figure that the obtained reaction products of each doping ratio are all apatite substances. With reference to Fig. 2, Fig. 2 is the hydroxyapatite infrared spectrogram of this selenium doping, can find out from the figure that the reaction product of each doping ratio all has obvious phosphate radical, selenite ion and hydroxyl peak; Thus it can be seen that the product The powder contains phosphate, selenite and hydroxyl groups. Referring to Fig. 3, Fig. 3 is a transmission electron microscope image of the selenium-doped hydroxyapatite, from which it can be seen that the shape is a long rod with a width of about 50nm and a length of about 150nm. Fig. 7 is the fluorescent probe result figure of this selenium-doped hydroxyapatite, can find out from the figure that the reaction products of each doping ratio all contain selenite, and the content of the selenite added during the reaction is relatively unanimous.

Example 2

Analytical pure calcium nitrate, diammonium hydrogen phosphate, and sodium selenite were selected, and nanoscale hydroxyapatite doped with 1% selenium was synthesized by this preparation method. The specific steps are:

(1) Add 7.085g of analytically pure calcium nitrate to 280ml of distilled water; 2.540g of analytically pure disodium hydrogen phosphate into 280ml of distilled water, and 0.047g of analytically pure sodium selenite into 40ml of distilled water. Stir until completely dissolved

(2) Adjust the pH value of the calcium nitrate solution to 9 with ammonia water, and use a constant temperature magnetic stirrer to raise its temperature to 80°C;

(3) While maintaining the conditions described in step (2), slowly add the diammonium hydrogen phosphate solution in step (1) into the calcium nitrate solution dropwise. Control the rate of addition so that the dropping process continues for 30 minutes;

(4) In step (3), when the reaction lasts for 15 minutes, slowly add 1.5ml of sodium polyacrylate dispersant dropwise to the reaction solution.

(5) 15 minutes after step (3) is completed, add the sodium selenite solution prepared in step (1) dropwise into the reaction vessel. The dropwise addition process lasted 10 minutes. During the dropping process, the pH value of the reaction solution was adjusted to be 10 by adding ammonia water dropwise, and the temperature was kept at 80° C. with a constant temperature magnetic stirrer;

(6) After the reaction in step (4) is completed, keep the pH value of the reaction solution at 10 by dropping ammonia water or nitric acid, keep the temperature at 80°C with a constant temperature magnetic stirrer, and react for 24 hours;

(7) The selenium-doped hydroxyapatite powder obtained in step (6) was dialyzed and washed 5 times with triple distilled water, and dried overnight at 60° C. to obtain the nano-scale selenium-doped hydroxyapatite.

Referring to Fig. 1, Fig. 1 is the X-ray diffraction pattern of the selenium-doped hydroxyapatite, and it can be seen from the figure that the obtained reaction products of each doping ratio are all apatite substances. With reference to Fig. 2, Fig. 2 is the hydroxyapatite infrared spectrogram of this selenium doping, can find out from the figure that the reaction product of each doping ratio all has obvious phosphate radical, selenite ion and hydroxyl peak; Thus it can be seen that the product The powder contains phosphate, selenite and hydroxyl groups. Referring to Figure 4, Figure 4 is a transmission electron microscope image of the selenium-doped hydroxyapatite, from which it can be seen that the shape is a long rod, about 30nm wide, and about 140nm long Figure 7 is the hydroxyapatite doped with selenium Fluorescent probe results, it can be seen from the figure that the reaction products of each doping ratio contain selenite, which is consistent with the content of selenite added during the reaction.

Example 3

Analytical pure calcium nitrate, diammonium hydrogen phosphate, and sodium selenite were selected, and nanoscale hydroxyapatite doped with 1% selenium was synthesized by this preparation method. The specific steps are:

Choose analytically pure calcium nitrate, diammonium phosphate, and sodium selenite. The process of synthesizing 5% hydroxyapatite doped with selenium by this operational route is:

(1) Add 3.542g of analytically pure calcium nitrate to 140ml of distilled water; 1.150g of analytically pure diammonium hydrogen phosphate into 140ml of distilled water, and 0.115g of analytically pure sodium selenite into 20ml of distilled water. Stir until completely dissolved

(2) Adjust the pH value of the calcium nitrate solution to 9.5 with ammonia water, and use a constant temperature magnetic stirrer to raise its temperature to 80°C;

(3) While maintaining the conditions described in step (2), slowly add the diammonium hydrogen phosphate solution in step (1) into the calcium nitrate solution dropwise. Control the rate of addition so that the dropping process continues for 30 minutes;

(4) In step (3), when the reaction lasts for 15 minutes, slowly add 1ml of sodium polyacrylate dispersant dropwise to the reaction liquid.

(5) 15 minutes after step (3) is completed, add the sodium selenite solution prepared in step (1) dropwise into the reaction vessel. The dropwise addition process lasted 10 minutes. During the dropping process, the pH value of the reaction solution was adjusted and maintained at 10.5 by adding ammonia water dropwise, and the temperature was maintained at 80° C. with a constant temperature magnetic stirrer;

(6) After the reaction in step (4) is completed, keep the pH value of the reaction solution at 10 by dropping ammonia water or nitric acid, keep the temperature at 80°C with a constant temperature magnetic stirrer, and react for 24 hours;

(7) The selenium-doped hydroxyapatite powder obtained in step (6) was filtered and washed 5 times with triple-distilled water, and dried overnight at 60°C.

Referring to Fig. 1, Fig. 1 is the X-ray diffraction pattern of the selenium-doped hydroxyapatite, and it can be seen from the figure that the obtained reaction products of each doping ratio are all apatite substances. With reference to Fig. 2, Fig. 2 is the hydroxyapatite infrared spectrogram of this selenium doping, can find out from the figure that the reaction product of each doping ratio all has obvious phosphate radical, selenite ion and hydroxyl peak; Thus it can be seen that the product The powder contains phosphate, selenite and hydroxyl groups. Referring to Fig. 5, Fig. 5 is a transmission electron micrograph of the selenium-doped hydroxyapatite, and it can be seen from the figure that the shape is a long rod with a width of about 40nm and a length of about 120nm. Fig. 7 is the fluorescent probe result figure of this selenium-doped hydroxyapatite, can find out from the figure that the reaction products of each doping ratio all contain selenite, and the content of the selenite added during the reaction is relatively unanimous.

Example 4

Analytical pure calcium nitrate, diammonium hydrogen phosphate, and sodium selenite were selected, and nanoscale hydroxyapatite doped with 1% selenium was synthesized by this preparation method. The specific steps are:

(1) Add 7.085g of analytically pure calcium nitrate to 280ml of distilled water; 2.229g of analytically pure diammonium hydrogen phosphate into 280ml of distilled water, and 0.444g of analytically pure sodium selenite into 40ml of distilled water. Stir until completely dissolved

(2) Adjust the pH value of the calcium nitrate solution to 10 with ammonia water, and use a constant temperature magnetic stirrer to raise its temperature to 80°C;

(3) While maintaining the conditions described in step (2), slowly add the diammonium hydrogen phosphate solution in step (1) into the calcium nitrate solution dropwise. Control the rate of addition so that the dropping process continues for 30 minutes;

(4) In step (3), when the reaction lasts for 15 minutes, slowly add 1.5ml of sodium polyacrylate dispersant dropwise to the reaction liquid.

(5) 15 minutes after step (3) is completed, add the sodium selenite solution prepared in step (1) dropwise into the reaction vessel. The dropwise addition process lasted 10 minutes. During the dropping process, the pH value of the reaction solution was adjusted and maintained at 10.5 by adding ammonia water dropwise, and the temperature was maintained at 80° C. with a constant temperature magnetic stirrer;

(6) After the reaction in step (4) is completed, keep the pH value of the reaction solution at 10 by dropping ammonia water or nitric acid, keep the temperature at 80°C with a constant temperature magnetic stirrer, and react for 24 hours;

(7) The selenium-doped hydroxyapatite powder obtained in step (6) was dialyzed and washed 5 times with triple distilled water, and dried overnight at 60°C.

Referring to Fig. 1, Fig. 1 is the X-ray diffraction pattern of the selenium-doped hydroxyapatite, and it can be seen from the figure that the obtained reaction products of each doping ratio are all apatite substances. With reference to Fig. 2, Fig. 2 is the hydroxyapatite infrared spectrogram of this selenium doping, can find out from the figure that the reaction product of each doping ratio all has obvious phosphate radical, selenite ion and hydroxyl peak; Thus it can be seen that the product The powder contains phosphate, selenite and hydroxyl groups. Referring to Fig. 6, Fig. 6 is a transmission electron microscope image of the selenium-doped hydroxyapatite, from which it can be seen that the shape is a long rod, with a width of about 20nm and a length of about 150nm. Fig. 7 is the fluorescent probe result figure of this selenium-doped hydroxyapatite, can find out from the figure that the reaction products of each doping ratio all contain selenite, and the content of the selenite added during the reaction is relatively unanimous.

The above embodiments are only used to illustrate the technical solutions of the present invention without limitation. Although the present invention has been described in detail with reference to preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced. Without departing from the spirit and scope of the technical solutions of the present invention, all of them should be included in the scope of the claims of the present invention.

Claims (9)

1. A selenium-doped hydroxyapatite, characterized in that the structure is an apatite structure, and the selenium element partially replaces the positions of phosphate and/or hydroxyl in the hydroxyapatite crystal in the form of selenite. 2. The hydroxyapatite doped with selenium according to claim 1, characterized in that, the hydroxyapatite doped with selenium has a molar substitution degree of 0.1% to 10% for phosphorus, that is, the hydroxyapatite doped with selenium The molar ratio of selenium to phosphorus in limestone is 0.1% to 10%. 3. The hydroxyapatite doped with selenium according to any one of claims 1 and 2, characterized in that, the hydroxyapatite can be controlled to nanoscale, its particle size distribution width is 20-60nm, and the length is 80~150nm. 4. a preparation method of the hydroxyapatite doped with selenium described in any one of claim 1 or 2, is characterized in that, the concrete steps of this preparation method are: (1) When the pH value is 9-10 and the reaction temperature is 80-85°C, add the phosphorus salt solution dropwise to the calcium salt solution to make it react completely, and the molar ratio of the calcium content in the calcium salt to the phosphorus content in the phosphorus salt is The ratio is 10/(6-0.667x); (2) After the first step reaction is completed for 30 to 40 minutes, a selenite solution with a molar ratio of 0.01mol/L to 0.1mol/L is added dropwise to the reaction solution, so that the molar number of selenium in the solution is equal to that of the step (1) The molar ratio of phosphorus in the phosphorus salt solution is x, and the pH value is controlled to be 10-10.5; (3) After the addition of selenite is completed, keep the pH value of the reaction, react for 24 hours, and keep the temperature at 75-80°C; (4) Centrifugal washing with water or dialysis to remove free nitrate and other impurity ions, drying, and finally obtain selenium-doped hydroxyapatite. 5. a kind of preparation method of the hydroxyapatite doped with selenium of nanoscale claimed in claim 3 is characterized in that, the concrete steps of this preparation method are: (1) When the pH value is 9-10 and the reaction temperature is 80-85°C, add the phosphorus salt solution dropwise into the calcium salt solution to make it react completely, the molar ratio of the calcium content in the calcium salt to the phosphorus content in the phosphorus salt 10/(6-0.667x), then add dispersant; (2) After the first step reaction is completed for 30 to 40 minutes, a selenite solution with a molar ratio of 0.01mol/L to 0.1mol/L is added dropwise to the reaction solution, so that the molar number of selenium in the solution is equal to that of the step (1) The molar ratio of phosphorus in the phosphorus salt solution is x, and the pH value is controlled to be 10-10.5; (3) After the addition of selenite is completed, keep the pH value of the reaction, react for 24 hours, and keep the temperature at 75-80°C; (4) Centrifugal washing with water or dialysis to remove free nitrate and other impurity ions, and drying to obtain nano-scale selenium-doped hydroxyapatite. 6. the preparation method of the hydroxyapatite doped with selenium according to claim 5, is characterized in that, described dispersant is sodium polyacrylate. 7. The method for preparing selenium-doped hydroxyapatite according to any one of claims 4 to 6, characterized in that the calcium salt is calcium nitrate. 8. The preparation method of the hydroxyapatite doped with selenium according to any one of claims 4 to 6, wherein the phosphorus salt is diammonium hydrogen phosphate, ammonium dihydrogen phosphate, disodium hydrogen phosphate, phosphoric acid dipotassium hydrogen. 9. The method for preparing selenium-doped hydroxyapatite according to any one of claims 4 to 6, wherein the selenite is sodium selenite.

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