CN115504443A

CN115504443A - Preparation method of dental bone filling material and finished product thereof

Info

Publication number: CN115504443A
Application number: CN202110698565.1A
Authority: CN
Inventors: 程瀚毅
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-06-23
Filing date: 2021-06-23
Publication date: 2022-12-23

Abstract

The invention provides a preparation method of a dental bone filling material and a finished product thereof, wherein the preparation method comprises the following steps: step (a): preparing a diammonium hydrogen phosphate aqueous solution and a calcium carbonate aqueous solution; a step (b): mixing the diammonium phosphate aqueous solution and the calcium carbonate aqueous solution to obtain a mixed solution; a step (c): putting the mixed solution into a pressure kettle to carry out multi-stage hydrothermal reaction with sequential temperature rise to obtain an initial product, wherein the temperature of the multi-stage hydrothermal reaction is 90-305 ℃; and a step (d): cooling, cleaning and drying the primary product to obtain the dental bone filling object. By means of multistage hydrothermal reaction, the present invention can control the crystal phase ratio between hydroxyapatite and beta-tricalcium phosphate in the prepared dental bone filling material, and this can meet the practical requirement.

Description

Preparation method of dental bone filler and finished product thereof

Technical Field

The invention relates to a preparation method of dental bone filling material and its finished product, in particular to a preparation method of hydroxyapatite and beta-tricalcium phosphate as dental bone filling material and its finished product.

Background

Teeth are one of the essential organs essential for human body to chew and eat and speak, however, the teeth are worn and damaged during human body activities or chewing. As the human body ages, the self-healing mechanism of the human body also gradually decreases, making the loss of teeth more severe.

Therefore, finding suitable implantable biomedical material substitutes to help regenerate teeth and provide original support function has been a subject of considerable attention.

In recent years, calcium phosphate compounds have been studied and used as implantable suitable biomedical materials. The chemical composition of the calcium phosphate compound is similar to that of human bones, so that the calcium phosphate compound has the advantages of good biocompatibility (biocompatibility) and no biological toxicity (free of toxicity) in human bodies, and has quite wide application.

Among them, hydroxyapatite (HAp) and β -tricalcium phosphate (β -TCP) have relatively good biocompatibility and osteoconductivity, can provide a supporting function to facilitate tooth regeneration, and are very suitable as biomedical materials to be implanted into teeth. Hydroxyapatite and beta-tricalcium phosphate play different roles when osseointegration occurs, and the hydroxyapatite has stronger strength and high stability, so the hydroxyapatite is not easy to lose after being filled in and can guide the growth of osteocytes, but finally the hydroxyapatite cannot be metabolized by human bodies and has weaker strength than human bones; the beta-tricalcium phosphate can be completely metabolized by human body, so that autologous bone can be completely formed at the filling position, but the metabolic rate of the beta-tricalcium phosphate is faster than the growth rate of the autologous bone, therefore, the hydroxyapatite and the beta-tricalcium phosphate respectively play different functions and supplement each other to achieve the purposes of providing bone tissue growth framework and guiding the growth of new bone tissue.

The main method of artificially synthesizing the composition containing hydroxyapatite and beta-tricalcium phosphate is chemical coprecipitation, which has the advantages of cheap equipment, good crystallinity of the prepared product, etc. However, the chemical coprecipitation method has a complex phase change during the preparation process, and it is difficult to control the ratio between the final hydroxyapatite and the β -tricalcium phosphate, and it is impossible to adjust the ratio in time according to different ratio requirements.

Disclosure of Invention

In view of the technical defects of the prior art, the present invention aims to provide a method for preparing dental bone filler, which can control the crystal phase ratio of hydroxyapatite and beta-tricalcium phosphate contained in the prepared dental bone filler as much as possible, so that the crystal phase ratio between the hydroxyapatite and the beta-tricalcium phosphate is similar to an estimated value.

In order to achieve the above object, the present invention provides a method for preparing a dental bone filler, comprising the steps of: a step (a): preparing a diammonium phosphate aqueous solution and a calcium carbonate aqueous solution, wherein the pH value of the diammonium phosphate aqueous solution is 7.8-8.2, and the pH value of the calcium carbonate aqueous solution is 9.5-10.2; step (b): mixing the diammonium phosphate aqueous solution and the calcium carbonate aqueous solution to obtain a mixed solution; step (c): putting the mixed solution into a pressure kettle to carry out multi-stage hydrothermal reaction, and obtaining an initial product, wherein the temperature of the multi-stage hydrothermal reaction is 90-305 ℃, the multi-stage hydrothermal reaction sequentially comprises a first-stage hydrothermal reaction, a second-stage hydrothermal reaction, a third-stage hydrothermal reaction and a fourth-stage hydrothermal reaction, and the temperature of the first-stage hydrothermal reaction, the temperature of the second-stage hydrothermal reaction, the temperature of the third-stage hydrothermal reaction and the temperature of the fourth-stage hydrothermal reaction are sequentially increased; and a step (d): cooling, washing and drying the primary product to obtain the dental bone filler, wherein the dental bone filler comprises hydroxyapatite powder and beta-tricalcium phosphate powder.

The invention can effectively control the crystal phase proportion between hydroxyapatite and beta-tricalcium phosphate in the prepared dental bone filler by controlling the technical means of the multi-stage hydrothermal reaction. Specifically, the crystalline phase ratio between the hydroxyapatite and the β -tricalcium phosphate in the product can be estimated in advance according to the molar ratio of the calcium and the phosphorus initially added (for example, if the molar ratio of the calcium and the phosphorus initially added in the reaction is 2.

In addition, the technical means is favorable for improving the purity and the powder uniformity of the prepared dental bone filling material. Therefore, the preparation method of the invention not only can simplify the complexity of the prior art which needs to control a plurality of reaction conditions (such as temperature, pH value, supersaturation degree, type and amount of impurities, stirring speed and the like), but also can inhibit or alleviate the defects of aggregation, non-uniformity, low purity and the like of powder in the product.

Preferably, the temperature of the first stage hydrothermal reaction is 90 ℃ to 100 ℃, the temperature of the second stage hydrothermal reaction is 140 ℃ to 150 ℃, the temperature of the third stage hydrothermal reaction is 220 ℃ to 230 ℃, and the temperature of the fourth stage hydrothermal reaction is 295 ℃ to 305 ℃. Preferably, the temperature of the first-stage hydrothermal reaction is 95 ℃; the temperature of the second stage hydrothermal reaction is 145 ℃; the temperature of the hydrothermal reaction in the third stage is 225 ℃; the temperature of the hydrothermal reaction in the fourth stage is 300 ℃.

Preferably, the first, second, third and fourth hydrothermal reactions are performed in a temperature-holding manner, the temperature-holding time of the first hydrothermal reaction is 3 hours to 5 hours, the temperature-holding time of the second hydrothermal reaction is 5 hours to 8 hours, the temperature-holding time of the third hydrothermal reaction is 8 hours to 12 hours, and the temperature-holding time of the fourth hydrothermal reaction is 12 hours to 15 hours. More preferably, the holding time of the first-stage hydrothermal reaction is 5 hours; the holding time of the second stage hydrothermal reaction is 8 hours; the holding time of the hydrothermal reaction in the third stage is 12 hours; the temperature holding time of the hydrothermal reaction in the fourth stage is 15 hours.

Preferably, the pressure of the multistage hydrothermal reaction is between 0.3GPa and 0.5GPa.

Preferably, in step (b), the molar ratio of calcium contained in the aqueous solution of calcium carbonate to phosphorus contained in the aqueous solution of diammonium phosphate is from 5 to 6.

Preferably, in the step (b), the pH value of the mixed solution is between 9 and 10.

Preferably, the temperature rise rate of the multistage hydrothermal reaction is 1 ℃ to 1.5 ℃ per minute.

Preferably, in the step (d), the drying temperature is between 100 ℃ and 110 ℃.

The invention also provides a dental bone filler which comprises hydroxyapatite powder and beta-tricalcium phosphate powder which are stacked mutually, wherein the hydroxyapatite powder and the beta-tricalcium phosphate powder are stacked together and formed with holes distributed between the hydroxyapatite powder and the beta-tricalcium phosphate powder.

Preferably, the hydroxyapatite powder and the β -tricalcium phosphate powder are stacked together in a Hexagonal Close Packing (HCP) manner to form the dental bone filler, and the dental bone filler is cylindrical or spherical.

Preferably, the dental bone filler is cylindrical, and has a diameter greater than or equal to 2 millimeters (mm) and less than or equal to 5mm, and a length greater than or equal to 5mm and less than or equal to 10 mm.

Preferably, the dental bone filler is spherical and has a diameter of 2mm or more and 5mm or less

In the specification, a range represented by "a small value to a large value" means a range from greater than or equal to the small value to less than or equal to the large value, if not specifically indicated. For example: from 90 ℃ to 305 ℃, i.e., it means that the range is "greater than or equal to 90 ℃ to less than or equal to 305 ℃".

According to the invention, by adopting a multi-stage hydrothermal reaction technical means, the crystal phase ratio between hydroxyapatite and beta-tricalcium phosphate can be effectively controlled, and the purity and uniformity of the dental bone filling material can be improved, so that the dental bone filling material is more suitable for being implanted into a body to be used as a dental bone filling material.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to these drawings without creative efforts.

FIG. 1 is a flow chart of a method for manufacturing dental bone augmentation of the present invention.

Fig. 2 is a schematic view of a cylindrical dental bone filler in example 1 of the present invention.

Fig. 3 is a schematic view of a spherical dental bone filler in example 2 of the present invention.

The main reference numbers illustrate:

in fig. 2:

1. a cylindrical dental bone restoration;

11. hydroxyapatite;

12. beta-tricalcium phosphate;

13. a void;

in fig. 3:

2. spherical dental bone fillings;

21. hydroxyapatite;

22. beta-tricalcium phosphate;

23. a hollow space.

Detailed Description

The technical solutions of the present invention will be described in detail with reference to the following specific examples in order to clearly understand the technical features, objects and advantages of the present invention, but the present invention should not be construed as being limited to the implementable scope of the present invention.

Example 1

Referring to fig. 1, the method for manufacturing the dental bone filler of example 1 is completed according to the processes described in S1 to S4, and the dental bone filler is obtained.

According to the molar ratio of calcium to phosphorus being 2.

Subsequently, an aqueous solution of calcium carbonate was slowly added to an aqueous solution of diammonium hydrogen phosphate, and the mixed solution was stirred with a magnet. Deionized water was added to the mixed solution to adjust the volume of the solution to 42mL.

Subsequently, the mixed solution was placed in an autoclave at a filling rate of 70% to perform a multistage hydrothermal treatment. Specifically, the temperature is raised to 95 ℃ at the rate of 1 ℃ per minute, and the first-stage hydrothermal reaction is continuously carried out for 5 hours; then, the temperature of the pressure kettle is raised to 145 ℃ and the second-stage hydrothermal reaction is continuously carried out for 8 hours; then, the temperature of the pressure kettle is raised to 225 ℃, and the reaction of the third stage is continuously carried out for 12 hours; and finally, raising the temperature of the pressure kettle to 300 ℃ and continuously carrying out the fourth-stage hydrothermal reaction for 15 hours, thus completing the multi-stage hydrothermal reaction and obtaining the initial product.

And finally, cooling the temperature of the pressure kettle to room temperature, washing the primary product by deionized water, filtering by a filter screen with the aperture of 0.5mm-1.0mm, drying for 2 hours at 100 ℃, and then compacting to obtain the cylindrical dental bone filler containing hydroxyapatite powder and beta-tricalcium phosphate powder. And then the dental bone filling object is sent to a ultramicro industrial safety laboratory to be analyzed by a TOPAS semi-quantitative analysis method, the crystalline phase proportion of the hydroxyapatite powder relative to the beta-tricalcium phosphate powder is 1.68.

As shown in fig. 2, the dental bone filler manufactured by the compacting step has a cylindrical structure with a diameter of 2mm to 5mm and a length of 5mm to 10mm, and the cylindrical dental bone filler 1 includes hydroxyapatite 11 and β -tricalcium phosphate 12, which are randomly stacked, and has voids 13 between the hydroxyapatite 11 and the β -tricalcium phosphate 12 stacked one on another.

Example 2

Example 2 the procedure is substantially the same as in example 1, except that the dental bone filler is pressed into a round spherical structure by a compacting step, the result of which is shown in fig. 3. The spherical dental bone filler 2 has a diameter of 2mm to 5mm, and the spherical dental bone filler 2 simultaneously comprises hydroxyapatite 21 and beta-tricalcium phosphate 22, which are randomly stacked, and has voids 23 disposed between the hydroxyapatite 21 and the beta-tricalcium phosphate 22.

Comparative example

The procedure of the comparative example is substantially the same as example 1, except that the hydrothermal reaction is not carried out in a stepwise manner. In the comparative example, after a mixed solution of an aqueous solution of calcium carbonate and an aqueous solution of diammonium hydrogen phosphate was placed in a pressure kettle, the temperature was raised to 300 ℃ at a rate of 1 ℃ per minute and a hydrothermal reaction was continued for 40 hours, and finally, a dental bone prosthesis containing hydroxyapatite powder and β -tricalcium phosphate powder was obtained, wherein the ratio of the crystal phase of the hydroxyapatite powder to the crystal phase of the β -tricalcium phosphate powder was 2.39.

If the molar ratio of calcium to phosphorus initially added in the reaction is 2. Comparing the preparation methods of example 1 and comparative example and the results thereof, the ratio of the crystalline phase between hydroxyapatite and β -tricalcium phosphate in the dental bone grafts of example 1 and comparative example was 1.68 and 2.39, respectively, and it can be seen that, in the product obtained by the multistage hydrothermal reaction method described in example 1 (i.e., controlling the hydrothermal reaction at a specific temperature and holding it for a specific time), the ratio of the crystalline phase between hydroxyapatite and β -tricalcium phosphate (1.68) was quite close to the estimated value (1.7; in contrast, in the product obtained by the single-stage hydrothermal reaction of the comparative example, the ratio of the crystal phase between hydroxyapatite and β -tricalcium phosphate (2.39. Therefore, the multi-stage hydrothermal reaction preparation method can accurately control the crystal phase ratio between the hydroxyapatite and the beta-tricalcium phosphate in the product, and the dental bone filling material with the crystal phase ratio between the hydroxyapatite and the beta-tricalcium phosphate approximate to an estimated value is obtained if necessary.

In summary, the preparation method of the dental bone filler of the present invention is to keep the temperature at a specific temperature for a specific time by hydrothermal reactions of multiple stages, so as to control the crystal phase ratio between hydroxyapatite and beta-tricalcium phosphate contained in the final product to be similar to an estimated value, thereby meeting the changeable demands in the market; in addition, the product has the advantages of high purity, good uniformity and the like, and is more suitable for being used as a dental bone filler to be implanted into a human body, so that the industrial value and the application range of the product are improved.

It should be understood that the above description is only exemplary of the invention, and is not intended to limit the scope of the invention, so that the replacement of equivalent elements or equivalent changes and modifications made in the present invention should be included within the scope of the present invention. In addition, the technical features and the technical inventions of the present invention, the technical features and the technical inventions, and the technical inventions can be freely combined and used.

Claims

1. The preparation method of the dental bone filler is characterized by comprising the following steps:

a step (a): preparing a diammonium hydrogen phosphate aqueous solution and a calcium carbonate aqueous solution, wherein the pH value of the diammonium hydrogen phosphate aqueous solution is 7.8 to 8.2, and the pH value of the calcium carbonate aqueous solution is 9.5 to 10.2;

step (b): mixing the diammonium hydrogen phosphate aqueous solution and the calcium carbonate aqueous solution to obtain a mixed solution;

step (c): putting the mixed solution into a pressure kettle to carry out multi-stage hydrothermal reaction, and obtaining an initial product, wherein the temperature of the multi-stage hydrothermal reaction is 90-305 ℃, the multi-stage hydrothermal reaction sequentially comprises a first-stage hydrothermal reaction, a second-stage hydrothermal reaction, a third-stage hydrothermal reaction and a fourth-stage hydrothermal reaction, and the temperature of the first-stage hydrothermal reaction, the temperature of the second-stage hydrothermal reaction, the temperature of the third-stage hydrothermal reaction and the temperature of the fourth-stage hydrothermal reaction are sequentially increased; and

step (d): cooling, washing and drying the primary product to obtain the dental bone filler, wherein the dental bone filler comprises hydroxyapatite and beta-tricalcium phosphate.

2. The method according to claim 1, wherein the temperature of the first-stage hydrothermal reaction is 90 ℃ to 100 ℃, the temperature of the second-stage hydrothermal reaction is 140 ℃ to 150 ℃, the temperature of the third-stage hydrothermal reaction is 220 ℃ to 230 ℃, and the temperature of the fourth-stage hydrothermal reaction is 295 ℃ to 305 ℃.

3. The method according to claim 2, wherein the temperature of the first-stage hydrothermal reaction is 95 ℃, the temperature of the second-stage hydrothermal reaction is 145 ℃, the temperature of the third-stage hydrothermal reaction is 225 ℃, and the temperature of the fourth-stage hydrothermal reaction is 300 ℃.

4. The preparation method according to claim 1, wherein the first, second, third and fourth hydrothermal reactions are carried out in a temperature-maintaining manner, and the temperature-maintaining time of the first hydrothermal reaction is 3 to 5 hours, the temperature-maintaining time of the second hydrothermal reaction is 5 to 8 hours, the temperature-maintaining time of the third hydrothermal reaction is 8 to 12 hours, and the temperature-maintaining time of the fourth hydrothermal reaction is 12 to 15 hours.

5. The production method according to claim 4, wherein the holding time for the first-stage hydrothermal reaction is 5 hours, the holding time for the second-stage hydrothermal reaction is 8 hours, the holding time for the third-stage hydrothermal reaction is 12 hours, and the holding time for the fourth-stage hydrothermal reaction is 15 hours.

6. The production method according to any one of claims 1 to 5, characterized in that the pressure of the multistage hydrothermal reaction is 0.3GPa to 0.5GPa.

7. The process according to any one of claims 1 to 5, characterized in that the aqueous solution of calcium carbonate in step (b) comprises calcium in a molar ratio with respect to the phosphorus contained in the aqueous solution of diammonium phosphate comprised between 5 and 3.

8. The method according to any one of claims 1 to 5, wherein the pH of the mixed solution in the step (b) is 9 to 10.

9. A dental bone filler comprising hydroxyapatite powder and beta-tricalcium phosphate powder stacked one on another, wherein the hydroxyapatite powder and the beta-tricalcium phosphate powder are stacked together and formed with voids distributed between the hydroxyapatite powder and the beta-tricalcium phosphate powder.

10. The dental bone filler of claim 9, wherein the hydroxyapatite powder and the β -tricalcium phosphate powder are co-stacked in a hexagonal close-packed arrangement to form the dental bone filler, and wherein the dental bone filler is cylindrical or spherical.