JP3725935B2 - Method for producing calcium phosphate ceramics - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a calcium phosphate ceramic using a specific chelating agent. The calcium phosphate ceramics obtained by the method of the present invention can be used as a substitute for living hard tissues such as artificial bones, artificial tooth roots, and artificial joints. Moreover, it can coat on the surface of a bio-hard tissue substitute member having a high strength made of titanium, alumina or the like to improve their bioactivity.
[0002]
[Prior art]
It is known that a calcium phosphate compound is excellent in biological activity, and its sintered body is a material that is chemically bonded to or replaced by bone in the living body. And this compound is synthesize | combined by various methods, such as the precipitation method from a liquid phase, the sol gel method. This sol-gel method has many advantages such as the ability to obtain target ceramics such as apatite at a low temperature, and since it is liquid, it is easy to coat and is excellent in shape imparting properties such as wire formation.
[0003]
However, in general, in the sol-gel method, especially in the case of a multi-component system, how to control the hydrolysis rate of each component is a big problem. When producing calcium phosphate compounds, calcium alkoxides are rapidly hydrolyzed and phosphorus alkoxides are very slow. Therefore, the calcium content settles quickly, and the phosphorus content remains in the liquid, and it is very difficult to obtain the target composition ratio.
[0004]
[Problems to be solved by the invention]
In the present invention, the above problems are solved, and by using a chelating agent containing phosphorus, a homogeneous and stable solution in which a chelating compound containing calcium and phosphorus is dissolved can be easily prepared. The present invention provides a method for producing a calcium phosphate ceramic by drying and firing this solution.
[0005]
[Means for Solving the Problems]
The method for producing a calcium phosphate-based ceramic of the first invention includes a step of preparing a solution by dissolving a salt containing calcium and a chelating agent containing phosphorus in a solvent, a step of removing the solvent by drying the solution, and And baking the residue from which the solvent has been removed.
[0006]
The method for producing a calcium phosphate ceramic of the second invention comprises a step of preparing a solution by dissolving a salt containing calcium and a chelating agent containing phosphorus in a solvent, a step of drying the solution and removing the solvent, It comprises heat-treating the residue from which the solvent was removed to produce a calcium phosphate compound, and firing the calcium phosphate compound.
[0007]
As the “salt containing calcium”, the following various inorganic salts and organic salts can be used. Examples of inorganic salts include nitrates, chlorides, bromides, iodides, chlorates, chlorites, nitrites and sulfites. As the organic salt, acetate, oxalate, lactate, tartrate, citrate, benzoate, isobutyrate, maleate and the like can be used. However, a salt that is hardly soluble in a solvent such as water, such as carbonate and sulfate, is not preferable because the chelation reaction is slow.
[0008]
Examples of the above-mentioned “chelating agent containing phosphorus” include 1-hydroxyethane-1,1-bisphosphonic acid, methylenediphosphonic acid, methylphosphonic acid, propane-1,2-diphosphonic acid, nitrilo-tri- (methylenephosphonic Acid), butane-1,4-diphosphonic acid, N- (carboxymethyl) iminobis- (methylphosphonic acid) and N-ethyliminobis- (methylphosphonic acid).
[0009]
Further, phosphonomethyliminodiacetic acid, N-2-phosphonoethyliminodiacetic acid, phosphoric acid-1-glucose, hydrogen phosphate fructose, phosphoric acid-1-glycerol and the like can also be used. In addition, any complex phosphorus compound containing two or more phosphorus atoms can be used as long as it is a chelating agent containing phosphorus, and is not particularly limited.
[0010]
As the “solvent”, any solvent that dissolves a salt containing calcium and a chelating agent containing phosphorus can be used. Examples thereof include alcohols such as methanol and ethanol, and ketones such as acetone and methyl ethyl ketone, with alcohols being particularly preferred. These organic solvents have a smaller surface tension than water and are easily wetted with substrates such as metals and ceramics. Therefore, when these substrates are coated, a film having a uniform thickness can be obtained even if the substrate has particularly severe surface irregularities. In general, it has a low boiling point and can be easily removed by heating after coating the substrate.
[0011]
Water can also be used as the solvent. In the case of water, it is easily chelated to produce a stable chelate compound. However, water is difficult to wet with metals, and when these substrates are coated, the film may become thick or uneven, particularly at the corners. In addition, since the boiling point is high, drying and removal require heating at a higher temperature for a longer time.
[0012]
The “solution” is usually prepared by dissolving a salt containing calcium in a solvent and then adding a chelating agent containing phosphorus. And the stable chelate compound which the phosphate part coordinated to calcium ion produces | generates rapidly. Moreover, there is no precipitation of calcium or the like, and a homogeneous and transparent solution is obtained. This solution is “dried” and “fired” to obtain a calcium phosphate ceramic. The drying conditions may be set as appropriate depending on the boiling point of the solvent and the like, and in a solvent having a relatively high boiling point such as water, drying under reduced pressure is also effective.
[0013]
The firing conditions differ depending on the presence or absence of the heat treatment described in the second invention. This “heat treatment” is performed by removing an organic component (such as a carbon component in the chelate compound) from a “residue” (substantially the entire amount is a chelate compound) after removing the solvent, ”Is generated. The heat treatment conditions are preferably in the range specified in the third invention. If the treatment temperature is less than 250 ° C. or the treatment time is less than 5 minutes, the organic component may not be sufficiently removed, which is not preferred. In addition, the organic content can be sufficiently removed within the upper limits of temperature and time, and when the heat treatment is performed beyond the upper limit, the base material may be oxidized particularly in a base material made of a metal such as titanium. It is not preferable.
[0014]
If the above heat treatment step is not provided separately, the organic component may be removed, and baking is performed in an oxidizing atmosphere such as air at a temperature of 600 to 1300 ° C., particularly 700 to 1000 ° C. for 30 minutes to 2 hours. There is a need. Since this method is exposed to a high temperature in an oxidizing atmosphere, it cannot be applied when coating on a substrate that is easily oxidized, such as titanium. However, it can be applied to substrates such as alumina that do not have oxidation problems. Moreover, it is possible to carry out this method even in the case where only the calcium phosphate compound is formed into an appropriate shape and then fired, instead of coating the substrate.
[0015]
On the other hand, when the above heat treatment is performed, the firing does not need to be performed in an oxidizing atmosphere, and thus can be performed in an inert atmosphere such as argon or nitrogen, or in a high vacuum. Therefore, even a base material that is easily oxidized, such as titanium, can be fired after coating on the surface thereof. However, since titanium forms titanium nitride in a nitrogen atmosphere, it is preferably fired in a rare gas atmosphere such as argon or in a high vacuum. Further, the firing temperature can be set to the same level as above, and the firing time can be 5 to 30 minutes, particularly about 7 to 15 minutes, which can be shorter than that in the case where no heat treatment is performed.
[0016]
When a film is formed by coating on the surface of a substrate such as titanium, usually, only a very thin film of about several hundred nm can be obtained by one coating. However, in the use of a bio-hard tissue replacement member, a coating of about several hundred nm may melt before the bone is formed. Therefore, the coating of the solution, drying, and heat treatment are repeated several times, and then baking is performed to form a film with a predetermined thickness.
[0017]
In addition, it is preferable to add 0.1-10 mol acid to said solution with respect to 1 mol of calcium contained in a salt like 4th invention. This keeps the solution homogeneous and stable over a long period of time without causing phase separation, precipitation or the like. Examples of the acid include inorganic acids such as nitric acid and hydrochloric acid, and organic acids such as acetic acid and oxalic acid. The addition amount may be appropriately adjusted depending on the type of acid.
[0018]
The acid is usually added after dissolving the salt and chelating agent in a solvent. If the amount of acid added is less than 0.1 mol, the effect of stabilizing the solution is insufficient. If the amount added exceeds 10 moles, the acidity becomes too strong, the film may become deliquescent, or the film may foam due to chlorine gas generated during heat treatment. Further, when titanium is used as a base material, it also causes oxidation. The added amount is preferably 0.3 to 5 mol, particularly about 0.5 to 3 mol, and the solution becomes more stable within this range.
[0019]
Furthermore, as in the fifth invention, the diol also has the effect of making the solution more stable. In the case of a diol, the addition amount is in the range of 0.01 to 10 mol with respect to 1 mol of the solvent. As the diol, relatively low molecular weight ethylene glycol, propylene glycol, butylene glycol and the like can be used.
[0020]
If the amount of diol added is less than 0.01 mol, the stabilizing effect is not sufficient, and if it exceeds 10 mol, drying is difficult, which is not preferable. This added amount is preferably about 0.1 to 5 mol, particularly about 0.2 to 3 mol, and the solution becomes more stable within this range. This diol may be added after dissolving a salt and a chelating agent in a solvent in the same manner as the above acid, or may be mixed in advance in a solvent.
[0021]
In addition, said acid and diol may each be used independently, and may use both together. When used in combination, the amount added may be about the same as the range when each is used alone, but in particular, the acid should be about 0.3 to 5 mol and the diol should be about 0.1 to 5 mol. Is preferred.
[0022]
Moreover, it is preferable that the atomic ratio (Ca / P) of calcium and phosphorus in the solution is 1.40 to 1.75. Firing is performed in the temperature range of 600 to 1300 ° C. with the atomic ratio in this range. Thereby, a hydroxyapatite phase (HAp: Ca / P = 1.67) is obtained, and when the amount ratio of phosphorus is high, a tertiary calcium phosphate phase (TCP: Ca / P = 1.5) is obtained. . This atomic ratio of calcium and phosphorus can be easily controlled by the Ca / P ratio of the starting material, and can also be a mixed phase of HAp and TCP.
[0023]
In the present invention, as described above, the solution is dried as it is, molded, and then fired to obtain a calcium phosphate ceramic, and a biohard tissue substitute member having excellent bioactivity can be obtained. Alternatively, the solution can be coated on the surface of a living body hard tissue substitute member made of a metal or ceramics other than calcium phosphate by a method such as coating, spraying, drying, and firing. Thereby, the biological hard tissue substitute member by which the film which consists of calcium phosphate ceramics was formed in the surface of biological hard tissue substitute members, such as a metal, is obtained.
[0024]
A bio-hard tissue replacement member made of metal such as titanium, titanium alloy, and stainless steel, or ceramic such as alumina and zirconia has high strength and is not toxic, but has poor bioactivity. On the other hand, the bio-hard tissue substitute member made of calcium phosphate ceramics is low in strength but excellent in bioactivity. Therefore, if the coating film as described above is formed, a biohard tissue substitute member excellent in strength and bioactivity can be obtained. In the method of the present invention, a chelate compound containing calcium and phosphorus is dissolved to obtain a homogeneous and stable solution. Therefore, a uniform-thickness film can be easily formed, and a bio-hard tissue substitute member with excellent performance can be obtained.
[0025]
In the present invention, since a chelating agent containing phosphorus is used, it is very easy to control the composition ratio between calcium and phosphorus. Therefore, the calcium phosphate compound obtained by removing the solvent and organic components from the solution has high homogeneity and high purity. Conventionally, this calcium phosphate compound has been obtained, for example, by a sol-gel method. In this method, water is added and partially hydrolyzed, so that it is provided as a stable sol state for coating or the like. However, especially in a multi-component system having different hydrolysis rates, it is difficult to stabilize the sol-gel and it is difficult to obtain a uniform film.
[0026]
Conventionally, in the solution method, an ordinary chelating agent such as ethylenediaminetetraacetic acid (EDTA) has been used. This EDTA has a large amount of organic components, and in order to remove this, heating at a high temperature of 500 to 600 ° C. is required in an oxidizing atmosphere. However, titanium, which is particularly frequently used as a bio-hard tissue replacement member, is considerably oxidized at this temperature, so that it is difficult to apply it to titanium coating.
[0027]
In addition, since EDTA does not dissolve in organic solvents, there is a problem that it is difficult to form a uniform film. Note that EDTA does not contain calcium or phosphorus, and is used only to form a stable solution. On the other hand, the chelating agent containing phosphorus used in the present invention itself contains an element constituting the calcium phosphate compound, which is advantageous also in this respect. Furthermore, it is excellent in operability, and a homogeneous calcium phosphate ceramic without an impurity phase can be obtained without requiring a special apparatus.
[0028]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail by way of examples.
(1) Example of calcining only calcium phosphate compound Example 1
Calcium nitrate was dissolved in methanol. Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). This solution was dried at 60 ° C. for 30 minutes to remove methanol. Then, it baked at 800 degreeC in the air atmosphere for 1 hour, and while removing the organic component in a chelate compound, the sintered compact was obtained. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products.
[0029]
Example 2
A sintered body was obtained in the same manner as in Example 1 except that calcium nitrate was replaced with calcium chloride. The crystal phase of the obtained sintered body was a chlorapatite single phase having no impurity phase such as decomposition products. When the firing conditions were 1100 ° C. and 1 hour, the crystal phase of the sintered body was a HAp single phase having no impurity phase.
[0030]
Example 3
Calcium nitrate was dissolved in distilled water. Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). This solution was dried at 60 ° C. for 30 minutes and then fired in the same manner as in Example 1 to obtain a sintered body. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products.
[0031]
Example 4
Calcium thiocyanate was dissolved in methanol. Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). This solution was dried in the same manner as in Example 1, and then fired to obtain a sintered body. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products.
[0032]
Example 5
Calcium nitrate was dissolved in methanol. Further, methylene diphosphonic acid was added so that the atomic ratio (CA / P) of calcium to phosphorus in the solution was 1.67 (total molar concentration of calcium and phosphorus; 0.05 mol / L) was stirred. This solution was dried in the same manner as in Example 1, and then fired to obtain a sintered body. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products.
[0033]
(2) Example where solution was coated on substrate and baked Example 6
Calcium nitrate was dissolved in methanol. Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). Thereafter, this solution was coated on the surface of a substrate made of titanium and dried in the same manner as in Example 1. Thereafter, the organic component in the chelate compound was removed by heat treatment at 350 ° C. for 10 minutes in an air atmosphere. Next, it was baked at 800 ° C. for 10 minutes in an argon atmosphere. The formed film had no residual carbon and no cracks were observed.
[0034]
FIG. 1 shows the result of X-ray diffraction of the coating formed on the surface of titanium. According to this, it can be seen that the crystal phase is a single HAp phase having no impurity phase such as decomposition products. In addition, since titanium also had a low heat treatment temperature, no titanium oxide phase was observed.
[0035]
Example 7
A film was formed in the same manner as in Example 6 except that alumina was used instead of titanium and the firing atmosphere was an air atmosphere. There was no residual charcoal in this coating, and no cracks were observed. The crystal phase was a HAp single phase without an impurity phase such as a decomposition product, and no reactant phase with alumina was observed.
[0036]
Example 8
A coating was formed in the same manner as in Example 6 except that a Ti-6Al-4V alloy was used instead of titanium. There was no residual charcoal in this coating, and no cracks were observed. The crystal phase was a HAp single phase without an impurity phase such as a decomposition product, and no reactant phase with the alloy was observed.
[0037]
(3) Example in which acid or diol was coexisted in the system Example 9
Calcium nitrate was dissolved in methanol. Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). Furthermore, 0.75 mol of nitric acid was added to 1 mol of calcium. This solution was dried in the same manner as in Example 1, and then fired to obtain a sintered body. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products. The solution before drying was stable for a long period.
[0038]
Example 10
Calcium nitrate was dissolved in a mixed solvent of methanol and ethylene glycol (volume ratio 8/2). Furthermore, 1-hydroxyethane-1,1-bisphosphonic acid was added so that the atomic ratio (Ca / P) of calcium to phosphorus in the solution was 1.67 (total moles of calcium and phosphorus). (Concentration: 0.05 mol / liter). This solution was dried in the same manner as in Example 1, and then fired to obtain a sintered body. The crystal phase of the obtained sintered body was an HAp single phase having no impurity phase such as decomposition products. The solution before drying was stable for a long period.
[0039]
Comparative Example 1
Calcium ethoxide was dissolved in methanol. Triethyl phosphate was added to this solution, and water diluted with methanol was gradually added to cause partial hydrolysis. As a result, only the calcium content settled and phase separation occurred.
[0040]
【The invention's effect】
According to the first invention and the second invention, a stable solution in which a chelate compound containing calcium and phosphorus is dissolved can be easily prepared. In addition, the chelating agent used is soluble in organic solvents and has a low organic content. Therefore, homogeneous calcium phosphate ceramics can be easily obtained from the above solution. In addition, by forming a coating film made of the above ceramics on the surface of a bio-hard tissue substitute member made of titanium, alumina, or the like, a bio-hard tissue substitute member having high strength and excellent bioactivity can be obtained.
[Brief description of the drawings]
1 is a chart showing the results of X-ray diffraction of a HAp phase formed on the surface of titanium in Example 6. FIG.

Claims (5)

A step of preparing a solution by dissolving a salt containing calcium and a chelating agent containing phosphorus in a solvent, a step of drying the solution to remove the solvent, and a step of firing the residue from which the solvent has been removed The manufacturing method of the calcium-phosphate type ceramics characterized by the above-mentioned. A step of preparing a solution by dissolving a salt containing calcium and a chelating agent containing phosphorus in a solvent, a step of drying the solution to remove the solvent, and heat-treating the residue from which the solvent has been removed, A method for producing a calcium phosphate-based ceramic, comprising: a step of producing a calcium phosphate compound; and a step of firing the calcium phosphate compound. The method for producing a calcium phosphate ceramic according to claim 2, wherein the temperature of the heat treatment is 250 to 400 ° C and the time is 5 to 20 minutes. The method for producing a calcium phosphate ceramic according to any one of claims 1 to 3, wherein 0.1 to 10 mol of an acid is added to the solvent with respect to 1 mol of calcium contained in the salt. The method for producing a calcium phosphate ceramic according to any one of claims 1 to 3, wherein 0.01 to 10 mol of a diol is added to the solvent with respect to 1 mol of the solvent.

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