JPH02180705A - Tetracalcium phosphate and its cured body - Google Patents

Abstract

PURPOSE:To obtain high-purity tetracalcium phosphate of stabilized quality in good yield by adding a specified amt. of an Al compd. to a mixture of Ca- source material powder and P-source material powder, and heating the mixture to a (half)molten state. CONSTITUTION:The Ca-source material powder (e.g. CaCO3) and P-source material powder (e.g. CaHPO3) having <=20mum particle diameter and about 5mum average particle diameter are mixed in 2 molar ratio of Ca/P. From 0.005 to 5 pts.wt. of an Al compd. [e.g. Al(OH)3] as Al2O3 based on the 100 pts.wt. of the theoretical yield of tetracalcium phosphate to the mixed powder. The mixed powder is (half)melted at >=1400 deg.C, and then naturally cooled to obtain tetracalcium phosphate. A mixed powder of 100 pts.wt. of the obtained tetracalcium phosphate powder and 0.005-50 pts.wt. of the silica-alumina-based amorphous glass powder having <=10mum particle diameter and about 3mum average particle diameter is mixed with an aq. soln. contg. 30-60wt.% of the internal acid (e.g. citric acid) or polyacrylic acid shown by the formula (n is 1000-100,000) to obtain a tetracalcium phosphate cured body.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to tetracalcium phosphate, hardened tetracalcium phosphate, and methods for producing these, which are useful as artificial bone materials, dental materials, and the like.

In this specification, "molten state" refers to a state in which the raw material powder becomes fluid as a result of being heated, and "semi-molten state" refers to a state in which the raw material powder is heated and becomes fluid as a whole. , refers to a state in which the powder particles have apparently disappeared and formed a homogeneous phase, although they are not welded to flow. Furthermore, the term "porous state" refers to a state in which the raw material powder is heated and reacts on the surface of each powder particle, but each powder particle remains as it is without losing its shape.

Furthermore, in this specification, "parts" and "%" represent "parts by weight" and "% by weight," respectively.

Prior art and its problems Tetracalcium phosphate is a phosphoric acid compound that is a major inorganic component of bones, teeth, etc. It has high chemical activity and easily reacts with inorganic acids, saturated and unsaturated organic acids, homopolymers and copolymers of unsaturated organic acids, aqueous solutions thereof, physiological saline, etc. at room temperature, and cures. It has the property of These hardened products have biocompatibility and are useful as artificial bone materials, dental materials, and the like.

Conventionally, as raw materials for producing tetracalcium phosphate, CaCO3 and Cab have been used as Ca sources.

Ca(OH)2 etc. are used, and P2 is used as a P source.
O3, H3PO4, NH4H2PO4, (NH4)
2 HP OA, etc. are used, and furthermore, CaHPO4, Ca (H2PO4)2, etc. are used as Ca and P sources. There are various methods for producing tetracalcium phosphate depending on the raw materials used, but CaCO3 and Ca HP
The most common method is the dry manufacturing method described below, in which OA is mixed with OA and fired.

2CaCO3 + 2CaHPO4 → Ca, 4 (po4) 20 + H20 + 2CO2 In this method, the raw material powder mixture is fired at a temperature of about 1300 to 1600°C, and then rapidly cooled to about 400°C (cooling rate 10
℃ per minute or more), and a phosphoric acid compound mixture containing a large amount of tetracalcium phosphate is obtained. In this method, when the firing temperature is 1600°C or higher, the product forms a mixed phase of porous parts and semi-molten parts,
Inconsistency in the quality of tetracalcium phosphate is a problem. In addition, even if the firing temperature is in the temperature range of about 1300 to 1600°C, the obtained tetracalcium phosphate is highly reactive and very unstable, so if the cooling rate is low,
Hydroxyapatite is easily produced by absorbing water vapor in the atmosphere in the temperature range of 1200 to 400°C. Therefore, in this method, in order to increase the yield of tetracalcium phosphate and obtain a product with stable quality, the firing temperature, moisture content in the atmosphere inside the firing furnace during cooling, cooling rate, etc. must be strictly controlled. need to be managed.

However, removing moisture from the atmosphere inside the firing furnace is
This is difficult in actual operation. Furthermore, forcibly cooling the product in the firing furnace is not only technically difficult, but also causes damage to the furnace wall refractories due to rapid cooling.

Means for Solving the Problems As a result of intensive research in view of the current state of the technology as described above, the present inventor has found that when a raw material mixture to which a specific amount of aluminum compound is added is heated to a semi-molten or molten state. It has been found that the problems of the prior art are greatly reduced or substantially eliminated. It has also been found that the cured product obtained from tetracalcium phosphate thus obtained also has physical properties comparable to those of conventional products.

That is, the present invention provides the following tetracalcium phosphate, a cured product of tetracalcium phosphate, and a manufacturing method thereof: ■Producing tetracalcium phosphate using calcium source material powder and phosphorus source material powder as raw materials. During production, CaHPO4
(molar ratio), and further added 0.005 to 5 parts of aluminum compound as A1□03 to 100 parts of theoretical production amount of tetracalcium phosphate, and heated at a temperature of 1400℃ or higher. A method for producing tetracalcium phosphate, which is characterized by semi-melting or melting the tetracalcium phosphate.

■Tetracalcium phosphate produced by the method described in category (1) above.

■ A powder mixture consisting of 100 parts of tetracalcium phosphate powder produced by the method described in item (1) above and 0.005 to 50 parts of silica-alumina amorphous glass powder is added to 1. A method for producing a cured tetracalcium phosphate, which comprises mixing 60% of a body acid or polyacrylic acid represented by (CH2-CH) n 0OH (n is 1000 to 1'00000).

(2) A hardened tetracalcium phosphate product produced by the method described in item (3) above.

In the present invention, the raw materials for producing tetracalcium phosphate may be the same as those used in the conventional method described above. However, when using the produced tetracalcium phosphate as a biomaterial, it is necessary to use substances that are approved as food additives from the viewpoint of safety, such as calcium phosphate.
HP O4, Ca HP O4 Red 2 H20, Ca
Preferably, CO3, Ca3(PO4)2, etc. are used. These are usually less than 20μm, average 5μm
It is used as a powder of about m.

In addition, aluminum compounds to be added to the raw materials for producing tetracalcium phosphate include Al2O3, AQ (OH)3
, AQ (PO)3 , ARPot, AQ (H2
PO4)a, AQB2, AQcQ3, AlF2, A
Q■3, AR2 (Si03)3, AQ2 (SO4)
3, AQ2 Ti05, etc., which may be used alone or in combination of two or more. Among these, Al2O3 is more preferable from the viewpoint of uniformity of the fired product, adjustment of the firing temperature, color tone of the product, etc. The aluminum compound is also used as a powder, usually 20 μm or less, with an average size of about 5 μm.

In the present invention, such raw materials are blended so that the Ca/P molar ratio is 2, and an aluminum compound is added as Al2O3 to 100 parts of the theoretical amount of tetracalcium phosphate produced from this raw material blend. After adding 0.005 to 5 parts and firing at a temperature of 1400°C or higher to semi-melt or melt, the mixture is allowed to cool naturally in a furnace. The cooling rate can vary widely depending on the amount of raw materials used, the capacity and structure of the furnace, etc., but in any case, compared to the rapid cooling of 10°C/min or more as in conventional methods, it is extremely slow. It's cooling. During firing, the raw powder mixture containing all of the above components is shaped to the extent that it does not disintegrate, and if it is semi-melted, there is no need for a container to contain the raw powder mixture, and it is easy to handle. This is advantageous because it allows effective use of the volume. A more preferable amount of the aluminum compound to be added is 1 to 2 parts per 100 parts of the tetracalcium phosphate crystal ring, and a more preferable firing temperature is 1500 to 1550°C.

Figure 1 shows the amount of Al2O3 added to a raw material mixture with a Ca/P molar ratio of 2 (the amount added to 100 parts of the theoretical amount of tetracalcium phosphate to be produced), the firing temperature, and the semi-molten and molten states. shows the relationship between From Figure 1,
It is clear that the semi-molten and molten states can be adjusted quite freely by adjusting the blending amount of 1!203. For example, if the blending amount of Al2O3 is 5%, a semi-molten product can be obtained by setting the firing temperature to about 1450°C.

Figure 2 also shows the amount of AQ203 added to a raw material mixture with a Ca/P molar ratio of 2 (the amount added to 100 parts of the theoretical amount of tetracalcium phosphate to be produced), the calcination temperature, and the amount in the product. The relationship with the proportion of tetra-calcium phosphate is schematically shown.

If the amount of Al2O3 added exceeds 5%, only hydroxyapatite will be formed, so it is clear that the amount of Al2O3 added should be 5% or less.

The tetracalcium phosphate obtained as described above is baked very hard and hardly converted into hydroxyapatite. In addition, tetracalcium phosphate obtained by conventional firing methods is usually grayish white, but depending on the type of raw materials used, the influence of trace impurities, etc., the fired product may be partially or completely dark colored, grayish green, etc. colored,
In many cases, they lose their value as biomaterials from an aesthetic point of view. However, the tetracalcium phosphate obtained by the method of the present invention in which A92 o3 is blended is not affected by the type of raw materials used or trace impurities, and is uniformly colored from pale blue to light blue as a whole and is beautiful.

The properties of the tetracalcium phosphate according to the present invention can be improved by further adding other additives to the raw material mixture. For example, in order to impart X-ray contrast properties, antibacterial properties, etc. to tetracalcium phosphate, BaSO
4. Alkaline earth metal compounds such as BaCO3, SrSO4, SrCO3, BaS i F6, SnF2,
One or more fluorine-containing compounds such as CaF2, NaFSAIF3, Na2SiF6, etc. can be added. These optional additives can be used in place of up to about 60% of the aluminum compound as Al2O3. These optional additives are also used in the form of powder, usually 20 μm or less, with an average size of about 5 μm.

The cured product of tetracalcium phosphate according to the present invention is obtained by adding the powder mixture to a powder mixture consisting of 100 parts of the tetracalcium phosphate powder produced by the above method and 0.005 to 50 parts of silica-alumina amorphous glass powder. 30-60 of polymerization
% of body acid or polyacrylic acid represented by the following formula (a) (CH2CH) n (a)0OH (n is 1000 to 100000).

The particle size of tetracalcium phosphate powder is usually 20 μm or less,
The average size is about 5 μm.

Silica-alumina glass is made by melting, rapidly cooling, vitrifying, and pulverizing raw materials whose main components are silica and alumina, and which may also contain small amounts of calcium, fluorine, sodium, phosphorus, titanium, strontium, etc. is used.

When the amount of the silica-alumina amorphous glass powder is less than 0.005% based on 100 parts of the tetracalcium phosphate powder, almost no effect is observed due to the addition. On the other hand, 5
When it exceeds 0%, there is almost no improvement in strength, or there is a tendency for the strength to decrease. The amount of the silica-alumina amorphous glass powder is more preferably 8 to 15 parts. The particle size of the silica-alumina amorphous glass powder is usually 10 μm or less, with an average of about 3 μm.

Examples of the internal acids used in the present invention include citric acid, malonic acid, malic acid, maleic acid, lactic acid, fumaric acid, ascorbic acid, succinic acid, gluconic acid, glutaric acid, and pyruvic acid. One or more acrylic acids can be used, if necessary in the form of an aqueous solution. The amount of these internal acids and/or polyacrylic acid used (as acid) is about 30 to 60% of the total weight of the tetracalcium phosphate powder and the silica-alumina amorphous glass powder.

Since the tetracalcium phosphate hardened product obtained in this way has a large bulk specific gravity of the tetracalcium phosphate powder, the bulk specific gravity itself is significantly larger than that of conventional products.
The crushing strength is also high.

Therefore, such a hardened product is useful as a biomaterial such as an artificial bone material or a dental material.

Effect of the invention According to the present invention, the following remarkable effects can be obtained.

(1) Unlike the conventional method, the operation of semi-melting or melting the unblended raw material powder eliminates the need for rapid cooling, dehumidification and drying in the firing furnace, etc.

Therefore, a firing furnace with a special structure is not required, and manufacturing can be carried out using a normal firing furnace, thereby reducing manufacturing costs.

(2) The yield of tetracalcium phosphate is high, and the obtained tetracalcium phosphate has high purity.

(3) When firing a Ca source compound and a P source compound, they will not melt unless the temperature is about 1600° C. or higher, although it depends on the purity of the compounds used. On the other hand, the method of the present invention in which Al2O3 is used in combination is advantageous in terms of energy since the semi-melting or melting temperature is significantly lowered.

(4) By using Al2O3 in combination, the semi-melting temperature range is expanded, so variations due to product loft and non-uniformity of component composition inside the product are greatly reduced, resulting in products with uniform and stable quality. can get.

(5) If only the Ca source compound and P source compound are fired,
Even if the product is not aesthetically pleasing, by using Al2O3 in combination, a beautiful product that is uniformly colored from light blue to light blue can be obtained.

(6) The cured tetracalcium phosphate material according to the present invention has a large bulk specific gravity and high crushing strength.

EXAMPLES Examples and comparative examples are shown below to further clarify the features of the present invention.

Example 1 Powdered CaCO3 and CaHPO4 with a particle size of about 5 μm were mixed at a molar ratio of 1:1, Al2O3 was added at a ratio of 0.1% of the weight of the mixture, and the mixture was heated at 1600°C in the atmosphere for 2 hours. After firing in a furnace and semi-melting it, it was allowed to cool naturally in the furnace, and when the temperature decreased to 400'C, it was taken out of the furnace.

The X-ray diffraction results of the product are shown in the upper part of FIG.

From the results shown in Figure 3, it is clear that the product consists essentially of tetracalcium phosphate.

Comparative Example 1 The same operation as in Example 1 was performed except that the firing temperature was 1500°C. The product was porous.

The results of X-ray diffraction of the product are shown in the lower part of Figure 3.

From the results shown in Figure 3, it is clear that the product contains a large amount of hydroxyapatite in addition to tetracalcium phosphate.

Example 2 The same operation as in Example 1 was performed except that the amount of Al2O3 added was in the range of 0.005 to 50% and the firing temperature was in the range of 1350 to 1600°C.

The X-ray diffraction results of the product are shown in Figures 4A-F.

The relationship between FIG. 4 A to F, the amount of AQ203 added, and the firing temperature is as follows.

■, 48th A! 203: 50% Firing temperature: 1350°C ■, Figure 4 B Al2O3: 20% Firing temperature: 1400°C ■, Figure 4 C AQ20a: 10% Firing temperature: 1450°C ■, Figure 4 D AQzO3: 5% firing Temperature: 1450°C ■, 4th pipe EI2203: 1.5% Firing temperature: 1500°C ■, Figure 4 F A (2203: 0.005% Firing temperature: 1600°C Results shown in Figure 4 A-F) From, AQ203 addition amount is 5%
If it is below, the melting temperature will drop significantly and tetracalcium phosphate will also be produced satisfactorily. However, Al2O
Even if the amount of Al2O3 added exceeds 5%, no significant decrease in the melting temperature will be observed, and on the contrary, the production of tetracalcium phosphate will be inhibited.
The upper limit is %.

Example 3 Tetracalcium phosphate (A12203
Addition amount: 1.5%) powder (average particle size 5 μm) 100 parts of silica-alumina glass powder (50% silica, 30% alumina, and 2 trace components such as 5rSTi and Ca)
45% citric acid, 45% malic acid or 30% malic acid and polyacrylic acid (formula (a) ), 50 parts of an aqueous solution containing 15% of n=approximately 16,000) was added as an acid to obtain a cured product.

On the other hand, for comparison, a cured product was obtained in the same manner as above except that a conventional tetracalcium phosphate powder containing no A12203 was used.

Crushing strength of each cured product after 24 hours (kgf/cJ)
were as shown in Table 1.

In Table 1, each symbol represents the following.

A: Amount of silica-alumina glass powder used = 10
Portion: Amount of silica-alumina glass powder used = 30
Part C: Usage amount of silica-alumina glass powder = 50
Part 2... Citric acid... Malic acid... Malic acid + Polyacrylic acid Table 1 Acid - Ho Conventional product A 653 810 803 C 580 751 766 Example A 1035 1260 1124 C
720 880 893 The crushing strength of the cured tetracalcium phosphate obtained by the present invention is higher than that of conventional tetracalcium phosphate cured in the same manner.
It has reached about 1.5 times.

[Brief explanation of the drawing]

Figure 1 shows the l! for a raw material formulation with a Ca/P molar ratio of 2. 2 is a graph showing the relationship between the amount of No. 203 added, the firing temperature, and the semi-molten and molten states. FIG. 2 is a graph showing the relationship between the amount of Al2O3 added to a raw material mixture with a Ca/P molar ratio of 2, the firing temperature, and the production rate of tetracalcium phosphate in the product. FIG. 3 is a chart showing the X-ray diffraction results of the products obtained in Example 1 and Comparative Example 1. 4A to 4F are charts showing the X-ray diffraction results of each product obtained in Example 2. (Above) Procedural proceedings (spontaneous) March 6, 1999 Director General of the Japan Patent Office Yoshi 1) Moon Takeshi, N1 Indication of the case Patent Application No. 332463 of 1988 2 Name of the invention Tetracalcium phosphate and Tetracalcium Phosphate Hardened Product 4 Agent Sawanotsuru Building Sponsored, 2-1-2 Hirano-cho, Chuo-ku, Osaka 6 ``Claims'' in the specification to be amended and [Details of the amendment 1 Specification The scope of claims in the document is corrected as shown in the attached sheet. ~ 2 On page 3 of the specification, lines 3 to 4, “The surface of each powder particle...
The phrase ``as it is'' is corrected to ``Although each powder particle reacts with each other, each powder particle does not completely lose its shape and remains roughly the same.'' 3. On page 3, lines 13-14 of the specification, the phrase "copolymers and aqueous solutions thereof" is corrected to "aqueous solutions of copolymers, etc." 4. On page 14, line 7 of the specification, “pyruvic acid” has been replaced with “
Pyruvic acid,” he corrected. 5 On page 7, lines 9 and 10 of the specification, the statement r (CH2CH)n is corrected to 0OHJ [(CH2CH)n. OOHJ 6 On page 13 of the specification, lines 2-3, replace r (CH2CH)n (a) with C
Correct it as 0OHJ r (CH2CH)n (a). C0OHJ (and above) Claims ■ When producing tetracalcium phosphate using calcium source material powder and phosphorus source material powder as raw materials, Ca/P=
Both material powders are blended so that the molar ratio is 2 (molar ratio), and the aluminum compound is added to A/! for 100 parts of the theoretical production amount of tetracalcium phosphate. A method for producing tetracalcium phosphate, which comprises adding 0.005 to 5 parts of 203 and semi-melting or melting at a temperature of 1400°C or higher. (2) Tetracalcium phosphate produced by the method according to claim (1). (1) To a powder mixture consisting of 100 parts of tetracalcium phosphate powder produced by the method according to claim (1) and 0.005 to 50 parts of silica-alumina amorphous glass powder, 30 to 30 parts of the weight of the powder mixture is added. A method for producing a hardened tetracalcium phosphate material, which comprises mixing polyacrylic acid represented by 60% internal acid or procedurally corrected writing type (n is 1,000 to 100,000). (2) A cured tetracalcium phosphate produced by the method according to claim (3). 1 Indication of the case Patent Application No. 332463 of 1988 2 Name of the invention Tetracalcium phosphate and tetracalcium phosphate 4 Agent Sawanotsuru Building, 2-1-2 Hirano-cho, Chuo-ku, Osaka April 25, 1999 6 Section 7 "Brief explanation of drawings" in the specification subject to amendment Contents of amendment 1 As shown in the attached sheet Contents of amendment 1 Page 22 of the specification, lines 13 to 14 "Figures 4 A-F
is...a chart. '' should be corrected as follows. "Figure 4 is a chart showing the X-ray diffraction results of each product obtained in Example 2." (End)

Claims (4)

[Claims] (1) When producing tetracalcium phosphate using calcium source material powder and phosphorus source material powder as raw materials, Ca/P
= 2 (molar ratio), and further added 0.005 to 5 parts of aluminum compound as Al_2O_3 to 100 parts of theoretical production amount of tetracalcium phosphate, and heated to a temperature of 1400°C or higher. A method for producing tetracalcium phosphate, which is characterized by semi-melting or melting the tetracalcium phosphate. (2) Tetracalcium phosphate produced by the method according to claim (1). (3) A powder mixture consisting of 100 parts of tetracalcium phosphate powder produced by the method according to claim (1) and 0.005 to 50 parts of silica-alumina amorphous glass powder is added to A method for producing a cured tetracalcium phosphate, which comprises mixing 30 to 60% of a body acid or polyacrylic acid represented by (CH_2-CH)_nCOOH (n is 1000 to 100000). (4) A cured tetracalcium phosphate product produced by the method according to claim (3).