JPH01100039A - Powder for producing calcium phosphate based cured body and production of composite composition and cured body - Google Patents

Abstract

PURPOSE:To obtain a powder for producing a calcium phosphate based cured body, capable of uniformly, sufficiently and moderately advancing curing reaction within a neutral region and providing a cured body having a high curing strength without biological histotoxicity, by calcining hydroxyapatite having a specific ratio of Ca/P under reduced pressure condition. CONSTITUTION:This powder for producing a calcium phosphate based cured body is formed from a blend of alpha-tricalcium phosphate with tetracalcium phosphate obtained by calcining hydroxyapatite having >1.5-<=1.8 Ca/P ratio at 1,150-1,450 deg.C temperature under reduced pressure condition. A composite composition for producing the calcium phosphate based cured body is formed from this powder and a solution agent consisting of an aqueous solution of gluconic acid or an acidic aqueous solution prepared by adding one or two or more selected from monosaccharides, oligosaccharides, sugaralcohols and polyhydric alcohols. The resultant composite composition is subsequently kneaded and cured to form the aimed calcium phosphate based cured body.

Description

Detailed Description of the Invention "Field of Application" The present invention relates to a powder and a composite composition for producing a calcium phosphate-based hardened product, and a method for producing the hardened product, and more specifically to a material for medical or dental cement or a bone material. The present invention relates to powders and composite compositions for producing calcium phosphate-based hardened bodies useful as prosthetic materials, and methods for producing hardened bodies useful as block-shaped hardened bodies, artificial bones, artificial tooth roots, etc.

"Prior Art and its Problems" In recent years, various calcium phosphate compounds, particularly hydroxyapatite, have attracted attention as materials with excellent biocompatibility. It is well known that hydroxyapatite is an inorganic component constituting bones and teeth, and the use of these calcium phosphate compounds as biomaterials is being considered. By the way, it is said that calcium phosphates other than hydroxyapatite are converted to hydroxyapatite by hydrolysis, but it has been discovered that under certain conditions the generated hydroxyapatite can be hardened, and this property can be used to harden the hydroxyapatite. , the use of calcium phosphate powder as dental or medical cement has been actively researched (for example, Japanese Patent Application Laid-Open No. 1982-12).
No. 705, No. 61-161206, No. 59-1822
No. 63, Publication No. 59-88351, etc.).

Currently, active calcium phosphates that are raw materials for such calcium phosphate-based hardened products include α-tricalcium phosphate (Caw(POg)z), tetracalcium phosphate CCaa(PO4)*O), and these two types. Mixtures of are known. As for its manufacturing method, α-tricalcium phosphate is produced by mixing calcium carbonate and calcium pyrophosphate and calcined at 1250'C, and tetracalcium phosphate is produced by mixing carbonic acid and calcium pyrophosphate by attrition.
The method of firing at 500° C. and the method of manufacturing these mixtures include a method of mixing the three materials manufactured as described above by rubbing.

However, since all of these production methods involve solid-phase reactions, the resulting powders lack uniformity in composition. For this reason, the reaction does not proceed uniformly during curing,
This was one of the causes of decreasing the strength of the cured product. Furthermore, since the firing temperature is high, the activity of the powder obtained is low, resulting in a prolonged curing time and a decrease in cured strength due to incomplete curing.

In addition, the powder made of calcium phosphate obtained in this way and the curing liquid to be kneaded should reduce the pH of the mixed substance and allow the curing reaction to proceed in a neutral region, thereby eliminating harm to living tissues. From this point of view, a citric acid aqueous solution was conventionally considered the best solution, but there remained room for further improvement in this respect as well.

``Object of the Invention'' The object of the present invention is to obtain a calcium phosphate-based cured product that has high cure strength and is not harmful to living tissues by allowing the curing reaction to proceed uniformly, sufficiently, and moderately in a neutral region. An object of the present invention is to provide a method for producing the cured product, as well as a powder and a composite composition for producing the cured product.

"Structure of the Invention" The powder for producing a calcium phosphate-based hardened product according to the present invention is prepared by preparing hydroxyapatite having a Ca/P ratio of more than 1.5 and less than 1.8 under reduced pressure at a temperature of 1150°C to 1450°C. It is characterized by being composed of a mixture of α-tricalcium phosphate and tetracalcium phosphate obtained by firing at

Moreover, the composite composition for producing a calcium phosphate-based hardened product in the present invention includes the above-mentioned powder, an aqueous gluconic acid solution, or a monosaccharide. ! It is characterized by comprising an acidic aqueous solution containing one or more selected from the group consisting of alcohols, sugar alcohols, and polyhydric alcohols.

The present invention further provides a method for producing a calcium phosphate-based cured product by kneading the powder with the liquid and curing the mixture.

As mentioned above, the powder for producing a calcium phosphate-based hardened product according to the present invention has a Ca/P ratio of more than 1.5 and 1.8.
Hydroxyapatite which is below 1150℃~14
It consists of a mixture of α-tricalcium phosphate and tetracalcium phosphate obtained by firing under reduced pressure conditions at a temperature of 50°C.

Hydroxyapatite, which is used as a raw material in the preparation of this powder, can be easily synthesized by a wet method in which a phosphoric acid aqueous solution and a calcium hydroxide suspension are reacted by a known method, but its CaZP ratio exceeds 1.5 and 1 ．．
It needs to be in a range of 8 or less, and more preferably in a range of 1.6 to 1.8. That is, when the Ca/P ratio is 1.5, the target compound becomes α-tricalcium phosphate itself,
This is because if the CaZP ratio exceeds 1.8, calcium oxide, which has an adverse effect on living organisms, will be produced during firing, which is undesirable. The Ca/P ratio of hydroxyapatite used as a raw material can be changed by changing the ratio of calcium hydroxide and phosphoric acid reacted in the manufacturing process.

And CaZP of hydroxyapatite used as raw material
By changing the ratio, the ratio of α-tricalcium phosphate and tetracalcium phosphate finally produced can be changed to a desired value.

Hydroxyapatite used as a raw material is desirably synthesized by a wet method, for example, and then pulverized by means such as filtration, centrifugation, or spray drying. It is desirable to thoroughly dry the material by calcining it at a temperature of about 500 to 700 DEG C. to remove as much moisture as possible.

In the powder of the present invention, the above-mentioned hydroxyapatite is fired under reduced pressure at a temperature of 1150"C to 1450°C. This is because at temperatures below 1150°C, decomposition reactions do not occur even if the degree of vacuum is lowered. On the other hand, 1450℃
This is because if the temperature exceeds , the activity of the resulting mixture of α-tricalcium phosphate and tetracalcium phosphate will be reduced, and the reason why reduced pressure conditions are adopted is that this lowers the calcination temperature. This is because the activity of the product can be increased, and the process can be simplified and the manufacturing cost can be reduced. Note that the reduced pressure condition is preferably 10 Pa or less, and 10-"Pa
The following are more preferred.

The mixture of α-tricalcium phosphate and tetracalcium phosphate prepared in this manner is optionally subjected to mechanical pulverization or the like to form a powder.

The liquid used to harden the powder prepared as described above is an aqueous gluconic acid solution or an acidic aqueous solution containing one or more selected from monosaccharides, oligosaccharides, sugar alcohols, and polyhydric alcohols. be.

When using an aqueous gluconic acid solution as a liquid agent, it is desirable that its concentration is 40% by weight or more, more preferably 50 to 90% by weight. This is because if the concentration is less than 40% by weight, the curing reaction tends to slow down considerably.

When an acidic aqueous solution containing the above additives is used as the liquid agent, this may be an acidic aqueous solution containing dissolved various inorganic and organic acids.

Examples of acids include inorganic acids such as phosphoric acid, or organic acids such as acetic acid, lactic acid, citric acid, malic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, and polyacrylic acid. In the present invention, these acids are preferably used at a concentration of 25% by weight or more, more preferably from 25 to 55% by weight. When the acid concentration is less than 25% by weight, the strength of the cured product tends to be insufficient.

In the present invention, as described above, one or more of monosaccharides, oligosaccharides, sugar alcohols, and polyhydric alcohols are added to the acidic aqueous solution as additives. These additives allow the curing reaction to proceed mildly.

Examples of the class Ii that can be used include glucose, fructose, and the like. Also, Sho I! Examples of alcohols include saccharose, maltose, lactose, raffinose, etc.; examples of sugar alcohols include sorbitol, mannitol, xylit, etc.; and examples of polyhydric alcohols include glycols such as ethylene glycol, glycerin, etc. These additives may be used alone or in combination.

The amount of these additives to be used can be determined as appropriate depending on the situation, but if it is too small, the effect of the addition will not be achieved. The concentration of alcohols, sugar alcohols, and polyhydric alcohols is preferably 5 to 5 in total.
40% by weight, more preferably 10 to 30% by weight in total. If the amount of these additives is less than 5% by weight, the effect of the addition will not be apparent, and if it exceeds 40% by weight, these additives will become difficult to dissolve in the acidic aqueous solution.

In the present invention, by kneading the powder and liquid prepared as described above, a hydrolysis reaction of α-tricalcium phosphate and tetracalcium phosphate is caused to generate hydroxyapatite, and a hardened product is produced. It's something you get. At that time, the kneading ratio of the powder agent (P) and the liquid agent (L) is such that the amount of the powder agent to the liquid agent (P/L) is 0.4 to 2 by weight.
．． It is preferable to set the value to 7. If this ratio is less than 0.4, the strength of the resulting cured product will be weak due to the small solid content, while if it exceeds 2.7, uniform kneading of the powder and liquid will become difficult.

Incidentally, the powder prepared as described above may be formed into granules, and then mixed with a liquid and hardened at the time of use.

"Examples of the Invention" Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto. In the examples, "%" means "% by weight" unless otherwise specified.

Example 1 A phosphoric acid aqueous solution and a calcium hydroxide suspension were reacted and dried by a known method to obtain hydroxyapatite. The obtained product was confirmed by X-ray diffraction. This X-ray diffraction diagram is shown in FIG. Furthermore, the Ca/P ratio of the obtained hydroxyapatite was determined to be 1 by chemical analysis.
．． It was calculated as 67.

This hydroxyapatite was heated to a temperature of 1200 ”C1 pressure 1.3×10” ”Pa” 7:! It was baked for 1 hour. When the obtained product was examined by X-ray diffraction in the same manner as above, peak a for α-tricalcium phosphate and peak b for tetracalcium phosphate appeared as shown in Figure 2, indicating that the heat of hydroxyapatite It was confirmed that a mixture of α-tricalcium phosphate and tetracalcium phosphate was produced by the decomposition.

The mixture of α-tricalcium phosphate and tetracalcium phosphate thus obtained was made into a powder, and 3 g of this powder was added to a commercially available aqueous gluconic acid solution (manufactured by Wako Pure Chemical Industries, Ltd., 50% concentration).
When kneaded with 2 g, a hydrolysis reaction occurred and the mixture was cured after about 1 hour.

Example 2 Powders prepared in the same manner as in Example 1 were mixed with liquids having various compositions as shown in Table 1 in a weight ratio of powder:liquid: 1
:1, to obtain a cured product. Table 1 shows the curing time and heating temperature at this time.

Table 1 Example 3 1 g of a powder prepared in the same manner as in Example 1 and 1 g of a liquid having the composition shown in Table 2 were kneaded to obtain a cured product. The curing time at this time is shown in Table 2.

Table 2 Comparative Examples When 1 g of a powder prepared in the same manner as in Example 1 and 1 g of a 40% phosphoric acid aqueous solution were kneaded, they reacted violently with a large amount of heat generated and hardened once, but immediately disintegrated. .

"Effects of the Invention" The powder for producing a calcium phosphate-based hardened product of the present invention is α-tricalcium phosphate and tetracalcium phosphate obtained by firing hydroxyapatite at a temperature of 1150°C to 1450°C under reduced pressure conditions. Since it is made of a mixture of powder, it is uniform, and it is fired at a lower temperature than the conventional method, so it has significantly higher activity. By using the powder of the present invention, the curing reaction can proceed uniformly and sufficiently. , a cured product with high curing strength can be obtained.

On the other hand, by using an acidic aqueous solution to which monosaccharides, oligosaccharides, sugar alcohols, or polyhydric alcohols are added as a liquid agent, the curing reaction can proceed moderately and mildly.

Therefore, the present invention provides already cured biomaterial molded articles,
For example, it is not only possible to provide cured substances such as block-shaped cured substances, artificial bones, and artificial tooth roots, but also to be used in medical clinics for kneading powders and liquids immediately before use, filling defective areas such as bones and teeth, and curing them. Powders and composite compositions useful as dental or dental cement materials or bone replacement materials can also be provided.

[Brief explanation of the drawing]

FIG. 1 is an X-ray diffraction diagram of hydroxyapatite synthesized in Example 1 of the present invention, and FIG. 2 is an X-ray diffraction diagram of the powder prepared in Example 1 of the present invention. Explanation of symbols a...Peak of α-tricalcium phosphate b...Peak of tetracalcium phosphate Patent applicant Asahi Optical Co., Ltd.

Claims (1)

[Claims] 1. α-phosphoric acid obtained by calcining hydroxyapatite with a Ca/P ratio of more than 1.5 and less than 1.8 at a temperature of 1150°C to 1450°C under reduced pressure conditions. A powder for producing a calcium phosphate-based hardened product, characterized by comprising a mixture of tricalcium and tetracalcium phosphate. 2. A liquid preparation consisting of the powder according to claim 1 and an aqueous gluconic acid solution or an acidic aqueous solution containing one or more selected from monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols. A composite composition for producing a calcium phosphate-based cured product. 3. The composite composition according to claim 2, wherein the concentration of the gluconic acid aqueous solution is 40% by weight or more. 4. The composite composition according to claim 2, wherein the acid concentration of the acidic aqueous solution is 25% by weight or more, and the total concentration of monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols is 5 to 40% by weight. 5. A method for producing a calcium phosphate cured product, which comprises kneading and curing the composite composition according to claim 2.