JP2662984B2 - Composite composition for producing calcium phosphate-based cured product and method for producing cured product - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a composite composition for producing a calcium phosphate-based cured product and a method for producing a cured product, and more particularly to a material for medical or dental cement or a bone filling material. TECHNICAL FIELD The present invention relates to a composite composition for producing a calcium phosphate-based cured product useful as a cured product and a method for producing a cured product useful as a block-shaped cured product, an artificial bone, an artificial tooth root, and the like.

"Prior art and its problems" In recent years, various calcium phosphate compounds, particularly hydroxyapatite, have been attracting attention as materials having excellent biocompatibility. It is well known that hydroxyapatite is an inorganic component constituting bone and dentin, and the use of these calcium phosphate compounds as biomaterials is being studied. By the way, calcium phosphate other than hydroxyapatite is said to be converted into hydroxyapatite by hydrolysis, but under certain conditions, it has been found that the generated hydroxyapatite can be cured, and this property is utilized. The use of calcium phosphate powder as a dental or medical cement has been actively studied (for example, see JP-A-62-1270).
No. 5, No. 61-161206, No. 59-182263, No. 59-88351).

At present, active calcium phosphates which are the raw materials of such a calcium phosphate-based cured product include α-tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] and tetracalcium phosphate [Ca ₄
(PO ₄ ) ₂ O] and mixtures of these two are known.
As the production method, α-tricalcium phosphate is a method in which calcium carbonate and calcium pyrophosphate are mixed and calcined at 1250 ° C, and tetracalcium phosphate is a method in which carbonic acid and calcium pyrophosphate are crushed and mixed, and calcined at 1500 ° C. ,Also,
As a method of producing these mixtures, a method of crushing and mixing the two produced as described above is employed.

However, all of these production methods are solid phase reactions, and thus the composition of the resulting powder lacks uniformity. For this reason, the reaction does not proceed uniformly during curing, which has been one of the causes of reducing the strength of the cured product. In addition, since the firing temperature is high, the activity of the obtained powder is low, and the curing time is prolonged and the curing strength is reduced due to incomplete curing.

In addition, the thus-obtained powder composed of calcium phosphate and a hardening liquid to be kneaded reduce the pH of the kneaded material and promote a hardening reaction in a neutral region, thereby eliminating harm to living tissue. In view of the above, the citric acid aqueous solution has been conventionally considered to be the best, but there is still room for improvement in this respect.

"Object of the Invention" An object of the present invention is to promote a curing reaction uniformly and sufficiently in a neutral region and moderately moderately to obtain a cured product having a high curing strength and no harm to living tissues. And a composite composition for producing the cured product.

"Composition of the invention" The composite composition for producing a calcium phosphate-based cured product according to the present invention is obtained by calcining hydroxyapatite having a Ca / P ratio of more than 1.5 and 1.8 or less at a temperature of 1150 ° C to 1450 ° C under reduced pressure. And a powder comprising a mixture of α-tricalcium phosphate and tetracalcium phosphate, and one or more selected from aqueous gluconic acid solutions or monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols And a solution comprising an acidic aqueous solution to which is added.

The present invention further kneads the powder with the liquid,
It is intended to provide a method for producing a calcium phosphate-based cured product by curing.

As described above, the powder for producing a calcium phosphate-based cured product according to the present invention is obtained by calcining hydroxyapatite having a Ca / P ratio of more than 1.5 and not more than 1.8 at a temperature of 1150 ° C to 1450 ° C under reduced pressure. It consists of a mixture of the obtained α-tricalcium phosphate and tetracalcium phosphate.

Hydroxyapatite 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 the Ca / P ratio exceeds 1.5 and 1.8. It is necessary to be in the following range, more preferably 1.6
It is in the range of ~ 1.8. That is, the Ca / P ratio is 1.5
Then, α-tricalcium phosphate, which is one of the target compounds, becomes itself, and if the Ca / P ratio exceeds 1.8, calcium oxide, which has an adverse effect on living organisms, is generated during firing. This is not preferred. The Ca / P ratio of hydroxyapatite as a raw material can be changed by changing the ratio of calcium hydroxide and phosphoric acid reacted in the production process. Then, by changing the Ca / P ratio of hydroxyapatite as a raw material, the ratio of α-tricalcium phosphate and tetracalcium phosphate finally produced can be changed to a desired ratio.

Also, hydroxyapatite as a raw material is preferably synthesized by a wet method, and then powdered by means such as filtration, centrifugation, or spray drying.
It is desirable to dry sufficiently by calcining at a temperature of about 500 to 700 ° C. before thermal decomposition after firing in a later step to remove water as much as possible.

In the powder of the present invention, the hydroxyapatite as described above is calcined at a temperature of 1150 ° C to 1450 ° C under reduced pressure. This means that at temperatures below 1150 ° C., the decomposition reaction does not occur even if the degree of vacuum is reduced, while at temperatures above 1450 ° C., the activity of the resulting mixture of α-tricalcium phosphate and tetracalcium phosphate is reduced. The reason why the pressure reduction condition is adopted is that the firing temperature can be lowered, so that the activity of the product can be increased, further simplifying the process and manufacturing. This is because the cost can be reduced. The decompression condition is 10
Pa or lower is preferable, and 10 ^-2 Pa or lower is more preferable.

The mixture of α-tricalcium phosphate and tetracalcium phosphate thus prepared is subjected to mechanical pulverization or the like, if necessary, to obtain a powder.

The liquid used for curing the powder prepared as described above is a gluconic acid aqueous solution or an acidic aqueous solution to which one or more selected from monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols are added. is there.

When an aqueous solution of gluconic acid is used as the liquid agent, the concentration is preferably at least 40% by weight, more preferably 50 to 90% by weight. This is because if the concentration is less than 40% by weight, the curing reaction tends to be extremely slow.

When an acidic aqueous solution containing the above-mentioned additives is used as the liquid agent, it may be an acidic aqueous solution containing various inorganic and organic acids dissolved therein. Examples of the acid include an inorganic acid such as phosphoric acid and an organic acid 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 25 to 55% by weight. If 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 an additive. These additives allow the curing reaction to proceed gently.

Monosaccharides that can be used include, for example, glucose, fructose, and the like. Further, as oligosaccharides, for example, saccharose, maltose, lactose, raffinose, etc., as sugar alcohols, for example, sorbitol, mannitol, xylit, etc., further as a polyhydric alcohol,
For example, glycols such as ethylene glycol, glycerin and the like can be mentioned. One type of these additives may be used alone, or a plurality of types may be used in combination.

The amount of these additives used can be appropriately determined depending on the situation. However, if the amount is too small, the additive effect is not exhibited. In general, the concentration of monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols is preferably 5 to 40% by weight in total, 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 appear, and
If the amount is more than 10% by weight, these additives are difficult to dissolve in the acidic aqueous solution.

In the present invention, by kneading the powder and the liquid prepared as described above, a hydrolysis reaction of α-tricalcium phosphate and tetracalcium phosphate is caused to generate hydroxyapatite, and a cured product is formed. What you get. At this time, the mixing ratio of the powder (P) and the liquid (L) is preferably such that the blending amount (P / L) of the powder with respect to the liquid is 0.4 to 2.7 by weight. When the ratio is less than 0.4, the solid content is small, and the strength of the obtained cured product is low. On the other hand, when it exceeds 2.7, uniform mixing of the powder and the liquid becomes difficult.

The powder prepared as described above may be formed into granules, and mixed with a liquid before use to cure.

"Examples of the Invention" Next, the present invention will be described 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. Confirmation of the obtained product was performed by X-ray diffraction. The X-ray diffraction pattern is shown in FIG. The Ca / P ratio of the obtained hydroxyapatite was 1.67 by chemical analysis.
It was calculated.

This hydroxyapatite is heated at a temperature of 1200 ° C and a pressure of 1.3
It was fired at × 10 ^-4 Pa for 1 hour. When the obtained product was examined by X-ray diffraction in the same manner as described above, a main peak a of α-tricalcium phosphate and a main peak b of tetracalcium phosphate were expressed as shown in FIG. It was confirmed that a mixture of α-tricalcium phosphate and tetracalcium phosphate was generated by thermal decomposition of.

The mixture of α-tricalcium phosphate and tetracalcium phosphate thus obtained was used as a powder, and 3 g of this powder was added to a commercially available gluconic acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd .;
%) And kneaded with 2 g, a hydrolysis reaction occurs, and about 1
Cured after hours.

Example 2 A powder having various compositions as shown in Table 1 was added to a powder prepared in the same manner as in Example 1 in a weight ratio of powder: liquid.
The mixture was kneaded so as to be 1: 1 to obtain a cured product. Table 1 shows the curing time and the heat generation temperature at this time.

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.

COMPARATIVE EXAMPLE 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, the mixture rapidly reacted with a large amount of heat and hardened once, but immediately collapsed.

"Effects of the Invention" In the present invention, a powder for producing a calcium phosphate-based cured product is α-tricalcium phosphate and tetracalcium phosphate obtained by firing hydroxyapatite at a temperature of 1150 ° C. to 1450 ° C. under reduced pressure. , It is homogeneous and has a significantly higher activity since it is fired at a lower temperature than the conventional method. By using the above-mentioned powder, the curing reaction proceeds uniformly and sufficiently, and a cured product having high curing strength can be obtained.

On the other hand, the use of an acidic aqueous solution to which a monosaccharide, oligosaccharide, sugar alcohol or polyhydric alcohol is added as a liquid agent allows the curing reaction to proceed moderately and moderately.

Therefore, the present invention can provide not only a cured biomaterial molded product, for example, a cured product such as a block-shaped cured product, an artificial bone, and an artificial tooth root, but also kneading a powder and a liquid immediately before use to form a bone or a tooth. It is also possible to provide a powder and a composite composition useful as a medical or dental cement material or a bone filling material for filling and curing a defect such as.

[Brief description of the drawings]

FIG. 1 is an X-ray diffraction pattern of the hydroxyapatite synthesized in Example 1 of the present invention, and FIG. 2 is an X-ray diffraction pattern of the powder prepared in Example 1 of the present invention. Explanation of symbols a: Main peak of α-tricalcium phosphate b: Main peak of tetracalcium phosphate

Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location C04B 24:06 24:10 24:02)

Claims (4)

(57) [Claims] An α-tricalcium phosphate and a tetracalcium phosphate obtained by calcining hydroxyapatite having a Ca / P ratio exceeding 1.5 and not more than 1.8 at a temperature of 1150 ° C. to 1450 ° C. under reduced pressure. And a liquid formulation comprising an aqueous solution of gluconic acid or an acidic aqueous solution to which one or more selected from monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols have been added. A composite composition for producing a calcium phosphate-based cured product. 2. The composite composition according to claim 1, wherein the concentration of the aqueous gluconic acid solution is 40% by weight or more. 3. The composite composition according to claim 1, wherein the acidic aqueous solution has an acid concentration of 25% by weight or more, and the total concentration of monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols is 5 to 40% by weight. 4. A method for producing a calcium phosphate-based cured product, comprising kneading and curing the composite composition according to claim 1.