JPH01160560A - Human body hard tissue substituting composition - Google Patents

Abstract

PURPOSE:To obtain human body hard tissue substituting composition which meets body compatibility, set hardening speed, and strength after hardening by preparing using a powder containing octacalucium phosphate as the main ingredient and a kneading liquor. CONSTITUTION:The human hard tissue substituting composition consists of a powder containing octacalcium phosphate (Ca8H2(PO4)6.5H2O) and a kneading liquor. More in detail, the human hard tissue substituting composition is prepared by adding a mixture of calcium phosphate to a micropowder of octacalcium phosphate, and then further mixing with a polymer or copolymer of unsaturated carboxylic acid or aqueous solution of an inorganic acid or organic acid to make the mixture into a form of fluid or plastic. The powder of octacalcium phosphate is obtained by mixing anhydrous substance of calcium hydrogen phosphate and calcium carbonate homogeneously in a molar ratio of 2:1, drying, calcinating at 1000-1300 deg.C for about 1 hour and grinding into a micropowder of 350 mesh. The powder is hydrated, washed with neutral water, dried at ordinary temperature and calcinated. The powder of a mixture of calcium phosphate is obtained by mixing calcium hydrogen phosphate and calcium carbonate homogeneously in a molar ratio of 1:1, and calcinating for about 1 hour at 1300-1600 deg.C to make into a micropowder of at most 10mum in the particle diameter.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a human hard tissue replacement composition for replacing living tissue, and more specifically, it relates to a composition for replacing bone and teeth caused by pathological or external causes. The present invention relates to a human body hard tissue substitute composition that is used in areas and voids to facilitate the generation of new bone, and which is later integrated with the hard tissue of the living body.

[Prior Art] Conventionally, the following biological hard tissue substitute materials have been used.

Zinc phosphate cement, polycarboxylic acid cement, glass ionomer cement, etc. have been used as hard tissue substitute materials in the dental field.

Furthermore, in the medical field, methacrylate-based bone cement has been used as a bonding filling material.

However, these hard tissue compositions are different from the components of bones and teeth, and therefore cannot be said to have sufficient biocompatibility.

Therefore, in order to solve the problem regarding biocompatibility, we have developed artificial bones, artificial joints, and artificial tooth roots made of alumina single crystal or alumina sintered bodies, which are said to have relatively good compatibility with living bodies, or sintered hydroxyapatite. Artificial bones, artificial tooth roots, etc. made of aggregates have been proposed.

Furthermore, recently, a method of obtaining a cured product by kneading with an aqueous solution of an inorganic salt or an organic acid polymer, such as α-tricalcium phosphate powder called a hydroxyapatite precursor, has been known. (For example, see Japanese Patent Application Laid-Open No. 59-182263.) A method of kneading tetracalcium phosphate powder with an aqueous solution of acids has also been proposed. (JP-A-62 [Problems to be Solved by the Invention]) However, the above-mentioned conventional techniques each have the following drawbacks.

Living tissue substitute materials made of alumina single crystals, alumina sintered bodies, or hydroxyapatite sintered bodies are
Although it is suitable for use as an implant material, it has the disadvantage that it cannot be used as a filling material or a luting material for defective areas or cavities in bones or teeth.

In addition, in the case of a cured product obtained by kneading α-tricalcium phosphate powder with an aqueous solution of an inorganic salt or an organic acid polymer, and a cured product obtained by kneading a tetracalcium phosphate powder with an aqueous solution of an acid, strength, It could not be said that it was sufficient in terms of biocompatibility.

[Means for Solving the Problems] Therefore, the present inventors solved the following three requirements for biological hard tissue substitute materials: biocompatibility, predetermined curing speed, and strength after curing.
The present invention was arrived at as a result of intensive research into human hard tissue substitute compositions that satisfy the above points.

That is, according to the present invention, octacalcium phosphate (CaaH2(PO4)a''58a
A human hard tissue substitute composition comprising a powder containing O) as a main component and a kneading solution is provided.

The present invention will be explained in more detail.

The hard tissue replacement composition of the present invention is prepared by adding a calcium phosphate mixture produced by a specific method to fine powder of octacalcium phosphate produced by the specific method described below, and then adding a calcium phosphate mixture produced by a specific method to form a polymer of unsaturated carboxylic acid. , a copolymer, or an aqueous solution of an inorganic acid or an organic acid to form a fluid or plastic state.

The octacalcium phosphate powder used in the composition of the present invention is obtained as follows.

That is, after uniformly mixing calcium hydrogen phosphate anhydride and calcium carbonate at a molar ratio of 2:1 and thoroughly drying,
The product is calcined at around 200°C for about 1 hour, and the resulting product is pulverized into a fine powder of 350 meshes. This fine powder 100
It is mixed with water whose pH has been adjusted to 8 to 9 at a rate of 2 fL/g to perform a water utilization reaction.

After carrying out a hydration reaction for about 4 hours, it is thoroughly washed with neutral water, dried at room temperature, and then calcined at 300 to 400°C for 1 hour to obtain octacalcium phosphate powder.

Next, in order to adjust the curing time of the composition of the present invention, a powder of a calcium phosphate mixture, which is added as necessary, is obtained as follows.

That is, calcium hydrogen phosphate and calcium carbonate are uniformly mixed at a molar ratio of 1:1, and
It is obtained by calcining at a temperature of preferably around 1550°C for about 1 hour, and pulverizing the resulting product into a fine powder with a particle size of 10IL11 or less.

It was confirmed by X-ray diffraction that this product was a mixture of tetracalcium phosphate, hydroxyapatite, α-tricalcium phosphate, etc.

The kneading hardening liquid used to impart fluidity and plasticity to the above-mentioned octacalcium phosphate powder includes (i) an aqueous solution of 2N or less of an inorganic acid such as orthophosphoric acid, birophosphoric acid, hydrochloric acid, etc. (ii) tartaric acid, apple Aqueous solutions of biologically derived organic acids such as citric acid and malonic acid (iii) Homopolymers of unsaturated organic acids such as acrylic acid, itaconic acid, fumaric acid and maleic acid, or polymers in combination of two or more Examples include an aqueous solution of the combination.

Particularly preferred is an aqueous solution of a mixture of a biologically derived organic acid and an inorganic acid such as phosphoric acid. The acrylic acid copolymer is well known as a conventional dental cement and the like.

The organic acid aqueous solution used as the kneading solution generally has a
Used as a 40% by weight solution. For example, in the case of a citric acid aqueous solution, it is particularly preferable that the aqueous solution has a concentration range of 25 to 30% by weight. It is also possible to replace about 10% by weight or less of the aqueous citric acid solution with a water-soluble acid such as hydrochloric acid, malic acid, malonic acid, phosphoric acid, or acrylic acid polymer.

Furthermore, in the composition of the present invention, the weight mixing ratio (powder-liquid ratio) of octacalcium phosphate and mixed calcium phosphate powder (P) and kneading liquid (L), that is, P/L, is 1.0 to 2.8.
It is desirable that it be within the range of . Particularly preferably P/L=
It is in the range of 1.4 to 1.8.

[Examples] Hereinafter, the present invention will be explained in more detail based on Examples, but it will be clear that the present invention is not limited to these Examples.

(Examples 1 to 5) (Powder I) Calcium hydrogen phosphate anhydrous CaHPO4
2 moles of calcium carbonate and 0.1 mole of calcium carbonate were mixed well to be homogeneous, fired at 12O0°C for 2 hours, and then taken out into the open air and rapidly cooled. After making the powder into a fine powder that passed through 350 meshes, 2 g of water with a pH of 8 was added to 100 g of this powder to perform a hydration reaction. After 4 hours of reaction, the mixture was filtered, washed several times with water, and then dried at room temperature. It was confirmed by X-ray diffraction that it was octacalcium phosphate.

(Powder■) Calcium hydrogen phosphate anhydrous CaHPO4
1 mole of calcium carbonate and 1 mole of calcium carbonate CaCO3 were mixed well to be homogeneous, fired at 1550°C for 2 hours, and then taken out into the open air and rapidly cooled. Next, X-ray diffraction revealed that this powder contained tetracalcium phosphate (75%) and hydroxyapatite (20%).
It was confirmed that it was a mixture of α-calcium phosphate (5%).

These powders I and ① were kneaded with a kneading solution of 0.5 normal aqueous solution of hydrochloric acid containing 20% by weight of citric acid and 10% by weight of malonic acid according to the combinations shown in Table I to give a powder-liquid ratio of 1.5. The curing time and compressive strength were measured.

(Examples 6 to 11) The granules of octacalcium phosphate (powder I) and calcium phosphate mixture (powder ■) obtained in the above examples were kneaded with any of the following kneading solutions.

a, 0.2N aqueous hydrochloric acid solution containing 30% by weight of citric acid, C, 43% by weight aqueous solution of acrylic acid (85%) itaconic acid (15%) copolymer, 45% by weight aqueous solution of phytic acid The results are shown in Table- As per H.

(Hereinafter, blank space) Table I [Effects of the Invention] As explained above, the human hard tissue substitute composition of the present invention contains octacalcium phosphate as a main component, and if necessary, a curing time adjusting agent. Since the composition contains a calcium phosphate mixture as It has the advantage of

Therefore, the present invention compensates for the lack of autologous bone and functions as an ideal human hard tissue replacement composition.

Claims (3)

[Claims] (1) Octacalcium phosphate (Ca_8H_2(PO_4)
)_6.5H_2O) A human body hard tissue substitute composition consisting of a powder containing as a main component and a kneading liquid. (2) The powder is calcium hydrogen phosphate anhydrous (Ca
HPO_4) and calcium carbonate (CaCO_3) are uniformly mixed at a molar ratio of 1:1, then calcined at 1300°C to 1600°C, and then pulverized to obtain a powder, which is contained in a range of 10 to 50%. The composition according to item 1. (3) The composition according to claim 1, wherein the kneading liquid is an aqueous solution of a mixture of an organic acid and an inorganic acid.