JPH0564659A - Bioactive cement and manufacture thereof - Google Patents

Abstract

PURPOSE:To achieve effective treatment without inducing inflammation in an organic tissue by producing and using a bioactive cement which sets by itself early enough to bond an artificial biomaterial securely and bonds chemically with an organic bone at a high strength. CONSTITUTION:A glass powder containing ammonia phosphate calcium hydrate and/or a crystallized glass powder and an aqueous solution composed mainly of organic acid are prepareded. The glass powder and/or crystallized glass powder containing calcium is mixed into an ammonium phosphate aqueous solution to harden and crushed to prepare a glass powder and/or crystallized glass powder containing ammonia phosphate calcium hydrate. The powder is mixed with the aqueous solution composed mainly of the above organic acid to produce a bioactive cement. Thus, a bonding material or a filling material is made for an artificial bone, artificial root of tooth or the like to be used in the medical and dental fields without inducing inflammation in an organic tissue thereby achieving higher treating effect.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a bioactive material used as an adhesive for artificial biomaterials such as artificial bones and artificial tooth roots used in the fields of medicine and dentistry, and as a filling material for bone and tooth defects. The present invention relates to cement and a manufacturing method thereof.

[0002]

2. Description of the Related Art In the field of orthopedics, when a part of bone is lost or excised due to a fracture or bone tumor, and in the field of dentistry, a jaw bone is damaged due to tooth extraction or alveolar pyorrhea. Metal to repair parts,
Artificial biomaterials such as ceramics and crystallized glass are used.

[0003] It is desirable that such an artificial biomaterial be embedded and fixed in the repair portion early and with good compatibility. For that purpose, the artificial biomaterial is ground according to the shape of the repair portion or the shape of the artificial biomaterial is changed. Although it is necessary to process according to the shape of the repaired portion, it is very difficult to perform such grinding and processing accurately.

Therefore, when an artificial biomaterial is generally used, a biomedical cement is used for the purpose of adhering and fixing it to a living bone. For example, PMMA (polymethylmethacrylate) cement is widely used in the orthopedic field. In the dental field, zinc phosphate cement and carboxylate cement are used. In addition, the shape is adapted by directly filling apatite or alumina ceramic granules into the restoration part.

[0005]

However, the above-mentioned various kinds of biomedical cements firmly adhere to artificial biomaterials but do not chemically bond to biomedical bones. May loosen or cause an inflammatory reaction in the surrounding tissues.

Since granules of apatite or alumina ceramic do not bond with each other, it is necessary to fix the granules with the above-mentioned living body cement or the like, and there is a risk of loosening with the living bone.

In view of the above circumstances, various bioactive cements that chemically bond to bone have been proposed in recent years, for example, C
A glass powder containing a as a constituent is mixed with an aqueous solution of ammonium phosphate as a hardening liquid to form a glass powder containing Ca.
²⁺ (calcium) ions react with HPO ₄ ^2- (phosphate) ions in the curing liquid to form hydroxyapatite through precursors such as amorphous calcium phosphates and ammonium calcium phosphate. Bioactive cements that are hardened by are also proposed. However, this bioactive cement has a problem that the initial strength is low, and it is difficult to obtain the early fixing property required for practical use.

According to the present invention, an artificial biomaterial can be early adhesively fixed by self-coagulation and hardening without inducing an inflammatory reaction to a living tissue, and further, it is chemically bonded to a living bone and has high strength. Therefore, it is an object of the present invention to provide a bioactive cement that is stable over a long period of time and a method for producing the same.

[0009]

The bioactive cement of the present invention is characterized by comprising glass powder and / or crystallized glass powder containing ammonium calcium phosphate hydrate and an organic acid aqueous solution.

In the method for producing a bioactive cement of the present invention, a glass powder and / or a crystallized glass powder containing Ca and an ammonium phosphate aqueous solution are mixed and hardened, and then crushed to form phosphoric acid. It is characterized in that glass powder containing ammonium calcium hydrate and / or crystallized glass powder is prepared, and then the powder is mixed with an organic acid aqueous solution.

The preferred composition of the glass powder and crystallized glass powder used in the present invention is Ca by weight percentage.
_{O 20~60%, SiO 2 20~50%} , P 2 O 5
0-30%, MgO 0-20%, CaF ₂ 0-5
%, And apatite crystals and wollastonite crystals precipitate inside the crystallized glass powder having such a composition. The smaller the particle size of the glass powder or the crystallized glass powder is, the higher the strength of cement can be obtained, and specifically, the maximum particle size is preferably 44 μm or less.

As the organic acid aqueous solution used in the present invention, for example, an aqueous solution of citric acid, malic acid or the like can be used.

In the present invention, the ratio of the Ca-containing glass powder or crystallized glass powder to the ammonium phosphate aqueous solution, that is, the powder-liquid ratio, is 0.1 to 0.5 ml of the aqueous solution to 1 g of the powder. In addition, the powder-liquid ratio of the glass powder or crystallized glass powder after crushing the cured product and the organic acid aqueous solution is 0.3 g of the aqueous solution per 1 g of the powder.
~ 0.6 ml is suitable. Further, it is preferable to pulverize the cured product so that the maximum particle size becomes powder having a particle size of 44 μm or less.

[0014]

In the present invention, when a glass powder or a crystallized glass powder containing Ca as a constituent component is first mixed with an ammonium phosphate aqueous solution, Ca ²⁺ ions and the ammonium phosphate aqueous solution eluted on or around the surface of the powder HP
O ₄ ²⁻ (phosphate) ions and NH ₄ ⁺ (ammonium) ions react with each other to form calcium ammonium phosphate hydrate, which causes hardening.

Further, a glass powder or a crystallized glass powder containing ammonium calcium phosphate hydrate produced by crushing the hardened product to a predetermined particle size is used as a hardening liquid, and an aqueous solution of an organic acid such as citric acid or malic acid. When is mixed, Ca ²⁺ ions in the glass powder or crystallized glass powder and the COOH group in the aqueous solution form a chelate bond, and crystals such as calcium citrate and calcium malate are produced and hardened. Furthermore, since the calcium ammonium phosphate hydrate contained in the original powder also binds to each other, it will be hardened early. Ammonium calcium phosphate hydrate in the cured product gradually elutes ammonium in the living body,
In addition, it changes to hydroxyapatite, has excellent chemical bondability with living bone, and can be a stable substance in vivo.

Generally, when an aqueous solution of an organic acid is used as a hardening liquid, it may cause an inflammatory reaction to living tissues. However, the bioactive cement of the present invention contains ammonium calcium phosphate hydrate, and And has a good affinity, it is cured early even if inflammation occurs.

The glass powder and the crystallized glass powder are Ca
The elution rate of ²⁺ ions is different, the elution rate of glass powder is higher than that of crystallized glass powder, and the curing time is shorter.
The curing time also varies depending on the combination with the concentration of COOH groups in the curing liquid, but the mixing ratio of the glass powder and the crystallized glass powder should be adjusted so as to have an appropriate Ca ²⁺ ion elution rate depending on the use needs. Just choose.

In the present invention, coarse particles of an inorganic material such as aluminum oxide, silicon oxide, zirconium oxide, zinc oxide, etc. or fibrous particles thereof, or a reinforcing material such as whiskers are added to 100% by weight of powder. On the other hand, it becomes possible to further increase the strength by adding 1% by weight or more. However, it is not preferable to add a large amount of the reinforcing material because the curing time becomes long.

[0019]

EXAMPLES The present invention will be described in detail below based on examples.

Table 1 shows examples of the present invention (Sample Nos. 1 to 1).
5) and the bioactive cements of Comparative Examples (Sample Nos. 6 to 9).

[0021]

[Table 1]

The glass powders A and B in the table were produced as follows.

First, in terms of weight percentage, CaO 47.0%,
SiO ₂ 35.5%, P ₂ O ₅ 17.0%, CaF ₂
A raw material prepared to be a glass having a composition of 0.5% was melted at 1500 ° C. for 2 hours, vitrified, and roll-molded, and then this molded body was crushed by a ball mill,
The powder was classified by a sieve to obtain a glass powder A having a maximum particle size of 44 μm or less. Further, the same glass molded body was put into a ball mill, and further, an ammonium phosphate aqueous solution was mixed and pulverized so as to have a volume ratio of 1 with respect to the glass 10, and the powder was classified by a sieve to have a maximum particle diameter of 44 μm or less. Glass powder B containing calcium ammonium phosphate hydrate
Got

The crystallized glass powders C and D in the table are
It was produced as follows.

A glass molded body similar to the above-mentioned glass powder A was crystallized by firing at 1050 ° C. for 4 hours, and then this crystallized glass molded body was crushed by a ball mill and classified by a sieve to obtain the maximum particle size. A crystallized glass powder C having a particle size of 44 μm or less was obtained. Further, the same crystallized glass molded body was placed in a ball mill, and further, an ammonium phosphate aqueous solution was mixed and pulverized so as to have a volume ratio of 1 with respect to the crystallized glass 10, pulverized, and classified by a sieve to obtain a maximum particle size of
Crystallized glass powder D having a particle size of 4 μm or less and containing ammonium calcium phosphate hydrate was obtained.

As the hardening liquid, a weakly acidic citric acid aqueous solution and malic acid aqueous solution, in which citric acid and malic acid were mixed with distilled water, were used.

The powder-liquid ratio in the table is the ratio of each powder to the curing liquid, and the value that maximizes the compressive strength was selected.

For the evaluation of the characteristics of cement, the relationship between the compressive strength for obtaining fixability and the living bone or tissue was examined.

The compressive strength is measured according to JIS T 6602 (dental zinc phosphate cement),
After thoroughly kneading each powder and the curing liquid, the mixture was poured into a predetermined mold and left to cure for 1 hour, then taken out from the mold and immersed in a simulated body fluid for 24 hours, and then the wet compressive strength was measured.

For the inflammatory reaction, after kneading each powder and the hardening liquid, the mixture was poured into a mold having a diameter of 10 mm and a thickness of 2 mm.
After allowing to stand for a minute, the kneaded product was embedded under the skin of the rat, and it was judged by observing the soft tissue around it with a microscope.There were some with necrosis and some without necrosis. And

Further, for the connection with the living bone, a hole of 4 mmφ was made in the tibia condyle of the rat, and each sample after kneading was filled in the hole and sacrificed after 4 weeks, and the surrounding tissue of the cement was excised to surround it. The bondability with bone was observed with a microscope, and the curing time was measured according to JIS T 6602 (dental zinc phosphate cement). The kneaded product had a weight of 300 g and a cross-sectional area of 1 mm ^2. It was calculated from the time when the needle was dropped and the needle mark disappeared.

As a result, No. 1 is the embodiment of the present invention. 1
Each of the samples Nos. 5 to 5 had a compressive strength of 80 MPa, had no inflammatory reaction with surrounding living tissues, showed binding with surrounding bone, and self-coagulated and hardened earlier.

On the other hand, No. 1 in which glass powder A and citric acid aqueous solution were mixed was used. Sample No. 6 has compressive strength of 60MP
a, which was low, and No. 1 in which crystallized glass C and an aqueous citric acid solution were mixed. Sample 7 required a long cure time.
Further, No. 1 in which glass A and an ammonium phosphate aqueous solution were mixed. The sample of No. 8 has a low compressive strength of 50 MPa, and is No. 8 showing PMMA cement. Sample No. 9 had a high compressive strength of 80 MPa, but caused an inflammatory reaction in the surrounding tissues, and no binding to the surrounding bone was observed.

[0034]

INDUSTRIAL APPLICABILITY As described above, the bioactive cement of the present invention can self-coagulate and cure an artificial biomaterial at an early stage without inducing an inflammatory reaction to a living tissue, and also the living body can be fixed. Since it has a high strength as well as a chemical bond with bone, it is stable without being loosened with living bone even after long-term use. Further, it is also possible to make it into various shapes and use it as a filling material for a defect portion of bone or tooth.

Claims (2)

[Claims] 1. A bioactive cement comprising a glass powder and / or a crystallized glass powder containing calcium ammonium phosphate hydrate and an organic acid aqueous solution. 2. A glass powder and / or a crystallized glass powder containing Ca, which is hardened by mixing with an ammonium phosphate aqueous solution, and then crushed to contain ammonium calcium phosphate hydrate. And / or a crystallized glass powder is produced, and then the powder is mixed with an organic acid aqueous solution, which is a method for producing a bioactive cement.