JPH0739577A - Calcium phosphate-based curable composition - Google Patents

Abstract

(57) [Abstract] [Purpose] It is an object of the present invention to provide a calcium phosphate-based hardening composition having practical properties suitable for medical materials and dental materials used for tooth and bone defects and voids. The present invention comprises (1) calcium phosphate powder containing polyvinylpyrrolidone, and (2) an aqueous solution containing polyacrylic acid or a copolymer of acrylic acid and another unsaturated organic acid and a specific polysaccharide compound. And a curable composition comprising: The composition is excellent in biocompatibility, has sufficient operation margin time, and has practical compressive strength and adhesiveness.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for a medical material or a dental material, which is used for a defective portion or a void portion of a bone or a tooth caused by a pathological or external cause.

[0002]

2. Description of the Related Art Calcium phosphate-based materials are the main components of bones and teeth in the living body and are useful as biomaterials. Especially hydroxyapatite [Ca
₁₀ (PO ₄ ) ₆ (OH) ₂ ; hereinafter HAp] and β-tricalcium phosphate [β-Ca ₃ (PO ₄ ) ₂ ; hereinafter β-T
CP] has been attracting attention as a biocompatible material for a long time and has already been put into practical use. However, HAp
Since β-TCP and β-TCP have low chemical activity, there is a restriction that they must be molded at high temperature except when they are used in powder or granules, and application to kneading filling is limited. . Among the calcium phosphates, tetracalcium phosphate [Ca ₄ (PO ₄ ) ₂ O; 4CP below] and α-tricalcium phosphate [α-Ca ₃ (P
O ₄ ) ₂ ; hereinafter α-TCP] is water or physiological saline,
It is known that when it is kneaded with an aqueous solution of polyacrylic acid and various organic acids, it cures at room temperature. Utilizing this property, bone cement, dental cement and pulp capping material, root canal filling material, remineralization acceleration It is considered to be applied to wood and bone replacement materials.

The curable composition is usually used in any form by mixing and kneading a powder material mainly containing 4CP or α-TCP and a liquid material to form a paste or clay. Needs to be cured and cures quickly,
It is necessary that it be firmly adhered and fixed to the affected area and exhibit excellent biocompatibility. However, even if any of the above-mentioned hardened materials is taken, these performance requirements cannot be satisfied. That is, 4CP and α-TC which are the main components of the powder material
The chemical activity of P is high, and when it is mixed with a liquid material, the curing reaction proceeds rapidly, and it is difficult to obtain a uniform composition that maintains an appropriate consistency for a certain period of time. Furthermore, when the composition contains polyacrylic acid or the like, it has a certain degree of adhesiveness to bones and teeth, but at present, it has not yet reached a practical strength.

Therefore, for the purpose of prolonging the time until the composition is cured, the component concentration of the liquid material is lowered and the pH is lowered.
Attempts have been made to add regulators and the like. Also for powder materials, low-activity calcium phosphates such as HAp and calcium monohydrogen phosphate, calcium oxide, magnesium oxide,
Attempts have been made to suppress the curing reaction of 4CP and / or α-TCP as much as possible by blending various metal oxides such as zinc oxide or various fluorine compounds such as calcium fluoride, strontium fluoride and sodium fluorophosphate. There is. In addition, HAp was formed on the surface of 4CP by the hydration
A method of coating is also reported. However, even with these methods, although the properties of the 4CP and / or α-TCP curable composition are remarkably reduced, no improvement in the curing properties to the extent of compensating for them is observed, and the method is fundamentally improved. Has not arrived.

Further, for the purpose of improving the adhesiveness to bones and teeth, attempts have been made to increase the concentration of polyacrylic acid in the liquid material or increase the molecular weight of polyacrylic acid, but in any case, mixing The viscosity of the composition becomes high, an appropriate consistency cannot be obtained, and the compressive strength also decreases. Also,
It has been proposed to add a polysaccharide compound to a liquid material as a calcium phosphate-based composition having an appropriate consistency and adhesiveness, but there are still problems in compressive strength and operability.

[0006]

DISCLOSURE OF THE INVENTION It is an object of the present invention to provide a calcium phosphate-based curable composition having practical operability, strength and adhesiveness suitable for use as a medical material or a dental material. It was made as.

[0007]

DISCLOSURE OF THE INVENTION As a result of intensive studies conducted by the present inventors in view of the above-mentioned state of the art, calcium phosphate powder containing polyvinylpyrrolidone, polyacrylic acid or acrylic acid and other impurities were found. It has been found that a curable composition comprising a copolymer of a saturated organic acid (hereinafter referred to as polycarboxylic acid) and an aqueous solution containing a polysaccharide compound substantially solves the above-mentioned problems, and has completed the present invention.

The present invention comprises (1) calcium phosphate powder containing 0.01 to 5.0% by weight of polyvinylpyrrolidone (hereinafter,% is% by weight); and (2) polyacrylic acid or acrylic acid and other 10. A copolymer of unsaturated organic acid
0 to 40.0% and 0.1 to 10.0 of one or more polysaccharide compounds selected from the group consisting of ethyl cellulose, sodium chondroitin sulfate, sodium dextran sulfate, sodium carboxymethyl cellulose, dextrin, gum arabic and sodium alginate. %
The present invention relates to a curable composition comprising an aqueous solution (curing liquid) containing the polyvinylpyrrolidone, wherein the polyvinylpyrrolidone is coated on the surface of calcium phosphate powder, and the calcium phosphate relates to α-tricalcium phosphate and / or tetracalcium phosphate. It is a thing.

When the powder of the present invention and the curing liquid are mixed, the operation allowance time can be extended without delaying the initial curing. This is because the polyvinylpyrrolidone in the powder influences the wetting of the curing liquid and the powder temporarily. This effect becomes more remarkable when the calcium phosphate powder is coated with polyvinylpyrrolidone. In this case, it is also possible to make the particle diameter of the calcium phosphate particles relatively small, which leads to improvement in compressive strength. Further, it is a known fact that polycarboxylic acid contributes to the adhesiveness to bones and teeth, but in the present invention, the above action of polyvinylpyrrolidone enables the use of polycarboxylic acid having a higher molecular weight than usual. And the adhesiveness is dramatically improved. Furthermore, the addition of the polysaccharide compound improves the wettability of the admixture composition to bones and teeth and further improves the adhesiveness.

The polyvinylpyrrolidone used in the present invention can be any industrially produced one having a molecular weight, and a part thereof can be replaced with another water-soluble polymer compound. When coating the calcium phosphate particles with polyvinylpyrrolidone, a plasticizer may be added for the purpose of improving the film-forming property. The coating method is a method of coating the powder surface by a normal method, or dissolving or suspending polyvinylpyrrolidone in a solvent such as alcohol, mixing the solution with calcium phosphate powder, and removing the solvent by means such as drying. Or a method of forming a film by a spray drying device.

The use ratio of polyvinylpyrrolidone is 0.01 to 5.0% with respect to the calcium phosphate powder,
It is particularly preferably in the range of 0.05 to 2.0%. When the content of polyvinylpyrrolidone is less than 0.01%, the above-described effects are not sufficiently exhibited, and when it is more than 5.0%, the viscosity of the mixed composition becomes too high.

The calcium phosphate powder used in the present invention is preferably a powder containing 4CP and / or α-TCP as a main component, and may be synthesized by any method. Further, a part of the powder may be replaced with other calcium phosphate, fluoride or the like as long as the required physical properties are not impaired. The particle size of the powder is preferably 100 μm or less, particularly preferably 5 to 45 μm. The particle size of the powder is 100
When it is larger than μm, there is a feeling of roughness when the powder and the liquid are mixed, and operability becomes a problem. Further, the effect of reducing the specific surface area impairs the curing characteristics and also leads to a decrease in the compressive strength.

The polycarboxylic acid used in the present invention may be any of those generally used, but powders at room temperature are particularly preferable. For example, acrylic acid / itaconic acid copolymers, acrylic acid / acrylic acid Examples include fumaric acid copolymers. The usage ratio is 10.0 to 4 in the curing liquid.
0.0%, particularly preferably 25.0 to 35.0%
Is the range. If the proportion of the polycarboxylic acid is less than 10.0%, the adhesiveness of the composition will be reduced, and if it exceeds 40.0%, the viscosity of the entire admixture composition will be too high and the operability will be a problem.

The polysaccharide compound used in the present invention is selected from the group consisting of ethyl cellulose, sodium chondroitin sulfate, sodium dextran sulfate, sodium carboxymethyl cellulose, dextrin, gum arabic and sodium alginate. The polysaccharide compound may be used alone or in combination of two or more. Especially 2
Those containing species or more are preferred. The ratio of the polysaccharide compound used is 0.1-10.
It is 0%, and particularly preferably 0.5 to 5.0%.
If the proportion is less than 0.1%, the above-mentioned effects are not exhibited and the adhesiveness is reduced. On the other hand, if it exceeds 10.0%, the viscosity of the whole admixture composition becomes too high and the operability becomes a problem.

The curing liquid contains orthophosphoric acid, pyrophosphoric acid, and
Inorganic acids such as hydrochloric acid, organic acids derived from living bodies such as tartaric acid, malic acid, citric acid, malonic acid, and lactic acid may be added. If necessary, fluorine compounds, various antibacterial agents, pH
A small amount of a regulator may be added.

The calcium phosphate compound of the present invention is a calcium phosphate powder (P) containing polyvinylpyrrolidone.
And mixing ratio (powder / liquid ratio) by weight of the curing liquid (L), that is, P /
It is desirable that L is in the range of 0.8 to 3.0. Particularly preferably, it is in the range of P / L = 1.0 to 1.8. P /
If L is too large, the operability will be poor, and if it is too small, the physical properties of the resulting composition will be poor.

[0017]

EFFECTS OF THE INVENTION The calcium phosphate-based curable composition of the present invention has excellent biocompatibility, sufficient operating margin, and practical compressive strength and adhesiveness. In addition, the powder treated with the polyvinylpyrrolidone has improved storage stability.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

【Example】

(Powder I) Calcium hydrogen phosphate dihydrate [CaHPO
_An equimolar mixture of 4.2H ₂ O] and calcium carbonate [CaCO ₃ ] was calcined at 1600 ° C. for 2 hours and rapidly cooled in the open air. The fired product was crushed with a ball mill to obtain a powder having a particle size of 25 μm or less. It was confirmed by X-ray diffraction that this powder was a powder containing 4 CP as a main component.

(Powder II) 1 mol of calcium carbonate [CaCO ₃ ] is mixed with 2 mol of calcium hydrogen phosphate dihydrate [CaHPO ₄ .2H ₂ O], and the mixture is heated to 1200 ° C.
It was fired for 2 hours at room temperature and quenched in the open air. The fired product was crushed with a ball mill to obtain a powder having a particle size of 25 μm or less. It was confirmed by X-ray diffraction that this powder was a powder containing α-TCP as a main component.

(Powder III) By a spray drying device,
(Powder I) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. (Powder I) 100 g
Polyvinylpyrrolidone 0.1% ethanol solution 100
g was used as the coating liquid.

(Powder IV) By a spray drying device,
(Powder I) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. (Powder I) 100 g
Polyvinylpyrrolidone 0.5% ethanol solution 100
g was used as the coating liquid.

(Powder V) By a spray drying device,
(Powder I) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. (Powder I) 100 g
Polyvinyl pyrrolidone 1.0% ethanol solution 100
g was used as the coating liquid.

(Powder VI) With a spray dryer,
(Powder I) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. (Powder I) 100 g
Polyvinylpyrrolidone 2.0% ethanol solution 100
g was used as the coating liquid.

(Powder VII) By a spray drying device,
(Powder II) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. For 100 g of (Powder II),
Polyvinylpyrrolidone 0.1% ethanol solution 100
g was used as the coating liquid.

(Powder VIII) By a spray drying device,
(Powder II) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. For 100 g of (Powder II),
Polyvinylpyrrolidone 0.5% ethanol solution 100
g was used as the coating liquid.

(Powder IX) By a spray drying device,
(Powder II) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. For 100 g of (Powder II),
Polyvinyl pyrrolidone 1.0% ethanol solution 100
g was used as the coating liquid.

(Powder X) With a spray dryer,
(Powder II) was mixed with polyvinylpyrrolidone (Mn: 40,00).
0) Powder treated with coating. For 100 g of (Powder II),
Polyvinylpyrrolidone 2.0% ethanol solution 100
g was used as the coating liquid.

(Curing liquid I) An aqueous solution containing 15% citric acid and 30% acrylic acid / itaconic acid copolymer (Mn: 20,000).

(Curing liquid II) citric acid 15%, acrylic acid / itaconic acid copolymer (Mn: 20,000) 30%,
Aqueous solution containing 2% sodium chondroitin sulfate.

(Curing liquid III) citric acid 15%, acrylic acid / itaconic acid copolymer (Mn: 20,000) 30%,
An aqueous solution containing 1.2% sodium chondroitin sulfate and 0.8% sodium dextran sulfate.

(Curing liquid IV) citric acid 15%, acrylic acid / itaconic acid copolymer (Mn: 20,000) 30%,
An aqueous solution containing 1.2% sodium chondroitin sulfate and 0.8% sodium carboxymethyl cellulose.

(Curing liquid V) 15% citric acid, 30% acrylic acid / itaconic acid copolymer (Mn: 20,000),
An aqueous solution containing 1.2% dextran sulfate sodium and 0.8% arabic gum.

(Mixing and kneading method and method for measuring physical properties of the obtained composition) P / L =
The mixture was mixed and kneaded at a ratio of 1.1. The composition obtained is JIS
According to T6602, the consistency and crushing effect (compressive strength) were measured. Further, the tensile adhesive strength of each composition to the extracted enamel of bovine teeth was also measured. The measurement results are shown in Table 1.

[0034]

[Table 1]

Claims (3)

[Claims] (1) 0.01 to 0.01% of polyvinylpyrrolidone.
Calcium phosphate powder containing 5.0% by weight, and (2)
From 10.0 to 40.0% by weight of polyacrylic acid or a copolymer of acrylic acid and other unsaturated organic acid, and from ethyl cellulose, sodium chondroitin sulfate, sodium dextran sulfate, sodium carboxymethyl cellulose, dextrin, gum arabic and sodium alginate. A curable composition comprising an aqueous solution (curing solution) containing 0.1 to 10.0% by weight of one or more polysaccharide compounds selected from the group consisting of: 2. The curable composition according to claim 1, wherein polyvinylpyrrolidone is coated on the surface of calcium phosphate powder. 3. The curable composition according to claim 1, wherein the calcium phosphate is α-tricalcium phosphate and / or tetracalcium phosphate.