JPH03127709A - Hard tissue-filling paste having mitigated stimulation to living body and production thereof - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Application The present invention relates to a kneaded material for medical or dental hard tissue prosthesis materials.

"Prior art and its problems" Some types of calcium phosphates, such as α-tricalcium phosphate, have hydration-setting properties, and when an aqueous acid solution such as citric acid is used, curing proceeds more rapidly. Attempts to use materials as medical or dental hard tissue prosthesis materials have become very popular in recent years, and many reports have been made (for example, Japanese Patent Application Laid-Open No. 88351/1983;
No. 59182263, No. 60-36404, No. 61
-191606, 61-234868, 61-
No. 236644, No. 61-270249, No. 61-7
No. 2363, Publication No. 61-833/19, etc.).

However, when these materials are completely cured outside the body and then implanted in the body, the processing to adapt the hardened material to the shape of the replacement part is complicated, and on the other hand, conventional medical and dental When implanted in an unhardened state, that is, in a plastic state, such as various types of cement, it is extremely easy to adapt it to the shape of the replacement part, but when implanted in a living body, unreacted acid There was a problem in that it elutes, irritates living tissues, and causes inflammation.

``Object of the Invention'' The purpose of the present invention is to create a hard tissue filling compound that reduces irritation to living tissue when a calcium phosphate compound is implanted in a living body in a plastic state before completely hardening. The objective is to provide products and methods of manufacturing them.

"Structure of the Invention" The hard tissue filling kneaded product according to the present invention is characterized by having a thin film of a biodegradable substance that is immiscible with water on the surface of the kneaded product of a calcium phosphate powder and an acid aqueous solution.

According to the method of the present invention, this kneaded material for hard tissue filling is obtained by immersing a kneaded material produced by kneading a calcium phosphate powder and an acid aqueous solution in a solution of a biodegradable substance that is immiscible with water, and then kneading it. Manufactured by forming a thin film on the surface of an object.

A hardened product is obtained by kneading a calcium phosphate powder and an acid aqueous solution, but in the present invention, the material is immersed in a liquid of a biodegradable material that is immiscible with water in a plastic state before being completely hardened.

The calcium phosphate-based powder used in the present invention may be any powder used for producing a calcium phosphate-based hardened product, and specifically, contains α-tricalcium phosphate and/or tetracalcium phosphate as an essential component. .

In addition to the above-mentioned essential ingredients, the powder may further contain hydroxyapatite or β-tricalcium phosphate, but α-tricalcium phosphate and/or tetracalcium phosphate accounts for 1/3 or more of the total. Requires inclusion. If the content of these components is less than ⅓, the composition will not be sufficiently cured. Hydroxyapatite or β
- Addition of tricalcium phosphate improves the strength of the cured product, so it is preferable to use a powder containing tricalcium phosphate. Additionally, these powder components may not be completely pure and may contain small amounts of impurities generated during synthesis.

On the other hand, the acid aqueous solution used as the curing liquid may contain 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. These acids are preferably 25% by weight or more, more preferably 2% by weight or more.
It is used as an aqueous solution with an acid concentration of 5 to 55% by weight. If the acid concentration of the acidic aqueous solution is less than 25% by weight, the cured product obtained by mixing with the powder will not exhibit the desired strength.

In the present invention, one or more of monoIIIi, oligosaccharides, polysaccharides, sugar alcohols and polyhydric alcohols can be added to the acid aqueous solution as an additive.

These additives act to moderate the curing reaction and improve moldability when cross-wired.

Examples of monosaccharides that can be used include glucose and fructose, and examples of oligosaccharides include saccharose, maltose, lactose, and raffinose. Furthermore, when polysaccharides are added, the curing reaction is significantly relaxed and a gummy kneaded product is produced, which is preferable when filling in defective areas. Polysaccharides that can be used include, for example, carboxymethyl chitin, glycol chitin, pullulan, pectin, highly methoxylated pectin, hyaluronic acid and chitosan, with chitosan being particularly preferred. In addition, in this specification, "chitosan" means
Partially or fully deacetylated chitin is meant. The degree of deacetylation of chitosan and the degree of substitution of carboxymethyl chitin and glycol chitin are not particularly limited.

Examples of sugar alcohols include sorbitol, mannitol, xylit, etc., and examples of polyhydric alcohols include glycols such as ethylene glycol, glycerin, and the like.

The amount of these additives to be used can be appropriately determined depending on the situation, but if the amount is too small, the effect of the addition will not be exhibited. - For boat fishing, the concentration of monosaccharides, oligosaccharides, sugar alcohols and polyhydric alcohols is preferably at most 40% by weight in total, more preferably at most 30% by weight in total. When the amount added exceeds 40% by weight, these additives become difficult to dissolve in the acid aqueous solution. On the other hand, polysaccharides are 0.05
It is preferable to add it to the acid aqueous solution at a concentration of % by weight or more.

In addition to the additives involved in the hardening reaction mentioned above, various metal oxides, antibiotics, tannic acid, tannic acid derivatives, sodium monofluorophosphate, and citric acid are proposed to be added to hard tissue prosthetic materials. Sodium acid, collagen, etc. can be added.

In the present invention, a cured product is produced by kneading the powder and liquid prepared as described above. that time,
The kneading ratio of the powder agent (P) and the liquid agent (L) is preferably such that the mixing ratio of the powder agent to the liquid agent (P/L) is 0.4 to 2.7 in terms of weight ratio.

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, it will be difficult to uniformly mix the powder and liquid. becomes.

In the present invention, the above-mentioned powder and liquid are kneaded, and the kneaded product, which is still plastic, is immersed in a liquid of a biodegradable substance that is immiscible with water. The plastic state and its duration vary depending on the type, concentration, and powder/liquid ratio of the powder and liquid used.

In the present invention, the water-immiscible biodegradable substance used to form a thin film on the surface of the kneaded product may be any of a variety of substances that are liquid at room temperature or non-toxic to living organisms that liquefy when heated. Specific examples include unsaturated fatty acids, vegetable or animal fats, and base polymers or copolymers.

Examples of unsaturated fatty acids include palmitoleic acid, oleic acid, linoleic acid, and α-lylunic acid. Further, examples of vegetable oils and fats include olive oil and sesame oil, and examples of animal oils and fats include liver oil and the like. Further, as the base polymer or copolymer, for example, L-lactic acid/δ-valerolactone copolymer is known to be biodegradable and can be used in the present invention.

In the present invention, the water-immiscible biodegradable substance forms a thin film on the surface of the kneaded material, and unreacted acids in the kneaded material are dissolved and eluted by body fluids until the kneaded material is hardened. Therefore, it is preferable that the substance used be one that is quickly metabolized and excreted in the body. The immersion time depends on the biodegradable material used, but usually around 2 seconds is sufficient.

"Examples of the Invention" Next, the present invention will be described in more detail based on Examples, but the present invention is not limited thereto.

Example 1 A hydroxyapatite slurry was synthesized by a known wet method using a calcium hydroxide slurry and an aqueous phosphoric acid solution. After the obtained slurry was spray-dried and powdered, it was heated at 1200°C under reduced pressure (approximately 10''Pa), and the hydroxyapatite powder was completely thermally decomposed and α ~
A mixture of tricalcium phosphate and tetracalcium phosphate was obtained. This was made into a powder, and 2 g of this powder was kneaded with 1 g of a 45% citric acid aqueous solution containing 15% glucose and 1% chitosan (manufactured by Kyowa Yushi Kogyo ■, trade name Flonanc N) as a liquid. After 3 minutes from the start), the kneaded product was immersed in 10mH of olive oil (manufactured by Kosakai Pharmaceutical ■, product compliant with the Japanese Pharmacopoeia) for 2 seconds, and then taken out.

In order to examine the state of acid elution from the obtained soaked kneaded product, the kneaded product was put into distilled water and the pH was measured after 5 minutes.The pn was approximately 5.9, which was used as a reference. Almost no decrease in pl+ was observed from the distilled water used (approximately 6.0).

Example 2 A kneaded product having a thin film of sesame oil on the surface was produced by carrying out the same operation as in Example 1, except that sesame ura (manufactured by Kosakai Pharmaceutical ■, product compliant with the Japanese Pharmacopoeia) was used instead of olive oil. . When this was poured into distilled water, the pl+ of the water after 5 minutes was about 5.9, and almost no decrease in pl+ was observed from distilled water (pH 6.0).

Comparative Example The same operation as in Example 1 was performed except that the kneaded product was not immersed in olive oil, and p17 was about 4.8.
A decrease in l+ was observed. This is considered to be due to unreacted citric acid being eluted from the kneaded product.

``Effects of the Invention: Even if the kneaded product according to the present invention is implanted in a living body in an uncured state, it does not elute acid, so stimulation to the living body is significantly reduced, and it can be implanted in a plastic state. Taking advantage of this advantage, it can be suitably used as a hard tissue replacement material such as bone.

Claims (1)

[Scope of Claims] 1. A hard tissue filling material that reduces irritation to living organisms, characterized by having a thin film of a biodegradable substance that is immiscible with water on the surface of a kneaded product of a calcium phosphate powder and an acid aqueous solution. Mixture. 2. The hard tissue filling compound according to claim 1, wherein the biodegradable substance that is immiscible with water is a liquid at room temperature or a non-toxic substance that liquefies when heated. 3. The hard tissue filling compound according to claim 2, wherein the water-immiscible biodegradable substance is an unsaturated fatty acid, a vegetable or animal oil, a synthetic polymer, or a synthetic copolymer. 4. The kneaded material for hard tissue filling according to claim 1, wherein the calcium phosphate powder contains α-tricalcium phosphate and/or tetracalcium phosphate as an essential component. 5. The acid aqueous solution is an inorganic acid such as phosphoric acid, or acetic acid, lactic acid, citric acid, malic acid, malonic acid, succinic acid, glutaric acid,
The kneaded material for hard tissue filling according to claim 1, which is an aqueous solution of an organic acid such as tartaric acid or polyacrylic acid. 6. The hard tissue filling kneaded product according to claim 5, wherein the acid aqueous solution contains one or more of monosaccharides, oligosaccharides, polysaccharides, sugar alcohols, and polyhydric alcohols. 7. A biomaterial characterized by immersing a kneaded product produced by kneading a calcium phosphate powder and an acid aqueous solution in a liquid of a biodegradable substance that is immiscible with water to form a thin film on the surface of the kneaded product. A method for producing a hard tissue filling compound that reduces irritation to the skin. 8. The method for producing a hard tissue replacement compound according to claim 7, wherein the biodegradable substance that is immiscible with water is a liquid at room temperature or a non-toxic substance that liquefies when heated. 9. The method for producing a kneaded product for hard tissue filling according to claim 7, wherein the calcium phosphate powder contains α-tricalcium phosphate and/or tetracalcium phosphate as an essential component. 10. The acid aqueous solution is an inorganic acid such as phosphoric acid, acetic acid, lactic acid,
The method for producing a hard tissue filling kneaded product according to claim 7, which is an aqueous solution of an organic acid such as citric acid, malic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, or polyacrylic acid. 11. Claim 1 wherein the acid aqueous solution contains one or more of monosaccharides, oligosaccharides, polysaccharides, sugar alcohols, and polyhydric alcohols.
A method for producing a kneaded material for hard tissue filling according to 0.