JPH03162864A - Curable material for medical and dental purposes - Google Patents

Abstract

PURPOSE:To eliminate the harmful effect on the living body and to prolong the curing time by using a specific org. acid as a curing soln. in powder essentially consisting of tetracalcium phosphate and using tannin and tannin deriv. as a curing retarding agent. CONSTITUTION:The calcium phosphate essentially consisting of at least 4CP in 4CP and alpha-TCP is used as the essential material and the org. acid is used as the curing soln. At least one kind selected from the group consisting of the tannin, tannin deriv. and collagen is used as the curing retarding agent. One kind selected form the group consisting of citric acid, malic acid, malonic acid, glyeric acid and glutaric acid is used alone or >=2 kinds thereof are used in combination as the org. acid. These org. acids form a hard cured material when the acids are intimately mixed with the calcium phosphate powder and are kneaded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to medical and dental hardenable materials used for bone cement, dental cement, root canal filling materials, and the like.

[Background technology]

In recent years, dental cements such as hydroxyapatite (hereinafter referred to as rHApJ) and α-tricalcium phosphate [α-Cat(PO4)i] have been used as powders.

Hereinafter, "α-TCPJ" is used, and a polyacrylic acid aqueous solution is used as the curing solution.The powder and the curing solution are mixed and kneaded to form a cured product. Unreacted polyacrylic acid may remain, and its elution poses a problem of harm to living organisms.

Bone cement has traditionally been made of polymethyl methacrylate (P
Products using polymeric materials such as MMA) and methyl methacrylate (MMA) are commercially available. However, bone cement using polymeric materials has the following three problems.

First of all, if the bone tissue of the host to be implanted and the bone cement are not directly bonded, and the bone cement is left in the body for a long period of time due to the interposition of fibrous tissue, problems such as loosening may occur. Second, the heat generated during curing reaches a temperature of about 90 to 100°C, which causes necrosis of surrounding cells. Thirdly, there is a problem that unreacted heptamers and oligomers are eluted and have an adverse effect on bones.

On the other hand, α-TCP and tetracalcium phosphate (C a
4 (P 04) 1 0. Hereinafter, a biomaterial using r4cPJ] has been proposed. α-TCP and 4CP have high chemical activity and can be converted to HAp under conditions equivalent to in vivo or oral cavity conditions. A material that combines 40P powder and an aqueous solution of citric acid and malic acid is
Reported to be useful in dental cement and bone cement. Although this material and its cured product are not harmful to living organisms, increasing the calcium phosphate powder/curing solution ratio (hereinafter simply referred to as the "powder/?&. ratio") to increase the strength will significantly increase the curing time. There is a problem that it becomes too short and cannot be put to practical use.

C. Purpose of the Invention In view of the above, the present invention provides a cure for medical and dental use that cures at room temperature or at a temperature near the body temperature of a living body, has a long curing time, and is not harmful to living organisms. The purpose is to provide sexual materials.

[Disclosure of the invention]

In order to achieve the above object, the present invention provides a medical and dental hardening material which is mainly composed of calcium phosphate powder containing at least 4CP of 4CP and α-TCP as an essential component, and which contains, as a hardening retarder, The object of the present invention is to provide a curable material for medical and dental use, characterized in that at least one selected from the group consisting of tannin, tannin conductor, and collagen is used.

This invention will be explained in detail below.

The medical and dental curable material according to the present invention comprises at least a combination of calcium phosphate powder and a curing solution.

4CP occupies part or all of the calcium phosphate powder. The remainder of the powder is comprised of α-TCP, HAp, abatite carbonate, β-tricalcium phosphate, calcium hydrogen phosphate dihydrate, and the like. Calcium phosphate powder is part 10
-100% by weight is 4CP, O~90% by weight is α-
TCP and preferably 0 to 30% by weight HAp. 4CP is lOffif of calcium phosphate powder
If it is less than fl %, a problem may arise in that the physical strength of the cured product after kneading is extremely reduced. I-I A
If p exceeds 30% by weight of the calcium phosphate powder, the curing time may be shortened, which may cause a problem in that sufficient linearization cannot be achieved. 4CP has higher reactivity than α-TCP and may have a shorter pot life, making it difficult to use. Therefore, by adding α-TCP, the reactivity is suppressed. In addition, 4CP, α-TCP and HA
It is preferable that the content of substances other than p is 40% by weight or less of the calcium phosphate powder. If these substances exceed this proportion, the physical strength of the kneaded and cured product may be extremely reduced. It is preferable that the powder has an average particle diameter of 1 to 25 μm. If the average particle size of the powder is less than 1 μm, the physical strength of the cured product will improve, but the curing time may be shortened, and if it exceeds 25 μm, especially when used in dental cement, The film thickness of the cured product is 30
There may be a problem that the thickness is not smaller than μm.

4CP is, for example, r-CazPzOt and CaCO
．． It is obtained by calcining a mixture with a molar ratio of 1:2 at 300° C. or higher and then pulverizing it, but it can also be obtained by other methods. α-TCP is, for example, r Ca
It is obtained by calcining an equimolar mixture of t Pg 01 and (:, a C O 1 at 1200°C or higher and then pulverizing it, but it can also be obtained by other methods.}i
Ap, etc. may be calcium phosphate derived from living organisms such as bone powder, or may be HAp, abatite carbonate β-tricalcium phosphate, etc. obtained by well-known or publicly known methods. None of these calcium phosphates has biohazardous properties.

As the curing solution, a solution of a biologically related substance is used.

As the biologically related substance, at least one selected from the group consisting of tannins, tannin derivatives, and biologically relevant organic acids (hereinafter referred to as "organic acids") is used. The tannin, tannin derivative, and the organic acid are
All of these substances are biologically related substances and are not harmful to living organisms.

Any tannin or tannin derivative may be used, but it is preferable to use tannic acid. Although tannic acid will be explained below as an example, tannins and tannin derivatives other than tannic acid can be used in the same manner. Tannic acid is a curing agent that has a slower curing rate than conventional curing agents, that is, it is a curing agent and a curing retardant. In addition, when tannic acid is used in hardenable dental materials, it has a healing effect on oral cavity and pharyngeal mucus inflammation.
It is expected to be effective in preventing tooth decay by inhibiting the dissolution of tooth proteins. The tannic acid concentration of the tannin rII solution is not particularly limited, but is preferably in the range of 0.1 to 70% by weight. 0.51 in the presence of acid. The preferred range is 1 to 30% by weight, and 0.0% in the presence of collagen. The preferred range is 1 to 20% by weight, and 0.0% in the presence of organic acid and collagen. A range of 1 to 10% by weight is preferred. If it is below each of these ranges, the curing retardation effect may not be exhibited, and if it exceeds each of these ranges, the cured product may disintegrate in the aqueous solution.

As the organic acid, one type selected from the group consisting of citric acid, malic acid, malonic acid, glyceric acid, and glutaric acid is used alone, or two or more types are used in combination.

These organic acids produce a hard cured product by mixing and kneading with calcium phosphate powder. The organic acid concentration of the organic acid solution is not particularly limited, but is 0.1 to 90f.
The range of fiffl% is preferable, and in the coexistence of tannic acid, the range is 0. The range is preferably from 1 to 90% by weight, and in the coexistence of collagen, O. The range is preferably from 1 to 70% by weight, and in the coexistence of tannic acid and collagen, the range is preferably from 0.1 to 70% by weight. If it is below each of these ranges, the physical strength of the cured product will be extremely reduced after kneading, and it may collapse in the aqueous solution. Crystals may precipitate.

As the collagen, it is preferable to use atelocollagen, but other collagens may also be used. Atelocollagen is collagen in which part or all of the telopeptide at the molecular end has been removed by enzymatic treatment, and is non-toxic to living organisms. Collagen may be used after being dissolved in a hardening solution, or may be used in a solution separate from the hardening solution, or may be used in a powdered state. The collagen concentration of the collagen solution is not particularly limited, but is 0.
The range of 0.01 to 35% by weight is preferable, and the range of 0.05 to 35% by weight is preferable in the coexistence of an organic acid, and the preferable range of 0.01 to 30fHL% is preferable in the coexistence of tannic acid. 0.01 to 30 in the coexistence of
A weight percent range is preferred.

If it is below each of these ranges, the hardening retardation effect of collagen and tannic acid may not be exerted, and if it exceeds each of these ranges, collagen may be decomposed in the organic acid solution before kneading or the solution viscosity may decrease. Sometimes it gets too high. When collagen is used in an unhulled state, it is preferable to have the above-mentioned average particle diameter for the above-mentioned reasons.

In this invention, the progress of the hardening reaction of calcium phosphate powder is slowed down by using at least one selected from the group consisting of tannin, tannin derivatives, and collagen. This improves the operability during kneading, increases the powder/liquid ratio, and provides a cured product with higher strength. Furthermore, it can be used in applications that require a relatively long time for filling, such as a root canal filling material for filling cavities in tooth root canals. Note that the hardening retardation effect is greater when both tannic acid and collagen are used together than when both are used individually.

The curable material for medical and dental purposes according to the present invention can be cured by mixing and kneading at room temperature or at a temperature near the body temperature, thereby preventing problems such as cell necrosis due to reaction heat. do not have.

Examples of the medical and sterile curable materials according to the present invention include the following.

■ A system consisting of a combination of calcium phosphate powder, organic acids and tannic acid.

In this system, the organic acid acts as a curing agent and the tannic acid acts as a curing retarder. Tannic acid may be used in a solution separate from the organic acid solution, or may be used after being dissolved in the organic acid solution.

The proportion of the materials of the type (2) used is not particularly limited, but is based on 30 to 80 parts by weight of powder, 5 to 60 M parts of organic acid, and 0.00 M parts of tannic acid. A range of 1 to 10 parts by weight is preferred. If the organic acid is below this range, curing may be insufficient, and if it is above this range, sufficient kneading may not be possible at room temperature. If the tannic acid content is below this range, the curing retardation effect may not be exhibited, and if it exceeds this range, sufficient kneading may not be possible at room temperature. The reaction mechanism of the material of the type (2) is believed to be, for example, as follows, based on analysis results using X-ray powder diffraction, infrared absorption spectra, scanning electron microscopy images, etc. When calcium phosphate powder, organic acid solution and tannic acid are mixed and kneaded at room temperature or at a temperature close to the body temperature,
A chelate bond is formed between 4CP(7)Ca in the powder or Ca in α-TCP and the carboxyl group of the organic acid, and the neutralization reaction progresses. On the other hand, tannic acid forms aggregates (possibly fibrous), and its chelates aggregate into the aggregates. In the presence of water, its chelate and unreacted 4CP and α at room temperature or around the body temperature.
-TCP undergoes a permanent reaction to form octacalcium phosphate (Ca.H2(PO4).・5H.O.
rOcPJ] and non-quality calcium phosphate (Ca-(PO4)*・nHzOo or less, rAC
PJ], and these ocp and ACP are called HAp.
HAp crystallizes into tannic acid aggregates and hardening progresses.

When the materials of each system (1) to (2) are mixed and kneaded, the hardening progresses more slowly than when tannic acid or collagen is not used. For example, at room temperature or at a temperature about the body temperature of a living body, it hardens within 5 to 60 minutes after the start of kneading, and a hard cured product is obtained. Therefore, the calcium phosphate powder/organic acid ratio can be increased, thereby increasing the strength of the cured product. In particular, when collagen is used, the compressive strength increases without increasing the calcium phosphate powder/organic acid ratio, and even after the hardening, the compressive strength increases over time and becomes highly elastic. The materials of each of the systems ① to ② can be used, for example, as materials for filling biological hard tissues such as bone cement and dental cement, and as materials for prosthetics.

The initial hardened product obtained by mixing and kneading each of the materials of
BS: Phosphate Buffered
If the material is immersed in saline), the crushing resistance will improve over time. That is, when each of the above materials (1) and (2) is used as a bone cement, the strength improves over time even after implantation. This is considered to be due to the use of collagen.

When the materials ① to ② are used as bone cement and implanted into the bone of a living body, the cement itself is bioactive and becomes a bone-like structure, and becomes integrated with the bone tissue.

That is, among the curable materials according to the present invention, if one using an organic acid as a curing agent and at least one of tannic acid and collagen as a curing retarder is used as a bone cement, the Over time, it replaces the bone cord tissue and integrates with the existing part.

It should be noted that each of the above-mentioned materials (1) to (2) may contain materials other than those mentioned above, as long as they do not hinder the achievement of the object of the present invention.

Further, the usage is not limited to the above example.

Examples of the present invention are shown below along with comparative examples, but the invention is not limited to the following examples.

(Examples 1 to 13 and Comparative Examples 1 to 4) A solution containing tannic acid, collagen, and an organic acid at the concentrations shown in Table 1 was prepared, and this solution was combined with calcium phosphate powder having the composition shown in Table 1. The mixture was mixed at the powder/liquid ratio shown in Table 1 and kneaded manually for about 1 minute. Using this kneaded mud, the following measurements were carried out and the results are shown in Table 1. The following measurements were all carried out under the conditions of temperature 23±2° C1 relative humidity 50±10% according to ADAS II&I61.

However, in Examples 1 and 2, measurements were performed using ADAS Ik57.

(al) Initial hardening time measurement Each kneaded mud was poured into a cylindrical stainless steel mold with an inner diameter of 10n+ and a height of 5mm placed on a glass plate with a length and width of 15 mm x 15 m x 15 mm to make the surface flat. One minute after the kneading was completed, it was transferred to a constant temperature chamber at a temperature of 37±1°C and a relative humidity of 100% to form a test piece. Mass: 2.9
A needle of 4N (300 g) bottle force (cross-sectional area of the needle is 1-) is gently dropped onto the surface of the test piece, and the initial curing time is calculated from the time when no needle marks are left behind, starting from the start of kneading. And so. The initial curing time was expressed as the average of three measurements, rounded to the nearest 15 seconds.

(bl) Crushing Drag Measurement A cylindrical stainless steel mold with an inner diameter of 6 mm and a height of 12 nm was filled with each kneaded mud, and both ends were sandwiched between thick glass plates and pressurized.

2.5 minutes after the start of kneading, the temperature was increased to 37±1'c while pressurized.
, and transferred to a thermostat at 100% relative humidity. After 1 hour, the cured product was taken out of the mold and immersed in distilled water at 37±t'c, and 24 hours after the start of kneading, it was taken out from the distilled water and used as a test piece. This test piece was attached to a Shimadzu Autograph AC-20
The crushing drag was measured using 00A. The crosshead speed was 1/min, and the measurement was performed on 6 test pieces, and the average value of the remaining values excluding the value of -15% or less of the total average value was taken as the measured value. However, -15 of the total average value
% or less, the test was conducted again.As shown in Table 1, the materials of Examples 1 and 2 showed faster initial curing progress than those using organic acids as curing agents. is slow,
Initial curing time suitable for root canal filling material was shown. Example 3~
Comparing 11 with Comparative Example 1.3, the initial curing time of Example was longer. Even if the crushing resistance of the cured product was increased by increasing the powder/liquid ratio as in Examples 12 and 13, the initial curing time was long enough to cause no practical problems. However, in Comparative Example 2.4, the initial curing time became extremely short due to the increased powder/liquid ratio, making it difficult to put it into practical use. Furthermore, in Examples 5 to 7, 9, 10.13) in which collagen was used, the crushing resistance of the initially cured products was clearly improved, and this was particularly remarkable when used in combination with tannic acid.

When each material of Examples 3 to 13 and Comparative Examples 1 to 4 was immersed in PBS, it was found that the crush resistance of the materials using collagen improved over time even after initial hardening.

In addition, each of the materials of Examples 3 to 13 and Comparative Examples 1 to 4 was initially hardened into a cylindrical bead with a diameter of 61 mm and a length of 12 mm, and the bead was implanted into the femoral bone defect of a dog for 2 weeks and 4 hours. week,
After 6 weeks, they were taken out, and the tissue of the adhesion surface with the bone tissue was observed and the adhesion force with the bone was evaluated by extrusion method. As a result, two weeks after transplantation, with the materials of Comparative Examples 1 to 4,
Although direct integration with bone had begun, slight round cell infiltration was observed. In contrast, the materials of Examples 3 to 13 had no such inflammatory reaction, and direct bonding with the bone had already progressed. Four and six weeks after the transfer, in the materials of Comparative Examples 1 to 4, the inflammatory symptoms gradually disappeared, and the bone shape gradually increased in this area. In each of the materials of Examples 3 to 13, bone cells were also present at the interface with the bone tissue. In particular, in those using collagen, a large number of bone cells were present around the interface, and the adhesion to bone was dramatically enhanced.

〔Effect of the invention〕

As described above, the medical and dental curable materials according to the present invention are mainly composed of calcium phosphate powder containing at least 4CP of 4CP and α-TCP as an essential component, and contain tannins, tannin derivatives and Since at least L type selected from the group consisting of collagen is used, it cures at room temperature or at a temperature close to the body temperature, and can lengthen the curing time, and is not harmful to the body. do not have. Therefore, the medical and dental curable material according to the present invention can be used in applications that require a long time to cure, or applications that require a high strength cured product by increasing the ratio of calcium phosphate powder to curing agent. It can be used for.

Claims (1)

[Claims] (1) A curable material for medical and dental use consisting of a combination of calcium phosphate powder containing at least tetracalcium phosphate as an essential component out of tetracalcium phosphate and α-tricalcium phosphate, and a curing solution containing an organic acid. Malic acid, citric acid and/or malonic acid are used as organic acids, and as curing retarders,
A curable material for medical and dental use, characterized in that at least one selected from the group consisting of tannins and tannin derivatives is used.