JPH0595993A - Hydration reaction-type calcium phosphate biomaterial having room temperature caking properties - Google Patents

Abstract

PURPOSE:To improve ordinary temp. caking properties and to attempt to improve strength without spoiling workability by forming a biomaterial being useful as a hard system replacing material having biocompativility from a powder wherein calcium phosphate compd. is a main ingredient and a soln. wherein fine particles of a metal oxide are dispersed in water. CONSTITUTION:A biomaterial being suitable for curing and repairing of a loss or cavity part of a tooth in the dental region consists of a powder wherein calcium phosphate is a main ingredient and a soln. wherein using water as a dispersing medium, fine particles of a metal oxide are coloidally dispersed in water. As the calcium phosphate compd., alpha-type tricalcium phosphate and tetracalcium phosphate are pref. used and as the metal oxide, silicic anhydride, zirconia and zircon are used. In addition, the soln. is a mixture of a colloidal soln. of at least one among silicic anhydride, zirconia and zircon and a colloidal soln. of another metal oxide. This biomaterial is cured by being accompanied with conversion to hydroxyapatite.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a biomaterial useful as a hard tissue substitute material having biocompatibility,
In particular, the present invention relates to a hydration-reactive calcium phosphate-based biomaterial suitable for various applications in the treatment and repair of tooth-deficient voids in the dental field.

[0002]

2. Description of the Related Art As a hard tissue substitute material in the fields of medicine and dentistry, a calcium phosphate-based compound having a composition extremely similar to an inorganic component of bone and dentin is increasingly important as a biocompatible material. ing.

Needless to say, the main component of the inorganic component is hydroxyapatite. However, in order to make the synthetic hydroxyapatite powdery substance into a solid product, the synthetic product itself does not have self-reaction hardening property. For example, there is no choice but to rely on a special method such as applying a material obtained as a fired body at a high temperature by molding. Therefore, the clinical treatment method based on the room temperature curing reaction between the powder and the liquid, which is generally found in many materials in the clinical field, cannot be adopted, and its direct use is limited.

However, in recent years, some of the apatite-like calcium phosphate compounds represented by α-type tricalcium phosphate are condensed by the hydration reaction with water, and the solidified ones are converted into hydroxyapatite. ,
A method of applying it was found. For example, such a method is disclosed in JP-B-61-9265 and JP-A-59-18.
2263 and the like. Especially in the dental field, etc., although the composition can be used by the same operation method as conventional materials, the composition is completely different from the conventional product, and the solid product after reaction curing is a composition that is as close as possible to the affected tissue. Become a thing. However, the kneaded product with water has some problems such as difficulty in operability in the form of dry sand or slurry liquid, too much time for curing, insufficient strength, etc., It was also found that this could not be immediately applied clinically.

Therefore, in order to solve these problems, many proposals have been reported thereafter. For example, Japanese Patent Publication 6
As disclosed in JP-A-2-42625, a method using a water-soluble polymeric acid as a curing liquid agent, or JP-A-62-1270.
As shown in No. 5, a method using an organic acid aqueous solution has been proposed. However, the curing reaction of these compositions has a different reaction mechanism than the hydration reaction. That is, although the curing is completed in a short time in a room temperature environment, the cured product is not immediately converted into hydroxyapatite by the reaction, and the calcium phosphate composition remains as a nucleophile in the base matrix as it is. The calcium phosphate composition as the nucleosome, for example, α-type tricalcium phosphate has the possibility of being converted into hydroxyapatite in the living environment over time, but its progress rate is extremely slow and the number of days is long. At the same time, the entire cured product may not be converted to hydroxyapatite depending on the kind of the composition and the state of the environment.

[0006] On the other hand, some original proposals for improvement have been made mainly on a hydroxyapatite conversion type composition by a hydration reaction. For example, as disclosed in JP-B-3-33676, a method of mixing dicalcium phosphate hydrate with α-type tricalcium phosphate, or JP-A-3-1280.
As shown in No. 63, the second addition to α-type tricalcium phosphate
A method of mixing anhydrous calcium phosphate has been proposed. However, even with these improved compositions,
Basically, operability, curability, strength, etc. are as described above
It is the same as that of JP-A-9265 and JP-A-59-182263, and needs further improvement.

[0007] Another approach is Japanese Patent Publication No. 3
As disclosed in JP-A-41423 and JP-A-63-25291, a method of adding a fluorine compound to a calcium phosphate compound has been proposed. Improvements have been made in various fields such as operability, curing time, and mechanical strength, and some have been suggested to have potential for clinical application. However, according to these methods, an acid, which can be said to be an excessive amount for the purpose of hydration reaction, is used in the curing liquid agent in any of the compositions. In Japanese Examined Patent Publication No. 3-41423, a hydrated self-hardening composition is kneaded in accordance with the regulations and hydrated to give a cured product of fluorapatite having excellent hardness. On the other hand, in JP-A No. 63-25291, hydration hardening is basically carried out by mixing with water. On the other hand, in practical use, in all reports, curable materials contain acids such as organic acids and inorganic acids as curing accelerators. In addition, an organic or inorganic acid is used as a curing accelerator in order to proceed or adjust the curing reaction in the vicinity of the living body temperature in a relatively short time. As is clear from this, it is presumed that these are not completely hydration type compositions. That is, it is considered that curing is achieved in a well-balanced manner by an intermediate mechanism between the acid aqueous solution reaction type and the hydration reaction type. In these reports, there is no explicit demonstration that the conversion to the complete apatite structure is completed immediately after the completion of curing.

[0008]

It should be noted here that these conventional hydration-condensation reactions are controlled by the ambient temperature.

This reaction proceeds even at room temperature (about 25 ° C. or lower, which will be referred to as room temperature in the present), and the condensation is completed with the conversion to hydroxyapatite, but in this case, it takes a considerably long time (days). A) and a continuous supply of water is essential. Therefore, in practice, when the mixture of the α-type tricalcium phosphate composition and water is left to stand in a room at room temperature, the water content of the mixture will soon evaporate and volatilize. Then, the reaction proceeds to a solid state as a powder agglomerate and the reaction progresses.

When the surface of the solid material itself is pushed under a certain prescribed method, for example, a constant load of several hundred grams by a rod-shaped metal needle, no needle mark is left and it is judged that the solidification is completed. It is also possible to do it, and it may be used as a certain standard, but it is not true condensation, and naturally, this solid material is crushed with a slight stress and returns to the original powdery material. For example, when compressive strength is measured, the strength value is 0 or a value close to 0.

[0011] Even with such a phenomenon, when the environmental temperature is 37 ° C, which is close to the living body temperature, the reaction greatly progresses in a short time (several hours) and is completely converted into hydroxyapatite, and as a cured product having strength. It becomes a solid object of. However, in order to obtain a faster curing, the above-mentioned Japanese Patent Publication No. 61-926.
No. 5, JP-A-59-182263 and the like achieve the object by adding a curing accelerator such as various water-soluble acids and salts, but in this case also, an environment of 37 ° C. is required. Needless to say.

On the other hand, the calcium phosphate compositions reported in Japanese Patent Publication Nos. 3-33676, 3-41423, and JP-A-3-128063, which are obtained by improving these basic compositions, have an environment at the time of curing. All require 37 ° C.

At present, in order to make an α-type tricalcium phosphate-based composition into a solid product as a completely hardened product, at present, another reaction mechanism, namely, an acid solution of a water-soluble polymer or various organic acid aqueous solutions is used. However, in this case, as described above, at the time of completion of initial curing,
Conversion to hydroxyapatite does not occur and the subsequent conversion is extremely slow.

The inside of the oral cavity is not a closed living environment, but is constantly in contact with the changing external environment, and the temperature environment is not always kept at 37 ° C. at the time of adapting the material. There are also many. Therefore, even a hydration reaction type material having a curing ability in a low temperature environment of 37 ° C. or less is desired. On the other hand, if the curing reaction is further promoted by heating and the conversion to hydroxyapatite also progresses rapidly and becomes a solid product as a complete aggregate, it is extremely convenient as a calcium phosphate-based composition having room temperature setting ability. Should be.

If a hydration active composition such as α-type tricalcium phosphate or tetracalcium phosphate becomes a true aggregate even at room temperature, and conversion to hydroxyapatite can be completed in a short time. , Its application range as a biocompatible material is further expanded.

In view of the above-mentioned circumstances, the present invention intends to provide a room temperature curing method different from an organic acid or polymer acid aqueous solution curing method, that is, a water-curable calcium phosphate-based composition having a hydroxyapatite conversion ability. Is.

[0017]

DISCLOSURE OF THE INVENTION The present invention is a room temperature coagulation comprising a powder having a calcium phosphate compound as a main component and a solution in which water is used as a main dispersion medium and fine particles of a metal oxide are colloidally dispersed in water. The main point is a hydration-reactive calcium phosphate-based biomaterial having the ability.

[0018]

EFFECTS OF THE INVENTION The conventional water-curable calcium phosphate-based composition is improved in operability, that is, the kneaded product does not have a dry, dry sandy form, has an appropriate viscosity, and is easy to handle and easy to operate. It becomes a good paste.

The curing reaction proceeds even at room temperature, and the cured product is a solid product as a complete aggregate, and the compressive strength does not become 0 or close thereto.

In the 37 ° C. temperature environment, the reaction proceeds further without receding.

The conversion to hydroxyapatite can be completed promptly without delaying the conversion to hydroxyapatite like other room temperature-curable calcium phosphate-based compositions using an aqueous solution of a polymeric acid or an organic acid.

[0022]

EXAMPLES The present invention comprises a hydration reaction type composition comprising a powdery agent mainly composed of a calcium phosphate compound and a solution in which water is used as a main dispersion medium and fine particles of a metal oxide are colloidally dispersed. A hydration-type calcium phosphate-based biomaterial having the following room temperature coagulation ability.

Here, the calcium phosphate compound is α
Type tricalcium phosphate is preferred, but other calcium phosphate compounds such as tetracalcium phosphate may be used as long as they have hydration activity.

As the metal compound, silicic acid anhydride (SiO 2
2), zirconia (ZrO2), zircon (ZrSiO)
4) etc. are the most preferable. The solution in this case may be a known one generally called silica sol or zirconia sol. Further, other metal oxides such as aluminum, lithium, antimony, iron, cerium, yttrium, chromium, and the like, or a mixed solution of the above oxides may be used. There is no limit.

The dispersion medium of these metal oxide colloidal solutions does not impair the hydration reaction of the calcium phosphate compound,
Water is most preferable also for the purpose of giving an effect of promoting coagulation and not exerting a harmful effect on the living body.

Further, various surfactants may be added to such a solution to improve operability,
It is also possible to add a small amount of various organic acids, inorganic acids, or organic solvents such as ethanol to contribute to the improvement of various physical properties. For example, when phosphoric acid is added, the order in which the electrolyte influences the stability of the silica sol is examined. Since the phosphate ions are arranged on the side where gelation is unlikely to occur, the stability period is shortened, but it can be used.

The particle size of the metal oxide is generally from 1 to
Although it is an ultrafine particle of 100 nm, the present invention is not limited to this size. The shape of the fine particles is generally spherical, but may be rod-shaped, needle-shaped, elongated such as fibrous, or indeterminate. In addition, it is also possible to combine the above-mentioned materials having different sizes and shapes to improve performance. The concentration of this metal oxide is generally 20 wt% to 40%.
Although wt% is commercially available as a variety, a higher concentration can be used in consideration of the stability of the sol. For example, if a sol having a desired concentration cannot be found in a commercially available sol, a sol having an appropriate concentration may be concentrated and the concentration may be increased before use.

The metal oxide colloidal solution represented by silica sol has advanced to various fields such as the ceramic industry, the metal industry, the catalyst science, the textile industry and the food industry due to its special property, but in recent years, much study has been made so far. Movements are beginning to be made for effective use even in fields that have not been developed.

In the present invention, the gelation phenomenon due to the destruction of the electric double layer possessed by the fine particle colloidal solution and its binding ability are evaluated by using calcium phosphate compounds as biomaterials, especially α-type tricalcium phosphate or phosphate having hydration activity. As a result of trying various tests with the idea of applying it to tetracalcium etc.,
We obtained various new findings and found their usefulness.

The internal structure of the α-type tricalcium phosphate-water hydration reaction aggregate generally exhibits a fine porous structure having a high porosity. That is, since it is a coagulate having voids, it may be convenient as a biocompatible material in a sense, but on the other hand, in terms of various physical properties, there are problems such as insufficient strength. is doing. Therefore, the application of the metal oxide colloidal solution to the curing liquid agent such as the composition of the present invention is suitable for such a hydration active substance,
It contributes to the increase in strength by appropriately densifying the pores of the fine porous structure.

On the other hand, with respect to the coagulation ability, the hydration reaction of the conventional water-based composition is active in the high temperature region of 37 ° C. or higher, as compared with the composition of the present invention. Due to its application as a curing liquid agent, strong coagulation is completed even at room temperature, and the phenomenon of rapid rapid conversion to hydroxyapatite in the biological environment later is difficult to handle due to its low initial physical properties. It can be said that the performance is extremely favorable in place of the conventional hydration reaction composition.

As described in Schulz-Hardy's law, Hofmeister permutation, etc., some sols have a destabilizing factor to the colloid of the electrolyte, in which cations cause aggregation due to polyvalent cations having large valences. In addition, although there are those that are expected to have unknown uses that exhibit many other interesting phenomena, in the present invention, those phenomena were applied to biomaterials, and the suitability with calcium phosphate compounds having hydration activity was searched for. Is.

The instability factor of the metal oxide colloidal solution itself is governed by the pH as well, but in the composition of the present invention, for example, the silica sol usually has a stable range of pH 8 to 10 and a metastable range of pH 2 to 4. Both are characterized by a wide range of applications in which the above object can be achieved. In particular, not only conventional acid aqueous solution compositions but also water-curable compositions have always been adjusted with an acidic substance, but the fact that they can be set even in the alkaline range expands the application range of calcium phosphate compounds. Important in terms. In addition, even if the pH of the sol is a metastable region solution in the acidic range, the pH of the kneading paste of the composition was measured and showed no acidity around 8.0, which is suitable as a composition for living organisms. It turned out to be.

In terms of operability, since the metal oxide colloidal solution itself has an appropriate viscosity, the state of the kneaded product becomes a paste that is extremely easy to handle, and the state of dry or dry sand like conventional aqueous compositions or wet sand. It has become possible to eliminate the difficulty of handling the condition.

Since the viscosity of this sol can be freely controlled, the state of the kneading paste can naturally be freely selected.

Here, it should be further noted that even if the viscosity of the kneading paste is selected according to the operator's preference or the application, the effect on the strength is extremely small. Conventional powder-liquid type compositions, whether they are water-curable compositions or acid-curable compositions, are greatly affected by the powder-liquid ratio in terms of strength. That is, the strength of the coagulum having a larger amount of the powder agent than that of the liquid agent becomes higher, but the strength of the condensate having a smaller amount becomes lower. Therefore, at the time of use, it is desirable to increase the powder portion in order to obtain high strength, but the kneaded product with many powder portions becomes more excessively dry and the powder-liquid ratio above a certain range may be actually obtained. It cannot be done, and the strength is limited. Moreover, even if the amount of powder is increased forcibly, the supply of water necessary for the hydration reaction will not catch up, and the factor of destruction of the kneaded substance will act more dominantly than the reaction rate, which will in turn reduce the strength. I will leave. However, in the composition of the present invention, the influence of the powder-liquid ratio on the strength is much smaller than in the conventional type, and it is possible to select an appropriate viscosity according to the operator's preference. That is, since various factors peculiar to the metal oxide colloidal solution described above are compounded and expressed, it is possible to always stably obtain a high-strength aggregate even in the form of a paste that has few powder parts and is easy to handle. is there.

As described above, it was found that the use of the colloidal dispersion solution of the metal oxide as the curing agent for the calcium phosphate compound having the hydration activity gives various favorable factors not found in the conventional type.

The method for producing the calcium phosphate compound having hydration activity may be any method and is not particularly limited. For the purpose of improving various properties, other calcium phosphate compounds such as hydroxyapatite, octacalcium phosphate, dibasic calcium phosphate, monobasic calcium phosphate, β-tricalcium phosphate, etc. are added as an aggregate, and X-ray contrast property, pharmacological action and pH are added. Various additives for imparting adjustability, such as barium sulfate, bismuth subcarbonate, calcium tungstate, iodoform, zirconium compounds, fluorine compounds, antibacterial agents, calcium hydroxide, calcium oxide, magnesium hydroxide, magnesium oxide, etc. It is possible to add.

The effects of the present invention will be specifically described below by showing experimental examples.

Experimental Examples 1 to 4 and Comparative Examples 1 to 2 In order to confirm that the compositions of the present invention have room temperature coagulation ability, powders were prepared in an environment of room temperature of 23 ± 2 ° C. and relative humidity of 50 ± 10%. 4 mm diameter x 8 height
The sample was filled in a mold so as to obtain a cylindrical solid sample body of mm, left for 5 hours and 30 hours in the same environment, and then taken out from the mold and the compression strength was measured.

The powder has an average particle size of 4 at 50 wt%.
α-type tricalcium phosphate (Experimental Examples 1 and 2) and tetracalcium phosphate (Experimental Examples 3 and 4) having a specific surface area of 0.8 m ² / g in μm were used.

The solution is an acidic type sol having a small particle diameter and a normal concentration and having a silicic acid anhydride content of 20 to 21% and a particle diameter of 10 to 10.
20nm, pH 2-4 ST-O (manufactured by Nissan Chemical Industries, Ltd.)
(Experimental Examples 1-1 and 3-1), the same zirconia sol having a zirconium oxide content of 20%, a particle diameter of 5 to 10 nm, and a p
H0.7-1 solution (manufactured by Nissan Chemical Industries, Ltd.) (Experimental Example 1-
2, 3-2), a solution having a zirconium silicate content of 28%, a particle diameter of 10 nm, and a pH of 1.0 to 1.3 (manufactured by Nissan Chemical Industries, Ltd.) (Experimental Examples 2-2, 4-2) as the zircon sol.
In addition, as an alkaline type large-sized high-concentration sol, silicic anhydride content 40-41%, particle size 70-100n
ST-ZL (manufactured by Nissan Chemical Industries, Ltd.) (Experimental Examples 2-1 and 4-1) having a pH of 9 to 10.5 was used.

A powder-liquid ratio of 2.0 to 2.
Various samples were prepared by kneading in the range of 5 and used for measurement.

On the other hand, as conventional hydration reaction solid sample bodies, α-type tricalcium phosphate used in Experimental Examples 1 and 2 (Comparative Example 1) and tetracalcium phosphate used in Experimental Examples 3 and 4 (Comparative Samples were prepared in the same manner as in the experimental example using physiological saline as a liquid agent, and stored in the same temperature environment as a comparative example, and used for the measurement.

[0045]

[Table 1] The results are shown in Table 1. As is clear from Table 1,
In the conventional type, the compressive strength is so weak that it cannot be measured at all, whereas in the composition of the present invention, the acidic type sol, the alkaline type sol, or any of the metal oxide sols after 5 hours. Compression resistance has already appeared, and after 30 hours, 200 Kgf / cm
^It showed a strong compressive strength of ² or more. Although the compressive strength of Comparative Example 1 was not 0, it was a weak solid substance that easily collapsed into a powder when crushed with fingers.

Experimental Examples 5-9 and Comparative Examples 3-7 The compositions of the present invention are superior in compressive strength as compared with the conventional water-curable compositions. Therefore, the compressive strength by immersion in water at 37 ° C. was calculated in consideration of the biological environment temperature, and the effect of the hydration reaction was compared with the conventional type. The reference value is 37 ℃
The hydration reaction strength after storage in air was also determined. The size of the sample and other preparation conditions are the same as in Experimental Examples 1 to 4.

The powder was the α-type tricalcium phosphate used in Experiments 1 and 2 (Experiments 5-9), and the liquid was Experiments 1 and 3.
The ST-O used in Example 1 (Experimental Examples 5 to 7), a sol obtained by concentrating the silicic acid anhydride concentration thereof about 3 times (Experimental Example 8) and a sol to which a small amount of phosphoric acid was added (Experimental Example 9) were added. ..

On the other hand, a conventional hydrated sample for comparison was prepared by using the α-tricalcium phosphate used in Experimental Examples 1 and 2 as a powder,
The physiological saline used in Comparative Examples 1 and 2 as a liquid agent (Comparative Example 3 to
5), dilute aqueous phosphoric acid solution (Comparative Example 6), and 1
An N-nitric acid aqueous solution (Comparative Example 7) was used.

[0049]

[Table 2] The strength after 24 hours is shown in Table 2. A statistically significant difference was found between the strengths of Experimental Examples 5-9 and Comparative Examples 3-7, and the composition of the present invention showed high compressive strength. Further, from the value of the composition of the present invention stored in air at 37 ° C., it can be estimated that the hydration reaction proceeds even when stored in air.

Experimental Examples 10 to 13, Comparative Examples 8 to 9 and Control Example
1-2 , in the case of using α-type tricalcium phosphate as a powder, confirmation of rapid conversion of the aggregate to hydroxyapatite can be confirmed by X
The peak heights of the diffraction patterns were qualitatively compared by the line diffraction method to carry out. The maximum diffraction intensity of hydroxyapatite occurs at d = 2.81 (JCPDS No. 9-432), which is the diffraction line of α-type tricalcium phosphate d = 2.8.
86 (JCPDS No. 29-359), and it is difficult to confirm its existence when the conversion rate is low, so it is excluded, and the diffraction lines of both do not overlap, and are often used as peaks for precise analysis. Generated relatively sharply d = 3.
The line of interest was 44 (hkl: 002). The height of this diffraction line was calculated by the following formula to find out how many times the height of the d-2.91 diffraction line height, which is the maximum diffraction intensity of α-type tricalcium phosphate, was calculated by the following formula and used as an evaluation index of the conversion rate. did.

Evaluation index of conversion rate = {(I HAP) /
(I TCP)} × 100 where I HAP is hydroxyapatite (d =
3.44) shows the diffraction line intensity, and I TCP shows the α-type tricalcium phosphate (d = 2.91) diffraction line intensity.

Unadded residual α-type tricalcium phosphate is
The larger this value is, the smaller it is. There is an exponential difference in this value, so comparing small numbers does not make much sense. Therefore, the final evaluation of conversion will be represented by the following symbols.

Symbol conversion rate evaluation index ∞ 1000 or more ++ 100 to 999 +10 to 99 ± 9 or less In the case of a water-curable composition, peaks occur relatively sharply. The conversion to hydroxyapatite is confirmed. Also,
In the case of 9 or less, it is difficult to determine the start of conversion, and it cannot be said that it is either.

[0054]

[Table 3] Table 3 shows an experimental example of the composition of the present invention and a comparative example using a conventional polymeric acid aqueous solution curable composition and an organic acid aqueous solution curable composition. The conversion ability to apatite was summarized as a control example. All the powders used here are Experimental Examples 1 and 2.
The same α-type tricalcium phosphate was used in common. The liquid agents were different as described in the table. The conversion rate of the one using acidic type sol as the liquid is the highest (Fig. 1),
It was then of alkaline type. Although not distinguishable from the symbols in the table, the conversion ability of the conventional water-curable composition using physiological saline is slightly lower than this (FIG. 3). A delay tends to be seen in aqueous solutions with the addition of inorganic acids.
Numerical values are added to some symbolic representations to clarify these differences. If a value is added to clarify the difference, the sample judged to have completed the initial setting in a room temperature environment is carefully immersed one week later in 37 ° C. water, and the conversion index is 100 or more (symbol: ++). When the elapsed time was examined, it was found that Control Example 1 required 14 days and Control Example 2 required 95 days, while Experimental Example 11 required 1 day.

Another conventional acid-curable composition,
That is, the progress is extremely slow in the polymeric acid aqueous solution curable compositions shown in Comparative Examples 8 to 9 and particularly in the organic acid aqueous solution curable compositions (FIG. 2).

As is clear from these results, the ability of the composition of the present invention to be converted into hydroxyapatite was extremely excellent, and it was proved that the composition could proceed in a short time. This conversion ability was not inferior to that of the conventional water-curable composition as a control. Further, this characteristic is not found in the conventional room temperature curable composition, that is, in the aqueous polymer acid aqueous solution curable composition or the organic acid aqueous solution curable composition.

Experimental Example 14 and Comparative Example 10 The composition of the present invention has little influence on the strength of the powder-liquid ratio.
An α-type tricalcium phosphate having an average particle size of 7 μm at 50 wt% and a specific surface area of 0.6 m ² / g is used as a powder, and a silicic acid content of 16% and a particle size of 10 are used as a liquid.
FIG. 4 shows the measurement results at each powder-liquid ratio after 24 hours of curing at 37 ° C. in air of the composition of the present invention using a non-spherical sol ST-OUP (manufactured by Nissan Chemical Industries, Ltd.) having a particle size of 20 μm and a pH of 2.8. (Experimental example 14).

The comparative example in FIG. 4 is a case where purified water is used as the liquid agent (Comparative Example 10).

As is clear from FIG. 4, the composition of the present invention is unlikely to be affected by the reduction of the powder-liquid ratio as in the conventional hydration hardening composition, and is not easily affected. There was found.

Experimental Example 15 A part of the kneaded product of Experimental Example 14 before coagulation was transferred to a dish, and a flat pH electrode was brought into direct contact with the kneaded product to adjust pH.
When the value of was read, the first measurement value was 7.9 and the second measurement value was 8.0. This value did not change with the passage of time, and the pH of the kneaded product did not become such a low value that it would last for a long time in a conventional room temperature curable composition using an aqueous acid solution even when an acidic liquid agent was used.

Experimental Example 16 The kneaded product of each of the powder-liquid ratios of Experimental Example 14 was sampled and subjected to various operation observations with a spatula. The kneaded product had fluidity and had an appropriate viscosity and leakage thread. It had a paste-like shape with excellent properties and was extremely easy to handle and had excellent operability.

In summary, according to the present invention, the room temperature (room temperature) setting ability of the hydration reaction type calcium phosphate-based composition is improved, the strength is enhanced without impairing the operability, and the conversion to hydroxyapatite is promoted. It has become possible to obtain a composition having excellent hydration activity.

[Brief description of drawings]

FIG. 1 is a diagram showing an example of an X-ray diffraction pattern showing conversion into hydroxyapatite, showing the state of Experimental Example 11 after 3 days.

FIG. 2 shows the state of Comparative Example 8 after 3 days.

FIG. 3 shows the state of Control Example 1 after 3 days.

FIG. 4 is a graph showing the relationship between compressive strength and powder-liquid ratio.

[Explanation of symbols]

 H: Hydroxyapatite, T: α-tricalcium phosphate main peaks ◆

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Claims (9)

[Claims] 1. A biomaterial useful as a hard tissue substitute material having biocompatibility, wherein fine particles of a metal oxide are colloidally dispersed in water by using a powder agent mainly composed of a calcium phosphate compound and water as a main dispersion medium. A hydration-reactive calcium phosphate-based biomaterial having room-temperature coagulation ability, which is characterized in that it is composed of a prepared solution. 2. The biomaterial according to claim 1, wherein the calcium phosphate compound is α-type tricalcium phosphate. 3. The biomaterial according to claim 1, wherein the calcium phosphate compound is tetracalcium phosphate. 4. A biomaterial, wherein the metal oxide is silicic acid anhydride. 5. The biomaterial according to any one of claims 1 to 3, wherein the metal oxide is zirconia. 6. The biomaterial according to any one of claims 1 to 3, wherein the metal oxide is zircon. 7. A solution in which fine particles of the metal oxide are dispersed in a colloidal form is a mixture of at least one colloidal solution of silicic acid anhydride, zirconia and zircon and a colloidal solution of another metal oxide. The biomaterial according to claim 1, which is 8. The room temperature coagulation ability is equal to or lower than a living body temperature.
The biomaterial according to claim 1, which can be a cured product at an environmental temperature not exceeding 5 ° C. 9. The biomaterial according to claim 5, wherein the cured product is converted into hydroxyapatite.