JPH0763502B2 - Human hard tissue replacement composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a human hard tissue replacement composition.

2. Description of the Related Art So-called powder-liquid type hard tissue replacement compositions using powders and liquids have been applied to various fields as various materials, and in the medical field, bone cement (methylmethacryl-based),
In the dentistry field, root canal filling materials and various dental cements (for bonding, filling, lining, covering, etc.) are typical examples.

Problems to be Solved by the Invention Although these materials are mainly composed of natural or synthetic resin-based or inorganic materials, the problem in the past is a harmful effect on the living body. That is, it can be said that the conventional biohard tissue replacement composition has some form of irritation of a living body and is poor in affinity with the living body because it is a material different from the living body.

Therefore, when a conventional human hard tissue substitute composition is used as a bone cement, there is a problem in irritation to a living body, affinity, operability, and various other physical properties, so that there is no irritation or heat generation,
In addition, it has been desired to realize a composition for substituting a hard tissue for human body, which is excellent in operability.

This invention aims at providing a human body hard tissue substitute composition which is capable of promptly and firmly hardening with proper operation margin time in each application without stimulating the living body. And

Means for Solving Problems The present invention comprises (a) Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8) as a main component, and (b) tetracalcium phosphate and triphosphate. The above object is achieved by kneading a powder containing at least one of calcium, hydroxyapatite or calcium oxide and an organic acid liquid agent capable of reacting with the powder to form a coagulation hardened product, to form a composition. It was done.

The greatest feature of this invention is that a specific calcium phosphate is used as a powder, and an organic acid in the TCA cycle is used as a main component in a liquid. As is well known, the inorganic component of biological hard tissues such as bones and teeth is calcium phosphate such as hydroxyapatite and pushite, and recently, inorganic biomaterials similar to this have attracted attention. The reason for this is that in addition to in vivo safety, biological activity (bioinert) and biological activity (bioa
ctive).

Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8) in the present invention
Is a biocompatible inorganic material similar to hydroxyapatite and is originally characterized by bone replacement due to biodegradability, but is chemically active and is known to be converted to hydroxyapatite under certain conditions. .

However, in order to actually use it as a material for cement or the like, it is necessary that a mixture of calcium phosphate and a liquid agent is hard and solidified, and that the solidified product is close to neutral and does not collapse. This area has not been fully studied yet. Although α-TCP is hardened by an organic acid, it has a high disintegration rate and a high acidity, and therefore may cause inflammation when used in a living body.

The feature of the present invention is that by kneading a specific calcium phosphate and an organic acid-based liquid agent, not only a strong setting and hardening product can be obtained, but also the disintegration rate of this is low, that is, the pH is near neutral. That is.

As the biocompatible inorganic material, Ca _{n + 2} in the present invention is used.
In addition to (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8), there are also hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, etc., except for α-tricalcium phosphate. Both are difficult to cure in the in vivo environment due to their low chemical activity.

By using an organic acid-based aqueous solution as the liquid agent, it is possible to impart appropriate viscosity to the kneading mud and, in addition, show a proper operation allowance time for each application, and quickly and firmly cure it in the human body environment. Therefore, the composition of the present invention has the following fields of application.

Medical applications include artificial bones to be inserted, bone cements for joining and filling joints between artificial joints and autogenous bones. It is also possible to mix powders and liquids and embed them in the bone defect as fluid mud to use as substitute bones.

As a dental cement, it can be mainly used for joint wear or for filling, but it can be said that it is suitable for lining and covering because of its excellent affinity.

As is well known, polycarboxylic acid cement, glass ionomer cement, zinc phosphate cement and the like are used for these applications, and the powder component and liquid component thereof are not the hard tissue replacement composition of the present invention. It is different.

The human hard tissue replacement composition of the present invention is composed of a powder and a liquid as shown in Table 4.

First, the powder will be described.

The powder which is Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8) is fired, for example, in the mixing ratio range of 2 <n ≦ 4.8 in the following reaction formula.

Of course, it is also possible to use CaO instead of CaCO ₃ in the reaction on γ-Ca ₂ P ₂ O ₇ + nCaCO ₃ → C _{n + 2} (PO ₄ ) ₂ O _n-1 + nCO ₂ . The suitable reaction temperature is 1200 to 1700 ° C.

The calcining reaction product is calcium phosphate represented by Ca _{n + 2} (PO ₄ ) ₂ O _n-1 , but the phosphoric acid may change depending on various conditions such as the calcining temperature, the temperature rise rate, and the moisture contained in the inflow cooling air after calcining. It is a calcium phosphate having the above composition containing 1 part of tetracalcium, tricalcium phosphate, hydroxyapatite, calcium oxide and the like.

The present invention contains at least one of the above-mentioned tetracalcium phosphate, tricalcium phosphate, hydroxyapatite or calcium oxide in addition to Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8). To do. Ca _{n + 2} (PO ₄ ) ₂ O in the present invention
It is desirable that _n-1 (2 <n ≦ 4.8) is contained in 80% by weight (hereinafter,% is based on weight) or more. Also, the above-mentioned Ca _{n + 2} (P
The reason why the composition of O ₄ ) ₂ O _n-1 is 2 <n ≦ 4.8 is that the acidity of the composition becomes strong when the ratio is 2 or less, and the alkalinity becomes strong when the ratio exceeds 4.8, and both are suitable as biomaterials. Because there is no.

When using the powder, it is made into powder of about 44 μm or less.
In addition, an X-ray contrast agent or the like can be included in the powder, if necessary.

Table 1 shows a part of the organic acid-based liquids, and so-called TCA cycle organic acids, namely citric acid, malic acid, malonic acid, tartaric acid, lactic acid, succinic acid, fumaric acid, aspartic acid, pyruvic acid, etc. Is used. Further, a small amount of phosphoric acid or hydrochloric acid may be added to this organic acid, if necessary.

It is desirable that the liquid agent contains 25 to 60% of the organic acid. If the amount of this organic acid is less than 25%, the organic acid that is involved in the chemical reaction may be insufficient and may not be completely solidified. Also
If it is more than 60%, a cured product excellent in physical properties can be obtained, but it is necessary to sacrifice the extremely important operability as a composition for substituting a hard tissue in the human body, and the kneading mud becomes too hard to use. . Further, the above-mentioned inorganic acid may be added within the range of 0.5 to 5% in order to improve the physical properties, particularly the crushing resistance.

In addition, a water-soluble calcium salt and a pH adjusting agent can be added if necessary.

When the liquid agent containing 25 to 60% of the organic acid described above is used, the mixing ratio of the powder agent and the liquid agent is 1 to 2 parts by weight per 1 part by weight of the liquid agent.
2 parts by weight is suitable. If the amount of the powder is less than this, the curing time is too long, and if the amount of the powder is too large, the mixture cannot be mixed.

Experimental Examples (Comparative Examples) 1 to 7 Using raw materials having a molar ratio as shown in Table-2, heating at a heating rate of 20 ° C / min until the firing temperature shown in Table-2 and holding for 2 hours After cooling at a rate of 40 ° C./min, the crushed particle size was adjusted.

Next, Table 3 shows an experimental example of a human hard tissue replacement composition. In Experimental Examples 1 to 7, the powder was fired under the conditions shown in the experiment and the particle size was adjusted. JIS measurement of physical properties
It was measured according to the test method of T 6602.

Examples 1 to 3 Powders shown in Table 4 were mixed with the powders prepared in Experimental Examples 2, 4 and 6 to obtain powders of Examples 1 to 3.

These powders were kneaded with the liquid preparations shown in Table 5 to obtain human hard tissue substitute compositions. These physical properties were measured in Experimental Examples 1 to 7
Similarly to, the measurement results of Table 5 were obtained according to the test method of JIS T6602.

EFFECTS OF THE INVENTION As is clear from the above description, according to the present invention, when the human body hard tissue substitute composition is used, the human body is not stimulated and the affinity for the living body is ensured while the living body environment is maintained. It can be hardened promptly and firmly with an appropriate operating margin.

Claims (2)

[Claims] 1. A) Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦ 4.8)
A composition for replacing hard tissues of human body, which comprises (b) a powder containing at least one of tetracalcium phosphate, tricalcium phosphate, hydroxyapatite, and calcium oxide, and (c) an organic acid-based solution. . 2. Among powders, Ca _{n + 2} (PO ₄ ) ₂ O _n-1 (2 <n ≦
The human hard tissue replacement composition according to claim 1, wherein the content of 4.8) is 80% by weight or more.