JPH0793942B2 - Curing liquid for biomaterials - Google Patents

Description

TECHNICAL FIELD The present invention relates to a hardening liquid for a calcium phosphate-based biomaterial.

2. Description of the Related Art Calcium phosphate-based biomaterials are used as biohard tissue repair materials that fill in biohard tissue defects.

The bio-hard tissue repair material is a method of inserting the material that has been molded into the desired shape in vitro, as it is or after making a multi-faceted modification, and by filling the kneaded product into the defective portion with a complicated shape. There is a method of hardening it in the body.

In any case, the material used must be compatible with the living body, non-irritating to the living body, and nontoxic, and in recent years, calcium phosphate-based biomaterials (ceramic powders) having a composition similar to that of living hard tissues have attracted attention. There is.

As described above, in order to make the powdery hardened product that can withstand use, the high temperature and high pressure sintering method and the like are employed in vitro as described above, but in general, the method of directly curing in vivo is desirable.

In this case, the kneaded product is a putty-like or paste-like mixture (mixed mud) that is kneaded with water, a physiological saline solution, an inorganic acid, an organic acid, salts thereof and a polyacrylic acid-based aqueous solution or the like capable of reacting and curing the powder. Is adapted to the affected area.

When kneaded with water, physiological saline solution, inorganic acid, some organic acids, aqueous solution of easily water-soluble salts, etc., it shows a so-called wet sandy state, and it remains dry and difficult to handle for a long time, and the setting completion time It is not practical because it is very long and the powder-liquid ratio is difficult to match.

On the other hand, the polyester acid-based curing liquid is solidified and cured in a short time by kneading, and the compression strength can be relatively high.

Problems to be Solved by the Invention However, in the case of conventional polyacrylic curing, since the viscosity (kinematic viscosity) of the curing liquid is considerably high at about 1,000 mm ² / s or more, the fluidity of the mixed mud decreases and the operability is reduced. In the clinical field, where importance is placed on, the advent of low-viscosity hardening liquid is desired. In the present specification, the term “viscosity” represents the viscosity of the liquid agent itself by a numerical value based on the kinematic viscosity, and is a measure showing the fluidity of the liquid agent and the ease of handling.

For example, in the endodontic field, a calcium phosphate biomaterial is used as a root canal sealer or a root canal filler in order to fill the root pulp cavity from which pulp has been removed by treatment. In that case, the fluidity of the mixed mud of the hardening liquid and the biomaterial becomes an indispensable factor, and the lack of fluidity makes it impossible to fill the root pulp cavity.

Therefore, in order to make the consistency of the mixed mud (in other words, the fluidity of the mixed mud) a preferable value for clinical operation and to fill the mixed pulp into the root pulp cavity, the amount of the powder is reduced and the powder / liquid formulation is used. (Powder / liquid ratio) must be significantly reduced. However, in this case, the amount of the powder is reduced, the desired physical properties or the affinity for the living body cannot be obtained, which is not preferable for clinical use.

On the other hand, if the viscosity is too low, the desired compressive strength is obtained, but the bending strength is insufficient and there is a fragile defect.

OBJECT OF THE INVENTION The present invention has been made in order to solve the above-mentioned drawbacks, and lowers the liquid viscosity specific to the curing liquid (the viscosity of the curing liquid) and raises the powder-liquid ratio of the mixed mud to a preferable value in clinical operation. Even so, it is an object of the present invention to provide a curable liquid for biomaterials, which can secure the fluidity of the admixture that is preferable in clinical operation and is easy to use clinically, obtains a desired bending strength, and has a tenacity.

SUMMARY OF THE INVENTION In order to achieve this object, the present invention is a hardening liquid used for a calcium phosphate-based biomaterial, wherein the hardening liquid is one of citric acid and DL-malic acid, and an average molecular weight of 24,000 to.
A curing liquid for biomaterials, which contains 28,800 acrylic acid itaconic acid copolymers, has a viscosity (kinematic viscosity) of 900 mm ² / s or less, and has a consistency of 30 or more when mixed with a powder. Is the gist.

Example The hardening liquid of this invention is used for the powder (powder) of a calcium-phosphate biomaterial. Examples of the calcium phosphate-based biomaterial targeted for this purpose include Ca ₁₀ (PO ₄ ) ₆ (OH)
₂ [alloy hydroxyapatite: HAP], amorphous calcium phosphate [Ca ₃ (PO ₄ ) ₂ · χH ₂ O: χ = 3 to 4.5], α
-Ca ₃ (PO ₄ ) ₂ [alpha-type tricalcium phosphate: αTC
P, β-Ca ₃ (PO ₄ ) ₂ [beta-type tricalcium phosphate:
_{βTCP], CaHPO 4 · 2H 2} O, CaHPO 4, Ca 8 H 2 (PO 4) 6 · 5H 2
O [octacalcium phosphate: OCP] and the like. The particle size of these biomaterials is adjusted to 20 to 50 μm or less to form a fine powder, and αTCP is most preferably used among them.

These calcium phosphate-based biomaterials may be used alone as a powder, or may be used as a mixed powder of 2 to several types.

On the other hand, an additive may be further added to the single or mixed powder of these calcium phosphate-based biomaterials. Examples of the additive to be added include calcium compounds, aluminum compounds, magnesium compounds, zinc compounds, silicon compounds, fluorine compounds, sodium compounds and the like. These are added as compounds such as oxides, hydroxides, phosphates and higher order compounds in an amount of 0 to 15% by weight based on the total amount of powder.

The main purpose of the addition is to improve the physical properties of the hardened setting material, and also to adjust the acidity in consideration of its use in living organisms. In any case, these additives should not significantly inhibit the curing reaction with the curing liquid, and therefore, for example, calcium oxide, calcium hydroxide, magnesium oxide, zinc oxide, calcium silicate, citric acid, etc. Examples thereof include calcium, sodium phosphate, zirconium silicate, aluminum oxide and the like.

The viscosity of the curable liquid of the present invention is 900 mm ² / s or less. Since the viscosity inherent in this hardening liquid is extremely low, when the hardening liquid of the present invention is used for the calcium phosphate-based biomaterial, the fluidity of the mixed mud of this biomaterial and the hardening liquid is extremely superior to that of the conventional mixed mud. ing.

For this reason, the admixture obtained is most suitable for the filling of narrow narrow constrictions, deep cavities, etc. in clinical therapy by positively utilizing the fluidity of the admixture.

For example, the obtained mixed mud is preferably used as a root canal filling sealer or a paste root canal filling material used for filling the root pulp pulp cavity from which pulp has been removed by treatment in the endodontic field.

In addition, as an application of the obtained mixed mud, in the dental field, for example, as a pulp pulp covering material or a lining cement that serves as a base for pulp protection when conserving and repairing enamel and dentine defects, preferable.

Since the viscosity of the hardening liquid is extremely low, even if the powder-liquid ratio of the mixed mud is increased, the value does not become too low, and the value can be made preferable for clinical operation, and the compression strength can be made high.

Comparative Examples 1 to 3 and Examples 4 to 16 Tables 1 to 3 show Comparative Examples 1 to 3 and Examples 4 to 16.

Here, the consistency is a numerical value of the flow of the powder and liquid after mixing, which is expressed by the spread of the mud after pressurizing under constant load, and is a measure showing the fluidity with the mixed mud and the ease of handling.

The viscosities of Examples 4 to 16 and Comparative Examples 1 to 3 shown in Table 1 were measured at a liquid temperature of 25 ± 0.5 ° C using a glass tube flow type capillary viscometer.

The consistency, setting time, and compressive strength of the mixed mud in Examples 4 to 16 and Comparative Examples 1 to 3 were measured by applying JIST-6602.

The curing liquids of Comparative Examples 1 to 3 are examples of an aqueous solution containing an easily aqueous carboxylic acid or its derivative as a main component, and these easily water-soluble carboxylic acids or their derivatives are, for example, formic acid, acetic acid, acrylic acid, and methacrylic acid. Fatty acids such as acids, carbocyclic carboxylic acids such as mellitic acid, dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid and maleic acid, tricarboxylic acids such as aconitic acid and tricarballylic acid, glycolic acid, lactic acid, Examples thereof include malic acid, glyceric acid, tartaric acid, alcoholic acids such as citric acid, and the like. Generally, non-toxic polybasic low fatty acids, especially α
Hydroxycarboxylic acid is desirable, citric acid, which is certified as a food additive as an acidulant and highly safe for living organisms, from the viewpoint of difficulty in solubility in water, operability of mixed mud, and various physical properties of a condensation hardening product, DL-malic acid and the like are preferred.

These easily water-soluble carboxylic acids or their derivatives may be used as an aqueous solution as a powder as a powder,
You may use it as several types of mixed aqueous solution.

By adding a predetermined amount of the easily water-soluble carboxylic acid or its derivative and an additive component or an additive component to this main component, if necessary, and thoroughly mixing with purified water, and heating as necessary to dissolve A hardening liquid can be obtained.

These easily water-soluble carboxylic acids or their derivatives are preferably contained in an amount of 5 to 65% by weight, but the solubilities differ depending on the respective acids, and the content changes depending on the blending ratio of additional components or the operability and various properties are optimal. Since the concentration exists, the content is more preferably 10 to 50% by weight.

Aqueous solution Carboxylic acid or derivative content 5% by weight
If it is less, the curing time will be delayed and the strength will not be sufficient.

In addition, the content of easily water-soluble carboxylic acid or derivative is 65
If it is more than wt%, the curing time will be too fast and the viscosity will increase, making it difficult to operate. Then the acidity increases (pH is too low and irritation occurs).

The curing liquids of Examples 4 to 16 consisted of aqueous solutions containing an unsaturated carboxylic acid copolymer of a water-soluble carboxylic acid or its derivative as a main component.

The unsaturated carboxylic acid copolymer acts effectively as a liquid viscosity modifier, but it can also improve various physical properties, and enhances and improves the compressive strength.

A main component is a predetermined amount of a water-soluble carboxylic acid or its derivative and an unsaturated carboxylic acid copolymer selected, and if necessary, an additional component or an additional component is added to the main component and well mixed with purified water, A hardening liquid can be obtained by heating and melt | dissolving as needed.

The total content of the readily water-soluble carboxylic acid or derivative and the unsaturated carboxylic acid copolymer is preferably 5 to 65% by weight.

If the total content is less than 5% by weight, the curing time will be delayed and the strength will be insufficient.

On the other hand, if the total content is more than 65% by weight, the curing time will be too fast and the viscosity will increase, making operation difficult. And the acidity increases (pH is too low and irritation occurs).

Further, if a large amount of this unsaturated carboxylic acid copolymer is added, it becomes the same as the conventional polyacrylic acid-based curing liquid, the liquid viscosity increases, and handling of the mixed mud becomes difficult. Therefore, the content may be 25% by weight or less based on the total amount of the curing liquid, and most preferably about 5 to 15% by weight.

If this additional compounding amount is more than 25% by weight, the liquid viscosity increases, the consistency of the mixed mud increases, and the fluidity deteriorates.

Examples of the unsaturated carboxylic acid copolymer include a copolymer of itaconic acid and acrylic acid, a copolymer of fumaric acid and acrylic acid, and a copolymer of maleic acid and allyl acid.

The acrylic acid itaconic acid copolymers of Examples 1 to 16 and Comparative Examples 1 to 3 have an average molecular weight of 24,000 to 28,800.

By the way, Comparative Example 3 and Examples 5 to 16 contain other minor addition components. The additional component is a chelating agent, PH for the purpose of further improving the operability of the mixed mud and the setting and hardening body, improving various physical properties, irritating to the living body, and mitigating harmful effects.
Regulators, amino acids, inorganic acids, etc. are added at any time.

For example, nitrilotriacetic acid [NT
A], NTA-2Na, NTA-3Na, ethylenediaminetetraacetic acid [E
DTA-4H], EDTA-4Na, Ca (OH) ₂ , Mg (OH) ₂ , Al
(OH) ₃ , NaOH, glycine, aspartic acid, glutamic acid, orthophosphoric acid, hydrochloric acid, nitric acid, Na ₂ HPO _{4 and the} like. These are added in an amount of about 0 to 10% by weight based on the total weight of the curing liquid.

In Comparative Examples 1 to 3 and Examples 4 to 6, 9 to 11 and 13 to 15, αTCP, which is a calcium phosphate-based biomaterial, is used as a dusting agent to form an admixture. In Examples 7, 8, 12, and 16, a mixture of αTCP and 5% by weight of calcium silicate is used as a dusting agent to prepare a mixed mud. The obtained mixed mud is neither irritating nor toxic to living organisms. Also, the state of the mixed mud is not dry. The curable liquids of Examples 4 to 16 of Comparative Examples 1 to 3 have a lower viscosity than that of the conventional polyacrylic acid-based curable liquids, and therefore have excellent fluidity of the mixed mud. be able to.

In addition, while ensuring the consistency of the mixed mud to a desirable value, αTC
It is possible to increase the powder-liquid ratio of P or the αTCP to which the additional component is added and the hardening liquid of each example, and the setting hardening product can obtain stronger compressive strength in a short time.

Table-2 shows the conventional comparative examples 17 and 18. Dust is αTC
P was used. In each of the comparative examples, the viscosity of the hardening liquid is at least 1000 mm ² / s or more, and the powder-liquid ratio of the mixed mud is lower than that of the examples of the present invention, and the consistency is low.

EFFECTS OF THE INVENTION According to the present invention, the liquid viscosity peculiar to the hardening liquid (viscosity of the hardening liquid) is lowered as compared with the conventional one, so that the powder-liquid ratio of the mixed mud composed of the calcium phosphate biomaterial and the hardening liquid of the present invention can be reduced. Even if the value is increased to a value preferable for clinical operation, the fluidity of the admixture that is preferable for clinical operation can be secured.

Therefore, in the clinical field (especially in the endodontic therapy field and the preservation / restoration field) where the conventional operability is important, the clinical operation of the calcium phosphate-based biomaterial becomes easy.

Further, using an acrylic acid itaconic acid copolymer having an average molecular weight of 24,000 to 28,800 and using it in combination with citric acid or DL-malic acid, the bending strength becomes good,
Excellent in fragility.

Claims (1)

[Claims] 1. A curing liquid for use in a calcium phosphate-based biomaterial, wherein the curing liquid contains one of citric acid and DL-malic acid and an acrylic acid itaconic acid copolymer having an average molecular weight of 24,000 to 28,800. Viscosity (kinematic viscosity) 900 mm ²
/ s or less and a consistency of 30 or more when mixed with a powder, and a hardening liquid for biomaterials.