JP2001259014A - Curable composition for medical treatment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To realize a curable composition for medical treatment which is safe to organism and is capable of forming the cured matter of high strength. SOLUTION: The curable composition for medical treatment includes at least one biscresoxy ethanol fluorene epoxy compound expressed by general formula (1) and a multifunctional acrylic monomer polymerizable with this biscresoxy ethanol fluorene epoxy compound. In the general formula (1), R denotes hydrogen atom or methyl group.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a curable composition, particularly to a curable composition for medical use.

[0002]

2. Description of the Related Art Multifunctional aliphatic acrylates are used as medical materials for repairing and repairing living hard tissues such as bones and teeth that have been lost or eroded and for manufacturing intraocular lenses for treating cataracts. Compounds containing a compound, a methacrylate compound, a bisphenol-based aromatic compound, and an inorganic aggregate as main materials are known. When such a medical material is used to repair, for example, a defective bone, the medical material to which a chemical catalyst (hardener) has been added is usually attached to or inserted into a bone repair site and cured. ing.

However, a cured product formed of such a medical material does not always have sufficient bending strength and marginal strength, and cannot be said to be high strength and high reliability particularly required for medical applications. . Also, this medical material
Since it contains a bisphenol-based aromatic compound which is recognized as a so-called environmental hormone as a main component, it may harm the living body in the future.

An object of the present invention is to provide a curable medical composition which is safe for living bodies and can form a cured product of high strength.

[0005]

Means for Solving the Problems The curable composition for medical use according to the present invention contains at least one biscrezoxyethanolfluorene epoxy compound represented by the following general formula (1). In the general formula (1), R represents a hydrogen atom or a methyl group.

[0006]

Embedded image

In another aspect of the present invention, there is provided a curable medical composition comprising at least one biscrezoxyethanol fluorene epoxy compound represented by the general formula (1) and the biscrezoxyethanol. It contains a fluorene epoxy compound and a polymerizable polyfunctional acrylic monomer.

The polyfunctional acrylic monomer used herein is, for example, at least one difunctional aliphatic acryl selected from the group consisting of a difunctional aliphatic acrylate compound and a difunctional aliphatic methacrylate compound. It is a mixture of a system monomer and at least one trifunctional aliphatic acrylic monomer selected from the group consisting of a trifunctional aliphatic acrylate compound and a trifunctional aliphatic methacrylate compound.

When such a polyfunctional acrylic monomer is used, the mixing ratio of the biscrezoxyethanol fluorene epoxy compound (a) and the difunctional aliphatic acrylic monomer (b) is usually set to satisfy the following conditions. The ratio of the trifunctional aliphatic acrylic monomer is 1 to 50 with respect to 100 parts by weight of the total amount of the biscrezoxyethanol fluorene epoxy compound and the difunctional aliphatic acrylic monomer. It is set to be parts by weight.

[0010]

(Equation 2)

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Biscrezoxyethanol fluo
Bisque Resolution butoxyethanol fluorene epoxy compound used in Ren epoxy compound present invention is a bisque-resolution butoxyethanol fluorene epoxy acrylate or bisque-resolution butoxyethanol fluorene epoxy methacrylate represented by the following general formula (1).

[0012]

Embedded image

In the general formula (1), R represents H (hydrogen atom) or CH ₃ (methyl group). Such a biscrezoxyethanol fluorene epoxy compound is usually used for the OH group of biscresol fluorene (for example, trade name “BCF” of Osaka Gas Co., Ltd.) which is a known substance available on the market. It can be produced by introducing an ethanol group by a method and reacting the ethanol group portion with glycidyl acrylate or glycidyl methacrylate according to a conventional method.

In the present invention, one of the biscrezoxyethanol fluorene epoxy compounds represented by the above general formula (1) may be used alone, or two of them may be used in combination. You may. That is, R in the general formula (1) is a hydrogen atom (that is, biscresoxyethanol full orange epoxy acrylate);
Alternatively, those in which R is a methyl group (ie, biscresoxyethanol full orange epoxy methacrylate) may be used alone, or those in which R is a hydrogen atom and those in which R is a methyl group are used as a mixture. You may be.

In the present invention, it is most preferable to use biscrezoxyethanol full orange epoxy methacrylate in which R in the general formula (1) is a methyl group alone.

Polyfunctional Acrylic Monomer The polyfunctional acrylic monomer used in the present invention is a component for forming a cured product by polymerizing with the above-mentioned biscrezoxyethanol fluorene epoxy compound. There is no particular limitation as long as it is capable of undergoing a polymerization reaction with the resoxyethanol fluorene epoxy compound, and various compounds can be used.

Examples of the polyfunctional acrylic monomer capable of undergoing a polymerization reaction with the biscrezoxyethanol fluorene epoxy compound include difunctional aliphatic acrylate compounds, difunctional aliphatic methacrylate compounds, and trifunctional aliphatic acrylates. And trifunctional aliphatic methacrylate compounds.

Here, the bifunctional aliphatic acrylate compounds include ethylene glycol diacrylate, diethylene glycol diacrylate, triethylene glycol diacrylate, butylene glycol diacrylate, neopentyl glycol diacrylate, propylene glycol diacrylate, and 1,3. -Butanediol diacrylate, 1,4-butanediol diacrylate and 1,6-hexanediol diacrylate can be exemplified.

The bifunctional aliphatic methacrylate compounds include ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, butylene glycol dimethacrylate, neopentyl glycol dimethacrylate, and propylene glycol dimethacrylate. Methacrylate, 1,3-butanediol dimethacrylate,
1,4-butanediol dimethacrylate, 1,6-
Hexanediol dimethacrylate can be exemplified.

On the other hand, examples of the trifunctional aliphatic acrylate compound include trimethylolpropane triacrylate, trimethylolethane triacrylate, trimethylolethanol triacrylate and trimethylolmethane triacrylate.
Examples of the trifunctional aliphatic methacrylate compound include trimethylolpropane trimethacrylate, trimethylolethanetrimethacrylate, trimethylolethanol trimethacrylate, and trimethylolmethane trimethacrylate.

The above-mentioned various polyfunctional acrylic monomers may be used alone or in combination of two or more. However, since the trifunctional aliphatic acrylate compound and the trifunctional aliphatic methacrylate compound can mainly function as a hardness regulator of a cured product comprising the medical curable composition of the present invention, Depending on the purpose of use of the curable composition, it is usually preferable to use the difunctional aliphatic acrylate compound and the difunctional aliphatic methacrylate compound in an auxiliary manner. By the way, when a trifunctional aliphatic acrylate compound or a trifunctional aliphatic methacrylate compound is mainly used as the polyfunctional acrylic monomer, a high-strength cured product is obtained, but the cured product becomes brittle due to the high strength, Depending on the purpose of medical use, it may be rather difficult to use.

As described above, preferred as the polyfunctional acrylic monomer used in the present invention is at least one selected from the group consisting of the above-mentioned difunctional aliphatic acrylate compounds and difunctional aliphatic methacrylate compounds. At least one trifunctional aliphatic acryl selected from the group consisting of one bifunctional aliphatic acrylic monomer and the trifunctional aliphatic acrylate compound and the trifunctional aliphatic methacrylate compound as described above; And a polyfunctional acrylic monomer mixture containing the same. When such a polyfunctional acrylic monomer mixture is used, the composition of the present invention can easily form a cured product having a strength suitable for various medical purposes.

Other Components The curable composition for medical use of the present invention may contain components such as other polymerizable monomers, curing catalysts, fillers and stabilizers, if necessary, in addition to the components described above.

Here, other polymerizable monomers are usually added for the purpose of adjusting the viscosity, curing rate, polymerization yield, etc. of the composition of the present invention, and adjusting the hardness of the cured product of the composition of the present invention. Things. Other polymerizable monomers that can be used include, for example, monomers such as methyl acrylate, methyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, tetrahydrofurfuryl acrylate, tetrahydrofurfuryl methacrylate, glycidyl acrylate and glycidyl methacrylate. Mention may be made of those oligomers, as well as difunctional aromatic acrylic monomers.

Here, as the bifunctional aromatic acrylic monomer, a bifunctional aromatic acrylate compound or a bifunctional aromatic methacrylate compound is used.
Examples of the bifunctional aromatic acrylate compound include 2,2-
Bis (acryloxyphenyl) propane, 2,2-bis
[4- (3-acryloxy) -2-hydroxypropoxyphenyl] propane, 2,2-bis (4-acryloxyethoxyphenyl) propane, 2,2-bis (4-acryloxydiethoxyphenyl) propane, 2, 2-bis (4-acryloxytriethoxyphenyl) propane, 2,2-bis (4-acryloxytetraethoxyphenyl) propane, 2,2-bis (4-acryloxypentaethoxyphenyl) propane, 2,2- Screw (4-
Acryloxypropoxyphenyl) propane, 2 (4-
Acryloxydiethoxyphenyl) -2 (4-acryloxydiethoxyphenyl) propane, 2 (4-acryloxydiethoxyphenyl) -2 (4-acryloxytriethoxyphenyl) propane, 2,2-bis (4- Acryloxypropoxyphenyl) propane, 2,2-bis (4-acryloxyisopropoxyphenyl) propane, 2 (4-acryloxydipropoxyphenyl) -2
(4-acryloxytriethoxyphenyl) propane can be exemplified.

Examples of the bifunctional aromatic methacrylate compound include 2,2-bis (methacryloxyphenyl) propane and 2,2-bis [4- (3-methacryloxy) -2-hydroxypropoxyphenyl] propane. 2,2-bis (4-methacryloxyethoxyphenyl) propane, 2,2-bis (4-methacryloxydiethoxyphenyl) propane, 2,2-bis (4-methacryloxytriethoxyphenyl) propane , 2,
2-bis (4-methacryloxytetraethoxyphenyl) propane, 2,2-bis (4-methacryloxypentaethoxyphenyl) propane, 2,2-bis (4-
(Methacryloxypropoxyphenyl) propane, 2
(4-methacryloxyethoxyphenyl) -2 (4-
(Methacryloxydiethoxyphenyl) propane, 2
(4-methacryloxydiethoxyphenyl) -2 (4
-Methacryloxytriethoxyphenyl) propane,
Examples thereof include 2,2-bis (4-methacryloxypropoxyphenyl) propane and 2,2-bis (4-methacryloxyisopropoxyphenyl) propane.

The above-mentioned bifunctional aromatic acrylic monomers may be used alone or in combination of two or more.

On the other hand, a curing catalyst is added to accelerate the curing of the curable composition for medical use of the present invention at room temperature for a limited time during various treatments such as surgery, and is usually added. And a redox polymerization catalyst or a photosensitive catalyst.

Here, as the redox polymerization catalyst, a combination of an amine compound such as N, N-dimethyl-p-toluidine and a peroxide such as benzoyl peroxide is usually used. Incidentally, when such a redox polymerization catalyst is used, the composition of the present invention is divided into two, and an amine compound is added to one of the two and a peroxide is added to the other.

On the other hand, as the photosensitive catalyst, for example, α-
One containing at least one photosensitizer selected from diketones, quinones and derivatives thereof, and at least one accelerator selected from aldehydes and derivatives thereof is used. Specifically, for example, at least one vicinal-diketone (photosensitizer) selected from camphorquinone, benzyl, and diacetyl;
Those containing (N, N-dimethylamino) benzoic acid or its lower alkyl ester (promoter) are used.
When such a photosensitive catalyst is used as a curing catalyst, the composition of the present invention can be cured only by irradiation with visible light or ultraviolet light.

The filler is appropriately added as a filler or a modifier.
Powders of inorganic substances such as glass beads, aluminum oxide, α-quartz powder, hydroxyapatite, and calcium phosphate compound are used. Two or more of these fillers may be used in combination. The particle size of the filler of such an inorganic substance can be appropriately selected according to the purpose of use of the present invention (the purpose of treatment using the composition of the present invention) and the like.
Although not particularly limited, for example, when used for dental purposes, it is generally preferably 100 μm or less, more preferably 50 μm or less. When the particle size exceeds 100 μm, the surface of the dental filler obtained by curing the composition of the present invention becomes rough, and discomfort such as roughness when the tongue is touched may be increased. In addition, plaque is likely to adhere, and an excessive point load may be generated on the teeth of the mating partner. In addition, a filler having a particle size of several μm or less can be used because it can enhance the surface smoothness of the cured product and increase the strength of the cured product.
Further, in order to improve the strength of the cured product, a filler having various particle sizes may be used in combination.

The above-mentioned filler is used in advance by using a silane coupling agent in order to increase the affinity or binding with the resin component and thereby further increase the strength of the cured product comprising the composition of the present invention. It is preferable to process it.
In this case, examples of the silane coupling agent include vinyltrichlorosilane, vinyltriethoxysilane, vinyltrimethoxysilane, vinyltris (β-methoxyethoxy) silane, ν-methacryloxypropyltrimethoxysilane, and N-β (amino Ethyl) v-aminopropyltrimethoxysilane and the like can be used.

Further, the stabilizer is for preventing the composition of the present invention from being cured before use, and usually a hydroquinone-based polymerization inhibitor is used. Examples of the hydroquinone-based polymerization inhibitor include hydroquinone monomethyl ether.

In the composition of the present invention, in addition to the above-mentioned components, for example, a dye for reproducing the same color tone as hard tissues such as human bones and teeth may be appropriately mixed.

Blending Ratio The blending ratio of each component constituting the curable composition for medical use of the present invention can be appropriately set according to the viscosity of the composition, the strength (hardness) of the composition after curing, and the like. There is no particular limitation. However, when a mixture of the above-mentioned difunctional aliphatic acrylic monomer and the above-mentioned trifunctional aliphatic acrylic monomer is used as the polyfunctional acrylic monomer, the biscrezoxyethanol fluorene epoxy compound (a) is usually used. And the proportion of the difunctional aliphatic acrylic monomer (b) is set so as to satisfy the following condition, and the total of the biscrezoxyethanol fluorene epoxy compound and the difunctional aliphatic acrylic monomer is The proportion of the trifunctional aliphatic acrylic monomer is 1 to 50 parts by weight (preferably 5 to 4 parts by weight) per 100 parts by weight.
(0 parts by weight).

[0036]

(Equation 3)

In this case, a more preferable mixing ratio of the biscrezoxyethanol fluorene epoxy compound (a) is from 18 to 70 parts by weight (more preferably, from 22 to 68 parts by weight). The more preferable mixing ratio of the bifunctional aliphatic acrylic monomer (b) is 7 parts by weight or more and 36 parts by weight or less (more preferably 10 parts by weight or more and 30 parts by weight or less).

In the case where the compounding ratio of the biscrezoxyethanol fluorene epoxy compound is less than 10 parts by weight in such a compounding ratio of the composition of the present invention, the strength of the cured product comprising the composition of the present invention and the hardness of the living body There is a possibility that adhesion to tissue and biocompatibility may become insufficient.
Conversely, if it exceeds 80 parts by weight, the cured product comprising the composition of the present invention may become brittle. When the blending ratio of the bifunctional aliphatic acrylic monomer is less than 5 parts by weight, the kneadability of the composition of the present invention may be reduced. Conversely, if it exceeds 50 parts by weight, the strength of the cured product comprising the composition of the present invention may be insufficient. Further, when the blending ratio of the trifunctional aliphatic acrylic monomer is less than 1 part by weight, the effect of using the monomer may not be sufficiently exerted. For example, the strength of a cured product comprising the composition of the present invention may be insufficient. On the other hand, when the amount exceeds 50 parts by weight, the strength of the cured product comprising the composition of the present invention is too high, and it may be difficult to use the cured product for medical use.

When the above-mentioned difunctional aromatic acrylic monomer is used as the other polymerizable monomer component, the compounding amount thereof is usually a biscrezoxyethanol fluorene epoxy compound, a difunctional aliphatic acrylic monomer. And in the total amount of 100 parts by weight of the bifunctional aromatic acrylic monomer, the proportion of the bifunctional aromatic acrylic monomer is 60 parts by weight or less, preferably 45 parts by weight or less.
It is set so as to be not more than 40 parts by weight, more preferably not more than 40 parts by weight. If the proportion of the bifunctional aromatic acrylic monomer exceeds 60 parts by weight, the physical properties of the cured product comprising the composition of the present invention, particularly the strength such as bending strength, may be reduced.

The curable composition for medical use of the present invention can be prepared by mixing the above-mentioned various components and kneading them to form a paste.

Here, when a redox polymerization catalyst is used as the above-mentioned curing catalyst, the other components except the curing catalyst are uniformly mixed, and the resulting mixture is divided into two parts. Then, an amine compound is added to one of the mixtures, a peroxide is added to the other mixture, and each mixture is kneaded to prepare two pastes.

On the other hand, when a photosensitive catalyst is used as a curing catalyst, all components including the curing catalyst are mixed and kneaded to prepare a paste.

Method of using the curable composition for medical use The curable composition for medical use of the present invention can be used in various medical fields, for example, for repairing bones damaged by fractures and the like and for treating eroded teeth such as caries. It is used in the field of treatment of living hard tissue. More specifically, for example, it is used as an artificial bone, a bone substitute, a bone cement, a dental filler, an artificial root, a dental adhesive, and the like. The compositions of the present invention can also be used to produce transparent intraocular lenses for use, for example, in treating cataracts. In the case of manufacturing an intraocular lens requiring transparency, the composition of the present invention preferably does not contain a component such as the above-mentioned filler that inhibits transparency.

When the composition of the present invention contains the above-mentioned redox polymerization catalyst, a paste containing an amine compound and a paste containing a peroxide are mixed at the time of use, and the mixture is placed, for example, at a repair site of a hard tissue. . As a result, the amine compound and the peroxide are integrated and the redox polymerization proceeds, and the composition of the present invention cures within a few minutes (for example, within 5 minutes) at normal temperature and normal pressure.

On the other hand, when the composition of the present invention contains the above-mentioned photosensitive catalyst, the composition is irradiated with visible light or ultraviolet light from various light sources (for example, a xenon lamp) when used. Thereby, the composition of the present invention is photopolymerized at normal temperature and normal pressure, and is usually cured in several tens of seconds (for example, about 10 to 60 seconds).

The cured product comprising the composition of the present invention thus cured has the necessary strength as a material for repairing and treating the hard tissue of a living body, that is, has good bending strength and compressive strength, and has a low water absorption. It is small, has good adhesion to hard tissue, and has excellent biocompatibility. Further, the above-mentioned biscrezoxyethanol fluorene epoxy compound contained in the composition of the present invention is not a substance that is harmful to a living body such as a so-called environmental hormone, and therefore the composition of the present invention is It is less harmful and safer.

[0047]

EXAMPLES Example 1 Two types of pastes (paste A) comprising the components shown in Table 1
-1 and paste B-1) were prepared. At this time, biscresoxyethanol full orange epoxy methacrylate (wherein R is a methyl group in the above general formula (1)) and a monomer component are mixed and then dissolved. , And α-quartz powder (filler) was further added. Then, the composition thus obtained was vacuum-degassed and then kneaded to prepare a target paste. Note that the α-
The quartz powder has been previously silane-treated with ν-methacryloxypropyltrimethoxysilane by an ordinary method. When equal amounts of the pastes A-1 and B-1 were collected and kneaded, the paste was cured in about 3 minutes.

[0048]

[Table 1]

Comparative Example 1 Two kinds of pastes (paste A-2 and paste B-2) shown in Table 2 and containing no biscrezoxyethanol full orange epoxy methacrylate were prepared. At this time, the monomer components were mixed and then dissolved, and a curing catalyst and a stabilizer were added to the dissolved material, and then α-quartz powder (filler) was further added. Then, the composition thus obtained was vacuum-degassed and then kneaded to prepare a target paste. The α-quartz powder used here was previously silane-treated with ν-methacryloxypropyltrimethoxysilane by a conventional method. When equal amounts of the pastes A-2 and B-2 were collected and kneaded, the paste was cured in about 3 minutes.

[0050]

[Table 2]

Example 2 Two types of pastes (Paste A) comprising the components shown in Table 3
-3 and paste B-3) were prepared in the same manner as in Example 1. This paste A-3 and paste B-3 were sampled in equal amounts and kneaded, and hardened in about 3 minutes.

[0052]

[Table 3]

Comparative Example 2 Two kinds of pastes (paste A-4 and paste B-4) shown in Table 4 and containing no biscrezoxyethanol full orange epoxy methacrylate were prepared in the same manner as in Comparative Example 1. Prepared. This paste A
-4 and paste B-4 were collected in equal amounts and kneaded, and were cured in about 3 minutes.

[0054]

[Table 4]

Evaluation A predetermined cured product was prepared using the pastes prepared in the examples and comparative examples, and the cured product was measured for flexural strength, compressive strength and water absorption according to the following methods. Table 5 shows the results.

[0056] Flexural width 2mm accordance strength ISO 4049, and a test piece of the cured product of the length 25 mm, was immersed for 24 hours in distilled water at the specimen 37 ° C.. Thereafter, the bending strength of the test piece was measured using a universal testing machine at a crosshead speed of 1 mm / min.

A test specimen of a cylindrical cured product having a compressive strength diameter of 6 mm and a thickness of 3 mm was prepared and immersed in distilled water at 37 ° C. for 24 hours. Then, using a universal testing machine, set the crosshead speed to 1m
The compressive strength of the test piece was measured at a setting of m / min.

A test piece of a disk-shaped cured product having a water absorption of 20 mm in diameter and 2 mm in thickness was prepared. The moisture contained in the test piece was removed in a desiccator containing a desiccant, and the test piece was made constant weight. Then, the test piece which had been made constant was immersed in distilled water at 37 ° C. for one week, and the water absorption was measured.

[0059]

[Table 5]

[0060]

According to the present invention, the curable composition for medical use of the present invention does not act as a so-called environmental hormone.
Since it contains the biscrezoxyethanol fluorene epoxy compound represented by the formula (1), it is possible to form a cured product for medical use having high strength and high safety for living bodies.

Continuation of the front page (51) Int.Cl. ⁷ Identification code FI Theme coat II (reference) A61L 24/00 C08F 20/30 C08F 20/30 A61L 25/00 A (72) Inventor Yasuhiro Suda Chuo-ku, Osaka-shi, Osaka 4-1-2 Hiranocho Osaka Gas Co., Ltd. F-term (reference) 4C081 AB04 AB22 AC04 CA081 CC01 4C089 AA06 BD02 BD04 BE03 CA03 4J100 AL62Q AL63Q AL66P AL66Q BA02P BA02Q BA03P BC43P BC48P CA04 JA51 JA52

Claims (4)

[Claims] 1. A curable medical composition comprising at least one biscrezoxyethanol fluorene epoxy compound represented by the following general formula (1). Embedded image (In the formula, R represents a hydrogen atom or a methyl group.) 2. At least one bis-cresoxyethanol fluorene epoxy compound represented by the following general formula (1): a polyfunctional acrylic monomer polymerizable with the bis-cresoxyethanol fluorene epoxy compound; A curable composition for medical use comprising: Embedded image (In the formula, R represents a hydrogen atom or a methyl group.) 3. The polyfunctional acrylic monomer comprises at least one difunctional aliphatic acrylic monomer selected from the group consisting of a difunctional aliphatic acrylate compound and a difunctional aliphatic methacrylate compound. The medical composition according to claim 2, wherein the mixture is a mixture with at least one trifunctional aliphatic acrylic monomer selected from the group consisting of a trifunctional aliphatic acrylate compound and a trifunctional aliphatic methacrylate compound. Curable composition. 4. The compounding ratio of the biscrezoxyethanol fluorene epoxy compound (a) and the bifunctional aliphatic acrylic monomer (b) is set so as to satisfy the following conditions, and the bisque The ratio of the trifunctional aliphatic acrylic monomer is set to be 1 to 50 parts by weight with respect to 100 parts by weight of the total amount of the resoxyethanol fluorene epoxy compound and the difunctional aliphatic acrylic monomer. The curable medical composition according to claim 3, wherein (Equation 1)