Adhesive composition for hard tissue repair

Abstract

The adhesive composition for hard tissue repair contains a polymerizable monomer (A), a polymer powder (B) and a polymerization initiator (C), the polymerization initiator (C) being represented by the following formula: [CH3(CH2)m-]2B-O(CH2)nCH3 (wherein m and n are each independently an integer of 1 to 4, and 2m+n≦10). The polymerization initiator does not burn or ignite even when it comes into contact with paper, porous fibrous material, etc. in the air, has high fluidity, can be accurately sampled in small amounts, can reduce adverse effects on the human body, and further provides high polymerizability to the polymerizable composition, hardens the polymerizable composition within a short period of time, and provides an adhesive composition suitable for hard tissue repair.

Description

[Technical Field]

[0001] The present invention relates to an adhesive composition for hard tissue repair and a polymerization initiator used therefor. More specifically, the present invention relates to an adhesive composition for hard tissue repair that has high curing performance and adhesive performance, and a polymerization initiator used therefor that has improved safety against ignition when attached to paper or the like. [Background technology]

[0002] Adhesive compositions using tributylboron as a polymerization initiator are known to have good adhesive properties for biological hard tissues (see Patent Document 1). However, trialkylboron is an extremely unstable substance in air, and when exposed to air, it reacts rapidly with oxygen and ignites, making it unsuitable for normal clinical use. For this reason, various technologies have been proposed to improve the safety of trialkylboron against ignition.

[0003] Patent Document 2 discloses a method for improving safety against fire by adding a hydrophobic, viscous substance such as petrolatum, paraffin, or silicone (silicone oil) to trialkylborane or its derivatives, and, if necessary, an adsorbent such as silicic acid or alumina, to form a paste.

[0004] Patent Document 3 discloses a dental or surgical adhesive that uses a polymerization initiator (partially oxidized trialkylboron) produced by reacting 0.3 to 0.9 moles of oxygen with trialkylboron. The invention in Patent Document 3 proposes a polymerization initiator that minimizes the activity of trialkylboron to improve safety against ignition. However, because this polymerization initiator involves a liquid / gas phase reaction between tributylboron and oxygen, it is difficult to obtain a stable product, which affects the stable curing rate of the adhesive composition. Furthermore, ignition potential could not be completely suppressed.

[0005] Patent Document 4 proposes a polymerization initiator prepared by adding organic oligomers or organic polymers such as silicone oil, wax, oligoesters, and oligoamides to an organoboron compound to form a uniform mixture. However, the large amount of additives reduces the activity of the polymerization initiator and increases its viscosity, making it difficult to obtain the correct amount to be used.

[0006] Patent Documents 5 and 6 propose a method of improving safety against fire by adding a polymer of an alkyl (meth)acrylate to tributyl boron or partially oxidized tributyl boron to form a paste. However, the addition of a large amount of additive tends to reduce the activity of the polymerization initiator, and at the same time, it may be difficult to obtain the correct amount of initiator composition to be used from the paste-like composition.

[0007] Patent Document 7 proposes a mixture containing, as a main component, alkylalkoxide boron obtained by reacting trialkylboron with alkyl alcohol, or a polymerization initiator whose safety is improved by further adding a polar organic compound or an inert diluent, in response to the flammability of trialkylboron; however, these proposals are still not sufficient.

[0008] Patent Document 8 proposes a method of improving safety by adding an aprotic solvent, or further an inert liquid or solid organic oligomer or polymer, to tributylboron or partially oxidized tributylboron. However, the addition of a large amount of additive tends to reduce the activity of the polymerization initiator, and the addition of the organic oligomer or polymer increases the viscosity of the initiator composition, which may make it difficult to obtain the correct amount to be used.

[0009] Patent Document 9 proposes a method of improving safety by adding specific alkanes and alcohols to tributylboron or partially oxidized tributylboron to suppress ignition. However, the effects of alkanes contained in the polymerization initiator, which cannot be absorbed or decomposed by the human body, on human health are unknown, and the addition of large amounts of additives tends to reduce the activity of the polymerization initiator. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] :Toku-Kokoku No. 14318-1967 [Patent Document 2] : JP 48-11892 [Patent Document 3] : JP 49-5143 [Patent Document 4] : JP 58-084803 [Patent Document 5] : JP 3-264509 [Patent Document 6] :CN1642933A [Patent Document 7] : JP 5-253284 [Patent Document 8] : JP 9-110913 [Patent Document 9] :CN1909870A

[0011] As described above, conventional adhesive compositions for hard tissue repair have room for improvement in terms of safety in use, convenience, and biosafety.

[0012] Invention Contents The object of the present invention is to provide a polymerization initiator and an adhesive composition suitable for hard tissue repair, which do not burn or ignite even when in contact with paper, porous fibrous materials, etc. in the air, have high fluidity, can be easily dispensed in small amounts accurately, can reduce adverse effects on the human body, and further impart high polymerizability to a polymerizable composition, allowing the polymerizable composition to harden within a short period of time.

[0013] As a result of extensive research to achieve the above object, the inventors have found that the use of a specific high-purity organoboron compound can suppress ignition and maintain high fluidity and high polymerization activity, leading to the completion of the present invention.

[0014] That is, the adhesive composition for hard tissue repair of the present invention contains a polymerizable monomer (A), a polymer powder (B) and a polymerization initiator (C), and the polymerization initiator (C) is represented by the following formula (1): [CH3(CH2)m-]2B-O(CH2)nCH3 (1) (wherein m and n each independently represent an integer of 1 to 4, and 2m+n≦10)

[0015] The polymerizable monomer (A) may be a (meth)acrylate or a combination of a (meth)acrylate and a polymerizable monomer having an acidic group; the polymer powder (B) is at least one polymer selected from the group consisting of a homopolymer of an alkyl (meth)acrylate, a copolymer of an alkyl (meth)acrylate, a copolymer of an alkyl (meth)acrylate and another polymerizable monomer, a copolymer of an alkyl (meth)acrylate and an alkylene di(meth)acrylate, and a copolymer of an alkyl (meth)acrylate and a butadiene-based polymerizable monomer.

[0016] The polymerization initiator (C) is an alkoxydialkylboron having a purity of 97% or more (including 97%); the polymerization initiator (C) is an alkoxydialkylboron having a purity of 98% or more (including 98%); the polymerization initiator (C) is butoxydibutylboron.

[0017] The adhesive composition for hard tissue repair contains 20 to 70 parts by weight of a polymerizable monomer (A), 20 to 70 parts by weight of a polymer powder (B), and 1 to 20 parts by weight of a polymerization initiator (C) (total of 100 parts by weight of (A), (B), and (C)).

[0018] The adhesive composition for hard tissue repair further contains a filler (D) in an amount of usually 20 to 150 parts by weight per 100 parts by weight of the total amount of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C). The filler (D) is an inorganic filler, an organic filler, or an organic-inorganic composite filler that is insoluble or does not swell in the polymerizable monomer (A).

[0019] According to the present invention, a polymerization initiator is obtained which does not burn or ignite even when it comes into contact with paper, porous fibrous materials, etc. in the air, has excellent fluidity and is easy to collect in small amounts, reduces adverse effects on the human body, and imparts high polymerizability to a polymerizable composition, and by using this, an adhesive composition suitable for hard tissue repair can be obtained.

[0020] It is generally believed that the reactivity of alkylborons with oxygen, i.e., the flammability of alkylborons when they come into contact with oxygen, is proportional to their polymerization initiation ability. However, in the present invention, the high-purity alkoxydialkylborons of the present invention surprisingly exhibit polymerization activity equivalent to that of trialkylborons and their partial oxides, despite being less flammable than trialkylborons and their partial oxides. While the reason for this is not entirely clear, one possible reason is that the alkoxydialkylborons of the present invention have a relatively mild reaction with oxygen compared to trialkylborons and their partial oxides. Therefore, the portion of the initial radical species generated by the reaction with oxygen that does not react with each other and contribute to polymerization initiation is relatively small, making them more effective for initiating polymerization.

[0021] As shown in Example 1, Comparative Example 1, and Comparative Example 2 in Table 1, a mixture of tributylboron partial oxide and butoxydibutylboron causes scorching and even ignition of filter paper when it comes into contact with the filter paper, whereas the high-purity butoxydibutylboron of the present invention does not cause scorching or ignition of the filter paper when it comes into contact with the filter paper, yet it exhibits polymerization activity equivalent to that of the mixture of tributylboron partial oxide and butoxydibutylboron.

[0022] MODE FOR CARRYING OUT THE INVENTION Polymerizable monomer (A) The polymerizable monomer (A) of the present invention can be used without any particular limitation as long as it can be polymerized with the polymerization initiator composition (C) described below. Furthermore, either a monofunctional polymerizable monomer or a polyfunctional polymerizable monomer can be used as the polymerizable monomer (A) depending on the purpose of use.

[0023] Examples of the polymerizable monomer (A) include (meth)acrylates and other vinyl compounds. Among these polymerizable monomers (A), (meth)acrylates are preferred because they are relatively less irritating to the human body (note that (meth)acrylates collectively refer to acrylates and methacrylates). Furthermore, among the polymerizable monomers (A), it is preferred to use them in combination with a polymerizable monomer having an acidic group because they have excellent adhesion to hard tissues and metals such as titanium for hard tissue repair.

[0024] Examples of monofunctional (meth)acrylates having no acidic group include alkyl (meth)acrylates such as methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, hexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, dodecyl (meth)acrylate, lauryl (meth)acrylate, cyclohexyl (meth)acrylate, benzyl (meth)acrylate, and isobornyl (meth)acrylate; 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, and the like. Hydroxyalkyl esters of (meth)acrylic acid such as acrylate, 3-hydroxypropyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 5-hydroxypentyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 1,2-dihydroxypropyl mono(meth)acrylate, 1,3-dihydroxypropyl mono(meth)acrylate, and erythritol mono(meth)acrylate; diethylene glycol mono(meth)acrylate, triethylene glycol mono(meth)acrylate, and polyethylene glycol Examples of the (meth)acrylate include polyalkylene glycol mono(meth)acrylates such as cholesteryl mono(meth)acrylate and polypropylene glycol mono(meth)acrylate; (poly)alkylene glycol monoalkyl ether (meth)acrylates such as ethylene glycol monomethyl ether (meth)acrylate, ethylene glycol monoethyl ether (meth)acrylate, diethylene glycol monomethyl ether (meth)acrylate, triethylene glycol monomethyl ether (meth)acrylate, polyethylene glycol monomethyl ether (meth)acrylate, and polypropylene glycol monoalkyl ether (meth)acrylate; fluoroalkyl esters of (meth)acrylic acid such as perfluorooctyl (meth)acrylate and hexafluorobutyl (meth)acrylate; silane compounds having a (meth)acryloxyalkyl group such as γ-(meth)acryloxypropyltrimethoxysilane and γ-(meth)acryloxypropyltri(trimethylsiloxy)silane; and (meth)acrylates having a heterocycle such as tetrahydrofurfuryl (meth)acrylate.

[0025] Examples of polyfunctional (meth)acrylates having no acidic group include poly(meth)acrylates of alkane polyols such as ethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, neopentyl glycol di(meth)acrylate, hexylene glycol di(meth)acrylate, 2-hydroxypropyl di(meth)acrylate, trimethylolpropane tri(meth)acrylate, and pentaerythritol tetra(meth)acrylate; polyoxyalkane polyol poly(meth)acrylates such as diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, dibutylene glycol di(meth)acrylate, and dipentaerythritol hexa(meth)acrylate; Alicyclic or aromatic di(meth)acrylate represented by the following formula (2): [ka] (In the above formula (2), R represents a hydrogen atom or a methyl group, m and n represent numbers of 0 to 10 which may be the same or different, and R 1 teeth [ka] ); Aliphatic or aromatic di(meth)acrylate having a hydroxyl group in the molecule, represented by the following formula (3): [ka] (In the above formula (3), R represents a hydrogen atom or a methyl group, n represents a number from 0 to 10, and R 1 teeth [ka] and polyfunctional (meth)acrylates having a urethane bond in the molecule represented by the following formula (4): [ka] (In the above formula (4), R represents a hydrogen atom or a methyl group, and R 1 teeth [ka] ); and others.

[0026] Among these (meth)acrylates, preferred monofunctional (meth)acrylates include alkyl (meth)acrylates such as methyl (meth)acrylate and ethyl (meth)acrylate; hydroxyalkyl esters of (meth)acrylic acid such as 2-hydroxyethyl (meth)acrylate, 1,3-dihydroxypropyl mono(meth)acrylate and erythritol mono(meth)acrylate; and polyethylene glycol mono(meth)acrylates such as triethylene glycol monomethyl ether (meth)acrylate and triethylene glycol mono(meth)acrylate.

[0027] Examples of polyfunctional (meth)acrylates include di(meth)acrylates having an ethylene glycol chain in the molecule, such as triethylene glycol di(meth)acrylate and polyethylene glycol di(meth)acrylate; and compounds represented by the following formula (2)-a: [ka] (In formula (2)-a, R, m, and n are defined as in formula (2)); A compound represented by the following formula (3)-a: [ka] (In formula (3)-a, the definition of R is the same as in formula (3)); A compound represented by the following formula (4)-a [ka] (wherein R is defined as in formula (4)-a); and the like are preferred.

[0028] These (meth)acrylates can be used alone or in combination of two or more.

[0029] Examples of polymerizable monomers having an acidic group include (meth)acrylic acid and its anhydride, 1,4-di(meth)acryloxyethylpyromellitic acid, 6-(meth)acryloxyethylnaphthalene, 1,2,6-tricarboxylic acid, and N-(meth)acryloyl-p-aminobenzoic acid. Acid, N-(meth)acryloyl-o-aminobenzoic acid, N-(meth)acryloyl-m-aminobenzoic acid, N-(meth)acryloyl-5-aminosalicylic acid, N-(meth)acryloyl-4-aminosalicylic acid, 4-(meth)acryloxyethyltrimellitic acid and its anhydride, 4-(meth)acryloxybutyltrimellitic acid and its anhydride, 4-(meth)acryloxyhexyltrimellitic acid and its anhydride, 4-(meth)acryloxydecyltrimellitic acid and its anhydride, 2-(meth)acryloyloxybenzoic acid, 3-(meth)acryloyloxybenzoic acid, 4-(meth)acryloyloxybenzoic acid, β-(meth Monomers having a carboxylic acid group or an anhydride group thereof, such as acryloyloxyethyl hydrogen succinate, β-(meth)acryloyloxyethyl hydrogen maleate, β-(meth)acryloyloxyethyl hydrogen phthalate, 11-(meth)acryloyloxy-1,1-undecanedicarboxylic acid, and p-vinylbenzoic acid; monomers having a phosphoric acid group, such as (2-(meth)acryloxyethyl)phosphoric acid, (2-(meth)acryloxyethylphenyl)phosphoric acid, and 10-(meth)acryloxydecylphosphoric acid; and polymerizable monomers having a sulfonic acid group, such as p-styrenesulfonic acid and 2-acrylamido-2-methylpropanesulfonic acid.

[0030] Among these polymerizable monomers having an acidic group, 4-methacryloxyethyltrimellitic acid and its anhydride are preferred. These polymerizable monomers having an acidic group can be used alone or in combination of two or more.

[0031] In the polymerizable monomer (A), the amount of the monofunctional (meth)acrylate monomer blended is preferably 80 parts by weight or more, more preferably 90 parts by weight or more, and even more preferably 95 parts by weight or more. When a polymerizable monomer having an acidic group is blended in the polymerizable monomer (A), it is preferably contained in an amount of 1 to 20 parts by weight per 100 parts by weight of the total polymerizable monomers contained in the adhesive composition for hard tissue repair of the present invention.

[0032] The blending amount of the polymerizable monomer (A) is preferably 20 to 70 parts by weight, more preferably 30 to 65 parts by weight, and even more preferably 35 to 60 parts by weight, per 100 parts by weight of the total of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C).

[0033] If the amount of polymerizable monomer added is less than the above range, the operability and the permeability into the adhesive composition tend to be poor, whereas if the amount of polymerizable monomer added exceeds the above range, the early adhesive strength and mechanical properties tend to be poor.

[0034] Polymer powder (B) The polymer powder (B) in the present invention is not particularly limited, and any polymer powder that dissolves or swells in the polymerizable monomer (A) can be used. Examples of such polymer (B) include alkyl(meth)acrylate polymers and other ethylene-based polymers. Among these, alkyl(meth)acrylate polymers, such as homopolymers of alkyl(meth)acrylate, copolymers of alkyl(meth)acrylate, copolymers of alkyl(meth)acrylate and other polymerizable monomers, copolymers of alkyl(meth)acrylate and alkylene di(meth)acrylate, and copolymers of alkyl(meth)acrylate and butadiene-based polymerizable monomers, are preferred. These polymer powders can be used alone or in combination.

[0035] Specific examples of alkyl (meth)acrylate polymers include non-crosslinkable polymers such as polymethyl (meth)acrylate, polyethyl (meth)acrylate, methyl (meth)acrylate-ethyl (meth)acrylate copolymer, methyl (meth)acrylate-butyl (meth)acrylate copolymer, and methyl (meth)acrylate-styrene copolymer; and crosslinkable polymers such as methyl (meth)acrylate-ethylene glycol di(meth)acrylate copolymer, methyl (meth)acrylate-triethylene glycol di(meth)acrylate copolymer, and copolymers of methyl (meth)acrylate and butadiene-based monomers.

[0036] The blending amount of the polymer powder (B) is preferably 20 to 70 parts by weight, more preferably 30 to 65 parts by weight, and even more preferably 35 to 60 parts by weight, per 100 parts by weight of the total of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C).

[0037] Polymerization initiator (C) The polymerization initiator (C) of the present invention is an alkoxydialkylboron represented by the following formula (1): [CH3(CH2)m-]2B-O(CH2)nCH3 (1) (wherein m and n each independently represent an integer of 1 to 4, and 2m+n≦10).

[0038] Specific examples of the alkoxydialkylboron include ethoxydiethylboron, ethoxydipropylboron, ethoxydibutylboron, ethoxydipentylboron, propoxydiethylboron, propoxydipropylboron, propoxydibutylboron, propoxydipentylboron, butoxydiethylboron, butoxydipropylboron, and butoxydibutylboron. Among these alkoxydialkylborons, ethoxydibutylboron, propoxydibutylboron, and butoxydibutylboron are preferred. More preferred are propoxydibutylboron and butoxydibutylboron, and particularly preferred is butoxydibutylboron.

[0039] These alkoxydialkylborons can be used alone or in combination of two or more.

[0040] The purity of the alkoxydialkylborane of the present invention is preferably 97% or more, more preferably 98% or more, and particularly preferably 98.5% or more. Surprisingly, when the purity of the alkoxydialkylborane of the present invention reaches a certain level or higher, its ignition property is clearly suppressed while at the same time exhibiting the same level of polymerization activity.

[0041] Alkoxydialkylboranes are prepared by reacting the corresponding m number of trialkylboranes in formula (1) with the corresponding n number of alcohols. The preparation of alkoxydialkylboranes by the reaction of trialkylboranes with alcohols must be carried out under oxygen-shielding conditions, but is also affected by the reaction temperature. Therefore, typically, only a mixture (primary product) consisting primarily of the target alkoxydialkylborane is obtained. The high-purity alkoxydialkylboranes of the present invention can be obtained by further subjecting the primary product to a reduced-pressure distillation process.

[0042] Alkoxydialkylboranes can also be prepared by the reaction of trialkylboranes with an oxidizing agent such as oxygen. In the case of the oxidation reaction of trialkylboranes using oxygen, the reaction conditions, such as the oxygen blowing rate and the liquid stirring rate, must be strictly controlled because the reaction is a gas-liquid heterophase reaction. The reaction product obtained by the oxidation reaction of trialkylboranes with oxygen is usually a mixture primarily composed of the target alkoxydialkylborane. The high-purity alkoxydialkylboranes of the present invention can be obtained by further subjecting the mixture to a reduced-pressure distillation process.

[0043] The amount of the polymerization initiator (C) to be blended is preferably 1 to 20 parts by weight, more preferably 2 to 15 parts by weight, and even more preferably 3 to 10 parts by weight, per 100 parts by weight of the total of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C).

[0044] Provided that the polymerization initiation performance of the polymerization initiator (C) of the present invention is not affected, 0.01 to 5 parts by weight of an alcohol having a boiling point of 60°C to 120°C can be added, if necessary, to 100 parts by weight of alkoxydialkylborane, preferably 0.05 to 4 parts by weight, more preferably 0.1 to 3 parts by weight.

[0045] Filler (D) The filler (D) of the present invention is not particularly limited, and an inorganic filler, an organic filler, or an organic-inorganic composite filler that is not dissolved or swelled in the polymerizable monomer (A) can be used.

[0046] Examples of the inorganic filler (D) include metal oxide powders such as zirconium oxide, bismuth oxide, titanium oxide, zinc oxide, and aluminum oxide particles; metal salt powders such as calcium carbonate, bismuth carbonate, calcium phosphate, zirconium phosphate, and barium sulfate; hydroxide apatite, carbonate apatite, and anhydrous calcium hydrogen phosphate; glass fillers such as silica glass, aluminum-containing glass, barium-containing glass, strontium-containing glass, and zirconium silicate glass; fillers with sustained silver ion release properties, and fillers with sustained fluorine release properties. These inorganic fillers can be used alone or in combination.

[0047] In order to obtain a strong bond between the inorganic filler and the resin, it is preferable to use an inorganic filler that has been subjected to a surface treatment such as silane treatment or polymer coating.

[0048] The amount of filler (D) in the composition of the present invention is preferably 20 to 150 parts by weight, more preferably 30 to 120 parts by weight, even more preferably 35 to 100 parts by weight, and particularly preferably 40 to 80 parts by weight, per 100 parts by weight of the total of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C).

[0049] Other ingredients The adhesive composition for hard tissue repair of the present invention may contain a polymerization inhibitor, if necessary. Examples of polymerization inhibitors include hydroquinone compounds such as hydroquinone and dibutylhydroquinone, phenols such as hydroquinone monomethyl ether, 2,6-di-tert-butylphenol and 2,6-di-tert-butyl-p-cresol, catechol, pyrogallol, benzoquinone, 2-hydroxybenzoquinone, p-methoxyphenol, tert-butylcatechol, butylated hydroxyanisole, butylated hydroxytoluene, and tert-butylhydroquinone. The polymerization inhibitors may be used alone or in combination. Among these, a mixture of hydroquinone monomethyl ether and 2,6-di-tert-butyl-p-cresol is preferably used.

[0050] The polymerization inhibitor is usually added to the polymerizable monomer (A). The amount of the polymerization inhibitor added is preferably 10 to 1000 ppm, more preferably 20 to 500 ppm, and even more preferably 25 to 200 ppm, relative to the polymerizable monomer (A).

[0051] The adhesive composition for hard tissue repair of the present invention may further contain an ultraviolet absorber, if necessary. Examples of ultraviolet absorbers include benzotriazole compounds. The amount of the ultraviolet absorber added is preferably 5 to 500 ppm, more preferably 10 to 200 ppm, based on the polymerizable monomer (A).

[0052] The adhesive composition for hard tissue repair of the present invention may further contain, as needed, anti-infective agents, antibacterial agents, antiviral agents, hemostatic agents, platelet activators, bone morphogenetic factors, bone growth factors, synthetic peptides with hemostatic activity, and other pharmaceutical or therapeutic ingredients.

[0053] The adhesive composition for hard tissue repair of the present invention may further contain, if necessary, a colorant for visually clearly distinguishing the adhesive composition for repair from the surrounding hard tissue.

[0054] The adhesive composition for hard tissue repair of the present invention is prepared by mixing a polymerizable monomer (A), a polymer powder (B), a polymerization initiator (C), and other components that may be included as needed, or by mixing a polymerizable monomer (A), a polymer powder (B), a polymerization initiator (C), a filler (D), and other components that may be included as needed.

[0055] The order in which these components are mixed is not limited, but in terms of achieving better stability in the resulting adhesive composition for hard tissue repair, it is preferable to first mix the polymerizable monomer (A) and the polymerization initiator (C), and then mix the polymer powder (B), or the polymer powder (B) and the filler (D).

[0056] Examples of methods for storing the components of the composition of the present invention include a method in which the polymerizable monomer (A), polymer powder (B), polymerization initiator (C), and other components that are included as needed are divided into three or more portions and stored in three or more components, respectively.When used, the components of each portion are mixed to prepare the composition. [Example]

[0057] The present invention will be described in more detail below based on examples, however, the present invention is not limited to these examples.

[0058] The abbreviations used below represent the following compounds. MMA: methyl methacrylate 4-META: 4-methacryloxyethyl trimellitic anhydride p-(MMA / BuMA): Copolymer of methyl methacrylate and butyl methacrylate (particle size 68 μm, MMA content approximately 25% by weight)

[0059] Example 1 (1) Preparation of polymerization initiator In a nitrogen atmosphere, 182 g of tributylborane was poured into a reaction vessel, the temperature of the reaction contents was kept below 80°C, and 74 g of anhydrous n-butyl alcohol was added dropwise while stirring. The temperature was then slowly raised while stirring to reflux. After 24 hours, heating was stopped to obtain a butoxydibutylborane mixture.

[0060] The butoxydibutylboron mixture was distilled under reduced pressure in a nitrogen atmosphere, and the 92-94°C / 8mmHg fraction was collected. Gas chromatograph revealed that it was butoxydibutylboron with a purity of 97.6%, the target polymerization initiator. The obtained polymerization initiator was stored in a nitrogen box.

[0061] (2) Ignition test 0.5 ml of the polymerization initiator obtained in (1) above was dropped onto a filter paper (Whatman, No. 3) at 23°C ± 2°C, and the state of ignition and burning was observed.

[0062] (3) Collectability test The polymerization initiator was dripped from the syringe and the dripping condition was visually judged. If it dripped drop by drop and there was no stringiness or air bubbles mixed in, it was judged as good collection; if the droplets dripped in a series, there was viscous stringiness, air bubbles mixed in, or it was impossible to drip, it was judged as poor collection.

[0063] (4) Polymerization activity test (curing time measurement) 1) In a room with a room temperature of 25°C ± 2°C, 8 drops (0.18 g) of polymerizable monomer consisting of MMA / 4-META = 95 / 5 (weight ratio) and 2 drops (0.011 to 0.015 g) of polymerization initiator were placed in a dappen dish, 0.16 g of p-MMA (number average molecular weight 400,000, average particle size approximately 25 μm) was added, and the mixture was lightly mixed for 10 seconds to make resin mud.

[0064] 2) A thin layer of Vaseline was applied to a glass plate, and a Teflon ring (outer diameter 13 mm, inner diameter 10 mm, thickness 5 mm) similarly coated with a thin layer of Vaseline was placed on top, and resin mud was poured into it.

[0065] 3) Within 30 seconds of starting mixing, the specimen was placed in an incubator at 37±2°C and 100% humidity, and a Vigor needle was gently dropped onto the surface of the specimen to check whether a needle mark was left. The time from the start of mixing until the needle mark disappeared on the specimen was recorded as the setting time.

[0066] The results are shown in Table 1.

[0067] [Table 1]

[0068] Comparative Example 1 The butoxydibutylboron mixture of Example 1 was used as the polymerization initiator (C), and evaluation was carried out in the same manner as in Example 1. The results are shown in Table 1.

[0069] Comparative Example 2 Reference 1. Preparation of partially oxidized tributylboron In a nitrogen atmosphere, 182 g of tributylborane was poured into a reaction vessel, and 0.5 molar oxygen equivalents of dry air were blown over the surface of the reaction solution over 6 hours while stirring, ensuring that the temperature of the reaction contents did not exceed 40°C, to obtain partially oxidized tributylborane (TBB·O). Store in a nitrogen atmosphere before use.

[0070] The above partially oxidized tributylboron was used as the polymerization initiator (C), and evaluation was carried out in the same manner as in Example 1. The results are shown in Table 1.

[0071] Comparative Examples 3 and 4 The above partially oxidized tributylboron was used as the polymerization initiator (C), and evaluation was carried out in the same manner as in Example 1. The results are shown in Table 1.

[0072] Comparative Example 5 The polymerization initiator (C) was prepared by reacting n-hexanol with tributylboron instead of n-butyl alcohol in Example 1, followed by distillation under reduced pressure at 126-128°C / 10 mmHg, and evaluation was performed in the same manner as in Example 1. The results are shown in Table 1.

[0073] Example 2 (adhesion strength with hard tissue) (1) Under water, the labial side of a bovine front tooth was cut with coarse emery paper to expose a flat enamel surface, and then polished with 600-grit emery paper to form an adhesive surface. After drying, the adhesive surface was treated with a phosphoric acid etching solution containing 35% by weight of phosphoric acid for 10 seconds, rinsed with water for 10 seconds, and air-dried for 15 seconds. After that, a piece of cellophane tape with a 4 mm diameter hole was applied to the adhesive surface to determine the adhesive area.

[0074] (2) A resin slurry was prepared in the same blending ratio as in the polymerization activity test in Example 1(4).

[0075] (3) This resin mud was applied to the adhesive surface prepared in (1), and an acrylic rod was attached to prepare a sample for the adhesion test. The sample for the adhesion test was left at room temperature for 30 minutes, and then immersed in distilled water at 37°C for 24 hours. A tensile test was then conducted to measure the adhesive strength between the acrylic rod and the tooth structure. The adhesive strength was the average value measured for five test pieces. The adhesive strength was 10.2 MPa.

[0076] As described above, according to the present invention, it is possible to provide a polymerization initiator and an adhesive composition suitable for hard tissue repair, which do not burn or ignite even when in contact with paper, porous fibrous materials, etc. in the air, have high fluidity, make it easy to accurately dispense small amounts, reduce adverse effects on the human body, and further impart high polymerizability to the polymerizable composition, allowing the polymerizable composition to harden within a short period of time.

[0077] The above content is a comparatively good embodiment of the present invention, and does not limit the present invention. Any modifications, equivalent replacements and improvements within the concept and principle of the present invention shall fall within the protection scope of the present invention.

Claims

1. An adhesive composition for hard tissue repair containing a polymerizable monomer (A), a polymer powder (B), and a polymerization initiator (C), The polymerization initiator (C) is butoxydibutylboron with a purity of 97.6%. The polymerizable monomer (A) is a (meth)acrylate or a combination of a (meth)acrylate and a polymerizable monomer having an acidic group; An adhesive composition for hard tissue repair, characterized in that the polymer powder (B) is at least one polymer selected from the group consisting of a homopolymer of alkyl (meth)acrylate, a copolymer of alkyl (meth)acrylate, and a copolymer of alkyl (meth)acrylate and another polymerizable monomer.

2. 2. The adhesive composition for hard tissue repair according to claim 1, characterized in that it contains 20 to 70 parts by weight of the polymerizable monomer (A), 20 to 70 parts by weight of the polymer powder (B), and 1 to 20 parts by weight of the polymerization initiator (C) (total of 100 parts by weight of (A), (B), and (C)).

3. An adhesive composition for hard tissue repair, further comprising 20 to 150 parts by weight of a filler (D) relative to 100 parts by weight of the total amount of the polymerizable monomer (A), the polymer powder (B), and the polymerization initiator (C), 2. The adhesive composition for hard tissue repair according to claim 1, wherein the filler (D) is an inorganic filler, an organic filler, or an organic-inorganic composite filler that does not dissolve or swell in the polymerizable monomer (A).

4. 2. The adhesive composition for hard tissue repair according to claim 1, wherein the other polymerizable monomer is an alkylene di(meth)acrylate or a butadiene-based monomer.

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