JP2013053096A - Dental curable composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a dental curable composition, in protection and repair of an infected part and a defected part in a contact part with the living tissue capable of regenerating the soft tissue such as the dental pulp and the periodontal membrane and the tissue such as the alveolar bones, for the purpose of protecting the dentine and protecting and regenerating the periodontal tissue and the peripheral tissue, in which growth factor protein sustainedly released from the composition can prompt the regeneration of the living tissue while filling up the infected part and the defected part by blockage by adhesion and intimate joining to the dentine and the bone tissue.SOLUTION: The dental curable composition is composed of a mixture including: (A) growth factor protein; (B) a radically polymerizable monomer; (C) a polymerization initiator; and (E) a hydrophilic material. The composition can contain (D) a filler as well.

Description

  The present invention relates to a dental curable composition that is advantageously used for restoration of a tooth or the like, particularly a site that comes into contact with periodontal tissue. Specifically, in the protection and repair of infected parts and defects at sites of contact with soft tissues such as dental pulp and periodontal ligament and living tissues that can regenerate tissues such as alveolar bone, the protection of tooth quality and the periodontal and bone tissue For the purpose of protection and regeneration, the growth factor protein that is released slowly from the composition adheres to the tooth tissue and bone tissue, and the infected part and defect part are compensated by blockade by close bonding. The present invention relates to a dental curable composition capable of promoting the above. More specifically, zinc phosphate cement, carboxylate cement and glass ionomer cement, composite resin, etc., which can be applied directly to the tooth and have good adhesion and insufficient adhesion, can also be applied. In addition, the present invention relates to a dental curable composition that can be used as an adhesive for adhering dental resins and dental materials represented by resin cement and the like.

In order to restore the tooth lost due to the tooth, the fracture or the wear, a material that reliably adheres to the restoration and the tooth is required. Uncertain adhesion may cause secondary caries due to bacterial invasion and propagation to create a gap with the restoration. Moreover, when the invading bacteria reach the pulp through the dentin dentinal tubule, pulpitis may be caused. Furthermore, the amount of adhesive could not be applied because the living tissue in contact with the amount of adhesive shows a rejection reaction with respect to the adhesive material at the site that is in contact with or embedded in the periodontal tissue.
In the case of dental restoration, the treatment method differs depending on the condition of the tooth and the position and size of the defect. For example, if caries progresses deep into the tooth and the dental pulp is exposed when it is removed by cutting, it is necessary to remove the nerve (remove the nerve) and perform endodontic treatment even if the dental pulp is not infected. However, such a pulpectomy root canal has an increased risk of infection, is likely to break, and has a short life span.

When repairing a broken root canal or filling a defect, the restoration comes in contact with periodontal tissues such as the periodontal ligament and alveolar bone, and this restoration lacks biocompatibility. If so, the healing of the contact area may not proceed. Further, when infection from the root canal tip (referred to as the apex) to the periodontal tissue occurs, a reverse root canal filling treatment is performed in which the root apex and the surrounding tissue are removed and sealed. However, if the root apex is not sufficiently sealed or the biocompatibility of the filling material is insufficient, the expected healing may not be achieved.
So far, an adhesive material composed of MMA, 4-META and tributylborane has been reported in Non-Patent Document 1 and Patent Document 1 as a composition that adheres to a tooth. Further, Non-Patent Document 2, Non-Patent Document 3, Non-Patent Document 4, and Non-Patent Document 5 report that the above adhesive material has high affinity for periodontal tissue. Furthermore, Non-Patent Document 6 reports the biocompatibility of the adhesive material to bone.
Therefore, Non-Patent Document 7 reports an attempt to promote bone growth by incorporating the bone formation growth factor protein BMP into the adhesive material. The composition is blended by mixing an aqueous BMP solution into a powder and then immobilizing it on a polymer powder by drying. However, there is a restriction that it cannot be applied to a growth factor protein that is denatured by drying and fixing.

Japanese Examined Patent Publication No. 6-99528

Journal of Japanese Denture Conservation, 28, 452-478 (1985) Japanese Dental Preservation Magazine, 40, 1453-1460 (1997) Journal of Japanese Denture Conservation, 45, 787-796 (2002) Japanese Dental Preservation Magazine, 45, 62-67 (2002) Nichido Preservation Journal, 48, no. 5, 733-742 (2005) Dental Materials and Instruments, 27, 455-465 (2008) Japanese Dental Preservation Magazine, 45, 434-440 (2002)

  The object of the present invention is therefore to adhere to the tooth structure at the site of contact with the periodontal tissue, and at the site to be contacted or embedded in the periodontal tissue, the contacted biological tissue is rejected against the curable composition. It is an object of the present invention to provide a dental curable composition that can solve the lack of biocompatibility and the lack of tissue regeneration, such as showing a reaction and tissue cells not regenerating on the surface of the curable composition.

Another object of the present invention is to contain (1) a growth factor protein capable of firmly adhering to and sequestering the tooth substance and (2) a hydrophilic material that is difficult to denature the growth factor protein. It is to provide a dental curable composition. Still other objects and advantages of the present invention will become apparent from the following description.
In the description of the following description of the present invention, the description of “XX to YY” in the preferred numerical range is “XX or higher and / or YY or lower, preferably XX or higher and It means "YY or less".

According to the present invention, the above objects and advantages of the present invention are:
This is achieved by a dental curable composition comprising (A) a growth factor protein, (B) a radical polymerizable monomer, (C) a polymerization initiator, and (E) a hydrophilic material. The composition may further contain (D) a filler. This (D) component can be obtained by curing a composition comprising the above (B) component in advance.

In the present invention, the component (A) is a growth factor protein. This is used, for example, as an aqueous solution or an aqueous suspension. Specifically, as such growth factor protein,
Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), Platelet-derived growth factor (PDGF), Transforming factor (PDGF), Transforming factor TGF), bone morphogenetic protein (BMP), insulin-like growth factor (IGF), nerve growth factor (NGF), epidermal growth factor (EGF) Liver parenchymal cell increase Factor (Hepatocyte growth factor: HGF), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Granulocyte-colony-stimulating factor (Granulocyte- colony stimulation factor) Bio-derived proteins such as factors (Brain-derived neurotrophic factor: BDNF), erythropoietin (EPO), thrombopoietin (TPO), and Osteopontin-DerivedGV. Examples include synthetic peptides such as u-Arg (SVVYGLR).

Optical micrograph of the surface of the cured product obtained in Example 3 Optical micrograph of the surface of the cured product obtained in Comparative Example 1

  When the dental curable composition of the present invention is 100 parts by weight, the content of (A) growth factor protein is preferably 0.0001 to 30 parts by weight, more preferably 0.001 to 10 parts by weight, Preferably it is 0.01-1 weight part. If it falls below the lower limit of the numerical range, it becomes difficult to ensure a sustained release concentration at which the effect of the growth factor is expressed, whereas if it exceeds the upper limit, the adhesive performance of the dental curable composition will be significantly reduced. Neither is preferred. The weight ratio (A / E) of (A) growth factor protein to (E) hydrophilic material is preferably 0.0001 / 60 to 30 / 0.1, more preferably 0.001 / 50 to 10 /. 1, more preferably 0.01 / 30 to 1/5. When the lower limit of the numerical range is not reached, (A) the efficiency of sustained release of the growth factor protein is inferior. On the other hand, when the upper limit is exceeded, the stability of the component (A) is lowered, which is not preferable. The concentration of the growth factor protein that is gradually released from the dental curable composition is preferably 0.01 ng / mL or more, more preferably 0.5 ng / mL or more, and further preferably 3 ng / mL or more.

In the present invention, examples of the (E) hydrophilic material include (E1) liquid hydrophilic material and (E2) solid hydrophilic material. Both are distinguished depending on whether they are in a liquid state (including sol) or a solid state (including gel) at room temperature and normal pressure (25 ° C., 1 atm).
(E1) As a liquid hydrophilic material, water and / or a hydrophilic organic solvent etc. are mentioned as a suitable example. These are preferably soluble or miscible with the growth factor protein. Of these, water is particularly preferred. First, I will explain about water.
Examples of water that can be used when the growth factor protein is made into an aqueous solution or an aqueous suspension include distilled water, ion-exchanged water, purified water, and physiological saline. In particular, distilled water, purified water and ion exchange water are preferably used. Further, redox water prepared by electrolysis, such as strongly acidic water or strong alkaline water, can also be used.

  Further, such water may contain a hydrophilic organic material such as an organic solvent. The organic solvent that can be used at this time is preferably a solvent that can be mixed and / or dissolved in water at a ratio of 1: 1 or more, preferably in any ratio. Further, the solvent is a liquid at 25 ° C. and has a boiling point at room temperature of preferably 200 ° C. or less, more preferably 150 ° C. or less, and most preferably 100 ° C. or less. Specific examples of the organic solvent include alcohols such as methanol, ethanol, and propanol; ethers such as tetrahydrofuran (THF); ketones such as acetone and methyl ethyl ketone; sulfoxides such as N, N-dimethyl sulfoxide (DMSO); Examples thereof include amides such as N, N-dimethylformamide (DMF). In addition, polyhydric alcohols such as ethylene glycol, propylene glycol, and glycerol can be used. Of these, alcohols such as ethanol and propanol, acetone, THF, DMSO, and the like are preferable in consideration of safety to the living body. Any of these compounds can be used in combination.

The hydrophilic organic solvent is not necessarily used together with water unless the growth factor protein is denatured so that a desired function cannot be expressed. The hydrophilic organic solvents can be used alone or in combination.
Advantages of using the growth factor protein together with the (E1) liquid hydrophilic material as a solution or suspension include that the growth factor protein can be prevented from being denatured by drying, and that heat is generated when the curable composition is polymerized and cured. It can be applied while maintaining the characteristics of the growth factor protein, such as avoiding the denaturation of the growth factor protein because the liquid hydrophilic material suppresses this.

  (E1) As the liquid hydrophilic material, a poly (poly () having preferably 1 to 60, more preferably 10 to 50, and still more preferably 20 to 40 repeating units derived from propylene glycol and / or ethylene glycol. Ethylene glycol and / or propylene glycol), that is, propylene glycol or ethylene glycol alone, or a polyether such as a diol compound in which propylene glycol and ethylene glycol are combined in an arbitrary ratio and arrangement (block or random), etc. A material (E1a) having a high viscosity (preferably a viscosity at 20 ° C. of 100 poise or more and 1 poise = 0.1 Pa · s) can also be used.

  Alternatively, (E1) as a liquid hydrophilic material, poly (ethylene glycol and / or propylene glycol) di (meth) having 4 to 60 repeating units derived from hydroxyethyl (meth) acrylate, propylene glycol and / or ethylene glycol ) Radical polymerization of acrylates, ie, di (meth) acrylates formed from diol compounds each of propylene glycol or ethylene glycol alone or combined with propylene glycol and ethylene glycol in any ratio and arrangement (block or random) Also included is a polymer (E1b) of a functional monomer. Among these monomers, preferred are hydrophilic monomers that can be mixed and / or dissolved in water at a ratio of 1: 1 or more, more preferably in an arbitrary ratio. Other non-hydrophilic monomers should not be included. (E1) When the liquid hydrophilic material is 100% by weight, these polymers are preferably 29% by weight or less, more preferably 15% by weight. % Or less, more preferably 5% by weight or less.

  On the other hand, (E2) the solid hydrophilic material is not particularly limited as long as it is a solid having hydrophilicity. For example, the hydrophilicity can be evaluated by measuring the contact angle of water droplets on the material surface. For simplicity, the hydrophilicity can be evaluated by immersing in a 1% methylene blue aqueous solution for 5 minutes and washing with water, and then dyeing it blue. To give a specific example, in the case of a copolymer of 2-hydroxyethyl methacrylate (HEMA) and trimethylolpropane tri (meth) acrylate (TMPT), in order to have the preferred hydrophilicity, the copolymer weight ratio HEMA / TMPT is preferably 10/90 or more, more preferably 50/50 or more, and still more preferably 70/30 or more. It is preferable that other materials have the same hydrophilicity.

(E2) Examples of the solid hydrophilic material include organic solid hydrophilic materials, inorganic solid hydrophilic materials, and mixtures and composites of these materials.
The organic solid hydrophilic material preferably has a hydrophilic group. For example, as a neutral group, a hydroxyl group, a polyether group (preferably (—R—O—) n, R: carbon number 1 -30 linear or branched alkyl group which may contain a hetero atom if necessary, n: a natural number of 4 to 60) ester group, ketone group, nitrile group, carboxyl group, amino group, The acidic group such as an amide group, sulfide group, thiol group, or disulfide group is preferably neutralized with a counter ion, such as carboxylate, phosphate, sulfonate, and others, an acetamide group, A sulfonamide group etc. can be mentioned as a preferable thing.

Furthermore, the organic solid hydrophilic material is preferably water-insoluble or can be adjusted as such, and its solubility is preferably 5, more preferably 1, with respect to 100% by weight of water. Preferably it is 0.1 or less. In addition, it is preferable not to melt | dissolve in (B) radically polymerizable monomer, and the solubility is (in the case where two or more types of component (B) are contained with respect to 100% by weight of component (B). Preferably 3 (more preferably 0.5, even more preferably 0.05) or less.
As the organic solid hydrophilic material, a polymer of a radical polymerizable monomer can be used.

  As the radical polymerizable monomer, for example, preferably 4 to 60 repeating units derived from hydroxyethyl (meth) acrylate, propylene glycol and / or ethylene glycol, more preferably 10 to 50, still more preferably. Poly (ethylene glycol and / or propylene glycol) di (meth) acrylate having 20 to 40, that is, propylene glycol or ethylene glycol alone or in any ratio and arrangement of propylene glycol and ethylene glycol (block or random) Di (meth) acrylate and trimethylolpropane tri (meth) acrylate, which are diol compounds bonded with each other, can be mentioned as preferred hydrophilic monomers. The polymer of the radical polymerizable monomer may be a copolymer of at least one of these hydrophilic monomers and, optionally, other radical polymerizable monomers. The other radical polymerizable monomer can be the same as the radical polymerizable monomer as the component (B) described below. Among them, a polymer made of hydroxyethyl (meth) acrylate is preferable. In addition, when a hydrophilic monofunctional monomer such as hydroxyethyl (meth) acrylate is included as a monomer for forming a polymer, the molecular chains are cross-linked to suppress the fluidity and solubility of the polymer. Therefore, it is preferable that at least a polyfunctional monomer such as trimethylolpropane tri (meth) acrylate having crosslinkability is contained. Accordingly, a polymer composed of hydroxyethyl (meth) acrylate and trimethylolpropane tri (meth) acrylate is preferred. The weight ratio HEMA / TMPT in the copolymer of 2-hydroxyethyl methacrylate (HEMA) and trimethylolpropane tri (meth) acrylate (TMPT) is preferably 99/1 or less, more preferably 97/3 or less, still more preferably 93/7 or less.

In addition, gelling agents such as synthetic polymers having acidic groups, polysaccharides having acidic groups, and growth factor proteins, such as polyacrylates, alginates, chitin, mannan, xanthan gum, pectin, etc. are also organic solid hydrophilic materials. A preferred example is as follows.
The inorganic solid hydrophilic material is not particularly limited, and specific examples include mesoporous silica, bentonite, zeolite, hydroxyapatite, silica alumina, and montmorillonite.
Furthermore, (E2) the solid hydrophilic material can adsorb or support the growth factor protein together with the liquid hydrophilic material, which is optionally used together with the outer surface of the solid particle (E1), and further inside the particle. Those having cavities or molecular gaps are also preferable because the growth factor protein can be retained there together with the liquid hydrophilic material (E1).
In order to enhance the bonding between the solid hydrophilic material and the matrix in the cured product obtained by polymerization and curing of the composition, a polyfunctional monomer may be added during the polymerization of the solid hydrophilic material, or the solid hydrophilic material may be added. It is also preferable to modify the surface with a compound having an active group and a polymerizable functional group that are easily reactively bonded to the surface.

(E2) The average particle size of the solid hydrophilic material is preferably 0.001 to 2000 μm, more preferably 0.01 to 1000 μm, and still more preferably 0.1 to 600 μm. When the value falls below the lower limit of the numerical range, the cohesiveness between the solid hydrophilic materials increases and the dispersibility to the matrix decreases, whereas when the value exceeds the upper limit, the adhesiveness decreases significantly. It is not preferable.
(E2) The solid hydrophilic material is used in the cured body so that the growth factor protein may be used together in some cases. (E1) It flows or diffuses as a solution or suspension of the liquid hydrophilic material. Inhibition and further reaction with an adhesive component or polymerization initiator, or physical restraint, it is physically blocked and the growth factor protein is stably retained.

  Since it has the function as described above, it is particularly preferable to use a combination of (E1) liquid hydrophilic material and (E2) solid hydrophilic material. The weight ratio (E1 / E2) of both is preferably 10/1 to 1/10, more preferably 5/1 to 1/5, and still more preferably 2.5 / 1 to 1 / 2.5. If the lower limit of the numerical range is not reached, the stability of the growth factor protein may be lowered. On the other hand, if the upper limit is exceeded, the component E2 may not be able to hold the component E1, both of which are not preferable. Or when the composition of this invention is 100 weight part, (E1) liquid hydrophilic material becomes like this. Preferably it is 0.1-50, More preferably, it is 1-20, More preferably, it is 3-10, (E2 ) The solid hydrophilic material is preferably 0.1 to 70, more preferably 1 to 50, still more preferably 5 to 30. As for E1, if it falls below the lower limit of the above numerical range, it may be difficult to stably maintain a sufficient amount of growth factor protein. On the other hand, if the upper limit is exceeded, the liquid phase separates and inhibits polymerization. Neither is desirable. For E2, if the value is below the lower limit of the above numerical range, it may be difficult to stably maintain a sufficient amount of growth factor protein, or the component E1 may not be retained, whereas the upper limit is exceeded. There is a risk that the adhesiveness of the composition may be hindered.

(E2) The solid hydrophilic material may be a mixture, a composite, or the like made of the hydrophilic material and other materials.
For example, from the group consisting of an organic solid hydrophilic material, an inorganic solid hydrophilic material, an organic solid non-hydrophilic material, an inorganic solid non-hydrophilic material under the condition that an organic solid hydrophilic material or an inorganic solid hydrophilic material is an essential component It may be an integrated form in which at least one selected material is mixed. In that case, for example, non-hydrophilic particles may be dispersed in a matrix of a solid hydrophilic material, or vice versa.
Alternatively, the surface of at least one material selected from the group consisting of an organic solid hydrophilic material, an inorganic solid hydrophilic material, an organic solid non-hydrophilic material, and an inorganic solid non-hydrophilic material is coated with an organic solid hydrophilic material and / or inorganic. The solid hydrophilic material may be a layered, coated or supported material. In that case, the solid hydrophilic material may be laminated, coated or supported on the surface of the solid non-hydrophilic material.
The liquid hydrophilic material may contain a regulator that stabilizes the growth factor protein such as a PH regulator and a radical scavenger.

When the dental curable composition of the present invention is 100 parts by weight, the (E) hydrophilic material is preferably 0.1 to 60 parts by weight, more preferably 1 to 50 parts by weight, still more preferably 5 to 30 parts by weight. Included in the department. When the value is below the lower limit of the numerical range, it becomes difficult to carry an amount capable of exhibiting the pharmacological effect of the growth factor protein. On the other hand, when the value exceeds the upper limit, the adhesiveness is remarkably lowered.
Furthermore, when the dental curable composition of the present invention is 100 parts by weight, when the weight part of the hydrophilic material is e and the weight part of the (D) filler used in some cases is d, e _{U in the} following formula is , Preferably 70, more preferably 50, still more preferably 30. d _U is preferably 70, more preferably 50, and even more preferably 30.
e / e _U + d / d _U ≦ 1
e _U and d _U, respectively, in the component of the formula described, corresponds to the preferred parts by weight upper limit in the case of using (E) a hydrophilic material, either alone respectively (D) a filler.
This is because (E) the hydrophilic material is present as non-adhesive particles, like fillers, and therefore has an upper limit of parts by weight that is a critical value that hinders the adhesive performance of the adhesive, and they are complementary to each other. Therefore, it is preferable to make it contain in the constraint range of the mathematical formula relationship as in the above formula.

  Note that (E2) the solid hydrophilic material is in the form of particles, and preferably is further impregnated with or supported by growth factor protein or (E1) liquid hydrophilic material. It is convenient and easy to mix with the mass, but there is a possibility of sticking to each other and agglomerating during storage. It is better to arrange fine powder or film. In particular, in the case of a membrane, it is preferable to design the membrane so that it does not hinder the sustained release of the growth factor protein, such as having permeability that allows the growth factor protein to permeate, or dissolving it when mixed with the monomer.

  In the dental curable composition of the present invention, the (B) radical polymerizable monomer is a compound having at least one radical polymerizable group in the molecule, such as a (meth) acryloyl group or a styryl group. And compounds having a vinyl group or an allyl group.

  Examples of the component (B) radical polymerizable monomer include methyl acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, (meth). Aliphatic esters of (meth) acrylic acid such as hexyl acrylate, 1,6-hexamethylene dimethacrylate (1,6-HX) neopentyl glycol di (meth) acrylate, trimethylolpropane tri (meth) acrylate; 2 -Hydroxyethyl (meth) acrylate, 2 or 3-propyl (meth) acrylate, glycerol mono (meth) acrylate, diethylene glycol mono (meth) acrylate, triethylene glycol mono (meth) acrylate, pentaethylene glycol mono (meth) acrylate, Polyethylene Hydroxyl-containing (meth) acrylates such as glycol mono (meth) acrylate, 2-hydroxy-3-phenoxypropyl (meth) acrylate, adducts of 1 mol of bisphenol A and 2 mol of glycidyl (meth) acrylate; methylol (meth) Hydroxyl-containing (meth) acrylamides such as acrylamide; ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, pentaethylene glycol di (meth) acrylate, nonaethylene glycol di (meth) ) Acrylate, polyethylene glycol di (meth) acrylate such as tetradecaethylene glycol di (meth) acrylate; propylene glycol di (meth) acrylate, dipropylene Polypropylene glycol di (meth) acrylates such as cold di (meth) acrylate, tripropylene glycol di (meth) acrylate, nonapropylene glycol di (meth) acrylate; the above polyethylene glycol di (meth) acrylate and polypropylene glycol di (meth) acrylate A mono (meth) acrylate in which either (meth) acryloyl group is substituted with a methyl group or an ethyl group; 2- (meth) acryloyloxyethyl isocyanate or 2,2,4-trimethylhexamethylene diisocyanate or 1, (Meth) acrylate having urethane bond such as adduct of 3,5-trimethylhexamethylene diisocyanate and 2-hydroxyethyl (meth) acrylate; Examples include 2,2-bis (4- (meth) acryloyloxypolyethoxyphenyl) propanes obtained by further condensation of (meth) acrylic acid to a product obtained by adding oxyethylene. These polymerizable monomers can be used alone or in combination. Of the component (B) of the present invention, a particularly preferred radical polymerizable monomer is a radical polymerizable monomer having a solubility in water of less than 5%.

  Other examples of the component (B) include aromatic vinyl compounds such as styrene and divinylbenzene: vinyl esters such as vinyl acetate; aromatic esters such as phenyl (meth) acrylate;

Here, R ¹ is H or CH ₃ and R ² is a phenyl group or a naphthyl group.

  Compounds such as 2-hydroxy-3-phenoxypropyl (meth) acrylate (HPPM), 1 mol of bisphenol A and 2 mol of glycidyl methacrylate adduct (Bis-GMA), 1 mol of bisphenol A glycidyl ether Condensation product of 2 mol of (meth) acrylic acid (VR90), 1 mol of bisphenol A ethylene oxide adduct and 2 mol of (meth) acrylic acid condensate (ethylene oxide addition chain number m + n ≧ 2; m + n = 2.6 is abbreviated as 2.6E), etc .; 2- (meth) acryloyloxyethyl isocyanate, 1 mol of 2,2,4- (or 2,4,4-) trimethyl -1,6-hexamethylene diisocyanate and 2 moles of 2-hydroxyethyl (meth) acrylate Adduct urethane represented by (UDMA) (meth) acrylate (= 12 or less chain number n) can be mentioned a polymerizable monomer, such as.

  As the component (B), a radical polymerizable monomer having an acidic group or acidic base in one molecule can be used. Examples of acidic groups include carboxylic acid groups, carboxylic anhydride groups, phosphoric acid groups, thiophosphoric acid groups, and sulfonic acid groups.

  For example, examples of the monofunctional polymerizable monomer having a carboxylic acid group or its anhydride group in one molecule include monocarboxylic acid, dicarboxylic acid, tricarboxylic acid, tetracarboxylic acid and polycarboxylic acid or anhydride thereof. it can. Here, examples of compounds that can be used include carboxylic acids and / or anhydrides (a2) described in JP-B-6-62688. In particular, for example, (meth) acrylic acid, maleic acid, p-vinylbenzoic acid, 11- (meth) acryloyloxy-1,1-undecanedicarboxylic acid (MAC-10), 1,4-di (meth) acryloyloxyethyl Pyromellitic acid, 6- (meth) acryloyloxyethylnaphthalene-1,2,6-tricarboxylic acid, 4- (meth) acryloyloxymethyl trimellitic acid and its anhydride, 4- (meth) acryloyloxyethyl trimellitic acid And its anhydride, 4- (meth) acryloyloxybutyl trimellitic acid and its anhydride, 4- [2-hydroxy-3- (meth) acryloyloxy] butyl trimellitic acid and its anhydride, 2,3-bis (3,4-Dicarboxybenzoyloxy) propyl (meth) acrylate, 2 or Or 4- (meth) acryloyloxybenzoic acid, N, O-di (meth) acryloyloxytyrosine, O- (meth) acryloyloxytyrosine, N- (meth) acryloyloxytyrosine, N- (meth) acryloyloxyphenylalanine, N- (meth) acryloyl p-aminobenzoic acid, N- (meth) acryloyl-O-aminobenzoic acid, N-phenylglycine or an adduct of N-tolylglycine and glycidyl (meth) acrylate, 4-[(2 -Hydroxy-3- (meth) acryloyloxypropyl) amino] phthalic acid, 3 or 4- [N-methyl N- (2-hydroxy-3- (meth) acryloyloxypropyl) amino] phthalic acid, (meth) acryloyl Examples include aminosalicylic acid and (meth) acryloyloxysalicylic acid It is possible. Of these, 11-methacryloyloxy-1,1-undecanedicarboxylic acid (MAC-10) and 4-methacryloyloxyethyl trimellitic acid (4-MET) or its anhydride (4-META) are preferably used. The polyfunctional polymerizable monomer that can be used as the component (A) is a dicarboxylic acid, tricarboxylic acid and tetracarboxylic acid or a derivative thereof as a polymerizable monomer having at least two carboxyl groups in one molecule. Can be mentioned. For example, 2-hydroxyethyl (meth) acrylate and pyromellitic dianhydride addition product (PMDM), 2 moles of 2-hydroxyethyl (meth) acrylate and 1 mole of maleic anhydride or 3,3 ′, 4 , 4′-benzophenonetetracarboxylic dianhydride (BTDA) or 3,3 ′, 4,4′-biphenyltetracarboxylic dianhydride and the like, 2- (3,4-dicarboxy) And benzoyloxy) 1,3-di (meth) acryloyloxypropane.

  Examples of the polymerizable monomer having at least one phosphate group in one molecule include 2- (meth) acryloyloxyethyl acid phosphate, 2 and 3- (meth) acryloyloxypropyl acid phosphate, 4- (meta ) Acryloyloxybutyl acid phosphate, 6- (meth) acryloyloxyhexyl acid phosphate, 8- (meth) acryloyloxyoctyl acid phosphate, 10- (meth) acryloyloxydecyl acid phosphate, 12- (meth) acryloyl oxide decyl acid phosphate Bis {2- (meth) acryloyloxyethyl} acid phosphate, bis {2 or 3- (meth) acryloyloxypropyl} acid phosphate, 2- (meth) acryloyloxyethyl phenyla Dohosufeto, etc. can be mentioned 2- (meth) acryloyloxyethyl p- methoxyphenyl acid phosphate. The phosphate group in these compounds can be replaced with a thiophosphate group. As the polymerizable monomer having a thiophosphate group, those described in JP-A Nos. 54-21438, 59-140276, and 59-142268 can be used. Specific examples include the following compounds, which may be tautomers shown by [].

  Among these, 2- (meth) acryloyloxyethylphenyl acid phosphate and 10- (meth) acryloyloxydecyl acid phosphate are preferably used. These polymerizable monomers having a phosphate group can be used alone or in combination.

Examples of the polymerizable monomer having a sulfonic acid group in one molecule include 2-sulfoethyl (meth) acrylate, 2 or 1-sulfo-1 or 2-propyl (meth) acrylate, and 1 or 3-sulfo-2- Butyl (meth) acrylate, 3-bromo-2-sulfo-2-propyl (meth) acrylate, 3-methoxy-1-sulfo-2-propyl (meth) acrylate, 1,1-dimethyl-2-sulfoethyl (meth) Examples include acrylamide. Of these, 2-methyl-2- (meth) acrylamidepropanesulfonic acid is preferably used.
The monomer having an acidic group may be used as a monomer in which part or all of the acidic group is converted to a salt such as a monovalent or polyvalent metal salt or ammonium salt. In the present invention, the above component (B) can be used alone or in combination of two or more.

  The content of the hydrophilic monomer (HEMA or the like) when the component (B) is 100% by weight is preferably 70% or less, more preferably 50% or less, and further preferably 30% or less. . Exceeding the upper limit of the above numerical range is not preferable because the adhesiveness is remarkably lowered. When the dental curable composition of the present invention is 100 parts by weight, the (B) radical polymerizable monomer is preferably 10 to 95 parts by weight, more preferably 30 to 80 parts by weight, and still more preferably 40 to 40 parts by weight. 65 parts by weight. If the value falls below the lower limit of the above numerical range, sufficient penetration / diffusion into the tooth will not be possible, resulting in a significant decrease in adhesiveness. On the other hand, if the upper limit is exceeded, sufficient pharmacological effects of the component (A) will not be exhibited. This is not preferable.

Examples of the (C) polymerization initiator in the present invention include organic peroxides, inorganic peroxides, organic boron compounds, photosensitizers, organic reducing agents, and inorganic reducing agents.
Specifically, for example, diacetyl peroxide, dipropyl peroxide, dibutyl peroxide, dicapryl peroxide, dilauryl peroxide, dilauryl peroxide, benzoyl peroxide (BPO), p, p′-dichlorobenzoyl peroxide, p, p′-dimethoxy Organic peroxides such as benzoyl peroxide, p, p′-dimethylbenzoyl peroxide, p, p′-dinitrodibenzoyl peroxide can be exemplified. Of these, BPO is preferred. Furthermore, inorganic peroxides such as ammonium persulfate, potassium persulfate, potassium chlorate, potassium bromate and potassium perphosphate can be mentioned.
The photosensitizer that can be polymerized by irradiation with ultraviolet rays or visible rays is not particularly limited, and examples thereof include (c11) α-ketocarbonyl compounds and (c12) acylphosphine oxide compounds. it can.

  Examples of the α-ketocarbonyl compound which is the component (c11) of the present invention include α-diketone, α-ketoaldehyde, α-ketocarboxylic acid, α-ketocarboxylic acid ester and the like. More specifically, diacetyl, 2,3-pentadione, 2.3-hexadione, benzyl, 4,4′-dimethoxybenzyl, 4,4′-diethoxybenzyl, 4,4′-oxybenzyl, 4,4 Α-diketones such as' -dichlorobenzyl, 4-nitrobenzyl, α-naphthyl, β-naphthyl, camphorquinone, camphorquinonesulfonic acid, camphorquinonecarboxylic acid, 1,2-cyclohexanedione; methylglyoxal, phenylglyoxal Α-ketoaldehydes such as: pyruvic acid, benzoylformic acid, phenylpyruvic acid, methyl pyruvate, ethyl benzoylformate, methyl phenylpyruvate, butyl phenylpyruvate and the like. Of these α-ketocarbonyl compounds, α-diketones are preferably used from the standpoint of stability. Of the α-diketones, diacetyl, benzyl, and camphorquinone (CQ) are preferable.

  Examples of the acylphosphine oxide compound as the component (c12) of the present invention include benzoyldimethoxyphosphine oxide, benzoylethoxyphenylphosphine oxide, benzoyldiphenylphosphine oxide, 2-methylbenzoyldiphenylphosphine oxide, 2,4,6-trimethylbenzoyldiphenyl. A phosphine oxide etc. can be mentioned. The components (B11) and (B12) can be used alone or in combination.

  When an organic peroxide or a photopolymerization initiator is used, a reducing compound can be used in combination. Examples of the organic reducing compound include N, N-dimethylaniline, N, N-dimethyl p-toluidine (DMPT), N, N-diethyl-p-toluidine, N, N-diethanol-p-toluidine (DEPT). ), N, N-dimethyl-p-tert-butylaniline, N, N-dimethylanisidine, N, N-dimethyl-p-chloroaniline, N, N-dimethylaminoethyl (meth) acrylate, N, N- Aromatics such as diethylaminoethyl (meth) acrylate, N, N-dimethylaminobenzoic acid and its alkyl esters, N, N-diethylaminobenzoic acid (DEABA) and its alkyl esters, N, N-dimethylaminobenzaldehyde (DMABAd) Amines; N-phenylglycine (NPG), N-tolylglycine (N G), N, N- (3--methacryloyloxy-2-hydroxypropyl) can be used in combination amines such as phenylglycine (NPG-GMA). Among these, DMPT, DEPT, DEABA, DMABAd, NPG, and NTG can be preferably used.

In addition, aromatic sulfinic acid such as benzenesulfinic acid, o-toluenesulfinic acid, p-toluenesulfinic acid, ethylbenzenesulfinic acid, decylbenzenesulfinic acid, dodecylbenzenesulfinic acid, chlorobenzenesulfinic acid, naphthalenesulfinic acid or salts thereof It can also be used together. Furthermore, a barbituric acid derivative can be used in combination.
Among the reducing compounds, as the inorganic compound, a reducing inorganic compound containing sulfur can be preferably used. As such a compound, a reducing inorganic compound used as a redox polymerization initiator that can be used when polymerizing a radical polymerizable monomer in a medium such as water or an aqueous solvent is preferable. For example, sulfurous acid, bisulfite, Sulfurous acid, metabisulfite, pyrosulfurous acid, thiosulfuric acid, 1 dithionic acid, 1,2 thionic acid, hyposulfite, hydrosulfurous acid and salts thereof may be mentioned. Of these, sulfites are preferably used, and sodium sulfite, potassium sulfite, sodium hydrogen sulfite, and potassium hydrogen sulfite are particularly preferable. These reducing inorganic compounds can be used alone or in combination.

In general, examples of the organic boron compound include an organic boron compound or a composition containing the same. Examples of the organic boron compound include triethyl boron, tripropyl boron, triisopropyl boron, tributyl boron, tri-sec-butyl boron, triisobutyl boron, tripentyl boron, trihexyl boron, trioctyl boron, tridecyl boron, and tridodecyl. Trialkylboranes such as boron, tricyclopentylboron, tricyclohexylboron; alkoxyalkylboranes such as butoxydibutylboron; dialkylborane such as butyldicyclohexylborane, diisoamylborane, 9-borabicyclo [3.3.1] nonane, etc. Can be mentioned. These compounds may be partially oxidized. Furthermore, these compounds can be used in combination. Among these, tributyl boron or partially oxidized tributyl boron is preferably used. As the partially oxidized tributyl boron, for example, one obtained by adding 0.3 to 0.9 mol of oxygen to 1 mol of tributyl boron is preferably used.
Further, in addition to the organoboron compound, a composition containing an aprotic solvent and / or a liquid or solid organic oligomer or polymer inert to the organoboron compound may be mixed with the component (C) and used. it can.

  When the dental curable composition of the present invention is 100 parts by weight, the proportion of (C) the polymerization initiator is preferably 0.001 to 20 parts by weight, more preferably 0.1 to 10 parts by weight, and still more preferably. Is 0.3 to 5 parts by weight. If the value is below the lower limit of the numerical range, the curing time is extremely shortened, resulting in a significant decrease in operability. On the other hand, if the value exceeds the upper limit, the curing is inferior. Alternatively, the weight ratio (B / C) of the (B) radical polymerizable monomer to the (C) polymerization initiator is preferably 100 / 0.001 to 100/20, more preferably 100 / 0.01 to 100 / 10, more preferably 100 / 0.1 to 100/8. If the value falls below the lower limit of the numerical range, the curing time becomes extremely short and the operability is remarkably lowered. On the other hand, if the value exceeds the upper limit, the property becomes poor when the value exceeds the upper limit.

  The component (D) in the present invention is a filler. Such a filler is at least one filler selected from, for example, an organic filler, an inorganic filler, and an organic composite filler. The filler used here mainly improves the curing time and degree of polymerization of the composition comprising the components (A), (B) and (C), or adjusts the viscosity, or improves the mechanical strength of the cured product. It is added for the purpose. Examples of the organic filler include a filler of a powder polymer obtained by pulverizing or dispersion-polymerizing a polymer of a polymerizable monomer used as the component (B) and a polymerizable monomer used as the component (B). Examples thereof include fillers obtained by pulverizing after crosslinking with a crosslinking agent. Here, there is no particular limitation on the type of the polymerizable monomer that is a raw material of the filler that can be used, but a filler made of a homopolymer or copolymer of the polymerizable monomer exemplified in the component (B), or An organic and inorganic filler in which an inorganic filler is blended with this (hereinafter abbreviated as an organic composite filler) can be mentioned. For example, polymethyl methacrylate (PMMA), polyethyl methacrylate, polypropyl methacrylate, polybutyl methacrylate (PBMA), polyvinyl acetate (PVAc), polyethylene glycol (PEG), polypropylene glycol (PPG), polyvinyl alcohol (PVA) And the like, and these can be insolubilized with a crosslinking agent.

Examples of the inorganic filler include silica, silica alumina, alumina, alumina quartz, glass (including barium glass), titania, zirconia (zirconium oxide), calcium carbonate, kaolin, clay, mica, aluminum sulfate, barium sulfate, calcium sulfate, Examples thereof include titanium oxide and calcium phosphate. These inorganic fillers may be surface-treated with a silane coupling agent or a titanate coupling agent in advance.
Examples of the organic composite filler include fillers obtained by polymerizing and coating the surface of the inorganic filler described above with a polymerizable monomer and then pulverizing. Specifically, among inorganic fillers, fine powdered silica is polymer-coated with a polymerizable monomer mainly composed of trimethylolpropane tri (meth) acrylate (TMPT), and a filler obtained by pulverizing the obtained polymer ( TMPT · f). Moreover, the filler obtained by adding and disperse | distributing the inorganic fillers, such as a silica and a zirconium oxide, when superposing | polymerizing the said polymer etc., after superposing | polymerizing can be mentioned.

  When the dental curable composition of the present invention is 100 parts by weight, the (D) filler is preferably 0.1 to 70 parts by weight, more preferably 1 to 50 parts by weight, still more preferably 1 to 20 parts by weight. Included. When the value is below the lower limit of the numerical range, it is difficult to adjust the viscosity. On the other hand, when the value exceeds the upper limit, the increase in viscosity becomes remarkable, causing problems in operability. More preferably, as described in the above description of (E2) solid hydrophilic material, it is determined in relation to the weight part of (E2) solid hydrophilic material.

The dental curable composition of the present invention has a hardness necessary for the cured product to protect the tooth, and also has wettability, tooth reactivity, Necessary conditions for adhesion such as tooth diffusibility and tooth permeability can be simultaneously provided and firmly adhered to a living hard tissue, particularly a tooth, without a gap. In applying the curable composition of the present invention to a tooth, in consideration of safety, it is preferably contacted as it is after being wet or lightly dried by air blow. However, in order to keep the tooth surface clean and hygienic, an etching material such as a solution or gel containing phosphoric acid, nitric acid, hydrochloric acid, sulfuric acid, citric acid, maleic acid, ethylenediaminetetraacetic acid, etc., which may contain a metal salt Alternatively, a pretreatment such as application by a conditioner and washing with water can be performed. It can also be treated with hypochlorite or / and compositions containing it. The dental material washed with water by applying the pretreatment material can be applied in the wet state and / or dried to the dental curable composition of the present invention.
EXAMPLES The dental composition of the present invention will be specifically described below with reference to examples, but the present invention is not limited to the examples.

MC3T3-E1 cells, which are mouse calvarial-derived osteoblast-like cells, were seeded in a 96-well plate at a concentration of 2 × 10 ⁴ cells / well using α-MEM medium containing 10% FBS, and 37 ° C., 5%. After culturing for 12 hours under CO ₂ , the following experiment was performed.

Example 1
Determination of FGF-2 addition concentration: medium replaced with two commercially available rhFGF-2 (Invitrogen; Calbiochem) or Trafermin (Fiblast Spray, Kaken Pharmaceutical) at 5, 10, 25, 50, 100 ng / mL After 24 hours of culturing, cell proliferation was evaluated by MTT assay. In addition, 5 ng / mL of each FGF-2 was added to a differentiation induction medium supplemented with 100 μg / mL ascorbic acid and 5 mM β-glyceryl phosphate and cultured for 3 days, and then cultured for 7 or 14 days without FGF-2. Then, Alkaline Phosphatase (ALP) activity was measured. From these, the addition concentration of FGF-2 in subsequent experiments was determined.
As a result, cell proliferation was significantly promoted at all concentrations of 5 to 100 ng / mL in all three types of FGF-2 as compared with the case where FGF-2 was not added (ANOVA, Fisher's PLSD test). , P <0.05), but there was no difference in effect due to the concentration of FGF-2. On the other hand, regarding the ALP activity, a significant decrease was observed in the 5 ng / mL FGF-2 added group as compared with the non-added group until the seventh day of culture. From these results, the concentration of FGF-2 added in the main culture system was determined to 5 ng / mL.

Example 2
Examination of the action of FGF-2 in the presence of a resin monomer: FGF-2 at a concentration determined in Experiment 1) in a medium in which 5 to 100 μg / mL 4-MET or 5 to 50 μg / mL MMA is dissolved And cultured for 24 hours, and cell proliferation was evaluated by MTT assay. In addition, the culture medium was replaced with a differentiation-inducing medium supplemented with FGF-2 and each monomer and cultured for 3 days. Thereafter, the culture was continued for 7 or 14 days without adding FGF-2 and monomers, and ALP activity was measured. .
As a result, both 4-MET and MMA showed significant acceleration of cell proliferation in the FGF-2 addition group (ANOVA, Fisher's PLSD test, p <0) as in the absence of monomer at all test concentrations. .05) was observed. In addition, the ALP activity was also confirmed to be decreased by the addition of FGF-2 up to the seventh day of culture in the presence of 4-MET or MMA at any concentration.
According to the results of Examples 1 and 2, addition of FGF-2 to the medium promoted the growth of MC3T3-E1 cells and continuously suppressed ALP activity until day 7, even in the presence of 4-MET or MMA. . These results indicate the possibility that FGF-2 can express its function even in an environment where unpolymerized monomers are eluted from the 4-META / MMA adhesive resin, and it has a FGF-2 sustained release ability. It was suggested that an adhesive resin is feasible.

Example 3
Next, the composition of the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.
(E) A method for producing a growth factor protein-holding carrier that contains a growth factor protein in a state where it coexists with water that is difficult to denature is as follows.

(E2) Preparation of solid hydrophilic material 90 parts by weight of 2-hydroxyethyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd., hereinafter, HEMA), 10 weights of trimethylolpropane trimethacrylate (manufactured by Shin-Nakamura Chemical Co., Ltd., hereinafter, TMPT) Part, 0.5 part by weight of benzoyl peroxide (manufactured by Tokyo Chemical Industry Co., Ltd., hereinafter referred to as BPO) was stirred. This was dried for 2 hours under normal pressure in a vacuum constant temperature dryer set at 120 ° C., and further dried for 16 hours under reduced pressure (≦ 0.1 MPa) to prepare a polymer. The polymer is finely pulverized with a planetary ball mill, and a powder material passing through a mesh of 100 mesh (150 μm) is collected to obtain (E2) a solid hydrophilic material (HEMA / TMPT = 90/10 parts by weight). It was.

(E2) Confirmation of hydrophilicity of solid hydrophilic material (E2) 100 parts by weight (HEMA), 70 parts by weight / 30 in the same preparation method as the above-mentioned (E2) solid hydrophilic material (HEMA / TMPT = 90/10 parts by weight) Parts by weight (HEMA / TMPT), 50 parts by weight / 50 parts by weight (HEMA / TMPT), 30 parts by weight / 70 parts by weight (HEMA / TMPT), 10 parts by weight / 90 parts by weight (HEMA / TMPT), 100 parts by weight A solid hydrophilic material to be (TMPT) was prepared. The degree of hydrophilicity of these solid hydrophilic materials was compared with the degree of dyeing using methylene blue, which is a water-soluble dye. Specifically, after various growth factor protein holding carriers are immersed in a 1% methylene blue aqueous solution for 5 minutes and washed with water, the degree of staining (blue) of the carrier is visually evaluated in 6 stages (0: no staining at all, 5: intense blue staining) ).

  The following (E2) solid hydrophilic material used was HEMA / TMPT = 90/10 parts by weight.

(A) Preparation of Growth Factor Protein Aqueous Solution After adding 0.1 g of albumin bovine serum-derived corn fraction pH 7.0 (manufactured by Wako Pure Chemical Industries, Ltd., hereinafter BSA) to 50 g of purified water, MIX rotor (MR-5, A growth factor protein aqueous solution was obtained by stirring with AZONE for several hours.

(A) Method of holding growth factor protein aqueous solution in (E2) solid hydrophilic material 50 g of the above (A) growth factor protein aqueous solution was charged with 3 g of component (E) and stirred overnight. After stirring, the purified water is removed by suction filtration (Kiriyama funnel filter paper, No. 5A), and the carrier particles holding the growth factor protein (A) component held in the component (E) (hereinafter referred to as growth factor protein) Retained particles). The water absorption amount (([polymer weight after water absorption] − [polymer weight before water absorption]) / [polymer weight before water absorption]) × 100 = 40% by weight.

Preparation of Cured Material Containing Growth Factor Protein-Retaining Particles Take about 0.09 g of superbond monomer liquid (manufactured by Sun Medical Co., Ltd.) containing 4-META and MMA as component (B) in a mixing dish, and as component (C) About 0.007 g of super bond catalyst (manufactured by Sun Medical Co., Ltd.) was dropped, and a mixture was prepared by mixing these with 0.07 g of the growth factor protein-supporting carrier particles. This mixture was filled in a Teflon mold (φ9.5 mm, thickness 0.5 mm) placed on a glass plate, and a transparent film and a glass plate were placed thereon and pressed for more than a day to obtain a cured body.

Comparative Example 1
Preparation of cured body containing growth factor protein non-retained particles About 0.09 g of superbond monomer solution (manufactured by Sun Medical Co., Ltd.) containing 4-META and MMA as component (B) in a mixing dish, component (C) As a superbond catalyst (manufactured by Sun Medical Co., Ltd.), about 0.007 g was dropped, and a mixture was prepared by mixing these with 0.07 g of (E2) solid hydrophilic material. This mixture was filled in a Teflon mold (φ9.5 mm, thickness 0.5 mm) placed on a glass plate, and a transparent film and a glass plate were placed thereon and pressed for more than a day to obtain a cured body.
Confirmation of the presence or absence of growth factor protein on the surface of the cured product containing the growth factor protein-retaining particles The cured product prepared as described above was evaluated for the presence or absence of growth factor protein by immunostaining.

Immunostaining
a) Various prepared sample pieces were washed with a phosphate buffer solution (hereinafter, PBS) three times at room temperature for 5 minutes.
b) A BSA antibody (manufactured by sc-50711 santa Cruz Biotechnology) diluted 50-fold with PBS as the first antibody was added dropwise to the sample piece after washing, and then allowed to stand at 4 ° C. for 24 hours.
c) The sample piece after standing was washed 3 times with PBS for 5 minutes at room temperature.
d) N-Histofine Simple Stain Mouse MAX PO (G) (manufactured by Nichirei) was added dropwise as a second antibody to the washed sample piece, and left at room temperature for 30 minutes.
e) The sample piece after standing was washed 3 times with PBS for 5 minutes at room temperature.
f) A simple stain DAB solution (manufactured by Nichirei) was dropped on the washed sample piece for the purpose of color development, and left at room temperature for 5 minutes.
g) Washed with purified water for the purpose of stopping color development of the sample piece after standing.
Then, the presence or absence of growth factor protein on the surface of the sample piece was observed with an optical microscope. In the cured product containing the growth factor protein-retaining particles produced in Example 3, color development as seen by the black arrows in FIG. 1 could be observed on the surface of the sample piece. On the other hand, in the cured body prepared in Comparative Example 1, the color development seen in FIG. 1 could not be observed on the surface of the sample piece as shown in FIG.
From the above, it was confirmed that the growth factor protein was present on the surface of the cured body containing the growth factor protein-retaining particles, and the existing growth factor protein was not inactivated.

Abbreviations are as follows.
E: Enamel,
D: Dentin 4-META: 4-methacryloxyethyl trimellitic anhydride,
4-MET: 4-methacryloxyethyl trimellitic acid,
SMR-M: 2-methacryloxyethyl acid phosphate MMA: methyl methacrylate 2.6E: 1 mol of ethylene oxide adduct of bisphenol A and condensate of 2 mol of methacrylic acid (addition chain number of ethylene oxide: m + n = 2.6)
UDMA: 1 mol of 2,2,4- (or 2,4,4-) trimethyl-1,6-hexamethylene diisocyanate and 2 mol of 2-hydroxyethyl (meth) acrylate adduct HPPM: 2-hydroxy- 3-phenoxypropyl methacrylate 3G: triethylene glycol dimethacrylate TBB: partial oxide of tributylborane (super bond C & B, catalyst)
CQ: d, l-camphorquinone, TMDPO: 2,4,6-trimethylbenzoyldiphenylphosphine oxide DMABA-BE: N, N-dimethylaminobenzoic acid n-butoxyethyl DSNa: sodium dodecyl sulfate R812: silica, containing SiO ₂ 99.8% rate, average particle size 7 × 10 ⁻³ μm

Claims (7)

  A dental curable composition comprising a mixture containing (A) a growth factor protein, (B) a radical polymerizable monomer, (C) a polymerization initiator, and (E) a hydrophilic material.   The dental curable composition according to claim 1, further comprising (D) a filler component.   The dental curable composition according to claim 1 or 2, wherein the (E) hydrophilic material is (E1) a liquid hydrophilic material and / or (E2) a solid hydrophilic material.   The dental curable composition according to claim 3, wherein the liquid hydrophilic material (E1) is water and / or a hydrophilic organic solvent.   The (E2) solid hydrophilic material is a polymer of poly (ethylene glycol and / or propylene glycol) or a radical polymerizable monomer having 1 to 60 repeating units derived from propylene glycol and / or ethylene glycol. The dental curable composition according to claim 3.   Poly (ethylene glycol and / or propylene glycol) di (meth) acrylate having 4 to 60 repeating units derived from hydroxyethyl (meth) acrylate, propylene glycol and / or ethylene glycol as the radical polymerizable monomer, and The dental curable composition according to claim 5, which is at least one selected from the group consisting of trimethylolpropane tri (meth) acrylate.   The (E) hydrophilic material is (E2) a solid hydrophilic material, and the (A) growth factor protein is retained in the (E2) solid hydrophilic material. Dental curable composition.