JP2013133290A - Trehalose derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel trehalose derivative used suitably especially as a polymerizable monomer component of a dental adhesive composition.SOLUTION: The trehalose derivative is represented by general formula (1). (In the formula, m is an integer of 1-8, n is an integer of 0-9, A is a trehalose residue obtained by removing hydroxyl groups to the number of m from trehalose, and each R independently represents a hydrogen atom or a methyl group).

Description

  The present invention relates to a novel trehalose derivative and a dental adhesive composition containing the trehalose derivative.

  When the tooth is damaged due to caries or the like, if the cavity due to the damage is relatively small, direct restoration is often performed with a composite resin from the viewpoint of aesthetics, simplicity of operation, and speed. On the other hand, when the cavity due to damage is relatively large, the cavity is repaired using a prosthesis made of metal, ceramics, or a cured resin.

  However, since these materials themselves do not have adhesiveness to the tooth, a dental adhesive is used for restoration. The adhesive material is required to have an adhesive strength that can overcome, for example, internal stress generated when the composite resin is cured, that is, tensile stress generated at the interface between the composite resin and the tooth. Otherwise, the composite resin may fall off due to long-term use in a harsh oral environment, and a gap will be created at the interface between the composite resin and the tooth, from which bacteria will invade and adversely affect the dental pulp. Because there is a fear. However, in general, methacrylate monomers used as the main component of dental adhesives often fail to provide adhesive strength sufficient to overcome this internal stress.

  The hard tissue of teeth consists of enamel and dentin, and the adhesive material is clinically required to adhere to both. Conventionally, for the purpose of improving adhesiveness, a method of pretreating a tooth surface prior to application of an adhesive has been used. As such a pretreatment material, an acid aqueous solution for decalcifying the tooth surface is generally used, and acid aqueous solutions such as phosphoric acid, citric acid and maleic acid have been used.

  In the case of enamel, the adhesion mechanism between the treated surface and the adhesive is a macro mechanical fit in which the adhesive penetrates and hardens on the rough surface formed by decalcification of the acid aqueous solution.

  On the other hand, in the case of dentin, it is said to be a micro mechanical fit in which an adhesive penetrates and hardens into fine voids of sponge-like collagen fibers exposed on the tooth surface after decalcification. Since the penetration into the collagen fibers is not as easy as the enamel surface, a penetration enhancer called a primer is generally used after the decalcification treatment with an acid aqueous solution. As a primer used for the permeation treatment, a polymerizable monomer composition containing a hydrophilic monomer having good affinity for the above-mentioned tooth such as hydroxyethyl methacrylate (HEMA) or an organic solvent is used.

That is, in order to obtain good adhesion strength to both enamel and dentin, before applying the dental adhesive, the following two-stage pretreatment:
(A) etching hard dental material (enamel mainly composed of hydroxyapatite),
(B) impregnating dentin with a penetration enhancer called a primer;
There is a problem that the operation is complicated and the operation must be performed in three steps.

  A variety of dental adhesives containing a polymerizable monomer having adhesiveness to the tooth for the purpose of reducing the complexity of the pretreatment operation with higher adhesive strength during the pretreatment as described above. Has been developed.

  For example, Patent Document 1 and Patent Document 2 propose a dental adhesive containing an acidic group-containing polymerizable monomer as at least a part of the polymerizable monomer component. In this adhesive, the acidic group-containing polymerizable monomer having an acidic group such as a phosphate group or a carboxylic acid group in the molecule has a high affinity for the tooth substance (hydroxyapatite or collagen). Higher adhesive strength is developed.

  Patent Documents 3 to 6 propose an adhesive in which an acidic group-containing polymerizable monomer coexists with water. Such an adhesive material has not only a deashing function of the acid aqueous solution but also a primer penetration promoting function by the action of the acidic group, so there is no need to separately apply a pretreatment agent, and a single coating operation. It is advantageous as an adhesive material (one-step type adhesive material) that can be used alone and has excellent operability. Due to this excellent operability, the one-step type adhesive has been actively used in the field of dental treatment recently.

  By the way, in recent years, a kind of disaccharide “trehalose” has attracted attention as a raw material for medicines and cosmetics. Trehalose has characteristics such as strong resistance to enzyme hydrolysis, resistance to metabolism in the human body, protection of DNA from degradation by ultraviolet rays, and elimination of specific malodors. As trehalose derivatives, there are known trehalose derivatives obtained by condensing trehalose and glycidyl ether, and trehalose derivatives obtained by condensing trehalose and an acetal compound (see Patent Documents 8 and 9). It does not have a polymerizable group in the molecule and is unsuitable for use as a curable composition.

: JP-A-52-113089 : JP-A-58-21687 : JP-A-2004-352698 : JP-A-9-263604 : JP 10-236912 A : JP 2001-72523 A : JP 2000-86421 A : JP 2005-2034 A : JP 09-3087 A

  As described above, the one-step adhesive has a deashing function and a primer penetration promoting function, so that it is not necessary to separately apply a pretreatment agent and is excellent in operability. It tends to have poor curability such as adhesive strength (hereinafter sometimes referred to as initial adhesive strength). The adhesive contains a relatively large amount of water, which is an essential component for providing a decalcification function. This water is necessary for decalcification, but when the adhesive is cured thereafter, This is because the composition which has been uniform by the separation is made non-uniform, and the curable properties such as the initial adhesive force are lowered.

  As a mitigation measure for this problem, it is conceivable to reduce the water content, but the deashing property is also reduced with the reduction of the water content, and thereby the curable properties such as initial adhesive strength are reduced. Problems arise. It is also possible to maintain deashing by reducing the amount of water and increasing the amount of acidic group-containing polymerizable monomer, but increasing the amount of acidic group-containing polymerizable monomer increases the hydrophilicity of the adhesive. Thus, there is a particular problem in the durability of adhesive strength when used for a long time in the oral environment (hereinafter sometimes referred to as adhesion durability). Furthermore, it is possible to reduce the blending amount of water and add an amphiphilic polymerizable monomer such as HEMA.

  Accordingly, a dental adhesive composition containing an acidic group-containing polymerizable monomer and a relatively large amount of water as essential components, and having excellent initial adhesive strength and adhesive durability Development is required.

  An object of the present invention is to provide a novel trehalose derivative that can be suitably used as a polymerizable monomer component of a dental adhesive composition. Another object of the present invention is a dental adhesive composition comprising the trehalose derivative, having an excellent initial adhesive force for both enamel and dentin, and excellent adhesion durability. Is to provide.

According to the present invention, the following general formula (1):
Where
m is an integer from 1 to 8,
n is an integer from 0 to 9,
A is a trehalose residue obtained by removing m hydroxyl groups from trehalose,
Each R is independently a hydrogen atom or a methyl group,
A trehalose derivative represented by the formula:

  In the trehalose derivative represented by the general formula (1), m is preferably 1 or 2.

  According to the present invention, the polymerizable monomer component (A) comprising the acidic group-containing polymerizable monomer (A1) having an acidic group in the molecule and the trehalose derivative (A2), water (B) And a water-soluble organic solvent (C). A dental adhesive composition is provided.

  The dental adhesive composition preferably further contains a polymerization initiator (D).

Since the trehalose derivative of the present invention has a surface activity, when used in a dental adhesive composition, it increases the penetration of the dental adhesive composition into dentin and improves the adhesion durability. Can do. Furthermore, since the trehalose derivative of the present invention has a hydroxyl group, it exhibits a strong interaction with hydroxyapatite {Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ } and has a hydrophobic group. Since it shows a strong interaction with collagen forming dentin, it is possible to improve the initial adhesive strength and adhesion durability to dentin.
In addition, since the trehalose derivative has many hydroxyl groups (—OH groups) in the trehalose residue, the water contained in the adhesive composition can be effectively used to enhance the decalcification effect. . And the hydroxyl group in a trehalose residue shows a strong interaction with hydroxyapatite {Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ }. As a result, it is possible to increase the initial adhesive strength and adhesion durability to the enamel.
When the trehalose of the present invention is used for the adhesive composition, when the composition is stored, the hydroxyl contained in the trehalose derivative retains the water contained in the adhesive composition, so that the acid and water act. This can prevent deterioration of the composition and improve storage stability.

It is IR spectrum of the trehalose derivative (1-MPTR) of this invention. Is a ¹ H-NMR trehalose derivatives of the present invention (1-MPTR). It is IR spectrum of the trehalose derivative (2-MPTR) of this invention. Is a ¹ H-NMR trehalose derivatives of the present invention (2-MPTR).

The trehalose derivative of the present invention has the following formula (1);
It is represented by

In the above formula (1), A means a trehalose residue obtained by removing m hydroxyl groups from trehalose. m is the following formula (2) that binds to trehalose;
Represents the number of glycidyl group-containing unsaturated compounds (hereinafter referred to as glycidyl group-containing unsaturated compounds), and is an integer of 1 to 8. n represents the number of CH ₂ constituting the methylene group bonded to the glycidyl group {CH ₂ CH (O) CH ₂ }, and is an integer of 0 to 9. Each R independently represents a hydrogen atom or a methyl group.

(Specific examples of trehalose derivatives of the present invention)
In the trehalose derivative of the present invention, m = 1 or 2 is preferable from the viewpoint of solubility in a water-soluble organic solvent and hydrophilicity when used in an adhesive composition, and m = 1 is particularly preferable. . Further, from the viewpoint of enhancing the surface activity ability, n = 0 or 1 is preferable, and n = 0 is particularly preferable.

The trehalose derivative of the present invention is obtained by reacting a hydroxyl group in trehalose with a glycidyl group using trehalose {see the following formula (3)} and a glycidyl group-containing unsaturated compound.

Trehalose has eight hydroxyl groups in the molecule, and any of them reacts with a glycidyl group. However, in consideration of the influence of steric hindrance, among the hydroxyl groups in trehalose, the hydroxyl groups corresponding to primary alcohols (that is, the hydroxyl groups at the 6th and 12th positions) are particularly highly reactive, so the trehalose of the present invention obtained by the reaction. In the derivatives, glycidyl group-containing unsaturated compounds are preferentially bonded to these hydroxyl groups. Therefore, the trehalose derivative of the present invention is a trehalose derivative {see the following formula (4)} obtained by reacting a hydroxyl group at the 6th or 12th position of trehalose with a glycidyl group-containing unsaturated compound when m = 1. In addition, when m = 2, it is a trehalose derivative {see the following formula (5)} obtained by reacting the 6th and 12th hydroxyl groups with a glycidyl group-containing unsaturated compound.
When m = 1, the trehalose derivative having the glycidyl group-containing unsaturated compound bonded to the 6-position and the trehalose derivative bonded to the 12-position are the same substances from the viewpoint of the three-dimensional structure.

  The trehalose derivative of the present invention generally exists as a brown oily liquid at normal temperature and pressure, and can be confirmed by the following means (a) to (c).

(A) By IR analysis, a signal of a hydroxyl group derived from trehalose, a signal of a carbonyl group derived from a (meth) acryl group, and the like are observed.
(B) By measuring a proton nuclear magnetic resonance spectrum ( ¹ H-NMR), a signal of an ethylenic proton derived from a (meth) acryl group, a signal of a methylene proton adjacent to oxygen derived from a (meth) acryl group, Peaks based on methacryl group-derived methyl proton signals, trehalose-derived CH signals, and the like appear. By comparing the relative spectral intensities, the number of protons in each linking group can be determined.
(C) Since the peak indicating M + 1 is confirmed by mass spectrometry, the trehalose derivative of the present invention can be identified.

(Production of trehalose derivatives)
The trehalose derivative of the present invention represented by the formula (1) can be obtained by reacting trehalose with a glycidyl group-containing unsaturated compound represented by the formula (2).

<Trehalose>
Trehalose is a disaccharide in which two molecules of D-glucose are bound to each other by reducing groups. Trehalose has three kinds of isomers, α, α-bond, α, β-bond, and β, β-bond, depending on the binding mode, but there is no particular limitation.

  In producing the derivative of the present invention, trehalose is preferably used in the state of crystalline or amorphous anhydrous trehalose substantially free of water. In the present specification, “substantially free of water” means that the water content is less than 3% (w / w) as measured by the Karl Fischer method. In particular, crystalline anhydrous trehalose is preferably used because it generally has a high trehalose content and can be obtained at a relatively low price. In general, the higher the trehalose content in anhydrous trehalose, the better. 70% or more, preferably 80% or more per solid content is used.

<Glycidyl group-containing unsaturated compound>
The glycidyl group-containing unsaturated compound used for the production of the trehalose derivative of the present invention is represented by the following formula (2):
Where
n is an integer from 0 to 9,
Each R is independently a hydrogen atom or a methyl group,
For example, it can be obtained by reacting (meth) acrylic acid with a hydroxyl group-containing glycidyl compound. As this glycidyl group containing unsaturated compound, the compound represented by the following formula | equation (6)-(8) can be mentioned, for example, These can be used individually or in mixture of 2 or more types.

<Reaction of trehalose with glycidyl group-containing unsaturated compound>
Specifically, the reaction between trehalose and the glycidyl group-containing unsaturated compound is such that trehalose is dissolved in a solvent, and the glycidyl group-containing unsaturated compound is added and reacted in the presence of a catalyst. As a result, the glycidyl group opens and reacts with any hydroxyl group of trehalose to produce the trehalose derivative of the present invention.

  Any known solvent can be used as long as it can dissolve trehalose and does not substantially react with the glycidyl group-containing unsaturated compound. Furthermore, the boiling point of the solvent is preferably equal to or higher than the reaction temperature. Examples of such a solvent include dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, N-acetylmorpholine, N-methylsuccinimide, and the like, from the viewpoint of high boiling point and availability. From this, dimethyl sulfoxide is preferably used.

  As for the solvent, it is preferable to remove moisture in advance as in the case of trehalose. This is because trehalose and the solvent are generally hygroscopic, and if the reaction is carried out while containing moisture, the glycidyl group-containing unsaturated compound is consumed by the reaction with water. Examples of the method for removing moisture include a method of dehydrating by heating under reduced pressure, a method of dissolving trehalose in a solvent, and then heating this solution and blowing dry nitrogen.

  As the catalyst, an acid known as an epoxy group reaction catalyst; an alkali such as sodium hydroxide, potassium hydroxide, tetraethylammonium hydroxide, trimethylbenzylammonium hydroxide; an amine such as N-dimethylbenzylamine; However, from the viewpoint of nucleophilic attack of the glycidyl group to cause ring opening, an alkali is preferable, and sodium hydroxide is particularly preferable. It is preferable that the usage-amount of a catalyst is 0.1-40 mass parts with respect to 100 mass parts of glycidyl group containing unsaturated compounds.

The glycidyl group-containing unsaturated compound is preferably added dropwise. This is for reacting the compound with trehalose while avoiding the reaction of the (meth) acryl group present in the compound. The dropping rate is preferably 0.1 to 5.0 ml / min. If the dropping speed is too fast, the (meth) acrylic group reacts, and if it is too slow, the reaction efficiency is deteriorated and there is no merit.
The mixing ratio (mole) of the glycidyl group-containing unsaturated compound and trehalose is preferably 1: 1.5 to 1: 4 when the target trehalose derivative is a mono-substituted product, that is, m = 1 in formula (1). More preferably, it is 1: 2 to 1: 2.5. Further, when the target trehalose derivative is a di-substituted product, that is, when m = 2 in the formula (1), it is preferably 1: 0.3 to 1: 1, more preferably 1: 0.4 to 1. : 0.8. If the amount of unsaturated compound containing glycidyl group is small, the yield will be poor, and if it is too much, the (meth) acryl group or glycidyl group in the unsaturated compound containing glycidyl group that has not been used for synthesis tends to cause an unnecessary reaction. .

  In order to avoid an unexpected reaction of the glycidyl group-containing unsaturated compound, it is preferable to previously dissolve a polymerization inhibitor such as hydroquinone, hydroquinone monomethyl ether, dibutylhydroxytoluene, etc. in a solvent. Therefore, hydroquinone is particularly preferable. The polymerization inhibitor is preferably used in the range of 0.01 to 2.0 parts by mass with respect to 100 parts by mass of the glycidyl group-containing unsaturated compound. If the amount of the polymerization inhibitor is small, the (meth) acrylic group of the glycidyl group-containing unsaturated compound reacts and there is no merit even if it is more than necessary.

  From the viewpoint of controlling the reaction rate, the reaction temperature is preferably 50 to 100 ° C. at the start of dropping (at the start of reaction), 80 to 150 ° C. at the end of dropping, and more preferably 90 to 120 ° C. When the reaction temperature is low, the reaction rate is slow, and when it is high, coloring tends to occur. What is necessary is just to set reaction time suitably with the kind and quantity of a glycidyl group containing unsaturated compound, a catalyst, reaction temperature, etc.

The reaction is terminated by adding a neutralizing agent (alkali or acid) to the acid or alkali of the catalyst to neutralize the catalyst. Examples of the neutralizing agent include hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, sodium hydroxide, sodium methylate and the like. When the catalyst is an alkali, it is preferable to use hydrochloric acid from the viewpoint of easy handling.
The completion of the reaction can be confirmed by tracing the presence of the glycidyl group-containing unsaturated compound using, for example, a gas chromatograph.

  After completion of the reaction, the reaction product is obtained by distilling off the solvent from the reaction product. The solvent is preferably distilled off at a temperature of 100 ° C. or lower under reduced pressure in order to avoid thermal decomposition of the reaction product.

The reaction product thus obtained contains the trehalose derivative of the present invention and the raw material trehalose. This reaction product is usually further purified by a conventionally known method. Examples of the purification method include the following methods.
That is, the reaction product is redissolved in hot ethanol, cooled and recrystallized to precipitate unreacted trehalose. Next, the filtrate is collected by suction filtration, and the filtrate is concentrated under reduced pressure. The obtained concentrated liquid is purified by a silica gel column. Specifically, the concentrated solution is passed through a column filled with silica gel, and ethyl acetate is allowed to flow through the column to wash away unreacted glycidyl group-containing unsaturated compounds. Thereafter, a developing solvent such as ethanol is passed through the column, and the trehalose derivative of the present invention is eluted and collected. Finally, ethanol is volatilized from the collected liquid to obtain the trehalose derivative of the present invention.

(Characteristics and uses of trehalose derivatives)
The trehalose derivative of the present invention thus obtained can be used as a polymerizable composition because it has a (meth) acrylate group. Moreover, it has a (meth) acrylate group which is a hydrophobic group and a trehalose residue which is a strong hydrophilic group with many hydroxyl groups, and exhibits high surface activity. Therefore, when the trehalose derivative of the present invention is used as a component of a dental adhesive composition, water contained in the composition and a slight amount of water contained in the tooth surface are retained by the hydroxyl group. To improve the decalcification efficiency.
Furthermore, it is possible to avoid water and the polymerizable monomer component from being phase-separated at the time of curing by retaining water at the hydroxyl group in the trehalose residue. That is, it is possible to avoid non-uniform solubility of the adhesive composition at the time of curing, and to eliminate a decrease in initial adhesive strength and adhesion durability to enamel and dentin.

Furthermore, the hydroxyl group in the trehalose derivative of the present invention has a strong interaction with the constituent component hydroxyapatite {Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ } occupying 95% by weight of the enamel and water occupying 4% by weight. Indicates. Therefore, when the trehalose derivative of the present invention is used in a dental adhesive composition, not only the macro mechanical mechanical fit between the rough surface formed in the enamel by decalcification and the adhesive composition, but also hydroxy By the interaction between the apatite and water and the trehalose derivative of the present invention, the initial adhesive force and adhesion durability to the enamel are greatly improved.

On the other hand, dentin consists of a resin-impregnated layer and dentinal tubules, and collagen fibers are present in the resin-impregnated layer. Constituent components of dentin are hydroxyapatite {Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ } 70 wt% (45 vol%), organic matter (collagen) 20 wt% (37 vol%), water 10 wt% (18 Volume%).
When the dentin is decalcified with acid and water, the dentin tubules and the resin-impregnated layer are exposed, and the collagen fibers in the resin-impregnated layer shrink by drying in the subsequent air blowing step. When the dental adhesive composition using the trehalose derivative of the present invention is applied, the excellent water retention of the trehalose derivative suppresses the shrinkage of collagen fibers during the air blow treatment. Further, due to the surface active ability of the trehalose derivative, the adhesive composition penetrates deep into the dentinal tubules and collagen tissues, and exhibits excellent tooth penetration. And since the (meth) acrylate group which is a hydrophobic group acts with an organic substance (collagen) and the trehalose residue which is a hydrophilic group acts with hydroxyapatite and water, the initial adhesive strength and adhesion durability of dentin are improved. . Furthermore, the grafting of trehalose residues with collagen further improves the initial adhesive strength and durability of dentin.

  Furthermore, when the trehalose derivative of the present invention is used in a dental adhesive composition, when the adhesive composition is stored before use, the water contained in the adhesive composition is converted into a hydroxyl group in the trehalose derivative. Therefore, the adhesive composition has hydrolysis resistance and excellent storage stability.

(Dental adhesive composition)
The dental adhesive composition of the present invention comprises an acidic group-containing polymerizable monomer having an acidic group in the molecule (hereinafter referred to as an acidic group-containing polymerizable monomer) (A1) and the trehalose derivative (A2). A polymerizable monomer component (A) containing water, water (B) and a water-soluble organic solvent (C). The composition may further contain a polymerization initiator (D). If necessary, inorganic fillers such as fumed silica and various compounding agents known in the dental field may be blended.

<Acid group-containing polymerizable monomer (A1)>
In the adhesive composition of the present invention, the acidic group-containing polymerizable monomer (A1) is a polymerizable monomer having at least one polymerizable unsaturated group and at least one acidic group in one molecule. It does not specifically limit and a well-known compound can be used.

  Here, as the polymerizable unsaturated group, a (meth) acryloyl group and a (meth) acryloyloxy group, a (meth) acryloylamino group, a (meth) acryloylthio group or other derivative group of a (meth) acryloyl group; a vinyl group : Allyl group; styryl group and the like are exemplified.

In the present invention, the acidic group means a phosphinico group {= P (═O) OH}, a phosphono group {—P (═O) (OH) ₂ }, a carboxyl group {—C (═O) OH}, sulfo Not only a free acidic group such as a group (—SO ₃ H) but also an acid anhydride structure {eg, —C (═O) —O—C (═O) —} in which two of the acidic groups are dehydrated and condensed, Alternatively, an acid halide group {for example, —C (═O) Cl} in which an OH of an acidic group is substituted with a halogen, and the like, an aqueous solution or aqueous suspension of a polymerizable monomer having the group is acidic. Say.

Specific examples of the acidic group-containing polymerizable monomer (A1) include (meth) acrylic acid, N- (meth) acryloylglycine, N- (meth) acryloylaspartic acid, N- (meth) acryloyl-5 Aminosalicylic acid, 2- (meth) acryloyloxyethyl to hydrogen succinate, 2- (meth) acryloyloxyethyl to hydrogen phthalate, 2- (meth) acryloyloxyethyl to hydrogen malate, 6- (meth) acryloyloxy Ethyl naphthalene-1,2,6-tricarboxylic acid, O- (meth) acryloyl tyrosine, N- (meth) acryloyl tyrosine, N- (meth) acryloylphenylalanine, N- (meth) acryloyl-p-aminobenzoic acid, N -(Meth) acryloyl-O-aminobenzoic acid P-vinylbenzoic acid, 2- (meth) acryloyloxybenzoic acid, 3- (meth) acryloyloxybenzoic acid, 4- (meth) acryloyloxybenzoic acid, N- (meth) acryloyl-5-aminosalicylic acid, N -(Meth) acryloyl-4-aminosalicylic acid and other polymerizable monomers having one carboxyl group in the molecule, and acid anhydrides and acid halides thereof; 11- (meth) acryloyloxyundecane-1,1 -Dicarboxylic acid, 10- (meth) acryloyloxydecane-1,1-dicarboxylic acid, 12- (meth) acryloyloxidedecane-1,1-dicarboxylic acid, 6- (meth) acryloyloxyhexane-1,1-dicarboxylic acid Acid, 2- (meth) acryloyloxyethyl-3′-methacryloyloxy-2 ′-(3,4-di Carboxybenzoyloxy) propyl to succinate, 1,4-bis (2- (meth) acryloyloxyethyl) pyromellitate, N, O-di (meth) acryloyltyrosine, 4- (2- (meth) acryloyloxyethyl) trimellitate to Anhydride, 4- (2- (meth) acryloyloxyethyl) trimellitate, 4- (meth) acryloyloxyethyl trimellitate, 4- (meth) acryloyloxybutyl trimellitate, 4- (meth) acryloyloxyhexyltri Melitate, 4- (meth) acryloyloxydecyl trimellitate, 4-acryloyloxybutyl trimellitate, 6- (meth) acryloyloxyethylnaphthalene-1,2,6-tricarboxylic acid anhydride, 6- (meth) Acryloyloki Ethylnaphthalene-2,3,6-tricarboxylic anhydride, 4- (meth) acryloyloxyethylcarbonylpropionoyl-1,8-naphthalic anhydride, 4- (meth) acryloyloxyethylnaphthalene-1,8- Polymerizable monomers having a plurality of carboxyl groups or acid anhydride groups in the molecule such as tricarboxylic acid anhydrides, and acid anhydrides and acid halides thereof (provided these are compounds having a carboxyl group) 2- (meth) acryloyloxyethyl dihydrogen phosphate, bis (2- (meth) acryloyloxyethyl) hydrogen phosphate, 2- (meth) acryloyloxyethyl phenyl hydrogen phosphate, 10- (meth) acryloyl Oxydecyl dihydrogen phosph Polymers having a phosphinicooxy group or a phosphonooxy group in the molecule such as 2-phosphate, 6- (meth) acryloyloxyhexyl dihydrogen phosphate, 2- (meth) acryloyloxyethyl 2-bromoethyl to hydrogen phosphate Monomers (also referred to as polymerizable acidic phosphate esters), and acid anhydrides and acid halides thereof; polymerizable monomers having a phosphono group in the molecule such as vinylphosphonic acid and p-vinylbenzenephosphonic acid; Examples thereof include polymerizable monomers having a sulfo group in the molecule such as 2- (meth) acrylamide-2-methylpropanesulfonic acid, p-vinylbenzenesulfonic acid, and vinylsulfonic acid. In addition to these, JP-A Nos. 54-11149, 58-140046, 59-15468, 58-173175, 61-293951 are disclosed. Described as a component of a dental adhesive in JP-A-7-179401, JP-A-8-208760, JP-A-8-319209, JP-A-10-236912, JP-A-10-245525, etc. The acidic monomer used can also be used suitably.
These acidic group-containing polymerizable monomers may be used alone or in combination of a plurality of types.

  Among the above acidic group-containing polymerizable monomers, a polymerizable acidic phosphate ester is particularly preferable because of its excellent adhesiveness to teeth. Moreover, it is preferable that it is a derivative group of a (meth) acryloyl group as a polymerizable unsaturated group at the point with the favorable polymerizability at the time of light irradiation.

  When the adhesive composition of the present invention is used as an adhesive for adhering a dental restoration such as a composite resin or a prosthesis and a tooth, it contains an acidic group per 100 parts by mass of the adhesive composition. The polymerizable monomer (A1) is preferably 5 parts by mass or more, particularly preferably 10 parts by mass or more. If the amount of the acidic group-containing polymerizable monomer (A1) is small, the adhesive composition of the present invention cannot be sufficiently decalcified, and the initial adhesive strength and adhesion durability to enamel and dentin. Sex is reduced.

<Trehalose derivative (A2)>
The polymerizable monomer component (A) contained in the dental adhesive composition of the present invention includes trehalose represented by the formula (1) in addition to the acidic group-containing polymerizable monomer (A1). Derivative (A2) is used. Since the trehalose derivative (A2) has a (meth) acrylate group that is a hydrophobic group and a trehalose residue that is a strong hydrophilic group, water (B) can be effectively used to improve the decalcification action. Furthermore, the permeability to dentinal tubules and collagen tissue is increased, and the initial adhesive force and adhesion durability to dentin are increased. Moreover, the initial adhesive force and enamel durability with respect to enamel are improved by many hydroxyl groups which exist in a trehalose residue. The compounding amount of the derivative (A2) is preferably 20 to 200 parts by mass, more preferably 40 to 140 parts by mass with respect to 100 parts by mass of the acidic group-containing polymerizable monomer (A1). If the amount of the derivative (A2) is small, the above-described effects cannot be obtained sufficiently, so that the effect of improving the initial adhesive strength and adhesion durability of enamel and dentin cannot be sufficiently obtained. When the blending amount is large, the adhesive composition has too high a viscosity, so that the permeability to the dentin is particularly impaired, and as a result, the initial adhesive strength and the adhesion durability to the dentin are also impaired. In addition, a trehalose derivative may be used individually by 1 type, and may mix and use multiple types.

  The dental adhesive composition of the present invention may further contain a polymerizable monomer (A3) in addition to the acidic group-containing polymerizable monomer (A1) and the trehalose derivative (A2). (Hereinafter also referred to as other polymerizable monomer (A3)). As the other polymerizable monomer (A3), in general, a (meth) acrylate-based polymerizable monomer is suitably used from the viewpoint of the curing speed and the mechanical properties of the cured product.

  Among these other polymerizable monomers (A3), examples of the polyfunctional polymerizable monomer include ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, and triethylene glycol di (meth) acrylate. , Nonaethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, dipropylene glycol di (meth) acrylate, 2,2-bis [4- (meth) acryloyloxyphenyl] propane, 2,2-bis [ 4- (meth) acryloyloxyethoxyphenyl] propane, 2,2-bis [4- (meth) acryloyloxydiethoxyphenyl] propane, 2,2-bis [4- (meth) acryloyloxypolyethoxyphenyl] propane, 1-phenoxy-2-hydroxypropi (Meth) acrylate, 1-naphthoxy-2-hydroxypropyl (meth) acrylate, bisphenol A diglycidyl (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (meth) acrylate, Examples include trimethylolpropane tri (meth) acrylate, urethane (meth) acrylate, 1,6-bis (methacrylethyloxycarbonylamino) trimethyloxane, and epoxy (meth) acrylate, and these are used alone or in combination of two or more. Can be used.

  Furthermore, among other polymerizable monomers (A3), examples of the water-soluble amphiphilic polymerizable monomer include 2-hydroxyethyl (meth) acrylate and 2-hydroxypropyl (meth) acrylate. , 3-hydroxypropyl (meth) acrylate, 2,3-dihydroxypropyl (meth) acrylate, 2,3-dihydroxybutyl (meth) acrylate, 2,4-dihydroxybutyl (meth) acrylate, 2-hydroxymethyl-3- Hydroxypropyl (meth) acrylate, 2,3,4-trihydroxybutyl (meth) acrylate, 2,2-bis (hydroxymethyl) -3-hydroxypropyl (meth) acrylate, 2,3,4,5-tetrahydroxy Pentyl (meth) acrylate, diethylene glycol mono (meth) acrylate , (Meth) acrylic acid esters of polyhydric alcohols such as triethylene glycol mono (meth) acrylate, tetraethylene glycol mono (meth) acrylate and pentaethylene glycol mono (meth) acrylate or polyethylene glycols, N-methylol Examples include (meth) acrylic acid amides of amino alcohols such as (meth) acrylamide and N-methylol (meth) acrylamide, and these can be used alone or in admixture of two or more. The term “water-soluble” means that the solubility in water at 20 ° C. is 20 g / 100 ml or more.

  Among these other polymerizable monomers (A3), the polyfunctional polymerizable monomer is 2,2-bis [4- (meth) acryloyloxyphenyl from the viewpoint of monomer viscosity and cured product strength. Propane, triethylene glycol di (meth) acrylate, bisphenol A diglycidyl (meth) acrylate, and the like are preferable. Moreover, as an amphiphilic polymerizable monomer, 2-hydroxyethyl (meth) acrylate, triethylene glycol mono (meth) acrylate, etc. are preferable from the viewpoint of penetrability into teeth.

  The blending amount of the other polymerizable monomer (A3) is not particularly limited, but is preferably 500 parts by mass or less, more preferably 300 parts by mass, per 100 parts by mass of the acidic group-containing polymerizable monomer (A1). It is as follows. When the amount of the other polymerizable monomer (A3) is large, the amount of the acidic group-containing polymerizable monomer (A1) is relatively small, and the decalcification of the dental adhesive composition of the present invention. Decreases, and the initial adhesive strength and adhesion durability to enamel and dentin are impaired.

<Water (B)>
The water (B) used in the adhesive composition of the present invention is essential for providing a decalcifying action together with the acidic group-containing polymerizable monomer (A1). Examples of water (B) include deionized water and distilled water from the viewpoints of storage stability and biocompatibility, and from the viewpoint that it is preferable that substantially no impurities harmful to adhesiveness are contained. It is done.

  The blending amount of water (B) in the adhesive composition of the present invention is not particularly limited and may be set as appropriate, but is 10 with respect to 100 parts by mass of the acidic group-containing polymerizable monomer (A1). Thru | or 120 mass parts is preferable, and 50 thru | or 100 mass parts is more preferable. If the amount of water is small, sufficient decalcification cannot be obtained, and if the amount is large, the trehalose derivative (A2) exceeds the capacity that can be retained and phase separation occurs during curing, resulting in low initial adhesive strength. There is a tendency.

<Aqueous organic solvent (C)>
As the water-soluble organic solvent (C), known organic solvents can be used as long as they exhibit water solubility. Water-soluble means that the solubility in water at 20 ° C. is 20 g / 100 ml or more. Examples of such a water-soluble organic solvent include methanol, ethanol, propanol, isopropyl alcohol, acetone, and methyl ethyl ketone. A plurality of these organic solvents can be mixed and used as necessary. In consideration of harmfulness to living bodies, ethanol, isopropyl alcohol and acetone are preferable. The blending amount of the water-soluble organic solvent (C) is preferably 100 to 600 parts by mass, more preferably 200 to 500 parts by mass, per 100 parts by mass of the acidic group-containing polymerizable monomer (A1). When the blending amount of the water-soluble organic solvent (C) is small, the viscosity of the adhesive composition is high, so that the deashing power and the penetrating power cannot be obtained, and the initial adhesive strength and the adhesive durability are greatly reduced. Become. Moreover, when there are many compounding quantities, a viscosity will become low, the adhesive composition before hardening raise | generates dripping, etc., and it is inferior to operativity.

<Polymerization initiator (D)>
In the adhesive composition of the present invention, a polymerization initiator (D) may further be used, but a polymerization initiator is blended in a composite resin, an inlay or the like used in the field together with the adhesive composition. In such a case, the radical generated during the curing reaction also acts on the adhesive composition, so that the polymerization initiator (D) can be omitted. The polymerization initiator (D) used is not particularly limited, and a photopolymerization initiator or a chemical polymerization initiator can be used favorably. However, it is preferable to use a photopolymerization initiator from the viewpoint of operability that does not require heating or the complexity of dividing the packaging into two or more materials in a redox system and mixing them immediately before use. .

  Such photopolymerization initiators include diacetyl, acetylbenzoyl, benzyl, 2,3-pentadione, 2,3-octadione, 4,4′-dimethoxybenzyl, 4,4′-oxybenzyl, camphorquinone, 9,10- Α-diketones such as phenanthrenequinone and acenaphthenequinone, benzoin alkyl ethers such as benzoin methyl ether, benzoin ethyl ether, and benzoin propyl ether, 2,4-diethoxythioxanthone, 2-chlorothioxanthone, Thioxanthone derivatives such as methylthioxanthone, benzophenone, benzophenone derivatives such as p, p′-dimethylaminobenzophenone, p, p′-methoxybenzophenone, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis (2, -Dimethoxybenzoyl) -2,4,4-trimethylpentylphosphine oxide, acylphosphine oxide derivatives such as bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide, and aryl borate compounds / dyes / photoacid generators A system consisting of Among these, a photopolymerization initiator composed of a combination of α-diketone, acylphosphine oxide derivative, and aryl borate compound / dye / photoacid generator is particularly preferable.

  As the α-diketone, camphorquinone and benzyl are preferable, and as the acylphosphine oxide derivative, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis (2,6-dimethoxybenzoyl) -2,4, 4-Trimethylpentylphosphine oxide and bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide are preferred. In addition, although these α-diketones and acyl phosphine oxide derivatives alone show photopolymerization activity, when used in combination with amine compounds such as ethyl 4-dimethylaminobenzoate, lauryl 4-dimethylaminobenzoate, and dimethylaminoethyl methacrylate. Higher activity can be obtained.

  As the photopolymerization initiator of the aryl borate compound / dye / photoacid generator system, those described in JP-A-9-3109 and the like are preferably used. More specifically, the aryl borate compound is used. Tetraphenylboron sodium salt and the like, and 3,3′-carbonylbis (7-diethylamino) coumarin and 3,3′-carbonylbis (4-cyano-7-diethylaminocoumarin) as the dye. As the generator, those using a halomethyl group-substituted s-triazine derivative such as 2,4,6-tris (trichloromethyl) -s-triazine or a diphenyliodonium salt compound can be particularly preferably used.

  These photopolymerization initiators can be blended not only alone but also in combination of a plurality of types as required. These blending amounts are not particularly limited as long as they are effective amounts within a range not inhibiting the effects of the present invention, and may be appropriately determined according to the use and purpose of the curable composition to be adjusted. Generally, it is 0.5 to 50 parts by mass, more preferably 1 to 20 parts by mass with respect to 100 parts by mass of the polymerizable monomer (A). When there are few photoinitiators, hardening will not start, and when there are many photoinitiators, the intensity | strength of adhesive composition will fall and adhesion durability will fall.

  In the present invention, when a chemical polymerization initiator is used as the polymerization initiator (D), a redox system that generates radicals by combining two or more compounds can be preferably used. Typical redox chemical polymerization initiators include organic peroxides and amines, organic peroxides and amines and organic sulfinic acids, organic peroxides and amines and aryl borates. A system comprising an aryl borate and an acidic compound, a system comprising a barbituric acid derivative, a copper compound and a halogen compound. The compounding amount of these chemical polymerization initiators is within a range that does not impair the effects of the present invention, and is an effective amount (generally, the polymerizable monomer (A) 100 mass as in the case of the photopolymerization initiator. 0.5 to 50 parts by mass, and more preferably within a range of 1 to 20 parts by mass), and may be determined as appropriate according to the use and purpose of the composition to be adjusted. .

<Other ingredients>
The adhesive composition of the present invention exhibits its effect if the components (A) to (C) or (A) to (D) are blended, but in a range that does not greatly impair the effect of the present invention, In order to improve the strength of the polymerizable composition, other blending components such as an inorganic filler may be blended. Inorganic fillers include, for example, borosilicate glass, soda glass, glass containing heavy metals (eg, barium, strontium, zirconium), aluminosilicate, glass ceramics, silica, silica / zirconia, silica / titania, silica / alumina, etc. An inorganic oxide etc. are mentioned, Among these, a silica is the most preferable.

  These inorganic fillers can be improved in mechanical strength and water resistance by being hydrophobized with a surface treatment agent typified by a silane coupling agent to improve the compatibility with the polymerizable monomer. Hydrophobization may be performed by a known method, and as a silane coupling agent, methyltrimethoxysilane, methyltriethoxysilane, methyltrichlorosilane, dimethyldichlorosilane, trimethylchlorosilane, vinyltrimethoxysilane, vinyltriethoxysilane, vinyl Trichlorosilane, vinyltriacetoxysilane, vinyltris (β-methoxyethoxy) silane, γ-methacryloyloxypropyltrimethoxysilane, γ-methacryloyloxypropyltris (β-methoxyethoxy) silane, γ-chloropropyltrimethoxysilane, γ- Chloropropylmethyldimethoxysilane, γ-glycidoxypropyltrimethoxysilane, γ-glycidoxypropylmethyldiethoxysilane, β- (3,4-epoxycyclohexyl) ethyl Trimethoxysilane, N- phenyl--γ- aminopropyltrimethoxysilane, etc. hexamethyldisilazane is preferably used.

  The blending amount of the hydrophobized inorganic filler used in the present invention is preferably 1 to 50 parts by mass with respect to 100 parts by mass of the polymerizable monomer (A). It is preferably used in the range of 5 to 25 parts by mass. If the amount of the inorganic filler subjected to the hydrophobizing treatment is small, the strength and water resistance of the adhesive composition are insufficient, and if it is large, the curability is insufficient, and the initial adhesive strength and adhesion durability with the tooth substance. Sex is reduced.

  Moreover, you may mix | blend other components well-known as a compounding component of a dental adhesive composition other than said inorganic filler with the adhesive composition of this invention. Examples of other known components include an ultraviolet absorber, a polymerization inhibitor, a polymerization inhibitor, a dye, a pigment, and an inorganic filler.

<Method for producing dental adhesive composition>
The manufacturing method of the dental adhesive composition of this invention is not specifically limited, What is necessary is just to follow the manufacturing method of a well-known dental adhesive composition. In general, all components to be blended may be weighed under inert light such as red light and mixed well until a uniform solution is obtained. In addition, when using the dental adhesive composition of this invention as an adhesive agent, this composition can be manufactured so that it may become forms, such as a 1 liquid 1 step type, a 2 liquid 1 step type, a 2 liquid 2 step type. From the viewpoint of operability during use, a one-component one-step type is preferable.

  The adhesive composition of the present invention can be advantageously used as an adhesive or a self-etching primer used when a dental restoration such as a composite resin or prosthesis is bonded to a tooth. When the dental adhesive composition of the present invention is used as an adhesive, it can be used in accordance with a known usage method. Generally, the dental adhesive composition of the present invention is applied to a tooth structure that becomes an adherend from which a carious portion is removed. After applying the adhesive composition of the invention and leaving it to stand for about 5 to 60 seconds, lightly blown compressed air or the like to volatilize the volatile components, and then irradiate with visible light using a dental irradiator to be polymerized and cured. That's fine. Thereafter, filling with a composite resin or a prosthesis is performed. When the adhesive is a two-component one-step adhesive, a two-component two-step adhesive, or the like, the adhesive is applied to the tooth after mixing all the solutions.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.

The following abbreviations and abbreviations were used in the examples.
(A1) an acidic group-containing polymerizable monomer;
PM1: 2-methacryloyloxyethyl dihydrogen phosphate PM2: bis (2-methacryloyloxyethyl) hydrogen phosphate MDP: 10-methacryloyloxydecyl dihydrogen phosphate (A2) trehalose derivative;
1-MPTR:
2-MPTR:
1-MBTR:
1-MDTR:
(A3) Other polymerizable monomers;
Bis-GMA: 2,2′-bis [4- (2-hydroxy-3-methacryloxy)
Propoxy) phenyl] propane 3G: triethylene glycol dimethacrylate HEMA: 2-hydroxyethyl methacrylate (C) water-soluble organic solvent;
IPA: isopropyl alcohol (D) polymerization initiator;
CQ: camphorquinone DMBE: ethyl p-N, N-dimethylaminobenzoate and others (inorganic filler);
F1: Amorphous silica having a particle size of 0.02 μm (treated with methyltrichlorosilane)
F2: Spherical silica-zirconia (γ-methacryloyloxypro) having a particle size of 0.4 μm
Pyrtrimethoxysilane hydrophobized product) and spherical silica with a particle size of 0.08 μm
-Titania (γ-methacryloyloxypropyltrimethoxysilane hydrophobized
70:30 mass ratio with the treated product)

(Measuring method)
Various measurements in Examples and Comparative Examples were performed by the following methods.

(1) Measuring method of dental adhesion (initial adhesive strength) a) Preparation method of adhesion test piece The bovine front teeth are removed within 24 hours after slaughter and parallel to the lip surface with # 600 emery paper under running water. So that the enamel and dentin planes were cut out. Next, compressed air was blown onto these surfaces for about 10 seconds to dry them, and then a double-sided tape with a hole having a diameter of 3 mm was fixed on either surface of enamel or dentin, and then a thickness of 0.5 mm. A paraffin wax having a hole with a diameter of 8 mm was fixed on the circular hole so as to have the same center, thereby forming a simulated cavity. A dental adhesive composition was applied to the simulated cavity and allowed to stand for 20 seconds, and then dried by spraying compressed air for about 10 seconds. The dental visible light irradiator (Tokuso Power Light, manufactured by Tokuyama Corporation) 10 Light irradiation for 2 seconds. Further, a dental composite resin (Esterite Σ, manufactured by Tokuyama Dental Co., Ltd.) was filled thereon and irradiated with light by the visible light irradiator for 30 seconds to prepare an adhesion test piece.
b) Adhesion test method After the above-mentioned adhesion test piece was immersed in water at 37 ° C for 24 hours, the test piece was pulled at a crosshead speed of 2 mm / min using a tensile tester (Autograph, manufactured by Shimadzu Corporation), and a tooth was obtained. The tensile adhesive strength of the composite resin was measured. Measurement was performed on four test pieces per one example or comparative example, and the average value thereof was used as the initial adhesive force to enamel or dentin, and the adhesion to the tooth was evaluated.

(2) Measuring method of adhesion durability Adhesive test pieces prepared in the same manner as in (1) were immersed alternately in water at 4 ° C and 60 ° C for 1 minute using a thermal shock tester, and this was repeated 3000 times. . Thereafter, the tensile adhesive strength was measured in the same manner as in (1). Measurement was performed on four test pieces per one example or comparative example, and the average value was defined as the adhesive strength after an endurance test for enamel or dentin, and the adhesive durability was evaluated.

(Production example)
The trehalose derivative (A2) of the present invention used in each example and comparative example was produced as follows.

<1-MPTR>
50 g (0.15 mol) of α-D-trehalose obtained by drying under reduced pressure at 90 ° C. for 4 hours and distilling off water was immediately dissolved in 160 mL of dimethyl sulfoxide, and a small amount of hydroquinone as a polymerization inhibitor (a glycidyl group-containing unsaturated compound). 0.4 parts by mass with respect to 100 parts by mass), and heated and stirred at 80 ° C. using an oil bath. After adding 2.0 g of sodium hydroxide to this solution, the following formula (6):
10.4 g (0.07 mol) of glycidyl methacrylate represented by the formula was added dropwise over 30 minutes (0.35 ml / min). After the dropwise addition, the reaction solution was heated to 100 ° C., and the glycidyl methacrylate in the reaction solution was traced using a gas chromatograph (G3440A manufactured by Agilent Technology) and stirred until the peak disappeared. After the disappearance of the peak, the reaction solution was neutralized by adding an equivalent amount of hydrochloric acid to terminate the reaction, and then dimethyl sulfoxide as a solvent was distilled off under reduced pressure. The residue was dissolved in 100 ml of hot ethanol, cooled to 4 ° C., unreacted trehalose was precipitated, and the filtrate was collected by suction filtration. The filtrate was concentrated under reduced pressure to obtain a concentrated solution.
Next, this concentrated solution was passed through a column packed with silica gel for C-200 column chromatography (manufactured by Wako Pure Chemical Industries, Ltd.). After this column was washed with ethyl acetate, ethanol was passed as a developing solvent, and the target component adsorbed on silica gel was eluted into ethanol and collected. When ethanol was distilled off from this recovered solution under reduced pressure, 29.2 g of a purified product (brown oily liquid), that is,
1-MPTR represented by the following was obtained.

It was confirmed by IR analysis, ¹ H-NMR analysis, and mass spectrometry that the obtained purified product was 1-MPTR.
Doing IR analysis, signal hydroxyl group derived from trehalose around 3325cm ^-1 is the signal of the carbonyl group derived from methacrylic group was observed at around 1715 cm ^-1. Further, as a result of ¹ HNMR analysis as a 10% dimethyl sulfoxide-d5 solution, signals of two types of ethylenic protons derived from methacrylic groups were observed in the vicinity of σ = 6.04 and σ = 5.67, σ = 3.8 to 4 A signal of two types of methylene protons adjacent to oxygen derived from a methacrylic group in the vicinity of 0.0, and a signal of a methyl proton derived from a methacrylic group around σ = 1.88, σ = 4.0 to 5.2 and σ = A trehalose-derived CH signal was observed in the vicinity of 3.0 to 3.8. Furthermore, as a result of mass spectrometry, M + 1 was 485. From these results, it was confirmed that the purified product was 1-MPTR.
The IR spectrum and ¹ H-NMR spectrum are shown in FIGS. 1 and 2, respectively.

<2-MPTR>
Trace using α-D-trehalose 12.5 g (0.04 mol), 12.5 g (0.09 mol) of glycidyl methacrylate represented by formula (6), and gas chromatograph, 2-MPTR was synthesized in the same manner as for 1-MPTR, except that stirring was performed until the peak ceased to decrease. As a result, 21.1 g of purified product (brown oily liquid), that is, the following formula:
The 2-MPTR represented by this was obtained.

It was confirmed by IR analysis, ¹ H-NMR analysis, and mass spectrometry that the obtained purified product was 2-MPTR.
Doing IR analysis, signal hydroxyl group derived from trehalose around 3311cm ^-1 is the signal of the carbonyl group derived from methacrylic group was observed at around 1715 cm ^-1. Further, as a result of ¹ HNMR analysis as a 10% dimethyl sulfoxide-d5 solution, signals of two types of ethylenic protons derived from methacrylic groups were observed at σ = 6.03 and σ = 5.67, σ = 3.8 to 4 A signal of two types of methylene protons adjacent to oxygen derived from a methacrylic group in the vicinity of 0.0, and a signal of a methyl proton derived from a methacrylic group around σ = 1.88, σ = 4.0 to 5.2 and σ = A trehalose-derived CH signal was observed in the vicinity of 3.0 to 3.8. Furthermore, M + 1 was 611 as a result of mass spectrometry. From these results, it was confirmed that the purified product was 2-MPTR.
IR spectrum and ¹ H-NMR spectrum are shown in FIGS. 3 and 4, respectively.

<1-MBTR>
50 g (0.15 mol) of α-D-trehalose, the following formula (7) instead of glycidyl methacrylate of formula (6);
1-MBTR was synthesized in the same manner as 1-MPTR, except that 10.6 g (0.07 mol) of the glycidyl group-containing unsaturated compound represented by formula (1) was added. As a result, 29.1 g of purified product (brown oily liquid), that is, the following formula:
1-MBTR represented by the following was obtained.

It was confirmed by IR analysis, ¹ H-NMR analysis, and mass spectrometry that the obtained purified product was 1-MBTR.
Doing IR analysis, signal hydroxyl group derived from trehalose around 3325cm ^-1 is the signal of the carbonyl group derived from methacrylic group was observed at around 1715 cm ^-1. Further, as a result of ¹ HNMR analysis as a 10% dimethyl sulfoxide-d5 solution, signals of two types of ethylenic protons derived from methacrylic groups were observed in the vicinity of σ = 6.04 and σ = 5.67, σ = 3.8 to 4 A signal of two types of methylene protons adjacent to oxygen derived from a methacrylic group in the vicinity of 0.0, and a signal of a methyl proton derived from a methacrylic group around σ = 1.88, σ = 4.0 to 5.2 and σ = A trehalose-derived CH signal was observed in the vicinity of 3.0 to 3.8. Furthermore, as a result of mass spectrometry, M + 1 was 495. From these results, it was confirmed that the purified product was 1-MBTR.

<1-MDTR>
50 g (0.15 mol) of α-D-trehalose, instead of glycidyl methacrylate of the formula (6), the following formula (8);
1-MDTR was synthesized in the same manner as for 1-MPTR, except that 18.8 g (0.07 mol) of the glycidyl group-containing unsaturated compound represented by formula (1) was added. As a result, 36.3 g of a purified product (brown oily liquid), that is, the following formula:
The 1-MDTR represented by these was obtained.

It was confirmed by IR analysis, ¹ H-NMR analysis, and mass spectrometry that the obtained purified product was 1-MDTR.
Doing IR analysis, signal hydroxyl group derived from trehalose around 3325cm ^-1 is the signal of the carbonyl group derived from methacrylic group was observed at around 1715 cm ^-1. Further, as a result of ¹ HNMR analysis as a 10% dimethyl sulfoxide-d5 solution, signals of two types of ethylenic protons derived from methacrylic groups were observed in the vicinity of σ = 6.04 and σ = 5.67, σ = 3.8 to 4 A signal of two types of methylene protons adjacent to oxygen derived from a methacrylic group in the vicinity of 0.0, and a signal of a methyl proton derived from a methacrylic group in the vicinity of σ = 1.88, σ = 4.0 to 5.2 and σ = A trehalose-derived CH signal was observed in the vicinity of 3.0 to 3.8. Furthermore, M + 1 was 611 as a result of mass spectrometry. From these results, it was confirmed that the purified product was 1-MDTR.

Example 1
The following formulation:
(A1) PM1 10.0g
(A2) 1-MPTR 10.0 g
(A3) Bis-GMA 12.0 g
3G 8.0g
(B) 7.6 g of water
(C) IPA 34.0 g
(D) CQ 0.5g
DMBE 0.5g
Each component was weighed in accordance with the above and stirred and mixed until a uniform solution was obtained, thereby preparing the dental adhesive composition of the present invention. Using this adhesive composition, initial adhesion strength and adhesion durability to enamel and dentin were tested. The composition of the adhesive composition is shown in Table 1, and the evaluation results are shown in Table 2.

(Example 2 to Example 14)
Adhesive compositions having different compositions were prepared according to the method of Example 1 and tested for initial adhesion and adhesion durability to enamel and dentin. The composition of the adhesive composition is shown in Table 1, and the evaluation results are shown in Table 2.

(Comparative Examples 1 to 8)
According to the method of Example 1, adhesive compositions having different compositions were prepared and tested for initial adhesion and adhesion durability to enamel and dentin. The composition of the adhesive composition is shown in Table 1, and the evaluation results are shown in Table 2.

In Examples 1 to 14, the results showed good initial adhesive strength and adhesion durability for enamel and dentin.
On the other hand, when Comparative Example 1 did not contain the trehalose derivative (A2), Comparative Example 2 did not contain the trehalose derivative (A2), but instead used as another polymerizable monomer (A3). When many polyfunctional polymerizable monomers are blended, the comparative example 3 is a conventional amphiphilic polymerizable monomer as the other polymerizable monomer (A3) instead of the trehalose derivative (A2). Comparative Example 4 is a case where F1 is further blended as an inorganic filler. In any case, since the demineralization power and penetrating power are insufficient, the initial adhesion strength and adhesion durability of enamel and dentin are greatly reduced.
Comparative Example 5 is a case where the acidic group-containing polymerizable monomer (A1) was not blended. Decalcification is not obtained, and the initial adhesive strength and adhesion durability to enamel and dentin are greatly reduced.
Comparative Example 6 is a case where water (B) was not blended. Decalcification is not obtained, and the initial adhesive strength and adhesion durability to enamel and dentin are greatly reduced.
Comparative Example 7 is a case where the water-soluble organic solvent (C) was not blended. The viscosity of the adhesive composition is increased, the decalcification and penetrability are insufficient, and the initial adhesive strength and adhesion durability to enamel and dentin are greatly reduced.
Comparative Example 8 is a case where the polymerization initiator (D) was not blended. Since it does not harden, initial adhesive strength and adhesion durability to enamel and dentin cannot be obtained.

Claims (4)

The following general formula (1);
Where
m is an integer from 1 to 8,
n is an integer from 0 to 9,
A is a trehalose residue obtained by removing m hydroxyl groups from trehalose,
Each R is independently a hydrogen atom or a methyl group,
A trehalose derivative represented by:   The trehalose derivative according to claim 1, wherein m is 1 or 2 in the general formula (1).   A polymerizable monomer component (A) comprising an acidic group-containing polymerizable monomer (A1) having an acidic group in the molecule and the trehalose derivative (A2) according to claim 1 or 2, water (B), And a dental adhesive composition comprising a water-soluble organic solvent (C).   The dental adhesive composition according to claim 3, further comprising a polymerization initiator (D).