Hydrolysis stable self-etching, self-priming adhesive

The present invention relates to a dental adhesive composition for adhering a dental restorative to dentin and / or enamel. More specifically, the present invention provides a one-part self-etching, self-priming dental adhesive composition comprising polymerizable acidic adhesive monomers that are stable to hydrolysis.

In US Pat. No. 4,539,382, Omura et al. Disclose a two-part adhesive. In CA2250333 (DE19746708 and EP0909761) Moszner et al. Disclose monomers that are stable to hydrolysis. In DE19918974 Loehden et al. Disclose polymerizable phosphonic acid esters. In DD273846 Haberland discloses polymerizable phosphonic acid amides. The two-part self-etching, self-priming dental adhesive system mixes the two parts and then applies them continuously or in one step. Both methods have inherent disadvantages due to clinical complications (saliva or blood contamination) that can occur between successive steps, or due to dosage issues when mixing is required prior to application of the self-etching adhesive. are doing. To overcome these clinical problems, it would be advantageous to provide self-etching adhesives as a one-part system that eliminates the need for continuous application or premixing.<patcit num="1"><text>U.S. Pat. No. 4,539,382</text></patcit><patcit num="2"><text>CA2250333</text></patcit><patcit num="3"><text>DE19746708</text></patcit><patcit num="4"><text>EP0909761</text></patcit><patcit num="5"><text>DE19918974</text></patcit><patcit num="6"><text>DD273846</text></patcit>

<p> The present invention relates to a one-part self-etching, self-priming dental adhesive that is stable to hydrolysis. The hydrolysis-stable one-part self-etching, self-priming dental adhesives of the present invention are preferably: (i) Hydrolyzable polymerizable compounds containing at least one inorganic acidic moiety, (ii) Polymerizable monomer stable for hydrolysis, (iii) Water-soluble organic solvent and / or water, (iv) Organic and / or inorganic acids, and (v) Polymerization initiators, inhibitors and stabilizers, including.</p><p> The hydrolyzable polymerizable compound having at least one inorganic acidic moiety can be selected from the group consisting of amines, thioethers, amides, urethanes, thiourethanes, ureas or thioureas. One-part self-etching, which is stable to hydrolyze organic and / or inorganic acids such as methacrylic acid, acrylic acid, fumaric acid, maleic acid, citric acid, itaconic acid, to increase their respective effects and adhesiveness. Can be added to self-priming dental adhesives. Preferred water-soluble organic solvents can be selected from the group consisting of alcohols and ketones such as ethanol, propanol, butanol, acetone, methyl ethyl ketone and the like.</p><p> In a preferred embodiment of the invention, hydrolysis-stable polymerizable compounds containing at least one inorganic acidic moiety are (meth) acrylamides. Most preferably, the hydrolyzable polymerizable compound containing at least one inorganic acidic moiety comprises at least one phosphonic acid moiety or sulfonic acid moiety.</p><p> Preferred polymerizable (meth) acrylamides containing at least one phosphonic acid moiety or sulfonic acid moiety for use in the hydrolysis-stable one-part self-etching, self-priming dental adhesive compositions of the present invention are: Expression:<chemistry num="13"><img file="JP4664591B2_D0001.tif" /></chemistry>Is within the range of During the ceremony R₁And R₂Independently hydrogen or substituted or unsubstituted C₁From C₁₈Alkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted C₅From C₁₈Alilen or heteroarylene, substituted or unsubstituted C₅From C₁₈Alkyl arylene or alkyl heteroarylene, substituted or unsubstituted C₇From C₃₀It is an alkylene allylene and R₃And R₄Independently, bifunctional or unsubstituted C₁From C₁₈Alkylene, bifunctional substituted or unsubstituted cycloalkylene, bifunctional substituted or unsubstituted C₅From C₁₈Alilen or heteroarylene, bifunctional or unsubstituted C₅From C₁₈Alkyl arylene or alkyl heteroarylene, bifunctional or unsubstituted C₇From C₃₀It is an alkylene allylene and n is an integer.</p><p> Hydrolyzable one-part self-etching, self-priming dental adhesive compositions of the present invention are preferred for the use of (meth) acrylamides in the formula:<chemistry num="14"><img file="JP4664591B2_D0002.tif" /></chemistry>Includes bis and mono (meth) acrylamides within the range of.</p><p> The hydrolysis-stable one-part self-etching, self-priming dental adhesive composition of the present invention preferably has the following formula:<chemistry num="15"><img file="JP4664591B2_D0003.tif" /></chemistry>Contains polymerizable monomers that are stable to hydrolysis within the range of During the ceremony R₁And R₃Are independently H or substituted or unsubstituted C₁From C₁₈Alkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted C₅From C₁₈Alilen or heteroarylene, substituted or unsubstituted C₅From C₁₈Alkyl arylene or alkyl heteroarylene, substituted or unsubstituted C₇From C₃₀It is an alkylene allylene and R₂Is a bifunctional or unsubstituted C₁From C₁₈Alkylene, bifunctional substituted or unsubstituted cycloalkylene, bifunctional substituted or unsubstituted C₅From C₁₈Alilen or heteroarylene, bifunctional or unsubstituted C₅From C₁₈Alkyl arylene or alkyl heteroarylene, bifunctional or unsubstituted C₇From C₃₀It is an alkylene allylene and R₄Is a monofunctional or polyfunctional substituted or unsubstituted C₁From C₁₈Alkylene, monofunctional or polyfunctional substituted or unsubstituted cycloalkylene, monofunctional or polyfunctional substituted or unsubstituted C₅From C₁₈Alilen or heteroarylene, monofunctional or polyfunctional substituted or unsubstituted C₅From C₁₈Alkyl arylene or alkyl heteroarylene, monofunctional or polyfunctional substituted or unsubstituted C₇From C₃₀It is an alkylene allylene and n is an integer.</p><p> The compositions of the present invention preferably contain at least bis or poly (meth) acrylamide, polymerizable monoacrylamide, initiators, stabilizers, water and / or organic solvents. The polymerization initiator is preferably a heat initiator or a redox initiator, or the photoinitiator preferably used is camphorquinone. To stabilize the dental composition, it is necessary to stabilize the absorption of radicals such as hydroquinone monomethyl ether, 2,6-di-t-butyl-p-cresol, tetramethylpiperidin N-oxyl radical, and galvanoxyl radical. Agents can be mentioned.</p><p> The hydrolyzable one-part self-etching, self-priming dental adhesive compositions of the present invention are hydrolyzable polymerizable monomers from 5% to 95% by weight, and 0.01 to 30% by weight. It preferably contains an organic acid and / or an inorganic acid.</p>

The present invention provides an aqueous one-pack self-etching and self-priming dental adhesive composition having a maximum pH of 2. (i) Polymerizable N-substituted alkylacrylic acid amide monomers or acrylic acid amide monomers that optionally contain an inorganic acidic moiety selected from phosphonic acid moieties or sulfonic acid moieties, and (ii) Curing system, including.

One-pack composition means that the composition of the invention is contained in only one container that can be stored, allowing the composition to be applied without any mixing prior to application and without any special equipment. ..

Self-etching means that the dental adhesive composition of the present invention can be applied to teeth without pre-etching the enamel in another method step. To include such self-etching characteristics, the compositions of the present invention are aqueous and have a maximum pH of 2. Preferably, the pH is 2 or less, more preferably 1.5 or less, and most preferably about 1. Thus, etching of the enamel is advantageously achieved by the one-pack composition of the present invention. This allows the adhesion of adhesives prepared from said dental compositions having an adhesive strength of at least 8 MPa, preferably at least 10 MPa to enamel and / or dentin.

Self-priming means that the dental adhesive composition of the present invention can be applied to teeth without prior application of a primer.

The polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, has the following structural formula:<chemistry num="16"><img file="JP4664591B2_D0004.tif" /></chemistry>It is preferable to have one of During the ceremony R₁And R_1”If one of them is hydrogen in equation (F1), the other is not hydrogen; R₁, R_1”And R₃Independently hydrogen or substituted or unsubstituted C₁From C₁₈Alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted C₅From C₁₈Aryl or heteroaryl group, substituted or unsubstituted C₅From C₁₈Alkylaryl group or alkylheteroaryl group, substituted or unsubstituted C₇From C₃₀It is an Aralkill group and R₂Is a bifunctional or unsubstituted C₁From C₁₈Alkylene group, bifunctional substituted or unsubstituted cycloalkylene group, bifunctional substituted or unsubstituted C₅From C₁₈Aryl or heteroaryl group, bifunctional or unsubstituted C₅From C₁₈Alkylaryl or alkylheteroaryl groups, bifunctional or unsubstituted C₇From C₃₀It is an Aralkill group and R₄Is a monofunctional or polyfunctional substituted or unsubstituted C₁From C₁₈Carbon chain group, monofunctional or polyfunctional substituted or unsubstituted cycloalkyl group, monofunctional or polyfunctional substituted or unsubstituted C₅From C₁₈Aryl or heteroaryl group, monofunctional or polyfunctional substituted or unsubstituted C₅From C₁₈Alkylaryl group or alkylheteroaryl group, monofunctional or polyfunctional substituted or unsubstituted C₇From C₃₀It is an Aralkill group and n is preferably an integer of 1 to 10, more preferably 3 to 4.

R₁, R_1”, R₂, R₃And R₄Substituents on the groups represented by₁From C₁₈It is preferably selected from alkyl groups. Especially preferred is C₁From C₆It is an alkyl group, with a methyl group being particularly preferred.

R₂And R₄Are independently bifunctional or polyfunctional substituted or unsubstituted C having at least one bond of ether, thioether, ester, thiocarbonyl, amide, carbonyl, sulfonyl, urethane, or substituted or unsubstituted amine bond.₁From C₁₈It is preferably a carbon chain group or a bifunctional or polyfunctional substituted or unsubstituted cycloalkylene group.

C₁From C₁₈A carbon chain group means a branched chain or straight chain hydrocarbon having at least two bonds or valences and 1 to 18 carbon atoms. For only one carbon atom, C₁Carbon chain groups can have 2 to 4 bonds or valences and 2 to 0 hydrogen substituents, ie C₁The carbon chain group has the following structural formula:<chemistry num="17"><img file="JP4664591B2_D0005.tif" /></chemistry>Can have one of

R₂Or R₄Is-(CH₂)₂-O- (CH₂)₂-O- (CH₂)₂-、<chemistry num="18"><img file="JP4664591B2_D0006.tif" /></chemistry>Is particularly preferable n is 2.

In a preferred embodiment of the invention, the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer optionally containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety has the following formula:<chemistry num="19"><img file="JP4664591B2_D0007.tif" /></chemistry>Selected from the group consisting of compounds represented by During the ceremony n is an integer from 2 to 6; x, y and z are independently integers from 1 to 10; Z is H or C₁From C₁₈It is an alkyl group. The formula with x, y, z is a mixture of compounds. Particularly preferred is a mixture with x + y + z of 5.3.

In a preferred embodiment of the invention, the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer optionally containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety is a (meth) acrylamide monomer. Classes, preferably secondary amides, are selected because they are particularly stable to hydrolysis.

In a preferred embodiment of the invention, the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, is at least such. It contains one inorganic acidic moiety, preferably a phosphonic acid moiety or a sulfonic acid moiety. Preferably, the above R₁, R_1”, R₂, R₃And R₄The group represented by can be replaced by a group containing at least one inorganic acidic moiety, preferably a phosphonic acid moiety or a sulfonic acid moiety. R₂And R₄However, it is particularly preferable to contain such an inorganic acidic moiety. Thus, it is not necessary to incorporate another acid into the composition of the invention to obtain a maximum pH of 2. Further, the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing an inorganic acidic moiety selected from the phosphonic acid moiety or the sulfonic acid moiety, in some cases, contains at least one acidic moiety as described below. It can be represented by the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer contained.

However, in the compositions of the present invention, the organic acids are selected from the group consisting of methacrylic acid, acrylic acid, fumaric acid, maleic acid, citric acid, itaconic acid, and formic acid, and the inorganic acids are phosphoric acid, sulfuric acid and fluorine. It can include organic or inorganic acids selected from hydrophosphite. Acid incorporation is when the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, which in some cases contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, does not contain an acidic moiety. is necessary.

However, in a further embodiment of the invention, the compositions of the invention are: It further comprises a polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (iii) containing at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety.

A polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing at least one inorganic acidic moiety has the following formula:<chemistry num="20"><img file="JP4664591B2_D0008.tif" /></chemistry>It is preferably selected from the group consisting of the compounds represented by During the ceremony R_1’And R_2’Are independent of each other, hydrogen atoms or substituted or unsubstituted C₁From C₁₈Alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted C₅From C₁₈Aryl or heteroaryl group, substituted or unsubstituted C₅From C₁₈Alkylaryl group or alkylheteroaryl group, substituted or unsubstituted C₇From C₃₀Represents an aralkyl group R_3’And R_4’Are bifunctionally substituted or unsubstituted C, independent of each other₁From C₁₈Carbon chain group, bifunctional substituted or unsubstituted cycloalkylene group, bifunctional substituted or unsubstituted C₅From C₁₈Aryl or heteroaryl group, bifunctional or unsubstituted C₅From C₁₈Alkylaryl or alkylheteroaryl groups, bifunctional or unsubstituted C₇From C₃₀Represents an aralkyl group R_5’Is H or substituted or unsubstituted C₁From C₁₈Represents an alkyl group n is preferably an integer from 1 to 18 or 1 to 4, and m is preferably an integer from 1 to 3.

R_1’, R_2’, R_3’, R_4’And R_5’The group that is optionally substituted for the group represented by is C₁From C₁₈It is preferably selected from alkyl groups. C₁From C₆Alkyl groups are particularly preferred, and methyl groups are most preferred. C₁From C₁₈The carbon chain groups are as defined above.

R_3’And R_4’Are bifunctionally substituted or unsubstituted C, independent of each other₁From C₁₈It is a carbon chain group or a bifunctional substituted or unsubstituted cycloalkylene group and has at least one bond of an ether, a thioether, an ester, a thiocarbonyl, an amide, a carbonyl, a sulfonyl, a urethane, or a substituted or unsubstituted amine bond.

More preferably R_3’Is-(CH₂)₂-Or<chemistry num="21"><img file="JP4664591B2_D0009.tif" /></chemistry>And R_4’Is-(CH₂)₂-O- (CH₂)₂-O- (CH₂)₂-.

In a preferred embodiment of the present invention, the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing at least one inorganic acidic moiety has the following formula:<chemistry num="22"><img file="JP4664591B2_D0010.tif" /></chemistry>Selected from one of the monomers according to.

In a particularly preferred embodiment of the invention, the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing at least one inorganic acidic moiety is a type of (meth) acrylamide monomer, preferably a secondary amide. , More preferably, acrylamide monomers of the secondary amide type are selected from these because they are particularly stable to hydrolysis.

In a particularly preferred embodiment of the invention, the organic or inorganic acids are not incorporated into the compositions of the invention and / or optionally contain an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety. When the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (i) does not contain an acidic moiety, the polymerization contains at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety. It is preferred that the sex N-substituted alkyl acrylate amide monomer or acrylate amide monomer (iii) be incorporated into the compositions of the present invention. However, said polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (iii) containing at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, the latter is also an organic acid or an inorganic acid. Either the polymerizable N-substituted alkyl acrylate amide monomer or the acrylate amide monomer (i) containing an inorganic acidic moiety selected from a phosphonic acid moiety containing an acid or an acidic moiety or a sulfonic acid moiety in some cases. When contained, it can be incorporated into the composition of the present invention. Further, the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety containing an inorganic acid and / or an organic acid and an acidic moiety. The polymerizable N-substituted alkylacrylic acid amide monomer containing at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety when both of the monomers (i) are incorporated into the compositions of the invention. Alternatively, the acrylate amide monomer (iii) can also be incorporated into the compositions of the present invention.

The compositions of the present invention are preferably stable to hydrolysis at a storage temperature of 50 ° C. for at least 1 week, from such adhesive compositions to enamel and / or dentin after such storage. The adhesive strength of the prepared adhesive is at least 8 MPa, preferably at least 10 MPa.

In addition to water, the aqueous composition of the present invention contains a water-soluble organic solvent preferably selected from alcohols and ketones.

The water-soluble organic solvent is preferably selected from ethanol, propanol, butanol, acetone and methyl ethyl ketone.

A polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer optionally containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety (i) is stable to hydrolysis by the following tests. Is preferable, i.e.

1.5 mmol of polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (i), and if the monomer does not contain an acidic moiety, 1 equivalent of ethane sulfone per alkyl acrylamide group or acrylamide group. The acid is dissolved in a 5 g solvent mixture consisting of 50 wt% ethanol and 50 wt% water to give a mixture, which is stored in a closed vial in an oven at 50 ° C;

After storage in this way for 2 weeks, hydrolysis of the test monomer is less than 50% of the absolute amount of alkylacrylic acid or acrylic acid formed by hydrolysis of the test monomer by HPLC analysis.

A polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (iii) containing at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety is hydrolyzable by the following tests. That is, A polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer (iii) containing at least one inorganic acidic moiety selected from 1.5 mmol phosphonic acid moieties or sulfonic acid moieties, 50 wt% ethanol and 50%. Dissolve in a 5 g solvent mixture consisting of% by weight of water to give the mixture and store the mixture in a closed vial in an oven at 50 ° C; After storage in this way for 2 weeks, hydrolysis of the test polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer is performed by HPLC analysis of the test polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer. Less than 50% of the absolute amount of alkylacrylic acid or acrylic acid formed by hydrolysis.

In a more preferred embodiment of the invention, the monomer (s) is stable to hydrolysis by the above test, and after storage for 1 week, the hydrolysis of the test monomer is hydrolyzed by HPLC analysis. Less than 10% of the absolute amount of alkylacrylic acid or acrylic acid formed by hydrolysis.

Both of the above-mentioned monomers (i) and (iii) are particularly stable to hydrolysis by the above test when both of the monomers (i) and (iii) are present in the composition of the present invention. preferable. However, if both the monomers (i) and (iii) are present, it is also possible that only one of the monomers (i) and (iii) is stable to hydrolysis by the above test. ..

Contains a polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, optionally containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, and / or at least one inorganic acidic moiety of the invention. The polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer is stable to hydrolysis according to the above test, but hydrolysis can occur to a small extent. Thus, a polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, optionally containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, and / or at least one inorganic acidic moiety of the invention. The polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing the above preferably contains at least two polymerizable groups. That is, when one amide bond is hydrolyzed, the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing at least two polymerizable groups is at least one polymerization that allows polymerization. It still contains sex groups. In this way, a high degree of adhesion to enamel and / or dentin is achieved. At least two polymerizable groups can be attached directly or indirectly. They are preferably bound by an amide bond that increases the stability of the composition and the adhesive strength of the adhesive composition to the enamel or dentin.

The composition of the present invention may further contain a nanofiller. In a more preferred embodiment of the invention, the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing at least one inorganic acidic moiety contains at least two inorganic acidic moieties.

The curing system in the composition of the present invention preferably contains a polymerization initiator, inhibitor or stabilizer, and the curable system is preferably a photocurable system. In a further embodiment of the invention (a) Polymerizable N-substituted alkyl acrylate amide monomers or acrylate amide monomers having at least two polymerizable moieties, (b) Polymerizable N-substituted alkyl acrylate amide monomers or acrylate amide monomers containing at least one inorganic acidic moiety, and (c) Curing system, Aqueous one-pack self-etching and self-priming dental adhesive compositions comprising.

The polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer having at least two polymerizable moieties (a) has the following formula:<chemistry num="23"><img file="JP4664591B2_D0011.tif" /></chemistry>It is preferably selected from the group consisting of the compounds represented by During the ceremony R₁, R_1”, R₂, R₃And R₄And n are as defined in claims 14-16.

In a particularly preferred embodiment, the polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer having at least two polymerizable moieties (a) has the following formula:<chemistry num="24"><img file="JP4664591B2_D0012.tif" /></chemistry>Selected from the group consisting of compounds represented by During the ceremony Z is H or substituted or unsubstituted C₁From C₁₈It is an alkyl group, and n, x, y, z are as defined in claim 17. In particular, since it is stable to hydrolysis, it is particularly preferable to select from the types of (meth) acrylamide monomers, preferably secondary amides.

In a further embodiment of the invention (I) The polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety. (II) Polymerizable N-substituted alkyl acrylate amide monomers or acrylate amide monomers containing at least one inorganic acidic moiety, and (III) Curing system, Aqueous one-pack self-etching and self-priming dental adhesive compositions comprising.

It is particularly preferred that the polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer (II) containing at least one inorganic acidic moiety contains at least two inorganic acidic moieties.

The polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer (II) containing at least one inorganic acidic moiety has a phosphonic acid moiety (s) or a sulfonic acid moiety (s). Expression:<chemistry num="25"><img file="JP4664591B2_D0013.tif" /></chemistry>It is preferably selected from the group consisting of the compounds represented by During the ceremony R_1’, R_2’, R_3’, R_4’, R_5’, N and m are as defined above.

The polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing at least one inorganic acidic moiety is a type of (meth) acrylamide monomers, preferably secondary amides, more preferably secondary amides. It is preferable to select from a class of acrylamide monomers because they are particularly stable to hydrolysis.

Any composition according to the invention is preferably packed in a light-shielded container.

According to the present invention, a polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety, and a polymerization containing an inorganic acidic moiety. The sex N-substituted alkyl acrylate amide monomer or acrylate amide monomer is (i) The polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety. (ii) The polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing at least one inorganic acidic moiety, and (iii) Curing system, It is useful for the preparation of water-based one-pack self-etching and self-priming dental adhesive compositions containing.

The method for preparing an aqueous one-pack self-etching and self-priming dental adhesive composition according to the present invention (A) A polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer, which optionally contains an inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety. (B) Curing system and (C) Water-containing solvent, Is characterized by mixing.

The novel dental adhesive can be obtained by polymerizing any one of the above compositions of the present invention.

The present invention provides a method of treating human or animal teeth, which comprises the application of one of the above compositions.

Furthermore, the present invention provides a kit containing one of the above compositions and instructions for use.

In addition, novel monomers are provided in the present invention. It has the following formula:<chemistry num="26"><img file="JP4664591B2_D0014.tif" /></chemistry>A polymerizable N-substituted alkyl acrylate amide monomer or acrylate amide monomer having at least two polymerizable moieties selected from the group consisting of the compounds represented by. During the ceremony R₁, R_1”, R₂, R₃, R₄And n are those of claims 14 to 16 as defined above.

The method for preparing the novel monomer is to use a diamine or polyamine compound as R.₃Is that of claim 14 as defined above and the formula CH where Hal is a halide.₂= CR₃-CO-Hal in some cases involves reacting with the substituted acryloyl halide.

The halide means chlorine, bromine, fluorine or iodine, preferably chlorine and bromine.

Furthermore, the present invention provides a novel monomer having an acidic inorganic moiety. It is a polymerizable N-substituted alkylacrylic acid amide monomer or acrylic acid amide monomer containing at least one inorganic acidic moiety selected from a phosphonic acid moiety or a sulfonic acid moiety and has the following formula:<chemistry num="27"><img file="JP4664591B2_D0015.tif" /></chemistry>Selected from the group consisting of compounds represented by During the ceremony R_1’, R_2’, R_3’, R_4’, R_5’, N and m are as defined above.

A method for preparing a novel monomer having at least one inorganic acidic moiety is (1) Reacting a diamine or polyamine compound with a vinyl phosphonate or a vinyl sulfonate; (2) R_1’Is as defined in claim 19 and the formula CH where Hal is a halide.₂= CR_1’-Reacting with CO-Hal halogenated alkyl acryloyl or halogenated acryloyl; (3) When the vinyl phosphonate is reacted in step (1), the product obtained in (2) may be reacted with trialkylhalokanesilane; (4) Hydrolyzing the product obtained in step (2) or (3), including.

The following formula:<chemistry num="28"><img file="JP4664591B2_D0016.tif" /></chemistry>The monomer represented by is particularly preferred, and R in the formula_1’, R_2’And R_3’Is as defined above.

The preparation method is (1) R₁Is as defined above and the formula CH where H is a halide₂= CR₁-CO-Hal halogenated alkyl acryloyl or halogenated acryloyl, N-hydroxysuccinimide and formula HO- (CH) where n is an integer from 1 to 18.₂)_n-NH₂To react with amino alcohols; (2) Reacting the product or methacryloylamide obtained in (1) with sodium hydride and propane sulfone; (3) Hydrolyzing the product obtained in step (2), including.

Here, the present invention will be described in more detail with reference to the following examples, tests and application examples.

N- (3-sulfopropyl) -methacrylamide (1) and N, N-bis (3-sulfopropyl) -methacrylamide<chemistry num="29"><img file="JP4664591B2_D0017.tif" /></chemistry>3.38 g (140.9 mmol) sodium hydride was carefully added dropwise to a stirred solution of 12 g (140.9 mmol) methacrylamide in 400 ml methylene chloride at a temperature of 0 ° C. The suspension was stirred at room temperature for 3 hours, then 18.943 g (155 mmol) of 1,3-propanesulfone was added. After stirring at room temperature for 12 days, 150 ml of water was carefully added dropwise to the reaction mixture while maintaining the temperature at 0 ° C. The aqueous phase was then separated and extracted 5 times with 100 ml methylene chloride. The water was then distilled off with a rotary evaporator and the resulting white solid was completely washed with acetone. The sodium sulfonic acid salt was re-dissolved in water and poured into an ion exchange column (Merck ion exchanger I). The resulting acidic aqueous solution was stabilized with 0.025 mol% hydroquinone and concentrated on a rotary evaporator. High decompression of water (8 × 10^-3By distillation (millibar), a mixture of N- (3-sulfopropyl) -methacrylamide 1 and N, N'-bis (3-sulfopropyl) -methacrylamide in a ratio of 2.6: 1 (NMR spectroscopy) was prepared. Obtained as a clear red highly viscous oil in an amount of 16.33 g (35% yield for N- (3-sulfopropyl) -methacrylamide 1).¹H-NMR (250MHz, d₆-DMSO, ppm) N- (3-sulfopropyl) -methacrylamide: 1.70 to 1.90 (m, 2H, CH₂-CH₂-CH₂), 1.84 (t, 3H, CH₃), 2.57 ~ 2.73 (m, 2H, CH₂-SO₃H), 3.36 ~ 3.47 (m, 2H, N-CH₂), 5.31 (s, 1H, CH =), 5.65 (s, 1H, CH =), 8.07 (t, 1H, NH).¹³C-NMR (63MHz, d₆-DMSO, ppm) N- (3-sulfopropyl) -methacrylamide: 19.17 (CH)₃), 25.31 (-CH₂), 38.58 (N-CH)₂), 49.78 (CH₂-SO₃H), 119.76 (CH)₂=), 140.35 (= C-CH₃), 168.18 (C = O).

N- (6-Hydroxyhexyl) -methacrylamide (2) A 20 ml chloroform solution of 22.56 g (0.215 mol) methacryloyl chloride was gradually added dropwise to a stirred solution of 24.84 g (0.215 mol) N-hydroxysuccinimide in 50 ml triethielamine and 500 ml chloroform at a temperature of 0 ° C. After stirring the solution at room temperature for 3 hours, 21.07 g (0.179 mol) 6-amino-1-hexanol in 20 ml chloroform was added. The reaction mixture was stirred at room temperature overnight and the solvent was evaporated under reduced pressure. The residue was taken in methylene chloride and the remaining solids were filtered off. The solution was then concentrated and the precipitate was filtered off again. The solution was then washed twice with 200 ml aqueous sodium hydroxide solution (20%). The combined aqueous layers were washed 4 times with 100 ml methylene chloride and the combined organic solutions were then dried over magnesium sulfate. Yellow oil was obtained as a crude product by filtration and solvent evaporation, which was stabilized at 0.025 mol% BHT. High vacuum distillation (140 ~ 143 ° C, 4 × 10^-3Miribar) gave compound 2 as a colorless, low-viscosity oil stabilized by the addition of 0.025 mol% BHT in an amount of 24.18 g (yield: 75%). IR (film, cm^-1) 3118 (s, b), 2930 (s), 2860 (m), 1655 (s), 1611 (s), 1534 (s), 1448 (m), 1374 (w), 1318 (w), 1218 ( m), 1051 (s), 925 (m).¹H-NMR (250MHz, CDCl₃, Ppm) 1.11 ~ 1.14 (m, 4H, CH₂), 1.29 ~ 1.1.35 (m, 4H, CH₂), 1.72 (s, 3H, = C-CH₃), 3.04 (q, 2H, CH₂-N), 3.35 (t, 2H, CH₂-O), 4.23 (bs, 1H, OH), 5.09 (s, 1H, CH =), 5.49 (s, 1H, CH =), 6.91 (t, 1H, NH).¹³C-NMR (63MHz, CDCl₃, Ppm) 18.16 (CH₃), 24.91, 26.15, 28.85, 31.94, 39.11 (CH)₂), 61.50 (CH₂-O), 119.08 (CH)₂=), 139.30 (= C-CH₃), 168.54 (C = O).

N- [9- (diethoxyphosphoryl) -7-oxa-nonyl] methacrylamide (3) To a 250 ml methylene chloride solution of 11.63 g (62.8 mmol) N- (6-hydroxyhexyl) -methacrylamide 2, 1.5 g (62.8 mmol) sodium hydride was added dropwise at a temperature of 0 ° C. After stirring at room temperature for 1 hour, 10.30 g (62.80 mmol) of diethyl vinyl phosphonate was added. The reaction mixture was stirred for a further 4 days and the reaction was terminated by the addition of 200 ml of water. The layers were separated and the organic layer was washed again with 100 ml of water. The organic layer was dried over magnesium sulfate and filtered. Evaporation of solvent by rotary evaporator under reduced pressure, and high vacuum (8 × 10) at 40 ° C until weight is constant^-3Millibar) drying gave 19.13 g (yield: 87%) of yellow oil stabilized at 0.025 mol% BHT. IR (film, cm^-1) 3327 (m), 2932 (m), 2863 (m), 1658 (m), 1617 (m), 1525 (m), 1447 (m), 1373 (m), 1310 (w), 1222 (s) , 1105 (s), 1025 (s), 957 (s), 792 (s).¹H-NMR (250MHz, CDCl₃, Ppm) 1.06 (t, 6H, CH₃), 1.01 ~ 1.17 (m, 4H, CH₂), 1.23 ~ 1.37 (m, 4H, CH₂), 1.68 (s, 3H, = C-CH₃), 1.75 ~ 1.88 (m, 2H, CH₂-P), 3.02 (q, 2H, CH₂-N), 3.15 (t, 2H, CH₂-O), 3.33 ~ 3.44 (m, 2H, CH₂-O), 3.82 (quin, 4H, CH₂-OP), 5.02 (s, 1H, CH =), 5.44 (s, 1H, CH =), 6.64 (t, 1H, NH).¹³C-NMR (63MHz, CDCl₃, Ppm) 15.57 and 15.67 (d, POCH)₂CH₃), 18.01, 25.04, 26.00 and 27.22 (d, CH)₂-P), 28.70, 38.77, 60.68 and 60.79 (d, POCH)₂CH₃), 63.66 (CH₃-O), 70.00 (CH₂-O), 118.10 (CH₂=), 139.56 (= C-CH₃), 167.82 (C = O).

N- [9- (dihydroxyphosphoryl) -7-oxa-nonyl] methacrylamide (4)<chemistry num="30"><img file="JP4664591B2_D0018.tif" /></chemistry> To a 100 ml methylene chloride solution of 18.57 g (53.1 mmol) N- [9- (diethoxyphosphoryl) -7-oxa-nonyl] methacrylamide 3, 22.06 g (144.1 mmol) trimethylsilyl bromide was added dropwise at room temperature. .. The mixture was refluxed for 4 hours, then the solvent was evaporated on a rotary evaporator and the residue was dissolved again in 200 ml methanol. After stirring this solution at room temperature for 2 hours, the solvent was distilled off to obtain a brown oil as a crude product. The substance was dissolved in 200 ml methylene chloride and extracted once with an aqueous solution of 4.1 g sodium hydroxide in 120 ml water. The aqueous layer was separated, washed 4 times with 100 ml methylene chloride, and then poured into an acidic ion exchange column (Merck ion exchanger I). The resulting acidic aqueous solution was concentrated on a rotary evaporator and extracted 3 times with 100 ml methylene chloride. After adding 0.025 mol% BHT, the aqueous layer is concentrated on a rotary evaporator and then highly depressurized at 40 ° C (3 × 10) until weight is constant.^-3Millibar) dried. This gave 11.24 g (yield: 72%) of clear brown oil. IR (film, cm^-1) 3317 (b, m), 2931 (m), 2862 (m), 1648 (w), 1545 (b, s), 1446 (m), 1373 (m), 1096 (s), 997 (s), 926 (s), 781 (s), 714 (s).¹H-NMR (250MHz, d₆-DMSO, ppm) 1.14 ~ 1.30 (m, 4H, CH₂), 1.33 ~ 1.51 (m, 4H, CH₂), 1.81 (s, 3H, = C-CH₃), 1.75 ~ 1.95 (m, 2H, CH₂-P), 3.06 (q, 2H, CH₂-N), 3.31 (t, 2H, CH₂-O), 3.50 (q, 2H, CH₂-O), 5.26 (s, 1H, CH =), 5.60 (s, 1H, CH =), 7.91 (t, 1H, NH), 10.04 (bs, 2H, POH).¹³C-NMR (63MHz, d₆-DMSO, ppm) 18.82, 25.51 and 26.39 (d, CH)₂-P), 27.67, 29.19, 29.79, 38.88, 65.18 (CH)₂-O), 69.87 (CH)₂-O), 118.84 (CH₂=), 140.14 (= C-CH₃), 167.45 (C = O).

N- [2- (diethoxyphosphoryl) -ethyl] acrylamide (5) 8.09 g (44.7 mmol) of (2-aminoethyl) phosphonic acid diethyl ester in 150 ml of methylene chloride, 6.06 g (67 mmol) of acryloyl chloride in 30 ml of methylene chloride so that the temperature is kept at 0-5 ° C. And a 30 ml aqueous solution of 2.68 g (67 mmol) sodium hydroxide were added simultaneously with stirring. The mixture was then stirred at room temperature for an additional 2 hours. The reaction was terminated by the addition of 100 ml of water. Some sodium chloride was added to achieve layer separation. The organic phase was separated and the aqueous solution was extracted twice with 50 ml methylene chloride. Combined organic liquids 50 ml 1nHCl, 50 ml 1nLVDS₃, And washed with 50 ml of water. It was dried over magnesium sulfate and filtered and solvent evaporated to give a crude yellow oil. For final purification, silica gel column chromatography of this material was performed using ethyl acetate as the eluate (R)._f= 0.27). This gave 6.72 g (yield: 63%) of yellow oil stabilized by the addition of 0.025 mol% BHT. IR (film, cm^-1) 3274 (m), 2983 (m), 2937 (w), 1660 (m), 1544 (m), 1444 (m), 1310 (m), 1219 (s), 1021 (s), 954 (s) , 828 (m), 788 (m), 698 (m).¹H-NMR (250MHz, CDCl₃, Ppm) 1.14 (t, 6H, CH₃), 1.81 ~ 1.94 (m, 2H, CH₂-P), 3.31 ~ 3.45 (m, 2H, CH₂-N), 3.85 ~ 3.97 (m, 4H, CH₂-O), 5.40 ~ 5.44 (dd, 1H, CH = C-CO), 5.93 ~ 6.13 (m, 2H, CH = CH-CO), 7.32 (t, 1H, NH).¹³C-NMR (63MHz, CDCl₃, Ppm) 15.93 and 16.04 (d, POCH)₂CH₃), 23.96 and 26.17 (d, CH)₂-P), 33.26 (CH)₂-N), 61.39 and 61.50 (d, POCH)₂CH₃), 119.08 (C =), 139.30 (C =), 165.41 (C = O).

N- [2- (dihydroxyphosphoryl) -ethyl] acrylamide (6)<chemistry num="31"><img file="JP4664591B2_D0019.tif" /></chemistry> 8.86 g (56.32 mmol) trimethylsilyl bromide was added dropwise to 5.83 g (24.81 mmol) of N- [2- (diethoxyphosphoryl) -ethyl] methacrylamide 5 in a 30 ml methylene chloride solution at room temperature with stirring. The mixture was heated to reflux for 4 hours. Then, the solvent was distilled off by a rotary evaporator, and the residue was dissolved in methanol. The solution was stirred at room temperature for 16 hours. The solvent was then distilled off and the remaining oil was dissolved in 30 ml water. The aqueous solution was washed twice with 20 ml methylene chloride, stabilized by the addition of 0.025 mol% BHT, and concentrated under reduced pressure. Decompress this material at 40 ° C for 19 hours (8 × 10)^-3After drying (millibar), 4.385 g (yield: 98%) of highly viscous yellow oil was obtained. IR (film, cm^-1) 2812 (b, s), 2359 (m), 1649 (m), 1547 (s), 1444 (m), 1365 (m), 1121 (s), 927 (s), 793 (s), 713 ( s).¹H-NMR (250MHz, d₆-DMSO, ppm) 1.77 ~ 1.99 (m, 2H, CH₂-P), 3.25 ~ 3.44 (m, 2H, CH₂-N), 5.62 (dd, 1H, CH = C-CO), 6.07 ~ 6.32 (m, 2H, CH = CH-CO), 8.40 (t, 1H, NH).¹³C-NMR (63MHz, d₆-DMSO, ppm) 27.11 and 29.23 (d, CH)₂-P), 34.05 (CH)₂-N), 125.74 (C =), 131.89 (C =), 165.14 (C = O).

N- [2- (diethoxyphosphoryl) -ethyl] -N-butylamine (7) 30.04 g (0.411 mol) n-butylamine and 67.41 g (0.411 mol) diethyl vinyl phosphonate were stirred at 65 ° C. for 24 hours. As a result, 97.32 g (yield: 100%) of colorless oil was obtained. IR (film, cm^-1) 3411, 3390 (OH), 2973, 2929, 2885 (CH)₂/ CH₃), 1390 (CH₂/ CH₃), 1078cm^-1(OH).¹H-NMR (250MHz, CDCl₃, Ppm) 1.39 (t, 3H, CH₃), 1.79 ~ 2.20 (m, 10H, CH₂, OCH₂CH₃), 2.40 ~ 2.71 (m, 2H, CH₂-P), 3.02 ~ 3.29 (m, 2H, CH₂-N), 3.39 ~ 3.62 (m, 2H, CH₂-N), 4.57 ~ 4.84 (m, 4H, POCH₂)。¹³C-NMR (63MHz, CDCl₃, Ppm) 13.70 (C₃H₆-CH₃), 16.23 (OCH)₂-CH₃), 20.26, 25.18 and 27.36 (d, CH₂-P), 31.86, 43.14, 49.08, 61.35 (OCH)₂-CH₃)。

N- [2- (diethoxyphosphoryl) -ethyl] -N-butyl acrylamide (8) 55.27 g (0.233 mol) N- [2- (diethoxyphosphoryl) -ethyl] -N-butylamine 7 in 100 ml methylene chloride solution, 23.19 g (0.256 mol) so that the temperature is kept at 0-5 ° C. A 130 ml methylene chloride solution of acryloyl chloride and a 200 ml aqueous solution of 10.25 g (0.256 mol) sodium hydroxide were added simultaneously with stirring. The mixture was then stirred at room temperature for an additional 2 hours. The reaction was terminated by the addition of 100 ml of water. The organic layer was separated and the aqueous solution was extracted twice with 30 ml methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS₃, And washed with 150 ml of water. The product solution was stabilized with 0.025 mol% BHT and dried over sodium sulphate. 40.07 g (yield: 59%) of colorless oil was obtained by filtration and evaporation of the solvent. IR (film, cm^-1) 2978/2962/2956 (CH₃/ CH₂), 1648 (CO), 1614 (C = C), 1456/1431/1371 (CH)₃/ CH₂), 794 (C = C).¹H-NMR (250MHz, CDCl₃, Ppm) 0.79 (t, 3H, CH₃), 1.11 ~ 1.31 (m, 8H, CH₂, OCH₂CH₃), 1.33 ~ 1.54 (m, 2H, CH₂), 1.87 ~ 2.12 (m, 2H, CH₂-P), 3.12 ~ 3.32 (m, 2H, CH₂-N), 3.38 ~ 3.57 (m, 2H, CH₂-N), 3.88 ~ 4.17 (m, 4H, POCH₂), 5.50 ~ 5.67 (m, 1H, CH = C-CO), 6.13 ~ 6.30 (m, 1H, CH = C-CO), 6.33 ~ 6.52 (m, 1H, C = CH-CO).¹³C-NMR (63MHz, CDCl₃, Ppm) 13.41 (C₃H₆-CH₃), 16.02 and 16.11 (d, POCH)₂-CH₃), 19.57, 22.78 and 24.94 (d, CH)₂-P), 31.40, 41.35, 48.19, 61.35 and 61.45 (d, POCH)₂-CH₃), 127.16 (C =), 127.62 (= C), 165.72 (C = O).

N- [2- (dihydroxyphosphoryl) -ethyl] -N-butyl acrylamide (9)<chemistry num="32"><img file="JP4664591B2_D0020.tif" /></chemistry> 33.56 g (0.219 mol) of trimethylsilyl bromide was added dropwise to 31.93 g (0.11 mol) of N- [2- (diethoxyphosphoryl) -ethyl] methacrylamide 8 in 100 ml methylene chloride solution at room temperature with stirring. The mixture was heated to reflux for 4 hours. Then, the solvent was distilled off by a rotary evaporator, and the residue was dissolved in 100 ml of methanol. The solution was stirred at room temperature for 4 hours. The product solution was stabilized by the addition of 0.025 mol% BHT and concentrated under reduced pressure. Decompress the substance at 40 ° C for 24 hours (8 × 10)^-3After drying (millibar), 21.65 g (yield: 84%) of white solid was obtained. IR (ATR, cm^-1) 3411, 3390 (OH), 2973, 2929, 2885 (CH)₂/ CH₃), 1390 (CH₂/ CH₃), 1078cm^-1(OH).¹H-NMR (250MHz, d₆-DMSO, ppm) 0.97 (t, 3H, CH₃), 1.27 ~ 1.45 (m, 2H, CH₂), 1.47 ~ 1.66 (m, 2H, CH₂), 1.93 ~ 2.17 (m, 2H, CH₂-P), 3.35 ~ 3.52 (m, 2H, CH₂-N), 3.55 ~ 3.75 (m, 2H, CH₂-N), 5.69 ~ 5.83 (m, 1H, CH = C-CO), 6.24 (dd, 1H, CH = C-CO), 6.64 ~ 6.81 (m, 1H, C = CH-CO).¹³C-NMR (63MHz, d₆-DMSO, ppm) 14.2 (C₃H₆-CH₃), 21.2, 25.8 and 27.9 (d, CH₂-P), 30.8, 32.6, 43.8, 128.9 (C =), 129.1 (C =), 168.4 (C = O).

(2,2 (4), 4) -trimethylhexamethylenebis (acrylamide) (10)<chemistry num="33"><img file="JP4664591B2_D0021.tif" /></chemistry> In a 100 ml methylene chloride solution of 60 g (0.379 mol) of (2,2 (4), 4) -trimethylhexamethylenediamine, 72.05 g (0.796 mol) of acryloyl chloride so that the temperature is kept at 0-5 ° C. A 130 ml methylene chloride solution and a 200 ml aqueous solution of 31.84 g (0.796 mol) sodium hydroxide were added simultaneously with stirring. The mixture was then stirred at room temperature for an additional 2 hours. The reaction was terminated by the addition of 100 ml of water. The organic phase was separated and the aqueous solution was extracted twice with 30 ml methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS₃, And washed with 150 ml of water. The product solution was stabilized with 0.025 mol% BHT and dried over sodium sulphate. 87 g (yield: 86%) of colorless highly viscous oil was obtained by filtration and evaporation of the solvent. IR (film, cm^-1) 3411, 3278 (NH), 2957 (CH2 / CH3), 1656 (NHCO), 1546 (C = C), 1241 (CH2 / CH3), 984/956 (C = C), 703 (C = C).¹H-NMR (250MHz, CDCl₃, Ppm) 0.7 ~ 3.4 (several m, 18H, CH₃, CH₂), 5.51 ~ 5.60 (m, 1H, CH = C-CO), 6.16 ~ 6.26 (m, 2H, CH = CH-CO), 7.12, 6.84, 6.70, 6.59 (4 × t, 2H, NH).¹³C-NMR (63MHz, CDCl₃, Ppm) 20.80, 22.21, 25.36, 26.01, 26.75, 27.90, 28.02, 29.04, 30.73, 32.80, 35.00, 35.68, 37.21, 38.79, 40.51, 45.16, 46.02, 47.02, 48.70, 125.66 (C =), 131.08 (C =) =), 165.82 (C = O), 166.09 (C = O).

<chemistry num="34"><img file="JP4664591B2_D0022.tif" /></chemistry> JEFFAMINE T-403 Polyoxypropylene Triamine Tris (acrylamide) (11) In a 100 ml methylene chloride solution of 73.25 g (0.166 mol) of JEFFAMINE T-403 polyoxypropylene triamine (x + y + z = 5.3), 47.46 g (0.524 mol) so that the temperature is kept at 0-5 ° C. A 130 ml methylene chloride solution of acryloyl chloride and a 200 ml aqueous solution of 20.98 g (0.524 mol) sodium hydroxide were added simultaneously with stirring. The mixture was then stirred at room temperature for an additional 2 hours. The reaction was terminated by the addition of 300 ml of water. The organic phase was separated and the aqueous solution was extracted twice with 100 ml methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS₃, And washed with 150 ml of water. The product solution was stabilized with 0.025 mol% BHT and dried over sodium sulphate. Filtration and evaporation of the solvent gave 86.1 g (yield: 85%) of clear yellow highly viscous oil. IR (film, cm^-1) 3411, 3280 (OH), 2970, 2929, 2872 (CH₂/ CH₃), 1657/1622 (CONH), 1542 (C = C), 1406/1374 (CH)₂/ CH₃), 1101cm^-1(ROR).¹H-NMR (250MHz, CDCl₃, Ppm) 0.74 ~ 0.95 (t), 0.99 ~ 1.25 (m), 1.27 ~ 1.53 (m), 2.90 ~ 3.73 (m), 4.04 ~ 4.31 (bs), 5.49 ~ 5.73 (m, 1H, CH = C- CO), 5.90 ~ 6.43 (m, 2H, CH = CH-CO).¹³C-NMR (63MHz, CDCl₃, Ppm) 7.5 (CH₂-CH₃), 17.0 / 17.5 (CH-CH)₃), 22.9, 32.0, 45.1 / 45.2 (CN), 71.6 / 74.8 / 75.1 (CH)₂-O), 125.7 (C =), 131.1 (C =), 164.9 (C = O).

Exam 1 Inspection of hydrolysis stability of N-substituted alkyl acrylate amide monomer or acrylate amide monomer containing acidic moiety

Typical examples of N-substituted alkylacrylic acid amide monomers or acrylic acid amide monomers are N- [2- (dihydroxyphosphoryl) -ethyl] -N-butylacrylamide9, and dihydroxyphosphorylmethylmethacryl ester as a comparative example. The following conditions were met: 1.5 mmol of acrylic acid amide monomer was dissolved in 5 g of a mixture of 50 wt% ethanol and 50 wt% water. The solution was stored in a sealed vial at 50 ° C. The type and duration of hydrolysis was measured by HPLC.

After 1 week 50% of the ester and after 6 weeks 83% are hydrolyzed to methacrylic acid and hydroxymethylphosphonic acid, while acrylamide 9 is 0% acrylic acid after 1 week and 7.9% acrylic acid after 6 weeks. And hydrolysis to amines.

Exam 2 Inspection of hydrolysis stability of N-substituted acrylic acid amide monomers containing no acidic moiety N-Butylacrylamide as a model compound of the N-substituted acrylic acid amide monomer and n-butylacrylic ester as a comparative example were subjected to the following conditions: 1.5 mmol of acrylic acid amide monomer was dissolved in 5 g of a mixture of 50 wt% ethanol and 50 wt% water with 1.5 mmol of ethanesulfonic acid. The solution was stored in a sealed vial at 50 ° C. The type and duration of hydrolysis was measured by HPLC.

After 1 week, 62% of the ester is hydrolyzed to acrylic acid and butanol, while the acrylamide does not hydrolyze until 7 weeks.

Application example 1 281.85mg (2,2 (4), 4) -trimethylhexamethylenebis (acrylamide) (10), 416.85mg JEFFAMINE T-403 polyoxypropylene triaminetris (acrylamide) (11), 286.00mgN- [2- (dihydroxyphosphoryl) )-Ethyl] -N-Butylacrylamide (9), 17.70 mg bis (2,4,6-trimethylbenzol) -phenylphosphine oxide, 8.20 mg dimethylaminoethyl benzoate ethyl ester and 7.10 mg camphorquinone, 166.67 mg formic acid , 66.67 mg ethanol and 266.67 mg water dissolved in a solution.

Tooth preparation For adhesion, the enamel is ground with 500 grit silicon carbide paper so that there is a substantially flat area about 5 mm in diameter. The teeth are then rinsed with running water and used within 2 hours as described below.

Preparation of adhesive sample Gelatin capsules for testing (# 5 supplied by Torpac) are filled to two-thirds of their total length with spectral TPH and cured by placing the capsules in a light oven. Six teeth were prepared for testing.

Lightly dry the surface of the tooth to be glued with tissue paper or air blow for 5 seconds and apply the treatment solution using an applicator tip or brush. The material is in contact with the teeth for 20 seconds, air dried for 5 seconds and photocured for 10 seconds using a spectrum lamp 800. The remaining space of the prefilled gelatin capsule is then filled with spectral TPH and placed on the prepared enamel surface. The spectrum TPH is then cured by irradiating the periphery of the capsule at regular intervals for 20 seconds three times.

After 2 hours storage at 37 ° C, the adhesiveness to enamel is 10.5 ± 2.8 MPa. Adhesion of 10.7 ± 2.2 MPa to enamel was measured when the sample was prepared according to the above method and heat cycled 1800 times between 5 ° C and 55 ° C in each bath with a 20 second presence time. Was done.

Further Examples: Hydrolyzable N-substituted alkyl acrylate amide monomers and acrylate amide monomers that are stable to hydrolysis

N, N'-bismethacryloyl-N, N'-dibenzyl-5-oxanonanediamine-1,9 102.16 g (0.3 mol) of N, N'-dibenzyl-5-oxanonanediamine-1,9 in 300 ml methylene chloride in a 4-neck 1 l flask equipped with a stirrer, thermometer and two 50 ml drop funnels. Dissolved in. After cooling to 0-5 ° C, 65.854 g (0.63 mol) of methacryloyl chloride dissolved in 30 ml of methylene chloride and 25.20 g (0.63 mol) of NaOH dissolved in 60 ml of water, to a temperature of 0 to 5 ° C. Add at the same time with stirring over 1.5 hours to maintain. The mixture was then stirred at room temperature for an additional 2 hours. The reaction mixture was hydrolyzed with 600 ml of ice water. The organic phase was separated and the aqueous solution was extracted twice with methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS to the recovered organic liquid₃, And occasionally with 150 ml of deionized water, until the water showed a pH value of approximately 7. NaSO organic solution₄It was dried in. Then NaSO₄Was filtered off and 0.1346 g of 2,6-di-t-butyl-p-cresol was added to this solution. Methylene chloride was distilled off under reduced pressure at 40 ° C., and the bismethacrylamide was dried. Yield: 136.66g (95.6% of theoretical amount), n_D²⁰= 1.5383, η = 1.65Pa^*s C₃₀H₄₀N₂O₃, 476.65 IR: 2941 (CH₂/ CH₃), 3086/3062/3030, (Ar), 1647 (CONR), 1626 (CH)₂= CH-), 1119cm^-1(ROR).

N, N'-bis-acryloyl-N, N'-dibenzylethylenediamine 29.198 g (0.12 mol) of N, N'-dibenzylethylenediamine was dissolved in 100 ml methylene chloride in a 4-neck 1 l flask equipped with a stirrer, a thermometer and two 50 ml dropping funnels. After cooling to 0-5 ° C, add 21.991 g (0.24 mol) of acryloyl chloride dissolved in 30 ml methylene chloride and 9.718 g (0.24 mol) NaOH dissolved in 40 ml of water to a temperature of 0-5 ° C. Add at the same time with stirring over 1.5 hours to maintain. The mixture was then stirred at room temperature for an additional 2 hours. The reaction mixture was hydrolyzed with 600 ml of ice water. The organic phase was separated and the aqueous solution was extracted twice with methylene chloride. 100 ml of 1nHCl, 100 ml of 1nLVDS to the recovered organic liquid₃, And occasionally with 100 ml of deionized water, until the water showed a pH value of approximately 7. NaSO organic solution₄It was dried in. Then NaSO₄Was filtered off and 0.028 g of 2,6-di-t-butyl-p-cresol was added to this solution. Methylene chloride was distilled off under reduced pressure at 40 ° C., and the bismethacrylamide was dried. Yield: 27.9g (65.9% of theoretical amount), m_p= 75.5 ~ 76.6 ° C, Tg = -7.2 ° C, M_n(vpo) = 350g / mol C₂₂H₂₄N₂O₂, 348.45 Calculated value C75.83 H6.94 N8.04 Measured value C76.00 H7.26 N8.05

N, N'-bis-acryloyl-N, N'-dibenzyl-4,4'-diaminodicyclohexylamine 60.551 g (0.16 mol) of N, N'-dibenzyl-4,4'-diaminodicyclohexylamine in 150 ml methylene chloride in a four-necked 1 l flask equipped with a stirrer, thermometer and two 50 ml dropping funnels. Dissolved. After cooling to 0-5 ° C, add 28.061 g (0.31 mol) of acryloyl chloride dissolved in 30 ml methylene chloride and 12.401 g (0.31 mol) of NaOH dissolved in 50 ml of water to a temperature of 0-5 ° C. Add at the same time with stirring over 1.5 hours to maintain. The mixture was then stirred at room temperature for an additional 2 hours. The reaction mixture was hydrolyzed with 500 ml of ice water. The organic phase was separated and the aqueous solution was extracted twice with methylene chloride. 100 ml of 1nHCl, 100 ml of 1nLVDS to the recovered organic liquid₃, And occasionally with 10 ml of deionized water, until the water showed a pH value of approximately 7. NaSO organic solution₄It was dried in. Then NaSO₄Was filtered off and 0.077 g of 2,6-di-t-butyl-p-cresol was added to this solution. Methylene chloride was distilled off under reduced pressure at 40 ° C., and the bismethacrylamide was dried. Yield: 54.0 g (69.9% of theoretical amount), Tg = 47.1 ° C

3, (4), 8, (9) -bis (2-propene amide methyl) -tricyclo-5,2,1,0^2,6Decane 96.01 g (0.35 mol) of 3, (4), 8, (9) -bis (aminomethyl) -tricyclo-5, in a four-necked 1-l flask equipped with a stirrer, thermometer and two 50 ml dropping funnels. 2,1,0^2,6Decane was dissolved in 350 ml methylene chloride. After cooling to 0-5 ° C, add 76.54 g (0.735 mol) of methacryloyl chloride dissolved in 35 ml methylene chloride and 29.40 g (0.735 mol) of NaOH dissolved in 70 ml of water to a temperature of 0-5 ° C. Add at the same time with stirring over 1.5 hours to maintain. The mixture was then stirred at room temperature for an additional 2 hours. The reaction mixture was hydrolyzed with 600 ml of ice water. The organic phase was separated and the aqueous solution was extracted twice with methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS to the recovered organic liquid₃, And occasionally with 150 ml of deionized water, until the water showed a pH value of approximately 7. NaSO organic solution₄It was dried in. Then NaSO₄Was filtered off, and 0.1157 g of 2,6-di-t-butyl-p-cresol was added to this solution. Methylene chloride was distilled off under reduced pressure at 40 ° C., and the bismethacrylamide was dried. Yield: 106.02g (91.6% of theoretical amount) C₂₀H₃₀N₂O₂, 330.47 IR: 2941 (CH₂/ CH₃), 3330/1647 (CONHR), 1626 (CH)₂= CH-).

N, N'-bismethacryloyl-3,6-dioxaoctanediamine-1,8 59.28 g (0.4 mol) of 3,6-dioxaoctanediamine-1,8 was dissolved in 300 ml methylene chloride in a four-necked 1-l flask equipped with a stirrer, a thermometer and two 50 ml dropping funnels. After cooling to 0-5 ° C, 87.47 g (0.84 mol) of methacryloyl chloride dissolved in 40 ml of methylene chloride and 33.60 g (0.84 mol) of NaOH dissolved in 80 ml of water to bring the temperature to 0-5 ° C. Add at the same time with stirring over 1.5 hours to maintain. The mixture was then stirred at room temperature for an additional 2 hours. The reaction mixture was hydrolyzed with 600 ml of ice water. The organic phase was separated and the aqueous solution was extracted twice with methylene chloride. 150 ml of 1nHCl, 150 ml of 1nLVDS to the recovered organic liquid₃, And occasionally with 150 ml of deionized water, until the water showed a pH value of approximately 7. NaSO organic solution₄It was dried in. Then NaSO₄Was filtered off, and 0.1137 g of 2,6-di-t-butyl-p-cresol was added to this solution. Methylene chloride was distilled off under reduced pressure at 40 ° C., and the bismethacrylamide was dried. Yield: 95.20 g (83.7% of theoretical amount), n_D²⁰= 1.5042, η = 2.17Pa^*s C₁₄H₂₄N₂O₄, 284.35 IR: 2926/2870 (CH₂/ CH₃), 3336/1659 (CONHR), 1620 (CH)₂= CH-), 1130cm^-1(ROR).