WO1994000096A1

WO1994000096A1 - Dental adhesive primer composition and dentin conditioning primer composition

Info

Publication number: WO1994000096A1
Application number: PCT/US1993/005666
Authority: WO
Inventors: Masayoshi Tsunekawa
Original assignee: The Regents Of The University Of California
Priority date: 1992-06-23
Filing date: 1993-06-11
Publication date: 1994-01-06
Also published as: JPH06122608A

Abstract

A dental adhesive primer composition comprises a mixture of (a) polymerizable compound of general formula (I) wherein R?1 and R2¿ are each lower alkylene; (b) hydroxy-group bearing lower alkyl ester of methacrylic acid (hereafter referred to as 'hydroxy monomers'); (c) polymerization accelerator; and (d) solvent. Dentin conditioning primer composition comprising a salt of compound (I) and having pH value 2.4-6.0. A method for improving the infiltration and adhesion of a dental adhesive primer comprising the compound (I) relies on administering hydroxy monomers in said composition, prior to application thereof to a surface of tooth.

Description

DENTAL ADHESIVE PRIMER COMPOSITION AND DENTIN CONDITIONING PRIMER COMPOSITION

BACKGROUND OF THE INVENTION

1. Field of the Invention This invention relates to the field of polymerizable compositions. In addition, this invention relates to compositions for use as adhesive primers for the repair of teeth. It relates to adhesive primer compositions being used before an adhesive substitute, and more particularly concerns dental adhesive primer composition suitable for improvign the bond strenght of above mentioned adhesive substitute and prevents marginal microleakage along the cementum or dentinal cavosurface margins of restoration. This invention also relates to a dentin conditioning primer composition suitable for removal of the smear layer and improving the bond strength of adhesive substitute used therewith.

2. Description of the Background Art

In the field of restorative dentistry, polymerizable compositions which would remove the smear layer or improve the bond strength of adhesive substitute as adhesive primers have been long sought. In restoration, where the area of dental caries is removed and the cavity is formed, the smear layer comprised by microorganisms and shavings is formed in the exposed part of the dentin surface. The smear layer has been considered to be detrimental (Brannstrόm et al . (1973) J. Prosthet . Dent. 30:303-310) , because it results in a pool of microorganisms, interferes with the adhesion of a dental material to tooth structure, and influences microleakage. Failure in marginal seal or the lack of adhesion are principle causes leading to pulp hypersensitivity. It has also been associated with the development of secondary caries. The effectiveness of the acid-etch technique in reducing microleakage of restorations surrounded by enamel has been well documented, see Buonocore et al . (1986) Arch. Oral Biol. 13:61-70 and Welsh et al . (1985) J. Prosthet . Dent. 54:370-373.

Some commercially available polymerizable compositions have been utilized as dental adhesives. For example, there has been introduced in Japan a dental liner composition, under the name "Clearfil Bond System F" (hereinafter, "Clearfil") , utilizing a two part resin_ system. And J.E. Bunker has described polymerizable composition which are used as dentin and enamel adhesive, see U.S. Patent Nos. 4,482,505 and 4,540,722.

R.L. Bowen has described another means for obtaining adhesion to dentin, through the use of a multiple step procedure. He has developed a surface active compound, N-phenyl glycine, and pyromellitic dimethacrylate. Although the adhesion mechanism of these compounds is not defined, they could involve the formation of a chelate bond to calcium of tooth structure, see U.S. Patent No. 4,251,565. Takeyama et al . (1978) J. Japan. Soc. Den. Appar. Mat. 19:179-185, also developed an adhesive with chelating potential, 4-methacryloxyethyl trimellitate anhydride (herein after referred to "4-META") . Marginal microleakage, however, along the cementum or dentin continues to be problem. Thus, difficulty in adhering perfect marginal seal along cervical margins represents a treatment challenge in restorative dentistry. The development of excellent bonding system, particularly dental adhesive primer composition and dentin conditioning primer composition is therefore required for composite resins to minimize microleakage and to improve the clinical success of composite restorations.

OBJECT OF THE INVENTION

The object of the invention is to provide an effective dental adhesive primer composition for composite restorations suitable for improving bond strength of an adhesive substitute and prevents marginal microleakage of restorations. Another object of this invention is to provide an effective dentin conditioning primer composition suitable for removing the smear layer and improving the bond strength of the adhesive substitute used therewith. Other and further objects of this invention will become obvious upon an understanding of the illustrative embodiments about to be described or will be indicated in the appended claims, and various advantages not referred to herein will occur to one skilled in the art upon employment of the invention in practice.

SUMMARY OF THE INVENTION

The present invention provides in one aspect, a dental adhesive primer composition comprising a mixture of:

(a) polymerizable compound of the general formula:

[ I ] H₂C=C(CH₃)C00-R¹-00CH₂C CBjCOO-R'-OOC (CH₃) C=CH₂

\ /

N-R²-N / \

H00CH₂C CH₂C00H

wherein R¹ and R² are each lower alkylene (hereafter referred to as compound [I] )

(b) hydroxy-group bearing lower alkyl ester of methacrylic acid (hereafter referred to as "hydroxy monomers" ) ,

(c) polymerization accelerator, and

(d) solvent.

The present invention in another aspect, provides dentin conditioning primer composition comprising a salt of compound [I] and having pH value 2.4-6.0.

The present invention also provides a method for improving the infiltration and adhesion of a dental adhesive primer comprising the compound [I] by administration of hydroxy monomers in said composition, prior to application thereof to a surface of tooth.

Said dental adhesive primers can be applied directly to dentin, and a dental bonding agent is then applied to the dental adhesive primer-treated surface of tooth, and if desired, a dental device is applied thereto. Then the bonding agent is cured and restoration of teeth is completed.

DESCRIPTION OF THE PREFERRED EMBODIMENT The present inventor has made a study from various aspects on a dental adhesive primer that can be used effectively to each of the above-mentioned application uses. Then it has been found that a dental adhesive primer composition comprising a mixture of the compound [I] and hydroxy monomers possesses good penetration into the microstructures of tooth surface and improves bond strength of bonding agent and prevents marginal microleakage of restorations.

The advantage of the compound [I] is not only having alpha-amino acid structure which works as a chelating agent, but also having two carboxyl groups and two polymerizable functional groups in a molecule. The compound [I] is conceived having a potential bonding to Ca²⁺ ions of the dentin. Two polymerizable functional groups are copolymerized with following monomers in a bonding resin. Administration of hydroxy monomers in the dental adhesive primer composition enhances infiltration hydrophilic dentin surface.

Furthermore the advantage of a salt of the compound [I] is infiltrating into porous region of the smear layer and forming a potential bonding to the smear layer and removing of the layer.

Polymerizable compound

With regard .to the compound [I] of the present invention, 'suitable "lower alkylene" as to R¹, is one having 1 to 5 carbon atom(s) , such as methylene, ethylene, trimethylene, propylene, tetramethylene, methyl- trimethylene, dimethylethylene, and the like, in which the most preferred one is ethylene.

As to R², suitable "lower alkylene" is one having 1 to 4 carbon atom(s) and may include methylene, ethylene, trimethylene, propylene, tetramethylene, methyl- trimethylene, dimethylethylene, and the like in which the most preferred one is ethylene.

Representative compounds [I] include:

H₂C=C(CH₃)C00H₂CH₂C00H₂C CH₂C00CH₂CH₂00C (CH₃) C=CH₂

\ /

N-CH₂CH₂-N

/ \

H00CH₂C CH₂C00H

H₂C=C ( CH₃) C00 ( CH₂) ₅00CH₂C CH₂C00 ( CH₂) ₅00C ( CH₃) C=CH₂

\ /

N-CH₂CH₂-N

/ \

H00CH₂C CH-C00H

as well as mixtures of more than one of the above compounds.

Preferably, the compound [I] are prepared by the addition reaction of hydroxy monomers (e.g., 2-HEMA) , and "lower-alkylene" diamine tetraacetic acid dianhydride (hereafter referred to as "dianhydride."

The dianhydride and hydroxylated monomers preferably can react at low temperature, and the reaction mixture will increase in viscosity, preferably reaching an equilibrium state that is stable over time. Preferably one molar of anhydride should be added to two molars of the hydroxylated monomers- so as to provide strong bonding performance ^' in adhesive primer compositions prepared therewith. Polymerization accelerator

Said polymerization accelerator promotes polymerization of the dental adhesive primer compositions of invention. Suitable polymerization accelerator include methacryloxyethyl-p- (N,N-dimethyl-amino) benzoate hereafter referred to as "MAEB") and the like. MAEB and camphorquinone are the most preferred ones. The amount of polymerization accelerator used is an amount sufficient to provide high immediate bonding strength and good handling performance in dental adhesive primers of the invention prepared therewith. A preferred amount for MAEB is between about 0.5 to 10 weight percent on the total weight of the dental adhesive primer composition and as to camphorquinone, a preferred amount is between about 0.1 to 5 weight percent on the total weight of the dental adhesive primer composition.

Hydroxy-group bearing lower alkyl ester of methacrylic acid.

Said hydroxy monomers acts as an enhancer of infiltration for the dental bonding compositions of this invention.

Suitable "lower alkyl" is one having 1 to 6 carbon atom(s) , such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, and like, in which the most preferred one is ethyl. The amount of Hydroxy-group bearing lower alkyl ester of methacrylic acid is an amount of sufficient to provide high bond strength and good handling performance in dental adhesive primer of the invention prepared therewith. A preferred amount is between about 10 to 30 weight percent of the dental adhesive primer composition.

Solvent

Said solvent serves to provide a good bond strength and handling performance, especially for treatment of the dental adhesive primer composition of this invention. Suitable solvent includes polar^" solvent, and acetone and ethanol are preferred ones. Other Adjuvants

Other adjuvants, such as surfactants, pigments, antioxidant, and the like can be contained in the dental adhesive primer compositions of the present invention. The amounts and kinds of such adjuvants, and their manner of addition in the dental manner of addition in the dental adhesive primer composition of the invention will be the same as currently used in existing adhesive primer compositions familiar to those skilled in the art.

Dentin conditioning primer composition

Dentin conditioning primer compositions comprise of 0.2 ,4- 1 M aqueous solution of a salt of the compound

[I] . The preferred salt is an alkali metal salt, and the most preferred one is potassium salt. Preferable pH value is in the range of 2.4-6.0.

Technique

The dentin conditioning primer compositions of the invention can be used as conditioners of dentin. They are applied to dentin preceding the application of dental adhesive primers and substitutes.

The dental adhesive primer compositions of the invention can be used as primers with adhesives for prepared dentin surfaces of a dental restoration. It can also be used as primers for the fixation of dental devices with dental adhesives. The dental adhesive primer compositions of the invention are applied in a manner in clinical use. However, high bond strength and absence of microleakage of the dental adhesive primer composition make the application technique simple and easy, thereby reducing the damage and hypersensitivity of pulp.

The invention will be understood more readily be reference to the following examples and experiments, however, these examples and experiments are intended to illustrate the invention and are not to be construed to limit the scope of the invention. Example

Example 1

The compound of the formula:

[ II ]

H₂C=C ( CH₃ ) C00H₂CH₂C00CH₂C CH₂C00CH₂CH₂00C ( CH₃) C=CH₂

\ /

N- CH₂CH₂-N

/ \

H00CH₂C CH₂C00H

was prepared from the addition reaction 2-hydroxyethyl methacrylate ( 2 mole equivalent ) to ethylenediaminetetraacetic acid dianhydride (1 mole equivalent) . Ethylenediaminetetraacetic acid dianhydride was obtained by dehydration of ethylenediaminetetraacetic acid.

A dental adhesive primer was prepared by mixing lOg of the compound [II] , 120g of aceton, and 20g 2- hydroxyethyl methacrylate in a closed glass bottle for 5 hours. Insoluble compound was filtered off. Into 9g of the acetone solution was added lg of 2-hydroxyethyl methacrylate, 0.08g of camphorquinone, and 0.4g of methacryloxyethyl p- (N,N-dimethyl amino) benzoate. The mixture was stirred in a closed amber glass bottle for 2 hours .

Example 2

A dental adhesive primer was prepared in the same method as Example 1 except for using ethanol instead of acetone.

Example 3 A dentin conditioning primer was prepared as follows; a 0.5M aqueous solution of the compound [II] was prepared which was buffered with potassium hydroxide to obtain a pH 4.6 solution. The test methods used in experiments are as follows :

Shear bond strength test

Extracted human molars that had been stored in a 1% chloramine solution at room temperature were used as test specimens. They were embedded with fast cure acrylic resin ("Sample-kwick" , Buehler, lake Blubb, IL) in a cylindrical plastic mold (h=30 mm, d=15 mm) . The crown of the tooth was removed using a low speed saw ("Isomet", Buehler, Lake Bluff, IL) . The exposed occlusal part of the dentin surface was ground wet on 800 grit silicon carbide paper on a polishing machine ("DAP-V", Struers, Copenhagen, Denmark) . The embedded teeth were washed in running fluoride-free water and dried with an oil-free air syringe. Each of the adhesive was applied to the dentin surface in accordance with its manufacture's instruction. The adhesion area was defined by using an adhesive water- repellant sticker with a 3 mm diameter opening in its center. A cylindrical plastic tube (d=5 mm, h=2-3 mm) was placed over the 3 mm opening and fixed with dental wax. A dentin conditioning primer was liberally applied to the dentin surface for one minute and then dried thoroughly with a compressed air stream. An unfilled bonding resin was uniformly applied with a brush onto the primed dentin. The bonding layer was not air thinned.

The unfilled bonding resin was cured for 20 seconds with a visible light source ("Optilux 400", Demetron Research Corp., CT) . Composite resin ("Silux", 3M Dental Products Division) was then placed onto the treated dentin surface in the cylindrical plastic tube. The resin cylinders were light-cured on the dental adhesive for 40 seconds.

After 24 hours immersion in 37° C distilled water, the test specimens were clamped horizontally into the shear adhesion apparatus and loaded parallel to the vertical axis of the composite resin. Bond strength was measured in a mechanical testing machine ("Instron Model 1011", Instron Corp., Canton, MA) at a cross head speed of 1 mm/rain. Total elapsed time from curing to fracture was 60±10 seconds. 10 specimens were tested for each variable.

Microleakage Test Extracted human molars stored under the same conditions as described in the shear bond strength test were used as test specimens. Only sound teeth were selected. Six V-shaped cavities were prepared, one on the mesial and one on the distal surface of each tooth. The preparations were approximately 1.5 mm deep, 5.0 mm wide, and 2.0 mm high. The cavities were prepared with a number 301 diamond bur (Shofu Dental, Kyoto Japan) in an ultra- high-speed hand piece using a waterspray coolant. All the enamel margins were acid etched for 60 seconds with "Scotch Gel" etchant (3M) . The dentin conditioning primer was liberally applied to the cavity surfaces for one minute and dried thoroughly with a compressed air stream. The unfilled bonding adhesive was uniformly applied with a brush onto the primed cavity surfaces. The bonding layer was not air thinned. The bonding agent was cured for 20 seconds with a visible light source. All preparations were filled with composite resin ("Silux", 3M) and light cured for 40 seconds. After immersion in 37° C water for 24 hours, all restorations were finished dry with finishing disks to simulate clinical finishing.

To prevent dye penetration in area other than the exposed margins, the teeth were sealed with nail varnish to within 2 mm of the restoration margins. The tooth apices were sealed with a light-cured composite resin. The teeth were placed in separate nylon mesh bags and thermocycled together for 200 cycles between 5° C and 55° C with a dwell time of one minute at each temperature. After thermocycling was completed, the specimens were placed in a 50% aqueous solution of silver nitrate for two hours in the absence of light and then thoroughly rinsed with distilled water. The teeth were placed in a photodeveloper solution under a fluorescent light for 2 hours to develop the penetration pattern and then rinsed thoroughly. The teeth were sectioned longitudinally in a mesial direction using an "Isomet" saw.

The degree of dye penetration in the cavity walls was assessed separately for occlusal and gingival walls using a binocular microscope at 25x magnification.

Experiments

Experiment 1

The dental adhesive primer of Example 1, the dentin conditioning primer of Example 3, and an adhesive "Visio Seal" (manufactured by Den Mat) were used as materials, resulting in an even primer film on the dentin surface. Then "Silus" (manufactured by 3M) as a composite resin was applied. In order to evaluate the effectiveness of the dentin conditioning primer, shear bond strength test was done and results thereof are summarized in Table 1. For comparative, 10% H₃ P0₄ solution and 0.5M aqueous solution of the compound [II] having pH value 7.5 was used as a dentin conditioning primer instead of the primer of Example 3.

TABLE 1

Shear bond strength to human dentin after 24 hours of immersion in 37° C water (n=10, MPa)

The dentin conditioning primer of Example 3 resulted in statistically significantly higher bond strength. Phosphoric ^' acid treated dentin showed poor adhesion. The 10% phosphoric acid solution probably denatured the collagen, which may be responsible for the poor adhesion. And 0.5 M aqueous solution of the compound [II] having pH value 7.5 also showed poor adhesion, which was used as a dentin conditioning primer.

Experiment 2

The dental adhesive primer of Example 2, the dentin conditioning primer of Example 3, and a bonding adhesive which was formulated in Table 2 were used as materials, resulting in an even primer film on the dentin surfaces. This bonding system was compared to commercial bonding agent systems: "All Bond" (BISCO, USA) , "XR Bond"

(Kerr, USA, "Universal Bond 3" (Caulk, USA) , and "D-Liner"

(Sun Medical, Japan) which is known as "Amalgam Bond"

(Parkell) in the United States.

TABLE 2 (Parts by weight)

MEAB* :Methacryloxyethyl-p- (N,N-dimethyl amino) benzoate

In order to evaluate the effectiveness of the dental adhesive primer, shear bond strength test and microleakage test 1 above-mentioned was done and results thereof are summarized in Table 3. TABLE 3

The bonding system consisting of the dental adhesive primer of Example 2, identified as "experimental" in Table 3, produced significantly higher bond strength than all other systems and no leakage. The comparisons had lower bond strength and showed leakage.

Experiment 3 In order to evaluate the effectiveness of the dental adhesive primer in case of root caries, microleakage test was done using the dental adhesive primer of Example 2. For the comparison commercial bonding systems, "Clearfil Liner Bond" (Kuraray Co. Osaka, Japan) , "All Bond" (Bisco Inc. Doners Grove, IL) , "Scotchbond 2" (3M Dental Products Minneapolis. MN) , "GLUMA" (Bayer AG. Leverkusen, FRG) , "Tenure" (Den-Mat Co. Santa Maria, CA) were used.

Microleakage test was done in the same method of Experiment 1, except for the manner as follows;

60 box shaped cavities were prepared; one on mesial and one on the distal root surface of each tooth. The preparations were approximately 1.5 mm deep, 5.0 mm wide and 2.0 mm high. All were placed below the cemento- enamel ^■ junction with the non-beveled cavosurface margins totally located in smooth cementum. The average degrees of microleakage, standard deviations, and the number of leakage free specimens at occlusal and apical walls are summarized in Table 4 (in occlusal walls) and Table 5 (in apical walls) .

TABLE 4

Microleakage depths at occlusal (cementum-dentin) walls of root caries restorations

Bonding sistem Microleakage depthNumber of leakage in 0.01 mm free specimen

Tenure 31 ± 24

*The bonding system of the invention.

TABLE 5

Microleakage depths at apical (cementum-dentin) walls of root caries restorations

Bonding sistem Microleakage depthNumber of leakage in 0.01 mm free specimen

*The bonding system of the invention. As clearly shown in Table 4 and Table 5 the dentin primer of this invention and "Clearfil Linear Bond" showed significantly better results in reducing microleakage along both occlusal and apical cemento-dentin walls than the other comparatives.

The degree of microleakage along the apical walls of root caries restorations was greater than the occlusal walls . The dentinal tubules at the occlusal aspect of the cavity run to the external tooth surface, which allows them to be more easily dried especially in vitro. This drying is more thorough, so there are more tags and a better marginal seal than those of the tubules on the apical wall of the cavity which run in the pulpal direction.

When compared to five commercially available dental bonding agents, the dental adhesive primer of this invention had significantly less microleakage in root caries restoration. This may predict the clinical success of the same in applying for root surface caries treatments.

Experiment 4 In order to evaluate the effectiveness in reducing microleakage in class II cavities, microleakage test was done using the dental adhesive primer of Example 2.

For the comparison, five commercial bonding system, the same as the Experiment 2, were used. Microleakage test was done in the same method of

Experiment 1, except for the manner as follows;

60 class II MO preparations with a cavosurface angle of 90° were placed in each tooth, with cervical margins finished approximately 1 mm below the cemento- enamel junction.

The average degrees of microleakage, standard deviations, and the number of leakage free specimens at gingival wall of class II MO restorations are summarized in

Table 6. TABLE 6

Microleakage depths at gingival (cementum-dentin) walls of Class II restorations

Bonding sistem Microleakage depthNumber of leakage in 0.01 mm free specimen

*The bonding system of the invention.

As clearly shown in Table 6, the dental adhesive primer of this invention showed significantly better results in reducing microleakage along gingival cemento- dentin walls in class II MO restoration than the other comparisons. This may predict the clinical success of the same in applying for posterior caries treatment.

As this invention may be embodied in several forms without departing from the spirit of essential characteristics thereof, the present embodiment is therefore illustrative and not restrictive, since the scope of the invention is defined by the appended claims rather than by the description preceding.

Claims

WHAT IS CLAIMED IS:

1. A dental adhesive primer composition for pretreatment of tooth surface prior to bonding comprising a mixture of : (a) polymerizable compound of the general formula:

[ I ] H₂C=C(CH₃)C00-R¹-00CH₂C C -COO-R^OOC(CH₃) C=CH₂

\ / N-R²-N

/ \

H00CH₂C CH₂C00H

Wherein R¹ and R² are each lower alkylene

(b) hydroxyl-group bearing lower alkyl ester of methacrylic acid.

(c) polymerization accelerator

(d) solvent

2. A dental adhesive primer composition as set forth in claim 1, which contains the compound [I] : from 1 to 10 parts by weight, said hydroxy-group bearing lower alkyl ester of methacrylic acid: from 10 to 30 parts by weight and said polymerization accelerator: from 0.5 to 10 parts by weight.

3. A dental adhesive primer composition as set forth in claim 2, wherein R^! -ethylene, R² is ethylene.

4. A dental adhesive primer composition as set forth in any one of claims 1 to 3, wherein said polymerization accelerator is methacryloxyethyl-p- (N,N- dimethyl amino) benzoate.

5. A dental adhesive primer composition as set forth in any one of claims 1 to 4, wherein said solvent is acetone.

6. A dental adhesive primer composition as set forth in any one of claims 1 to 5, wherein said solvent is ethanol .

7. A dentin conditioning primer composition having pH value 2.4-6.0 and comprising a salt of said compound [I] .

8. A dentin conditioning primer composition as set forth in claim 7, wherein R¹ is ethylene, R² is ethylene.

9. A dentin conditioning primer composition as set forth in claim 7 or 8, wherein said salt of the compound [I] is an alkali metal salt.

10. A dentin conditioning primer composition as set forth in any one of claims 7 to 9, wherein said salt of the compound [I] is a potassium salt.