IE44537B1 - Dental compositions - Google Patents

Description

This invention relates to polymerizable dental compositions. The compositions are suitable, for instance, as coatings, sealants for pits and fissures or as margin sealants for amalgam restorations, or as dental composites containing fillers.

Polymerizable dental compositions based on methacrylate monomers are known. One of the problems encountered with such compositions is a lack of colour stability, that is, stability to ultraviolet light. Curing systems conventionally used for restorative composites are redox catalysts or initiators the reductant portion of which may comprise various aromatic amines. These aromatic amines lead to colour formation, particularly under the influence of sunlight and other sources of ultraviolet radiation, so that the cured composition gradually changes colour from the original tooth matching shade and a distinct and unattractive differentiation between the tooth and the restoration may become apparent in a matter of months. Efforts to minimize the deleterious colour changes brought about by the amines have been made by chemically modifying the amines, as described by R.L. Bowen and H.Argenta? in J. Am. Den. Assoc., Vol. 75, No. 4, p. 918-923 (Oct. 1967). Nevertheless, total colour stability cannot be achieved with any of the aromatic amine systems, and it is necessary in conventional composites to incorporate ultraviolet stabilizers to minimize colour formation. However, the inclusion of such non-polymerizable, low molecular weight ingredients which are potentially capable of leaching, and hence, of pulpal irritation, is undesirable.

Conventional restorative compcsit.es use peroxides, most commonly benzoly peroxide, as the oxidant part of the redox system. Benzoyl peroxide has a short half-life, resulting in poor shelf-life stability.

Thus, if If by weight of benzcyl peroxide is dissolved in methyl methacrylate or triethylene glycol dimethacrylate or the like and the solution is allowed to stand at room temperature, polymer may be formed within a week. To retard premature polymerization, such composites are generally stored by the dentist in a refrigerator.

Redox systems employing certain hydroperoxides and thioureas have previously been described in the literature. Thus, U.S. Patent No. 3,591,433 discloses bonding accelerators comprising an aldehyde-amine condensation product and a reducing activator such as l-allyl-2-thiourea to accelerate the cure of a peroxy (including hydroperoxy) initiated acrylate-based adhesive or sealant composition. While functional for the intended purpose, the afcromertticnad three-component accelerator produces coloured compositions.

T. Sugimura et. al., in J. Poly. Sci., Vol. 3, p. 2935-2945 (1965) report the polymerization of acrylonitrile with t-butyl hydroperoxide and thiourea and such substituted thioureas as diphenyl-, ethylene, diacetyl-, monoacetyl- and diethyl thiourea.

According to the present invention a polymerizable dental composition comprises at least 20% by weight of at least one monomeric di-, tri- or tetra-ester of methacrylic acid having 2 to 4 polymerizable double bonds (hereinafter semetimas referred to simply as the methacrylate monomer); 0.5 co 5.Of, preferably 2.0 to 3.0%, by weight based on the methacrylate monomer of a hydroperoxide oxidizing agent; 45S37 0.3 to 2.0%, preferably 0.5 to 1.0%, by weight based on the methacrylate monomer of a substituted thiourea reducing agent as set forth below; and at least 73% by weight of the composition of particulate inorganic filler.

The composition may comprise also up to 5.0%, preferably 3.0% to .0%, by weight based'on the methacrylate monomer of silane coupling agent. · It has been found that such dental compositions can be polymerized to provide a cured composition of enhanced colour stability. The redox system employing a hydroperoxide oxidizing agent and a substituted thiourea reducing agent also affords an acceptable rate of cure for the monomer. Further, the compositions have enhanced shelf-life stability due to the hydroperoxide component and do not require storage in a refrigerator.

The hydroperoxide oxidizing agent may have a peroxy group attached to a tertiary carbon atom. Exemplary hydroperoxides are those having the formula: R - OOH wherein R is t-butyl, cumyl, p-methane or ^-isopropyl cumyl, Preferably the composition contains 1.0 to 2.0% by weight of oxidizing agent.

The. reducing agent employed in this invention is a substituted thiourea having the formula: 4483 Y S ι II X-N-C-Z wherein X represents hydrogen or Y; Y represents C-j to Cg alkyl such as methyl, butyl or octyl; Cg or Cg cycloalkyl, e.g. cyclopentyl or cyclohexyl; chloro-, hydroxy- or mercapto-substituted C-| to Cg alkyl such as chloroethyl, mercapto-ethyl, hydroxymethyl or chlorooctyl; C3 or C^ alkenyl such as allyl or methallyl; Cg to Cg aryl such as phenyl or xylyl; chloro-, hydroxy-, methoxy- sulphonyl- or vinyl-substituted phenyl such as chlorophenyl, phenylsulphonyl, hydroxyphenyl or methoxyphenyl; C? to Cg acyl such as acetyl, butyryl or octanoyl; chloro- or methoxy-substituted C2 to Cg acyl such as chloroacetyl, chlorobenzoyl, chlorotoluoyl or methoxybenzoyl C? or Cg aralkyl such as benzyl; or chloro- or methoxy-substituted C? or Cg aralkyl such as methoxybenzyl; and Z represents NH2, NHX or NX2.

Examples of suitable reducing agents are methyl thiourea, isopropyl thiourea, butyl thiourea, octyl thiourea, benzyl thiourea, acetyl thiourea, benzoyl thiourea, octanoyl thiourea, cyclohexyl thiourea, allyl thiourea , triphenyl thiourea, trimethyl thiourea, xylyl thiourea, £-tolylsulphonyl thiourea, 1-octyl-3-phenyl thiourea, o^-methoxyphenyl thiourea, m-hydroxyphenyl thiourea, 1,1-diallyl thiourea, 1,3-diallyl thiourea, 2-methallyl thiourea, o-metboxymethyl thiourea, l-(hydroxymethyl)-3-methyl thiourea, 1,1-dibutyl thiourea, 1,3-dibutyl thiourea, l-(£-chlorophenyl)-3-methyl thiourea, 1-butyl-3-butyryl thiourea, 453 7 1-acetyl-3-phenyl thiourea, T-methyl-3-(p-vinylphenyl) thiourea, 1-methyl-3-0-tolyl thiourea, l-methyl-3· pentyl thiourea, 3-methyl-l,1-diphenyl thiourea and l-acetyl-3-(2-mercaptoethyl) thiourea. While any of the aforementioned thioureas can be employed, preferred are the monosubstituted thioureas, that is, those having the aforementioned .- formula wherein X is H and Z is NHg. Particularly preferred are phenyl thiourea, acetyl thiourea and ally thiourea. Preferably, the composition contains from 0.5 to 1% by weight of reducing agent.

The methacrylate monomer is selected from materials having 2 to 4 polymerizable double bonds per molecule in order that the cured composite be crosslinked and thus better suited for use in the oral cavity. The most preferred monomers are those having two polymerizable double bonds per molecule. Desirable characteristics for such monomers include low polymerization shrinkage, low oxotherm during polymerization, low water sorption and the ability to cure rapidly and completely in the mouth. It is also desirable that the monomers be low in volatility and non-irritating to the pulp.

. Methacrylate monomers particularly useful in this invention are those represented by the following general formulae: [M ^-Tft-0)nAr}2C(CH3)2 -A~QCQ)2Ar (M-AJ/R, I (II) III M2R} \ (M-A-OCO- ~nh)2r3 CH,- M 1 ‘ CH — M* | IV V ch2-m VI 44837 wherein M represents methacryloyloxy, i.e. CHg CfCHgJCOO-; M1 represents methacryloyloxy or hydroxyl; A represents alkylene having 1 to 3 carbon atoms such as methylene, propylene or isopropylene, hydroxyalkylene having to 3 carbon atoms such as hydroxymethylene car 2-hydrcsy^axpylene, acetoxyalkylene having 3 to 5 carbon atoms in the alkylene group such as 2-acetoxypropylene or 3-acetoxyamylene; n is zero or 1; m is 2 or 3 and o is 1 or 2 with the proviso that the sum of m and £ is 4; R represents hydrogen, methyl, ethyl or -A-M wherein A and M are as previously defined; Ar represents phenylene, e.g. o-phenylene, m-phenylene or £-phenylene, alkyl substituted phenylene, e.g. tolylene or -t-butyl-m-phenylene, or cycloalkylene having 6 to 10 carbon atoms such as 1,3-cyclohexylene; and R^ represents alkylene having to 12 carbon atoms such as ethylene or dodecylene, or p p p p — R —f-0-R 0Rc - wherein R represents alkylene having 2 or 3 carbon atoms, namely ethylene, propylene or isopropylene, and x is zero or an integer from 1 to 5; and R represents phenylene, tolylene, methylene-bisphenylene or alkylene having 2 to 12 carbon atoms.

Monomers having the above formulae are well known and generally commercially available materials. Alternatively, they can readily be prepared by conventional routes, for example, by reacting a phenolic compound such as phloroglucinol or bisphenol A with glycidyl methacrylate in the presence of various tertiary amines or by reacting methacrylic acid with an epoxide-containing compound 44S37 such as the diglycidyl ether of a bisphenol. Some of these monomers can also be made by reacting appropriate alcohols with methacrylic acid, methacrylyl chloride of methacrylic anhydride.

Illustrative monomers include: ch2 = c(ch3)cooch2ch2-oco cooch2ch2ococ(ch3) = ch2 c-£ch2ococ(ch3) = ch214; CH3CH2C -f- CH2-0-C —C = CH2)3; ch3 CH2 = C(CH3)C00(CH2)60C0C(CH3) = CH2; CH2 = C(CH3)C00CH2CH20CH2CH20CH2CH20C0C(CH3) = ch2; ch2 C(CH3)C00CH2CH (OHJCK^-O 0-CH2“CH(OH)CH2OCOC(CH3) = CH2 ch2 = C(CH3)C00 c(ch3)2 -C0C(CH3) = ch2 CH2 = C(CH3)C00 CH2CH(0H)CH2-0 Γ ) y-OCH2CH(OH)OCOC(CH3)=CH2 0CH2CH(0H)0C0C(CH3) = CHg CH2=C(CH3)C00-CH2CH20C0NH NHC00CH2CH20C0C(CH3) = ch2 CH2 = C(CH3)C00-CH2CH-0C0NH - CHgCHgC — ch3 ch3 C-C -CH2-NHC00CH-CH2-0C0-C(CH3) = CH2 H CH3 CH3 4453? Monomers having the general formulae I, II, III and IV are preferred in the practice.of this invention. Of these monomers, Γ, II and III are particularly preferred, monomers IV preferably being employed in admixture with one or more of monomers I, II, and III.

Other useful methacrylate monomers suitable for use in the practice of this invention include those having the following formulae wherein M and Ar are as previously defined; (MR^OAr^CfCHg^ Λ C Γ wherein R is isopropylene; (MR 0Ar)g and (MR O^Ar wherein R5 is 2-hydroxypropylene; MA0R6M wherein R6 is hydroxycyclopentyl; M-A'-R M wherein A1 is hydroxycyclohexyl and ft 8 R is 2-hydroxyethylene; and MgR wherein R is Generally these monomers are commercially available. Preparative details for many of these monomers are given in U.S. Patents Nos. 3,066,112; 3,721,644; 3,730,947; 3,770,8η and 3,774,305. A ternary eutectic monomer mixture also suitable for use in this invention is described 1n U.S. Patent No. 3,539,526.

Mixtures of two or more appropriate methacrylate monomers may be used. Indeed, depending on the choice of monomers, mixtures are often highly desirable to optimize the characteristics of the resulting dental composition. Thus, it is preferred that the monomer or monomer blend have a viscosity of from 100 to 20,000 centipoises as determined using a Brookfield viscometer at 20 rpm at room temperature. More viscous masses are conveniently handled at higher temperatures.

The inorganic particulate fillers employed in the compositions of this invention include fused silica, quartz, crystalline silica, soda glass beads, glass rods, ceramic oxides, particulate silicate glass and synthetic minerals such as beta-eucryptite (LiAlSiO^), the last-mentioned having negative thermal expansion. It is also feasible to employ finely divided materials and powdered hydroxylapatite, although materials that react with silane coupling agents are preferred.

Small amounts of pigments to allow matching of the composition to various shades of teeth can be included. Suitable pigments include iron oxide black, cadmium yellows and oranges, fluorescent zinc oxides and titanium dioxide. The filler particles used will generally be smaller than 50 microns in diameter, preferably smaller than 30 microns.

Z0 The silane coupling agents or keying agents are materials that contain at least one polymerizable double bond to react with the methacrylate monomers. Examples of suitable coupling agents are vinyl trichlorosilane, tris(2-methoxyethoxy) silane, tris(acetoxy) vinyl silane, 1-N-(vinyl benzyl ami noethyl) aminopropyl trimethoxysilane-3, and 3-methacryloxypropyl trimethoxy silane. The last named material is preferred for use with methacrylate monomers because of the similarity in reactivity of the double bonds. 44337 The compositions of this invention can readily be prepared by conventional mixing techniques. For example, the methacrylate monomer, or monomer mixture, is mixed with the silane coupling agent and the reducing agent, then the inorganic particulate filler is added and mixed to a paste. This paste is supplied to the dentist together with oxidizing agent packaged separately. Accompanying instructions advise the dentist to mix an appropriate amount of oxidizing agent with the paste and then use the composition for the intended application, allowing the cure to take place in the oral cavity.

In another technique, the silane coupling agents can be bonded or. applied to the inorganic particulate filler before the latter is blended with the monomer. This can be accomplished by acid hydrolysis or alkaline hydrolysis, for example, by following the procedure described in U.S. Patent No. 3,066,112.

The following Examples illustrate the invention. All parts and proportions in the Examples and elsewhere throughout the specification are by weight.

EXAMPLE 1 A. Preparation of Composition A homogeneous solution having the following constitution was prepared by mixing the ingredients at room temperature: parts BIS-GMA (the reaction product of bisphenol A and glycidyl methacrylate, otherwise identified as bis 2,2'[4-(2-hydroxy-3methacryloxypropylJphenylj propane; 44*37 parts polyethylene glycol dimethacrylate having an average molecular weight of polyethylene glycol of 200; parts γ-methaeryloxypropyl trimethoxysilane; and 1.05 parts allyl thiourea.

To an amount of 2.0 g of this homogeneous solution was added .5 g of noncrystalline, colourless, fused silica which had been previously washed with 20% hydrochloric acid solution to remove metallic impurities and which passes a No. 325 U.S. Standard sieve. Upon mixing, a homogeneous paste was obtained. Then 0.004 g of cumene hydroperoxide (in a small amount of 1,6-hexanediol dimethacrylate) was added with spatulation to a 0.8 g portion of the homogeneous paste and the sample placed in a polytetrafluoroethylene mould and allowed to cure for approximately 3 minutes. The resulting sample was a cylindrical button having a diameter of J'1 and a thickness of 1/16.

B. Colour Stability Testing Testing for colour stability was carried out using the ultraviolet source described in American Dental Association Specification No. 12 for Denture Base Polymer with the following modifications. A round quartz window cooled by a water layer 1 cm in depth was placed under the light source in order to eliminate infrared light. A General Electric RS sunlamp which had been in use for 100 hours prior to this testing was employed as the lamp. The distance from bulb to turntable was 250-300 mm. To commence the test, half of the button was shielded from the light by covering it with aluminium foil. The covered portion served as the control. The button was exposed to ultraviolet light for 55 hours but no change in colour was observed upon comparing the covered part of the sample with the uncovered part. The test was terminated at this point. The colour is deemed stable if the uncovered sample does not show more than a slight change in colour after exposure for 24 hours.

EXAMPLES 2-12.

The general procedure of Example 1 was followed in preparing the compositions of Examples 2 - 12; the ingredients and proportions employed in these compositions are listed in Table 1. The amount of homogeneous solution taken to prepare the paste varied slightly in the Examples, but the amount of paste placed in the mould remained constant in accordance with Example 1. The oxidant and reductant are given in the table as per cent by weight of the amount of total monomer (major monomer and diluent monomer) employed in the composition. Filler is listed as per cent by weight of total composition The hydroperoxide was always added as a solution in 1,6-dexanediol .dimethacrylate to facilitate the addition of small amounts. The fused silica and BIS-GMA used in these Examples are as defined in Example 1. A selection of these compositions was tested for colour stability employing the equipment and method described in Example 1; these results are set forth in Table II. 44S37 Notes for Table I.

Wma 1,6-Hexanediol Dimethacrylate 2 Coupling agent - γ-Methacryloxypropyl Trimethoxysilane3pegdma Polyethylene Glycol Dimethacrylate A product of Hercules, Inc., Wilmington, Delaware, U.S.A. 5HBPDMA Hydrogenated Bisphenol A Dimethacrylate6bgdma 1,3-Butylene Glycol Dimethacrylate7tmetma 1,1,1-Trimethylolethane Trimethacrylate8tegdma Triethyleneglycol Dimethacrylate9dmip Bis(2- methacryloxyethyl) isophthalate Example TABLE II Exposure (hours) to Perceive Colour Change 2 > 55 3 > 24 4 >24 5 slight after 28 6 > 32 7 >28 8 not tested 9 not tested 10 barely perceptible after 31 11 12 noticeable after >31 ί >15 3 7 EXAMPLE 13 The following ingredients were added in the indicated order to a Silamat mechanical shaker manufactured by the Justi Company, U.S.A., and then mixed for about one minute to prepare a homogeneous paste: 0.55 g fused silica washed with 6N hydrochloric acid; 0.2 g of a 71:29 parts by weight mixture of BIS-GMA and polyethyleneglycol dimethacrylate containing 4% by weight γ-methacryloxy propyl trimethoxysilane; and 0.002 g allyl thiourea After the paste was removed from the shaker, 1 drop of cumene hydroperoxide solution in 1,6-hexanediol dimethacrylate (equivalent to 0.004 g of cumene hydroperoxide) was added with spatulation to provide a composite. A 1/16 inch diameter hole was drilled in a bovine tooth. The hole was filled with the composite, covered with polyethylene terephthalate film, clamped and allowed to cure for 30 minutes. Then the tooth was broken with a hammer. All parts of the composite were hard and dry, indicating that a cure had been effected.

COMPARATIVE EXAMPLE The general procedure of the preceding Examples was followed in preparing a composition employing a redox system used in commercial dental composites. A homogeneous solution was prepared from 71 parts of BIS-GMA, 26 parts of polyethylene glycol dimethacrylate and 5 parts of γ-methacryloxypropyl trimethoxysi lane. A paste was made by mixing 2.0 g of the homogeneous solution with 5.5 g of the fused silica described in Example 1. The paste was cured in the usual mould with 1% by weight benzoyl peroxide and 0.5% by weight ίί-bishydroxyethyl-p-toluidine, the per cent by weight being based on the sum of BIS-GMA and polyethylene glycol di methacryl ate.

Testing for colour stability following the procedure described in Example 1 revealed that the saiiple darkened considerably after 6 hours exposure of ultraviolet Tight.

Claims (16)

1. A polymerizable dental composition comprising at least 20% by weight of at least one methacrylate monomer having 2 to 4 polymerizable double bonds which is a monomeric di-, tri- or tetra-ester 5 of methacrylic acid; 0.5 to 5.0% by weight based on the methacrylate monomer of hydroperoxide oxidizing agent; 0.3 to 2.0% by weight based on the methacrylate monomer of a substituted thiourea reducing agent having the formula Y S I 11 X-- N - C -Z IQ wherein X represents hydrogen orY; Y represents C^ to C g alkyl; C g or Cg cycloalkyl; chloro-, hydroxy- or mercapto- substituted C^ to Cg alkyl; C g or C^ alkenyl; Cg to C g aryl; chloro-, hydroxy-, methoxy-, sulphonyl- or vinyl-substituted phenyl; C g to C g acyl; chloro- or methoxy- substituted Cg to C g acyl; 15 C? or C g aralkyl; or chloro- or methoxy-substituted C ? or C g aralkyl; and Z represents NHg, MIX or NX g ; and at least 73% by weight of the composition of particulate inorganic filler.

2. A composition as claimed in Claim 1 which comprises also up to 5.0% by weight based on the methacrylate monomer of silane coupling 20 agent.

3. A composition as claimed in Claim 2 conprising 3.0 to 5.0% by weight based on the methacrylate monomer of the silane coupling agent, 2.0 to 3.0» by weight based on the methacrylate monomer of the hydroperoxide oxidizing agent, and 0.5 to 1.0% by wpight based on the methacrylate mcncmer of the substituted thiourea reducing agent.

4. 5 4. A composition as claimed in any of the preceding Claims wherein the methacrylate monomer has a Brookfield viscosity at room temperature and 20 rpm of from 100 to 20,000 cps. 5. A composition as claimed in any of the preceding Claims wherein the hydroperoxide oxidizing agent contains a peroxy group attached to a 10 tertiary carbon atom.

5. 6. A conposition as claimed in Claim 5 wherein the oxidizing agent isjfc-butyl hydroperoxide.

6. 7. A composition as claimed in Claim 5 wherein the oxidizing agent : is cumene hydroperoxide. l.j

7. 8. A conposition as claimed in Claim 5 wherein the oxidizing ageht is jj-methane hydroperoxide.

8. 9. A composition as claimed in Claim 5 wherein the oxidizing agent is diisopropyl-benzene hydroperoxide.

9. 10. A composition as claimed in ahy of the preceding Claims wherein 20 the reducing agent is a ironosubstituted thiourea. lb A composition as clained in Claim 10 wherein the reducing agent is allyl thiourea. 1Z. A composition as claimed in Claim 10 wherein the reducing agent is acetyl thiourea. 44837

10. 13. A composition as claimed in Claim 10 wherein the reducing agent is phenyl thiourea.

11. 14. A composition as claimed in any of the preceding Claims wherein the methacrylate monomer has two polymerizable double bonds. b

12. 15. A composition as claimed in Claim 14 wherein the methacrylate monomer is a mixture of triethylene glycol dimethacrylate with the reaction product of bisphenol A and glycidyl methacrylate.

13. 16. A composition as claimed in Claim 14 wherein the methacrylate monomer is a mixture of 1,6-hexanediol dimethacrylate with the reaction 10 product of bisphenol A and glycidyl methacrylate.

14. 17. A composition as claimed in Claim 15 or Claim 16 (except when appendant to any of Claims 6, 8, 9, 11 and 13) wherein the oxidizing agent is cumene-hydroperoxide and the reducing agent is acetyl thiourea.

15. 18. A polymerizable dental conposition substantially as described 15 in any of the Examples 1 to 14.

16. 19. A dental composition comprising a composition as claimed in any of the preceding claims when cured.