Caries-resistant composite resin

Abstract

A direct filling composite resin restorative featuring a CTE that is similar to dentin and an antimicrobial is disclosed. The exemplary anti-microbial compound is zinc oxide. The CTE of the direct filling composite resin restorative is in the range of 12-15 ppm/° C. The low CTE is achieved by high filler loading of a trimodal distribution of low CTE filler. By maintaining a CTE substantially similar to that of dentin, the “Marginal Percolation” phenomenon is minimized, which decreases the incidence of secondary caries.

Claims

1. A direct fill composite restorative composition comprising of: an antimicrobial agent; at least one resin; a photo initiator; a trimodal filler distribution with a filler load of at least or greater than 79%; wherein said trimodal filler distribution is comprised of 15-25% by w/w % submicron filler glass, 1-15% by w/w % 1 micron filler glass and 50-80% by w/w % 5 micron filler glass all having a coefficient of thermal expansion of less than 1 ppm/C; and whereas said trimodal filler distribution allows for greater particle-to-particle interaction and particle flow resulting in the coefficient of thermal expansion of said direct fill composite restorative composition to be in the range of 10-17 ppm/° C. and be used in direct fill dental restorative procedures to fill dental caries.

2. The direct fill composite restorative composition of claim 1 wherein said antimicrobial agent is comprised of zinc oxide.

3. The direct fill composite restorative composition of claim 2 wherein said zinc oxide is in the range of 0.2-0.8 w/w %.

4. The direct fill composite restorative composition of claim 1 further comprising a flexural strength greater than 83.4 MPa.

5. The direct fill composite restorative composition of claim 1 wherein said trimodal filler distribution is radiopaque.

6. The direct fill composite restorative composition of claim 1 wherein said at least one resin is selected from the group consisting of ethoxylated bisphenol A dimethacrylate, Bis GMA, triethylene glycol dimethacrylate and combinations thereof.

7. The direct fill composite restorative composition of claim 1 wherein said coefficient of thermal expansion is in the range of 10-15 ppm/deg C.

8. The direct fill composite restorative composition of claim 7 wherein said coefficient of thermal expansion is in the range of 14-17 ppm/deg C.

9. A dual component direct fill composite restorative composition comprising: a first component; said first component comprises of a first component of a binary curing system, a filler comprising of a trimodal filler distribution, said filler has a filler load at least or greater than 79%, at least one resin and an anti-microbial agent; and a second component; said second component comprises of a second component of a binary curing system, a filler comprising of a trimodal filler distribution, said filler has a filler load at least or greater than 79%, an anti-microbial, at least one resin; wherein said trimodal filler distribution is comprised of 15-25% by w/w % submicron filler glass, 1-15% by w/w % 1 micron filler glass and 50-80% by w/w % 5 micron filler glass all having a coefficient of thermal expansion of less than 1 ppm/C; and wherein both components are admixed prior to use to form said direct fill composite restorative composition with a coefficient of thermal expansion in the range of 10-17 ppm/° C. and used in direct fill dental restorative procedures to fill dental caries.

10. The direct fill composite restorative composition of claim 9 wherein said coefficient of thermal expansion is in the range of 10-15 ppm/deg C.

11. The direct fill composite restorative composition of claim 9 wherein said coefficient of thermal expansion is in the range of 14-17 ppm/deg C.

12. The direct fill composite restorative composition of claim 11 wherein said antimicrobial agent is comprised of zinc oxide.

13. The direct fill composite restorative composition of claim 12 wherein said zinc oxide is in the range of 0.2-0.8 w/w %.

14. The direct fill composite restorative composition of claim 9 wherein said first component of said binary curing system is comprised of benzoyl peroxide.

15. The direct fill composite restorative composition of claim 9 wherein said second component of said binary curing system is comprised of dihydroxyethyl paratoluidine.

16. The direct fill composite restorative composition of claim 9 wherein said at least one resin comprises ethoxylated bisphenol A dimethacrylate, Bis GMA, triethylene glycol dimethacrylate or combinations thereof.

17. A method of manufacturing a direct fill composite restorative composition comprising the steps of: dissolving soluble components comprising of photoinitiators, inhibitors, and stabilizers into at least one resin; blending together a trimodal filler distribution comprised of 15-25% by w/w % submicron filler glass, 1-15% by w/w % 1 micron filler glass and 50-80% by w/w % 5 micron filler glass all having a coefficient of thermal expansion of less than 1 ppm/° C. to form a trimodal distribution of filler glasses; adding said trimodal distribution of filler glasses, fumed silica and at least one anti-microbial to said at least one resin to form said direct fill composite restorative composition; and said direct fill composite restorative composition is placed in a roll mill; wherein said direct fill composite restorative composition has a coefficient of thermal expansion in the range of 10-17 ppm/° C. for use in direct fill dental restorative procedures.

18. The method of claim 17 wherein said at least one anti-microbial comprises of zinc oxide.

19. The method of claim 18 wherein said zinc oxide is in the range of 0.2-0.8 w/w %.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Some dental materials have performed well in terms of inhibiting secondary caries when used as a restorative. Gold restorations for example, have performed best, often lasting a lifetime clinically. Gold foil restorations adapt well and perform well without adhesives. Gold crowns also perform well with proven refractory cements. Probably the most important feature of gold as a dental material is its CTE.

(2) Ideally, the CTE of dental materials should match the CTE of dentin or be substantially similar to the CTE of dentin. When this happens, the restorative and tooth expand and contract at the same rate as the temperature of the oral cavity cycles. This prevents stress from developing at the interface at the bond between the restorative and dentin helps maintain an integral bond between the materials. More importantly, a matched CTE between the materials will prevent a phenomenon referred to as “Marginal Percolation”. “Marginal Percolation” is a phenomenon whereby a gap expands and contracts in between the tooth and restorative. This gap changes dimensions because the dentin and restorative are expanding or contracting at different rates, allowing a continuous influx of bacteria and nutrients for established bacterial colonies into the gap. As discussed, there is a large difference in CTE between some dental restoratives and dentin (for example composites and amalgams have a CTE of about 30 ppm/° C. vs. 12 ppm/° C. for dentin). With temperature cycling, “Marginal Percolation” occurs and bacteria and nutrients percolate into the gap allowing bacterial growth. The existence of growing bacteria within the formed gap results in secondary caries. On the other hand, if the dentin and restorative are expanding and contracting at the same rate, this gap does not change in dimensions, resulting in less bacterial growth, and a corresponding decrease in secondary caries.

(3) Operator error often results in marginal gaps between the tooth and restoration. Clinical studies have shown that more than 50% of restorative failures are a result of operator error. This is a matter of operator technique and happens no matter how good the restorative or adhesive is. In the situation where gaps occur and where there is a large difference in CTE between the tooth and restoration, “Marginal Percolation” occurs within the gaps. With temperature cycling, “Marginal Percolation” occurs and bacteria and nutrients percolate into the gap allowing bacterial growth.

(4) Unfortunately, the importance of a matched CTE to the tooth has been marginalized in the past. The reason for this is that the difference is relatively small. All direct filling composites have a CTE of about 35 ppm/° C. vs. about 12 ppm/° C. for dentin (the high CTE is the result of the high CTE of polymers, about 80 ppm/° C.). The difference in CTE is small and probably has little effect on development of bond stresses compared to stress developed by polymerization shrinkage, which had been the focus of dental restorative research since the 1950s. As a result, the focus of past research has been to reduce polymerization shrinkage instead of matching the CTE.

(5) Also reducing the CTE of composite resins has not been achieved due to the reliance on already existing materials used in dental restoratives. Most polymers used in dental restoratives have a CTE in the range of about 80 ppm/° C. Polymers with aromatic backbone such as BisGma have lower CTE of about 60 ppm/° C. Addition of inorganic fillers has reduced the CTE of composite resins to about 35 ppm/° C., However, further reductions in CTE to match the tooth has not been successfully explored in the current landscape of dental restorative materials. As a result, from a materials standpoint, there has been an absence of materials to formulate dental composite resins which are effective at being a restorative material and have a CTE which is within the range of dentin.

(6) The present invention deals with a novel direct fill restorative that features resistance to the formation of secondary caries. Specifically, the primary feature of the direct fill composite resin disclosed below decreases the incidence of secondary caries by having a CTE that approximates dentin.

(7) A filler was selected that would incorporate the low CTE feature of this invention as well as other properties necessary for a direct filling material. The CTE of the filler is less than 1 ppm/° C. The filler also produces other features necessary in a direct filling restoration, for example, excellent handling, sculptability, esthetics, mechanical properties, x-ray radiopacity and durability in anterior and posterior restorations, etc. . . .

(8) As discussed above, simply selecting fillers with a low CTE is not sufficient to yield a composite resin with a CTE that approximates dentin. So, in addition to utilizing a filler with a low CTE, additional technology was introduced to improve particle-to-particle interaction while maintaining moldability and sculptability in the paste. A technique similar to the process of making steel was employed. In steel production, carbon particles are added to an iron matrix in a process called dispersion hardening. The result is the matrix is constrained and the composition is harder and stronger. The details of the ingredients and processing technology is a well-protected trade secret in the steel industry.

(9) As discussed above, utilizing a particle size distribution that increases particle-to-particle interaction can increase the influence that the filler's CTE has on the composition as a whole. The high loading of the filler by itself is not sufficient to explain the low CTE value. Table 3 shows the CTE values and wt % filler loading of a typical hybrid composite, Nuance®, sold by Den-Mat Holdings, LLC, versus the low CTE direct fill restorative described by this invention as exemplified by Example 3 below. The CTE of the Nuance® is 36.9 ppm/° C., which is exemplary of composite resins; whereas the low CTE direct fill restorative is 12-15 ppm/° C., which is dramatically lower.

(10) The low CTE value of the low CTE direct fill restorative cannot be explained simply by the increased filler loading in this case. Table 3 discloses the corresponding filler loading of both pastes. The wt % filler loading is similar for both pastes (78% vs. 79% by wt. correspondingly).

(11) TABLE-US-00003 TABLE 3 Coefficient of Thermal Material Expansion ppm/° C. Filler load wt % Nuance ® 36.9 78 Example 3 12.0-15.0 79

(12) While it is true that higher filler loading with low CTE fillers may reduce the total CTE of a composite, other factors must also be considered. When the filler loading is very high, handling factors disclosed above apply. Further, higher loaded composite resins typically use larger filler particles in the range 25 microns or larger. The larger particles make it difficult to finish and polish by the dentist. And with wear, the composite surface becomes dull and rough to the tongue. For this reason, composite resins containing large particles are not favored. Highly filled composite resins with filler loading greater than 85% by wt. are disfavored for this reason and other handling issues disclosed above. Today, the composite resin market is dominated by nanofilled resins with smaller nanofillers that have more favored advantages.

(13) In this invention, a trimodal distribution of filler particles is utilized to accomplish the low CTE values. The trimodal filler distribution allows for greater particle-to-particle interaction. It also allows filler particles to flow when a force is applied so that the paste may be molded and sculptured by the dentist. This results is an unexpectedly low CTE value of about 12-15 ppm/° C. in the cured paste, a match to the CTE of dentin.

(14) The process involves a trimodal filler distribution. The trimodal filler distribution comprises of the following filler glasses: 15-50% by wt. submicron fillers, 0-15% by wt % 1 micron filler and 50-90% by wt % 5 micron fillers. This blend was uniformly dispersed and silanated with a coupling agent, for example, gamma methacryloxytrimethoxy silane, by jar milling.

(15) When compounded into a paste, the interstitial space between the larger particles is filled with the medium sized particles, which allows greater particle-to-particle interaction. The smaller nanoparticle, (e.g. fumed silica), dispersion hardens the resin matrix further increasing particle-to-particle interaction. This contributes to the unexpectedly low CTE value.

(16) Additionally, this novel dental restorative includes a compound with antimicrobial properties that are long lasting clinically. The activity does not have to be strong but must be long lasting. For example, zinc oxide has mild antimicrobial activity, but appears to be long lasting; whereas silver has strong activity but may not last as long. However, antimicrobial activity alone does not necessarily guarantee caries resistance. Amalgams, for example, contain silver and demonstrate good antimicrobial activity initially, but in the long term have proven to have a high rate of caries incidence. To be effective, caries-resistant materials must have antimicrobial activity throughout its restorative life.

(17) Enduring antimicrobial activity may be related to the second important feature, ensuring that the dental restorative has a CTE that matches or is at least substantially similar to the CTE of dentin. As discussed, when this happens, the “Marginal Percolation” effect does not happen, and bacterial penetration and dilution of antimicrobials is minimized. The “Marginal Percolation” effect may help explain why some materials such as amalgams, lose their caries resistance over time. As illustrated in Table 1, silver in amalgams has strong antimicrobial activity, but amalgams also have a higher CTE value than the tooth. As a consequence, “Marginal Percolation” promotes dilution of the antimicrobial and also promotes bacterial penetration into the marginal gaps.

(18) The invention also includes an antimicrobial to kill any bacteria present and would be effective should new gaps occur. As an antimicrobial compound, zinc oxide has several advantages. It has a long history of mild antimicrobial activity and long-term effectiveness.

(19) Zinc oxide has been tested for antimicrobial activity in this invention according to a test that is based upon the International Standard AATCC TM 100-2012. The AATCC TM 100-2012 standard tests for microbial activity on textiles, so the test was modified for use on solid and composite materials. Under the modified AATCC TM 100-2012 test, zinc oxide has been found to be effective in killing bacteria.

(20) Table 4 below demonstrates the effect of zinc oxide on the antimicrobial activity of a direct filling composite resin. As discussed above, microbial activity is measured using a modified AATCC TM 100-2012 standard for use on solid and composite materials.

(21) TABLE-US-00004 TABLE 4 Effect of Zinc Oxide on e. coli Wt. Fract. ZnO % Reduction of e coli % reduction of strep mutans 0 0% 0% 1.0% 100% 100%

(22) When zinc oxide is incorporated into a chemical for use in the oral cavity, it is typically incorporated for its function as an opacifying agent and can be added to a product for this function alone. However, there is a limit to the amount that can be added. Resins are esthetic restorative materials and require high translucency to be esthetic. For this reason, the amount of zinc oxide that may be added is limited to less than 0.8 wt. fract. See Table 5 for the upper limits of zinc oxide that can be incorporated into a direct fill composite resin while maintaining high translucency.

(23) TABLE-US-00005 TABLE 5 Effect of Zinc Oxide on the translucency of a direct filling composite resin. Wt. Fract. ZnO Translucency 0 pass 0.8 pass 1.0 fail

(24) In Table 5, as the wt. fraction of Zinc Oxide is increased, the opacity also increases to a level that is not considered suitable for use as a dental composite resin for esthetic purposes. For esthetic purposes, the dental composite resin must be sufficiently translucent to mimic the appearance of natural dentin. Beyond this level, the opacity becomes too high and the restoration appears as chalky white.

(25) Dental restoratives used in core build up procedures are typically lower filled composite restoratives, used in internal portions of the teeth, where esthetics (color, translucency, surface finish) and wear properties are less important, and mechanical strength (>115 megapascals in flexural strength), microbial and CTE issues are of primary importance. Because of the decreased emphasis on esthetics for these types of dental restoratives, higher amounts, for example greater than 0.8%, of zinc oxide can be used. These materials are used to fill irregular, often small, undercut internal voids in the dentition, as well as being used to support implantable synthetic “core posts” (metal or fiber rods of 0.5-2 mm in diameter and 1-5 mm in length). Due to these variable uses, the viscosity of this class of materials is lower, not too dissimilar to that of an over the counter dentifrice.

(26) This class of materials are often light cured, chemically “self” cured (via benzoyl peroxide curatives) as well as dual cured, allowing for light and self-cure with the same material. The material discussed here is dual cure, allowing for a fast cure via photo initiation, or allowing the material to cure more slowly on its own. When the composition is light cured, a photo initiator compound is included into the composition. A fairly typical photo initiator used in light cured dental composite restoratives is camphorquinine. However, any other suitable photo initiator can be used.

(27) In order to prevent premature self-curing, this material is typically a two-component composition that are stored separately to allow the materials to maintain the desired viscosity (and not cure) and are admixed at the time of the dental procedure. The need for mixing as well as the aforementioned broad scope of use as a core material requires that the viscosity be relatively low, when compared to other conventional composite restoratives. Each component will contain compounds that are chemically inert by itself, however, when combined, will cure. In the embodiment discussed below in Table 6, component A contains benzoyl peroxide and component B contains dihydroxyethyl paratoluidine. When these chemicals are combined, the resulting chemical reaction will cure the resulting composition. Any other suitable binary curing system can be used instead of the combination of benzoyl peroxide and dihydroxyethyl paratoluidine.

(28) In particular, this dental restorative is a material that is stored in a dual chamber syringe, and is dispensed through a static mixer tip, and is intended to be dispensed by hand pressure alone (no mechanical aids such as a cartridge dispensing gun, or other devices that provide mechanical advantage and reduce the force needed to dispense). As such, there is an implicit maximum to how thick the material can be, and still be practicably dispensed from the packaging by dental professionals, including those with below average hand strength.

(29) Additionally, this dental restorative can also encompass the novel inclusion of bioactive components into the formulation. Bioactivity is determined in accordance with ISO/FDIS 23317. Such bioactive components allow for the formation of hydroxyapatite (the primary component of natural teeth) and allows the restoration to improve long term retention via the remineralized restoration surface “growing” into a single cohesive part of the tooth. As those skilled within the art are aware, the addition of bioactive materials imparts reduced mechanical properties of the final cured material.

(30) The need for strong mechanical properties, as well as lower viscosity requirements, the bioactivity requirements, low CTE and antimicrobial components, provide a difficult set of desired properties that each can reduce the other properties.

(31) An exemplary two-component direct fill dental restorative that incorporates zinc oxide and bioactive materials to yield a novel composite resin that exhibits antimicrobial materials and a CTE that is in the desired range to mimic dentin is as follows:

(32) TABLE-US-00006 TABLE 6 Example 1: Dual Component low CTE Direct Fill Dental Restorative Weight/ Chemical weight percentage Part A Hardener 0.15-0.30 diphenyl (2,4,6-trimehylbenzoyl) phosphine oxide 0.07-0.09 Ethyl 4-dimethylaminobenzoate 0.05-.15  Camphorquinone 0.05-0.15 Resin Blend 22-35 2-(2′ hydroxy-5′-octylphenyl) benzotriazole 0.4-0.5 butylated hydroxytoluene 0.008-0.01  Trimodal Filler Glass Blend 41-59 fumed silica blend 1.5 Anti-Microbial  0.2-0.75 Calcium fluoride   0-1.75 Part B dihydroxyethyl paratoluidine 0.6-0.9 diphenyl (2,4,6-trimehylbenzoyl) phosphine oxide 0.07-0.09 Ethyl 4-dimethylaminobenzoate 0.05-.15  Photo Initiator 0.05-0.15 Resin Blend 12-35 2-(2′ hydroxy-5′-octylphenyl) benzotriazole 0.4-0.5 butylated hydroxytoluene 0.008-0.01  Trimodal Filler Glass Blend 41-59 fumed silica blend 1.5 Anti-Microbial  0.2-0.75 Calcium fluoride   0-1.75 Bioactive component  9-12

(33) An alternative embodiment would be a single component direct fill dental restorative that is light cured only (Table 7). Because this embodiment lacks the ability to self-cure the entire composition can be stored in a single component. However, lack of self-curing reduces the dental professional's flexibility in use.

(34) TABLE-US-00007 TABLE 7 Single Component Low CTE Direct Fill Restoratives Weight/weight % Chemical Example 2 Example 3 diphenyl (2,4,6-trimehylbenzoyl) 0.07-0.09 phosphine oxide Ethyl 4-dimethylaminobenzoate 0.05-0.15 0.05-0.15 Photo Initiator 0.05-0.15 0.05-0.15 Resin Blend 32-90 20-35 2-(2′ hydroxy-5′-octylphenyl) benzotriazole 0.4-0.5 0.4-0.5 Butylated hydroxytoluene 0.008-0.01  0.008-0.01  Trimodal Filler Glass blend 50-71 75-85 Fumed Silica blend 1.5 0.5-1.5 Anti-Microbial  0.2-0.75 0.8-1.0 Calcium fluoride   0-1.75

(35) The method of manufacturing such a restorative is as follows:

(36) 1. Soluble components such as photoinitiators, inhibitors and stabilizers are dissolved into the resin.

(37) 2. The filler glasses and fumed silica (hydrophobic or hydrophilic or a blend of hydrophobic and hydrophilic) are pre-blended to create the trimodal filler distribution. The blend of filler glasses are silanated with a coupling agent.

(38) 3. The pre-blended filler glasses, fumed silica and zinc oxide are added to the resin in small increments until the desired viscosity of the dental restorative is achieved.

(39) 4. The ensuing composition is then placed in a roll mill.

(40) Low CTE was achieved by employing a trimodal distribution of low CTE x-ray radiopaque filler at high loading. For example, using a filler with a CTE value of <1 ppm/° C. vs. a more typical x-ray radiopaque filler which as a CTE of about 4 ppm/° C. The lower CTE value allows further reduction of the CTE of the composite resin to about 15 ppm/° C., well within the range of dentin.

(41) Zinc oxide is incorporated within the resin to provide enhanced antimicrobial activity. As illustrated by Tables 4 and 5, the amount of zinc oxide incorporated within the resin is sufficiently high enough to provide enhanced antimicrobial activity, but low enough to prevent opacity of the restorative.

(42) The resin can be selected from the group of resins commonly used in direct fill dental restoratives. For example, some commonly used resins can include, but is not limited to, ethoxylated bisphenol A dimethacrylate, Bis GMA or triethylene glycol dimethacrylate. The resin can either be present individually, or as a blend of resins. Inhibitors and stabilizers may be added to the resin to extend the shelf life of the direct fill dental restorative.

(43) The light curing direct filling composite restoratives disclosed in Tables 6 and 7 results in a restorative with excellent antimicrobial activity, mechanical properties and a CTE that closely approximates that of dentin (12-15 ppm/° C.). Moreover, the paste is very moldable and tooth anatomy may be sculptured into the restoration by the dentist. Antimicrobial activity follows the trend disclosed in Table 4.

(44) The CTE achieved by a typical light curing direct filling composite, Nuance® (high viscosity Universal Composite restorative) by Den-Mat Holdings, LLC, as compared to the direct fill restorative described by Example 3 is shown in table 8. Nuance® was selected for the comparison because its properties are representative of the current state of the art of dental restoratives. The CTE was measured using the ASTM D 695 standard.

(45) TABLE-US-00008 TABLE 8 Coefficient of thermal expansion (CTE) of direct filling composite resins Material CTE ppm/° C. Nuance ® 36.9 Example 3 16.1

(46) Because, the caries-resistant direct filling composite must also function as a restorative material, its material characteristics must meet or exceed the current standards set by currently available dental restoratives. Table 9 compares the flexural strength between the Example 3, and Nuance®. The flexural strength was measured in accordance with the ISO 4049. As Table 9 indicates, the flexural strength of Example 3 exceeds that of Nuance®.

(47) TABLE-US-00009 TABLE 9 Material Flexural Strength, Mpa Nuance ®  83.4 MPa Example 3 >113.0 MPa

(48) The foregoing description of the invention with the accompanying examples is not intended to be limiting. It is contemplated that other embodiments may be made without departing from the spirit or scope of the invention as set forth in the appended claims.