Compositions and methods for bioactive dental composites

Abstract

Described herein are compositions and methods which produce hydrolytically stable resin monomers, bioactive fillers, phosphorus coupling agent and surface coating method, which can be combined to produce new generation dental composites; compositions comprising the same, as well as methods of making and using the same are also described.

Claims

1. A dental composition comprising: a hydrolytically stable resin, the hydrolytically stable resin including a monomer lacking an ester or amide bond between a polymerizable double bond; a bioactive filler; and a coupling agent, the coupling agent lacking a hydrolysable ester bond, wherein the coupling agent has FA (fluoroapatite) or calcium phosphate binding groups, comprising phosphorus binding groups selected from the group consisting of phosphonic acid group (PO.sub.3H.sub.2) as well as its salt and combinations and mixtures thereof.

2. The dental composition according to claim 1, wherein the bioactive filler includes at least one material selected from the group consisting of FA (fluorapatite), HA (hydroapatite), FHA (fluorhydroxyapatite), ACP (amorphous calcium phosphate), TCP (tricalcium phosphate), TTCP (tetracalcium phosphate), DCP (dicalcium phosphate), MCP (monocalcium phosphate), bioglass, quartz, glass, silicate, Ba/Sr/silicate glass, metal oxides, YbF.sub.3, and mixtures thereof.

3. The dental composition of claim 1, wherein the filler can be used as major filler or minor filler.

4. The dental composition of claim 1, wherein the coupling agent includes a material selected from the group consisting of phosphorus group, carboxylic acid group, hydroxyl group, amino group, sulfonic acid group, as well as their salt, and combination and mixtures thereof.

5. A dental composition comprising: a hydrolytically stable resin, the hydrolytically stable resin including a monomer lacking an ester or amide bond between a polymerizable double bond; a bioactive filleri and a coupling agent, the coupling agent lacking a hydrolysable ester bond, wherein the coupling agent has the structure the general structure: ##STR00013## wherein the number of phosphonic groups and CC double bonds independently can be 1, 2, 3, 4, 5, 6, 7, 8, 9, and/or 10, wherein R, R1 and/ or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH2).sub.p, (CF2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 and any combination thereof, where p and q are independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein X, and/or X are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH2).sub.p, (CF2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2; wherein the number of a and b can each independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, and/ or 10; wherein the phosphorus group can be replaced by carboxylic, sulfonic, hydroxyl or amine group.

6. The dental composition of claim 1, wherein the filler can be coated after preparation of filler or with preferable method to combine surface coating and ball milling into one single step.

7. The dental composition of claim 1, wherein the monomer has greater water resistance than BisGMA and TEGDMA.

8. The dental composition of claim 1, wherein the monomer has the general structure: ##STR00014## wherein R is selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein Y, Z, Y and/ or Z are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH2)p, (CF2)q, (CHF)q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, or combination with any of OH, COOH, PO.sub.3H.sub.2, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein R1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; and wherein R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

9. The dental composition of claim 1, wherein the monomer has the general structure: ##STR00015## wherein R is selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 and any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein X, Y, X and/or Y are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 and any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein R1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 and any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; and wherein R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 and any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

10. The dental composition of claim 1, wherein the monomer has the general structure: ##STR00016## wherein R is selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein X, Y, Z, X, Y, and/or Z are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein R.sub.1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; and wherein R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p and q can each independently be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

11. The dental composition of claim 1, wherein the monomer includes a calcium binding group selected from the group consisting of phosphonic, phosphoryl, carboxylic, sulfonic, hydroxyl, amino, as well as their salt, and combination or mixtures thereof.

12. The dental composition of claim 1, wherein the hydrolytically stable resin is effective to resist hydrolysis.

13. The dental composition of claim 1, wherein the bioactive filler has similar chemical composition with tooth, including calcium, or phosphate, or fluoride or combination and mixtures thereof, thus the calcium and phosphate in saliva can remineralize on the filler or composite.

14. The dental composition of claim 1, wherein the coupling agent includes a polymerizable double bond and a calcium binding group selected from the group consisting of a phosphorus group, a carboxylic acid, an amino group, a hydroxyl group, a sulfonic group, and/or their salt form.

15. The dental com-position of claim 1, A dental composition comprising: a hydrolytically stable resin, the hydrolytically stable resin including a monomer lacking an ester or amide bond between a polymerizable double bond; a bioactive filler; and a coupling agent the coupling agent lacking a hydrolysable ester bond, wherein the coupling agent has the structure the general structure: ##STR00017## wherein R is selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, or any combination thereof, where p and q are independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; wherein X and X are independently selected from the group consisting of CH.sub.2, O, S, or N; where the number of a orb can independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; wherein the phosphorous group can be replaced by carboxylic, sulfonic, hydroxyl or amine groups; wherein the number of phosphonic group and CC double bonds can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 illustrates one scheme for the degradation of conventional resin and coupling agent resulting from the hydrolysis of the ester bonds. Such degradation leads to breakdown of polymer matrix and reduced mechanical strength;

(2) FIG. 2 illustrates one scheme showing less impact to the polymer backbone and mechanical strength from the degradation of the newly developed resins, which have high resistance to hydrolysis, because no ester bonds are within the main polymer backbone;

(3) FIG. 3 illustrates one scheme showing the synthesis of the monomer containing amide group;

(4) FIG. 4 illustrates one scheme showing the synthesis of monomers with an ester or amide on a side chain of the polymeric matrix;

(5) FIG. 5 illustrates one scheme of the synthesis of monomers with non-hydrolysable ether;

(6) FIG. 6 illustrates one synthesis of flexible TEGDMA analogues: ether, ester and amide;

(7) FIG. 7 illustrates one synthesis of hydrolytic stable resin containing phosphonic group;

(8) FIG. 8 illustrates one HNMR of the prepared monomer illustrated therein;

(9) FIG. 9 illustrates one synthesis of new coupling agent for FA or calcium phosphate filler;

(10) FIG. 10 illustrates one HNMR of the prepared monomer illustrated therein; and

(11) FIG. 11 illustrates an X-ray diffraction pattern of a prepared fluoroapatite (FA) filler.

DETAILED DESCRIPTION

(12) A variety of compositions may be prepared as described herein. For example a variety of exemplary syntheses are provided in FIGS. 3-7. Further exemplary materials are illustrated in FIG. 2 as well as shown in the resulting compositions in FIGS. 3-7.

(13) The monomers described herein may be used in a variety of applications, such as dental applications. For example, in one form, the monomer may be used to form a polymeric matrix for use in a dental composition. In another form, the monomer may be provided in a polymeric matrix along with bioactive filler, a coupling agent and an optional surface coating.

(14) In one form, the composition includes:

(15) ##STR00005##

(16) where R is selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p and q are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(17) where X, Y, Z, X, Y, and/or Z are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(18) where R1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(19) where R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

(20) In one form, the composition includes:

(21) ##STR00006##

(22) where R is selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p, q are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(23) where Y, Z, Y and/or Z are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, or combination with any of OH, COOH, PO.sub.3H.sub.2, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(24) where R1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(25) where R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

(26) According to one form, the composition includes:

(27) ##STR00007##

(28) where R is selected from the group consisting of: B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p, q are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(29) where X, Y, X and/or Y are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(30) where R1, R1, R2, and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(31) where R3, R4, R3, and/or R4 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2, COOH, PO.sub.3H.sub.2 or any combination thereof, where p, q, m are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

(32) According to one form, the monomer has the structure of formula 3b, which is prepared from less hydrolysable amide:

(33) ##STR00008##

(34) where R is selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, or any combination thereof, where p, q can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(35) where R1, and/or R1 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(36) where R2, and/or R2 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(37) where R3, and/or R3 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(38) where X, and/or X are each independently selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2O).sub.m, or any combination thereof, or combination with any of OH, COOH, PO3H2, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

(39) In yet another form, one type of the monomer has the structure of formula 6, which is prepared from non-hydrolysable ether:

(40) ##STR00009##

(41) where R is selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, or any combination thereof, where p, q can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(42) where X, and/or X are each independently selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(43) where Y, and/or Y are each independently selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(44) where R1, and/or R1 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(45) where R2, and/or R2 are each independently selected from the group consisting of H, OH, COOH, PO3H2, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(46) where R3, and/or R3 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

(47) In yet another form, one type of the monomer has the structure of formula 5b, wherein the ester or amide moieties are NOT within polymer backbone:

(48) ##STR00010##

(49) where R is selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, or any combination thereof, where p, q can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(50) where X, and/or X are each independently selected from the group consisting of O, or N;

(51) where Y, Z, Y, and/or Z are each independently selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(52) where R1, R1, R2, and/or R2 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(53) where R4, and/or R4 are each independently selected from the group consisting of H, OH, COOH, PO3H2, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

(54) where R3, and/or R3 are each independently selected from the group consisting of H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CH.sub.2CH.sub.2O).sub.m or any combination thereof, where p, q, m can each independently be=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

(55) It should be noted that the monomer can have calcium binding group selected from the group consisting of: phosphonic, phosphoryl, carboxylic, sulfonic, hydroxyl, amino, as well as their ester or salt (sodium, potassium, ammonium) and combination or mixtures thereof.

(56) In one form, the monomers of resin comprise the new resin monomers having greater water resistance than currently used BisGMA and TEGDMA.

(57) It should be understood that the synthetic pathways to form the resins of the preceding claims can be different reactions including coupling, click, addition, substitution, condensation, esterification, and amide reaction.

(58) According to one form, the bioactive filler may include at least one material selected from the group consisting of: FA (fluorapatite), HA (hydroapatite), FHA (fluorhydroxyapatite), ACP (amorphous calcium phosphate), TCP (tricalcium phosphate), TTCP (tetracalcium phosphate), DCP (dicalcium phosphate), MCP (monocalcium phosphate), bioglass, quartz, glass, silicate, Ba/Sr/silicate glass, metal oxides (ZrO.sub.2, TiO.sub.2, Al.sub.2O.sub.3), YbF.sub.3, and combinations thereof.

(59) In addition to the above bioactive fillers, additional filler such as bioglass, quartz, glass, silicate, Ba/Sr/silicate glass, metal oxides (ZrO.sub.2, TiO.sub.2, Al.sub.2O.sub.3), YbF.sub.3, and combinations thereof can be included.

(60) In one form, the coupling agent may include FA or calcium phosphate binding groups, comprising phosphorus binding groups selected from the group consisting of: phosphonic acid group (RPO3H2), phosphoryl acid group (OPO3H2), as well as their ester or salt (e.g., sodium or potassium, ammonium), and combinations and mixtures thereof. According to one form, the coupling agent includes a material selected from the group consisting of: phosphorus group, carboxylic acid group, hydroxyl group, amino group, sulfonic acid group, as well as their ester or salt (e.g., sodium or potassium, ammonium), and combination and mixtures thereof.

(61) For example, the coupling agent may have the general formula:

(62) ##STR00011##

(63) where R, R1 and/or R2 are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2 or any combination thereof, where p, q are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(64) where X, and/or X are each independently selected from the group consisting of B, C, Si, O, S, N, P, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, (CHF).sub.q, CO, CC, CC, benzyl, phenyl, F, Cl, Br, I, NO.sub.2;

(65) where the number of a, or b can each independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, and/or 10;

(66) where the phosphorus group can be replaced by carboxylic, sulfonic, hydroxyl or amine group.

(67) In another form, the coupling agent may have the general formula:

(68) ##STR00012##

(69) where R is selected from the group consisting of O, S, N, H, (CH.sub.2).sub.p, (CF.sub.2).sub.q, or any combination thereof, where p, q are independently=0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

(70) where X, or X are independently selected from the group consisting of CH2, O, S, or N;

(71) where the number of a, or b can independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10;

(72) where the phosphorus group can be replaced by carboxylic, sulfonic, hydroxyl or amine groups;

(73) wherein it has number of phosphonic group and CC double bonds can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

(74) According to one form, the surface coatings may include silane coupling agent, isocyanates coupling agent, titanate coupling agent, zirconate coupling agent, and the like.

(75) In one form, the filler can be coated after preparation of the filler or by combining surface coating and ball milling in a single step

EXAMPLES AND TESTS

(76) 1. Synthesis hydrolytically stable monomers

(77) 2. Synthesis FA filler

(78) 3. Synthesis coupling agent

(79) 4. Fabricate composites

(80) A number of strategies are contemplated for forming less hydrolysable resins. Strategy#1: synthesize monomers in which esters are replaced by amides. See, for example FIG. 3. Amide's hydrolysis half-life is 38,000 fold of ester. Recent studies on some amide resins for adhesive application confirmed the hydrolytic stability. Therefore, the amide resin has less mechanical reduction in the oral cavity than BisGMA.

(81) Strategy#2: synthesize monomers in which hydrolysable ester or amide bonds will be moved to the polymer side chain. Because hydrolysis of side chain does not breakdown the polymeric matrix (FIG. 4) this polymer has greater mechanical strength than n BisGMA after aging in the oral cavity.

(82) Strategy#3: synthesize ether-based monomer, such as shown in FIG. 5. Because ether is completely non-hydrolysable, the ether-based monomer is completely stable in the oral cavity and has no strength reduction with aging. In order to further reduce the shrinkage, the new monomers can be combined with rigid POSS (polyhedral oligomeric silsesquioxane) core (Strategy#5), thus the stiffness and strength can be improved, while the shrinkage will be reduced.

(83) SYNTHESIZE LOW DEGRADABLE AMIDE BASED MONOMERAMIDE A (3): Bisphenol-A (22.8 g) and NaOH (8.8 g) were added THF. Then, 2-chloroethylamine hydrochloride (29.0 g) was added and the solution was kept stirring at room temperature overnight. After being washed with saturated NaHCO.sub.3 and water, the solvent was removed by a rotavap. Then, the crude product of amino bisphenol A (31.4 g), 2.2 g of TEA (triethylamine) and 0.3 g BHT (Butylated hydroxytoluene) was added into the flask. Under Ar protection, methacryloyl chloride (20.9 g) was added dropwise under ice bath. Alkylation of 3a was performed in DMSO at room temperature.

(84) SYNTHESIZE MONOMERS WITH ESTER/AMIDE ON SIDE CHAINS OF POLYMERS: Propoxylated-bisphenol A (4) was synthesized via a direct nucleophilic ring-open of propylene oxide by bisphenol-A (FIG. 7). Bisphenol-A (57.0 g), and NaOH (20.0 g) were added into THF with Argon protection. After stirring at room temperature for 3 hours, propylene oxide (34.8 g) was added. After stirring overnight, the solution was acidified with 0.1 mol/L HCl and extracted with ethyl acetate, washed by water. After drying over anhydrous Na.sub.2SO.sub.4 overnight, the solvent was removed by a rotary evaporator.

(85) Ester-B (5a) was synthesized according to modified procedures for (2) with NaH. 34.4 g of (4), NaH (5.3 g) and 0.3 g BHT were added into dry THF. After stirring for 2 hours, methyl 2-(chloromethyl)acrylate (33.6 g) were added under Ar protection. After stirring at room temperature overnight, the product was purified as that for (4). The crude product was further purified by silica gel column with ethyl acetate and methylene chloride (1/1v/v) as the eluant.

(86) The formation of ester-B was confirmed by HPLC-MS. The chemical structure of ester-B was confirmed by .sup.1H NMR spectra, showing the characteristic chemical shifts at 7.1 ppm and 5.9 ppm, but with impurity of ethyl acetate (peaks a and c).

(87) SYNTHESIZE NON-DEGRADABLE MONOMER BASED ON ETHER BOND ABSENCE OF ESTER OR AMIDE: The ether based monomer (6) was synthesized via a one-step direct nucleophilic ring-open of allyl glycidyl ether on bisphenol-A (Ether-C). The synthesis was conducted according to that of (4) with the exception of using allyl glycidyl ether instead of propylene oxide.

(88) One-step preparation of ether-C (6) provided satisfactory result of synthesis. While HPLC measurement confirmed the formation of ether-C, the chemical structure was confirmed by .sup.1H NMR spectra (FIG. 11), showing the existence of chemical shifts at 7.1 ppm and 5.9 ppm. By comparing the integration ratio of the above two peaks, the yield of allyl substitution is calculated about 65%, confirming that single-step reaction is favorable.

(89) SYNTHESIZE MONOMER CONTAINING PHOSPHONIC ACID GROUP FOR ENHANCED BINDING WITH FA FILLER AND TOOTH: Synthesize Phosphonated Monomer (10 and 11): Phosphonated monomer was synthesized via a two step reaction. Bisphenol A diglycidyl ether (34.0 g) reacted with 38.3 g of aminoethylphosphonate dimethyl ester in dry THF under Ar at room temperature for 2 hours. Then, 25.3 g of TEA, 0.3 g of BHT, and 33.6 g of methyl 2-(chloromethyl)acrylate was added dropwise at room temperature and was kept overnight. Conversion from phosphonate ester (monomer 10) to phosphonic acid (ester-F, 11) was conducted according to Moszner's published method. (Moszner, N., Zeuner, F, Fischer, U. K., Rheinberger, V., Monomers for Adhesive Polymers, 2. Synthesis and Radical Polymerisation of Hydrolytically Stable Acrylic Phosphonic Acids, Macromolecular Chemistry and Physics, 1999, 200: 1062-1067.)

(90) PREPARE DENSE CERAMIC FA BY FURNACE: Dense ceramic FA powder was prepared according the chemical reaction: 3 -Ca.sub.3(PO.sub.4).sub.2+CaF.sub.2.fwdarw.2 Ca.sub.5 (PO.sub.4).sub.3F. -Tricalcium phosphate (-TCP, -Ca.sub.3(PO.sub.4).sub.2) was prepared by heating 1 mol of calcium carbonate (CaCO.sub.3) and 2 mol of calcium phosphate dibasic anhydrous (DCPA) in a furnace to 1200 C. for 6 hours and quenched in air. Calcium fluoride (CaF.sub.2) was dried in an oven 105 C. for 3 hours. For stoichiometric FA with Ca:P:F molar ratio 5:3:1, 3 mol of -TCP and 1 mol of CaF.sub.2 was mixed and heated in a furnace 1500 C. for 6 hours to complete the conversion. By adjusting the proportion of the various calcium phosphate and calcium fluoride components in the mixture, a range of other dense calcium phosphate and calcium fluoride particles can be prepared.

(91) XRD patterns from prepared FA is quantitatively similar to the standard FA JSPDS both in 2 and intensity, particularly for the strong peaks at (002), (211), (300), (310), (222) and (213) (FIG. 12). (Chen, M. Jiang, D., Li, D., Zhu, J., Li, G., Xie, J., Controllable Synthesis of Fluorapatite Nanocrystals with Various Morphologies: Effects of pH Value and Chelating Reagent, Journal of Alloys and Compounds, 2009, 485: 396-401.) No obvious peak from -TCP and CaF.sub.2 indicates the complete conversion into FA.

(92) PREPARATION OF FA MICRO- AND NANO-PARTICLES BY BALL MILLING: FA microparticles were ground by a Retsch Planetary Ball Mill (Model PM400) for 24 hours at 200 rpm. The FA nanoparticles were ground at 1000 rpm by a Pulverisette 7 Premium Line machine.

(93) SYNTHESIZE HYDROLYTICALLY STABLE COUPLING AGENT: The new coupling agent vinyl glycidyl ethylphosphonic acid (FIG. 9) was synthesized according to the phosphorylation method for compound 10. This agent has a phosphonic group, which can strongly bind with FA and teeth. Only ether moieties instead of esters existing in the entire molecule make it hydrolytically stable.

(94) COMBINE BALL MILLING AND SURFACE COATING: The phosphorus coupling agent was dissolved in ethanol to obtain concentrations relative to the filler in 1, 2, and 5% (w/w of coupling agent/filler). The fillers were coated by agitation or stirring for various times, preferably 2 hours, and were then separated using a centrifuge and washed by ethanol three times. The phosphorus coupling agent coated fillers were dried at room temperature under vacuum overnight.

(95) In order to enhance the interfacial adhesion between resin matrix and FA particles and prevent agglomeration, we combined ball milling and coating with the coupling agent, thus the FA particle can be stabilized immediately during grinding, thus prevent the agglomeration

(96) In ball milling, the phosphorus coupling agent was added to the dispersion of filler in n-propanol which was dissolved in ethanol to obtain concentrations of 1, 2, and 5% (w/w). The fillers were coated by agitation or stirring for various times, preferably 2 hours, and were then separated using a centrifuge and washed by ethanol three times. The phosphorus coupling agent coated fillers were dried at room temperature under vacuum overnight.

(97) COMPOSITES FABRICATION: The composite will be fabricated from the previously prepared hydrolytically stable monomers, densely ceramic FA filler, the initiator, and new phosphonic coupling agent coated FA particles. A monomer consisting of two monomers (one rigid and one flexible) at 1:1 mass ratio with 0.2% camphorquinone and 0.8% ethyl 4-N,N-dimethylaminobenzoate will be used for light-curable resin. Two types of FA, either nano-FA or micro-FA are milled as reinforcing materials at varied FA loading ratio. FA particles will be pre-mixed in varied mass ratio of micro-FA/nano-FA: 50:50%, 60:40%, 70:30%, and 80:20%. A monomer consisting of the same ratio of two monomers with 2% benzoyl peroxide, and 0.07% MEHQ will be used for heat curing. (Xu, H. H. K., Long-Term Water-Aging of Whisker-Reinforced Polymer-Matrix Composites, Journal of Dental Research, 2003, 82(1): 48-52.) Heat-curing will be conducted in an oven (Model 48, Fisher Scientific) at 140 C. for 30 min to produce bar specimens. The paste mixed from fillers and monomer will be cured in a stainless steel mold (2225 mm.sup.3).