REMINERALIZING DENTAL MATERIAL

Abstract

A subject of the invention is a remineralizing dental material, having at least one cation and at least one anion, which are configured as partner ions for forming a remineralization substance. In accordance with the invention at least one of the partner ions is multivalent and is included as counterion in a coacervate. A further subject of the invention is a kit for producing such a dental material, and also the use thereof.

Claims

1. A remineralizing dental material, having at least one cation and at least one anion, which are configured as partner ions for forming a remineralization substance, wherein at least one of the partner ions is multivalent and is included as counterion in a coacervate.

2. The dental material as claimed in claim 1, wherein one of the partner ions is multivalent and is included as counterion in a coacervate, and a second partner ion is included in aqueous solution.

3. The dental material as claimed in claim 1 or 2, wherein it further comprises a second polyelectrolyte, which has a different charge from the polyelectrolyte of the coacervate.

4. The dental material as claimed in claim 1, wherein both partner ions are multivalent and are included as counterion of a respective coacervate.

5. The dental material as claimed in any of claims 1 to 4, wherein the anionic polyelectrolytes for forming the coacervates with multivalent cations are selected from the group of organic polyelectrolytes, preferably consisting of a. polymers and copolymers which contain carboxylic acid groups, phosphoric acid groups, phosphonic acid groups and/or sulfonic acid groups, and also their salts and their partial esters; preferably polycarboxylic acids, polyalkylene phosphoric acids, polyalkylene phosphonic acids, and polysulfonic acids, and also their salts and their partial esters; more preferably poly(meth)acrylic acid, polyaspartic acid, polyitaconic acid, and polyglutamic acid, and also their salts; b. acidic proteins, acidic protein derivatives, and their salts, preferably of lysozyme or of gelatin (type B); c. acidic polysaccharides and their salts, preferably of carrageenan, of pectin, of algic acid, and of hyaluronic acid.

6. The dental material as claimed in any of claims 1 to 5, wherein the anionic polyelectrolytes for forming the coacervates with multivalent cations have average molecular weights (weight average Mw) of between 3 kDa and 1500 kDa, preferably between 5 and 500 kDa, more preferably between 8 kDa and 200 kDa, more preferably still between 8 and 50 kDa.

7. The dental material as claimed in any of claims 1 to 6, wherein the multivalent cations are selected from the group consisting of mineral-forming cations; preferably metal cations; more preferably the metals of groups 2A, 3B, and 3A of the PTE and also the lanthanoids; more preferably Ba.sup.2+, Ca.sup.2+, Sr.sup.2+, Tb.sup.3+, and Yb.sup.3+; more preferably Ca.sup.2+ and/or mixtures of metal cations with Ca.sup.2+.

8. The dental material as claimed in any of claims 1 to 7, wherein the cationic polyelectrolytes for forming the coacervates with multivalent anions are selected from organic polyelectrolytes, preferably from the group consisting of polymers and copolymers which contain primary, secondary and/or tertiary amino groups, and also their salts; preferably polyamines; more preferably polyallylamine, linear or branched polyethyleneimine, chitosan, polylycine, and polyarginine and also their salts; more preferably polyallylamine hydrochloride (PAH).

9. The dental material as claimed in any of claims 1 to 8, wherein the cationic polyelectrolytes for forming the coacervates with multivalent anions have average molecular weights (weight average Mw) of between 3 kDa and 1500 kDa, preferably between 5 and 500 kDa, more preferably between 8 kDa and 200 kDa, more preferably still between 8 and 50 kDa.

10. The dental material as claimed in any of claims 1 to 9, wherein the multivalent anions are selected from the group consisting of mineral-forming anions, preferably orthophosphate ions, diphosphate ions, metaphosphate ions, silicate ions, more particularly inorganic silicate ions, preferably ortho, ino, and band gap silicate ions, and partially organically modified silicate ions, more particularly alkyloxy-silicate ions, sulfate ions, tungstate ions, vanadate ions, molybdate ions, and carbonate ions, more preferably orthophosphate ions, diphosphate ions, metaphosphate ions, sulfate ions, tungstate ions, vanadate ions, molybdate ions, more preferably orthophosphate ions and/or mixtures of orthophosphate ions with mineral-forming anions.

11. The dental material as claimed in any of claims 1 to 10, wherein the fraction of the coacervate component is greater than 1 percent by weight, preferably greater than 2 percent by weight, more preferably greater than 5 percent by weight.

12. The dental material as claimed in any of claims 1 to 11, wherein it is a solid, preferably a powder.

13. The dental material as claimed in any of claims 1 to 11, wherein it is a liquid and/or an emulsion and/or a suspension, preferably having a dynamic viscosity of greater than 50 mPas, preferably greater than 100 mPas.

14. The dental material as claimed in any of claims 1 to 11, wherein it is a gel.

15. The dental material as claimed in any of claims 1 to 11, wherein it is a paste.

16. The dental material as claimed in any of claims 1 to 15, wherein it contains 1 to 100 wt % of partner ions and coacervate; preferred lower limits and/or upper limits are 5, 10, 15, 25, etc. up to 95 wt %.

17. The dental material as claimed in any of claims 1 to 16, wherein it comprises water, preferably between 5 and 95 wt %, preferably between lower limits and/or upper limits of 5, 10, 15, 25, etc. up to 95 wt %.

18. The dental material as claimed in any of claims 1 to 17, wherein the coacervate has a water content of 0.1 to 90 wt %, preferably 1 to 75 wt %, more preferably 5 to 60 wt %.

19. The dental material as claimed in any of claims 1 to 18, wherein the concentration of the polyelectrolyte forming the coacervates and of its counterions in the coacervate is between 10 and 100 wt %; preferred lower limits are 25 or 40, more preferably 45 wt %, preferred upper limits are 55 or 75, more preferably 85, 90 and 95 wt %.

20. The dental material as claimed in any of claims 1 to 19, wherein fluoride ions are included as partner ion.

21. The dental material as claimed in any of claims 1 to 20, wherein the partner ions are present in the dental material substantially in soluble form.

22. The dental material as claimed in any of claims 1 to 21, wherein it is self-curing.

23. The dental material as claimed in any of claims 1 to 22, wherein it has a working time and/or hardening time of between 1 and 5 minutes according to ISO 9917:2007.

24. The dental material as claimed in any of claims 1 to 23, wherein the cured dental material is self-bonding, preferably having a shear bond strength of at least 3.5 MPa on enamel and/or dentin.

25. The dental material as claimed in any of claims 1 to 24, wherein the cured dental material has a compressive strength of greater than 50, preferably greater than 100, more preferably greater than 200 MPa and a flexural strength of greater than 20, preferably greater than 25 MPa according to ISO 9917:2007.

26. A kit for producing a remineralizing dental material as claimed in any of claims 1 to 25, which comprises the following constituents: a. a first component which comprises at least one coacervate with one of the partner ions as counterion of the coacervate; b. a second component comprising water; wherein the second of the partner ions is included either as free ion in aqueous solution in component b and/or as counterion of a second coacervate in one of the two components.

27. The kit as claimed in claim 26, wherein at least one of the components is a solid, preferably a powder.

28. The kit as claimed in claim 26 or 27, wherein at least one of the components is a liquid, preferably having a dynamic viscosity of greater than 10 mPas, preferably greater than 50 mPas, more preferably greater than 100 mPas.

29. The kit as claimed in claim 26 or 27, wherein at least two of the components are pastes.

30. The kit as claimed in claim 26 or 27, wherein at least two of the components are a gel.

31. The kit as claimed in any of claims 26 to 30, wherein at least one of the components, preferably at least two of the components, has/have a pH of 7 to 10 at 23° C.

32. The kit as claimed in any of claims 26 to 31, which comprises a further component c, which preferably comprises an adhesion promoter.

33. The kit as claimed in any of claims 26 to 32, wherein components a and b are stored in an apparatus suitable for mixing, preferably in a mixing capsule, containing preferably a powder or a liquid, and/or in a multicompartment cartridge, as part of a cartridge system for extruding the components through a mixing needle, containing preferably two pastes or two gels.

34. The kit as claimed in any of claims 26 to 33, wherein one of the partner ions is multivalent and is included as counterion in a coacervate, and a second partner ion is included in aqueous solution, with at least one of the components further comprising a second polyelectrolyte, which has a different charge from the polyelectrolyte of the coacervate.

35. The kit as claimed in any of claims 26 to 33, wherein component a comprises at least one first coacervate powder comprising alkaline earth metal ions, preferably calcium ions as counterions, and at least one second coacervate powder comprising multivalent anions as partner ions.

36. A method for using a kit as claimed in any of claims 26 to 35, with the steps of: i. applying constituent b to dentin and/or enamel, preferably as liquid, ii. applying constituent a to the dentin with constituent b and/or to the enamel with constituent b, preferably as powder, paste, gel or viscous liquid.

37. A method for using a kit as claimed in any of claims 26 to 35, with the steps of: i. mixing constituent a and constituent b, ii. applying the mixture to dentin and/or enamel, preferably as paste or gel.

38. The use of the dental material as claimed in any of claims 1 to 25 as sealant, coating, as relining material and/or filling material.

Description

Examples 1-4

[0148] An aqueous polyacrylic acid sodium salt solution was admixed slowly, with vigorous stirring, with an aqueous calcium chloride solution or calcium strontium chloride solution. Phase separation was observed during the addition. Following complete addition, stirring took place for five minutes more and the phases were then left to rest for 10 minutes for further separation. The supernatant formed was poured off and the phase which remained was washed three times with 400 ml of ultrapure water in each case. A viscous liquid was obtained. The pH values were adjusted in each case using hydrochloric acid and/or sodium hydroxide solutions. The amounts, concentrations, and pH values of the solutions used are reported in table 1.

TABLE-US-00001 TABLE 1 Amounts, concentrations, and pH values of the solutions used for coacervate synthesis Na-PAA15 solution Alkaline earth metal Conc.* PAA100 solution salt solution Na- Conc.* Conc.* PAA15 Amount PAA100 Amount CaCl.sub.2 SrCl.sub.2 Amount pH Coacervate [mg/mL] [mL] pH [mg/mL] [mL] pH [mM] [mM] [mL] Example 1 100 60 9 — — — 200 — 200 6 Example 2 — — — 100 60 9 200 — 200 6 Example 3 100 60 9 — — — 125 — 200 6 Example 4 100 60 9 — — — 150 50 200 6 *Conc. = concentration

Synthesis of Coacervate Based on Polyallylamine Hydrochloride

Example 5

[0149] An aqueous polyallylamine hydrochloride solution was admixed slowly, with vigorous stirring, with an aqueous (NH.sub.4).sub.2HPO.sub.4 solution. Phase separation was observed during the addition. Following complete addition, stirring took place for five minutes more and the phases were then centrifuged at 7700 g for 3 minutes for further separation. The supernatant formed was poured off and the phase which remained was washed three times with 10 ml of ultrapure water in each case. A viscous liquid was obtained.

[0150] The pH values were adjusted in each case using hydrochloric acid and/or sodium hydroxide solutions. The amounts, concentrations, and pH values of the solutions used are reported in table 2.

TABLE-US-00002 TABLE 2 Amounts, concentrations, and pH values of the solutions used for coacervate synthesis PAH15 solution (NH.sub.4).sub.2HPO.sub.4 solution Conc.* Conc.* [mg/mL] Amount [mM] Amount Coacervate PAH15 [mL] pH (NH.sub.4).sub.2HPO.sub.4 [mL] pH Example 5 10 15 3 200 10 7 *Conc. = concentration

[0151] Water Content/Loss on Drying of the Viscous Liquids Obtained in Examples 1, 4 and 5

[0152] The water contents of the viscous liquids were determined by loss on drying. The loss on drying is reported as water content in table 3a.

TABLE-US-00003 TABLE 3a Loss on drying/water contents of the coacervates Water content Coacervate [% by weight] Example 1 55 Example 4 55 Example 5 35

[0153] Ion content of freeze-dried samples of the viscous liquid obtained in examples 1, 4 and 5 The ion content was determined as element content by means of energy-dispersive x-ray spectroscopy (EDX). The residual water content of the freeze-dried viscous gels was determined by thermogravimetry (TGA). Residual water contents and element contents are reported in table 3b.

TABLE-US-00004 TABLE 3b Residual water content determined by TGA and element contents determined by EDX for freeze-dried coacervates Coacervate Residual water Calcium Strontium Phosphorus [% by [% by [% by [% by weight] weight] weight] weight] Example 1 8 20 (20.sup.a) — — Example 4 8 14 8 — Example 5 8 — — 17 .sup.aTGA value

[0154] Production of Coacervate Powders

[0155] Coacervate Powder (P1)

[0156] Water was removed from the viscous liquid from example 1 by freeze drying. The resulting material was ground in a vibratory mill (Pulverisette 0, from Fritsch) for 7 h, then in a mortar mill (Pulverisette 2, from Fritsch) for 6 h, and lastly in a ball mill (ball distribution: 55×16 mm, 14×25 mm, 4×40 mm) for 18 h.

[0157] The residual water content of the white powder obtained was determined by TGA. The residual water content was 8% by weight. Particle size distribution: D.sub.10=1.0 μm and D.sub.50=4.4 μm

[0158] Coacervate Powder (P2)

[0159] Water was removed from the viscous liquid from example 5 by freeze drying. The resulting material was ground in a vibratory mill (Pulverisette 0, from Fritsch) for 7 h, then in a capsule mixer (1 ml; ball diameter: 3.15 mm; Silamat, from Ivoclar-Vivadent) for 60 s, and lastly in a capsule mixer (1 ml; ball diameter: 0.1 mm; Silamat, from Ivoclar-Vivadent) for 60 s. The residual water content of the white powder obtained was determined by TGA. The residual water content was 8% by weight. Particle size distribution: D.sub.10=2.4 μm and D.sub.50=24.6 μm

[0160] Polyallylamine Hydrochloride Powder (P3)

[0161] This powder is a second, cationic polyelectrolyte, which in accordance with the invention can be used together with a coacervate containing anionic polyelectrolyte and which promotes depth mineralization in the manner already referred to above and illustrated in the examples.

Example 6

[0162] Production of a Self-Adhesive, Self-Curing Dental Material from Coacervate Powders P1 and P2

[0163] To produce the dental material, 150 mg of powder P1 were mixed with 150 mg of powder P2. This powder mixture and also 0.2 ml of water were introduced separately from one another into a mixing capsule (Applicap, DMG Hamburg).

[0164] The powder and the liquid were mixed using a vibratory mixer (Silamat, Ivoclar Vivadent AG) for 20 s to give a ready-to-use treatment material.

[0165] Immediately after mixing, the resulting treatment material was delivered from the mixing capsule via the needle of the mixing capsule, and was processed.

Example 7

[0166] Production of a Self-Adhesive, Self-Curing Dental Material from Coacervate Powder P1

[0167] 300 mg of powder P1 and 0.2 ml of (NH.sub.4).sub.2HPO.sub.4 solution (130 mM, pH 9) were mixed manually with the aid of a spatula on a tray for around 30 s to form a ready-to-use treatment material.

Example 8

[0168] Production of a Self-Adhesive, Self-Curing Dental Material from Coacervate Powder P1

[0169] 300 mg of the ground powder P1 and 0.2 ml of a 130 mM (NH.sub.4).sub.2HPO.sub.4 and 100 mM sodium citrate solution, adjusted to a pH of 9, were mixed by manual mixing for around 30 s to form a ready-to-use treatment material. In comparison with example 7, this material cures much more quickly.

Example 9

[0170] 40 mg of the ground powder P1 and 1.75 ml of a 130 mM (NH.sub.4).sub.2HPO.sub.4 solution, adjusted to a pH of 9, were mixed manually by means of a spatula for around 30 s in a 2 ml reaction vessel (Eppendorf tube), briefly shaken and then stored horizontally at room temperature for 5 min and 24 h, respectively.

Example 10

[0171] 40 mg of coacervate powder P1 were mixed with 1.75 ml of an aqueous solution containing 130 mM (NH.sub.4).sub.2HPO.sub.4 and 100 nM sodium citrate (in analogy to example 8) in a 2 ml reaction vessel (Eppendorf tube), briefly shaken and then stored horizontally at room temperature for 5 min and 24 h, respectively.

[0172] Characterization

[0173] The Compressive Strength was Determined for the Dental materials of examples 6-8. The compressive strengths are reported in table 4.

TABLE-US-00005 TABLE 4 Compressive strengths of the dental materials Compressive strength Compressive strength after 1 h [MPa] after 4 d [MPa] Example 6 4.6 ± 1.2 21.2 ± 1.4 Example 7 12.6 ± 1.3  32.3 ± 3.1 Example 8 7.5 ± 2.1  9.3 ± 3.1

[0174] The compressive strength was highest for the material of example 7. For all of the dental materials the compressive strengths were higher after 4 days than 1 h after processing.

[0175] Shear Bond Strength (SBS)

[0176] The shear bond strength was measured for examples 6-8. The dental material is self-adhesive. In the specimens, cracking or deformation of the specimens occurred before they were sheared off.

[0177] Mineralization

[0178] The mineralization of the mixtures of examples 6, 9 and 10 was investigated by means of XRD. The mineral phases detected are reported in table 5.

TABLE-US-00006 TABLE 5 Detected mineral phases Mineral phases Mineral phases Mineral phases after 5 d after 5 min after 24 h Example 6 HAP, OCP, DCPD — — Example 9 — HAP HAP Example 10 — HAP HAP

[0179] Use Examples

[0180] Production of Model Substance

[0181] For the use examples below, model substances for demineralized dentin were first produced. Each model substance consists of a gel which is solid at room temperature.

[0182] At 40° C., 10 g of gelatin (A type, 300 bloom) were dissolved in 90 ml of an aqueous solution having a pH of 9, containing 130 mM diammonium hydrogen phosphate and 100 mM trisodium citrate tetrahydrate. The resulting gelatin solution was introduced into standard 24-well titer plates and allowed to cool to room temperature. As soon as room temperature was reached, the solid gel bodies were removed from the titer plate using a spatula and were stored in the aqueous solution.

[0183] Application of Dental Materials to the Model Substances

[0184] The dental materials were applied in each case to the surface of the model substance, i.e., to the top sides of the disk-shaped gel bodies, and were stored at room temperature in 10 ml of the aqueous solution (containing 130 mM diammonium hydrogen phosphate and 100 mM trisodium citrate tetrahydrate, pH 9) such that the dental material and the model substance were covered by the solution, or they were stored in a conditioning cabinet at 100% atmospheric humidity and room temperature. After 2 d, 3 d, 4 d, 8 d or 12 d, the gel bodies were removed and washed with ultrapure water. Then, using a razor blade, cross sections of the disk-shaped gel body were prepared. The cross sections were examined optically to ascertain whether mineralized material was evident under the model substance surface, and how deep this material reached into the model substance.

Examples 11 to 13

[0185] In the same way as for example 6, self-adhesive, self-curing dental materials were produced. The powders/powder mixtures and liquids used in this case are illustrated in table 6 below.

TABLE-US-00007 HPO.sub.4.sup.2− Citrate content content Aqueous of aqueous of aqueous Powder P1 Powder P3 solution solution solution Example [mg] [mg] [ml] [mM] [mM] 11 150 0 0.1 130 100 12, 13 150 50 0.13 130 100

[0186] The liquid constituent used is the aqueous solution containing (NH.sub.4).sub.2HPO.sub.4 and sodium citrate, as already used in example 8 also.

[0187] In examples 12 and 13, the powder mixture contains powder P3 as second, cationic polyelectrolyte, which is used together with the coacervate containing anionic polyelectrolyte (powder P1) and which promotes depth mineralization in the manner already mentioned above.

[0188] To produce the dental material, 150 mg of the respective powder/powder mixture and also the liquid constituent were introduced separately from one another into a mixing capsule (Applicap, DMG Hamburg). The powder and the liquid were mixed using a vibratory mixer (Silamat, Ivoclar Vivadent AG) for 20 s to form a ready-to-use treatment material. Immediately after mixing, the resulting treatment material was delivered from the mixing capsule via the needle of the mixing capsule, and processed.

[0189] The dental materials thus produced were applied to model substance, and the mineralization tested, in accordance with the use examples below.

Example 11

[0190] The dental material from table 6 above, example 11, was applied to the model substance and stored as described in the aqueous solution.

[0191] After 4 d, a slight depth mineralization was apparent. After 12 days, the depth mineralization observed was still only slight (FIG. 1). For the mineral formed in the gelatin, calcium, carbon, phosphorus, and oxygen were detected over the entire depth (FIG. 2). The mineral was identified by XRD as hydroxyl apatite (FIG. 3).

Example 12

[0192] The dental material from table 6 above, example 12, was applied to the model substance and stored as described in the aqueous solution.

[0193] After just 3 d, substantial depth mineralization is observed (FIG. 4). The dental material applied to the gelatin surface bonds to the surface, is stable, and does not break down. The mineral formed may be identified by XRD measurements as hydroxyl apatite (FIG. 5). For the mineral formed in the gelatin, calcium, carbon, phosphorus, and oxygen can be detected by EDX analyses (FIG. 6).

Example 13

[0194] The dental material from table 6 above, example 13, was applied to the model substance and stored as described in the conditioning chamber.

[0195] After just 2 d, pronounced depth mineralization was apparent (FIG. 7). The dental material bonds to the surface, is stable, and does not break down. The mineral formed was identified by XRD as hydroxyl apatite.