CALCIUM COACERVATES FOR REMINERALIZATION AND FOR DEMINERALIZATION INHIBITION

Abstract

The invention relates to calcium coacervate for use in a method for caries prevention and/or caries treatment, comprising a step during which dental enamel is infiltrated with calcium coacervate; and to kits that comprise: a) a phosphate ion-containing solution; and b1) a calcium coacervate-containing emulsion and/or b2) a second solution comprising polyanions and/or their salts, and a calcium ion-containing third solution.

Claims

1. A calcium coacervate for use in a method for caries prevention and/or caries treatment that comprises a step wherein dental enamel is infiltrated with calcium coacervate.

2. The calcium coacervate for use as claimed in claim 1, characterized in that the calcium coacervate is present in an emulsion.

3. The calcium coacervate for use as claimed in claim 1 or 2, characterized in that the method comprises steps wherein (a) the dental enamel is infiltrated with phosphate ions; and (b) subsequently the dental enamel is infiltrated with the calcium coacervate.

4. The calcium coacervate for use as claimed in claim 3, characterized in that the method comprises a step wherein (b1) between the infiltration in step (a) and the infiltration in step (b) the dental enamel is dried.

5. The calcium coacervate for use as claimed in either of claims 3 and 4, characterized in that the method comprises a step wherein (a1) prior to the infiltration in step (a) the pseudointact surface layer of the dental enamel is wholly or partly removed.

6. The calcium coacervate for use as claimed in any of the preceding claims, characterized in that the calcium coacervate is preparable in a method which comprises a step wherein a solution which comprises polyanions and/or their salts is mixed with a calcium ion-containing solution.

7. The calcium coacervate for use as claimed in claim 6, characterized in that the polyanions are polyacid anions, preferably polyacrylic acid anions.

8. The calcium coacervate for use as claimed in any of the preceding claims, characterized in that the calcium coacervate is preparable in a method which comprises steps wherein polyacrylic acid-containing solution and calcium ion-containing solution are mixed in a molar ratio of 70.5:10 to 70.5:35, preferably about 70.5:22.5, based on the concentration of polyacid and of calcium ions respectively.

9. A kit, characterized in that the kit comprises: a) a phosphate ion-containing solution; and b1) a calcium coacervate-containing emulsion and/or b2) a second solution, which comprises polyanions and/or their salts, and a calcium ion-containing third solution.

10. The kit as claimed in claim 9 for use in a method for caries prevention and/or caries treatment.

11. A method for preparing a calcium coacervate, characterized in that the method comprises steps wherein polyacrylic acid sodium salt is mixed with calcium chloride dihydrate in a molar ratio of 70.5:10 to 70.5:35, preferably about 70.5:22.5, based on the concentration of polyacid and of calcium ions respectively.

12. The use of calcium coacervate for caries prevention and/or caries treatment, characterized in that dental enamel is infiltrated with calcium coacervate.

Description

BRIEF DESCRIPTION OF FIGURES

[0030] Exemplary embodiments of the invention are represented schematically in the drawings, wherein:

[0031] FIG. 1 shows the average mineral profile in group 8. Relative to the healthy control area (healthy), the demineralized untreated control (demineralized) reveals a loss of mineral (area between healthy and demineralized curves) and also a somewhat more highly mineralized surface layer in the outer 20 μm. In the infiltrated areas “demineralized+1× infiltrated” and “demineralized+2× infiltrated”, conversely, the loss of mineral in the entire lesion body has decreased;

[0032] FIG. 2 shows the 2D transmission image of an enamel sample with three lesions A (demin. region), B (first effect area) and C (second effect area). The pale gray spots mark the measurement regions at the side edge and in the middle of the lesion. Measurements there were carried out in each case on the surface, in the lesion body and in the healthy enamel;

[0033] FIG. 3 Left: the diffraction pattern of an infiltrated lesion shows a pattern typical of hydroxylapatite (Li et al. 2009; H: hydroxylapatite; S: enamel; L: lesion; O: surface). Right: in an individual infiltrated sample, at a measurement point on the surface of the lesion, peaks were additionally demonstrated which are typical of octacalcium phosphate (Li et al. 2009; OP: octacalcium phosphate; S: enamel; L: lesion; O: surface);

[0034] FIG. 4 A: difference in mineral loss ddZ (vol % xpm) of the lesions after infiltration and exposure time for 10 min, 6 h and 24 h; B: difference in mineral loss ddZ (vol % xpm) of the lesions after triple infiltration and respective exposure time for 10 min, 6 h and 24 h;

[0035] FIG. 5 shows the difference in mineral loss ddZ (vol % xpm) between, before and after the de- and remineralization phase;

[0036] FIG. 6 shows the mean mineral profile of all of the 1× infiltrated samples tested (x-axis: lesion depth; y-axis: mineral content). Baseline: untreated lesions; infiltrated: lesions infiltrated with coacervate (from preceding experiment); infiltrated+demineralization: lesions exposed after infiltration to a demineralization solution; infiltrated remineralization: lesions exposed after infiltration to a remineralization solution;

[0037] FIG. 7 A: the mineral profile of an exemplary artificial carious lesion (screenshot); B: mineral profile (screenshot) of the same sample after single infiltration with coacervate and subsequent storage in a demineralization solution. Noteworthy is the zone of virtually complete remineralization at approximately 150 μm, while beneath it the demineralization has evidently proceeded further;

[0038] FIG. 8 shows a schematic representation of bovine enamel samples. After treatment with the various infiltration solutions, the samples were separated lengthwise (dashed line). While the direct infiltration effect was evaluated on one half (baseline), the second halves (effect) were exposed to a second demineralization or a pH cycle and evaluated thereafter;

[0039] FIG. 9 shows integrated loss of mineral (AZ in vol % xpm) of the individual sample areas and groups;

[0040] FIG. 10 shows the difference in the integrated mineral loss between infiltrated and untreated areas in the baseline halves (AZ in vol % xpm) of the individual groups;

[0041] FIG. 11 shows the difference in the integrated mineral loss between infiltrated and untreated areas in the effect halves (AZ in vol % xpm) after repeat exposure of the samples of group 1 to the demineralization solution and the exposure of the samples of groups 2 and 3 to pH cycling; and

[0042] FIG. 12 shows mineral loss Z (vol %) of the various sample areas at different sample depths. A: group 2: coacervate, pH cycling, B: group 3: Curodont™ Repair, pH cycling

EXAMPLES

[0043] Further advantages, characteristics, and features of the present invention will become clear from the detailed description below of working examples with reference to the appended drawings. The invention, however, is not limited to these working examples.

[0044] The remineralization of artificial enamel caries by calcium coacervate solutions was evaluated by means of the experimental examples below.

Example 1: Evaluation of the Optimum Composition of the Coacervate Solution

[0045] The optimal mixing ratio of the components of the coacervate solution was determined as follows:

[0046] Pretreatment of the Enamel Samples

[0047] For the infiltration experiments, bovine enamel samples with three demineralized regions each (A, B, C) were used, each representing an artificial carious lesion. For removal of the pseudointact surface layer, demineralized regions B and C were subjected to partial etching with 37% phosphoric acid gel for 5 seconds, while area A remained as an untreated control (demin.). The samples were subsequently rinsed off, dried, and placed for 60 minutes in a saturated dipotassium hydrogen phosphate solution (1 M).

[0048] Preparation of the Coacervates and Infiltration of the Samples

[0049] The calcium coacervate solutions were prepared with continuous stirring on a magnetic stirrer. For these solutions, 500 μl of polyacrylic acid sodium salt (PAA-Na; pH=9, Mw=15 kDa) in different concentrations (Table 1) were measured off using an Eppendorf pipette and introduced into a reaction vessel. The magnetic stirrer was switched on and then one of the volumes of calcium chloride dihydrate (CaCl.sub.2.2H.sub.2O; 50 mM, pH=6) defined in Table 1 was slowly added. The solution, depending on the amount of CaCl.sub.2.2H.sub.2O, acquired a more or less milkily hazy appearance.

TABLE-US-00001 TABLE 1 Composition of the groups CaCl.sub.2•2H.sub.2O PAA-Na conc. (50 mM) Group (500 μl) volume in μl N 1 2.5 mg/ml 100 10 2 170 9 3 240 9 4 5 mg/ml 200 9 5 250 9 6 300 10 7 10 mg/ml 400 8 8 450 9 9 500 8

[0050] After the calcium coacervate solutions had been prepared they were immediately applied in excess to the lesion areas B and C (infiltration). The excess of the infiltration solution was left on the lesion areas and not wiped off. The samples were stored overnight in a humidity chamber at room temperature. The next day the area C was again infiltrated with newly prepared calcium coacervate solution. This area was exposed for 5 minutes prior to commencement of the production of the thin sections.

[0051] Analysis

[0052] For the analysis of the mineral gain, 100 μm thin sections of the enamel samples were prepared and were subjected to Transverse Microradiography (TMR). The mineral loss (AZ) was determined on the individual effect areas with the aid of TMR software.

[0053] Results

[0054] Group 8, with the strongest and statistically significant mineral gain, is marked in Table 2 by underlining. In group 8, a significant mineral gain relative to the control, of 18% and 33%, respectively, was observed. The mineral profile curve (FIG. 1) shows a mineral gain relative to the untreated demineralized sample in the entire lesion body.

TABLE-US-00002 TABLE 2 Results of microradiographic analysis: mineral loss (ΔZ in vol % xμm) and change in the mineral loss relative to the untreated control (ΔΔZ % in %) ΔZ ΔZ 1x ΔZ 2x ΔΔZ Z % 1x ΔΔZ % 2x untreated infiltrated infiltrated infiltrated infiltrated median median median median median Group (Q25/Q75) (Q25/Q75) (Q25/Q75) (Q25/Q75) (Q25/Q75) 1 3927 3949 3833 −5 −2 (2837/4443) (3370/4897) (2051/4442) (−22/7)   (−9/28) 2 4345 4231 3591  7  8 (3411/4816) (3821/4730) (3484/3711)  (−9/15)  (−9/21) 3 2997 3499 3120 −4  6 (2656/4544) (2635/4406) (2834/3731) (−22/26)  (−5/18) 4 4381 4709 3514  5 15 (4154/5163) (4249/5293) (2993/4303) (−23/9)   (10/21) 5 2623 3439 2693  5 18 (2221/4555) (2442/3786) (2493/3530) (−9/7) (−13/26) 6 4530 4094 3602  8  1 (3368/5043) (3287/4571) (3141/4494)  (−2/19) (−14/32) 7 4434 4355 4188 −6  2 (3464/5136) (3747/5393) (3184/4923) (−29/16) (−37/27) 8 3548 3079 2360 18 33 (3099/4828) (2342/3953) (2008/2983)  (14/22)  (28/36) 9 3918 3725 3869 −1 17 (3030/5798) (3255/5552) (3095/4274) (−15/16) (−13/29)

Example 2: X-Ray Diffraction Analysis

[0055] The mineral composition of the infiltrated samples was analyzed as follows:

[0056] Experimental Procedure

[0057] Two enamel samples previously infiltrated with the optimal calcium coacervate solution were analyzed by x-ray diffraction at the Berlin Helmholtz Center of Materials and Energy (Bessy). For this purpose, the samples were irradiated with an x-ray beam having an energy of 18 keV, a wavelength of 0.69 Å and an approximate sample-detector distance of 24.7 cm.

[0058] The images were evaluated with the aid of the “XRDUA” program (De Nolf & Rickers, 2005, HASYLAB Jahresbericht 2004, ed. J. Schneider, HASYLAB, Hamburg, Germany) with the objective of producing a graphical representation of the entire dataset for each sample, in order to permit an assessment of which crystal compounds were present in the lesions. In a second step, a macro was produced for the “ImageJ” program in order to allow comparison of the entire dataset for each sample, consisting of a transmission scan and a diffraction scan. For the transmission images, the measurement points were scanned at a distance of 60 μm in the respective sample. In each lesion body, accordingly, it was possible to ascertain the precise image numbers with the associated diffraction pattern for precisely that point in the sample. The analysis extended from the surface of the lesion area over the lesion body to reach the healthy enamel (FIG. 2). Three measurement regions with three measurement points in each case were ascertained in this way. The diffraction patterns were represented graphically and compared in order to be able to draw conclusions regarding changes in the apatite structure. In a further step, the diffraction images were selected. These images were halved centrally, as they have symmetrical constructions.

[0059] Results

[0060] No fundamental differences were evident in the diffraction pattern in the different regions of the sample, which points to a homogeneous composition of the enamel.

[0061] For the crystal structure analysis of the three lesion areas, diffractograms were produced which originated from integration of the diffraction patterns (diffraction images not shown; for illustrative diffractograms see FIG. 3). The typical profile of a diffractogram for hydroxylapatite is depicted for comparison (Li et al., 2009, A novel jet-based nano-hydroxyapatite patterning technique for osteoblast guidance, J Roy Soc). 2-Theta deviates on the X-axis from the values of the axes represented below, since in the present experiment an x-ray source with a wavelength of λ=0.69 Å was used, whereas Li et al. used a Cu-Kα radiation source with a characteristic wavelength of λ=1.54 Å.

[0062] A diffractogram typical of hydroxylapatite was found at all measurement points (FIG. 3). Only the second sample exhibited a different diffractogram in the region of the surface of the sample, in the infiltrated lesion area sited in the middle. On the basis of its profile, this diffractogram indicated the presence of octacalcium phosphate. The demineralized control area and the externally sited infiltrated lesion area were shown by diffractograms which indicated the presence of hydroxylapatite and corresponded to the graphs for the first sample as represented in FIG. 3. For this reason, FIG. 3 shows only the graph which has a different profile from that shown by Li et al. (2009).

[0063] No substantial differences were demonstrated in terms of crystal compounds between the demineralized control area and the effect areas infiltrated with calcium coacervate solution.

Example 3: Analysis of the Consequences of Exposure Time and Repetition of the Infiltration

[0064] The consequences of different application times and application frequencies were analyzed as follows:

[0065] Pretreatment of the Enamel Samples

[0066] For the infiltration experiments, again, bovine enamel samples with three demineralized regions (A, B, C) in each case were used. In contrast to example 1, however, the sample here was divided lengthwise, allowing the original mineral content to be determined by means of the control half for each of the three lesions (demin. control). In the effect half of the samples, the demineralized regions A, B and C were subjected to partial etching with 37% phosphoric acid gel for 5 seconds in each case. The samples were subsequently rinsed off and dried. The saturated dipotassium hydrogen phosphate solution (1 M) was applied for 3 min, and the excess was wiped off, and the samples were dried.

[0067] Preparation and Application of the Coacervates

[0068] The calcium coacervate solutions were prepared as described in example 1. Corresponding to the best group from experiment 1, 500 μl of PAA (10 mg/ml, pH=9.0) and 450 μl of CaCl.sub.2.2H.sub.2O (50 mM, pH=6.0) were mixed. After the preparation of the calcium coacervate solutions, they were applied immediately in excess to the lesion areas A, B and C already infiltrated with phosphate ion-containing solution (infiltration). After 3 min, excesses were wiped off and the samples were stored for 10 min (A), 6 h (B) and 24 h (C) at 100% atmospheric humidity at 20° C. In group 1 the samples subsequently underwent microradiographic analysis. In group 2 the samples were infiltrated as described above two further times with corresponding exposure times for the different lesions (A, B, C).

[0069] Analysis

[0070] For the analysis of the mineral gain, 100 μm thin sections of the enamel samples were produced and subjected to analysis by microradiography (TMR). The mineral loss (AZ) on the individual effect areas was determined with the aid of TMR software.

[0071] Results

[0072] In group 1, in which the samples had undergone only 1-fold infiltration, a mineral gain of about 15-20% was apparent, whereas in group 2, in spite of three-fold infiltration, there was no significant additional mineral gain observable (FIG. 4).

Example 4: Analysis of the Consequences of Storage with Calcium Coacervate-Infiltrated Lesions in De- and Remineralization Solutions

[0073] Further, simulations were carried out of the behavior of infiltrated lesions when subjected additionally to a demineralizing (caries-promoting) or remineralizing medium. The gain or loss of mineral from artificial carious lesions, infiltrated in de- or remineralizing solutions with calcium coacervates, was analyzed for this purpose as follows:

[0074] Pretreatment of the Enamel Samples

[0075] Experimental Design: [0076] 37 enamel samples each with 3 free enamel areas (1, 2, 3) [0077] demineralization solution (as described below) for 17 days to generate artificial carious lesions [0078] isolation of half of the samples in each case for determination of the initial mineral loss (baseline)

[0079] Infiltration with coacervate solution as described above: [0080] Difference 1×: 1× infiltrated [0081] Difference 2×: 2× infiltrated [0082] Difference 3×: 3× infiltrated [0083] exposure time to dipotassium hydrogen phosphate and coacervate in each case 3 min. [0084] time between infiltrations: 10 min.

[0085] The samples subsequently underwent randomized division into two groups (n=18, n=19) and were stored for 10 days either in a demineralization solution or in a remineralization solution:

[0086] Further De- or Remineralization

[0087] Demineralization [0088] n=18 [0089] duration: 20 days [0090] pH: 4.95 (measured daily; adjusted if needed with: HCl 10 M/KOH 10 M) [0091] 38° C.

TABLE-US-00003 Substance Amount 1. Aqua dest. ad 5 l 2. CaCl.sub.2•2H.sub.2O 2.205 g 3. KH.sub.2PO.sub.4 2.041 g 4. MHDP 5.3 mg 5. CH.sub.3COOH 14.30 ml 6. KOH 10M pH adjusted to 4.95

[0092] Remineralization

TABLE-US-00004 Substance Amount 1. Aqua dest. ad 5 l 2. CaCl.sub.2•2H.sub.2O 1.103 g 3. KH.sub.2PO.sub.4 0.612 g 4. KCl 48.45 g 5. Hepes buffer 1M 100 ml 6. F.sup.− (0.1M) 263 μl 7. HCl 10%/KOH 1M Adjust pH to 7.00 [0093] n=19 [0094] duration: 10 days [0095] pH: 7.00 (measured daily; adjusted if needed with: HCl 10 M/KOH 10 M) [0096] 38° C.

[0097] Results

[0098] FIG. 5 shows the difference in the mineral content between, before and after the de- and remineralization phases. As expected, untreated samples in the remineralization solution showed a mineral gain (negative values) and the untreated samples in the demineralization solution showed a mineral loss (positive values). In both solutions, previously infiltrated samples showed a trend toward a slight mineral gain (exception 3× infiltrated & demin., slight mineral loss). This shows that the infiltration protects against further mineral loss.

[0099] A striking feature is the formation of comparatively highly mineralized zones in the former lesion body in spite of the demineralizing medium (FIG. 6, dashed curve; FIG. 7b). Moreover, there was no significant further net mineral loss. This effect was found to be the most pronounced for samples infiltrated only once.

[0100] Conclusions

[0101] The experiments described above showed that the infiltration of artificial carious lesions with the coacervate solutions resulted in a mineral gain in the lesions. The mineral deposit appeared to consist predominantly of hydroxylapatite. A 10 min. exposure time to the coacervate solutions was sufficient. No additional mineral gain appears to be achievable through multiple application of the coacervate solutions. Surprisingly, in a demineralizing medium, the samples infiltrated previously showed a trend toward remineralization, but virtually no demineralization. The treatment proposed and tested herein is therefore—evidently and happily—caries-protective in its effect.

Example 5: Evaluation of the Remineralization of Bovine Enamel Samples by Coacervates

[0102] A further investigation looked at the effect of the infiltration of artificial enamel caries with coacervates, especially in comparison with the Curodont™ Repair product, with subsequent simulation of a mouthlike environment.

[0103] Pretreatment of the Enamel Samples

[0104] For the experiment, enamel samples (n=95; 8×5×4 mm) were prepared from bovine incisors and were embedded in methacrylate polymer. Using nail varnish, two regions in each case were masked on the uncovered enamel surface in such a way as to form two exposed areas, while the masked areas remained as a “healthy control” (FIG. 8). The samples thus prepared were exposed for 22 days to a demineralization solution (pH=4.95, Tab. 3) in order to create artificial carious lesions in the regions not masked (FIG. 8). The samples pretreated in this way underwent randomized division into 3 groups (Tab. 4). While one of the two lesions per sample remained untreated subsequently (“untreated control”), the second lesion (“infiltrated”) was subjected to partial etching with 37% phosphoric acid gel for 5 s in order to remove the pseudointact surface layer.

TABLE-US-00005 TABLE 3 Composition of the de- and remineralization solutions Demineralization solution Remineralization solution pH = 4.95 pH = 7 (Buskes et al., 1985) (Buskes et al., 1985) CaCl.sub.2•2H.sub.2O (3 mM) CaCl.sub.2•2H.sub.2O (1.5 mM) KH.sub.2PO.sub.4 (3 mM) KH.sub.2PO.sub.4 (3 mM) MHDP (6 μM) KCl (130 mM) Hepes buffer (20 mM) NaN.sub.3 (3 mM) F.sup.− (5.26 mM) Buskes, J. A., Christoffersen, J., & Arends, J. (1985). Lesion formation and lesion remineralization in enamel under constant composition conditions. A new technique with applications. Caries Res, 19(6), 490-496.

TABLE-US-00006 TABLE 4 Infiltration solutions of the various groups Constituents/ Group Infiltrate concentration Name 1 Coacervate K.sub.2HPO.sub.4 (1M) Coacervate PAA-Na (10 mg/ml) demineralization CaCl.sub.2•2 H.sub.2O (50 mM) 2 Coacervate K.sub.2HPO.sub.4 (1M) Coacervate PAA-Na (10 mg/ml) pH cycling CaCl.sub.2•2 H.sub.2O (50 mM) 3 Curodont ™ see manufacturer Curodont ™ Repair information pH cycling LOT: 180524

[0105] Preparation of the Coacervates and Infiltration of the

[0106] Samples

[0107] For the infiltration with coacervates, after the phosphoric acid etching, the samples from groups 1 and 2 dried above were infiltrated for 3 min with 1M K.sub.2HPO.sub.4 and the samples were subsequently air-dried.

[0108] To prepare the coacervate solution, 500 μl of PAA-Na were measured off and introduced into an Eppendorf vessel. With continual stirring on a magnetic stirrer, 450 μl of CaCl.sub.2.2 H.sub.2O were added, after which the solution became milkily hazy. After the preparation of the coacervate solution, it was applied immediately in excess to the lesion areas (“infiltrated”, FIG. 8) for 10 min, after which the excess was removed.

[0109] Curodont™ Repair in group 3 was used in accordance with manufacturer information (batch number LOT: 180524).

[0110] After the infiltration, the samples were divided into two halves at right angles to the lesions (FIG. 8). While one half was analyzed directly as a baseline control (“baseline”), the second half (“effect”) was exposed to further simulation of an oral environment.

[0111] Group 1 was exposed again for 20 days to a demineralization solution (Tab. 4). Groups 2 and 3 were subjected to pH cycling for 28 days. The cycle consisted of demineralization phases of 3 h (demineralization solution Tab. 3) and remineralization phases of 21 h (remineralization solution Tab. 3). The solutions were introduced into the respective containers without direct contact with the samples, meaning that the samples were covered with a generous excess. In the case of the alternating solutions of the pH cycle, the previous solution was always pumped off entirely.

[0112] Analysis

[0113] For analysis of the mineral gain, 100 μm thin sections of the enamel samples were produced and subjected to analysis by microradiography (TMR). The mineral loss (ΔZ) on the individual effect areas was determined with the aid of TMR software.

[0114] Results

[0115] In groups 1 to 3, infiltration resulted in a slight mineral gain (FIG. 9). In group 3 (Curodont™, pH cycling), however, this gain was not significantly different from that of the untreated control (FIG. 10).

[0116] Following renewed exposure of the group 1 samples to the demineralization solution, a higher mineral loss in comparison to baseline was ascertained in the untreated areas. In the infiltrated areas, a smaller mineral loss was demonstrated than in the areas not infiltrated.

[0117] After the exposure of the samples of groups 2 and 3 to the pH cycling, a lower mineral loss in comparison to baseline was ascertained in the untreated areas. The pH cycling therefore resulted in a slight mineral gain in the untreated areas. In the infiltrated areas of group 2, however, a significantly higher mineral gain was found by comparison with the untreated areas, whereas in group 3 there was no significant difference found between the infiltrated and untreated areas of the exposed sample halves.

[0118] Whereas the mineral gain in the effect halves of the untreated sample areas after pH cycling, in comparison to baseline, was found primarily in the surface (formation of a pseudointact surface layer), a mineral gain in the entire lesion body was found in the infiltrated effect areas of group 2 (FIG. 12A; solid black curve). This effect was not observed in the case of group 3 (FIG. 12B; solid black curve).

CONCLUSIONS

[0119] Infiltration of the artificial enamel samples with coacervate solution results in a mineral gain. Where the samples infiltrated with coacervate are exposed to a calcium- and phosphate-containing solution (in order to simulate a mouthlike environment), a mineral gain is observed in the entire lesion body.

[0120] Coacervates can therefore evidently and happily be used as a remineralization-promoting product in dental medicine.

[0121] Although the present invention has been described in detail with reference to the working examples, it is self-evident to the skilled person that the invention is not limited to these working examples, but that instead modifications are possible in such a way that individual features may be omitted or different kinds of combinations of the individual features presented can be realized, provided the scope of protection of the appended claims is not departed. The present disclosure includes all combinations of the individual features presented.