Buffering polymers and polymer networks for dental applications

Abstract

Use of a radically polymerizable composition to reduce demineralization of teeth, during the remineralization of teeth, in reducing the drop in oral pH in patients after acid exposure, for the treatment or prevention of caries, of initial carious lesions and / or for caries protection in selected areas of the teeth. (1) 25 - 80 wt% solvent, (2) 10 - 20 wt% of at least one radically polymerizable monomer with buffer groups, (3) 0 - 20 wt% of at least one monofunctional radically polymerizable monomer, (4) 0 - 10 wt% of at least one crosslinking radically polymerizable monomer and (5) Contains 0.1 - 1 wt% of at least one radical polymerization initiator, based on the total mass of the composition.

Description

[0001] The present invention relates to the use of radically polymerizable compositions suitable for the treatment of initial caries lesions of fissures, smooth surfaces, interdental surfaces and tooth necks, for caries protection in selected tooth areas, for achieving a local buffering effect in the mouth of a patient and for the remineralization of teeth. Background of the invention

[0002] Tooth decay begins when acid leaches minerals from the hydroxyapatite component of the tooth enamel. This reduces the mineral's density and increases its porosity, making the enamel more permeable to liquids and ions. Acid can reach the teeth directly through food, especially acidic beverages. However, carbohydrates, particularly sucrose, are of greater importance, as they are fermented by biofilms on the teeth into organic acids, primarily lactic acid. This process can cause the pH within the biofilm to drop to approximately 4-5 within minutes (Lingstrom et al., 1993, J Dent Res, 72:865-870).

[0003] To date, good oral hygiene and the topical application of fluoride to teeth have proven particularly effective in preventing caries. Fluoride reduces the solubility of hydroxyapatite. In recent decades, fluorides have led to a significant decline in caries in children (Marthaler and Petersen, 2005, Int Dent J, 55:351-358). While the caries-reducing effect of fluorides in children's permanent teeth has been clinically clearly demonstrated, this success is unfortunately accompanied by frequent findings of fluorosis (Ismail and Hasson, 2008, J Am Dent Assoc, 139:1457-1468). These findings indicate that alternatives to fluorides must be found for caries prevention.

[0004] US Patent 2016 / 256362 A1 describes a process for the production of stabilized calcium phosphate. This involves reacting a solution or dispersion of calcium salts with an organic phosphate containing a polymerizable methacrylate or vinyl group. The stabilized calcium phosphate is intended for the production of dental materials that, through the release of calcium and phosphate ions, promote dentin regeneration.

[0005] US 2015 / 0335790 A1 describes cross-linked zwitterionic hydrogels that can be mineralized and are suitable, among other things, for the production of dental implants.

[0006] US Patent 8,779,024 B2 describes acid-neutralizing resins for dental applications. The neutralization of acids is intended to prevent the inactivation of amine co-initiators in dental materials.

[0007] US Patent 8,686,063 B2 describes the infiltration of tooth enamel for the prevention and treatment of caries lesions. The enamel area to be treated is etched with hydrochloric acid, then the infiltrant is applied and subsequently polymerized. The infiltrants contain radically polymerizable monomers and solvents and have a penetration coefficient of > 100 cm / s.

[0008] US 9,211,236 B2 describes infiltrants for dental applications containing crosslinking and acid-containing monomers. These infiltrants have a dynamic viscosity at 23°C of less than 50 mPa·s.

[0009] US 8,686,063 B2 and US 9,211,236 B2 describe the infiltration of tooth structure with infiltrants that, upon polymerization, form a dense plastic that is virtually impermeable to liquids and ions. This is equivalent to sealing with plastic, which prevents subsequent natural remineralization of the carious lesions.

[0010] EP 1 222 910 B2 describes dental materials based on multifunctional acrylamides, characterized by very good hydrolysis resistance under acidic conditions. The claimed compositions contain an acid-polymerizable monomer and a polymerization initiator, as well as optional solvents and fillers.

[0011] EP 0 909 761 B1 discloses polymerizable phosphonic acids with good hydrolysis stability under acidic conditions and their use in adhesives, cements or composites and dental materials containing at least one radical initiator and optionally comonomers, solvents or fillers.

[0012] German patent DE 103 39 912 A1 discloses dental coating materials containing at least one polysiloxane, an initiator for radical polymerization, and at least one radically polymerizable monomer with a phosphonic acid, sulfonic acid, mono-, or dihydrogen phosphoric acid ester group. The materials may additionally contain further radically polymerizable monomers and up to 20 wt% solvent. Upon curing, they form coatings with high abrasion resistance, providing mechanical protection for teeth. Brief description of the invention

[0013] The invention is based on the objective of providing materials suitable for the treatment of initial caries lesions of fissures, smooth surfaces, interdental surfaces and tooth necks, for caries protection in selected tooth areas, for the remineralization of teeth, and for the prevention and treatment of tooth erosion.

[0014] This task is solved by using radically polymerizable compositions to reduce demineralization of teeth, to remineralize teeth, to reduce the drop in oral pH in patients after acid exposure, to treat or prevent caries, initial caries lesions and / or caries protection in selected tooth areas. (1) 25 - 80 wt% solvent, (2) 10 - 20 wt% of at least one radically polymerizable monomer with buffer groups, (3) 0 - 20 wt% of at least one monofunctional radically polymerizable monomer, (4) 0 - 10 wt% of at least one crosslinking radically polymerizable monomer and (5) Contain 0.1 - 1 wt% of at least one initiator for radical polymerization.

[0015] According to a further preferred embodiment, the radically polymerizable compositions additionally contain (6) 1 - 3000 ppm, preferably 1 - 1000 ppm, particularly preferably 1 - 300 ppm stabilizer, based on the total mass of the composition.

[0016] The monomers (2), (3) and (4) are different substances.

[0017] These compositions can be applied intraorally to the tooth, where, after radical polymerization, they form an elastic, temporary protective film, for example, around orthodontic bands and clasps. It is also possible to apply them to demineralized areas of the tooth, where they penetrate the porous structure and are subsequently polymerized, for example, with light. This results in the formation of a protective, buffering polymer in the demineralized zones beneath the tooth surface. The compositions used according to the invention can also be polymerized extraorally into molded parts, which are then used as components intraorally.

[0018] The aim of this invention is to produce buffering polymers and polymer networks that can be used in the mouth. These prevent a drop in pH at the application site following acid exposure. In this way, demineralization of the teeth is prevented, and remineralizing conditions are maintained for an extended period. Once the acid attack is over, for example, after the acidic beverage has been swallowed, the buffering polymer or polymer network can release the absorbed protons upon contact with neutral saliva and is thus converted back into its basic form. The polymers are obtained by radical polymerization of the compositions used according to the invention. These contain at least one monomer with functional groups that have buffering properties. The polymers formed, orPolymer networks have a remineralization-promoting effect and prevent the progression of caries in demineralized teeth. They promote the deposition of calcium and calcium phosphate minerals from saliva, thus facilitating the remineralization of teeth. Detailed description of the invention

[0019] The compositions used according to the invention contain, as radically polymerizable monomers with buffer groups (buffering monomers), preferably radically polymerizable phosphonic acids and / or dihydrogen phosphates. Preferred phosphonic acid monomers are vinylphosphonic acid, 4-vinylphenylphosphonic acid, 4-vinylbenzylphosphonic acid, 2-methacryloyloxyethylphosphonic acid, 2-methacrylamidoethylphosphonic acid, 4-methacrylamido-4-methylpentylphosphonic acid, 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]acrylic acid (DHPOBAA), 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]ethyl acrylate (DHPOBAE), and 2-[4-(dihydroxyphosphoryl)-2-oxa-butyl]acrylic acid-2,4,6-trimethylphenyl ester.Preferred polymerizable phosphoric acid esters are 2-methacryloyloxypropyl dihydrogen phosphate, 1,3-bis(methacrylamido)propan-2-yl dihydrogen phosphate (DMAAPDHP), 2-(phosphonooxy)propane-1,3-diylbis(2-methylacrylate) (POPBMA), 2-methacryloyloxyethyl dihydrogen phosphate, 2-methacryloyloxyethylphenyl hydrogen phosphate, 10-methacryloyloxydecyl dihydrogen phosphate, phosphoric acid mono-(1-acryloylpiperidin-4-yl) ester, 6-(methacrylamido)hexyl dihydrogen phosphate and 1,3-bis-(N-acryloyl-N-propylamino)-propan-2-yl dihydrogen phosphate.

[0020] The buffering monomers can be used in their acidic form or in the form of their salts. Preferred salts are the sodium, potassium, and ammonium salts, as well as salts with quaternary cationic ammonium ions, which can be obtained from amines such as ethylenediamine, triethanolamine, cocoalkyl(dihydroxyethyl)amine, tetra(2-hydroxypropyl)ethylenediamine, and tris(hydroxymethyl)aminomethane (Tris).

[0021] The salts of the buffering monomers can be obtained by dissolving the monomer(s) in their acidic form in the solvent and then neutralizing them by adding a base. Preferred bases are ammonia, sodium hydroxide, potassium hydroxide, calcium hydroxide, as well as ethylenediamine, triethanolamine, cocoalkyl(dihydroxyethyl)amine, tetra(2-hydroxypropyl)ethylenediamine, and tris-(hydroxymethyl)aminomethane (Tris). This procedure is particularly advantageous for the calcium salts because they are often poorly soluble.

[0022] Hydrophilic monomers are preferred as monofunctional radically polymerizable monomers, i.e., monomers that possess one or more hydrophilic groups. Monofunctional radically polymerizable monomers are defined as monomers with one radically polymerizable group, while multifunctional radically polymerizable monomers are defined as monomers with two or more radically polymerizable groups. Preferred monofunctional monomers are HEMA, 1-hydroxymethylacrylic acid methyl ester or ethyl ester, 1-hydroxymethylacrylic acid 2-hydroxyethyl ester, 2,3-dihydroxypropyl methacrylate, 5,6-dihydroxyhexyl methacrylate, 2-hydroxy-3-methoxypropyl methacrylate, 2-Hydroxy-3-ethoxypropyl methacrylates, N,N-dimethylacrylamide, N-(hydroxymethyl)acrylamide, N-(hydroxymethyl)methacrylamide, N-methyl-N-(2-hydroxy-ethyl)acrylamide, N-(5-hydroxypentyl)acrylamide, N-(5-hydroxypentyl)methacrylamide, N-vinylpyrrolidone and N-Methyl-N-(3-hydroxypropyl)acrylamide.

[0023] Hydrophilic monomers are preferably used as crosslinking, radically polymerizable monomers. Crosslinking monomers are multifunctional monomers, i.e., monomers with two or more, preferably two to four, radically polymerizable groups. Preferred crosslinking monomers are bisacrylamides, such as methylene or ethylene bisacrylamide, N,N'-diethyl-1,3-bis(acrylamido)propane (NDEBAAP), 1,3-bis(methacrylamido)propane, 1,4-bis(acrylamido)butane, or 1,4-bis(acryloyl)piperazine. Bisacrylamides can be synthesized, for example, from the corresponding diamines by reaction with (meth)acrylic acid chloride. Further preferred hydrophilic crosslinking monomers are glycerin dimethacrylate, PEG-200, and PEG-400 dimethacrylate.

[0024] The compositions used according to the invention also contain at least one initiator for radical polymerization. Benzophenone, benzoin, and their derivatives, or β-diketones or their derivatives, such as 9,10-phenanthrenequinone, 1-phenylpropane-1,2-dione, diacetyl, or 4,4'-dichlorobenzil, are preferably used to initiate radical photopolymerization. Camphorquinone and 2,2-dimethoxy-2-phenylacetophenone are particularly preferred, and β-diketones in combination with amines as reducing agents are especially preferred. Preferred amines are 4-(dimethylamino)benzoic acid esters, N,N-dimethylaminoethyl methacrylate, N,N-dimethyl symmetric xylidine, and triethanolamine. Norrish type I photoinitiators are also particularly suitable, especially acylphosphine oxides (e.g., 2,4,6-trimethylbenzoyldiphenylphosphine oxide, TPO) or bisacylphosphine oxides (e.g.,Bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (Irgacure 819) as well as monoacyltrialkyl or diacyldialkylgermanium compounds, such as benzoyltrimethylgermanium, dibenzoyldiethylgermanium, or bis(4-methoxybenzoyl)diethylgermanium. Mixtures of the various photoinitiators can also be used, such as dibenzoyldiethylgermanium in combination with camphorquinone and ethyl 4-dimethylaminobenzoate.

[0025] Redox initiator combinations, such as combinations of benzoyl peroxide with N,N-dimethyl symmetric-xylidine or N,N-dimethyl p-toluidine, are preferably used as initiators for polymerization carried out at room temperature or under oral conditions (37 °C). For aqueous compositions, combinations of one or more inorganic peroxides, especially potassium and ammonium peroxodisulfate, with one or more reducing agents, such as sulfite, hydrogen sulfite, thiosulfate, sulfinic acids, amines, enediols, or Fe(II) salts, are particularly suitable. Furthermore, redox systems consisting of organic peroxides or hydroperoxides and reducing agents, such as ascorbic acid, barbiturates, thioureas, or sulfinic acids, are also particularly suitable. Transition metal compounds with at least two stable oxidation states can also be used as transition metal redox catalysts.These are primarily compounds of the elements copper, iron, vanadium, nickel, or cobalt, with copper compounds being particularly preferred, and these are preferably used as readily organosoluble compounds, such as acetylacetonate, naphthenate, or 2-ethylhexanoate. Mixtures of photo- and redox initiators can also be used.

[0026] Photoinitiators are classified as either monomolecular or bimolecular. TPO and bis(4-methoxybenzoyl)diethylgermanium are examples of monomolecular photoinitiators. Camphorquinone and amine, or peroxide and amine, are examples of bimolecular initiators. All quantities given for initiators refer to the total amount of each initiator component, e.g., the total amount of camphorquinone and amine, or the total amount of peroxide and amine, unless otherwise specified.

[0027] The compositions used according to the invention preferably contain water (H₂O) and / or a polar organic solvent. Water-miscible organic solvents are preferred, in particular ethanol (EtOH), acetone, isopropanol (iPr), propylene glycol (PPG), glycerol, ethylene glycol, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile, methanol, dimethylformamide (DMF), propanol, butanol, dioxane, methyl ethyl ketone, and monopropylene glycol monomethyl ether. Ethanol, isopropanol, propylene glycol, DMSO, mixtures thereof, and their mixtures with water are particularly preferred. In addition to the pure solvents, solvent mixtures can also be used.

[0028] Suitable stabilizers include aerobic inhibitors such as substituted phenols, e.g., 2,6-di-tert-butyl-4-methylphenol (BHT) or hydroquinone monomethyl ether (MEHQ), or anaerobic inhibitors such as phenothiazine and phenylenediamine, or stable radicals such as 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) or galvinoxyl (2,6-di-tert-butyl-α-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy). The stabilizers are intended to prevent premature or uncontrolled radical polymerization of the compounds.

[0029] Furthermore, the compositions used according to the invention may advantageously contain further additives, e.g. microbicidal agents, fluoride ion-releasing additives or UV absorbers, in particular neutralizers and / or soluble buffers.

[0030] Suitable neutralizers or soluble buffers are bases that are soluble in the compositions used according to the invention. Preferred examples are ammonia, sodium hydroxide, potassium hydroxide, ethylenediamine, triethanolamine, cocoalkyl(dihydroxyethyl)amine, tetra(2-hydroxypropyl)ethylenediamine, and tris(hydroxymethyl)aminomethane (Tris). Neutralizers serve to neutralize the pH of the composition, which is acidic due to the buffering or acidic monomers used.

[0031] Furthermore, the compositions used according to the invention can advantageously contain inorganic or organic salts. Metal salts, such as calcium, potassium, and ammonium salts, are preferred. Calcium salts that are readily soluble in polar organic solvents are particularly suitable. These include, in particular, calcium chloride and calcium nitrate, and other calcium salts with comparable solubility, such as calcium acetate and calcium lactate. Inorganic salts, such as calcium salts, can support remineralization.

[0032] Preferred compositions contain 0–55 wt% and preferably 0–30 wt% of at least one dissolved calcium salt, preferably calcium chloride and / or calcium nitrate. Calcium salts that are completely soluble in the solvent used and in the amount of solvent used at room temperature are referred to herein as soluble salts.

[0033] Compositions consisting of the aforementioned components are particularly preferred. Furthermore, compositions in which the individual components are selected from the preferred and particularly preferred substances mentioned above are preferred. The compositions used according to the invention are preferably in the form of solutions and therefore preferably contain no undissolved components, in particular no fillers.

[0034] To produce the compositions used according to the invention, the ingredients of the composition are dissolved in the solvent. The solvent primarily serves to dissolve the other components of the composition. On the other hand, it also ensures that the polymerization does not result in a dense plastic but rather a polymer or polymer network that is permeable to ions required for the remineralization of teeth, such as calcium and phosphate ions.

[0035] The buffering monomers or their salts serve to impart buffering properties to the polymer or polymer network. The buffering polymers and polymer networks are designed to be largely deprotonated at neutral pH values. If an acid attack occurs, for example, from acidic beverages or foods, or from the breakdown of sugars to organic acids by microorganisms, the polymer is able to accept protons and thus mitigate the pH reduction. The pKa of the buffering polymers and networks is preferably in the range of 5.5 to 7.5, particularly preferably from 6.0 to 7.5, and most preferably from 6.5 to 7.0. Therefore, starting from a naturally neutral pH in the mouth, the polymer or polymer network is able to reduce the drop in pH at the site of application during an acid attack, for example, from acidic foods, gastric acid, or acidic fermentation products of microorganisms.At pH values ​​below 6.5 to 7.0, the polymers absorb protons and release them again at pH values ​​above 6.5 to 7.0, enabling them to buffer again during the next acid attack. This minimizes mineral loss from the hard dental tissue (enamel, dentin). The pKa value of the buffering polymers and polymer networks can be adjusted by selecting the monomers, their proportions in the composition, and the crosslinking agent content. These pKa values ​​of the buffering polymers and / or networks effectively prevent the demineralization of hydroxyapatite and promote the remineralization of teeth by saliva, thus achieving optimal overall protection.

[0036] The compositions preferably also contain crosslinking monomers and / or comonomers. These optional comonomers serve to adjust the solubility of the buffering polymers or polymer networks in the solvent and / or water used. Crosslinking monomers ensure that the buffering polymers or polymer networks are not removed from the demineralized areas after polymerization.

[0037] Furthermore, the compositions used according to the invention contain at least one initiator for radical polymerization. If photoinitiators are used, they can be dissolved in the overall composition. When using redox initiators, the composition is divided into two portions. Then, one initiator component, e.g., the peroxide, is added to one portion and the second initiator component, e.g., the reducing agent (activator), to the other portion. The two portions are then mixed together for polymerization.

[0038] Other ingredients, such as stabilizers, neutralizers or additives, may also be added to the composition.

[0039] The compositions used according to the invention are applied to the surface to be treated and then polymerized, for example by photopolymerization. Unlike conventional adhesives, the compositions used according to the invention are not dried before polymerization. This prevents the solvent from evaporating. A polymer or polymer network is formed that is permeable to ions. In this way, elastic, temporary protective films can be created, for example around orthodontic bands and clasps. It is also possible to apply the compositions to demineralized areas of the tooth, where they can then penetrate the porous structure and be polymerized, for example, with light. This results in the formation of a protective, buffering polymer in the demineralized zones beneath the tooth surface.Before applying the composition, the enamel can optionally be superficially etched with acid to facilitate penetration. Phosphoric acid is preferably used for this purpose. The formulation is then applied and polymerized within the defect.

[0040] The compositions used according to the invention do not form a dense polymer during polymerization. Rather, after polymerization and replacement of the solvent with water from saliva, an ion-permeable polymer or polymer network is formed, which enables remineralization of the tooth. Accordingly, the removal of excess material from the tooth surface is also easily possible. Initial defects can thus be protected from further demineralization and remineralized with just a single treatment.

[0041] Alternatively, the compositions can be polymerized extraorally to form a molded part, which is then used intraorally as a component. Molded parts can be easily produced, for example, by crosslinking photopolymerization of mixtures of buffering monomers with one or more crosslinks and other hydrophilic comonomers in solution in the presence of photo- and / or redox initiators.

[0042] The compositions, buffering polymers, and polymer networks used according to the invention enable pH control at the sites where they are applied to the patient. They are therefore particularly suitable for the treatment and prevention of dental conditions associated with changes in pH, and especially with a decrease in pH. The compositions used according to the invention allow, in particular, local pH control or local buffering in the patient's mouth, e.g., a reduction in the drop in pH after acid exposure in fissures, the porosities of dental hard tissue, and around orthodontic clasps and appliances. "Local" is understood to mean pH control or buffering in a limited area of ​​the mouth, specifically where the buffering polymers or polymer networks have been applied.

[0043] The compositions, buffering polymers, and polymer networks used according to the invention are particularly suitable for preventing demineralization of teeth and dental hard tissue, especially after exposure to acid; for remineralizing teeth and dental hard tissue; for treating or preventing caries or initial carious lesions; for caries protection in selected areas of the teeth, e.g., fissures, smooth surfaces of teeth, interdental surfaces, and tooth necks; for preventing the progression of caries; and for treating and preventing dental erosion, particularly for the prevention and treatment of caries. The compositions used according to the invention are suitable for promoting the re-deposition of calcium and / or calcium phosphate minerals from saliva and thus for preventing and treating all indications associated with corresponding demineralization of the dental hard tissue.

[0044] As mentioned at the outset, the acid can originate from external sources, particularly from food, or be produced by internal processes, e.g., fermentation processes in the mouth. It can also be stomach acid that enters the oral cavity, for example, in cases of heartburn (reflux esophagitis) or frequent vomiting, such as in anorexia nervosa or bulimia. The compositions used according to the invention are also suitable for the prevention and treatment of reflux-related dental erosion or dental erosion caused by anorexia nervosa or bulimia.

[0045] Furthermore, the compositions used according to the invention are suitable for the prevention and treatment of pregnancy-related dental caries and erosion. The pH in the mouth of non-pregnant women is in the range of 6.6–7.6, with a relatively narrow 95% confidence interval of 7.3–7.6. In pregnant women, significantly lower pH values ​​between 5.9 and 7.6 are found, with a 95% confidence interval of 6.5–6.9. The solubility of tooth enamel is strongly pH-dependent and is approximately 3 mg / L of hydroxyapatite at pH 5, approximately 90 mg / L at pH 4, and approximately 1100 mg / L at pH 3. However, tooth enamel can already lose minerals at higher pH values. Even at pH 6.5, significantly higher calcium concentrations are found in water than at neutral pH. Pregnant women are therefore at increased risk of caries and erosion defects due to demineralization of the teeth.This can be effectively prevented by using the compositions used according to the invention.

[0046] The invention will be explained in more detail below using figures and examples. Fig. Figure 1 shows the titration curves of DHPOBAE and Poly(DHPOBAE) from Example 1 in water, titrated with NaOH solution (0.1 mol / l, 0.1 ml per 130 s). Fig. Figure 2 shows the titration curves for the multiple titration of the water-swollen network from Example 2, titrated with Ca(OH)₂ solution (0.02 mol / l, 0.1 ml each for 260 s) and back-titrated with HCl (0.04 mol / l, 0.1 ml each for 260 s). The polymer network was titrated three times consecutively from acidic to alkaline and back again. Fig. Figure 3 shows SEM images of cross-sections of the networks from Example 2, stored in water and SLS respectively, after freeze-drying. The network stored in SLS shows a significant densification of the morphology compared to the network stored in water. Fig. Figure 4 shows the EDX spectra of cross-sections of the freeze-dried networks from Example 2. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium. Fig. Figure 5 shows the titration curves of the water-swollen network from Example 3, titrated with Ca(OH)₂ solution (0.02 mol / l, 0.1 ml per 260 s) and back-titrated with HCl (0.04 mol / l, 0.1 ml per 260 s). The swollen network acts as a buffer in a pH range of 6.5 to 7.5 (marked area). Fig. Figure 6 shows SEM images of cross-sections of the networks from Example 3 that were stored in water (left) and SLS (right) and subsequently freeze-dried. Fig. Figure 7 shows the EDX spectra of cross-sections of the freeze-dried networks from Example 3. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium. Fig. Figure 8 shows the titration curves of the multiple titration of the water-swollen network from Example 4, titrated with Ca(OH)2 solution (0.02 mol / l, 0.1 ml per 260 s) and back-titrated with HCl (0.04 mol / l, 0.1 ml per 260 s). Fig. Figure 9 shows SEM images of cross-sections of the networks from Example 4 that were stored in water (left) and SLS (right) and subsequently freeze-dried. Fig. Figure 10 shows the EDX spectra of cross-sections of the freeze-dried networks from Example 4. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium. Fig. Figure 11 shows the titration curves of the water-swollen network from Example 5, titrated with Ca(OH)2 solution (0.02 mol / l, 0.1 ml per 260 s) and back-titrated with HCl (0.04 mol / l, 0.1 ml per 260 s). Fig. Figure 12 shows the EDX spectra of cross-sections of the freeze-dried networks from Example 5. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium. Fig. Figure 13 shows the results of test A in Table 2 from Example 7. The hardness profile on the treated and isolated side is almost identical. Therefore, storing the dentin test specimens in the demineralizing solution at pH 5.5 did not lead to any further decrease in hardness. Fig. Figure 14 shows the results of test B in Table 2 from Example 7. The hardness profile on the treated and isolated side is almost identical. Therefore, storing the dentin test specimens in the demineralizing solution at pH 5.5 did not lead to any further decrease in hardness. Fig. Figure 15 shows the results of experiment C in Table 2 from Example 7. The hardness profile of the untreated negative control is significantly lower than on the isolated side. Storing the untreated dentin test specimens in the demineralizing solution at pH 5.5 has therefore led to a further significant decrease in hardness. Examples of implementation Example 1: Investigation of the buffering effect of Poly(DHPOBAE)

[0047] A solution consisting of 0.4 g DHPOBAE, 0.002 g TPO, and 1.598 g ethanol was prepared for the monomer solution. This solution was injected between two glass slides separated by a 2 mm thick rubber ring and then photopolymerized by four minutes of exposure to an LED light source (Bluephase C8 G2, "high" setting, Ivoclar Vivadent, Schaan, Liechtenstein). During photopolymerization, the poly(DHPOBAE) precipitated. The resulting suspension was then dialyzed for at least five days in double-distilled water, which was changed at least twice daily, and subsequently for one day in ethanol (dialysis membrane consisting of regenerated cellulose, MWCO 1000 Da). The product obtained in this way was concentrated for drying and finally dried in a vacuum drying oven at room temperature for twelve hours.The poly(DHPOBAE) obtained in this way was investigated by acid-base titration and the results were compared with those of the monomer DHPOBAE.

[0048] The titration was performed using a Mettler Toledo T70 titrator with a Mettler Toledo DG111-SC pH electrode. NaOH solution with a concentration of 0.1 mol / l was used as the titrant. The titrant was added in 0.1 mL increments at 130 s intervals.

[0049] Fig. Figure 1 shows the titration curves (pH value versus titrant consumption) of the sample from Example 1. This is an example of a non-crosslinked buffering polymer. It is evident that the entire titration curve of poly(DHPOBAE) is shifted towards higher pH values ​​compared to the monomer. Furthermore, the titration of poly(DHPOBAE) does not show a second transition point in the pH range between 8 and 11. For the polymer, the pK values ​​become blurred and shift towards higher values. The polymer only releases protons at a higher pH than the monomer. Example 2: Investigation of the buffering effect and calcium uptake of a polymer network made of DHPOBAE and NDEBAAP

[0050] A solution consisting of 0.39 g DHPOBAE, 0.01 g NDEBAAP, 0.002 g TPO, and 1.598 g isopropanol was prepared for the monomer mixture. This solution was injected between two glass slides separated by a 2 mm thick rubber ring and then photocrosslinked by four minutes of exposure to an LED light source (Bluephase C8 G2, "high" setting, Ivoclar Vivadent, Schaan, Liechtenstein). The resulting, easily removable gel film was then stored in double-distilled water for at least five days, with the water changed at least twice daily. The treated, swollen network was then analyzed by acid-base titration using calcium hydroxide / hydrochloric acid solution.The samples were treated with artificial saliva (SLS, saliva-like solution, 0.72 mmol / l KH₂PO₄, 30 mmol / l KCl, 50 mmol / l 2-(4-(2-Hydroxyethyl)piperazin-1-yl)ethane-1-sulfonic acid (HEPES), 1.2 mmol / l CaCl₂, pH 7 (adjusted with 2 mol / l KOH solution)) for an extended period (14 days) with daily changes of the SLS solution. Following treatment with SLS, freeze-drying and examination by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were performed.

[0051] The titration was performed using a Mettler Toledo T70 titrator with a Mettler Toledo DG111-SC pH electrode. Ca(OH)₂ solution at a concentration of 0.02 mol / l and HCl solution at a concentration of 0.04 mol / l were used as the titrants. The titrant was added in 0.1 mL increments at 260 s intervals.

[0052] Fig. Figure 2 shows the titration curves (pH value versus titrant consumption) of the sample from Example 2. It is evident that the swollen network has a buffering effect in a pH range of 6.5 to 7.5 (marked area). The same sample was titrated three times from acidic to alkaline and then back-titrated from alkaline to acidic. This simulates repeated acid attack. Fig. Figure 2 shows that the buffering network is repeatedly able to buffer acid, as in the case of back titrations, and then releases its protons again at pH values ​​above approximately 6.5, thus being able to buffer acids again.

[0053] Fig. Figure 3 shows SEM images of cross-sections of the networks stored in water and SLS (storage time 13 days in each case, with daily solution changes) after freeze-drying. The network stored in SLS shows a significant densification of the morphology compared to the network stored in water.

[0054] The elemental composition of the cross-sections of the freeze-dried networks was investigated using EDX and evaluated with respect to the calcium content. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium (see [reference]). Fig. 4; Storage time 13 days each; Fig. Figure 4 shows the EDX spectra, normalized to the intensity at 3 keV). Example 3: Investigation of the buffering effect and calcium uptake of a polymer network made of DHPOBAA and NDEBAAP

[0055] A solution was prepared for the monomer mixture consisting of 0.34 g DHPOBAA, 0.06 g NDEBAAP, 0.002 g TPO, and 1.598 g ethanol / water (50 / 50, v / v). This solution was injected between two glass slides separated by a 2 mm thick rubber ring and then photocrosslinked by four minutes of exposure to an LED light source (Bluephase C8 G2, "high" setting, Ivoclar Vivadent, Schaan, Liechtenstein). The resulting, easily removable gel film was then stored for at least five days in double-distilled water, which was changed at least twice daily. The treated, swollen network was then analyzed by acid-base titration with calcium hydroxide solution / hydrochloric acid solution.The samples were treated with artificial saliva (SLS, saliva-like solution, 0.72 mmol / l KH₂PO₄, 30 mmol / l KCl, 50 mmol / l 2-(4-(2-Hydroxy-ethyl)piperazin-1-yl)ethane-1-sulfonic acid (HEPES), 1.2 mmol / l CaCl₂, pH 7, adjusted with 2 mol / l KOH solution) for an extended period (14 days), with daily changes of the SLS solution. Following treatment with SLS, freeze-drying and examination by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were performed.

[0056] The titration was performed using a Mettler Toledo T70 titrator with a Mettler Toledo DG111-SC pH electrode. Ca(OH)₂ solution at a concentration of 0.02 mol / l and HCl solution at a concentration of 0.04 mol / l were used as the titrants. The titrant was added in 0.1 mL increments at 260 s intervals.

[0057] Fig. Figure 5 shows the titration curves (pH value versus titrant consumption) of the sample from Example 3. It is clear that the swollen network has a buffering effect in a pH range of 6.5 to 7.5 (marked area).

[0058] Fig. Figure 6 shows SEM images of cross-sections of the networks stored in water and SLS (storage time 13 days in each case, with daily solution changes) after freeze-drying. The network stored in SLS shows a significant densification of the morphology compared to the network stored in water.

[0059] The elemental composition of the cross-sections of the freeze-dried networks was investigated using EDX and evaluated with respect to the calcium content. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium (see [reference]). Fig. 7; Storage time 13 days each; Fig. Figure 7 shows the EDX spectra normalized to the intensity at 3 keV). Example 4: Investigation of the buffering capacity and calcium uptake of a polymer network consisting of DHPOBAE, DHPOBAA and DEBAAP

[0060] A solution was prepared for the monomer mixture consisting of 0.17 g DHPOBAE, 0.17 g DHPOBAA, 0.06 g NDEBAAP, 0.002 g TPO, and 1.598 g ethanol / water (50 / 50, v / v). This solution was injected between two glass slides separated by a 2 mm thick rubber ring and then photocrosslinked by four minutes of exposure to an LED light source (Bluephase C8 G2, "high" setting, Ivoclar Vivadent, Schaan, Liechtenstein). The resulting, easily removable gel film was then stored for at least five days in double-distilled water, which was changed at least twice daily. The swollen network treated in this way was analyzed by acid-base titration with calcium hydroxide solution / hydrochloric acid solution.

[0061] The titration was performed using a Mettler Toledo T70 titrator with a Mettler Toledo DG111-SC pH electrode. Ca(OH)₂ solution at a concentration of 0.02 mol / l and HCl solution at a concentration of 0.04 mol / l were used as the titrants. The titrant was added in 0.1 mL increments at 260 s intervals.

[0062] Fig. Figure 8 shows the titration curves (pH value versus titrant consumption) of the sample from Example 4. It is evident that the swollen network has a buffering effect in a pH range of 6.5 to 7.5 (marked area). Here, the buffering monomers were used in their acidic form. Therefore, the titration starts at pH 4. After the addition of calcium hydroxide as a titrant, the pH initially dropped slightly because protons were released by the binding of calcium to the phosphonic acid monomer. The pH then rose (first titration). Subsequently, the polymer network was titrated back to acidic conditions with hydrochloric acid, revealing a pronounced buffering effect in the pH range of 6.5 to 7.5. A second titration with calcium hydroxide was then performed.

[0063] Fig. Figure 9 shows SEM images of cross-sections of the networks stored in water and SLS (storage time 13 days in each case, with daily solution changes) after freeze-drying. The network stored in SLS shows a denser morphology compared to the network stored in water.

[0064] The elemental composition of the cross-sections of the freeze-dried networks was investigated using EDX and evaluated with respect to the calcium content. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium (see [reference]). Fig. 10; Storage time 13 days each; Fig. Figure 10 shows the EDX spectra normalized to the intensity at 3 keV). Example 5: Investigation of the buffering effect, calcium uptake and caries protection effect of a polymer network made of DHPOBAE and NDEBAAP

[0065] A solution consisting of 0.34 g DHPOBAE, 0.06 g NDEBAAP, 0.002 g TPO, and 1.598 g DMSO was prepared for the monomer mixture. This solution was injected between two glass slides separated by a 2 mm thick rubber ring and then photocrosslinked by four minutes of exposure to an LED light source (Bluephase C8 G2, "high" setting, Ivoclar Vivadent, Schaan, Liechtenstein). The resulting, easily removable gel film was then stored in double-distilled water for at least five days, with the water changed at least twice daily. The swollen network treated in this way was analyzed by acid-base titration with calcium hydroxide solution / hydrochloric acid solution.

[0066] The titration was performed using a Mettler Toledo T70 titrator with a Mettler Toledo DG111-SC pH electrode. Ca(OH)₂ solution at a concentration of 0.02 mol / l and HCl solution at a concentration of 0.04 mol / l were used as the titrants. The titrant was added in 0.1 mL increments at 260 s intervals.

[0067] Fig. Figure 11 shows the titration curves (pH value versus titrant consumption) of the sample from Example 5. It is clear that the swollen network has a buffering effect in a pH range of 6.5 to 7.5 (marked area).

[0068] After storing cross-sections of the networks in water or SLS (storage time 13 days in each case, with daily solution changes) and freeze-drying, SEM images were acquired, the elemental composition of the cross-sections was analyzed using EDX, and the calcium content was evaluated. In contrast to the sample stored in water, the network stored in SLS shows a clear signal at 3.7 keV, which corresponds to the X-ray emission of calcium (see [reference]). Fig. 12; Fig. Figure 12 shows the EDX spectra normalized to the intensity at 3 keV). Example 6: Production of radically polymerizable compositions for the treatment of teeth

[0069] The solutions described in Table 1 were produced by mixing the components. Table 1: Compositions that form buffering networks through photopolymerization Lösungsmittel[Gew.-%] Monomer 1[Gew.-%] Monomer 2[Gew.-%] Vernetzer[Gew.-%] Initiator[Gew.-%] EtOH / H2O / iPr(80 / 15 / 5, V / V / V)[84.95] DHPOBAE

[10] - NDEBAAP [5] TPO [0,05] EtOH / H2O / iPr(80 / 15 / 5, V / V / V)[79.95] DHPOBAE

[10] - NDEBAAP

[10] TPO[0,05] EtOH / H2O / iPr(80 / 15 / 5, V / V / V)[79.95] DHPOBAE

[15] - NDEBAAP[5] TPO[0,05] EtOH / H2O(80 / 20, V / V)[79.9] DHPOBAE

[10] - NDEBAAP

[10] TPO[0,1] EtOH / H2O(80 / 20, V / V)[79.9] DHPOBAE

[15] - NDEBAAP[5] TPO[0,1] EtOH / H2O(50 / 50, V / V)[79.9] DHPOBAE[8,5] DHPOBAA[8,5] NDEBAAP[3] TPO[0,1] DMSO[79.9] DHPOBAE

[17] NDEBAAP[3] TPO[0,1] EtOH / H2O(50 / 50, V / V)[79.9] DHPOBAE

[17] - NDEBAAP[3] TPO[0,1] iPr[79.9] DHPOBAE

[17] NDEBAAP[3] TPO[0,1] iPr[79.9] DHPOBAE[19,5] NDEBAAP[0,5] TPO[0,1] PPG[79.9] DHPOBAE

[17] NDEBAAP[3] TPO[0,1] PPG[79.9] DHPOBAE[19,5] NDEBAAP[0,5] TPO[0,1] EtOH / H2O(50 / 50, V / V)[79.9] DHPOBAA

[17] - NDEBAAP[3] TPO[0,1] DMSO[79.9] DHPOBAA

[17] NDEBAAP[3] TPO[0,1] Example 7: Investigation of the caries-protective effect of polymer networks

[0070] Caries protection on the tooth was tested in a model with a chemically induced lesion in bovine dentin. To prepare the dentin test specimens, bovine teeth were embedded in resin, and the dentin was exposed using silicon dioxide (SiC) abrasive paper under water cooling. An artificial lesion was created in the dentin by storage for 7 days at 37°C in a demineralizing solution. The demineralizing solution contained 50.0 mmol / L acetic acid, 3.0 mmol / L potassium chloride (KH₂PO₄), 3.0 mmol / L calcium chlorite (CaCl₂) dihydrate (CaCl₂) dihydrate (DH₂O), 1.0 ppm methylenediphosphonic acid, and 100 ppm sodium azide as a preservative. The pH was adjusted to 5.0 with potassium hydroxide (KOH).

[0071] The lesions created in the dentin were partially isolated with nail polish to create an unaltered reference area. The remaining test area was treated with compositions A and B, respectively (see Table 2). Each composition was applied to the test surface with a brush and left in place for 2 minutes. Excess material was removed with a soft cellulose wipe, and the tooth was cured with a polymerization lamp (Bluephase G2, "high" mode, Ivoclar Vivadent, Schaan, Liechtenstein) for 60 seconds. The dentin test specimen was then stored at 37°C for 24 hours in artificial saliva and subsequently for 7 days in the demineralizing solution, this time adjusted to pH 5.5.For comparison, an untreated control was performed by isolating dentin test specimens with lesions, half of which were covered with nail polish, and then stored in the demineralizing solution at pH 5.5 for 7 days without treatment of the test area. Each treatment was performed on two teeth.

[0072] After storage, the dentin test specimens were briefly rinsed with water, patted dry, and the nail polish on the isolated half (reference surface) was removed with ethanol. The surface hardness of both the isolated reference surface and the treated test surface was measured on the dentin using a nanoindenter. The surfaces of the dentin test specimens were then coated with resin so that a cross-section of the tooth could be cut out using a diamond saw. After polishing the cross-section, three hardness profiles were measured on both the treated side and the isolated reference side (30 indentations each, spaced 20 µm apart, vertically to a depth of 600 µm, Berkovich indenter, 100 mN load, loading rate 600 mN / min, 2 s holding time at F). max The hardness profiles were created using the Vickers hardness values ​​automatically calculated by the device.

[0073] The following Fig. 14, Fig. 15 to Fig. Figure 16 shows the measured hardness profiles of the isolated reference halves and the treated test halves after 7 days of storage in the demineralizing solution. In the untreated negative control, the curve of the test half is significantly lower than that of the isolated half. Therefore, storing untreated dentin test specimens in the demineralization solution at pH 5.5 resulted in a further loss of hardness. However, treatments with compositions A and B from Table 2 prevented any further reduction in hardness on the test half compared to the isolated reference half when using the demineralization solution at pH 5.5. These compositions thus provided protection against demineralization. Table 2: Treatments of demineralized dentin test specimens Zus . DMSO EtOH H 2 O DHPOBAE NDEBAAP TPO Ca(NO 3 ) 2 ·4H 2 O A 79.9 - - 17.0 3.0 0.1 - B - 19.1 10.6 17.0 3.0 0.1 50.2 C Untreated negative control A: Monomer mixture from example 5 B: Solution of 0.34 g DHPOBAE, 0.06 g NDEBAAP, 0.002 g TPO, 1.0042 g Ca(NO3)2 ·4 H2O, 0.3826 g EtOH and 0.2112 g H2O C: Untreated negative control.

[0074] Fig.Figure 13 shows the results for composition A. The hardness profile on the treated and isolated sides is almost identical. Therefore, storing the dentin test specimens in the demineralizing solution at pH 5.5 did not lead to any further decrease in hardness.

[0075] Fig. Figure 14 shows the results for composition B. The hardness profile on the treated and isolated sides is almost identical. Therefore, storing the dentin test specimens in the demineralizing solution at pH 5.5 did not lead to any further decrease in hardness.

[0076] Fig. Figure 15 shows the results for composition C. The hardness profile of the untreated negative control is significantly lower than on the isolated side. Storing the untreated dentin test specimens in the demineralizing solution at pH 5.5 has therefore led to a further significant decrease in hardness.

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