IE63269B1 - Liquid for conditioning tooth or bone substance - Google Patents

Abstract

Liquids for conditioning of teeth or bone substance contain phosphonocarboxylic acids in aqueous solution, the solution having a pH in the range from 1 to 8.

Description

The invention relates to a liquid for conditioning defective tooth or bone substance for management with plastic synthetic material.

Hardening plastic synthetic materials are used particularly in dentistry as filling materials for the management of cavities in tooth or bone substance. Preferred as hardening synthetic materials are, in general, acrylate-based fillings. However, these polymeric fillings have the disadvantage that they adhere poorly to the dentine or the bone. In order to solve this problem, for example, in some cases hitherto undercuts have been effected; for this it was necessary to remove considerable amounts of fresh dentine beyond the region affected.

In order to avoid these disadvantages, the dentine or the bone has been pretreated in various ways in order to increase the adhesion of the synthetic material.

Thus, it is known to etch the dentine or the enamel surface with strong acids, for example phosphoric acid, and then to carry out the filling (Scand. J. Dental Res. 88, 348-351 (1981)). Apart from the irritant action of the strong acid in the region of the mouth, the adhesion of the filling is inadequate.

It is additionally known to pretreat the dentine with ethylenediaminetetraacetic acid (EDTA) and then to provide it with a coating agent composed of an aliphatic aldehyde or a ketone and an olefinically unsaturated monomer, for example an ester of acrylic or methacrylic acid (EP-A 0,141,324 and EP-A 0,109,057).

Liquids for conditioning tooth or bone substance have been found, which contain phosphono carboxylic acids of the formula R 11 1 in HO-P-C-COOH ί1)» I I OH CH2-C00H in which R denotes hydrogen or, optionally substituted by hydroxyl, carboxyl and/or the groups ll/OH -p and/or -COOR', \>H Cx- to C12-alkyl, C2- to C^-alkenyl, C3- to C8cycloalkyl, C8- to C12-aryl or C7- to C12-aralkyl, where R' represents hydrogen or a Cx to CX2-alkyl radical, and/or the salts thereof, in aqueous solution, the solution having a pH in the range 1 to 8.

The new liquids according to the invention condition tooth or bone substance before coating with a primer or liner. A plastic synthetic material applied to tooth or bone substance pretreated in this way undergoes durable bonding.

Within the scope of the present invention the radicals have the following meaning in general: Alkyl represents in general a straight-chain or branched hydrocarbon radical having 1 to 12 carbon atoms. Lower alkyl having 1 to, say, 6 carbon atoms, is preferred. Examples which may be mentioned are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl and isohexyl. Methyl and ethyl are particularly preferred.

Alkenyl represents in general a straight-chain or branched hydrocarbon radical having 2 to 12 carbon atoms and one or two, preferably one, double bond. Lower alkenyl having 2 to, say, 6 carbon atoms is preferred. Examples which may be mentioned are allyl, vinyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl and isohexenyl.

Cycloalkyl represents in general a cyclic hydrocarbon radical having 5 to 8 carbon atoms. Examples which may be mentioned are cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Cyclopentyl and cyclohexyl are particularly preferred.

Aryl represents in general an aromatic radical having 6 to, say, 12 carbon atoms. Preferred aryl radicals are phenyl, naphthyl and biphenylyl.

Aralkyl represents in general an aryl radical which has 7 to 12 carbon atoms and is bonded via an alkyl chain. Preferred aralkyl radicals have 1 to 5 carbon atoms in the aliphatic and 6 to 12 carbon atoms in the aromatic moiety. Examples which may be mentioned are the following aralkyl radicals: benzyl, naphthylmethy1, phenethyl and phenylpropyl.

Preferred within the scope of the present invention are phosphono carboxylic acids of the formula (I) in which R denotes hydrogen or Cx to Ce-alkyl which is optionally substituted by -COOH or llzOH -P. ,1 The following phosphono carboxylic acids may be mentioned by way of example: II (H0)2-P-CH-C00H ch2-cooh phosphonosuccinic acid (PSA) ch2-ch2-co2h II I 2 2 2 CH0)2-P-C-C02H 2 I 2 ch2-co2h 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTA) and II p CH2-CH2-P-<0H)2 II I 2 2 2 2-P-C-CO2H 2 I 2 ch2-co2h 2,4-diphosphonobutane-l,2-dicarboxylic acid (DPBD).

Salts of the phosphono carboxylic acids according to the invention which may be mentioned in particular are the alkali metal salts, preferably the sodium and potassium salts.

The proportion of the phosphono carboxylic acids or the salts thereof in the liquids according to the invention for conditioning tooth and bone substances is determined by the pH.

The pH is, according to the invention, in the range 1 to 8, preferably in the range 2 to 7, particularly preferably in the range 2.5 to 5.

It is possible to adjust the pH by addition of alkali metal hydroxide solutions, for example of sodium hydroxide or potassium hydroxide. The pH can be measured in a manner known per se, for example using suitable indicators or using potentiometric measurement methods (Ullmann, Volume 5, 926 to 936 (1980)).

The aqueous liquids according to the invention for conditioning tooth and bone substances may contain as further ingredient organic carboxylic acids having a pKa below 5, preferably in the range 1 to 4. The following carboxylic acids may be mentioned by way of example: pyruvic acid, citric acid and oxalic acid.

Furthermore, the liquids according to the invention may 10 contain amphoteric amino compounds having a pKa of 9.0 to 10.6 and having a pKB of 11.5 to 12.5.

Amphoteric amino compounds of the formula (II) H 1 1 Rz-C-Rl r3nh (II) in which R1 represents a carboxyl group R2 denotes hydrogen or a lower alkyl radical which is optionally substituted by hydroxyl, mercapto, methylthio, carboxyl, carbonamide, amino, phenyl, hydroxy-phenyl or the groups or H R3 denotes hydrogen or phenyl, H2N\ C*N- and h2it H Rl and R3 are connected by a propylene radical or in which R1 represents hydrogen, R2 denotes the group -A-NH3X in which A represents an alkylene radical having 1 to 6 carbon atoms, and X represents halogen, and R3 denotes hydrogen, may be mentioned as preferred.

The following amphoteric amino compounds may be mentioned by way of example: glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine, alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan, lysine, arginine, histidine, N-phenylglycine, ethylenediamino hydrochloride, ethylenediamine hydrobromide , propylenediamine hydrochloride, propylenediamine hydrobromide, butylenediamine hydrochloride and butylenediamine hydrobromide.

Particularly preferred amphoteric amino compounds are glycine, phenylalanine, lysine and ethylenediamine hydrochloride.

It is also possible to add complexing agents such as ethylenediaminetetraacetic acid (EDTA) and salts derived therefrom.

The aqueous liquids according to the invention for conditioning may contain, for example, per 100 parts by weight to 50 parts by weight of phosphono carboxylic acids, or salts derived therefrom, to 15 parts by weight of organic carboxylic acids, to 10 parts by weight of amphoteric amino compounds, to 10 parts by weight of ethylenediaminetetraacetic * acid, or salts derived therefrom.

A process for the preparation of liquids for conditioning tooth or bone substances has also been found, which is characterised in that an aqueous solution of a phosphono carboxylic acid of the formula R II I HO-P-C-COOH (I), OH CH2-COOH in which R denotes hydrogen or, optionally substituted by hydroxyl, carboxyl and/or the groups llzOH - p and/or -COOR XOH C1-C12-alkyl, C2- to Cu-alkenyl, C5- to C8-cycloalkyl, C6- to C12-aryl or C7- to C12-aralkyl, where R' represents hydrogen or a Cx to C^-alkyl radical, and/or the salts thereof, is prepared with the pH being maintained in the range 1 to 8.

The pH is in general adjusted by addition of alkali metal hydroxide solutions, for example of sodium hydroxide or potassium hydroxide.

In the preparation of the liquids according to the invention the components are in general mixed with vigorous stirring. The components are mixed in general at room temperature, for example in the temperature range 0 to 30’C.

The conditioning liquids according to the invention can furthermore contain thickening agents or surface-active substances in order to adjust the viscosity thereof or the wetting behaviour thereof to meet the special requirements. It is particularly beneficial to add polyvinylpyrrolidine or polyethylene glycols.

When used, the liquids according to the invention are applied to the defective tooth or bone substance, for example into a cavity. Cavities in the enamel or dentine may be mentioned as preferred in this connection.

After the liquids according to the invention have been applied they are in general dried, for example with warm air.

Before the management with the plastic synthetic material of the defective tooth or bone substance, and after the conditioning with the liquids according to the invention, preferably coating with a primer is carried out.

Primers which may be mentioned in particular in this connection are those described in EP-A 0,141,324 and EP-A 0,199,057.

Particularly preferred primers are those which contain an aldehyde or a ketone and an unsaturated monomer with active hydrogen. These primers are excluded from the scope of protection of the present invention.

Aldehydes which may be mentioned in this connection are formaldehyde, compounds which are able to liberate formaldehyde, and acetaldehyde, propionaldehyde, butyraldehyde and glutaraldehyde. Glutaraldehyde is particularly preferred.

Ketones which may be mentioned in this connection are cyclopentanone, benzophenone, cyclohexanone, 2,4pentanedione and camphorguinone. Camphorguinone is particularly preferred.

Olefinically unsaturated monomers with active hydrogen (Bronsted acid) which may be mentioned are acrylic esters, methacrylic esters and acrylic acid and methacrylic acid urethanes having OB, NH2, NH, SB or PB groups. Bydroxyethyl methacrylate is particularly preferred.

Particularly preferred primers are those which contain 1 to 50% by weight of an aliphatic aldehyde having 1 to 20 carbon atoms and 5 to 80% by weight of an olefinically unsaturated monomer with at least one active hydrogen atom in the form of OB, NH2 or SH groups and, where appropriate, water and/or toxicologically acceptable organic solvent. The hardening synthetic materials are essentially determined by the area of use. Thus, for example, it is possible in dentistry to use for the polymerisation only monomers which are physiologically acceptable and are able to polymerise in the region of the mouth. Monomers of this type for dental fillings are known per se (for example Ullmans Enzyklopadie der Technischen Chemie (Ullmann's Encyclopaedia of Industrial Chemistry)).

Examples of synthetic materials which may be mentioned are compositions of acrylate and/or methacrylate monomers, suitable catalysts, starters, accelerators and fillers.

Surprisingly, the conditioning of the defective tooth or bone substance with the liquids according to the invention results in a basis for management with synthetic materials which ensures high durability and strength of the repair.

Example 1 Conditioning liquids Solutions with the concentrations and pH values indicated below were prepared from phosphonosuccinic acid (PSA), glycine and water. The pH was adjusted in Examples B-D with 4N NaOH.

Example No. PSA [mol/1] Glycine [mol/1] PH 1 A 2.40 0.057 <1 1 B 0.44 0.057 3.5 1 C 0.44 0.057 6.0 1 D 0.44 0.057 8.0 1 E 2.40 0.316 3.5 Example 2 Conditioning liquids Solutions with the concentrations and pH values indicated below were prepared from 2-phosphonobutane-l,2,4tricarboxylic acid (PBTA), glycine and water. The pH was adjusted in Examples B-D with 4N NaOH.

Example No. PBTA [mol/1] Glycine [mol/1] pH 2 A 2.3 0.057 <1 2 B 0.46 0.057 3.5 2 C 0.46 0.057 6.0 2 D 0.46 0.057 8.0 2 E 2.1 0.323 3.5 Example 3 (Test of strength of bonding) In the example, the strength of bonding (tensile strength) between dentine or enamel and a commercially available synthetic filling composition is measured.

Used for this test are human teeth which have been extracted and stored under moist conditions. The teeth are embedded in epoxy resin by casting; a flat surface is produced by wet grinding. Final grinding is carried out with carborundum paper 1000.

The surface is then treated with a liquid from Example 1 or 2 for 60 seconds in each case. The treated area is then rinsed with distilled water and dried with air.

Subsequently the surface which has been conditioned with the liquids of Examples 1 or 2 is treated for 60 seconds with the coating agent composed of 5% by weight glutaraldehyde, 36% by weight hydroxyethyl methacrylate and 59% by weight water. The surface is then dried with air.

To prepare a specimen for measurement of the strength of bonding, a cylindrical split Teflon mould is clamped onto the treated surface described above (Scand. J. Dent. Ree. Ifi, 348 to 351 (1981)).

A thin film composed of a solution of 65% by weight bisphenol A diglycidyl methacrylate, 34.3% by weight of triethylene glycol dimethacrylate, 0.2% by weight of camphorquinone and 0.5% by weight of sulphonamide are applied into the mould, and then a light-activated synthetic filling material (Lumifor, Bayer AG) is introduced. Hardening is carried out with a photopolymerisation lamp for 60 seconds. After a further 15 minutes, the Teflon mould is removed, and the strength of bonding is determined using an Instron tensile test apparatus (Scand. J. Dent. Res. 88, 348 to 351 (1981)) with a traction rate of 5 mm/min.

The tensile strengths on dentine measured thereby were as follows: Conditioning liquid A 1 B 1 C 1 D E A 2 B 2 C 2 D 2 E Tensile strength [N/mm2] 6.1 t 0.4 17.3 ± 2.9 .4 ± 2.3 13.9 ± 3.1 17.5 ± 1.2 6.0 i 1.7 17.6 ± 1.7 16.7 1 0.6 17.8 ± 3.1 18.1 ± 4.0 Example 4 A solution with the following composition was prepared from 2,4-diphoephonobutane-l,2-dicarboxylic acid (DPBD), glycine, 4N NaOH and water: DPBD [mol/1] Glycine [mol/1] PH 0.45 0.057 3.5 The strength of bonding to enamel and dentine was measured by the method described in Example 3. The figures obtained were as follows: Enamel: 14.3 N/mm2 Dentine: 13.5 N/mm2 Example 5 Agueous conditioning liquids were prepared from 2phosphonobutane-1,2,4-tricarboxylic acid (PBTA), citric acid (CA), EDTA magnesium salt (Mg EDTA) and polyethylene glycol 4000 (PEG), and the strengths of bonding were determined as in Example 3.

Example No. 5A 5B PBTA [% by wt · ] 1 5 MgEDTA [% by wt.] CA [% by wt.] PEG [% by wt.] Strength of bonding to dentine [N/mm2] Strength of bonding to enamel [N/mm2] 17.711.4 .114.7 19.812.7 16.013.7

Claims (11)

Claims

1. Liquids for conditioning tooth or bone substances, containing phosphono carboxylic acids of the formula 0 R » I HO-P-C-COOH I 1 )' I I OH CH 2 -COOH in which R denotes hydrogen or, optionally substituted by hydroxyl, carboxyl and/or the groups and/or -COOR', \ϊΗ Cj- to C 12 -alkyl, C 2 - to C 12 -alkenyl, C 5 - to C 8 cycloalkyl, C 6 - to C^-aryl or C 7 - to C 12 -aralkyl, where R' represents hydrogen or a C x to C^-alkyl radical, and/or the salts thereof, in aqueous solution, the solution having a pH in the range 1 to 8.

2. Liquids according to Claim 1, characterised in that they have a pH in the range 2 to 7.

3. Liquids according to Claims 1 and 2, characterised in that they contain an organic carboxylic acid having a pKa below 5.

4. Liquids according to Claims 1 to 3, characterised in that they contain an amphoteric amino compound having a pKa in the range 9.0 to 10.6 and having a pK B in the range 11.5 to 12.5. 5. Conditioning tooth or bone substance, characterised in that an aqueous solution of phosphono carboxylic acids of the formula 0 II HO-PI OH in which H I C-COOH | (Ib ch 2 -cooh denotes hydrogen or, optionally substituted by hydroxyl, carboxyl and/or the groups llzOH -P and/or -COOR', \>H C x - to C u -alkyl, C 2 - to C u -alkenyl, C 5 - to C 8 cycloalkyl, C 8 - to C^-aryl or C 7 - to C 12 -aralkyl, where R' represents hydrogen or a C x to C 12 -alkyl radical, and/or the salts thereof, is prepared with the pH 20 being maintained in the range 1 to 8.

5. Liquids according to Claims 1 to 4, characterised in that they contain ethylenediaminetetraacetic acid and/or the salts thereof.

6. Process for the preparation of liquids for

7. Use of liquids according to Claims 1 to 5 as basis for preparing agents for management of cavities in tooth or bone substance with synthetic material.

8. A liquid according to Claim 1, substantially as hereinbefore described with particular reference to the accompanying Examples.

9. A process according to Claim 6 for the preparation of 5 a liquid for conditioning tooth or bone substances, substantially as hereinbefore described with particular reference to the accompanying Exampes.

10. a liquid for conditioning tooth or bone substances, whenever prepared by a process claimed in a preceding claim. Ίθ

11. Use according to Claim 7. substantially as hereinbefore described .