AU602012B2

AU602012B2 - Dental material for the control of caries and paradentitis

Info

Publication number: AU602012B2
Application number: AU79557/87A
Authority: AU
Inventors: Rudolf J. Michl
Original assignee: Ivoclar AG
Current assignee: Ivoclar AG
Priority date: 1986-10-11
Filing date: 1987-10-12
Publication date: 1990-09-27
Anticipated expiration: 2007-10-12
Also published as: DE3779855D1; CA1332812C; EP0264660A3; EP0264660A2; ATE77229T1; AU7955787A; DE3634697A1; EP0264660B1; DE3779855T

Abstract

The material contains a combination of the active substances thymol and/or carvacrol and chlorhexidine and/or the physiologically tolerated salts thereof. The material can be a dental lacquer or cement or the like which remains for a lengthy period in the oral cavity and out of which the combination of active substances can diffuse.

Description

LI COMMONWEALTH OF AUSTRALIA Patents Act i6 0 2 0 COMPLETE SP E.C I F.I-CI.A T I ON

(ORIGINAL)

Application Number Lodged This document contains the amendments made under Section 49 and is correct for printing.

Complete Specification Lodged Accepted Published Priority 11 October 1986

I

Related Art Name of Applicant Address of Applicant Actual Inventor/s Address for Service IVOCLAR AG P.O. Box FL-9494, Schaan, Liechtenstein Rudolf J. Michl RICE CO., Patent Attorneys, 28A Montague Street, Balmain N.S.W. 2041 Complete Specification for the invention entitled: DENTAL MATERIAL FOR THE CONTROL OF CARIES AND PARADENTITIS The following statement is a full description of this invention including the best method of performing it known to us:i. ila- The invention relates to the subject matter of claims 1 to Despite research over many decades and numerous attempts to achieve prophylactic and therapeutic treatment of caries and paradentitis, they still constitute an unmastered problem.

°o Medical treatment has hitherto largely been based on fluorides, a cf. Dr. Hans Joachim Schmidt, "Zahnhalskariesprophylaxe durch oo Fluoride", Dr. Alfred Huthig Verlag, Heidelberg, 2nd edition, 1967.

CO

0 However, it is only appropriate to administer fluoride tablets up to o 0 the end of tooth formation, i.e. up to about 12 years of age. After this time, it is mainly a question of the local application of active 0 0 substances for the prophylactic and therapeutic treatment of caries 0 4 S and paradentitis.

o° Fluorides and other active substances and in particular anti- B° microbially active substances have hitherto been largely incorporated oO into mouth and tooth treatment products and have been used during daily oral hygiene. However, the action period thereof is short, because the active substances are very rapidly diluted and rinsed out as a result of permanent salivation and the absorption of food.

To obviate these disadvantages, it has already been proposed for therapeutic treatment of paradentitis to introduce into the parodontium antimicrobially active substances such as chlorhexidine embedded in a film as a system with delayed active substance delivery, i: i? 2 cf. Coventry, J. and Newman, J. Clin. Periodontol. 9, 129-133 (1982) and Friedman, M. and Golomb, J. Periodontol. 17, 323-328 (1982). A further chlorhexidine-containing system with delayed active substance delivery for use in the dental area was described by T.E.Balanyk and H.J.Sandham in J. Dent.Res. 64, 1356-1360 (1985). It consists of a solution of a chlorhexidine salt in benzoin resin, which forms a firm film on drying from which the active substance is delivered in a delayed manner. The described in vitro tests reveal that i0 after 14 days only 3 to 10 mg of chlorhexidine had been supplied by the system and the remaining active substance was not available. Table 1 also shows that the antiseptics thymol s and iodine are the least effective.

The problem of the present invention is to provide an agent S for the effective prophylactic and therapeutic control of caries and paradentites and in particular dental neck caries, Swhich remains over a long period or permanently in the oral cavity, so that it has a longer action period as a treatment L'-0 agent for the mouth and teeth and whilst avoiding the Saforementioned disadvantages has an improved antimicrobial Sactivity, whilst also hardening the attacked dentine.

O 0 Goe This problem is solved according to the invention.

e It has surprisingly been found that the inventive use of a 4 combination of the antimicrobial active agents thymol and/or o carvacrol of formulas CH3 CH,

OH

OH O H

CH

3 C H CH 3 Jlp- -3o o o

OC

0 0 0 a 0 and the antimicrobial active agent chlorhexidine of formula NH H NH NH c1-a NH-C-NH-C-H-ICH-NH-C-NH-NH -0 -a and/or physiologically compatible salts thereof in a dental material, results in an increase in themicrobicidal activity of these substances. In addition surprisingly there is a significant and selective hardening of the carious dentine through the use of the S active substance combination of thymol and/or carvacrol and 0 chlorhexidine or salts thereof in a dental material.

o The active agent combination can be used in any dental material as a carrier, which can be hardened or is hard and i Q from which the active substances can diffuse. Preferably use is made of a material from which the active substances can diffuse into the dentine.

According to the invention the term "dental material"leevers those carrier materials, which remain for a certain period, from hours to years in the oral cavity.

According to a preferred embodiment of the invention the carrier is constituted by a solution of colophony in an organic solvent, particularly preferred solvents being ethanol, propanol and amyl acetate. Good results have also been obtained with e.g. 1,2- )0 dichloroethylene. The solution can be applied to the dental neck by painting, dripping or spraying and form there a firmly adhering varnish, which serves as the active agent reservoir and from which the active agent combination uniformly and completely diffuses ^w^i~ ,j .s 0~d0 L -1" 4 into the dentine.

It has also proved effective to apply the dental material, e.g. as a dental varnish to a solid substrate, where it optionally may harden. According to the invention the term "solid substrate" indicates substrates like artificial teeth, crowns and bridges, toothpicks, toothsilk and similar devices, to which the dental material of the invention can be applied and subsequent to the use or mounting of which within the 1 Q mouthcavity the combination of the invention can develop its activity.

For example a toothvarnish may be applied to the tip of a toothpick and the active agent combination of the invention may be applied to the teeth when cleaning the same.

According to further embodiments of the invention the active agent combination is incorporated into dental materials such as cements, underfilling, filling, sealing, fixing, prosthetic, crown cLO and bridge materials, as well as materials for producing prostheses or in adhesives.

Thymol and/or carvacrol is used in a quantity of approximately to 0.05% by weight, preferably 5 to 0.25% by weight and in particularly preferred manner 2 to 0.5% by weight, in each case based on the dental material. Chlorhexidine is used in a quantity of approximately 2 to 0.01% by weight, preferably I to 0.05% by weight and in particularly preferred manner 0.5 to 0.1% by weight, also based on the dental material.

The aforementioned active substances can be used as such, or in JO3 the form of their physiologically compatible salts.

5 o o c o 4i Usable chlorhexidine salts are e.g. chlorhexidine-di-D-gluconate, chlorhexidine-dihydrochloride and chlorhexidine-diacetate. According to the invention, it is also possible to use related compounds of chlorhexidine such as alexidine, picloxydine or vantocil, as well as those of thymol,such as e.g. aristol.

The inventive dental material can also contain fluoride ions, e.g. in the form of sodium fluoride, in quantities of e.g. 5 to 0.05 and preferably 2 to 0.1% by weight, based on the total formulation.

In place of fluoride ions, it is also possible to use zinc ions, e.g.

as chloride or acetate, tin ions, e.g. as chloride, divalent copper ions, e.g. as copper nitrate and molybdenum ions, e.g. as Na 2 Mo0 4 ,2H 2 0 or mixtures thereof.

The inventive dental material acts both prophylactically and therapeutically against bacteria, the action time being essentially dependent on the carrier system chosen. If, e.g. accrrding to a preferred embodiment of the invention, a solution of colophony is used in high percent ethanol, then it can be painted, dripped or sprayed as a varnish, particularly on to the dental neck. This varnish adheres for a certain time and during this period delivers the active substances contained in an almost complete form to the dental neck.

Although the varnish is removed after a relatively short time by saliva, it maintains its therapeutic action over a longer period. Surprisingly there is a rapid diffusion of the inventive active substance combination into the dentine and from there a uniform delivery of active agent is taking place. This was not foreseeable. The susceptibility of the dental neck to bacteria is consequently considerably reduced and, to the extent that an attack has already taken place, the dentine is hardened and stabilized against spread of the attack.

4 4 44*r ii 6 oio Go 0 00a 33 0 3 030R 33 Carrier materials for dental, varnishes are alsc shellac, benzoin resin, polyvinylpyrrolidone or other artificial or natural resins, which can be dissolved in a solvent and which after evaporation of the solvent become hard.

If the inventive active agent combination is incorporated into cements or other dental materials, then a uniform active agent delivery can take place over a period of several weeks and months.

For example the inventive active agent combination can be incorporated into an underfilling material and then the constant delivery of the active agents effectively prevents the occurrence of secondary caries.

It is also conceivable to incorporate the antibacterial substance combination into a light-hardening or conventionally curing filling material, in order to decrease the rate of formation of secondary caries. Further the active agents used according to the invention can also be incorporated into prosthetic materials, so that the finished prosthesis constantly delivers very small amounts of the active substances and consequently counteracts the spread of plaque, which would lead to caries on the natural teeth which are still present. The invention has a similar effect in false teeth.

Underfilling materials, filling materials, prosthetic materials, false teeth, etc. are well known to the Expert and do not form part of the invention. Such dental materials are e.g. disclosed in DE-OS 24 03 211, DE-OS 27 49 564 and US patent 3 047 408.

The invention is further illustrated hereinafter by means of examples.

A -7- EXAMPLE 1 Preparation of a Varnish 3 g of colophony are placed in a flask, mixed with 6 ml of pure 96% ethanol and after sealing the flask undergoes shaking for 24 hours until they dissolve. 2 ml of distilled water are added to the solution, followed oy 0.1 g of thymol, 0.02 g of chlorhexidine and 0.01 g of sodium fluoride,. being dissolved by shaking again in the liquid. The varnish obtained is stored in a sealed plastic vessel at room temperature.

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'Ic: 8 EXAMPLE 2 The activity of the varnish according to example 1 on the dentine of healthy and carious cattle teeth was investigated in the following way.

Cattle teeth were kept initially for 14 days at 37°C in an artificial caries solution. The solution contained 6% by weight of carboxymethyl cellulose and the pH-value was 4.5. The teeth were completely covered with solution throughout this period. The teeth were then removed, rinsed with water and dried.

In two successive tests, in each case 5 of the teeth treated with S 0 the caries solution and 5 untreated, healthy cattle teeth were coated 0 0 o S with the varnish prepared according to example 1. The action of the varnish on the dentine hardness was determined, in that the Knoop hardness (500 g load) of the varnish-coated teeth was determined in comparison with the corresponding teeth not coated with the varnish.

The results are given in table 1.

oi V Table 1 Knoop hardness measurement length of the impression in pm Dentine Without Caries Dentine With Caries oL Test Without Varnish With Varnish Without Varnish With Varnish 1 358 25 350 18 1233 t 96 970 71 2 356 24 343 29 1200 75 1063 t 61 The results show that the hardness of the healthy, untreated dentine is not or is only insignificantly influenced by the inventive varnish according to example 1. However, the hardness of the carious dentine is significantly improved by the varnish treatment.

_i I 9 EXAMPLE 3 The antimicrobial activity of the inventive active substance combination was proved in the agar diffusion test using streptococcus mutans.

The following test solutions were used: A) Varnish according to example 1 B) Varnish according to example 1 without fluoride ions C) Varnish according to example I without thymol S, D) Varnish according to example 1 without chlorhexidine.

o a 0 0.05 ml of each solution was brought on to the streptococcus es mutans-inoculated agar plates on a Petri dish and the diameters of the inhibition zones after incubating the plates for 18 hours were measured at 37°C. The results are given below in table 2.

Table 2 Test Solution Inhibition Zone Diameter, mm A B SC SD 13 A )0 The results given in table 2 show that the antimicrobial effect of the combination of thymol and chlorhexidine is considerably improved compared with that of the individual components alone. However, the presence of fluoride ions did not influence the inhibition zone diameter.

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Claims

1. Dental material as hereinbefore defined for the control of caries and paradentitis with a content of antibacterial active substances, characterized in that it contains a combination of thymol and/or carvacrol with chlorhexidine in a dental material as the carrier. 2, Dental material according to claim 1 wherein at least part of the chlorhexidine is a physiologically compatible salt thereof.

3. Dental material according to claim 1, characterized in that it contains the thymol and/or carvacrol or salts 0 00 ao thereof in a quantity of 10 to 0.05% by weight and the Sn a chlorhexidine or salts thereof in a quantity of 2 to 0.01% 0 o° by weight, in each case based on the dcntal material. 000 Q0 oooQO 4. Dental material according to either one of claims 1 or 2, characterized in that it contains the thymol and/or carvacrol or the salts thereof in a quantity of 5 to 0.25, preferably 2 to 0.5% by weight and the chlorhexidine or the salts thereof in a quantity of 1 to 0.05, preferably to 0.1% by weight. Dental material according to any one of the claims 1 to 4, characterized in that it additionally contains fluoride ions.

6. Dental material according to any one of the claims 1 to 5, characterized in that the material is a dental varnish, dental cement, underfilling, prosthetic, crown, bridge, filling, sealing or fastening material or adhesive.

7. Dental material according to claim 6, characterized in that the material is a dental varnish based on a solution of colophony in an organic solvent.

8. Dental material according to claim 7, characterized in that the organic solvent is ethanol, propanol or amyl acetate. 'q 06. L N 11

9. A dental material, as hereinbefore defined, comprising a combination of thymol and/or carvacrol with chlorhexidine or physiologically compatible salts thereof, when used for the control of caries and paradentitis A method of controlling caries and/or paradentitis wherein the dental material according to any one of claims 1-8 is applied to a solid substrate and is introduced into the mouthcavity by means of said solid substrate.

11. The method according to claim 10, characterized in that the solid substrate is a toothpick.

12. A dental material substantially as described with S. reference to Examples 1 and 2. 0 o DATED this 14 day of May 1990 o o IVOCLAR AG o Patent Attorneys for the F.B. RICE CO; k 5