ZA200107757B - Denture adhesive compositions. - Google Patents

Description

DENTURE ADHESIVE COMPOSITIONS

BACKGROUND OF THE INVENTION

Ordinary removable dentures, dental plates and the like, comprise teeth mounted in a suitable plate or base. Denture stabilizers are used to fill the interstices between the _ dentures and the gums or tissues. Prior to placement of the denture in the oral cavity, a denture stabilizer is applied to the denture-plate surface which, for a perfect fit, should uniformly contact the gums and mucous tissues. The denture stabilizer is formulated not ) only for its adherent properties, but also to provide a cushion or gasket between the denture and the gums or tissues, thereby positioning the denture securely in the oral cavity.

Considerable effort has been made over the years to develop improved denture adhesive compositions. Both synthetic and natural polymers and gums have been used singly, in combination, and in combination with various adhesives and other materials in an attempt to lessen certain deficiencies. These deficiencies include inadequate holding power, oozing of the adhesive from under the dental plate during insertion and throughout the wearing period, and messiness and difficulty of removing the residual adhesive from the mouth and dentures. Additionally, food may become trapped between the denture and the oral cavity of the wearer.

Alkyl vinyl ether-maleic copolymers and salts thereof are known in the art for use in denture adhesive compositions. Such disclosures include: U.S. Patent 3,003,988 to

Germann et al., issued October 10, 1961; U.S. Patent 4,980,391 to Kumar et al., issued

December 25, 1990; U.S. Patent 5,073,604 to Holeva et al., issued December 17, 1991;

U.S. Patent 5,900,470, Prosise et al., issued May 4, 1999; U.S. Patent 5,037,924, Tazi et al, issued August 6, 1991; U.S. Patent 5,082,913, Tazi et al,, issued January 21, 1992; and

U.S. Patent 5,525,652 to Clarke, issued June 11, 1996. In addition strip or insert denture adhesives are also known. For example, U.S. Patent 4,880,702 to Homan et al., issued 11/14/89 discloses a denture stabilizer in the form of a strip consisting of three layers. The two outside layers consist of a polymer selected from the group consisting of polyethylene oxide having an average molecular weight of about 200,000 to 10,000,000, sodium carboxymethyicellulose, polyvinyl alcohol, and mixtures thereof. The inside layer consists of microcrystalline wax and a polymer sufficient to adhere the inside layer to gums and a denture base, after contact with water, when the outside layers have been dissolved. European Patent Application 0,353,375 to Altwirth published 2/7/90, discloses an adhesive insert for dentures consisting of a adhesive permeated fibrous fleece and an adhesive consisting of a pasty mixture of alginate and/or carboxymethylcellulose, polyvinyl acetate and an alcoholic solvent. Despite the above-noted technologies as well as many others, a need still exists for denture stabilizing compositions providing improved hold.

In accordance with the present invention, it has been discovered that denture ’ adhesive compositions comprising alkyl vinyl ether-maleic acid copolymers and/or terpolymers with isobutylene comprising magnesium and zinc mixed salts together with specific levels of free acid provide superior denture hold. The present denture adhesive compositions may also be effectively used as a wound dressing, underwater adhesive, a bioadhesive, a delivery vehicle for other actives, and/or any other application that requires adhesion to skin or tissue, including cosmetic pore cleansing strips.

An object of the present invention is to provide alkyl vinyl ether-maleic copolymers and/or terpolymers comprising magnesium and zinc mixed salts, together with specific levels of free acid for adhesive compositions for firm hold, which may be used with dentures. These composition effectively hold dentures in place for a prolonged period of time.

SUMMARY OF THE INVENTION

The present invention relates to a denture adhesive composition comprising mixed salts of an alkyl vinyl ether-maleic acid copolymer and/or terpolymers with isobutylene wherein the mixed salt contains a cationic salt function comprising, or in the alternative consists essentially of, from about 5% to about 50% zinc cations; from 0% to about 2.5% of a cation selected from the group consisting of iron, boron, aluminum, vanadium,

chromium, manganese, nickel, copper, yttrium, titanium, and mixtures thereof, from about 30% to about 60% free acid component; an effective adhesive amount of magnesium cations; and an effective adhesive amount of a cation selected from the group consisting of calcium, strontium, and mixtures thereof, wherein the total level of magnesium, calcium and strontium is from about 5% to about 65%, of the total initial carboxyl groups reacted. In addition the present invention relates to denture adhesive compositions comprising the above composition and at least one non-adhesive self- supporting layer. The present denture adhesive compositions can optionally comprise one or more additional adhesive components. The present invention further relates to a method of increasing the adhesion of dentures to the oral cavity by applying the above _ compositions to dentures, directly to the oral cavity, palate or ridge of the oral cavity, or ’ applying it to both, and thereafter securing the denture to the ridge or palate of the oral cavity.

DETAILED DESCRIPTION OF THE INVENTION

The denture adhesive compositions of the present invention comprise magnesium and zinc mixed salt of an alkyl vinyl ether-maleic copolymer and/or terpolymer with isobutylene (preferably copolymers) with specific free acid levels, and comprising a cation selected from the group consisting of calcium, strontium, and mixtures thereof. The adhesive compositions may be in the form of a powder, cream, paste, liquid, aerosol, and/or wafer. Powder forms are sprinkled on a dental prosthesis, moistened and then inserted into the oral cavity. The compositions may also be combined with various conventional delivery vehicles to form liquids or pastes which are applied to a dental prosthesis and inserted into the oral cavity. These compositions can optionally comprise at least one non-adhesive self-supporting layer. Denture adhesive compositions with a self-supporting layer are thoroughly moistened and applied to dentures. A detailed description of essential and optional components of the present invention is given below.

Definitions

The term "safe and effective adhesive amounts” or “effective adhesive amount”, as used herein, means an amount sufficient to provide adherence to the oral cavity and/or adherence of a dental prosthesis to the palate and ridge of the oral cavity, without toxicity to the user, damage to oral tissue, and alteration of the denture material.

The term “AVE/MA” as used herein refers to alkyl vinyl ether-maleic acid copolymer. The term “AVE/MA/IB” refers to terpolymers with alkyl vinyl ether, maleic acid or anhydride, and isobutylene. The term "mixed polymer salts” or “mixed salts”, as used herein, refers to salts of AVE/MA and/or AVE/MA/IB where at least 2 different cations are mixed on the same polymer with each other or with other ester functions. The present invention comprises mixed polymer (copolymer or terpolymer) salts containing as essential salts: zinc and magnesium cations. The term "free acid" “FA” component, as used herein, refers either to the unreacted carboxyl groups (-COOH) of AVE/MA copolymer and/or AVE/MA/IB plus any other monovalent cations of carboxyl groups; e.g, -COONa, of the polymer. Monovalent cations include Group IA cations, such as _ sodium, potassium, hydrogen, etc. Preferably, the term “free acid” refers to the unreacted carboxyl groups (-COOH) of AVE/MA and/or AVE/MA/IB plus sodium and potassium cations. More preferably, the term “free acid” refers only to the unreacted carboxyl groups (COOH) of the AVE/MA and/or AVE/MA/IB. The term “additional adhesive component”, as used herein, refers to adhesives other than those described as essential

AVE/MA and/or AVE/MA/IB mixed salts of the present invention.

The percentages used herein to describe the mixed salt function of the copolymers or terpolymer are defined as the stoichiometric percent of the total initial carboxyl groups reacted on the polymer. All other percentages used herein are by weight unless otherwise indicated.

Polymer

The alkyl vinyl ether-maleic acid copolymer comprises the repeated structural unit:

ty

In

ET i owt C=—=0

HO In n wherein R represents an alkyl radical, preferably a C, to Cs alkyl radical, n is an integer 5 greater than one representing the number of repeated occurrences of the structural unit in - a molecule of the polymer.

The “terpolymer” or “terpolymer with isobutylene” means a terpolymer of maleic anhydride or acid, an alkyl vinyl ether (preferably with a C,-Cs alkyl radical), and isobutylene, having a structure of (A-B), where A is maleic anhydride or acid and B is alkyl vinyl ether (preferably with a C,-Cs alkyl radical), and/or isobutylene. The specific viscosity of the starting anhydride or acid of the terpolymer is preferably at least about 5.5, preferably at least about 6, preferably measured as a 1% weight/volume solution of methyl ethyl ketone at 25°C. The terpolymer must contain at least some isobutylene.

The present denture adhesive compositions comprise mixed salts of an AVE/MA copolymer and/or terpolymer wherein the mixed salt contains a cationic salt function comprising (or in the alternative consists essentially of) an effective adhesive amount of magnesium cations, from about 5% to about 50% zinc cations, from 0% to about 2.5% of a cation selected from the group consisting of iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, titanium, and mixtures thereof, and an effective adhesive amount of a cation selected from the group consisting of calcium, strontium, and mixtures thereof, of the total initial carboxyl groups reacted, the mixed salt containing from about 30% to about 60% free acid component. The AVE/MA copolymers have a range of specific viscosities. For example, the specific viscosity is preferably from 1.2 to 14, as preferably measured as a 1% weight/volume solution of the starting anhydride or acid of the copolymer, in methyl ethyl ketone at 25°C. Other methods and solvents can be used to measure the specific viscosity such as a 1%

weight/volume solution in DMF (dimethyl formamide) at 25°C and a 1% weight/volume solution in 2-butanone at 25°C.

Preferably, the total level of magnesium, calcium and strontium is from about 10% to about 60%, more preferably from about 15% to about 55%, of the initial carboxyl § groups reacted. In addition, preferably the cationic salt function contains from about 10% to about 45% zinc, more preferably from about 15% to about 40% zinc cations, of the initial carboxyl groups reacted; preferably from about 0.001% to about 2.5 %, more preferably from about 0.01% to about 2% of a cation selected from the group consisting of iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, titanium, and mixtures thereof, more preferably from about 0.01% to about 2% iron - cations, of the initial carboxyl groups reacted. Preferably the cationic salt function contains from about 37.5% to about 55%, more preferably from about 37.5% to about 50%, free acid component, of the total initial carboxyl groups.

The alkyl vinyl ether maleic anhydride copolymers are obtained by co- polymerizing an alkyl vinyl ether monomer, such as methyl vinyl ether, ethyl vinyl ether, divinyl ether, propyl vinyl ether and isobutyl vinyl ether, with maleic anhydride to yield the corresponding alkyl vinyl ether-maleic anhydride copolymer which is readily hydrolyzable to the acid copolymer. Suitable copolymers may be prepared by well-known methods of the prior art, for example US 2,782,182, and US 2,047,398, both of which are incorporated herein by reference in their entirety. Both anhydride and acid forms are also available from commercial suppliers. For example, the ISP Corporation, Wayne, N.J. provides both the polymeric free acid form (I) and the corresponding anhydride form under its "GANTREZ" trademark as the "GANTREZ S Series” and "GANTREZ AN

Series", respectively. When the anhydride copolymer dissolves in water, the anhydride linkage is cleaved so that the highly polar, polymeric free acid (I) is formed. Accordingly, the anhydride form, which is relatively less expensive than the acid form, may be used as a convenient and cheaper precursor for the acid. Elevated temperatures may be advantageously employed to enhance the rate of anhydride-to-acid hydrolysis. The terpolymers can be made by the methods discussed in U.S. Patent 5,900,470, Prosise et al, issued May 4, 1999; U.S. Patent 5,037,924, Tazi et al., issued Aug. 6, 1991; and U.S.

N WO 00/61071 PCT/US00/10185

Patent 5,082,913, Tazi et al., issued Jan. 21, 1992, herein incorporated by reference in their entirety.

The salt form of the subject polymers may be prepared by the interaction of the

AVE/M anhydride or acid copolymer or terpolymer with at least one cationic salt function, such as magnesium, zinc, calcium, sodium, potassium, iron, or ammonium compounds having a functional group typical of reactants of a carboxylic acid, such as, for example, the hydroxide, oxide, acetate, halide, lactate, etc. in an aqueous medium. In a preferred embodiment, the zinc oxide, magnesium oxide, combined with strontium carbonate and/or calcium hydroxide are utilized. Mixed polymer salts comprising iron cations can be prepared by the interaction of the AVE/M anhydride/acid polymers with - iron compounds, in the form of a salt, such as iron sulfate n-hydrate.

Ions that form toxic, irritating or contaminating by-products should be avoided, or special precautions and treatment provided to assure the removal and absence of such by- ) products from the polymeric salt end-product. The particular compound used should be substantially pure to assure obtaining a substantially pure, polymeric salt end-product.

If the salt form of the polymer is desired, then an aqueous dispersion of particulate zinc oxide is combined with magnesium oxide (combined with strontium carbonate and/or calcium hydroxide) and, optionally, ferric sulfate n-hydrate. This is combined with the powder polymer, in the form of a slurry, in an amount sufficient to provide the desire cationic content desired in the end-product. This is done at ambient temperature and then slowly heated to 70°-95°C with continuous vigorous mixing so as to prevent localized precipitation of the cationic polymeric salt; mixing is continued to ensure that all the salt forming compound is reacted with the copolymer.

Alternatively, the polymer is hydrolyzed and neutralized in an aqueous mixture or slurry of one or more divalent and/or monovalent metal bases by heating the copolymer/base mixture to a temperature ranging from about 45°C to about 100°C.

Reaction of the mixed polymer salt with iron cations is obtained through addition of iron salts to the hydrolyzed and neutralized mixed salt of the polymer. Completion of the reaction with iron cations is indicated by an increase in viscosity to stabilization.

Alternatively, iron salts may be blended with the polymer/metal base mixture prior to the hydrolysis and neutralization reactions.

In either of the above processes, the resulting slurry or solution is transferred to shallow stainless steel drying trays and placed in a forced air mechanical convection oven at 60-70°C for a time sufficient to evaporate the reaction medium (water) and remove water from the polymer (about 18-24 hours). Altematively, the resulting slurry or solution can be drum-dried at 100° to 200°C with hot steam to evaporate the water content and recover the polymer in the flake form. After drying, the polymer forms brittle flakes which can easily be peeled off from the trays or drum surface and ground to a fine powder as desired to provide satisfactory denture stabilizing properties. Methods of making these mixed salts of AVE/MA polymers are further disclosed in U.S. Patent Nos. 5,073,604, Holeva et al., issued Dec. 17, 1991; 5,872,161, Liang et al., issued Feb. 16, - 1999; 5,830,933, Synodis et al., issued Nov. 3, 1998, all of which are herein incorporated by reference in their entirety. : )

The mixed salt polymers have exceptional adhesive qualities when contacted with water or saliva such that they are extremely useful as denture adhesive materials in denture compositions. The compositions of the present invention comprise a safe and effective adhesive amounts of the mixed salt polymers, preferably at least 20 percent by weight, and more preferably at least 30 percent by weight of the composition, as the sole adhesive component or as a co-adhesive in joint usage with other adhesive components.

Optional Non-Adhesive Self-Supporting Layer

The present denture adhesive compositions optionally comprise at least one non- adhesive self-supporting layer. The non-adhesive self-supporting layer is characterized by its ability to maintain strength and provide integrity for the adhesive composition in the presence of water and/or saliva. The non-adhesive self-supporting layer may include materials such as polyester, polypropylene, nylon, rayon, cellulose acetate, non-adhesive cellulose derivatives, cloth, fibrous fleece, paper, plastic, leather, microcrystalline wax, synthetic fibers, natural fibers, and mixtures thereof. Preferred are non-adhesive cellulose derivatives, polyester, polypropylene, nylon, rayon, cloth, paper, microcrystalline wax, and mixtures thereof. More preferred are polyester, polypropylene, rayon, nylon, cloth and paper.

The non-adhesive self-supporting layer may be in any physical form suitable for providing strength and/or integrity to the present adhesive compositions. Such physical

Claims (11)

WHAT IS CLAIMED IS:

1. A denture adhesive composition comprising a mixed salt of a copolymer of alkyl vinyl ether and maleic acid or anhydride, the mixed salt containing a cationic salt function comprising: a) from 5% to 50% zinc cations, preferably from 15% to 40%: b) an effective adhesive amount of magnesium cations; c) an effective adhesive amount of a cation selected from the group consisting of calcium, strontium, and mixtures thereof: d) from 0% to 2.5%, preferably from 0.01% to 2%, of a cation selected from the group consisting of iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, titanium, and mixtures thereof; and e) from 30% to 60% free acid component; wherein the total level of magnesium, calcium and strontium cations is from 5% to 65%, preferably from 15% to 55%.

2. The denture adhesive composition according to Claim 1 wherein the specific viscosity of the copolymer is greater than 5.5.

3. A denture adhesive composition comprising a mixed salt of a terpolymer of alkyl vinyl ether, maleic acid or anhydride, and isobutylene, the mixed salt containing a cationic salt function comprising: a) from 5% to 50% zinc cations, preferably from 15% to 40%, b) an effective adhesive amount of magnesium cations; c) an effective adhesive amount of a cation selected from the group consisting of calcium, strontium, and mixtures thereof: d) from 0% to 2.5%, preferably from 0.01% to 2%, of a cation selected from the group consisting of iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, titanium, and mixtures thereof: and e) from 30% to 60% free acid component; wherein the total level of magnesium, calcium and strontium cations is from 5% to 65%, preferably from 15% to 55%.

4. The denture adhesive composition according to Claim 1 or 3 further comprising one or more ingredients selected from the group consisting of additional adhesive

A Y ’ ) components, plasticizers, colorants, preservatives, thickeners, vehicles, flavors, fragrances, sensates, and mixtures thereof,

5. The denture adhesive composition according to Claim 4 wherein the additional adhesive component is selected from the group consisting of natural gums, synthetic polymers, mucoadhesive polymers, hydrophilic polymers, natural polymers, saccharide derivatives, cellulose derivatives, preferably selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl-cellulose, sodium carboxymethyleellulose, and mixtures thereof, mixed salts of AVE/MA copolymers, AVE/MA copolymer acid, alkyl vinyl ether-maleic anhydride copolymer, and mixtures thereof.

6. The denture adhesive composition according to Claim 4 wherein the vehicle is selected from the group consisting of petrolatum, liquid petrolatum, mineral oil, glycerin, and mixtures thereof,

7. The denture adhesive composition according to Claim 1 or 3 wherein the composition further comprises at least one non-adhesive self-supporting layer.

8. The denture adhesive composition according to Claim 7 wherein the non-adhesive self-supporting layer is selected from the group consisting of polyester, polypropylene, nylon, rayon, cellulose acetate, non-adhesive cellulose derivatives, cloth, fibrous fleece, paper, plastic, leather, microcrystalline wax, synthetic fibers, natural fibers, and mixtures thereof,

9. The denture adhesive composition according to Claim 8 wherein the non-adhesive self-supporting layer is in a physical form selected from the group consisting of non-woven, woven, continuous, chopped, and combinations thereof. 1 Qe Aiiethod-o incr oasing-the-adhesion-of-dentures-to-the-oral-cavity-by-applying-the secubing-the-denture-io-the-eral-envityr

22 PCT/US00/10185

10. The use of a composition according to claim 1 or 3 to increase the adhesion of dentures to the oral cavity.

11. The denture adhesive composition substantially as described herein and with reference to the examples. AMENDED SHEET