Tartar control denture adhesive compositions

CA 02393594 2005-03-29

TARTAR CONTROL 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 dentureplate surface which, for a perfect fit. should uniformly contact the gums and mucous tissues. The denture stabilizer is formulated not only for its adherent propenies, 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 alone, in combination, and in combination with various adhesives and other materials in an attempt to improve hold and reduce oozing of the adhesive from under the dental plate, messiness and difficult}· of removing the residual adhesive from the mouth and dentures. For example, alkyl vinyl ether-maleic copolymers and salts thereof are known for providing good hold in denture adhesive compositions. Such disclosures include: U.S Patent 3,003,988, Germann et al., issued October 10, 1961; U.S. Patent 4,980.391, Kumar et al., issued December 25, 1990; U.S. Patent 5,073,604, Holeva et al., issued December 17, 1991; U.S. Patent 5,525,652, Clarke, issued June 11, 1996; U.S. Patent 5,340,918, Kittrell et al., issued Aug. 23, 1994; U.S Patent 5,830,933, Synodis et al., issued Nov. 3, 1998.

In addition to adhesion, it is desirable to deliver anticalculus or antitartar benefits in a denture adhesive composition especially for those denture wearers who still have some natural teeth remaining. Tartar is a deposit which forms on the surfaces of teeth. Mature calculus consists of an inorganic portion which is largely calcium phosphate arranged in a hydroxyapatite crystal lattice structure similar to bone, enamel and dentine. An organic portion is also present and consists of desquamated epithelial cells, leukocytes, salivary sediment, food debris, and microorganisms.

It is generally known that certain polyphosphates are effective anticalculus agents when delivered to the oral cavity by incorporation into aqueous based compositions like dentifrice or mouthrinsc compositions. For example US 5,096, 699, issued March 17, 1992, Gaffar et al. assigned to Colgate, teaches dentifrice and mouthrinse compositions comprising azacycloalkane-2,2-diphosphonic acids (AAP) and salts thereof and a synthetic anionic polymeric polvcarboxylate (SAPP). In addition, US 4,913,895, Miyake et al., issued April 3, 1990, teaches dentifrice and mouthrinse compositions with selected polyphosphates and menthol, anethol, or mixtures. These references, however, only disclose the deliver}' of polyphosphates via aqueous dentifrice and mouthrinse compositions, where the deliveiy is also dependent, at least in part, on brushing or rinsing of the oral cavity. The prior art. then, does not suggest that

CA 02393594 2006-09-18 anticalculus agents would be available and delivered in sufficient quanities to render an anticalculus benefit, when placed in a non-aqueous composition, also comprising adhesive components.

Despite the above-noted technologies, as well as others, a need still exists for denture stabilizing compositions providing both superior hold and anticalculus (or antitartar) benefits to the denture wearer. In accordance with the present invention, denture adhesive compositions comprising a denture adhesive component combined with an anticalculus agent provide anticalculus benefits, while providing superior denture hold.

SUMMARY OF THE INVENTION

The present invention relates to a non-aqueous denture adhesive composition comprising:

(a) a safe and effective adhesive amount of a denture adhesive component selected from the group consisting of natural gums, synthetic polymeric gums, AVE/MA, salts of AVE/MA, AVE/MA/IB, salts of AVE/MA/IB, divalent salts of a copolymer of maleic anhydride and ethylene, divalent salts of copolymer of maleic anhydride and styrene, divalent salts of a copolymer of maleic anhydride and isobutylene, polyacrylic acid and polyacrylates thereof, water-soluble hydrophilic colloids or polymers having the property of swelling upon exposure to moisture to form a mucilaginous mass, hydrophilic polymers, saccharide derivatives, cellulose derivatives, and mixtures thereof;

(b) a safe and effective amount of an anticalculus agent selected from the group consisting of a copolymer of maleic anhydride or acid and ethylene and monovalent (e.g. sodium, potassium) and ammonium salts thereof; a copolymer of maleic anhydride or acid and styrene and monovalent (e.g. sodium, potassium) and ammonium salts thereof; copolymer of maleic anhydride or acid and isobutylene and monovalent (e.g. sodium, potassium) and ammonium salts thereof; polyitaconic acid and monovalent (e.g. sodium, potassium) and ammonium salts thereof; and mixtures thereof; and (c) a non-aqueous denture adhesive carrier.

CA 02393594 2010-03-29

In accordance with an aspect of the present invention, there is provided a denture adhesive composition comprising:

(a) from about 20% to about 50% by weight of the composition of a denture adhesive component selected from the group consisting of salts of alkyl vinyl ether-maleic acid or anhydride copolymer, divalent salts of a copoljmer of maleic anhydride and ethylene, divalent salts of copolymer of maleic anhydride and styrene, divalent salts of a copolymer of maleic anhydride and isobutylene, polyacrylic acid and polyacrylates thereof, and mixtures thereof;

(b) from about 0.1% to about 25% by weight of the composition of an anticalculus agent selected from the group consisting of a copolymer of maleic anhydride or acid and ethylene and monovalent and ammonium salts thereof: a copolymer of maleic anhydride or acid and styrene and monovalent and ammonium salts thereof; copoly mer of maleic anhydride or acid and isobutylene and monovalent and ammonium salts thereof; polyitaconic acid and monovalent and ammonium salts thereof; and mixtures thereof; and (c) a non-aqueous denture adhesive carrier.

In accordance with an aspect of a denture adhesive composition of the present invention, there is provided a denture adhesive component comprised of a salt of alkyl vinyl ether-maleic acid or anhydride copolymer, the salt containing a cationic salt function comprising a cation selected from the group consisting of Group 1A and Group 2A cations of the periodic table, yttrium, titanium, zirconium, vanadium, chromium, manganese, iron, nickel, copper, zinc, boron, aluminum, sodium, and mixtures thereof.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a denture adhesive component comprised of a salt of alkyl vinyl ether-maleic acid or anhydride copolymer, the salt containing a cationic salt function comprising a cation selected from the group consisting of strontium, zinc, iron, magnesium, calcium, sodium, and mixtures thereof.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a denture adhesive component comprised of a salt of alkyl vinyl ether-maleic acid or anhydride copolymer, the salt containing a cationic salt function comprising a mixture of two or more cations selected from the group consisting of strontium, zinc, iron, magnesium, calcium, sodium, and mixtures thereof.

in accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a anticalculus agent selected from a group consisting of a copolymer of maleic anhydride or acid and ethylene and monovalent sails thereof; a copolymer of maleic anhydride or acid and styrene and monovalent salts thereof; and mixtures thereof.

2a

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In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a non-aqueous denture adhesive carrier selected from a group consisting of a non-aqueous vehicle and a non-adhesive self supporting layer.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a non-aqueous vehicle selected from the group consisting of liquid petrolatum, petrolatum, mineral oil, glycerin, natural and synthetic oils, fats, silicone and silicone derivatives, polyvinylacetate, natural and synthetic waxes, vegetable oil waxes, vegetable oils, and mixtures thereof.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a carrier comprised of a non-adhesive self-supporting layer, selected from a group consisting of polyester, polypropylene, nylon, rayon, cellulose acetate, non-adhesive cellulose derivatives, cloth, fibrous fleece, paper, plastic, leather, synthetic fibers, natural fibers and mixtures thereof.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a use to reduce, inhibit, control, or prevent calculus or tartar in an oral cavity.

In accordance with a further aspect of a composition of the present invention, there is provided a use in relation to the preparation of a medicament for reducing, inhibiting, controlling, or preventing calculus or tartar in an oral cavity.

In accordance with a further aspect of a denture adhesive composition of the present invention, there is provided a use to reduce, inhibit, control, or prevent calculus or tartar in an oral cavity to secure a denture in the oral cavity.

In accordance with a further aspect of a composition of the present invention, there is provided a use in relation to the preparation of a medicament for reducing, inhibiting, controlling, or preventing calculus or tartar in an oral cavity to secure a denture in the oral cavity.

In accordance with a further aspect of a composition of the present invention, there is provided a use for securing a denture in an oral cavity while simultaneously reducing, controlling, or preventing calculus or tartar in said oral cavity.

2b

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In accordance with a further aspect of a composition of the present invention, there is provided a use in relation to the preparation of a medicament for reducing, inhibiting, controlling, or preventing calculus or tartar in an oral cavity wherein said composition is for securing a denture in said oral cavity.

DETAILED DESCRIPTION OF THE INVENTION

A detailed description of essential and optional components of the present invention is given below.

Definitions

The term anticalculus” or antitartar” agent, as used herein, means a material effective in reducing, controlling, inhibiting, preventing, and/or minimizing mineral (e.g., calcium phosphate) deposition related to calculus or tartar formation. The term safe and effective adhesive amounts as used herein means an amount sufficient to provide adherence to the oral cavity and/or provide adherence of a dental prosthesis to the oral cavity, without toxicity to the user or damage to oral tissue.

By safe and effective amount”, as used herein, is meant an amount of an agent (e.g.. anticalculus agent) high enough to significantly (positively) modify the condition to be treated, but low enough to avoid serious side effects (at a reasonable benefit/risk ratio), within the scope of sound medical/dental judgment. The safe and effective amount of an agent (e.g., anticalculus agent) may vary with the particular condition

2c

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WO 01/41711 PCT/USOO/33413 being treated, the age and physical condition of the patient being treated, the severity of the condition, the duration of treatment, the nature of concurrent therapy, the specific form of the source employed, and the particular vehicle from which the agent is applied.

The term “AVE/MA” as used herein refers to alkyl vinyl ether-maleic acid or anhydride 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 salts of AVE/MA/IB where at least 2 different cations are mixed on the same polymer with each other or with other salts.

The term “free acid” or “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 percentages used herein to describe the cationic salt function of the alkyl vinyl ether-maleic acid or anhydride copolymers are defined as the stoichiometric percent of the total initial carboxyl groups reacted on the polymer.

All other percentages used herein are by weight of the composition unless otherwise indicated.

Denture Adhesive Components

The present invention comprises a safe and effective adhesive amount of a denture adhesive component, generally at a level of from about 10% to about 90%, in another embodiment from about 15% to about 70%, and in another embodiment from about 20% to about 50%, by weight of the composition. In one embodiment the compositions of the present invention comprise at least 20 percent by weight, and in another embodiment at least 30 percent by weight of the composition, of a denture adhesive component.

“Denture adhesive components” include natural gums, synthetic polymeric gums, AVE/MA. salts of AVE/MA, AVE/MA/IB, salts of AVE/MA/IB, divalent salts of copolymer of maleic anhydride and ethylene, divalent salts of copolymer of maleic anhydride and styrene, divalent salts of copolymer of maleic anhydride and isobutylene, polyacrylic acid and polyacrylates thereof, water-soluble hydrophilic colloids or polymers having the property of swelling upon exposure to moisture to form a mucilaginous mass, hydrophilic polymers, saccharide derivatives, cellulose derivatives, and mixtures thereof. Examples of such materials include karaya gum, guar gum, gelatin, algin, sodium alginate, tragacanth, chitosan, polyethylene glycol, polyethylene oxide, acrylamide polymers, carbopol, polyvinyl alcohol, polyamines, polyquartemaiy compounds, ethylene oxide polymers, polyvinylpyrrolidone, cationic polyacrylamide polymers, AVE/MA, AVE/MA/IB, mixed salts of AVE/MA, mixed salts of AVE/MA/IB, and mixtures thereof.

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PCT/US00/33413

In one embodiment the adhesives are salts of AVE/MA, salts of AVE/MA/IB, mixed salts of AVE/MA, mixed salts of AVE/MA/IB, cellulose derivatives, polyethylene glycol, polyethylene oxide, karaya gum, sodium alginate, chitosan, polyvinyl alcohol, and mixtures thereof. In yet another embodiment the adhesives are mixed salts of AVE/MA and cellulose derivatives such as methylcellulose, carboxymethylcellulose, hydroxvethylcellulose, hydroxypropylcellulose, hydroxy-propylmethylcellulose, and mixtures thereof.

Alkvl Vinvl Ether-Maleic Copolymer

In one embodiment of the invention the denture adhesive is AVE/MA or salts of AVE/MA. The alkyl vinyl ether-maleic acid co-polymer comprises or consists essentially of the repeated structural unit:

(I)

OR

--CH₂--CH--CH—CH-O=C C=O

HO OH wherein R represents an alkyl radical, preferably a Ci to C₅ alkyl radical, n is an integer greater than one representing the number of repeated occurrences of the structural unit in a molecule of the polymer.

In one embodiment, the adhesive component is AVE/MA and salts thereof, preferably mixed salts of AVE/MA, wherein the copolymer contains a cationic salt function comprising a cation selected from the group consisting of Group IA and Group 2A cations of the periodic table, yttrium, titanium, zirconium, vanadium, chromium, manganese, iron, nickel, copper, zinc, boron, aluminum, cations and mixtures thereof. In another embodiment, the adhesive component is a mixed salt of AVE/MA containing a cationic salt function comprising a cation selected from the group consisting of strontium, zinc, iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, titanium, magnesium, calcium, sodium, cations and mixtures thereof, and in yet another embodiment the the cation is selected from the group consisting of strontium, zinc, iron, magnesium, calcium, sodium, cations, and mixtures thereof.

AVE/MA contains, in one embodiment, a cationic salt function comprising from about 5% to about 50%, in another embodiment, from about 10% to about 40%, in yet another embodiment, from about 10% to about 35% (of the total initial carboxyl groups reacted) zinc cations. These zinc cations can be mixed with other cations selected from the group consisting of: from about 5% to about 65%, preferably from about 10% to about 60%, strontium cations, from about 0.001% to about 2.5%, preferably from about

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0.01% to about 2% of iron, boron, aluminum, vanadium, chromium, manganese, nickel, copper, yttrium, and/or titanium cations, from about 5% to about 65%, preferably from about 15% to about 50% of calcium and/or magnesium cations.

AVE/MA and salts thereof and AVE/MAÆB and salts thereof, are also described in U.S. Patent Nos. 5,073,604 to Holeva et al., issued 12/17/91; 5,525,652, issued Jun. 11, 1996, Clarke et al.;

4,758,630, issued July 19, 1988, Shah et al.; 5,304, 616, issued April 19, 1994, Rajaiah et al.; 5,424,058, issued June 13, 1995, Rajaiah; 5,424,058, issued 6/13/95, Rajaiah et al.; 4,758,630, issued July 19, 1988, Shah et al.; 5,830,933, issued Nov. 3, 1998, Synodis et al.; 2,047,398, issued July 14, 1936, Voss et al.; 3,003,988, issued Oct. 10, 1961, Germann et al.; 5,880,172, Rajaiah et al., issued March 9, 1999; 5,900,470, Prosise et al,, issued 5/4/99; 5,037,924, Tazi et al., issued 8/6/91; 5,082,913, Tazi et al. issued 1/21/92 . Salts of AVE/MA are also described in P&G U.S. and Canadian patent and application numbers: US Patent

No. 6,355,706 issued Mar. 12,2002. Rajaiah et al.; CA 2372265 filed Apr. 13,2000, Rajaiah et al.;

Canadian Patent No. 2,369,233 issued Dec, 14, 2004: and US. Patent No. 6,617,374 issued Sept. 9,2003.

In one embodiment the free acid level of the salts of the .- VE/ΜΑ or AVE/MA/DB is at least about 36%, in another embodiment is from about 36% to about 60%, and even in another embodiment is from about 40% to about 55%, of the total initial caiboxyl groups of the copolymer or terpolymer.

The specific viscosity of the starting copolymer acid or copolymer anhydride is from about 1.2 to about 14, when preferably measured in a 1% weight/volume solution in MEK (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 2butanone at 25°C.

Suitable AVE/MA copolymers may be prepared by well-known methods of the prior art: see, for example, US 2,782,182, and US 2,047,398^

The salt form of the subject polymers may be prepared by the interaction of the acid or anhydride polymer with at least one cationic salt function as described above, 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 one embodiment, the zinc oxide, strontium carbonate, iron sulfate η-hydrate, etc are utilized.

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.

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The salt form of the polymer can be made by mixing the salts (sodium hydroxide, zinc oxide, strontium carbonate, ferric sulfate n-hydrate, calcium hydroxide and/or magnesium oxide, etc.) in an aqueous dispersion. This is combined with the powder alkyl vinyl ether-maleic acid or anhydride copolymer, in the form of a slurry, in an amount sufficient to provide the desired 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 AVE/MA copolymer 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.

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 copolymer (about 18-24 hours). Alternatively, 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 copolymer 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 and 5,872,161, Liang et al., issued Feb. 16, 1999.

The Anticalculus Agent

The present compositions comprise a safe ani effective amount of at least one anticalculus agent This amount is generally from about 0.01% to about 40% by weight of the composition, in another embodiment is from about 0.1% to about 25%, in vet another embodiment is from about 1.5% to about 20%, and in yet another embodiment is from about 3% to about 15%, in yet another embodiment is from about 3% to about 5%, by weight of the composition. An effective amount of the anticalculus agent is released from the denture adhesive composition. The anticalculus agent should also be essentially compatible with the other components of the composition.

The anticalculus agent of the present invention is selected from the group consisting of copolymer of maleic anhydride or acid and ethylene and monovalent (e g. sodium, potassium) and ammonium salts thereof; copolymer of maleic anhydride or acid and styrene and monovalent (e g. sodium, potassium) and ammonium salts thereof; copolymer of maleic anhydride or acid and isobutylene and monovalent (e g sodium, potassium) and ammonium salts thereof; polyitaconic acid and polyitaconates and monovalent (e.g. sodium, potassium) and ammonium salts thereof; and mixtures thereof.

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More specifically, the anticalculus agent of the present invention is selected from the group consisting of:

(a) A copolymer of maleic anhydride and ethylene, having recurring groups

WO 01/41711

PCT/US00/33413 __CH₂ __CH₂ --CH

CH —

COOM COOM-j and an average molecular weight of about 1,500 and greater; and wherein M and Mi are monovalent salts, for example hydrogen, sodium, potassium, and/or ammonium salts and wherein M and Mi are the same or different; and n is an integer greater than one representing the number of repeated occurrences of the structural unit in a molecule of the polymer;

(b) A copolymer of maleic anhydride and styrene, having recurring groups — CH — CH₂—CH---COOM

<img file="CA2393594C_D0001.tif" />

COOM-iJ _n and an average molecular weight of about 1,500 and greater; and wherein M and Mi are monovalent salts, for example hydrogen, sodium, potassium, and/or ammonium salts and wherein M and Mi are the same or different; and n is an integer greater than one representing the number of repeated occurrences of the structural unit in a molecule of the polymer;

(c) A copolymer of maleic anhydride and isobutylene, having recurring groups ch₃ — C —CH₂—CH---CH₃ COOM

CH —

I

COOM-ι J ¹ n and an average molecular weight of about 1,500 and greater; and wherein M and Mi are monovalent salts, for example hydrogen, sodium, potassium, and/or ammonium salts and wherein M and Mi are the same or different; and n is an integer greater than one representing the number of repeated occurrences of the structural unit in a molecule of the polymer;

(d) A polyitaconic acid, and polyitaconates thereof, having recurring groups

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CH-&gt;~ COOM

I ’ — ch₂ — CI

COOM-, and an average molecular weight of about 1,500 and greater; and wherein M and Mi are monovalent salts, for example hydrogen, sodium, potassium, and/or ammonium salts and wherein M and Mi are the same or different; and n is an integer greater than one representing the number of repeated occurrences of the structural unit in a molecule of the polymer;

Non-Aoueous Denture Adhesive Carrier

The non-aqueous denture adhesive carrier is selected from the group consisting of a non-aqueous vehicle and a non-adhesive self supporting layer. The level of non-aqueous vehicle is from 10% to about 90%, in another embodiment is from about 20% to about 80%, and in yet another embodiment is from about 20% to about 60%, by weight of the composition.

Non-aqueous Vehicles

The non-aqueous vehicle is generally any chemical in any’ physical form that does not contain water. The non-aqueous vehicle is selected from the group consisting of liquid petrolatum, petrolatum, mineral oil, glycerin, natural and synthetic oils, fats, silicone and silicone derivatives, polyvinylacetate, natural and synthetic waxes such as animal waxes like beeswax, lanolin and shellac, hydrocarbons, hydrocarbon derivatives, vegetable oil waxes such as carnauba, candelilla and bayberry wax, vegetable oils such as caprylic/capric triglycerides; in another embodiment is selected from the group consisting of liquid petrolatum, petrolatum, mineral oil, vegetable oils such as com, soy bean, cottonseed, castor, palm and coconut oils and animal oil such as fish oil and oleic acid, and mixtures thereof; and in yet another embodiment is mineral oil.

Caprylic/capric triglycerides are triglycerides of medium chain fatty acids where the —C=O—R group is 8-10 carbons and is obtained by the addition of glycerol to a mixture of capric and caprylic acids:

Caprylic add: CH₃(CH2)6CO₂H

Capric acid: CH₃(CH₂)₈CO2H

Therefore, vegetable oils comprised of saturated medium chain fatty acids such as caprylic acid, capric add and mixtures thereof, can be used in the present invention. These vegetable oils and other non-aqueous vehicles for denture adhesive compositions are further described in US Patent No. 5,561.177. issued on Oct. 1, 1996, Khaledi et al.

Non-Adhesive Self-Supporting Laver

The non-aqueous carrier can comprise at least one non-adhesive self-supporting layer. The nonadhesive self-supporting layer is characterized by its ability to maintain strength and provide integrity for

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WO 01/41711 PCT/US00/33413 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 forms include non-woven, woven, continuous, chopped, foam, and combinations thereof. In addition, the non-adhesive selfsupporting layer may be formed by any process commonly known in the art. Such processes include unbonded, spraybonded, spun-bonded, needle-punched, carded, thermal bonded hydroentangled, meltblown, aperture print bonded, needled, wet-laid, dry-laid, and combinations thereof.

The present denture adhesive compositions which comprise a non-adhesive self-supporting layer may also comprise a coating which is sticky to dry dentures and, if present, will be placed on one side of the denture adhesive composition. Compositions suitable for use as this type of adhesive layer include silicones, rubbers, petrolatum, natural polymers, synthetic polymers, and mixtures thereof. The adhesive layer may be present at a level of from about 0% to about 70%, and in another embodiment from about 0.5% to about 20%, by weight of the composition.

Miscellaneous Carriers

Other suitable ingredients include colorants, preservatives (such as methyl and propyl parabens), thickeners such as silicon dioxide, and polyethylene glycol. Colorants, preservatives, thickeners may be present at levels of from about 0% to about 20%, by weight of the composition.

Plasticizers

In addition one or more toxicologically-acceptable plasticizers may also be included in the present compositions. The term toxicologically-acceptable, as used herein, is used to describe materials that are suitable in their toxicity profile for administration to humans and/or lower animals. Plasticizers that may be used in the present compositions include dimethyl phthalate, diethyl phthalate, dioctyl phthalate, glycerin, diethylene glycol, triethvlene glycol, Igepal®, Gafac®, sorbitol, tricresyl phosphate, dimethyl sebacate, ethyl glycolate, ethylphthalyl ethyl glycolate, o- and p-toluene ethyl sulfonamide, and mixtures thereof. Plasticizers may be present at a level of from about 0% to about 70%, in another embodiment from about 1% to about 30%, by weight of the compositions.

Flavors, Fragrance, Sensates

The compositions of the present invention may also include one or more components which provide flavor, fragrance, and/or sensate benefit (warming or cooling agents). Suitable components include natural or artificial sweetening agents, menthol, menthyl lactate, Wintergreen oil, peppermint oil, spearmint oil, leaf alcohol, clove bud oil, anethole, methyl salicylate, eucalyptol, cassia, 1-menthyl acetate,

CA 02393594 2005-03-29 sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon, vanillin, thymol, linalool, cinnamaldéhyde glycerol acetal known as CGA, and mixtures thereof, as well as coolants. The coolant can be any of a 'vide variety of materials. Included among such materials are carboxamides, menthol, ketals, diols, and mixtures thereof. Preferred coolants in the present compositions are the paramenthan carboxyamide agents such as N-ethyl-p-menthan-3-carboxamide, known commercially as WS-3, N,2,3-trimethyl-2isopropylbutanamide, known as “WS-23,” and mixtures thereof. Additional preferred coolants are selected from the group consisting of menthol, 3-1menthoxypropane-l,2-diol known as TK-10 manufactured by Takasago, menthone glycerol acetal known as MGA manufactured by Haarmann and Reimer, and menthyl lactate known as Frescolat® manufactured by Haarmann and Reimer. The terms menthol and menthyl as used herein include dextro- and levorotatory isomers of these compounds and racemic mixtures thereof. TK-10 is described in U.S. Pat. No. 4,459,425, Amano et al., issued 7/10/84. WS-3 and other agents are described in U.S. Pat. No. 4,136,163, Watson, et al., issued Jan. 23, 1979.

These agents may be present at a level of from about 0% to about 50%, by weight of the composition.

Other Optional Ingredients

The denture adhesive compositions may also be used as a denture adhesive and/or bioadhesive and comprise one or more therapeutic actives suitable for topical administration. Therapeutic actives may be present at a level of from about 0% to about 70%, by weight of the composition, and in one embodiment from about 1% to about 20% by weight of the compostion. Therapeutic actives include antimicrobial agents such as iodine, tricolsan, peroxides, sulfonamides, bisbiguanides, or phenolics; antibiotics such as tetracycline, neomycin, kanamycin, metronidazole, cetylpyridium chloride, or clindamycin; antiinflammatory agents such as aspirin, acetaminophen, naproxen and its salts, ibuprofen, ketorolac, flurbiprofen, indomethacin, eugenol, or hydrocortisons; dentinal desensitizing agents such as potassium nitrate, strontium chloride or sodium fluoride; fluorides such as sodium fluoride, stannour fluoride, MFP; anesthetic agents such as lidocaine or benzocaine; anti-fungals such as those for the treatment of Candida albicans; aromatics such as camphor, eucalyptus oil, and aldehyde derivatives such as benzaldehyde; insulin; steroids; herbal and other plant derived remedies; baking soda, and anti-neoplastics. It is recognized that in certain forms of therapy, combinations of these agents in the same delivery system may be useful in order to obtain an optimal effect. Thus, for example, an antimicrobial and an antiinflammatory agent may be combined in a single delivery system to provide combined effectiveness.

Process for Preparation of the Composition

A process for preparing denture adhesive compositions of the present invention (creams, powders, wafers, non-aqueous liquids, aerosols, pastes) comprises conventional methods disclosed in the art Conventional methods are taught in US 5,525,652, issued June 11. 1996, Clarke et al.; US 3,003,988, 10

CA 02393594 2005-03-29 issued Oct. 10, 1961, Germaim et al.; US 5.073,604, Holeva et al., issued Dec. 17, 1991; and US 5,872,161, Liang et al., issued Feb. 16, 1999.

A process for the preparation of the present denture adhesive compositions comprising a nonadhesive self-supporting layer, comprises coating a we ighed amount of the adhesive components onto the non-adhesive self-supporting layer. This process is disclosed in US 5,877,233, Liang et al, issued March 2, 1999; US 5,872,160, issued 2/16/99, Liang et al.; US 5,880,172, Rajaiah et al., filed Oct. 25, 1996,

Composition Use

The adhesive compositions may be in the form of a powder, cream, paste, non-aqueous liquid, aerosol, and/or wafer. Cream, paste and other compositions of the present invention are generally applied to the denture prosthesis and thereafter the denture is secured to the oral cavity as known in the art.

The following examples further describe and demonstrate embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention. Many variations of these are possible without departing from the spirit and scope of the invention.

EXAMPLEI

Denture stabilizing compositions in cream form are made by blending together the following ingredients:

<td></td><td> A</td><td> B</td><td> C</td>

<td></td><td> Grams</td><td> Grams</td><td> Grams</td>

<td> White Mineral Oil</td><td> 23.93</td><td> 23.93</td><td> 23,93</td>

<td> Petrolatum, White</td><td> 19.8</td><td> 16.87</td><td> 16.87</td>

<td> Carboxymethylcellulose Sodium</td><td> 20.00</td><td> 20.00</td><td> 20.00</td>

<td> Silicon Dioxide. Colloidal</td><td> 1.14</td><td> 1.14</td><td> 1.14</td>

<td> Colorant (Opatint Red Dye)</td><td> 0.06</td><td> 0.06</td><td> 0.06</td>

<td> Any AVE/MA salt with Zn&lt;35%</td><td> 33.00</td><td> 33.00</td><td> 33.00</td>

<td> Sodium salt of a copolymer of maleic anhydride and ethylene</td><td> 2.05</td><td> -</td><td> 2.50</td>

<td> Sodium salt of a copolymer of maleic anhydride and stvrene</td><td></td><td> 5.00</td><td> 2.50</td>

The red dye, petrolatum, and mineral oil are weighed, heated and mixed in a glass jar at 50 to 60 ^QC until visually uniform. Then the powders (colloidal silicon dioxide. CMC, AVE/MA, and sodium salt of a copolymer of maleic anhydride and ethylene and/or sodium salt of a copolymer of maleic anhydride and styrene) are weighed and shaded blended together in a container. Thereafter, the powders are mixed into the liquid with a spatula until visually a uniform pink cr eam. The above compositions can be modified by

CA 02393594 2002-06-04

WO 01/41711

PCT/US00/33413 increasing or decreasing the level of sodium salt of a copolymer of maleic anhydride and styrene or the level of sodium salt of a copolymer of maleic anhydride and ethylene by 0 to 15 grams, AVE/MA by 0 to 15 grams, petrolatum by 0 to 15 grams, and/or the CMC by 0 to 15 grams. The above compositions can also be modified by using any other suitable anticalculus agent. The subject places from 0.1 to 5 grams of the cream on the denture. Then the subject inserts the denture into his/her mouth and presses it into place.

EXAMPLE II

Denture adhesive compositions in powder form are made by blending together the following ingredients:

<td></td><td> A</td><td> B</td><td> c</td>

<td></td><td></td><td></td><td></td>

<td> Carboxymethylcellulose Sodium</td><td> 20.00</td><td> 20.00</td><td> 20.00</td>

<td> Silicon Dioxide, Colloidal</td><td> 1.14</td><td> 1.14</td><td> 1.14</td>

<td> Any AVE/MA salt with Zn&lt;35%</td><td> 33.00</td><td> 33.00</td><td> 33.00</td>

<td> Sodium salt of a copolymer of maleic anhydride and ethylene</td><td> 2.05</td><td> -</td><td> 2.50</td>

<td> Sodium salt of a copolymer of maleic anhydride and styrene</td><td> -</td><td> 5.00</td><td> 2.50</td>

All components are blended together. The above compositions can be modified by increasing or decreasing the level of sodium salt of a copolymer of maleic anhydride and styrene or the level of sodium salt of a copolymer of maleic anhydride and ethylene by 0 to 15 grams, AVE/MA by 0 to 15 grams, and/or the CMC by 0 to 15 grams. The above compositions can also be modified by using any other suitable anticalculus agents. The subject places from 0.1 to 5 grams of the composition into a denture, moistens it, inserts the denture into his/her mouth and presses it into place.

EXAMPLE III

Denture adhesive compositions in wafer form are made by wetting a 58 by 20 non-woven polyester (non-adhesive self-supporting layer) with water. This wet sheet is uniformly coated with 1 to 3 times the weight of compositions listed above in example-II. Thereafter, the layer is rewetted with water. Then the layer is dried. The composition is mechanically softened tby ring-roller, and then smoothed on a hydraulic press. The composition is die-cut into desired shapes. These wafer compositions are moistened and applied to the dentures. Then the denture is inserted into the mouth and pressed into place.