GB2562800A

GB2562800A - Oral care composition, process for preparation and method of use thereof

Info

Publication number: GB2562800A
Application number: GB1708500.2A
Authority: GB
Inventors: Lindsay Grant Sarah; Alexander Livingstone Mark; Morgan Trevor; Gregory Walsh Dominic
Original assignee: Biofilm Ltd
Current assignee: Biofilm Ltd
Priority date: 2017-05-26
Filing date: 2017-05-26
Publication date: 2018-11-28
Also published as: WO2018215789A1; GB201708500D0

Abstract

An oral care composition, such as a toothpaste, comprising a film-forming polymer which is water insoluble and exhibits pH independent swelling, such as ethyl cellulose, poly (alkyl acrylate) (e.g. polymethyl acrylate) and poly (alkyl alkylacrylate) (polymethylmethacrylate); a first adhesive polymer which is water soluble, such as natural gum, synthetic gum, agar, multivalent salts of agar, polyalkylene glycol, carboxy alkyl cellulose, hydroxyalkyl cellulose and polyvinyl pyrrolidone; a second adhesive polymer which is water insoluble and exhibits pH dependent swelling, such as alginic acid, multivalent salt of alginic acid, polyacrylic acid, salt of polyacrylic acid; and an oral care active agent, such as a bleaching agent, a dental remineralisation agent, a dental desensitising agent, an anti-infective agent, an ant-caries agent, an anti-calculus agent, an anti-inflammatory agent and a biomolecule. Also disclosed is a process for the preparation of the oral care composition and a method of administering the oral care composition to teeth.

Description

(54) Title of the Invention: Oral care composition, process for preparation and method of use thereof Abstract Title: Oral care composition process for preparation and method of use thereof (57) An oral care composition, such as a toothpaste, comprising a film-forming polymer which is water insoluble and exhibits pH independent swelling, such as ethyl cellulose, poly (alkyl acrylate) (e.g. polymethyl acrylate) and poly (alkyl alkylacrylate) (polymethylmethacrylate); a first adhesive polymer which is water soluble, such as natural gum, synthetic gum, agar, multivalent salts of agar, polyalkylene glycol, carboxy alkyl cellulose, hydroxyalkyl cellulose and polyvinyl pyrrolidone; a second adhesive polymer which is water insoluble and exhibits pH dependent swelling, such as alginic acid, multivalent salt of alginic acid, polyacrylic acid, salt of polyacrylic acid; and an oral care active agent, such as a bleaching agent, a dental remineralisation agent, a dental desensitising agent, an anti-infective agent, an ant-caries agent, an anti-calculus agent, an anti-inflammatory agent and a biomolecule. Also disclosed is a process for the preparation of the oral care composition and a method of administering the oral care composition to teeth.

ORAL CARE COMPOSITION, PROCESS FOR PREPARATION AND METHOD OF USE THEREOF

FIELD OF THE INVENTION

The present invention provides an oral care composition, particularly an oral care composition carrying an oral care active agent. The oral care composition can be provided as a single-layer adhesive film, which does not require any further layers such as a support or barrier layer. Also provided is a process for the manufacture of the oral care composition and a method of administering an oral care active to a tooth or teeth using such an oral care composition.

BACKGROUND

Oral care compositions are used in oral hygiene to keep the mouth clean and free from disease as well as to maintain and improve the aesthetic appearance of teeth. Such compositions may carry a variety of active agents, such as anti-infectives, remineralisation agents for teeth, and dental bleaching agents to remove staining.

Many oral care compositions are provided as gels or pastes, which must be applied to teeth in a mold, often requiring administration by a dental practitioner. These gels or pastes must then be cleaned off teeth after use. Other oral care compositions may be provided as a solid, often in the form of a strip, which adheres to teeth upon contact with saliva. These solid strips are simple to use and may be applied by a dental practitioner or the individual desiring treatment. However, such solid compositions may lack sufficient adhesion to remain on the teeth for an appropriate treatment duration or may disintegrate after contact with saliva making complete removal of the composition difficult.

A need exists for oral care compositions which addresses one or more of these problems. The present invention provides oral care compositions which may carry a variety of oral care active agents while maintaining tooth adhesion and sufficient integrity for the treatment duration to allow removal without leaving portions of the composition on teeth.

SUMMARY OF INVENTION

In a first aspect, there is provided an oral care composition comprising:

a film-forming polymer which is water insoluble and exhibits pH independent swelling in water;

a first adhesive polymer which is water soluble;

a second adhesive polymer which is water insoluble and exhibits pH dependent swelling in water; and an oral care active agent.

In one embodiment, the oral care composition is provided as a film. Preferably, the oral care film may be a single layer i.e. the oral care film may consist of a single layer, such that it is free of any other layer or layers such as barrier layers or supporting substrates.

In one embodiment, the oral care composition, particularly such an oral care composition provided as a film, adheres to a tooth or teeth within 10 seconds of contact.

In another embodiment, the oral care composition, particularly such an oral care composition provided as a film, adheres to a tooth or teeth for at least 15 minutes after contact.

In another embodiment, the oral care composition retains integrity such that it can be removed substantially intact from a tooth or teeth after a period of at least 15 minutes adhesion.

The film-forming polymer is water insoluble and exhibits pH independent swelling. As used herein, the term film-forming polymer is intended to mean a polymer which is capable of forming a layer with the other components ofthe composition. The layer comprising the film-forming polymer should have sufficient strength and integrity to carry the other components ofthe composition. As used herein, the term water insoluble is intended to represent a polymer in which 1 g of polymer is insoluble in 100 g or less of water at 20 °C. As used herein, the term pH independent swelling is intended to represent a polymer having a degree of swelling in water which is independent of pH. Such polymers lack moieties which exhibit pH dependent behaviour at a pH of less than 7, in particular such polymers lack acidic moieties which may deprotonate in aqueous solution to provide an anionic polymer at a pH of less than 7. In some cases, such polymers may comprise moieties which may be protonated at a pH or less than 7. As used herein, the term acidic moiety is intended to mean a substituent group which may dissociate in water to liberate H⁺ cations, such as HsO⁺, and leave an anionically charged residue on the polymer. The film-forming polymer is not anionic in water at a pH of less than 7. Consequently, such polymers are free from moieties having an acid dissociation constant (also known as an acid ionisation constant, pKa) of less than 7. In preferred embodiments, the film-forming polymer in water is not an anionic polymer at any pH.

In one embodiment, the film-forming polymer comprises one or more ofthe group selected from ethyl cellulose, poly(aIkyl acrylate), poly(aIky alkylacrylate) and copolymers of alkyl acrylate and alkyl alkylacrylate. The alkyl group is independently selected from C1-5 alkyl, preferably methyl or ethyl.

As used herein, the term poly(alkyl acrylate) is intended to represent polymers ofthe alkyl esters of acrylic acid (i.e. CH2CHC(=O)O-alkyl) by polymerisation of the carbon-carbon double bond of the acrylic acid. The poly(alkyl acrylate) may be selected from poly(methyl acrylate), poly(ethyl acrylate), poly(propyl acrylate), poly(butyl acrylate) and poly(pentyl acrylate).

As used herein, the term poly(alkyl alkylacrylate) is intended to represent polymers of alkyl esters of a I kylacry lie acids by polymerisation of the carbon-carbon double bond of the a I ky lacrylic acid. The poly(a I ky I alkylacrylate) may be selected from polymers of C1-5 alkyl esters of C1-5 alkyl acrylic acid by polymerisation of the carbon-carbon double bond, such as polymers of methyl methacylate, methy ethylacrylate, methyl propylacrylate, ethyl methacrylate, ethyl ethylacrylate, ethyl propylacrylate and the like.

In another embodiment, the film-forming polymer which is water insoluble comprises a copolymer of ethyl acrylate and methyl methacrylate. Most preferably the molar ratio of ethyl acrylate to methyl methacrylate in the copolymer is in the range of from 1:1 to 3:1, preferably in the range of from 1.5:1 to 2.5:1, more preferably about 2:1.

In another embodiment, the film-forming polymer which is water-insoluble is permeable. Such permeable film-forming polymers which are water insoluble may be a copolymer of methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate and trimethyl ammonioethyl methacrylate chloride. The molar ratio of ethyl acrylate to methyl methacrylate to trimethyl ammonioethyl methacrylate chloride in the copolymer may be 1:2:0.1.

The film-forming polymer, such as a copolymer of ethyl acrylate and methyl methacrylate, may have a weight average molecular weight in the range of from 500,000 to 1,000,000, preferably in the range of from 650,000 to 850,000, more preferably about 750,000. The film-forming polymer which is water-insoluble and permeable may have a weight average molecular weight in the range of from 100,000 to 200,000, preferably about 150,000.

In another embodiment, the film-forming polymer may be present in a proportion of from 35 to 60 wt.% by dry weight of the total composition. Preferably, the film-forming polymer is present in a proportion of from 40-55 wt.% by dry weight of the total composition.

The first adhesive polymer is water soluble. As used herein, the term water soluble is intended to represent a polymer in which 1 g of polymer is soluble in 30 g or less of water at 20 °C. As used herein, the term adhesive is intended to represent a polymer which will adhere to a surface. Such an adhesive must wet the surface to which it is applied, in this case a surface of a tooth. It must adhere to the surface and stay in position due to its tackiness. The first adhesive polymer may adhere to a surface of a tooth more quickly compared to the second adhesive polymer discussed below. That is, it may develop tackiness more quickly than the second adhesive polymer to provide initial adhesion.

The first adhesive polymer may or may not be swellable in water. However, if the first adhesive polymer is swellable in water, it should exhibit pH independent swelling, that is, as discussed above it should be free from moieties which exhibit pH dependent behaviour, such as acidic moieties which may deprotonate in aqueous solution to provide an anionic polymer. The first adhesive polymer is not anionic in water and does not contain moieties which have an acid dissociation constant, pKa of less than 7.

In one embodiment, the first adhesive polymer may be selected from one or more of the group comprising pectin, polyvinyl alcohol, pullulan, natural gum, synthetic gum, polyalkylene glycol, carboxyalkyl cellulose or a salt thereof, hydroxyalkyl cellulose or a salt thereof and polyvinyl pyrrolidone. The alkyl group is independently selected from C1-5 alkyl, preferably methyl, ethyl or propyl. The alkylene group is independently selected from C2-5 alkyl, preferably ethylene. The salt of carboxyalkyl cellulose or hydroxyalkyl cellulose may be independently selected from the sodium (i.e. Na⁺) salt and calcium (i.e. Ca²⁺) salt.

The natural gum may be selected from carrageenan, tragacanth and polysaccharide gums. More preferably, when the first adhesive polymer is a natural gum, it is tragacanth gum.

In one embodiment, the first adhesive polymer has a molecular weight of less than or equal to 1.5 million.

In another embodiment, the polyalkylene glycol is preferably polyethylene glycol.

In another embodiment, the first adhesive polymer preferably comprises one or more of a carboxymethyl cellulose, a polyethylene glycol and a polyvinyl pyrrolidone.

In another embodiment, the first adhesive polymer preferably comprises a plurality of polyethylene glycols having different average molecular weights. More preferably, the polyethylene glycol may comprise a first PEG having an average molecular weight in the range of from 300 to 500 and a second PEG having an average molecular weight in the range of from 7,000 to 9,000. The proportion, by weight, of the first PEG to the second PEG may be in the range of from 1:1 to 2:1, preferably about 1.5:1. Polyethylene glycols with a molecular weight in the range of from 300 to 500 do not swell in water. Polyethylene glycols of higher molecular weight, such as those in the range of from 7,000 to 9,000 exhibit pH independent swelling.

In another embodiment, the polyvinyl pyrrolidone is uncrosslinked polyvinyl pyrrolidone.

The polyvinyl pyrrolidone may preferably have a weight average molecular weight in the range of from 900,000 to 1.5 million, more preferably about 1.3 million.

In another embodiment, when the oral care active agent is hydrogen peroxide and the first adhesive polymer comprises polyvinyl pyrrolidone, they may be present as a complex.

In another embodiment, the first adhesive polymer comprises polyethylene glycol and polyvinyl pyrrolidone. Alternatively, the first adhesive polymer comprises carboxymethyl cellulose and polyvinyl pyrrolidone.

In another embodiment, the first adhesive polymer which is water-soluble may be present in a proportion of from 10 to 50 wt.% by dry weight of the total composition.

The second adhesive polymer is water insoluble. As used herein, the term water insoluble refers to a polymer in which 1 g of polymer is insoluble in 100 g or less of water at 20 °C. As used herein, the term adhesive is intended to represent a polymer which will adhere to a surface. Such an adhesive must wet the surface to which it is applied, in this case a surface of a tooth. It must adhere to the surface and stay in position due to its tackiness. The second adhesive polymer may adhere to a surface of a tooth less quickly compared to the first adhesive polymer discussed above. That is, it may develop tackiness less quickly than the first adhesive polymer, but the adhesion provided by the second adhesive polymer increases over time, and may ultimately exceed that of the first adhesive polymer.

The second adhesive polymer exhibits pH dependent swelling in water. As used herein, the term pH dependent swelling is intended to represent a polymer having a degree of swelling in water which is dependent of pH. Such polymers comprise moieties which exhibit pH dependent behaviour, such as acidic moieties which may deprotonate in aqueous solution to provide an anionic polymer. The second adhesive polymer may form an anionic polymer in water. The acidic moieties may comprise carboxyl groups i.e. -C(=O)OH groups, which can deprotonate to provide a carboxylate ion -CO2 on the second adhesive polymer. Preferably, the acidic moiety on the second adhesive polymer has an acid dissociation constant, pKa, in the range of from 5 to 6.5. It has been found that an acidic moiety with a dissociation constant of less than 5 dissociates too readily such that the active acidic species, such as H⁺, particularly HsO⁺, may lead to tooth demineralisation. When an acidic moiety on the second adhesive polymer has an acid dissociation constant, pKa, greater than 6.5, it may exhibit excessive swelling due to anionic repulsion between the anionic residues on the polymer, such as carboxylate ions, leading to poor adhesion.

In one embodiment, the second adhesive polymer may be selected from one or more of the group comprising alginic acid, multivalent salt of alginic acid, a polyacrylic acid, salt of polyacrylic acid, polyalkyl acrylic acid and salt of polyaIkylacrylic acid. The alkyl group is independently selected from C1-5 alkyl, preferably methyl or ethyl. The multivalent salt of alginic acid may be the calcium salt. The salt of polyacrylic acid or the salt of polyaIkylacrylic acid may be independently selected from the group comprising ammonium salt, such as

NH4⁺; alkali metal salt, such as sodium (i.e. Na⁺) salt or potassium (i.e. K⁺) salt; and alkaline earth metal salt, such as calcium (i.e. Ca²⁺) salt. As used herein, the terms salt of polyacrylic acid and salt of polyaIkylacrylic acid are intended to mean that a portion of the carboxyl groups ofthe polymer is converted into the corresponding carboxylate salt. Preferably, some, but not all of the carboxyl groups of the polymer are converted into the corresponding carboxylate salt.

As used herein, the term polyacrylic acid is intended to represent a polymer of acrylic acid by polymerisation ofthe carbon-carbon double bond ofthe acrylic acid. Such polyacrylic acid comprises carboxyl groups.

As used herein, the term polyalkyl acrylic acid is intended to represent a polymer of an alkylacrylic acid by polymerisation ofthe carbon-carbon double bond ofthe acrylic acid. Such polyalkyl acrylic acid comprises carboxyl groups. Examples of suitable alkylacrylate monomers include methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylic acid and pentylacrylic acid.

Alginic acid is a polysaccharide. It is a linear copolymer comprising homopolymeric blocks of (l-4)-linked β-D-mannuronate (M) and its C-5 epimer α-L-guluronate (G) residues. Both monomers comprise carboxyl groups.

In one embodiment the second adhesive polymer may have a molecular weight of greater than 1.5 million, preferably greater than 2 million.

In one embodiment, the second adhesive polymer may be a hydrocolloid. As used herein, the term hydrocolloid means a hydrophilic polymer, which contains hydrophobic groups and forms a gel in the presence of water, that is, a heterogeneous system with a solid hydrocolloid network containing a liquid water phase. Examples of such hydrocolloid polymers include polyacrylic acid and polyaIkylacrylic acid such as polymethacrylic acid or polyethylacrylic acid.

The second adhesive polymer may be a polymer of acrylic acid or an alkylacrylic acid as defined above. High molecular weight polyacrylic acid is also known as carbomer. Polymers of acrylic acid which may be either crosslinked or uncrosslinked. Examples of crosslinking agents include allyl ether pentaerythritol, allyl ethers of sucrose or ally ethers of propylene. Crosslinked polymers of acrylic acid are sold under the trade name Carbopol® by Lubrizol Corporation.

The polyacrylic acid may be provided as a salt, such as an ammonium, alkali metal or alkaline earth metal salt. Cross-linked polyacrylic acid, such as those cross-linked with divinyl glycol may be provided as salts such as alkaline earth metal salts, particularly calcium salts, also known as polycarbophils.

In another embodiment, the second adhesive polymer may be present in a proportion of from 0.5 to 30 wt.% by dry weight of the total composition.

In another embodiment, the total amount of the first and second adhesive polymers may be present in a proportion of from 30 to 60 wt.% by dry weight of the total composition. Preferably, the total amount of the first and second adhesive polymer may be present in a proportion of from 35 to 55 wt.% by dry weight of the total composition.

In one embodiment, the oral care active agent is selected from the group comprising a bleaching agent, a dental remineralisation agent, a dental desensitising agent, an antiinfective agent, an anti-caries agent, an anti-calculus agent, an anti-inflammatory agent and a biomolecule.

In one embodiment, the oral care active agent may be present in a proportion of from 0.05 to 25.0 wt.% by dry weight of the total composition.

In one embodiment, the oral care active agent is a bleaching agent selected from the group comprising a peroxide, such as hydrogen peroxide or organic peroxy acids optionally together with a stabilizing agent, and chlorites, such as an alkali metal chlorite.

In one embodiment, the oral care composition may further comprise one or more optional components selected from the group comprising a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, a surfactant and a delivery enhancing polymer.

In one embodiment, the oral care composition has a pH in the range of from 5 to 6.5.

Thus, there is also provided an oral care composition comprising:

a film-forming polymer which is water insoluble and is free from acidic moieties having an acid dissociation constant of less than 7;

a first adhesive polymer which is water soluble;

a second adhesive polymer which is water insoluble and comprises acidic moiety having an acid dissociation constant in the range of from 5 to 6.5; and an oral care active agent.

In a second aspect, there is provided a process for the preparation of the oral care composition as described above, said process comprising at least the steps of:

mixing a first film-forming polymer which is water insoluble and exhibits pH independent swelling, a first adhesive polymer which is water soluble, a second adhesive polymer which is water insoluble and exhibits pH dependent swelling, an oral care active agent and water to provide an aqueous oral care liquid;

applying the aqueous oral care liquid to a substrate to provide a substrate carrying the aqueous oral care liquid;

drying the aqueous oral care liquid to provide an oral care composition on the substrate.

In one embodiment, the oral care composition is provided as an oral care film on the substrate after drying.

In one embodiment, prior to mixing, the second adhesive polymer which is water insoluble is swollen into a gel-like state by mixing at high shear, for instance at a rate in the range of from 80 to 4000 rpm.

In another embodiment, the first film-forming polymer which is water insoluble, first adhesive polymer which is water-soluble and oral care active agent are mixed with the second adhesive polymer which is water insoluble swollen into a gel-like state.

In another embodiment, the mixing step further comprises mixing one or more optional components selected from the group comprising a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, a surfactant and a delivery enhancing polymer.

In another embodiment, the first adhesive polymer and second adhesive polymer may be added to water and mixed. An optional pH adjusting agent, such as an alkali agent, may then be added if the second adhesive polymer has not already formed a gel. The oral care active can then be added. Further pH adjusting agent may then be optionally added to bring the pH of the aqueous mixture to a desired value, such as a pH in a range of from 5 to 6.5. The film-forming polymer may then be added, preferably with mixing. The mixture may then be optionally degassed. Additional oral care active agent may then optionally be added to increase the concentration of the oral care active agent, if necessary. The composition may then be mixed. The mixture may then be optionally degassed.

In one embodiment, the process further comprises the step of:

separating the oral care composition from the substrate to provide an oral care film.

In another embodiment, the process further comprises the step of:

degassing the aqueous oral care liquid to provide a degassed aqueous oral care liquid.

The degassing step may be carried out after the mixing of the components of the oral care composition with water and before the step of applying of the degassed aqueous oral care liquid to the substrate.

In another embodiment, the drying step comprises:

drying the aqueous oral care liquid in air at a temperature of up to 60 °C.

In a further embodiment the drying of the aqueous oral care liquid in air is carried out at a temperature in the range of from 45 to 55 °C. In a further embodiment, the drying may be carried out in a linear drying oven in which the aqueous oral care liquid is passed through the oven at a rate in the range of from 0.2 to 2.0 m/min, preferably in a range of from 0.5 to 1.5 m/min.

In a further embodiment, the drying step is carried out for a period of 80 minutes or less, preferably for a period of 35 minutes or less, more preferably for a period of 25 minutes or less. The drying step may be carried out for a period of at least 8 minutes, preferably for a period of at least 15 minutes, more preferably for a period of at least 20 minutes. Thus the drying step may be carried out for a period of from 8 to 80 minutes, preferably from 15 to 35 minutes and more preferably from 20 to 25 minutes.

Thus, there is also provided a process for the preparation of the oral care composition as described above, said process comprising at least the steps of:

mixing a first film-forming polymer which is water insoluble and is free from acidic moieties having an acid dissociation constant of less than 7, a first adhesive polymer which is water soluble, a second adhesive polymer which is water insoluble and comprises acidic moiety having an acid dissociation constant in the range of from 5 to 6.5, an oral care active agent and water to provide an aqueous oral care liquid; applying the aqueous oral care liquid to a substrate to provide a substrate carrying the aqueous oral care liquid;

In a third embodiment, there is provided an oral care composition or oral care film obtainable by the process of the second aspect and its embodiments.

In a fourth aspect, there is provided a method of administering an oral care active agent to a tooth or teeth comprising at least the step of:

applying the oral care composition or oral care film obtained as described herein to one or more teeth of a subject.

In one embodiment, the oral care active is a bleaching agent, such that the method is a method of administering a bleaching agent i.e. a tooth whitening method. The method may be a cosmetic method, particularly a solely cosmetic method.

In one embodiment, the oral care composition is applied to a subject in the form of a film, preferably a film which is not attached to or supported on any other layers.

In another embodiment, the oral care composition or oral care film is applied to one or more teeth of a subject for a period of less than or equal to 60 minutes, preferably for a period of from 15 to 45 minutes.

DETAILED DESCRIPTION

The present invention provides oral care compositions, which can be provided as films, particularly films which do not require the presence of further layers, such as barrier layers or supporting substrates.

The oral care composition provides good adhesion to tooth surfaces so that the oral care active agent can act upon a tooth or teeth, while also retaining good structural integrity such that the composition remains intact when removed, thereby avoiding leaving deposits of the composition on teeth after removal.

Preferably, the oral care composition exhibits adhesion such that it adheres to a tooth or teeth within 30 s of contact, preferably 10 s of contact, while retaining adhesion for at least 30 minutes, preferably at least 60 minutes.

The mucoadhesive properties of the oral care composition are achieved by a combination of a first and second adhesive polymers, in which the first adhesive polymer is water soluble while the second adhesive polymer is water insoluble. Without wishing to be bound by theory, the first adhesive polymer and second adhesive polymer provide complementary functions. The first adhesive polymer which is water soluble provides a fast initial adhesion, whilst the second adhesive polymer which is a hydrocolloid provides sustained adhesion over time. This is achieved because the first adhesive agent exhibits pH independent swelling and provides the initial adhesion. The second adhesive agent exhibits pH dependent swelling and will swell over time, maintaining the adhesion of the composition to a tooth.

The oral care composition comprises a film-forming polymer which is water insoluble. This film-forming polymer provides integrity to the composition and allows its removal after use.

As used herein, the term water soluble polymer refers to a polymer in which 1 g of polymer is soluble in 30 g or less of water at 20 °C. The term water insoluble polymer refers to a polymer in which 1 g of polymer is insoluble in 100 g or less of water at 20 °C.

The film-forming polymer may be selected from a one or more of the group comprising ethyl cellulose, poly(aIkyl acrylate), poly (alky alkylacrylate) and copolymers of alkyl acrylate and alkyl alkylacrylate. Preferably the alkyl acrylate is a C1-5 alkyl acrylate and the alkyl alkylacrylate is a C1-5 alkyl methacrylate or C1-5 alkyl ethacrylate. More preferably the alkyl acrylate is ethyl acrylate and the alkyl alkylacrylate is methyl methacrylate. Still more preferably the water-insoluble polymer comprises a copolymer of ethyl acrylate and methyl methacrylate. Most preferably the molar ratio of ethyl acrylate to methyl methacrylate monomer residues in the copolymer is in the range of from 1:1 to 3:1, preferably in the range of from 1.5:1 to 2.5:1, more preferably about 2:1.

The film-forming polymer which is water-insoluble, such as a copolymer of ethyl acrylate and methyl methacrylate, may have a weight average molecular weight in the range of from 500,000 to 1,000,000, preferably in the range of from 650,000 to 850,000, more preferably about 750,000.

A copolymer of methyl acrylate, ethyl acrylate, methyl methacrylate and ethyl methacrylate may be a permeable polymer. Such permeable copolymers may contain quaternary ammonium salt groups. Preferred ammonium salt group anions are the halogens, such as the chloride ion. For instance, trimethyl ammonioethyl methacrylate chloride may be used as a co-monomer to incorporate the ammonium salt groups into the polymer. The molar ratio of ethyl acrylate to methyl methacrylate to trimethyl ammonioethyl methacrylate chloride monomer residues in the copolymer is preferably 1:2:0.1. Such copolymers may have a weight average molecular weight in the range of from 100,000 to 200,000, preferably about 150,000.

The film-forming polymer which is water-insoluble may be present in a proportion of from 35 to 60 wt.% by dry weight of the total composition. Preferably, the water-insoluble polymer is present in a proportion of from 45-55 wt.% by dry weight of the total composition.

The oral care composition comprises a first adhesive polymer which is water soluble. This first adhesive polymer provides adhesion to the composition to a tooth or teeth during use. The adhesion may be activated by contact with water, such as water present in saliva.

The first adhesive polymer may be selected from the group comprising pectin, natural gum, synthetic gum, agar or a multivalent salt thereof, polyalkylene glycol, carboxyalkyl cellulose or a salt thereof, hydroxyalkyl cellulose or a salt thereof and polyvinyl pyrrolidone. The alkyl group is independently selected from C1-5 alkyl, preferably methyl, ethyl or propyl. The multivalent salt of agar may be calcium (i.e. Ca²⁺) agar. The salt of carboxyalkyl cellulose or hydroxyalkyl cellulose may be independently selected from the sodium (i.e. Na⁺) salt and calcium (i.e. Ca²⁺) salt.

When the first adhesive polymer is a natural gum, it may be xanthan gum or tragacanth gum, with tragacanth gum being preferred.

Preferably, the first adhesive polymer is present in a proportion of from 20 to 30 wt.% by dry weight of the total composition, particularly when the first adhesive polymer is tragacanth gum.

The first adhesive polymer preferably comprises one or more of a carboxyalkyl cellulose, polyalkylene glycol and a polyvinyl pyrrolidone. More preferably, the first adhesive polymer comprises one or more of the group comprising carboxymethyl cellulose, polyethylene glycol and polyvinyl pyrrolidone.

Carboxymethyl cellulose, when used as the first adhesive polymer, may have a molecular weight in the range of from 49,000-725,000, a viscosity in the range of from 25 to 4,500mPa.S and degree of substitution of 0.7-1.2. For instance, the carboxymethyl cellulose may have a molecular weight of 90 500, a viscosity in the range of from 25 to 50 mPa.s and a degree of substitution of 0.7.

Polyethylene glycol (PEG), when used as the first adhesive polymer, may have an average molecular weight in the range of from 200 to 10,000. Preferably a plurality of polyethylene glycols having different average molecular weights may be used as the first adhesive polymer. For instance, a combination of a low and a high molecular weight PEG may be used, in which the low molecular weight PEG has an average molecular weight in the range of from 200 to 1000, preferably from 300 to 500 and the high molecular weight PEG has an average molecular weight in the range of from greater than 1000 to 10,000, preferably from 7,000 to 9,000. The proportion, by weight, of low molecular weight to high molecular weight PEG may be in the range of from 1:1 to 2:1, preferably about 1.5:1.

A polyvinyl pyrrolidone, when used as the first adhesive polymer, may be one or more selected from the group comprising uncrosslinked polyvinyl pyrrolidone, crosslinked polyvinyl pyrrolidone, a copolymer of vinyl pyrrolidone and acrylic acid, a copolymer of vinyl pyrrolidone and vinyl acrylate, or alkylated polyvinyl pyrrolidone. Preferably the polyvinyl pyrrolidone comprises uncrosslinked (i.e. linear) polyvinyl pyrrolidone.

The polyvinyl pyrrolidone may preferably have a weight average molecular weight in the range of from 900,000 to 1.5 million, still more preferably about 1.3 million.

The polyvinyl pyrrolidone is preferably used in combination with another first adhesive polymer, such that the first adhesive polymer comprises polyethylene glycol and polyvinyl pyrrolidone. Alternatively, the first adhesive polymer comprises carboxymethyl cellulose and polyvinyl pyrrolidone.

The first adhesive polymer which is water soluble may be present in a proportion of from 10 to 50 wt.% by dry weight of the total composition. Preferably, the first adhesive polymer is present in a proportion of from 10 to 30 wt.% by dry weight of the total composition, particularly when the first adhesive polymer is a combination of carboxymethyl cellulose and polyvinyl pyrrolidone. Alternatively, the first adhesive polymer is preferably present in a proportion from 35-55 wt.% by dry weight of the total composition, particularly when the first adhesive polymer is a combination of polyethylene glycol and polyvinyl pyrrolidone.

The oral care composition comprises a second adhesive polymer which is water insoluble. This second adhesive polymer provides adhesion to the composition to a tooth or teeth during use.

The second adhesive polymer which is water insoluble may be one or more selected from the group comprising alginic acid, a multivalent salt of alginic acid, a polyacrylic acid, a salt of polyacrylic acid, polyalkyl acrylic acid and a salt of polyacrylic acid. The alkyl group is independently selected from C1-5 alkyl, preferably methyl or ethyl. The multivalent salt of alginic acid may be the calcium salt. The salt of polyacrylic acid or the salt of polyaIkylacrylie acid may be independently selected from the group comprising ammonium salt, such as NH4⁺; alkali metal salt, such as sodium (i.e. Na⁺) salt or potassium (i.e. K⁺) salt; and alkaline earth metal salt, such as calcium (i.e. Ca²⁺) salt.

Preferably, the second adhesive polymer which is water insoluble is a polyacrylic acid. High molecular weight polyacrylic acid is also known as carbomer. Polymers of acrylic acid may be either crosslinked or uncrosslinked. Examples of crosslinking agents include allyl ether pentaerythritol, allyl ethers of sucrose or ally ethers of propylene. Crosslinked polymers of acrylic acid are sold under the trade name Carbopol® by Lubrizol Corporation.

The second adhesive polymer may be present in a proportion of from 0.5 to 30 wt.% by dry weight of the total composition. Alternatively, the second adhesive polymer is preferably present in a proportion from 0.5 to 5 wt.% by dry weight of the total composition, more preferably from 1-3 wt.% by dry weight of the composition, particularly when the second adhesive polymer is a polyacrylic acid.

When the first adhesive polymer comprises tragacanth gum and the second adhesive polymer comprises polyvinyl pyrrolidone, the weight ratio of first adhesive polymer to second adhesive polymer is 1:2.5 to 1:0.8. Alternatively, when the first adhesive polymer comprises polyethylene glycol and polyvinyl pyrrolidone and the second adhesive polymer comprises polyacrylic acid, the weight ratio of first adhesive polymer to second adhesive polymer is in the range of from 20:1 to 24:1.

Alternatively, when the first adhesive polymer comprises polyethylene glycol and polyvinyl pyrrolidone and the second adhesive polymer comprises polyacrylic acid, the weight ratio of polyethylene glycol to polyacrylic acid is in the range of from 7:1 to 6:1.

The oral care active agent is selected from the group comprising a bleaching agent, a dental remineralisation agent, a dental desensitising agent, an anti-infective agent, an anti-caries agent, an anti-calculus agent, an anti-inflammatory agent and a biomolecule.

In one embodiment, the bleaching agent may be an organic or inorganic bleaching agent. Examples of organic bleaching agents are organic peroxy acids including 6(phthalimido)peroxyhexanoic acid and benzoyl peroxide. Organic peroxy acids may be provided with a stabilizing agent such as dipicolinic acid or sodium stannate. Examples of inorganic bleaching agents include hydrogen peroxide and peroxymonosulphuric acid and chlorites.

Preferably the chlorite is an alkali metal chlorite, such as sodium chlorite. Preferably, the peroxide is selected from one or more ofthe group comprising hydrogen peroxide, peracids, such as percarboxylic acids, benzoyl peroxide, carbamide peroxide, sodium perborate and sodium percarbonate. Most preferably the bleaching agent comprises hydrogen peroxide.

Preferably, when the bleaching agent comprises hydrogen peroxide, at least a portion ofthe hydrogen peroxide is present with a polyvinyl pyrrolidone as a complex. The bleaching agent may be present entirely complexed with the polyvinyl pyrrolidone, or a portion of the bleaching agent may be present with the polyvinyl pyrrolidone in a complex with the remainder ofthe bleaching agent is present in the composition in uncomplexed form i.e. unbound to polyvinyl pyrrolidone.

The hydrogen peroxide can form hydrogen bonds with the carbonyl group ofthe pyrrolidone ring to form the complex. One hydrogen peroxide molecule may form a hydrogen bond with at least one carboxyl group ofthe pyrrolidone. However, one hydrogen peroxide molecule may also form two hydrogen bonds, each one with the carbonyl group of two adjacent pyrrolidone rings. Thus, the molar ratio of pyrrolidone groups to hydrogen peroxide in such a complex may be in the range of about 1:1 to 2:1. This results in complexes which may comprise from 15 to 20 wt.% by weight hydrogen peroxide and from 80 to 85 wt.% by weight polyvinyl pyrrolidone depending upon the degree of coordination between hydrogen peroxide and carbonyl groups.

The polyvinyl pyrrolidone polymer in the complex may be one or more selected from the group comprising uncrosslinked polyvinyl pyrrolidone, crosslinked polyvinyl pyrrolidone, a copolymer of vinyl pyrrolidone and acrylic acid, a copolymer of vinyl pyrrolidone and vinyl acrylate, or alkylated polyvinyl pyrrolidone. The polyvinyl pyrrolidone may preferably have a weight average molecular weight in the range of from 1 million to 1.5 million, still more preferably about 1.3 million.

Suitable pyrrolidone polymer complexes with hydrogen peroxide are sold under the trade name Peroxydone™ by Ashland.

The bleaching agent may be present in a proportion of from 0.1 to 25.0 wt.% by dry weight of the total composition. When the bleaching agent is a peroxide, it may be present in a proportion of from 5.0 to 20.0 wt.% by dry weight of the total composition. For the avoidance of doubt, the above-mentioned proportions refer to the proportion of bleaching agent rather than bleaching agent complex, and do not include any corresponding complexing polymer such as a polyvinyl pyrrolidone.

Preferably, the polyvinyl pyrrolidone-hydrogen peroxide complex may be present in a proportion of about 17.5 to 45 wt.% by dry weight of the total composition.

When the bleaching agent is 6-(phthalimido)peroxyhexanoic acid, it may be present in a proportion of from 0.1 to 10.0 wt.% by dry weight of the total composition.

In one embodiment, the dental remineralisation agent is a bioactive glass. Bioactive glasses can facilitate the remineralisation to tooth enamel. Consequently, they may also function as tooth desensitizing agents. Preferably the bioactive glass is a phosphosilicate, such as calcium sodium phosphosilicate. More preferably the bioactive glass is a milk protein comprising casein phosphopeptide amorphous calcium phosphate, such as Recaldent™ of Cadbury Enterprises Pte Ltd.

The dental remineralisation agent may be present in a proportion of from 1 to 25 wt.% by dry weight of the total composition. Preferably the dental remineralisation agent is present in a proportion of from 5 to 15 wt.% by dry weight of the total composition.

In one embodiment, the dental desensitizing agent is selected from one or more ofthe group comprising an oxalate such as an alkali metal oxalate, arginine, alkali metal citrate, alkali metal chloride, alkali metal tartrate, alkali metal bicarbonate, alkali metal nitrate, salts of strontium and a fluoride such as an alkali metal fluoride. Preferably the alkali metal is sodium or potassium. More preferably the desensitizing agent is selected from one or more of the group comprising potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and sodium fluoride.

The dental desensitizing agent may be present in a proportion of from 0.05 to 25 wt.% by dry weight of the total composition. Preferably the dental desensitizing agent is present in a proportion of from 1 to 10 wt.% by dry weight of the total composition.

In one embodiment, the anti-infective agent is selected from one or more of the group comprising an antibacterial, an antiviral and an antifungal. The anti-infective preferably comprises an antibacterial, and particularly an antibacterial for the treatment of biofilms.

Antibacterials may be one or more compounds selected from the group comprising benzoyl peroxide, triclosan, chlorhexidine, copper-, zinc- and stannous salts such as zinc citrate, sodium zinc citrate and stannous pyrophosphate, sanguinarine extract, metronidazole, quaternary ammonium compounds and salts thereof. Quaternary ammonium compounds suitable as antibacterials include cetylpyridinium chloride; bis-guanides such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenolic compounds such as 2,2' methylenebis-(4-chloro-6-bromophenol).

A preferred antibacterial is chlorohexidine or a salt thereof, such as chlorohexidine dihydrochloride, chlorohexidine diacetate or chlorohexidine digluconate.

The anti-infective agent, such as an antibacterial, may be present in a proportion of from 0.05 to 25 wt.% by dry weight of the total composition. Preferably the anti-infective agent, such as an antibacterial, is present in a proportion of from 0.1 to 10 wt.% by dry weight of the total composition.

Anti-caries agents may be one or more compounds selected from the group comprising sodium fluoride, stannous fluoride, amine fluorides, monosodium fluorophosphate, casein and plaque buffers. Exemplary plaque buffers include urea, calcium lactate, calcium glycerophosphate and strontium polyacrylates.

Anti-calculus agents may be one or more compounds selected from the group comprising alkali metal pyrophosphates, hypophosphite containing polymers, organic phosphonates and phosphocitrates.

Anti-inflammatory agents may be steroidal anti-inflammatory agents or non-steroidal antiinflammatory agents. Preferably, the anti-inflammatory agents comprise one or more compounds selected from the group comprising ibuprofen, flurbiprofen, aspirin and indomethacin.

Exemplary biomolecules include bacteriocins, antibodies and enzymes.

The oral care composition may further comprise one or more optional components. The one or more optional components may be selected from one or more of the group comprising, a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, a surfactant and a delivery enhancing polymer.

The pH adjusting agent may be selected from the group comprising, sodium hydroxide, potassium hydroxide, citric acid, lactic acid, phosphoric acid and sodium bicarbonate. Preferably the pH adjusting agent is sodium hydroxide. The pH of the oral care composition affects the level of swelling of the second adhesive polymer because it contains dissociable acidic species, such as carboxyl groups. Furthermore, too low a pH may result in the undesirable etching of teeth. Preferably the oral care composition has a pH in the range of from 5 to 6.5.

The flavouring agent may be an artificial flavouring or a natural flavouring. The flavouring agent may be one or more selected from the group comprising herb flavouring, such as mint, for instance spearmint or peppermint, a spice flavouring such as ginger, cinnamon or vanilla, or a fruit flavouring such as apple, grape, orange, pear or strawberry. Preferably the flavouring agent is peppermint. Preferably the flavouring agent is present in a proportion of from 0.1 wt.% to 10 wt.% by dry weight of the oral care composition.

The sweetener may be a sugar substitute, such as an artificial sugar substitute or a natural sugar substitute. The artificial sugar substitute may be selected from the group comprising sucralose, aspartame, advantame, saccharin, acesulfame potassium and cyclamate, with sucralose being preferred. The natural sugar substitute may be selected from the group comprising erythritol, mannitol, stevia, sorbitol and xylitol. Preferably the sweetener is sucralose. Preferably the sweetener is present in a proportion of from 0.1 wt.% to wt.5% by dry weight of the oral care composition.

The plasticizer is a physiologically acceptable plasticizer. In one embodiment, the plasticizer is a hydrophilic plasticizer, such as one or more of the group comprising a polyol such as glycerol, polyethylene glycol, polyethylene glycol monomethyl ether, propylene glycol and sorbitol sorbitan. The preferred plasticizer is glycerol. Preferably the plasticizer is present in a proportion of from 1 wt.% to 15 wt.% by dry weight of the oral care composition.

The surfactant may be an ionic surfactant or a non-ionic surfactant. Preferably the nonionic surfactant comprises one or more fatty acids, which may be saturated or unsaturated. More preferably the non-ionic surfactant comprises at least one unsaturated fatty acid such as oleic acid and/or linoleic acid and optionally at least one saturated fatty acid such as palmitic acid and/or stearic acid. Preferably the surfactant is present in a proportion of from 0 to 5 wt.% by dry weight of the oral care composition.

A polymeric compound which enhances the delivery of the oral care active agent may also be present. Examples of such delivery enhancing polymers include copolymers of polyvinylmethylether with maleic anhydride.

Still further optional components of the oral care composition may include preservatives, opacifying agents, and colouring agents. The preservative may be selected from the group comprising butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and potassium sorbate. The opacifying agent may be titanium dioxide. The colouring agent may be FD & C blue no. 1 and lakes thereof.

The oral care composition is prepared from an aqueous oral care liquid. The aqueous oral care liquid is a mixture of the components of the oral care composition with water.

In the mixing step, the first film-forming polymer, first adhesive polymer, second adhesive polymer and oral care active agent are mixed with water. The water may be any potable water. The water is typically distilled water. De-ionised water may also be used.

The mixing step may further comprise the addition of one or more further components of the oral care composition. The one or more further components may be selected from one or more of the group comprising, a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, a surfactant and a delivery enhancing polymer.

Preferably, the mixing is carried out under shear. Some components of the oral care composition, such as the film-forming polymer, are susceptible to damage at high rates of shear. Consequently, such components, for instance the film-forming polymer, may be the last polymeric component to be added to the composition, and may be mixed at lower shear, for instance at a shear rate in the range of from 80 to 160 rpm.

The order of mixing the components of the oral care composition may affect the stability of the composition or one or more of its components. For instance, the first adhesive polymer and second adhesive polymer may be added to water and mixed, for instance under a shear of about 160 rpm. A pH adjusting agent, such as an alkali agent, may be added to cause the formation of a gel either with the first and second adhesive polymers or after they have been mixed with water.

Next, the oral care active can be added. Further pH adjusting agent may then be added to bring the pH of the aqueous mixture to a desired value, such as a pH of 6. Then, the filmforming polymer may be added, preferably with mixing, such as a shear in the range of from 80 to 160 rpm. The mixture may then be degassed. Additional oral care active agent may then optionally be added to increase the concentration of the oral care active agent, if necessary. The composition may then be mixed, for instance at a shear of about 80 rpm. The mixture may then be degassed.

Mixing may be carried out in an overhead mixer, or for industrial quantities a Kilia Bowl cutter operated at low shear, such as a knife speed in the range of 80 to 160 rpm.

Alternatively, any pH adjusting agent may be added incrementally. Incremental addition is normally accompanied by monitoring of the pH of the mixture. For example, the pH can be monitored during the addition of the pH adjusting agent, either if it is added when the first and second adhesive polymers are mixed with water or if it is added after the first and second adhesive polymers have been mixed with water. The pH may then be monitored again after the addition of the oral care active agent, and if necessary further pH adjusting agent added to reach a target pH.

Once the components are mixed with water to provide the aqueous oral care liquid, the mixture may be applied to a substrate. The aqueous oral care liquid may be applied by known film-forming processes, such as dipping, spraying, knife over roller casting, extrusion and injection moulding.

A casting device may be used to apply the aqueous oral care liquid to the substrate such as a caster, spreader, die or hopper. The aqueous liquid may be pumped into a spreader. If necessary, the temperature of the aqueous liquid may be held constant by heating elements in order to carefully control the viscosity of the mixture.

The spreader distributes the aqueous oral care liquid homogeneously over a substrate and controls the thickness profile of the film. The spreader typically has a slot through which the aqueous oral care liquid is cast. The slot is preferably designed to ensure that the hydrostatic pressure between the centre and the edges of the cast film is equilibrated. Preferably, the aqueous liquid is maintained at a constant temperature to ensure a constant viscosity and therefore homogenous thickness distribution of the resulting film.

Many different materials can be used for the substrate such as copper; silver plated copper; chromium plated steel; stainless steel; metal coated with polyvinyl alcohol or gelatin; paper such as silicone coated paper; or polymer films such as polyethylene, polypropylene, polyester such as polyethylene terephthalate (PET), particularly siliconized PET, polytetrafluoroethylene (PET) films. Preferably the substrate comprises paper, paper coated with a release layer such as silicone, polyethylene, polypropylene, polytetrafluoroethylene (PET) or a polyester such as polyethylene terephthalate (PET), particularly siliconized PET films.

The aqueous oral care liquid carried on the substrate can then be dried. Exemplary drying methods include indirect heating, heating by radiation and air stream drying.

In one embodiment, an air feed stream with no or a low moisture content is directed towards the aqueous liquid on the substrate and an air exhaust stream loaded with water vapour is removed. The air exhaust stream loaded with moisture may be vented or passed to condensers for the condensation and separation of liquid water.

In one embodiment, both surfaces of the aqueous oral care liquid carried on the substrate may be dried. This can be achieved by looping the film around a series of polished rollers and directing air feed streams to each exposed film surface in turn.

The air feed stream may be at ambient temperature. Alternatively, the air feed stream may be a heated air feed stream. The heated air feed stream may have a temperature in the range of greater than ambient to 60 °C. Preferably, the heated air stream may have a temperature in the range of from 25 °C to 55 °C.

Alternatively, heated rollers may or radiative heaters such as infra-red lamps may be used to dry the aqueous liquid to provide the film. These may heat the aqueous tooth whitening composition carried on the substrate to a temperature in the range of from ambient to 60 °C, preferably to a temperature in the range of from 25 °C to 55 °C.

In one embodiment, the drying step may comprise first drying of a first surface of the aqueous oral care liquid carried on the substrate to provide a first dried oral care film carried on the substrate. The first surface of the aqueous oral care liquid may be the outer surface of the composition opposite to a second surface adjacent to the support. The first dried oral care film may then be separated from the substrate. The second surface of the first dried oral care film may then be second dried to provide a second dried oral care film. The first and second drying may be independently carried out as discussed above.

The oral care film may be stored on a support, such as a plastic or paper support, particularly a paper support having a silicone release layer, although this is not required.

The oral care film may be stored in sterile packaging, such as a sealed packet. The sealed packet may be water tight, and more preferably water and aid tight. The packet may be made of a metallic foil such as aluminium foil, or a plastic film coated with a metallic layer.

The oral care film has a thickness of less than 1000 micrometers, preferably in the range of from 50 to 250 micrometres, more preferably the film has a thickness in the range of from

130 to 170 micrometres, still more preferably about 150 micrometers.

Preferably, the oral care film has a length of from 50 to 70 mm, more preferably about 60 mm and preferably a width of form 15 to 20 mm, more preferably about 17.5 mm.

The oral care film may have a weight in the range of from 100 to 250 mg, preferably 130 to 200 mg, and more preferably about 150 mg.

The oral care composition or film obtainable by the process disclosed herein may be used in a method of administering an oral care active agent to a tooth or teeth. The method comprises at least the step of:

When the oral care active agent is a bleaching agent, the method may be a cosmetic method, preferably a solely cosmetic method.

The oral care composition or oral care film may first be released from its sterile packaging. Subsequently, any support is removed, for instance by peeling the oral care composition or film from the support. Once the oral care composition or oral care film is free from any other layers, it may be applied to one or more teeth. Such an application does not require the action of a dentist, dental hygienist or dental nurse, and can be carried out by any person wishing to treat their teeth.

The oral care composition or oral care film provides good adhesion to tooth surfaces so that the oral care active agent can act upon a tooth or teeth. The oral care composition or oral care film may adhere to a tooth or teeth within 10 seconds of contact. Adhesion may occur with or without the action of saliva on the first and/or second adhesive polymers. The action of saliva on adhesive polymer, such as polyvinyl pyrrolidone, renders it tacky. The oral care composition or oral care film can adhere to a tooth or teeth for at least 15 minutes after contact.

The oral care composition or oral care film can be applied to one or more teeth of a subject for a period of more than 5 minutes and less than or equal to 60 minutes, preferably for a period of from 15 to 30 minutes. After the desired application duration, the oral care composition or oral care film may be removed from the tooth or teeth, for instance by simply peeling it away from the tooth or teeth.

Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

As used herein, the term film refers to an article having dimensions defined by three mutually perpendicular axes in which two of the dimensions are larger than the third.

Typically, the two larger dimensions are at least an order of magnitude greater than the smallest dimension.

The composition of the oral care composition is defined in terms of the dry weight of the composition i.e. the weight of components in the composition with the exclusion of water, expressed as percentages by total dry weight of the composition. The proportions of the first film-forming polymer, first adhesive polymer, second adhesive agent, oral care active agent and optionally one or more further components, when expressed as a percentages by weight of the dry composition, should total 100 weight %.

Other aspects and embodiments of the invention provide the aspects and embodiments described above with the term comprising replaced by the term consisting of and the aspects and embodiments described above with the term comprising replaced by the term consisting essentially of.

It is to be understood that the application discloses all combinations of any of the above aspects and embodiments described above with each other, unless the context demands otherwise. Similarly, the application discloses all combinations of the preferred and/or optional features either singly or together with any of the other aspects, unless the context demands otherwise.

Modifications of the above embodiments, further embodiments and modifications thereof will be apparent to the skilled person on reading this disclosure, and as such these are within the scope of the present invention.

All documents mentioned in this specification are incorporated herein by reference in their entirety for all purposes.

The term and/or where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example A and/or B is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.

Certain aspects and embodiments of the invention will now be illustrated by way of example and with reference to the figures described above and the following tables.

Examples

Components

Eudragit NE 30 D is a 30% aqueous dispersion of a neutral 2:1 copolymer of ethyl acrylate and methyl methacrylate sold by Evonik Industries, Germany. It is a first film-forming polymer which is water-insoluble and film-forming.

Eudragit NE 40 D is a 40% aqueous dispersion of a neutral 2:1 copolymer of ethyl acrylate and methyl methacrylate sold by Evonik Industries, Germany. It is a first film-forming polymer which is water-insoluble and film-forming.

CIVIC is carboxymethyl cellulose type Blanose 7LF of Ashland. This comprises a cellulose backbone in which hydroxyl groups have been replaced with -OCH2COOH groups. It has a MW of 90 500, a viscosity of 25-50 mPa.s and a degree of substitution of 0.7. It is a first adhesive polymer.

PEG 400 is a low molecular weight, hydrophilic, water soluble polyethylene glycol. It is a first adhesive polymer.

PEG 8000 is a polyethylene glycol with an average molecular weight of 8000. It is a first adhesive polymer.

Carbopol 974P NF is a polymer of acrylic acid. It is a second adhesive polymer.

Tragacanth gum is a natural gum extracted from the sap of a plant ofthe genus Astragalus and was supplied by IMCD. It contains both water soluble (hydrophilic) polysaccharides/tragacanthin polymers and water insoluble (hydrophobic) bassorin polymers of fucose, xylose, arabinose, galacturonic acid and rhamnose. The insoluble bassorin component is typically present between 60-70 % by weight. It is a first adhesive polymer.

Sodium hydroxide is a pH adjusting agent supplied by Sigma Aldrich.

Hydrogen peroxide is supplied by Sigma Aldrich. It is an oral care active agent, particularly a bleaching agent.

Peroxydone K-90 is a stable complex of polyvinyl pyrrolidone and hydrogen peroxide supplied by Ashland Inc. It contains approximately 16-20 wt.% peroxide. It has a molecular weight of approximately 1.3 million. It is an oral care active agent, particularly a bleaching agent, and a first adhesive polymer.

Perdrogen is a 35% w/w solution of hydrogen peroxide in water supplied by Univar. It is an oral care active agent, particularly a bleaching agent.

Kollidon K90 is a polyvinyl pyrrolidone polymer supplied by BASF. It is a first adhesive polymer.

Eureco HC Pll is a powdered complex of 6-(phthalimido)peroxyhexanoic acid and cyclodextrin manufactured by Solvay. It contains approximately 11 wt.% 6(phthalimido)peroxyhexanoic acid. It is an oral care active agent, particularly a bleaching agent.

Eureco HC L17 is liquid comprising 17 wt.% 6-(phthalimido)peroxyhexanoic acid manufactured by Solvay. It is an oral care active agent, particularly a bleaching agent. It is not a complex.

Carbimide peroxide is a complex of urea and hydrogen peroxide. It is an oral care active agent, particularly a bleaching agent.

Benzoyl peroxide is an oral care active agent, particularly a bleaching agent supplied by Sigma Aldrich.

Vitryxx is a calcium sodium phosphosilicate bioactive glass supplied by Schott. It is an oral care active agent, particularly a remineralisation agent.

Dipotassium oxalate is an oral care active agent, particularly a dental desensitizing agent supplied by Sigma Aldrich.

Sodium fluoride is an oral care active agent, particularly a remineralisation agent supplied by Sigma Aldrich.

Experimental

Example A

A variety of dental bleaching compositions are prepared through a one-pot process. The weight of the components of each sample composition is provided in Table 1 below. The relative proportions of the dry components by dry weight of the composition are expressed as a percentage in parenthesis. Ref. 1-3 are reference Examples, while Ex. 1-3 are Examples of the invention.

The CMC and any Tragacanth gum components are initially swollen into a gel-like state with water under shear in an Ultra TurraxT-50 dispersing instrument fitted with a S50N-G45G dispersing element. A rate of shear of 500 to 8000 rpm, preferably from 4000 to 6000 rpm was used. The Eudragit NE 30 D, hydrogen peroxide and, if present, Peroxydone K90 are then incorporated under a lower shear than that of the CMC and Tragacanth gum, such as by hand mixing or with an IKA RW 20 overhead stirrer fitted with a 3 blade propeller shaft. A rate of shear of from 100 to 500 rpm, preferably about 300 rpm was used. Degassing under vacuum is performed to produce a de-aerated viscous liquid.

The liquid is then cast as wet film to a thickness in the range of from 750 to 1350 micrometers, preferably from 900 to 950 micrometers, with a casting knife onto uncoated backing paper and dried at a temperature in the range of from 35 to 40 °C for a time in the range of from 40 to 100 minutes, preferably from 50 to 55 minutes.

Table 1: Dental bleaching compositions

Ingredient		Quantity (g) (% Dry Weight)
Ref. 1	Ref. 2	Ref. 3	Ex. 1
DEV03760	DEV03772	DEV03785	DEV03735
Eudragit NE30D	150.0	183.4	150.0	100.0
	(45.0)	(55.0)	(45.0)	(45.3)
Tragacanth Gum	-	-	22.2 (22.2)	16.7 (25.3)
CMC	42.0 (42.0)	32.0 (32.0)	-	3.3 (5.0)
Glycerol	5.0 (5.0)	5.0 (5.0)	-
30% w/w Hydrogen	26.7	26.7	16.7	9.4
Peroxide Solution	(8.0)	(8.0)	(5.0)	(4.3)
Peroxydone K90*			27.8 (27.8) H₂O₂ (5) PVP (22.8)	13.3 (20.1) H₂O₂ (3.6) PVP (16.5)
Water	249.2	220.3	402.5	174.1

* 18 wt% hydrogen peroxide, 82 wt% polyvinyl pyrrolidone

Results and Discussion

The films were tested on teeth for a period of 30 minutes. The dimensions and mass of the films before application to teeth and after removal from teeth were measured. If the film lost adhesion prior to the end of the 30 minute duration, the actual length of time for which the adhesion occurred was recorded. The test subjects were also asked to note any loosening of the films, the time at which this occurred and whether the film retained adhesion even if loose. After removal of the films, they were assessed for structural integrity, and the number and size of any fracture points recorded.

Upon testing, Reference 1 (DEV03760) was found to adhere to teeth for approximately 15 minutes after which there was movement and slippage of the film. The film lost integrity and began to break up on removal. Reference 1 contains 42% wt. water-soluble first adhesive polymer CMC, but does not contain a second adhesive polymer which exhibits pH dependent swelling.

The Reference 2 (DEV03772) film contained a decreased proportion of water-soluble first adhesive polymer CIVIC and remained intact upon removal. However, it does not contain a second adhesive polymer and was only capable of adhering to teeth for 20-30 minutes.

The Reference 3 (DEV03785) film contained first adhesive polymers PVP and tragacanth gum. It does not contain a second adhesive polymer and did not provide sufficient adhesion to teeth.

The Example 1 (DEV03735) film according to the invention contained both short- and longterm adhesives. It adhered to teeth fora 30 minute period and could be removed intact in one piece.

The analysis ofthe compositions shown in Table 1 indicate that a balance is required between obtaining fast initial adhesion ofthe composition, maintaining the adhesion over time in the mouth where there is a significant quantity of moisture present and maintaining the physical integrity of the composition for the desired time period so that it remains largely intact and has the strength to be removed in one piece when desired.

The analysis indicated that the composition of Ex. 1 (DEV03735) remained intact for a 30 minute period on the teeth and could be removed in one piece. The adhesion ofthe film of Example 1 on teeth was activated by absorption of moisture from saliva. The film was held in place until sufficient moisture had been taken up to enable adhesion to the teeth to take place.

Additionally the use of two sources of hydrogen peroxide; Peroxydone K90 and a 30% solution of hydrogen peroxide enables a formulation to be developed which has a higher peroxide concentration (10% w/w), without requiring a corresponding increase in the concentration of PVP from the Peroxydone K90 complex.

Thus, a dental bleaching composition can be prepared which produce films that stick immediately to the teeth, remain in place for at least 15 minutes and can be removed intact.

Example B

Further dental bleaching compositions were prepared through a one-pot process. The weight of the components of each sample composition is provided in Table 2 below. The relative proportions of the dry components by dry weight of the composition are expressed as a percentage in parenthesis. Ex. 2-7 are Examples ofthe invention.

The mixing is carried out in an Ultra Turrax T-50 dispersing instrument fitted with a S50NG45G dispersing element. The first adhesive polymer and second adhesive polymer, namely

PEG 400, PEG 8000 and Carbopol 974P NF are added to water and mixed under vacuum at shear of approximately 3000 - 5000 rpm to allow initial uptake of water and swelling. Next, aqueous sodium hydroxide is added until a gel is produced. The oral care active, hydrogen peroxide, is then added as a polymer complex, Peroxydone K90, and the composition is mixed. The remainder of the aqueous solution of sodium hydroxide is added, adjusting the pH of the mixture to approximately 6. Then the film-forming polymer, Eudragit 40D is added and the composition is mix at a low shear in the range of from 50 to 400 rpm and the 5 mixture is degassed. Optionally, further oral care active, a 35 w/w% solution of hydrogen peroxide, may be added (Examples 7-11) in order to increase the concentration of bleaching agent. The composition is then mixed at 50 - 400 rpm and degassed.

Table 2: Dental Bleaching Compositions

Material	Ex. 2 DEV04042 (Subbatch 1)	Ex. 3 DEV04042 (Sub-batch 2)	Ex. 4 DEV04042 (Sub-batch 3)	Ex. 5 DEV04042 (Subbatch 4)	Ex. 6 DEV04091	Ex. 7 DEV04090
Weight/ g [dry weight active/ g] (dry weight active as % of dry com	position)
Eudragit 40D	258.60 [103.44] (51.06%)	45.50 [18.20] (48.92%)	45.50 [18.20] (47.29%)	45.50 [18.20] (45.66%)	1034.40 [413.76] (43.92%)	1034.40 [413.76] (40.76%)
Carbopol 974P NF	4.04 [4.04] (1.99%)	0.71 [0.71] (1.91%)	0.71 [0.71] (1.84%)	0.71 [0.71] (1.78%)	16.16 [16.16] (1.72%)	16.16 [16.16] (1.59%)
PEG 400	16.00 [16.00] (7.90%)	2.82 [2.82] (7.58%)	2.82 [2.82] (7.33%)	2.82 [2.82] (7.07%)	64.00 [64.00] (6.79%)	64.00 [64.00] (6.30%)
PEG 8000	10.68 [10.68] (5.27%)	1.88 [1.88] (5.05%)	1.88 [1.88] (4.88%)	1.88 [1.88] (4.72%)	42.72 [42.72] (4.54%)	42.72 [42.72] (4.21%)
IM Sodium Hydroxide	4.00 [0-15 g] (0.07%)	0.70 [0.03 g] (0.08%)	0.70 [0.03 g] (0.08%)	0.70 [0.03 g] (0.08%)	67.62 [2.60 g] (0.28%)	67.62 [2.60 g] (0.26%)
Peroxydone K90	68.28 [68.28] H₂O₂ [12.29] (6.07%) PVP [55.99] (27.64%)	12.01 [12.01] H2O2 [2.16] (5.80%) PVP [9.85] (26.47%)	12.01 [12.01] H2O2 [2.16] (5.61%) PVP [9.85] (25.59%)	12.01 [12.01] H2O2 [2.16] (5.42%) PVP [9.85] (24.71%)	333.00 [333.00] H2O2 [59.94] (6.36%) PVP [273.06] (28.99%)	333.00 [333.00] H2O2 [59.94] (5.90%) PVP [273.06] (26.90%)

Perdrogen (35% w/w H2O2 soln)		4.45 [1.56] (4.19%)	8.11 [2.84] (7.38%)	12.04 [4.21] (10.56%)	199.06 [69.67] (7.40%)	408.50 [142.98] (14.08%)
Water	490.96	86.38	86.38	86.38	1963.84	1963.84
Total dry weight	202.59	37.21	38.49	39.86	941.91	1015.22

[...] dry weight component

(...) wt.% component by dry weight of composition

The quantity of hydrogen peroxide added to the composition can be tailored depending on the desired strength of the product. This can be carried out either by increasing the quantity of hydrogen peroxide added from the Peroxydone K90 component (examples 2 and 6 in above table) or by increasing the quantity added from a peroxide solution (examples 3-7 in the table above).

In these Examples, two molecular weights of polyethylene glycols, namely PEG400 and PEG800, as the first adhesive polymer, are blended together to provide initial and medium duration adhesion. The smaller molecular weight first adhesive polymer, PEG400, has a faster water uptake and therefore adhesion, compared to the higher molecular weight first adhesive polymer, PEG8000. A further first adhesive polymer, polyvinyl pyrrolidone is also present complexed with at least a portion of the hydrogen peroxide dental bleaching agent.

Example C

Further dental bleaching compositions using alternative peroxides as the dental bleaching agent were prepared through a one-pot process as described above. The weight of the components of each sample composition is provided in Table 3 below. The relative proportions of the dry components by dry weight of the composition are expressed as a percentage in parenthesis. Ex. 8-14 are Examples of the invention.

Table 3: Dental Bleaching Compositions

Ingredient	% Dry Weight
Ex. 8	Ex. 9	Ex. 10	Ex. 11	Ex. 12	Ex. 13	Ex. 14
DEV 04158	DEV 04159	DEV 04175	DEV 04176	DEV 04177	DEV 04181	DEV 04182
Eureco HC Pll (% PAP)	9.05 (1.00)	16.60 (1.83)
Eureco HC L17 (% PAP)			9.97 (9.97)
Carbimide Peroxide (% H2O2)				2.86 (1.00)	14.26 (4.99)

Benzoyl Peroxide			1.00	10.00
Eudragit NE 30D	46.21	42.35	45.72	49.34	43.55	50.28	45.71
Kollidon K90	30.70	28.14	30.39	32.79	28.94	33.41	30.38
Carbopol 974P NF	1.81	1.67	1.80	1.94	1.71	1.98	1.80
PEG 400	7.19	6.59	7.12	7.68	6.78	7.83	7.12
PEG 8000	4.80	4.40	4.75	5.13	4.53	5.23	4.75
1.0M NaOH	0.24	0.25	0.24	0.26	0.23	0.26	0.24

Thus, a range of dental bleaching compositions can be prepared using different dental bleaching agents.

Example D

Further oral care compositions using alternative oral care actives such as dental remineralisation agents and desensitizing agents were prepared through a one-pot process as described above in which a remineralisation agent or a desensitising agent is substituted 10 for the dental bleaching agent. The weight of the components of each sample composition is provided in Table 4 below. Ex. 15-19 are Examples of the invention.

Table 4: Oral Care Active Compositions

Ingredient	Enamel Remineralisation Examples
% Dry Weight
Ex. 15	Ex. 16	Ex. 17	Ex. 18	Ex. 19
DEV 04173	DEV 04157	DEV 04174	DEV 04160	DEV 04183
Vitryxx	1.00	9.05	20.00
Dipotassium Oxalate				9.05
Sodium Fluoride					1.00
Eudragit NE 30D	50.28	46.21	40.65	46.21	50.14
Kollidon K90	33.42	30.70	27.02	30.70	33.32
Carbopol 974P NF	1.98	1.81	1.60	1.81	1.97
PEG 400	7.83	7.19	6.33	7.19	7.81
PEG 8000	5.23	4.80	4.23	4.80	5.21
1.0M NaOH	0.26	0.24	0.21	0.24	0.54

Claims

CLAIMS:

1. An oral care composition comprising:

a film-forming polymer which is water insoluble and exhibits pH independent swelling;

a first adhesive polymer which is water soluble;

a second adhesive polymer which is a water insoluble and exhibits pH dependent swelling; and an oral care active agent.

2. An oral care composition comprising:

a first adhesive polymer which is water soluble;

a second adhesive polymer which is water insoluble and comprises an acidic moiety having an acid dissociation constant in the range of from 5 to 6.5; and an oral care active agent.

3. The composition of claim 1 or claim 2, wherein the film-forming polymer may be selected from one or more of the group comprising ethyl cellulose, poly(aIkyl acrylate) and poly(aIky alkylacrylate) in which the alkyl group is independently selected from C1-5 alkyl, preferably methyl or ethyl.

4. The composition of any of the preceding claims, wherein the first adhesive polymer may be selected from one or more of the group comprising pectin, natural gum, synthetic gum, agar, multivalent salts of agar, polyalkylene glycol, carboxy alkyl cellulose, hydroxyalkyl cellulose and polyvinyl pyrrolidone, in which the alkyl group is independently selected from C1-5 alkyl, preferably methyl, ethyl or propyl.

5. The composition of any of the preceding claims, wherein the second adhesive polymer may be selected from one or more of the group comprising alginic acid, multivalent salt of alginic acid, polyacrylic acid, salt of polyacrylic acid, polyaIkylacrylic acid and salt of polyaIkylacrylic acid, in which the alkyl group is independently selected from C1-5 alkyl.

6. The composition of any of the preceding claims, wherein the oral care active agent is selected from the group comprising a bleaching agent, a dental remineralisation agent, a dental desensitising agent, an anti-infective agent, an anti-caries agent, an anti-calculus agent, an anti-inflammatory agent and a biomolecule.

7. The composition of claim 6 wherein the oral care active agent is a bleaching agent such as a bleaching agent selected from the group comprising a peroxide, such as hydrogen peroxide, organic peroxy acids optionally together with a stabilizing agent; and chlorites, such as an alkali metal chlorite.

8. The composition of any of the preceding claims, wherein the film-forming polymer is present in a proportion of from 35 to 60 wt.% by dry weight of the total composition, the first adhesive polymer is present in a proportion of from 10 to 50 wt.% by dry weight of the total composition, the second adhesive polymer is present in a proportion of from 0.5 to 30 wt.% by dry weight of the total composition and the oral care active agent is present in a proportion of from 0.05 to 25.0 wt.% by dry weight of the total composition.

9. The composition of any of the preceding claims in which the oral care composition further comprises one or more optional components selected from the group comprising a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, a surfactant and a delivery enhancing polymer.

10. The composition of any of the preceding claims, wherein the composition is a film having a single layer.

11. A process for the preparation of an oral care composition, said process comprising at least the steps of:

mixing a film-forming polymer which is water insoluble and which pH independent swelling, a first adhesive polymer which is water soluble, a second adhesive polymer which is water insoluble and which exhibits pH dependent swelling, an oral care active agent and water to provide an aqueous oral care liquid;

12. The process of claim 10 wherein the second adhesive polymer is swollen into a gellike state by the mixing with water.

13. The process of claim 11 or claim 12, wherein the mixing step further comprises mixing one or more optional components selected from the group comprising a pH adjusting agent, a flavouring agent, a sweetener, a plasticizer, surfactant and a delivery enhancing polymer.

14. The process of any one of claims 11 to 13, wherein the oral care composition is a film having a single layer.

15. An oral care composition obtainable by the process of any of claims 11 to 14.

16. A method of administering an oral care active agent to a tooth or teeth comprising at least the step of:

applying the oral care composition according to any of claims 1 to 10 or an oral care composition according to claim 15 to one or more teeth of a subject.

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