Dissolvable teeth whitening films, process of manufacture thereof

Abstract

The present invention relates to dissolvable teeth whitening films having compositions useful for the delivery of naturally occurring active agents. More particularly, to compositions suitable for formation of orally soluble, mucoadhesive films that include proteolytic enzymes. Also provided is a process of manufacturing the films and a method of using the films.

Description

[0001] DISSOLVABLE TEETH WHITENING FILMS, PROCESS OF MANUFACTURE THEREOF

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to dissolvable teeth whitening films having compositions useful for the delivery of naturally occurring active agents. More particularly, to compositions suitable for formation of orally soluble, mucoadhesive films that include proteolytic enzymes. Also provided is a process of manufacturing the films and a method of using the films.

[0004] BACKGROUND

[0005] Human teeth naturally exhibit a variety of colours, which can be influenced by a number of factors, such as diet and / or medications. For instance, a number of foods (such as berries) and drinks (such as tea and red wine) contain chromogens which can stain teeth. Tobacco may also darken teeth. Other substances, such as acidic fruits and drinks, can promote staining by eroding dental enamel, softening teeth and making it easier for chromogens to attach. Consequently, there is a desire to whiten teeth to remove such staining.

[0006] Current solutions for the treatment of stained teeth are mainly delivered in the form of liquids, pastes, gels, patches, disks and pressed tablets. These forms often spread easily, or get dislocated and cause their effects throughout the oral mucosa. Other oral compositions may be provided in the solid state in the form of a strip or film with a backing layer, which adheres to teeth or mucosal surfaces 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, it can be difficult to incorporate an active agent into such strips or films. For instance, active agents may lack the requisite solubility to form a solid solution in the oral composition. Instead, the active agent precipitates as solid particulates in the composition, which may be unevenly distributed throughout the solid composition. Further, the backing strips must be peeled from the treated teeth and discarded after use. The stability of active agents within the strips can also be difficult to manage, with some hydrogen peroxide strips "degrading" over time, such that the effective concentration of peroxide within the strip significantly depletes in storage.

[0007] A common active agent for inclusion in oral compositions that is particularly effective at whitening teeth is hydrogen peroxide (H2O2). However, prolonged use of hydrogen peroxide has been linked to dental hypersensitivity (DH) issues. As an alternative, non-hydrogen peroxide bleaching whitening agents, such as phthalimido peroxy caproic acid (PAP) can be used. However, these agents typically do not exhibit comparable whitening efficacy to hydrogen peroxide based whitening agents. Further,there is a limit as to the total amount of PAP that can be reasonably added to a formulation due to stability issues, and the relationship between PAP concentration and whitening efficacy is not linear (i.e. increased PAP does not necessarily provide a more efficacious product, beyond a certain wt.% content of the product).

[0008] It is an object of at least one aspect of the present invention to provide a dissolvable teeth whitening strip or film that comprises at least one whitening agent that exhibits comparable or improved whitening to traditional bleaching agent containing strips, whilst addressing issues surrounding dental hypersensitivity, active agent stability and distribution. Example "traditional bleaching agents" include hydrogen peroxide and PAP.

[0009] It is a further object of the present invention to provide a dissolvable teeth whitening strip or film that comprises at least one whitening agent that is compatible with traditional whitening agents (such as hydrogen peroxide and / or PAP) for enhanced whitening.

[0010] It is a further object to provide a dissolvable teeth whitening strip or film that provides a long-lasting activity compared to existing products.

[0011] It is also an object of at least one aspect of the present invention to mitigate at least one or more of the aforementioned problems.

[0012] It is a further object of the present invention to provide a process for manufacturing the dissolvable teeth whitening strip or film.

[0013] A yet further object of the present invention is to provide a cosmetic treatment for teeth whitening and / or teeth bleaching using a dissolvable teeth whitening strip or film.

[0014] SUMMARY OF INVENTION

[0015] According to a first aspect, there is provided a teeth whitening strip or film comprising: at least one proteolytic enzyme, wherein the or each at least one proteolytic enzyme comprises papain and / or bromelain, wherein the concentration of the or each at least one proteolytic enzyme is between 0.1 to 10.0 wt.% of the strip or film.The present invention therefore provides a tooth whitening strip or film which overcomes previous problems.

[0016] The teeth whitening strip or film may comprise: 0.1 to 10.0 wt.%; 0.5 to 9.0 wt.%; 0.5 to 8.0 wt.%; 1.0 to 7.0 wt.%; 1.0 to 6.0 wt.%; 1.5 to 5.0 wt.%; or 2.0 to 4.0 wt.% of the or each at least one proteolytic enzyme.

[0017] The teeth whitening strip or film may comprise: 2.0 wt.% or 4.0 wt.% papain; and / or 2.0 wt.% or 4.0 wt.% bromelain. These preferred proteolytic enzymes have been found to provide enhanced dental whitening, comparable to traditional bleaching agents (such as hydrogen peroxide) whilst avoiding inducing dental hypersensitivity.

[0018] The teeth whitening strip or film may further comprise a whitening agent (such as hydrogen peroxide) and / or a dental hypersensitivity agent (such as hydroxyapatite).

[0019] The tooth whitening agent of the teeth whitening strip or film may comprise: hydrogen peroxide and / or a hydrogen peroxide-polyvinyl pyrrolidone complex and / or 6-phthalimido peroxy caproic acid (PAP).

[0020] Where the whitening agent comprises PAP, it may advantageously be provided as a complex of peroxy carboxylic acid and a carbohydrate, such as dextrin. Advantageously, complexes of a peroxy carboxylic acid, such as PAP, with a carbohydrate, such as dextrin, provide the bleaching agent with improved stability, particularly improved thermal and chemical stability.

[0021] In particular, where hydrogen peroxide is used in the strip or film of the present invention, in combination with bromelain and / or papain, enhanced whitening is provided. Further, less hydrogen peroxide may be used overall in the strip or film, thereby reducing the incidence and severity of any dental hypersensitivity that would have been induced by the peroxide.

[0022] Where the teeth whitening strip or film comprises hydrogen peroxide in combination with papain and / or bromelain, the concentration of hydrogen peroxide in the strip or film may be: about 1.0 wt.% to 15.0 wt.% of the strip or film; about 1 wt.% to 12 wt.% of the strip or film; about 2 wt.% to 12 wt.% of the strip or film; about 3 wt.% to 12 wt.% of the strip or film; about 4.0 wt.% to 10.0 wt.% of thestrip or film; about 4.0 wt.% to 9.0 wt.% of the strip or film; or about 5.0 wt.% to 9.0 wt.% of the strip or film.

[0023] Where the teeth whitening strip or film comprises PAP in combination with papain and / or bromelain, the concentration of PAP in the strip or film may be: about 0.1 wt.% to 10.0 wt.% of the strip or film; about 0.1 wt.% to 5.0 wt.% of the strip or film; about 0.1 wt.% to 2.0 wt.% of the strip or film; or about 1.0 wt.% to 2.0 wt.% of the strip or film.

[0024] Where the teeth whitening strip or film comprises a dental hypersensitivity agent, said agent may comprise: Hydroxyapatite; potassium nitrate; strontium; arginine; calcium carbonate; stannous fluoride; biomimetic glass (novamin®).

[0025] The teeth whitening strip or film may further comprise one or more polyphosphates. Wherein the polyphosphates may comprise one or more cyclic and / or one or more linear polyphosphates. Advantageously, polyphosphates have been found to greatly improve the whitening efficacy of the strips containing bromelain and / or papain. This effect is even further improved with the addition of hydrogen peroxide and / or PAP to the bromelain and / or papain + polyphosphate strips.

[0026] Most advantageously, where bromelain and papain are used in combination in a peroxide + polyphosphate containing teeth whitening strip, surprisingly, the peroxide content of the strip is far more stable.

[0027] Where the teeth whitening strip or film comprises polyphosphates, the cyclic and / or linear polyphosphates may be present in a total amount of from: 2% to 9% by weight of the strip or film; 3% to 8% by weight of the strip or film; or 3% to 4% by weight of the strip or film.

[0028] Formulations of the present strip may be adjusted to provide a rapid whitening strip, showing significant improvement in whitening efficacy over less treatments. An example tooth whitening strip in accordance with the present invention, that provides rapid whitening, may comprise: at least 4 wt.% papain; 3 to 6 wt.% hydrogen peroxide; and at least one cyclic and at least one linear polyphosphate in a total amount of from: 2% to 9% by weight of the strip. Preferably, the papain content is between 4 wt.% and 10 wt.%. Preferably the papain content is 4 wt.%. Preferably the hydrogen peroxide content is 6 wt.% and may optionally be in the form of liquid peroxide or a complex of hydrogenperoxide with PVP. Preferably the at least one cyclic and at least one linear polyphosphates are present in an amount of 3.5 wt.% each.

[0029] The teeth whitening strip or film may further comprise any one or combination of the following: one or more water soluble film-forming polymers;

[0030] one or more plasticizers; and / or

[0031] one or more emulsifiers.

[0032] The one or more soluble film-forming polymers may be one or more of the group comprising: polyvinylpyrrolidone (PVP); pullulan; pectin; starch; dextrin; chitosan; alginic acid; salts of alginic acid and / or cellulose derivatives.

[0033] The one or more plasticizers may be selected from the group comprising a polyol such as: glycerol, polyalkylene glycol, polyalkylene glycol monomethyl ether, monosaccharide, oligosaccharide, sorbitol, sorbital and sorbitan, in which the alkylene groups are independently selected from Cl-5 alkylene, preferably methylene, ethylene or propylene.

[0034] The one or more emulsifiers may be selected from the group comprising a fatty acid derivative, a lecithin and / or a polysorbate.

[0035] The strip or film may further comprise one or more further components selected from the group comprising: colourant, gelling agent, flavouring, sweetener, antioxidant, anti-malodour agent, and / or non-hydroxide whitening agent.

[0036] The teeth whitening strip or film may be dissolvable, such that it dissolves completely or substantially completely within the oral cavity of a user. Advantageously, the strip or film dissolves completely or substantially completely when used in an oral cavity of a user over a period of: 15 to 30 minutes; 30 to 60 minutes; 30 minutes to 2 hours; 1 to 5 hours; 1 to 10 hours; or 1 to 22 hours.

[0037] The teeth whitening strip or film may have a thickness ranging from: about 50 pm to about 500 pm; about 50 pm to about 250 pm; about 50 pm to about 100 pm; or about 100 pm to about 200 pm.

[0038] In a second aspect, there is provided a process for the manufacture of a teeth whitening strip or film, the process comprising at least the steps of:mixing at least one proteolytic enzyme (such as papain and / or bromelain) in a total amount of about 0.1% to about 10% by weight, one or more water soluble film-forming polymers in a total amount of about 30% to about 95% by weight, one or more plasticizers in a total amount of about 0.1% to about 15% by weight and one or more emulsifiers in a total amount of about 0.1% to about 10% by weight,

[0039] with water to provide an aqueous teeth whitening liquid;

[0040] applying the aqueous teeth whitening liquid to a substrate to provide a substrate carrying the aqueous teeth whitening liquid;

[0041] drying the aqueous teeth whitening liquid to provide a teeth whitening strip or film on the substrate, said strip or film having a thickness from about 50 pm to about 500 pm.

[0042] The mixing step of the process may further comprise mixing one or more further components selected from the group comprising: colourant, gelling agent, flavouring, sweetener, antioxidant and chelating agent.

[0043] Preferably, the proteolytic enzyme added to provide the aqueous teeth whitening liquid comprises bromelain and / or papain.

[0044] In a third aspect, there is provided a teeth whitening strip or film obtainable by the above process.

[0045] BRIEF DESCRIPTION OF DRAWINGS

[0046] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which:

[0047] Figure 1 shows the overall colour change (AE) of test substrates of a first whitening study after 3 and 7 applications with tooth whitening films in accordance with the present invention, comprising 2 wt.% or 4 wt.% of papain, in comparison with tooth whitening films comprising hydrogen peroxide;

[0048] Figure 2 shows the overall colour change (AE) of test substrates of a first whitening study 3 and 7 applications with tooth whitening films in accordance with the present invention, comprising 2 wt.% or 4 wt.% of papain, in comparison with tooth whitening films comprising phthalimido peroxy caproic acid (PAP);Figure 3 shows the overall colour change (AE) of test substrates of a second whitening study after 3 and 7 applications with tooth whitening films in accordance with the present invention, comprising 2 wt.% or 4 wt.% of papain and / or bromelain;

[0049] Figure 4 shows the overall colour change (AE) of further test substrates of the second whitening study after 3 and 7 applications with tooth whitening films in accordance with the present invention, comprising 2 wt.% or 4 wt.% of papain and / or bromelain, in comparison with tooth whitening films comprising hydrogen peroxide;

[0050] Figure 5 shows the overall colour change (AE) of further test substrates of the second whitening study after 3 and 7 applications with tooth whitening films in accordance with the present invention, comprising 2 wt.% or 4 wt.% of papain and / or bromelain, in comparison with tooth whitening films comprising PAP;

[0051] Figure 6 shows comparison of the peroxide and PAP only containing strips with the natural whitening agent strips of the second whitening study;

[0052] Figure 7 shows a bar chart of a peroxide stability study, showing % Decrease in H2O2 content in the teeth whitening films according to the present invention during accelerated ageing;

[0053] Figure 8 is a comparative study results from Intertek in-vitro whitening study that evaluated performance of enzyme containing non-peroxide strips against non-peroxide dissolving and nondissolving whitening strips;

[0054] DETAILED DESCRIPTION

[0055] The present invention relates to dissolvable teeth whitening films. In particular, the present invention relates to dissolvable teeth whitening films having compositions useful for the delivery of naturally occurring active agents, such as proteolytic enzymes. More particularly, to compositions suitable for formation of orally soluble, mucoadhesive films that include proteolytic enzymes. Also provided is a process of manufacturing the films and a method of using the films.The invention therefore provides a dissolvable teeth whitening strip or film comprising proteolytic enzymes that act to reduce staining and whiten a user's teeth when said strip or film is applied to said user's teeth.

[0056] The dissolvable teeth whitening strip or film preferably comprises at least one proteolytic enzyme. Preferably, the dissolvable teeth whitening strip or film comprises about 0.1 wt.% to about 10 wt.% of the or each at least one proteolytic enzyme.

[0057] The or each at least one proteolytic enzyme is capable of reducing staining of teeth. The or each at least one proteolytic enzyme is capable of making teeth appear whiter. Without wishing to be bound by theory, it is believed that the active stain reduction and tooth whitening is achieved by the proteolytic enzyme(s) disrupting the protein portion of the pellicle layer on the teeth that forms over time, therefore, the stains that are bound to this layer of a tooth / teeth are removed.

[0058] Advantageously, production of dissolvable teeth whitening strips or films that comprise proteolytic enzymes as an alternative to traditional whitening agents (such as hydrogen peroxide, or phthalimido peroxy caproic acid (PAP)) offer a more "natural" whitening product (comprising naturally occurring whitening actives).

[0059] The present invention provides a dissolvable or substantially dissolvable teeth whitening strip or film comprising at least one proteolytic enzyme with the concentration of: about 0.1 wt.% to 10 wt.% of the strip or film; about 0.5 wt.% to 9 wt.% of the strip or film; about 0.5 wt.% to 8 wt.% of the strip or film; about 1.0 wt.% to 7.0 wt.% of the strip or film; about 1.0 wt.% to 6.0 wt.% of the strip or film; about 1.5 wt.% to 5.0 wt.% of the strip or film; or about 2.0 wt.% to 4.0 wt.% of the strip or film.

[0060] Preferred proteolytic enzymes that may be used in the dissolvable teeth whitening strip or film include papain and / or bromelain. Surprisingly, these particular proteolytic enzymes exhibit enhanced stain removal and tooth whitening.

[0061] Surprisingly, when the dissolvable teeth whitening strip or film includes papain and bromelain in combination, there is a synergistic whitening effect, which enhances the overall whitening provided in comparison to a strip comprising an equal overall wt.% of either papain or bromelain alone (see Figure 3, also discussed below).The present invention provides a dissolvable or substantially dissolvable teeth whitening strip or film comprising papain and / or bromelain, with the concentration of each of papain and / or bromelain being: about 0.1 wt.% to 10 wt.% of the strip or film; about 0.5 wt.% to 9 wt.% of the strip or film; about 0.5 wt.% to 8 wt.% of the strip or film; about 1.0 wt.% to 7.0 wt.% of the strip or film; about 1.0 wt.% to 6.0 wt.% of the strip or film; about 1.5 wt.% to 5.0 wt.% of the strip or film; or about 2.0 wt.% to 4.0 wt.% of the strip or film.

[0062] A particular preferred composition of proteolytic enzyme in the dissolvable or substantially dissolvable teeth whitening strip or film of the present invention is: 2.0 wt.% to 4.0 wt.% papain and / or 2.0 wt.% to 4.0 wt.% bromelain.

[0063] Optionally, the dissolvable teeth whitening strip or film may comprise two or more different proteolytic enzymes. The different proteolytic enzymes can be used in varying compositions of the strip or film to provide tailored benefits.

[0064] The present invention may also provide a dissolvable teeth whitening strip or film that comprises at least one proteolytic enzyme in combination with other whitening agents. The optional additional whitening agents include: hydrogen peroxide; a hydrogen peroxide-polyvinyl pyrrolidone complex; and 6-phthalimido peroxy caproic acid (PAP), or any combination thereof.

[0065] The dissolvable or substantially dissolvable teeth whitening strip or film may therefore comprise at least one proteolytic enzyme (such as papain and / or bromelain) in combination with: hydrogen peroxide and / or a hydrogen peroxide-polyvinyl pyrrolidone complex (such as Peroxydone®) and / or PAP (such as Eureco HCP11®). Advantageously, this provides a dissolvable teeth whitening strip or film that comprises different whitening agents that have different methods of whitening teeth respectively, for further enhanced stain removal and tooth whitening efficacy. The dissolvable teeth whitening strip or film that comprises a proteolytic enzyme in combination with other whitening agent(s) is therefore advantageously a multi-treatment modality strip or film.

[0066] Where the present invention provides a dissolvable or substantially dissolvable teeth whitening strip or film comprising at least one proteolytic enzyme (such as papain and / or bromelain) and hydrogen peroxide (optionally as a hydrogen peroxide-polyvinyl pyrrolidone complex), the concentration of hydrogen peroxide in the strip or film may be: about 1 wt.% to 15 wt.% of the strip or film; about 1 wt.% to 12 wt.% of the strip or film; about 2 wt.% to 12 wt.% of the strip or film; about 3 wt.% to 12wt.% of the strip or film; about 3 wt.% to 10 wt.% of the strip or film; about 3 wt.% to 9 wt.% of the strip or film; about 3 wt.% to 8 wt.%; or about 3 wt.% to 6 wt.% of the strip or film. As an example, Peroxydone K-30® is a dental bleaching agent formed from a complex of 17.0 to 20.0 wt.% hydrogen peroxide and polyvinyl pyrrolidone having a molecular weight of 58,000 supplied by Ashland Inc. Therefore, where 39.7 wt.% Peroxydone K-30® is used as a source of hydrogen peroxide in a strip or film of the present invention, the strip or film is provided with approximately 6.75 wt.% to 7.94 wt.% content hydrogen peroxide.

[0067] Accordingly, the teeth whitening strip may comprise: 2 to 4 wt.% papain and / or 2 to 4 wt.% bromelain; and 1 to 15 wt.% hydrogen peroxide (optionally as a hydrogen peroxide-polyvinyl pyrrolidone complex). Optionally, the strip comprises 3 to 6 wt.% hydrogen peroxide. Optionally the strip comprises about 3 wt.% or about 6 wt.% hydrogen peroxide. Optionally, the strip may comprise 2 wt.% papain and 2 wt.% bromelain.

[0068] Where the present invention provides a dissolvable or substantially dissolvable teeth whitening strip or film comprising at least one proteolytic enzyme (such as papain and / or bromelain) and PAP, the concentration of PAP in the strip or film may be: about 0.1 wt.% to 10.0 wt.% of the strip or film; about 0.1 wt.% to 5.0 wt.% of the strip or film; about 0.1 wt.% to 2.0 wt.% of the strip or film; or about 1.0 wt.% to 2.0 wt.% of the strip or film. As an example, Eureco HC-P11® is an 11 wt.% PAP non-hydrogen peroxide bleaching agent complex with p-cyclodextrin supplied by Solvay. Therefore, where 10.1% Eureco HC-P11® is used as the source of PAP in a strip or film of the present invention, the strip or film is provided with approximately 1.11 wt.% content PAP.

[0069] Accordingly, the teeth whitening strip may comprise: 2 to 4 wt.% papain and / or 2 to 4 wt.% bromelain; and 0.1 wt.% to 10.0 wt.% PAP (optionally as a complex of peroxy carboxylic acid and a carbohydrate, such as dextrin). Optionally, the strip comprises about 0.1 to 5 wt.% PAP. Optionally the strip comprises about 1 wt.% to 2 wt.% PAP. Optionally, the strip may comprise 2 wt.% papain and 2 wt.% bromelain.

[0070] A peroxy carboxylic acid bleaching agent may be provided as a complex, such as a complex of peroxy carboxylic acid and a carbohydrate, for instance dextrin. Complexes of a peroxy carboxylic acid, such as PAP, with a carbohydrate, such as dextrin, provide the bleaching agent with improved stability, particularly improved thermal and chemical stability. The bleaching agent is less reactive because it is intermolecularly bonded with the carbohydrate, such as within a dextrin ring, thereby providing athermal energy barrier to degradation. Energy is required to dissociate the peroxy carboxylic acid from the complex before it can be degraded.

[0071] Accordingly, the present invention provides a dissolvable strip or film that is formulated to contain proteolytic enzymes that provide a whitening effect on teeth on their own, or alternatively, to supplement more traditional whitening agents, such as PAP or hydrogen peroxide, for further enhanced tooth whitening.

[0072] Advantageously, where a proteolytic enzyme is combined with hydrogen peroxide or PAP, it provides more efficacious whitening and stain removal, therefore, the content of hydrogen peroxide and PAP can be reduced whilst maintaining whitening levels. This therefore saves money for manufacturing costs and also allows for the inclusion of further agents into the strip or film. Use of lower levels of hydrogen peroxide also reduces the risk and severity of induced dental hypersensitivity. The increase in efficacy is achieved without addition of increased levels of peroxide or PAP, but instead the addition of papain at either 2 or 4%. Use of lower levels of PAP has the advantage of greater strip stability.

[0073] The present invention may also provide a dissolvable teeth whitening strip or film that comprises a proteolytic enzyme in combination with dental hypersensitivity (DH) agents, such as hydroxyapatite (HAP). The dissolvable or substantially dissolvable teeth whitening strip or film may therefore comprise: at least one proteolytic enzyme (such as papain and / or bromelain); optionally hydrogen peroxide and / or PAP; and optionally HAP. Other dental hypersensitivity agents which may be included in the strip or film in any combination include: potassium nitrate; strontium; arginine; calcium carbonate; stannous fluoride; biomimetic glass (novamin®).

[0074] The present invention may also provide a dissolvable teeth whitening strip or film that further comprises one or more polyphosphates.

[0075] The polyphosphates of the dissolvable teeth whitening strip or film may be present as one or more cyclic polyphosphates and / or one or more linear polyphosphate.

[0076] The Applicant has found that use of one or more cyclic and / or one or more linear polyphosphates in the dissolvable teeth whitening strip or film improves the whitening efficacy of the at least one proteolytic enzyme and optional whitening agent (or agents) within the strip. Therefore, such adissolvable teeth whitening strip or film provides one or both of enhanced whitening (or bleaching) and improved stain removal when the strip is applied to the teeth of a user.

[0077] In addition, enhanced whitening efficacy may be achieved at lower concentrations of the proteolytic enzyme, and optional additional whitening agent(s), due to the presence of the polyphosphates.

[0078] In one embodiment, the one or more cyclic polyphosphates are defined by formula (II):

[0079]

[0080] In which "a" is a whole number from 3 to 10. Preferably "a" is a whole number from 4 to 8. More preferably "a" is 6. "M" is selected from one or more of the group comprising hydrogen and an alkali metal. Preferred alkali metals comprise one or both of Na and K, more preferably Na.

[0081] For the avoidance of doubt, the one or more cyclic polyphosphates of formula (II) are defined by the repeat unit [-P(=O)(OM)-O-], with the term 'a' representing the number of repeat units present. The arc joining the two free bonds of the repeat unit of formula (II) is intended to represent the cyclic nature of the polyphosphate. The cyclic polyphosphate may thus be represented by the formulaa(PO3)a- Thus, when "a" = 6, a hexametaphosphate is provided.

[0082] Preferably, the one or more cyclic polyphosphates comprise sodium hexametaphosphate.

[0083] The one or more cyclic polyphosphates may be present in the dissolvable strip or film in a total amount of from about 2% to about 9% by weight of the dissolvable strip or film. Preferably the one or more cyclic polyphosphates may be present in a total amount of from about 3% to about 8% by weight of the dissolvable strip or film. More preferably 3% to 4% by weight of the dissolvable strip or film. Stillmore preferably, the one or more cyclic polyphosphates may be present in a total amount of about 3.5% by weight of the dissolvable strip or film.

[0084] In one embodiment, the one or more polyphosphates may further comprise one or more linear polyphosphates. The one or more linear polyphosphates may comprise a compound of formula (III):

[0085]

[0086] in which "b" is a whole number from 2 to 5. Preferably "b" is 3 or 4. Still more preferably, "b" is 3. "M" is selected from one or more of the group comprising hydrogen and an alkali metal. Preferred alkali metals comprise one or both of Na and K, more preferably Na.

[0087] For the avoidance of doubt, substituent "M" of formulae (II) and (III) may be selected independently, although in a preferred embodiment they may be the same, such as Na.

[0088] For the avoidance of doubt, the one or more linear polyphosphates of formula (III) are defined by the repeat unit [-P(=O)(OM)-O-], with the term 'b' representing the number of repeat units present. The linear polyphosphate may thus be represented by the formula Mb+2O(PC>3)b. Thus, when "b" = 3, a tripolyphosphate is provided.

[0089] Preferably, the one or more linear polyphosphates are selected from the group comprising sodium dipolyphosphate, sodium tripolyphosphate and sodium tertrapolyphosphate. More preferably, the one or more linear polyphosphates comprises sodium tripolyphosphate.

[0090] The one or more linear polyphosphates may be present in the dissolvable strip or film in a total amount of from 2% to 9% by weight of the dissolvable strip or film. Preferably the one or more linear polyphosphates may be present in a total amount of from 3% to 8% by weight of the dissolvable strip or film. More preferably the one or more linear polyphosphates may be present in a total amount of from 3% to 4% by weight of the dissolvable strip or film. Still more preferably, the one or more linearpolyphosphates may be present in a total amount of about 3.5% by weight of the dissolvable strip or film.

[0091] In a preferred embodiment, the one or more polyphosphates comprise sodium hexametaphosphate and sodium tripolyphosphate. Preferably sodium hexametaphosphate is present in the dissolvable strip or film in an amount of from 2% to 9% by weight of the dissolvable strip or film and sodium tripolyphosphate is present in an amount of from 2% to 9% by weight of the dissolvable strip or film. More preferably sodium hexametaphosphate is present in an amount of from 3% to 8% by weight of the dissolvable strip or film and sodium tripolyphosphate is present in an amount of from 3% to 8% by weight of the dissolvable strip or film. Still more preferably sodium hexametaphosphate is present in an amount of from 3% to 6% by weight of the dissolvable strip or film and sodium tripolyphosphate is present in an amount of from 3% to 6% by weight of the dissolvable strip or film. Still more preferably, the one or more cyclic polyphosphates and the one or more linear polyphosphates may each be present in a total amount of about 3.5% by weight of the dissolvable strip or film to provide a total polyphosphate content of 7% by weight of the dissolvable strip or film.

[0092] Where the dissolvable strip or film of the present invention comprises a complex of hydrogen peroxide with polyvinylpyrrolidone (PVP) as an optional whitening agent, a preferred source is Peroxydone K-30®. The hydrogen peroxide is complexed with the polymer (e.g. PVP), so an increase in the content of hydrogen peroxide (H2O2) in the formulation is accompanied by an increase in PVP / Polymer component of the strip or film. Utilisation of hydrogen peroxide in a complexed form with PVP has the advantage that it may act as a whitening agent and a film forming agent at the same time, reducing the need to add a separate film forming polymer, or in other embodiments, removing the need for further film forming polymers entirely.

[0093] An advantage of using the hydrogen peroxide / PVP complex is that a higher percentage of hydrogen peroxide (H2O2) remains in the strip or film post-manufacture than would be the case if the strip or film were comprised of a formulation consisting of PVP and hydrogen peroxide added separately. This appears to be due to a greater stability of the complexed composition versus the non-complexed composition when exposed to the drying process required to make thin films. In an alternative embodiment, the strip or film of the present invention may comprise PVP as a separate agent to liquid peroxide. These agents may therefore be used as separate source materials during the method of manufacturing the strip or film of the present invention.Plasticiser may be used to ensure acceptable physical properties of the strip or film of the present invention. Other ingredients such as colouring and flavouring agents may be chosen to ensure acceptable appearance and taste respectively.

[0094] The present invention may also provide strips or films with selective dissolution time, such that the formulation may be adapted to extend or shorten the amount of time it takes for said strip or film to dissolve in the oral cavity of the user. The dissolution time may be adjusted through adjusting the thickness of the strip or film and / or by adding dissolution extending agents.

[0095] Advantageously, the dissolution time can be tailored to provide optimal treatment times of the proteolytic enzyme, and optional additional whitening agents, relative to the concentrations of those agents within the strip or film. This therefore optimises the treatment efficacy of the active agents on the teeth of the user when the strip or film is in use within the oral cavity.

[0096] The dissolvable or substantially dissolvable teeth whitening strip or film may be adapted to dissolve completely or substantially completely when used in an oral cavity of a user over a period of: 15 to 30 minutes; 30 to 60 minutes; 30 minutes to 2 hours; 1 to 5 hours; 1 to 10 hours; or 1 to 22 hours. Most preferably, the dissolvable or substantially dissolvable teeth whitening strip or film may be adapted to dissolve completely or substantially completely when used in an oral cavity of a user over a period of 15 to 30 minutes.

[0097] It has also been found that the addition of additional components such as polycarbophils (such as Noveon®) may be used to adjust a dissolution time for the strip or film. Noveon® is a synthetic polymer of polyacrylic acid cross-linked with divinyl glycol.

[0098] The dissolvable or substantially dissolvable teeth whitening strip or film may have a thickness ranging from: about 50 pm to about 500 pm; about 50 pm to about 250 pm; about 50 pm to about 100 pm; or about 100 pm to about 200 pm.

[0099] The dissolvable or substantially dissolvable teeth whitening strip or film may have a length of: from 10 to 100mm; or 40 to 70 mm; or more preferably from 50 to 60 mm.

[0100] The dissolvable or substantially dissolvable teeth whitening strip or film may have a width of: from 8 to 20 mm; or more preferably from 10 to 15 mm.The dissolvable or substantially dissolvable teeth whitening strip or film may further comprise water. The water may be present in the film in an amount of less than about 15 wt.%, particularly from about 0.1 wt.% to 15 wt.%. Typically, the tooth whitening film may further comprise water in an amount of from about 3 wt.% to 12 wt.%, preferably from about 5 wt.% to 10 wt.% by weight of the strip or film.

[0101] The dissolvable or substantially dissolvable teeth whitening strip or film may further comprise one or more further components selected from any one of or combination of the group comprising: colourant; gelling agent; flavouring; sweetener; acidifier; antioxidant and chelating agent.

[0102] The dissolvable or substantially dissolvable teeth whitening strip or film is defined in terms of the dry weight of the film i.e. the weight of components dried to exclude water, expressed as percentages (i.e. wt.%) by total dry weight of the film alone i.e. without any backing sheet or support.

[0103] The dissolvable or substantially dissolvable teeth whitening strip or film is flexible such that it is mouldable to, and can adopt the surface shape of the teeth.

[0104] The strip or film is dissolvable, such that it dissolves completely or substantially completely within the oral cavity of a user.

[0105] The dissolvable or substantially dissolvable teeth whitening strip or film may comprise one or more water soluble film-forming polymers. The water soluble film-forming polymer provides structure to the film and may control the release of the whitening agents during tooth whitening. As used herein, a "water soluble" polymer is one in which one gram of polymer is soluble in 30 g or less of water. For instance, a polymer may be water soluble if 1 g of polymer is soluble in 25 g water.

[0106] The one or more water soluble film-forming polymers may be one or more selected from the group comprising: a polyvinyl pyrrolidone (such as Peroxydone®, Luviskol® or Plasdone®); polyacrylic acid or a salt thereof; pullulan; pectin; starch; dextrin; chitosan; alginic acid; salts of alginic acid and / or cellulose derivatives.

[0107] Preferably the water soluble film-forming polymer may be selected from the group comprising any one of or combination of the following: polyvinyl pyrrolidone; pullulan; pectin; starch; carboxyalkyl cellulose or a salt thereof; hydroxyalkyl cellulose or a salt thereof, in which the alkyl group isindependently selected from Ci-5alkyl, alginic acid, salt of alginic acid, polyalkylene glycol in which the alkylene group has 2 or 3 carbon atoms and copolymers thereof, polyacrylic acid or a salt thereof and combinations thereof.

[0108] More preferably, the water soluble film-forming polymer comprises a water soluble film-forming polymer selected from any one of or combination of the following: polyvinyl pyrrolidone; pullulan; or pectin.

[0109] The polyvinyl pyrrolidone may be selected from any one of or combination of the following: 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.

[0110] The polyvinyl pyrrolidone may have a weight average molecular weight in the range of from 10,000 to 1,500,000. Preferably, the polyvinyl pyrrolidone may have a weight average molecular weight in the range of from: 10,000 to 200,000; or 10,000 to 100,000; or 20,000 to 80,000; or 30,000 to 70,000; or 1,000,000 to 1,500,000. Still more preferably, the polyvinyl pyrrolidone may preferably have a weight average molecular weight of 58,000. Such a molecular weight PVP may be provided as Peroxydone K-30®. Alternatively, the polyvinyl pyrrolidone may preferably have a weight average molecular weight of 1,300,000. Such a molecular weight PVP may be provided as Plasdone K-90®. Alternatively, the PVP may be provided as a combination of two different weight average molecular weight PVP.

[0111] The hydroxyalkyl cellulose may be one or both of hydroxyethyl cellulose and hydroxypropyl cellulose. With regard to the hydroxyalkyl alkyl cellulose, the hydroxyalkyl group may be independently selected from hydroxyethyl and hydroxypropyl while the alkyl cellulose may be independently selected from the group comprising methyl cellulose, ethyl cellulose and propyl cellulose. Preferably, the hydroxyalkyl cellulose is hydroxypropyl cellulose. Suitable hydroxypropyl cellulose is sold under the trade name Klucel’by Ashland.

[0112] The carboxyalkyl cellulose or a salt thereof many be carboxymethyl cellulose or an alkali metal salt thereof, such as sodium. Preferably the carboxyalkyl cellulose salt is sodium carboxymethyl cellulose. Suitable sodium carboxymethyl cellulose is sold under the trade name Blanose® by Hercules Inc.Certain water soluble film-forming polymers may also function as adhesives, aiding attachment of the tooth whitening film to one or more teeth. Such adhesive water soluble film-forming polymers may be one or more selected from the group comprising: polyvinyl pyrrolidone, a carboxyalkyl cellulose, a salt of carboxyalkyl cellulose, carbomer, dextrin, chitosan and polyethylene glycol. Polyethylene glycol, also known as polyethylene oxide, is a preferred adhesive water soluble film-forming polymer.

[0113] The one or more film forming polymers may be present in the film in a total amount of from about 40 wt.% to about 95 wt.% of the dissolvable strip or film. Preferably, the one or more film forming polymers may be present in a total amount of from about 60 wt.% to about 90 wt.% of the dissolvable strip or film. More preferably, the one or more film forming polymers may be present in a total amount of from about 70 wt.% to about 85 wt.% of the dissolvable strip or film. Still more preferably, the one or more film forming polymers may be present in a total amount of from about 75 wt.% to about 80 wt.% of the dissolvable strip or film.

[0114] The dissolvable or substantially dissolvable teeth whitening strip or film may comprise one or more plasticizers. Preferably the plasticizer should be a physiologically acceptable plasticizer.

[0115] The one or more plasticizers may be selected from the group comprising any one of or combination of the following: a polyol such as glycerol; polyalkylene glycol in which the alkylene groups are independently selected from from Ci-5alkylene, polyalkylene glycol monomethyl ether in which the alkylene groups are independently selected from from Ci-5alkylene, monosaccharide, oligosaccharide, sorbital and sorbitan, preferably ethylene or propylene. Preferred polyalkylene glycols are one or both of polyethylene glycol and polypropylene glycol. A preferred polyalkylene glycol monomethyl ether is polyethylene glycol monomethyl ether.

[0116] The plasticizer may be 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, sorbital and sorbitan. The preferred plasticizer is glycerol.

[0117] The one or more plasticizers may be present in the film in a total amount of from about 0.1 wt.% to about 15 wt.% by weight. Preferably the one or plasticizers may be present in a total amount of from about 1 wt.% to about 15 wt.% by weight. More preferably, the one or plasticizers may be present in the film in a total amount of from about 3 wt.% to about 12 wt.% by weight. Most preferably, the one or plasticizers may be present in the film in a total amount of from about 8 wt.% to about 12 wt.% by weight of the dissolvable strip or film.The dissolvable or substantially dissolvable teeth whitening strip or film may comprise one or more emulsifiers. The one or more emulsifiers may be selected from ionic emulsifiers and non-ionic emulsifiers.

[0118] Preferably the non-ionic emulsifier is selected from the group comprising a saturated fatty acid derivative, a lecithin (such as soy lecithin) or a polysorbate (such as Polysorbate 80). The fatty acids may be saturated or unsaturated. More preferably the non-ionic emulsifier comprises one or both of 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 or a polysorbate.

[0119] Polysorbates are polyethoxylated esters of sorbital, sorbitans and isosorbide. Preferred saturated fatty acid derivatives include sucrose esters of saturated fatty acids; mono-, di- or tri-glycerides of saturated fatty acids; or sorbitan esters of saturated fatty acids. A preferred emulsifier is Sorbital, such as T80® supplied by Azelis.

[0120] The one or more emulsifiers may be present in the dissolvable or substantially dissolvable teeth whitening strip or film in a total amount of from: about 0.1 wt.% to about 10.0% wt.%; preferably in the range of from about 1.0 wt.% to about 6.0 wt.%; or more preferably 1.5 wt.% to 4.5 wt.% of the dissolvable or substantially dissolvable teeth whitening strip or film.

[0121] The dissolvable teeth whitening strip or film may further comprise one or more optional components selected from the group comprising any one of or combination of following: colourant, gelling agent, flavouring, sweetener, and / or anti-malodour agent.

[0122] Where the dissolvable teeth whitening strip or film of the present invention optionally further comprises anti-malodour agents, these may include: Zinc acetate and / or other zinc salts; Cetyl pyridinium chloride; chlorohexidine; triclosan or any combination thereof.

[0123] The gelling agent may be a hydrocolloid. Typically, the gelling agent may be a hydrocolloid which also functions as an adhesive agent. As used herein, the term "hydrocolloid" means a hydrophilic polymer, which may be of any origin such as plant, animal, microbial or synthetic, 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. The hydrocolloid adhesive agent may beselected from a natural gum, a polyacrylic acid or a poly alkylacrylic acid in which the alkyl group is methyl or ethyl. The alkyl group may be methyl or ethyl i.e. poly methacrylic acid or poly ethacrylic acid. The natural gum may be selected from alginic acid and its salts, agar, carrageenan, tragacanth and polysaccharide gums. More preferably, when the hydrocolloid gelling agent is a natural gum, it is tragacanth gum comprising a mixture of water-soluble and water-insoluble polymers, particularly polysaccharides, such as a mixture of tragacanthin and bassorin polymers. The bassorin polymer may be a polymer of fucose, xylose, arabinose, galacturonic acid and rhamnose.

[0124] Alternatively, the hydrocolloid adhesive agent 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.

[0125] The polyacrylic acid may be provided as a salt, such as an ammonium, sodium, potassium, magnesium or calcium salt. Cross-linked polyacrylic acid, such as those cross-linked with divinyl glycol may be provided as salts such as magnesium or calcium salts, particularly calcium salts, also known as polycarbophils. Suitable polycarbophils are sold under the trade name Noveo® by Lubrizol Corporation.

[0126] The gelling agent may be present in a range of from about 0.1 wt.% to 10 wt.% of the dissolvable teeth whitening strip or film.

[0127] The flavouring may be an artificial flavouring or a natural flavouring. The flavouring may be selected from the group comprising menthol, peppermint and an alkyl alkanoate, in which the alkyl group may be straight chained or branched and may comprise from 1 to 8 carbon atoms, and the alkanoate group may comprise from 1 to 5 carbon atoms. Preferably the alkyl group of the alkyl alkanoate has 1, 2, 5 or 8 carbon atoms and the alkanoate group of the alkyl alkanoate may comprise from 1 to 5 carbon atoms, preferably 1, 4 or 5 carbon atoms. Preferred alkyl alkanoates are methyl butyrate [apple / pineapple], ethyl butyrate [orange / pineapple], iosamyl acetate [banana / pear], pentyl butyrate [pear / apricot], pentyl pentanoate [apple], octyl acetate [orange].Peppermint is preferred in the teeth whitening strip or film. Peppermint flavouring contains menthol as well as other components such as menthone, menthofuran, cineol, pulegone, together with some lesser ingredients.

[0128] Preferably the flavouring agent is present in a proportion of from about 0.1 wt.% to about 10 wt.% by dry weight of the teeth whitening strip or film, more preferably from 1 wt.% to 5 wt.% by dry weight of the teeth whitening strip or film.

[0129] The sweetener may be a sugar substitute, such as an artificial sugar substitute or a natural sugar substitute. An artificial sugar substitute may be one or more selected from the group comprising sucralose and cyclamate aspartame, advantame, saccharin, acesulfame potassium. A natural sugar substitute may be selected from the group comprising stevia, erythritol, mannitol, sorbital and xylitol. Preferably the sweetener is sucralose.

[0130] Preferably the sweetener is present in a proportion of from about 0.01 wt.% to about 5 wt.% by dry weight of the teeth whitening strip or film. More preferably the acidifier is present in a proportion of from 0.05 wt.% to 0.5 wt.% by dry weight of the teeth whitening strip or film.

[0131] A preservative may also be present in the tooth whitening film. Typical preservatives may be one or more compounds selected from the group comprising potassium sorbate, benzoic acid and its salts, propionic acid and its salts, salicylic acid and its salts and triclosan.

[0132] Preferably the preservative is present in a proportion of from about 0.01 wt.% to about 5 wt.% by dry weight of the teeth whitening strip or film. More preferably the preservative is present in a proportion of from 0.05 wt.% to 0.5 wt.% by dry weight of the teeth whitening strip or film.

[0133] Also disclosed herein is a process for the manufacture of a dissolvable or substantially dissolvable teeth whitening strip or film. The film does not require the presence of further layers, such as barrier layers or supporting substrates.

[0134] The dissolvable teeth whitening strip or film is prepared from an aqueous tooth whitening liquid. The aqueous tooth whitening liquid is a mixture of the components of the dissolvable teeth whitening strip or film with water.The proteolytic enzyme (such as papain and / or bromelain), optional further whitening agents (hydrogen peroxide; and / or a complex of hydrogen peroxide and PVP; and / or PAP) and water soluble film-forming polymer components of the dissolvable teeth whitening strip or film can be mixed with water to provide an aqueous tooth whitening liquid. The water is typically potable water. Distilled or de-ionised water may also be used. Preferably, the components are added to water under shear.

[0135] The mixing step may further comprise the addition of one or more further components of the dissolvable teeth whitening strip or film. The one or more further components may be selected from one or more of the group comprising colourant, gelling agent, flavouring, sweetener, acidifier, antioxidant and chelating agent.

[0136] The mixing step may therefore comprise mixing a proteolytic enzyme (such as papain and / or bromelain) in a total amount of about 0.1% to about 10% by weight; one or more water soluble filmforming polymers in a total amount of about 30% to about 95% by weight; one or more plasticizers in a total amount of about 0.1% to about 15% by weight; and one or more emulsifiers in a total amount of about 0.1% to about 10% by weight; with water to provide an aqueous teeth whitening liquid.

[0137] The mixing step may also further comprise mixing an additional whitening agent, such as hydrogen peroxide, a complex of hydrogen peroxide with PVP, or PAP. Therefore, the mixing step may comprise mixing the proteolytic enzyme (such as papain and / or bromelain) with hydrogen peroxide and / or a hydrogen peroxide-polyvinyl pyrrolidone complex (such as Peroxydone®) and / or PAP (such as Eureco HCP11®). The mixing step may therefore comprise mixing a proteolytic enzyme (such as papain and / or bromelain) in a total amount of about 0.1% to about 10% by weight; hydrogen peroxide and / or a hydrogen peroxide-polyvinyl pyrrolidone complex in a total amount of about one or more water soluble film-forming polymers in a total amount of about 30% to about 95% by weight; one or more plasticizers in a total amount of about 0.1% to about 15% by weight; and one or more emulsifiers in a total amount of about 0.1% to about 10% by weight; with water to provide an aqueous teeth whitening liquid.

[0138] The mixing parameters, such as shear force and duration, will be dependent upon the scale of the process of manufacture, as well as the component of the dissolvable teeth whitening strip or film to be mixed. This in turn will affect the choice of equipment to be employed in the mixing step.Typically, the mixing step is initiated by adding a water soluble film-forming polymer and plasticizer into the water together with any optional gelling agent, further polymers or gums. Typically, any acidifier and any optional further components such as colourant, sweetener or other low level additives also will be added at this stage. The water soluble film-forming polymer and any other polymeric components or gums will be added in an order which prevents an early excessive viscosity build, i.e. the polymers or gums which produce the lowest viscosity build will be added first. Typically, any flavours will be mixed at the latter stages to prevent any degradation of thermally sensitive components or the loss of volatile components. At the laboratory scale, should a non-hydrogen peroxide bleaching agent, such as a peroxy carboxylic acid, particularly such as a complex of PAP and polysaccharide such as dextrin, be incorporated into the dissolvable teeth whitening strip or film, it can be incorporated near the end of mixing to prevent unnecessary exposure to heat which may result in degradation. At the industrial scale, the build-up of heat during mixing is significantly reduced, and so the non-hydrogen peroxide bleaching agent, can be added at any point in the mixing step.

[0139] A laboratory scale process may involve a batch size in the range of from 50 g to 10 kg. Suitable mixing apparatus for such laboratory scale batch sizes include bench-top homogenisers such as those by Silverson Machines Ltd. or IKA England LTD and overhead stirrers, such as those by IKA England LTD. An industrial scale process may involve a batch size of greater than 10 kg, such as a batch size in the range of from 15 kg to 40 kg or more. Suitable mixing apparatus for such industrial scale batch sizes include an industrial bowl cutting machine, such as those by Kilia (Fleischerei- und Spezial-Maschinen-Fabrik GmbH).

[0140] For example, the proteolytic enzyme (such as papain and / or bromelain) and optional further whitening agents (hydrogen peroxide; and / or a complex of hydrogen peroxide and PVP; and / or PAP), can be mixed at a shear rate in the range of from 1000 to 6000 rpm. For smaller quantities on a laboratory scale, the shear rate may be in a range of from 2000 to 6000 rpm, preferably in a range of from 3000 to 4000 rpm. For larger quantities on an industrial scale, the shear rate may be in a range of from 1500 to 2500 rpm, preferably approximately 2000 rpm. The mixing time for smaller quantities on a laboratory scale can be in a range of from 5 to 20minutes, preferably from 5 to 10 minutes. For larger quantities on an industrial scale, the mixing time may be in a range of from 10 to 20 minutes, preferably approximately 15 minutes.Once the components are mixed with water to provide the aqueous tooth whitening liquid, it may be applied to a substrate. The aqueous tooth whitening liquid may be applied by known film-forming processes, such as dipping, spraying, knife over roller casting, extrusion and injection moulding.

[0141] A casting device may be used to apply the aqueous tooth whitening 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 liquid.

[0142] The spreader distributes the aqueous tooth whitening liquid homogeneously over a substrate and controls the thickness profile of the film. The spreader typically has a slot through which the aqueous tooth whitening 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 tooth whitening liquid is maintained at a constant temperature to ensure a constant viscosity and therefore homogenous thickness distribution of the resulting film.

[0143] 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 (PTFE) films. Preferably the substrate comprises paper, paper coated with a release layer such as silicone, polyethylene, polypropylene, polytetrafluoroethylene (PTFE) or a polyester such as polyethylene terephthalate (PET), particularly siliconized PET films.

[0144] The aqueous tooth whitening liquid carried on the substrate can then be dried. Exemplary drying methods include indirect heating, heating by radiation and air stream drying.

[0145] In one embodiment, an air feed stream with no or a low moisture content is directed towards the aqueous tooth whitening 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.It is possible to dry both surfaces of the aqueous tooth whitening liquid on the substrate. This can be achieved by looping the drying tooth whitening film around a series of polished rollers and directing air feed streams to each exposed surface in turn.

[0146] The air feed stream may be at ambient temperature. Alternatively, the air feed stream may be a heated air feed stream. Where a bleaching agent, such as PAP, has been incorporated into the invention, said PAP melts above 75°C and the chemical degrades with the evolution of carbon dioxide to a-phthalimido pentanol, such that the heated air stream should have a temperature below 60°C. Preferably, the heated air feed stream may have a temperature in the range of from greater than ambient to 60°C. More preferably, the heated airstream may have a temperature in the range of from 25°C to 55°C, still more preferably in the range of from 45 to 55°C. The heating may be carried out in a belt heater with a belt speed in the range of from 0.2 to 2.0 m / min, and preferably at a speed in the range of from 0.5 to 1.5 m / min.

[0147] Alternatively, heated rollers or radiative heaters such as infra-red lamps may be used to dry the aqueous liquid to provide the dissolvable teeth whitening strip or film of the present invention. These may heat the aqueous tooth whitening liquid carried on the substrate to a temperature in the range of from greater than ambient to 60°C, preferably to a temperature in the range of from 25°C to 55°C.

[0148] The drying step may comprise first drying of a first surface of the aqueous tooth whitening liquid carried on the substrate to provide a first dried tooth whitening film carried on the substrate. The first surface of the aqueous tooth whitening liquid may be the outer surface of the liquid opposite to a second surface adjacent to the support. The first dried tooth whitening film may then be separated from the substrate. The second surface of the first dried tooth whitening film may then be second dried to provide a second dried tooth whitening film. The first and second drying may be independently carried out as discussed above.

[0149] In this way, a dissolvable teeth whitening strip or film can be provided which comprises less than 15% water by dry weight of the film. The water content is preferably in a range of from 3 to 12% by dry weight of the film, more preferably in a range of from 5 to 10% by dry weight of the film and even more preferably in a range of from 5 to 7% by dry weight of the film.

[0150] The dissolvable teeth whitening strip or 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 dissolvable teeth whitening strip or film may be stored in sterile packaging, such as a sealed packet. The sealed packet may be water tight, and more preferably water and air tight. The packet may be made of a metallic foil such as aluminium foil, or a plastic film coated with a metallic layer.

[0151] The dissolvable teeth whitening strip or film obtainable by the method disclosed herein may be used in a method of bleaching teeth. The method may comprise at least the step of:

[0152] applying the dissolvable teeth whitening strip or film, obtained as described herein, to one or more teeth of a subject.

[0153] The method may be a solely cosmetic method. As used herein, "solely cosmetic method" means a cosmetic method which does not encompass the treatment or prevention of a medical condition.

[0154] In the method, dissolvable teeth whitening strip or film may first be released from its sterile packaging. Subsequently, any support is removed, for instance by peeling dissolvable teeth whitening strip or film from the support. Once the dissolvable teeth whitening strip or 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 whiten their teeth.

[0155] The dissolvable teeth whitening strip or film provides good adhesion to tooth surfaces so that the proteolytic enzyme (such as papain and / or bromelain), and optional further whitening agents (hydrogen peroxide; and / or a complex of hydrogen peroxide and PVP; and / or PAP), can act upon a tooth or teeth, while also dissolving in the oral cavity during bleaching such that subsequent removal of the film by the subject is not required. For instance, the tooth whitening film may adhere to a tooth or teeth within 10 seconds of contact. Adhesion may occur by the action of saliva on the PVP and / or film forming component of the film, rendering it tacky, or may be as a result of the presence of an adhesive water soluble polymer. The tooth whitening film can adhere to a tooth or teeth for at least 15 minutes after contact.

[0156] The tooth whitening 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 which the film disintegrates in the oral cavity due to the water solubility of the water soluble filmforming polymer component. Consequently, it is not necessary for the subject to remove the tooth whitening film after use.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.

[0157] 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".

[0158] 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.

[0159] 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.

[0160] As used herein, the term 'saturated' refers to an organic compound or group which does not contain any carbon-carbon bonds which are double, triple or aromatic bonds. Analogously, the term 'unsaturated' refers to an organic compound or group which contains one or more carbon-carbon bonds which are double, triple or aromatic bonds. In this context, the terms 'saturation' and 'unsaturation' do not refer to bonds between a carbon atom and a heteroatom, such as nitrogen and oxygen, such that for instance an organic compound having a carbonyl group may fall within the definition of an unsaturated organic compound.

[0161] As used herein, the term "peroxy carboxylic acid" refers to an organic compound comprising a -C(=O)-O-O-H group.

[0162] As used herein, the term "alkyl" refers to a monovalent alkane produced by the removal of a hydrogen atom. Preferably, the alkyl is a Ci-5alkyl, more preferable a C1-3 alkyl.

[0163] Certain aspects and embodiments of the invention will now be illustrated by way of example and with reference to the following tables and the figures.

[0164] 1Examples

[0165] The present invention may be exemplified as follows and the components of the respective examples are detailed below.

[0166] Eureco HC-P11® is an 11 wt.% PAP non-hydrogen peroxide bleaching agent complex with p-cyclodextrin supplied by Solvay.

[0167] Peroxydone K-30® is a dental bleaching agent formed from a complex of 17-20 wt.% hydrogen peroxide and polyvinyl pyrrolidone having a molecular weight of 58,000 supplied by Ashland Inc. Peroxydone K-90® is a dental bleaching agent formed from a complex of 16-20 wt.% hydrogen peroxide and polyvinyl pyrrolidone having a molecular weight of 1,300,000 supplied by Ashland Pectin is a polysaccharide water soluble film-forming polymer supplied by CP Kelco.

[0168] Glycerol is a plasticiser is supplied by Brenntag.

[0169] Polysorbate 80® is an emulsifier also known as Sorbital T80® and is supplied by Azelis.

[0170] Peppermint is a flavouring supplied by IMCD.

[0171] Sucralose is a sweetener supplied by Azelis.

[0172] Sodium tripolyphospate (STPP) is a linear polyphosphate supplied by Brenntag.

[0173] Sodium hexametaphosphate (SHMP) is a cyclic polyphosphate supplied by Brenntag.

[0174] Pullulan is a neutral, simple polysaccharide produced by the growth of Aureobasidium pullulans. Hydroxyapatite is a synthetic or natural powder with the chemical formula Caio (PCUMOH . The powder can be either a micro or nano-particle.

[0175] Luviskol® (also known as Kollidon® 90 F) is a polyvinyl pyrrolidone water soluble film-forming polymer having a weight average molecular weight in the range of from 100,000 to 150,000 supplied by BASF.

[0176] Hydrogen peroxide is an aqueous solution of approximately 35% concentration.

[0177] Soy Lecithin is an emulsifier / surfactant used to stabilise dispersions.

[0178] Papain is an extract from the papaya fruit.

[0179] Bromelain is an extract from the pineapples.

[0180] Whitening Studies

[0181] In each whitening study, for each sample, three hydroxyapatite discs were stained and treated. Three disks also acted as a control and underwent all stages of the whitening study, but were not treated with any samples. A total of 7 treatments were carried out with colour measurements taken after 3 and 7 treatments.First Whitening Study - Example 1

[0182] Table 1 shows the formulations of the teeth whitening strips that were used in a first whitening study of Figure 1. Figure 1 is a bar chart showing treatment number vs AE for several whitening formulations comprising hydrogen peroxide. AE represents the overall colour change of test substrates. A higher value indicates a larger shift from starting point (stained test substrate) to lighter / whiter test substrate.

[0183] Table 1 - Dental whitening film formulations for whitening study of Figure 1

[0184]

[0185] Table 2: Change in colour (AE) of samples after treatment with dental whitening film formulations of the whitening study of Figure 1

[0186]

[0187]

[0188] From this whitening study (represented in Figures 1), it can be observed that the addition of 2 wt.% and 4 wt.% papain into a 6 wt.% hydrogen peroxide strip shows increased whitening efficacy (AE) after 3 and 7 treatments compared to the non-papain containing hydrogen peroxide strips.

[0189] It can be observed that when a whitening strip in accordance with the present invention comprises 2 wt.% papain in combination with hydrogen peroxide (DEV05602), it exhibits improved whitening (AE) over hydrogen peroxide only strips (DEV05599), both after 3 treatments and 7 treatments (4.0 and 7.5 vs 3.7 and 6.6 respectively).

[0190] When polyphosphates are added to the hydrogen peroxide strip (DEV05632 - 6% H2O2 + [P]3) and to the 2 wt.% papain + hydrogen peroxide strip (DEV05618 - 6% H2O2 + [P]3+ 2% papain), a significant increase in AE is observed in each sample after 7 treatments. However, the 2 wt.% papain strip (DEV05618) significantly outperforms the non-papain strip (DEV05632) after both 3 and 7 treatments (5.0 and 15.7 vs 3.0 and 13.0 respectively).

[0191] The same effect is observed for the 4 wt.% papain + hydrogen peroxide strips (DEV05607 and DEV05619) vs non-papain containing hydrogen peroxide strips (DEV05599 and DEV05632). Specifically, it can be observed that when a whitening strip in accordance with the present invention comprises 4 wt.% papain in combination with hydrogen peroxide (DEV05607), it exhibits improved whitening (AE) over hydrogen peroxide only strips (DEV05599), both after 3 treatments and 7 treatments. The improvement is most significant after 7 treatments (4.9 and 9.8 vs 3.7 and 6.6 respectively).

[0192] When polyphosphates are added to the hydrogen peroxide strip (DEV05632 - 6% H2O2 + [P]3) and to the 4 wt.% papain + hydrogen peroxide strip (DEV05619 - 6% H2O2 + [P]3+ 4% papain), a significant increase in AE is observed in each sample after 7 treatments. However, the 4 wt.% papain strip (DEV05619) significantly outperforms the non-papain strip (DEV05632) after 3 treatments (8.0 vs 3.0).The 4 wt.% papain strip (DEV05619) provides enhanced whitening over the non-papain strip (DEV05632) after 7 treatments (13.3 vs 13.0 respectively).

[0193] There is therefore a surprising technical effect that an increase in papain content from 2 wt.% to 4 wt.% gives a significant change in AE after 3 treatments. However, after 7 treatments, the AE for the 4 wt.% papain strip + hydrogen peroxide + polyphosphates (DEV05619) is actually less in this embodiment than the 2 wt.% papain strip + hydrogen peroxide + polyphosphates (DEV05618). Accordingly, an unexpected technical effect of a high papain content strip (for example, 4 wt.% papain) is that it provides an increased rate of whitening vs a lower papain containing strip (for example, 2 wt.% papain), but does not provide an overall increased change in AE after prolonged use (for example, after a 7 treatment course). Therefore, use of a high papain content strip (such as 4 wt.%) has the unexpected technical benefit that a rapid whitening strip is provided, exhibiting an increased rate of whitening over the lower papain containing strip.

[0194] Further, in providing a 4 wt.% papain whitening strip (DEV05619) that only needs 3 treatments to provide an improved whitening effect (AE 8.0) than that which can be achieved over 7 treatments with a hydrogen peroxide only strip (AE 6.6) allows the user to save money, as less whitening products are required per treatment cycle. Even further, the reduced number of treatments with hydrogen peroxide significantly reduces the likelihood of onset or severity of dental hypersensitivity (DH), or could even prevent DH entirely.

[0195] It can also be observed that the non-polyphosphate containing strips, comprising hydrogen peroxide + 2 wt.% papain (DEV05602) and 4 wt.% papain (DEV05607) provided enhanced whitening over the hydrogen peroxide only strip (DEV05599) after 3 and 7 treatments. They also provide enhanced whitening over the hydrogen peroxide + polyphosphate strip (DEV05632) after only 3 treatments.

[0196] It is also an unexpected technical effect that the combination of papain and polyphosphates would provide such an increase in the relative whitening capability of hydrogen peroxide. In this regard, both papain and polyphosphates have been shown to increase the whitening efficacy of hydrogen peroxide when used separately: see DEV05599 vs DEV05632 for hydrogen peroxide alone vs in combination with phosphates, providing AE 6.6 and 13.0 respectively after 7 treatments; and DEV05599 vs DEV05602 and DEV05599 for hydrogen peroxide alone vs in combination with 2 wt.% and 4 wt.% papain, providing AE 6.6, 7.5 and 9.8 respectively after 7 treatments. However, when the combinationof papain and phosphates is used, there is a synergistic whitening effect, that provides the significant increase in AE, providing AE 6.6, 15.7 and 13.3 respectively after 7 treatments.

[0197] Example 2

[0198] Table 3 below shows the formulations of the teeth whitening strips that were used in the first whitening study of Figure 2. Figure 2 is a bar chart of a whitening study, showing treatment number vs AE for several whitening formulation comprising PAP. The measurements from the whitening study are presented in Table 4.

[0199] Table 3 - Dental whitening film formulations for whitening study of Figure 2

[0200]

[0201] Table 4: Change in colour (AE) of samples after treatment with dental whitening film formulations of the whitening study of Figure 2

[0202]

[0203] From this whitening study (represented in Figure 2), it can be observed that the addition of 2 wt.% and 4 wt.% papain into a PAP strip (DEV05633 and DEV05634 respectively) shows increased whitening efficacy (AE) after 7 treatments compared to the non-papain containing PAP strip (DEV05638) (7.4 and 6.6 vs 3.3 respectively).

[0204] When polyphosphates are added to the PAP strip (DEV05627 - PAP + [P3]) and to the 2 wt.% papain + PAP strip (DEV05620 - PAP + 2% Papain + [P3]), a significant increase in AE is observed in each sample after 7 treatments (12.6 and 8.2 respectively). The 2 wt.% papain strip (DEV05620) significantly outperforms the non-papain strip (DEV05632) after 7 treatments, providing a significant overall improvement in whitening.

[0205] The same effect is observed for the 4 wt.% papain + PAP strips (DEV05634 and DEV05621) vs non-papain containing PAP strips (DEV05638 and DEV05627). Specifically, it can be observed that when a whitening strip in accordance with the present invention comprises 4 wt.% papain in combination with PAP (DEV05634), it exhibits significantly improved whitening (AE) over the PAP only strip (DEV05638) after 7 treatments. The improvement is most significant after 7 treatments (11.3 and 8.2 respectively).

[0206] When polyphosphates are added to the PAP strip (DEV05627 - PAP + [P3]) and to the 4 wt.% papain + PAP strip (DEV05621 - PAP + 4% Papain + [P3]), a significant increase in AE is observed in each sample after 7 treatments.The 4 wt.% papain strip + PAP + polyphosphates (DEV05621) provides significantly enhanced whitening over the 2 wt.% + PAP + polyphosphates (DEV05620) after 3 treatments (7.4 vs 3.9 respectively). This is therefore further exemplary of the surprising technical effect that the increase in papain content from 2 wt.% to 4 wt.% gives a significant change in AE after 3 treatments. However, after 7 treatments, the AE for the 4 wt.% papain strip + PAP + polyphosphates (DEV05621) is actually less than the 2 wt.% papain strip + hydrogen peroxide + polyphosphates (DEV05620). Accordingly, an unexpected technical effect of a high papain content strip (for example, 4 wt.% papain) is that it provides an increased rate of whitening vs a lower papain containing strip (for example, 2 wt.% papain), but does not provide an overall increased change in AE after prolonged use (for example, after a 7 treatment course). Therefore, use of a high papain contain strip has the unexpected technical benefit that a rapid whitening strip is provided, exhibiting an increased rate of whitening over the lower papain containing strip.

[0207] Further, in providing a 4 wt.% papain whitening strip that only needs 3 treatments to provide an improved whitening effect allows the user to save money, as less whitening products are required per treatment cycle. Even further, the reduced number of treatments reduces the likelihood of onset and severity of dental hypersensitivity (DH).

[0208] It can also be observed that the PAP + 2% Papain + polyphosphates strip (DEV05620) provided comparable whitening after 7 treatments to the 6% hydrogen peroxide + 2% Papain + polyphosphates strip (DEV05618), with AE 12.6 and 13.0 respectively. This is particularly surprising, as PAP alone is typically less effective than hydrogen peroxide. This therefore provides an alternative strip to hydrogen peroxide whitening strips, to further reduce the likelihood of DH. Further, some markets have strict limits on hydrogen peroxide content in strips, therefore, a PAP + papain based strip offers an alternative for such markets.

[0209] The PAP + 2% Papain + polyphosphates strip (DEV05620) also notably provided AE 6 units greater than that of the peroxide only strip after 7 treatments (AE6.6).

[0210] It is also an unexpected technical effect that the combination of papain and polyphosphates would provide such an increase in the relative whitening capability of PAP. In this regard, both papain and polyphosphates have been shown to increase the whitening efficacy of hydrogen peroxide when used separately: see DEV05638 vs DEV05627 for PAP alone vs in combination with phosphates, providing AE 3.3 and 8.2 respectively after 7 treatments; and DEV05638 vs DEV05633 and DEV05634 for PAPalone vs in combination with 2 wt.% and 4 wt.% papain, providing AE 3.3, 7.4 and 6.6 respectively after 7 treatments. However, when the combination of papain and phosphates is used, there is a synergistic whitening effect, that provides the significant increase in AE for the PAP containing strips, see DEV05638 vs DEV05620 and DEV05621, providing AE 3.3, 12.6 and 11.3 respectively after 7 treatments.Second Whitening Study - Example 3

[0211] Table 5 shows the formulations of teeth whitening strips that were used in a second whitening study of Figure 3. Figure 3 is a bar graph showing treatment number vs AE for whitening formulations comprising bromelain and / or papain. The measurements from the whitening study are presented in Table 6.

[0212] Table 5: Dental whitening film formulations of the whitening study of Figure 3

[0213]

[0214] Table 6: Change in colour (AE) of samples after treatment with dental whitening film formulations of the whitening study of Figure 3

[0215]

[0216] From this whitening study (Figure 3), it can be observed that whitening strips comprising 2 wt.% bromelain (DEV05752) or 2 wt.% papain (DEV05786), in the absence of polyphosphates, produced similar AE values after 7 treatments (AE values of 11.45 and 11.07 respectively). However, after only 3 treatments, the 2wt.% bromelain strip outperformed the papain strip by nearly 2AE units.

[0217] It was also observed that whitening strips comprising 4 wt.% papain (DEV05787) gave a AE value of 13.74 after 7 treatments, whilst a combination of 2 wt.% bromelain and 2 wt.% papain gave a AE value of 15.83 after 7 treatments. Therefore, in each case, there is an evident boost in whitening efficacy highlighted when compared to the placebo strip.

[0218] The combination of 2 wt.% bromelain and 2 wt.% papain (DEV05753) outperformed each of the 2 wt.% bromelain, 2 wt.% papain and 4 wt.% papain strips after 3 and 7 treatments. This is therefore indicative of a synergistic whitening effect. Regarding strips comprising proteolytic enzymes in combination with polyphosphates, following 3 and 7 treatments, the greatest AE values (14.99 and 20.55 respectively) were produced from discs treated with placebo films containing [P]3+ 2% bromelain (DEV05728). At both testing points, this formulation affords a greater whitening efficacy than placebo films containing bromelain and papain alone.Table 7 - Dental whitening film formulations for whitening study of Figure 4

[0219]

[0220] Table 8: Change in colour (AE) of samples after treatment with dental whitening film formulations of the whitening study of Figure 4

[0221]

[0222] The 2 wt.% bromelain and 2 wt.% papain combination strip (DEV05801) provided greater whitening efficacy after 3 and 7 treatments than that of the hydrogen peroxide only strip (DEV05798) and the 2 wt.% bromelain + hydrogen peroxide strip (DEV05800). The effect after 7 treatments is most notable, with the combination strip having a AE of 14.5, whilst DEV05798 and DEV05800 have AE values of 11.03 and 10.32 respectively.

[0223] This is indicative of a synergistic whitening effect when bromelain and papain are combined in a strip with hydrogen peroxide. This could also have the advantage of removing the need for further boosting agents, such as polyphosphates in hydrogen peroxide strips.

[0224] Discs treated with a combination of [P]3with the proteolytic enzymes papain and / or bromelain afford higher AE values than 6% H2O2 alone.Table 9 - Dental whitening film formulations for whitening study of Figure 5

[0225]

[0226] Table 10: Change in colour (AE) of samples after treatment with dental whitening film formulations of the whitening study of Figure 5

[0227]

[0228] After 7 treatments, discs treated with PAP + 2% bromelain afforded a higher AE value than discs treated with PAP only (AE values of 14.01 and 10.87 respectively).

[0229] Discs treated with PAP + [P]3outperformed all PAP formulations tested (AE value of 18.21), and the addition of proteolytic enzymes to PAP + [P]3strips afford similar AE values.Table 11 - Dental whitening film formulations for whitening study of Figure 6

[0230]

[0231] Table 12: Comparison of change in colour (AE) of samples after treatment with dental whitening film formulations of the present invention

[0232]

[0233] Discs treated with PAP or 6% H2O2 formulations containing proteolytic enzymes (in the absence of [P]3) afford a similar or enhanced whitening efficacy compared to discs treated with PAP or 6% H2O2 containing no proteolytic enzymes.

[0234] In this study, the most significant benefit in whitening efficacy displayed by the addition of proteolytic enzymes can be seen in discs treated with placebo strips. Placebo strips containing [P]3and 2% bromelain outperformed discs treated with PAP + [P]3and 6% H2O2 + [P]3. There is also an evident enhancement in the whitening properties of strips when both bromelain and papain are combined in a strip in the absence of [P]3. This is also true in 6% H2O2 strips. In both cases, bromelain and papain outperformed the presence of papain and / or bromelain alone.

[0235] In placebo strips, a combination of both 2% papain and 2% bromelain have a comparable AE value to 6% H2O2 +[P]3stirps. The introduction of enzymes can act as an alternative to [P]3. In placebo films, the addition bromelain and / or papain boosts whitening efficacy, with a combination of 2% bromelain and 2% papain being the optimum loading in strips with no [P]3, and 2% bromelain in strips containing [P]3.

[0236] Stability Studies

[0237] It is known that the presence of polyphosphates in peroxide containing strips negatively impacts the stability of the hydrogen peroxide in said strips.Strips according to one aspect of the present invention, comprising hydrogen peroxide in combination with proteolytic enzymes (bromelain and / or papain), have been subjected to accelerated ageing conditions so as to compare the stability of the peroxide content. For each formulation, the H2O2 content was determined by titration with potassium permanganate. Results were obtained for each batch after ageing at 2 weeks at 50°C, 75% RH, up to 3 months at 40°C, 75% RH and 3 months at 25°C / 60% RH (ambient) conditions. At every timepoint, the total loss in H2O2 content for each batch versus time 0 was calculated. The results are presented in Figure 7. Table 9 gives the batches tested in the stability study.

[0238] Table 9: Dental whitening film formulations for stability study of Figure 7

[0239]

[0240] The addition of 2% papain and bromelain into 6% H2O2 strips in place of polyphosphates does not significantly decrease the stability of the H2O2. After 3 months of accelerated ageing, the decrease in H2O2 amongst all strips containing no polyphosphates are comparable.At all timepoints, the most significant H2O2 loss is observed in 6% + polyphosphate strips, the greatest loss being 50.29%, observed after 3 months accelerated ageing.

[0241] However, the addition of the enzyme's bromelain and papain in the presence of polyphosphates reduces this loss. 6% + polyphosphates strips containing 2% bromelain and 2% papain have notably less H2O2 loss compared to 6% + polyphosphates strips containing no enzymes.

[0242] Accordingly, the addition of proteolytic enzymes to hydrogen peroxide containing strips according to the present invention does not accelerate H2O2 loss to the extent of polyphosphates, whilst greatly enhancing the whitening efficacy that may be imparted by the strip (see whitening studies). Therefore, the addition of bromelain and / or papain appear to be a successful alternative to polyphosphates for whitening efficacy boosting without jeopardising product stability.

[0243] Therefore, a particularly advantageous formulation of the present invention, comprises: hydrogen peroxide (1 to 10 wt.%); papain (1 to 5 wt.%) and / or bromelain (1 to 5 wt.%).

[0244] Surprisingly, the proteolytic enzymes also reduce H2O2 loss in the presence of polyphosphates, such that they may be combined to reduce the instability that may be imparted by polyphosphates, whilst still providing an overall enhancement to the whitening efficacy of the strip. The addition of bromelain and / or papain may therefore have an alternative function to diminish H2O2 loss in tooth whitening strips containing polyphosphates.

[0245] Therefore, a further particularly advantageous formulation of the present invention, comprises: hydrogen peroxide (1 to 10 wt.%); papain (1 to 5 wt.%) and / or bromelain (1 to 5 wt.%); and one or more polyphosphates (2 to 9 wt.%).

[0246] We now present data (in-vitro whitening studies) related to observed effects associated with the inclusion of a combination of both Bromelain and Papain (Enzymatic whitening agents) into a dissolving whitening strip.

[0247] In addition, formulations are presented that broaden the range of peroxide in strips from about 3-12%.Additionally an example formulation for a non-peroxide (PAP) strip that uses PVP as major film former is included alongside a peroxide strip that contains hydroxyapatite. Details of formulations used in in-vitro studies are also presented.

[0248] Whitening study

[0249] In-vitro study completed by Intertek. Human enamel blocks were polished, lightly etched, and stained using a tea- and coffee-based solution, then their baseline colour was recorded with a CM-700d spectrophotometer.

[0250] Samples received 28 thirty-minute applications of the assigned whitening strip, with colour re-measured at key timepoints. Changes in L*, a*, and b* values were used to calculate Delta E, and a pre-determined calibration allowed these Delta E values to be expressed as the number of VITA® Bleachedguide shades whitened.

[0251] Products tested during this study:

[0252] Table 10

[0253]

[0254] Results from whitening study are presented in Figure 8.

[0255] Figure 8 is a comparative study results from Intertek in-vitro whitening study that evaluated performance of enzyme containing non-peroxide strips against non-peroxide dissolving and nondissolving whitening strips.Non-peroxide Enzyme strip vs. non-peroxide non-dissolving competitor

[0256] The enzyme-containing strip (DEV05964) showed both directional and statistically significant superiority over the non-peroxide, non-dissolving comparator at multiple measured timepoints. This indicates that the enzymatic mechanism delivered more rapid and more pronounced whitening and highlights the benefit of the dissolving modality over a non-dissolving delivery format.

[0257] Non-peroxide Enzyme strip vs. non-peroxide dissolving strip

[0258] By the sixth treatment, DEV05964 delivered directionally greater whitening than the non-peroxide dissolving strip (DEV05967). This observation suggests that the enzyme system begins to outperform the alternative peroxide-free technology early in the treatment regimen, but there is additional benefits at treatment numberslO, 14, 21 and 28.

[0259] Whitening study - 329-LAB-WHI-23-003 Laboratory Report 2 Final Version 1.05thJune 2024

[0260] In-vitro study completed by Intertek. Human enamel blocks were polished, lightly etched, and stained using a tea- and coffee-based solution, then their baseline colour was recorded with a CM-700d spectrophotometer. Samples received 28 thirty-minute applications of the assigned whitening strip, with colour re-measured at key timepoints. Changes in L*, a*, and b* values were used to calculate Delta E, and a pre-determined calibration allowed these Delta E values to be expressed as the number of VITA® Bleachedguide shades whitened.

[0261] Products tested during this study:

[0262] Table 11

[0263]

[0264] Results from whitening study are presented in Figure 9.

[0265] Figure 9 is a comparative study results from Intertek in-vitro whitening study that evaluated performance of enzyme containing peroxide strips against peroxide dissolving and non-dissolving whitening strips.

[0266] Peroxide Enzyme strip vs. peroxide dissolving strip

[0267] At almost every treatment point DEV05965 delivered directionally greater whitening than the peroxide dissolving strip (23054). This observation suggests that the enzyme system begins to outperform the alternative peroxide only technology early in the treatment regimen.

[0268] Peroxide Enzyme strip vs. Peroxide non-dissolving strip

[0269] The enzyme-containing strip (DEV05965) showed directional and statistically significant (after 28 treatments) whitening over the peroxide, non-dissolving comparator at multiple measured timepoints. This indicates that the enzymatic mechanism delivered more rapid and more pronounced whitening and highlights the benefit of the dissolving modality over a non-dissolving delivery format.

[0270] Additional formulations that relate to broader range of peroxide and the use of liquid peroxide / PVP are disclosed alongside formulation details related to the samples tested in the in-vitro studies in Table 12.Ta ble 12: Formulation details for additional examples and products tested in in-vitro studies.

[0271]

[0272]

Claims

CLAIMS1. A teeth whitening strip or film comprising:at least one proteolytic enzyme, wherein the or each at least one proteolytic enzyme comprises papain and / or bromelain, wherein the concentration of the or each at least one proteolytic enzyme is between 0.1 to 10.0 wt.% of the strip or film.

2. The teeth whitening strip or film of claim 1, wherein the strip or film comprises: 0.5 to 9.0 wt.%; 0.5 to 8.0 wt.%; 1.0 to 7.0 wt.%; 1.0 to 6.0 wt.%; 1.5 to 5.0 wt.%; or 2.0 to 4.0 wt.% of papain; and / or 0.5 to 9.0 wt.%; 0.5 to 8.0 wt.%; 1.0 to 7.0 wt.%; 1.0 to 6.0 wt.%; 1.5 to 5.0 wt.%; or 2.0 to 4.0 wt.% of bromelain.

3. The teeth whitening strip or film of either claim 1 or claim 2, wherein the strip or film comprises: 2.0 wt.% or 4.0 wt.% papain; and / or 2.0 wt.% or 4.0 wt.% bromelain.

4. The teeth whitening strip or film of any preceding claim, wherein the strip or film further comprises a whitening agent and / or a dental hypersensitivity agent.

5. The teeth whitening strip or film of claim 4, wherein the whitening agent comprises: hydrogen peroxide and / or a hydrogen peroxide-polyvinyl pyrrolidone complex and / or 6-phthalimido peroxy caproic acid (PAP).

6. The teeth whitening strip or film of claim 5, wherein the whitening agent comprises a complex of peroxy carboxylic acid and a carbohydrate; optionally wherein the carbohydrate is dextrin.

7. The teeth whitening strip or film of either claim 5 or claim 6, wherein the concentration of hydrogen peroxide in the strip or film is between 1.0 wt.% to 15.0 wt.% of the strip or film and / or the concentration of PAP in the strip or film is between 0.1 wt.% to 10.0 wt.% of the strip or film.

8. The teeth whitening strip or film of any one of claims 5 to 7, wherein the concentration of hydrogen peroxide in the strip or film is: about 1 wt.% to 12 wt.%; about 2 wt.% to 12 wt.%; about 3 wt.% to 12 wt.%; about 3 wt.% to 10 wt.%; about 3 wt.% to 9 wt.%; about 3 wt.% to 8 wt.%; or about 3 wt.% to 6 wt.% of the strip or film.

9. The teeth whitening strip or film of any one of claims 5 to 8, wherein the concentration of PAP in the strip or film is: about 0.1 wt.% to 10.0 wt.%; about 0.1 wt.% to 5.0 wt.%; about 0.1 wt.% to 2.0 wt.%; or about 1.0 wt.% to 2.0 wt.% of the strip or film.

10. The teeth whitening strip or film of any one of claims 4 to 9, wherein the dental hypersensitivity agent comprises Hydroxyapatite.

11. The teeth whitening strip or film of any preceding claim, further comprising one or more polyphosphates.

12. The teeth whitening strip or film of claim 11, wherein the polyphosphates comprise one or more cyclic and / or one or more linear polyphosphates.

13. The teeth whitening strip or film of claim 12, wherein the one or more cyclic polyphosphates are defined by formula (II):wherein a is a whole number from 3 to 10, preferably from 4 to 8, more preferably 6 and M is selected from one or more of the group comprising hydrogen and an alkali metal, preferably H, Na or K, more preferably Na.

14. The teeth whitening strip or film of claim 12 or claim 13, wherein the one or more linear polyphosphates are defined by formula (III):wherein b is a whole number from 2 to 5, preferably 3 or 4, more preferably 3 and M is selected from one or more of the group comprising hydrogen and an alkali metal, preferably H, Na or K, more preferably Na.

15. The teeth whitening strip or film of any one of claims 12 to 14, wherein the cyclic polyphosphates are present in a total amount of from: 2% to 9% by weight of the strip or film; 3% to 8% by weight of the strip or film; or 3% to 4% by weight of the strip or film; and / or the linear polyphosphates are present in a total amount of from: 2% to 9% by weight of the strip or film; 3% to 8% by weight of the strip or film; or 3% to 4% by weight of the strip or film.

16. The teeth whitening strip or film of any preceding claim, wherein the strip or film further comprises any one of, or combination of the following:one or more water soluble film-forming polymers;one or more plasticizers; and / orone or more emulsifiers.

17. The teeth whitening strip or film of claim 16, wherein the one or more soluble film-forming polymer is one or more of the group comprising: polyvinylpyrrolidone (PVP); pullulan; pectin; starch; dextrin; chitosan; alginic acid; salts of alginic acid and / or cellulose derivatives.

18. The teeth whitening strip or film of claim 16 or claim 17, wherein the one or more plasticizers are selected from the group comprising a polyol such as: glycerol, polyalkylene glycol, polyalkylene glycol monomethyl ether, monosaccharide, oligosaccharide, sorbitol, sorbital and sorbitan, in which the alkylene groups are independently selected from Ci-5alkylene, preferably methylene, ethylene or propylene.

19. The teeth whitening strip or film of any one of claims 16 to 18, wherein the one or more emulsifiers are selected from the group comprising a fatty acid derivative, a lecithin and / or a polysorbate.

20. The teeth whitening strip or film of any preceding claim, wherein the strip or film is dissolvable, such that it dissolves completely or substantially completely within the oral cavity of a user; optionally wherein the strip or film dissolves completely or substantially completely when used in an oral cavity of a user over a period of: 15 to 30 minutes; 30 to 60 minutes; 30 minutes to 2 hours; 1 to 5 hours; 1 to 10 hours; or 1 to 22 hours.

21. The teeth whitening strip or film of any preceding claim, wherein the strip or film has a thickness ranging from: about 50 pm to about 500 pm; about 50 pm to about 250 pm; about 50 pm to about 100 pm; or about 100 pm to about 200 pm.

22. A process for the manufacture of a teeth whitening strip or film, the process comprising at least the steps of:mixing a proteolytic enzyme in a total amount of about 0.1% to about 10% by weight, one or more water soluble film-forming polymers in a total amount of about 30% to about 95% by weight, one or more plasticizers in a total amount of about 0.1% to about 15% by weight and one or more emulsifiers in a total amount of about 0.1% to about 10% by weight, with water to provide an aqueous teeth whitening liquid;applying the aqueous teeth whitening liquid to a substrate to provide a substrate carrying the aqueous teeth whitening liquid;drying the aqueous teeth whitening liquid to provide a teeth whitening strip or film on the substrate, said strip or film having a thickness from about 50 pm to about 500 pm.

23. The process of claim 22, wherein the mixing step further comprises mixing one or more further components selected from the group comprising: colourant, gelling agent, flavouring, sweetener, antioxidant and chelating agent.

24. The process of claim 22 or claim 23, wherein the proteolytic enzyme comprises bromelain and / or papain.

25. A teeth whitening strip or film obtainable by the process of any of claims 22 to 24.

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