Oral care solid films and methods of use

Abstract

Disclosed herein are oral care solid films comprising one or more enzymes, such as papain, and one or more water-soluble polymers, such as pectin. The oral care solid films may further comprise one or more additional components, such as reducing agents. Also disclosed herein are methods of using the oral care solid films for treating and / or preventing dental plaque, oral biofilm, dental calculus, teeth discoloration or oral lesions.

Description

ORAL CARE SOLID FILMS AND METHODS OF USECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority from U.S. Provisional Patent Application No. 63 / 709,003, filed 18 October 2024, the contents of which are hereby incorporated herein by reference in its entirety.BACKGROUND

[0002] Dental plaque, in the form of a film, is present to some degree on virtually all dental surfaces. It is a byproduct of microbial growth and comprises a dense microbial layer made up of a mass of microorganisms embedded in a polysaccharide matrix. Plaque may form on any part of the tooth surface and is found particularly at the gingival margin, in cracks in the enamel, and on the surface of dental calculus. The danger associated with the formation of plaque on the teeth lies in the tendency of plaque to build up and eventually produce gingivitis, periodontitis, and other types of periodontal disease, as well as dental caries and dental calculus.

[0003] Oral care compositions such as toothpastes, gels, and mouthwashes are designed to loosen and remove plaque in conjunction with a regular oral care regimen. However, plaque adheres firmly to dental surfaces. It is often difficult to remove even when using a rigorous brushing regimen. Moreover, plaque rapidly reforms on the tooth surface after it is removed.

[0004] Many commercial oral care compositions do not sufficiently remove plaque from the teeth, particularly high density plaque that is resistant to mechanical and / or detergent removal.

[0005] There remains a need in the art for oral care products that remove plaque, for example, from teeth, including when conventional brushing is insufficient.BRIEF SUMMARY

[0006] This summary is intended merely to introduce a simplified summary of some embodiments of one or more implementations of the present disclosure. Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. This summary is not an extensive overview, nor is it intended to identify all elements of the present teachings, nor to delineate the scope of the disclosure. Rather, its purpose is merely to present one or more concepts in simplified form as a prelude to the detailed description below.

[0007] In certain embodiments, there is provided an oral care solid film comprising one or more enzymes and one or more water-soluble polymers. In certain embodiments, the oral care solid filmis for use in treating dental plaque, oral biofilm, dental calculus, teeth discoloration or oral lesions. Also disclosed herein is a method of treating dental plaque, oral biofilm, dental calculus, teeth discoloration or oral lesions, which comprises applying to the oral cavity (such as the teeth, tongue, gums, cheek, hard palate, soft palate, or lips) of a subject in need thereof an oral care solid film comprising one or more enzymes and one or more water-soluble polymers.

[0008] Exemplary enzymes for use in the oral care solid film comprise, for instance, papain, ficin, bromelain, chymotrypsin, subtilisin A, glucoamylase, amylase, tannase, lipase, lysozyme, glucanase, dextranase, mutanase, glucose oxidase, galactose oxidase, lactose peroxidase, lactoferrin, krillase, or a combination thereof. In some embodiments, the one or more enzymes comprise a proteolytic enzyme, such as papain. The one or more enzymes can be present in the oral care solid film in an amount ranging from, for instance, about 0.01 wt% to about 10 wt%, about 0.1 wt% to about 7%, or about 0.5 wt% to about 5 wt%, based on the total weight of the oral care solid film.

[0009] Exemplary water-soluble polymers for use in the oral care solid film comprise, for instance, pectin, polyvinylpyrrolidone (PVP), polyvinylpyrrolidone / vinyl acetate (PVP / VA), polyethylene glycol, poly vinyl alcohol, hyaluronic acid, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), cetyl hydroxyethylcellulose, carrageenan, cellulose ethers, xanthan gum, pullulan, gum acacia, locust bean gum, dextran, chitosan, or a salt of any of these polymers, or a combination thereof. In certain embodiments, the one or more water-soluble polymers comprise pectin. The one or more water-soluble polymers can be present in the oral care solid film in an amount ranging from, for instance, about 30 wt% to about 90 wt%, about 40 wt% to about 80 wt%, or about 50 wt% to about 70 wt%, based on the total weight of the oral care solid film.

[0010] In certain embodiments of the oral care solid film and methods of the disclosure, the one or more enzymes in the oral care solid film comprise papain, and the one or more water soluble polymers in the oral care solid film comprise pectin.

[0011] In further embodiments of the disclosure, the oral care solid film further comprises one or more reducing agents. Exemplary reducing agents for use in the oral care solid film include, for instance, ascorbic acid or a salt thereof (such as sodium ascorbate), ascorbyl phosphate or a salt thereof, sodium metabisulfite, erythorbic acid or a salt thereof (such as sodium erythorbate), sodium tetrathionate, sodium stannate, ammonium sulfate, vitamin E, vitamin E acetate, a metalgallate, 3,5, -di-tert-butyl-4-hydroxytoluene (BHT), cysteine, or a combination thereof. In certain embodiments, the one or more reducing agents comprise ascorbic acid or an alkali metal salt thereof. The one or more reducing agents can be present in the oral care solid film in an amount ranging from, for instance, about 0.01 wt% to about 20 wt%, about 0.1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, or about 3 wt% to about 8 wt%, based on the total weight of the oral care solid film.

[0012] In certain embodiments of the disclosure, the one or more enzymes in the oral care solid film comprise papain, the one or more water soluble polymers in the oral care solid film comprise pectin, and the one or more reducing agents comprise sodium ascorbate.

[0013] The oral care solid film disclosed herein may also further comprise additional orally acceptable components, such as one or more surfactants and one or more plasticizers. The one or more plasticizers may comprise glycerin, for example. In certain embodiments, glycerin is present in the oral care solid film in an amount less than about 30 wt%, less than about 25 wt%, less than about 20 wt%, less than about 10 wt%, or less than about 5 wt%, based on the total weight of the oral care solid film.

[0014] Additional embodiments of the disclosure comprise applying the oral care solid film to the oral cavity of the subject for at least about 2 minutes, at least about 5 minutes, at least about 10 minutes, or at least about 15 minutes. The treated subject may be a human or an animal such as a canine or feline, for example, a human or animal that has or is at risk of developing gingivitis, periodontitis, implantitis, mucositis, peri-implant mucositis, aphthous ulcers, irritation, dry mouth, xerostomia, malodor, bleeding, or gingival recession.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The features and advantages of the disclosure will be apparent from the following more detailed description of certain embodiments and as illustrated in the accompanying Figures in which:

[0016] FIG. 1 is a graph illustrating the standard curve for a fluorometric assay after 20 minutes of reaction.

[0017] FIG. 2 is a bar graph illustrating papain activity in dissolved pectin film solutions relative to a standard after 20 minutes of reaction in the presence of reducing agents.

[0018] It should be understood that the disclosure is not limited to the particular embodiments and results shown in the Figures.DETAILED DESCRIPTION

[0019] For illustrative purposes, the principles of the present disclosure arc described by referencing various exemplary embodiments thereof. Although certain embodiments of the disclosure are specifically described herein, one of ordinary skill in the art will readily recognize that the same principles are equally applicable to, and can be employed in, other methods. Before explaining various embodiments of the present disclosure in detail, it is to be understood that the disclosure is not limited in its application to the details of any particular embodiments disclosed herein. The terminology used herein is for the purpose of description and not of limitation.

[0020] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular form of any class of the ingredients refers not only to one chemical species within that class, but also to a mixture of those chemical species. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be used interchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but are not limited to”.

[0021] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. It should be appreciated and understood that the description in a range format is merely for convenience and brevity, and should not be construed as an inflexible limitation on the scope of any embodiments or implementations disclosed herein. Accordingly, the disclosed range should be construed to have specifically disclosed all the possible subranges as well as individual numerical values within that range. Any value within the range can be selected as the terminus of the range. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc.

[0022] The term “about” when referring to a number means any number within a range of 10% of the number. For example, the phrase “about 2 wt%” refers to a number between and including 1.8 wt% and 2.2 wt%.

[0023] The abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning. The abbreviation “wt%” means percent by weight. The symbol “°” refers to a temperature degree. The symbol “mil” refers to 0.001 inches. The units “pL” and “pg” refer to micro liters and micrograms, respectively. The unit “ml” refers to milliliters.

[0024] Any member in a list of species that are used to exemplify or define a genus may be mutually different from, or overlapping with, or a subset of, or equivalent to, or nearly the same as, or identical to, any other member of the list of species. Further, unless explicitly stated, such as when reciting a Markush group, the list of species that define or exemplify the genus is open, and it is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0025] The phrases, “a mixture thereof,” “a combination thereof,” or a combination of two or more thereof’ do not require that the mixture include all of A, B, C, D, E, and F (although all of A, B,C, D, E, and F may be included). Rather, it indicates that a mixture of any two or more of A, B, C,D, E, and F can be included. In other words, it is equivalent to the phrase “one or more elements selected from the group consisting of A, B, C, D, E, F, and a mixture of any two or more of A, B, C, D, E, and F.” Likewise, the term “a salt thereof’ also relates to “salts thereof.” Thus, where the disclosure refers to “an element selected from the group consisting of A, B, C, D, E, F, a salt thereof, and a mixture thereof,” it indicates that one or more of A, B, C, D, E and F may be included, one or more of a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included, or a mixture of any two of A, B, C, D, E, F, a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included.

[0026] All components and elements positively set forth in this disclosure can be negatively excluded from the claims. In other words, the oral care solid films for use in the methods of the instant disclosure can be free or essentially free of all components and elements positively recited throughout the instant disclosure. In some instances, the oral care solid films may be substantially free of non-incidental amounts of the ingredient(s) or compound(s) described herein. A nonincidental amount of an ingredient or compound is the amount of that ingredient or compound that is added into the oral care solid film by itself. For example, an oral care solid film may be substantially free of a non-incidental amount of an ingredient or compound, although such ingredient(s) or compound(s) may be present as part of a raw material that is included as a blend of two or more compounds.

[0027] One embodiment of the disclosure is an oral care solid film comprising one or more enzymes and one or more water-soluble polymers. The oral care solid film may be used for removing and / or preventing the formation of dental plaque in an oral cavity, for example. In someembodiments, the oral care solid film may be used for treating and / or preventing oral biofilm (such as microbial biofilm), dental calculus, teeth discoloration or oral lesions (such as cuts or sores).

[0028] Another embodiment of the disclosure is a method of treating dental plaque, oral biofilm (such as microbial biofilm), dental calculus, teeth discoloration or oral lesions (such as cuts or sores), which comprises applying to the oral cavity of a subject in need thereof an oral care solid film comprising one or more enzymes and one or more water-soluble polymers. Some embodiments comprise applying the oral care solid film to the teeth, tongue, gums, cheek, hard palate, soft palate, or lips of the subject.

[0029] As explained in this disclosure and demonstrated in the Examples, the oral care solid film comprising one or more proteolytic enzymes, for example, and one or more water-soluble polymers is efficacious for the removal of plaque from teeth, including for the removal of plaque that is resistant to mechanical and / or detergent removal.

[0030] In some embodiments, the one or more enzymes comprise a proteolytic enzyme. As used herein, a “proteolytic enzyme,” also known as a protease, indicates an enzyme having the ability to catalyze a proteolysis reaction and thereby break down a protein into smaller polypeptides or single amino acid units. In certain embodiments, a proteolytic enzyme, by breaking down a protein into smaller polypeptides, is capable of forming a new protein product or products. Proteolysis occurs by cleaving peptide bonds with a protein through a hydrolysis reaction, i.e., wherein water serves to cleave the peptide bonds.

[0031] Any known enzyme may be used in the oral care solid films and methods disclosed herein. Exemplary enzymes that can be included in the oral care solid film include, for instance, papain, ficin, bromelain, chymotrypsin, subtilisin A, glucoamylase, amylase, tannase, lipase, lysozyme, glucanase, dextranase, mutanase, glucose oxidase, galactose oxidase, lactose peroxidase, lactoferrin, krillase, or a combination thereof. In some embodiments, the one or more enzymes comprise papain. The Examples below illustrate oral care solid films comprising papain as a proteolytic enzyme. In further embodiments, papain is the only enzyme included in the oral care solid film. The one or more enzymes can be present in the oral care solid film in an amount ranging from, for example, about 0.01 wt% to about 10 wt%, about 0.1 wt% to about 7%, or about 0.5 wt% to about 5 wt%, based on the total weight of the oral care solid film. In certain embodiments, the one or more enzymes (e.g., papain) is present in the oral care solid film in an amount ranging from about 1 wt% to about 10 wt%, such as from about 2 wt% to about 9 wt%, about 3 wt % to about 8wt%, about 4 wt% to about 7 wt%, about 5 wt% to about 7 wt%, about 5 wt% to about 6.5 wt%, about 5.5 wt% to about 6 wt%, about 5 wt%, about 5.5 wt%, or about 6.25 wt%, based on the total weight of the oral care solid film.

[0032] The oral care solid film disclosed herein further comprises one or more water-soluble polymers. As used herein, a “water-soluble polymer” indicates an organic substance that may be dispersed or dissolved in water, thereby becoming gelled, stabilized, concentrated, or emulsified. A water-soluble polymer may be either natural or synthetic. In certain embodiments, the water- soluble polymer is biodegradable.

[0033] Any known water-soluble polymer may be used in the oral care solid films and methods disclosed herein. Exemplary water-soluble polymers that can be included in the oral care solid film include, for instance, pectin, polyvinylpyrrolidone (PVP), polyvinylpyrrolidonc / vinyl acetate (PVP / VA), polyethylene glycol, poly vinyl alcohol, hyaluronic acid, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), cetyl hydroxyethylcellulose, carrageenan, cellulose ethers, xanthan gum, pullulan, gum acacia, locust bean gum, dextran, chitosan, a salt thereof, or a combination thereof. In some embodiments, the one or more water-soluble polymers comprise pectin. The Examples below illustrate oral care solid films comprising pectin as a water-soluble polymer. In further embodiments, pectin is the only water-soluble polymer included in the oral care solid film. The one or more water-soluble polymers can be present in the oral care solid film in an amount ranging from, for example, about 30 wt% to about 90 wt%, about 40 wt% to about 80 wt%, or about 50 wt% to about 70 wt%, based on the total weight of the oral care solid film. In certain embodiments, the one or more water-soluble polymers (e.g., pectin) is present in the oral care solid film in an amount ranging from about 45 wt% to about 70 wt%, such as from about 48 wt% to about 68 wt%, about 50 wt% to about 67 wt%, about 50 wt% to about 66 wt%, about 55 wt% to about 66 wt%, about 50 wt% to about 60 wt%, about 50 wt% to about 55 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 60 wt%, about 50 wt%, about 57 wt%, or about 66 wt%, based on the total weight of the oral care solid film.

[0034] Certain embodiments of methods of the disclosure comprises applying to the oral cavity (such as the teeth) of a subject in need thereof an oral care solid film comprising one or more proteolytic enzymes and one or more water-soluble polymers. In certain embodiments of themethods disclosed herein, the one or more proteolytic enzymes comprise papain, and the one or more water soluble polymers comprise pectin.

[0035] In additional embodiments of the disclosure, the oral care solid film further comprises one or more reducing agents. Without being bound to a particular theory, it is believed that the reducing agent can act as a stabilizer for the one or more enzymes during preparation of the oral care solid films. As detailed in the Examples, one method of preparing the oral care solid films comprises preparing an aqueous composition of the film components, casting the composition in the form of a film, then drying the cast composition to prepare the oral care solid film. Exposure of the one or more enzymes to water in the aqueous composition is believed to oxidize the enzyme, thereby reducing the enzyme’s activity. The reducing agent is believed to counteract oxidation of the enzyme and restore the enzyme’s activity.

[0036] Exemplary reducing agents that can be included in the oral care solid film include, for instance, ascorbic acid or a salt thereof (such as sodium ascorbate), ascorbyl phosphate or a salt thereof, sodium metabisulfite, erythorbic acid or a salt thereof (such as sodium erythorbate), sodium tetrathionate, sodium stannate, ammonium sulfate, vitamin E, vitamin E acetate, a metal gallate, 3,5,-di-tert-butyl-4-hydroxytoluene (BHT), cysteine, or a combination thereof.

[0037] In some embodiments, the one or more reducing agents comprise ascorbic acid or an alkali metal salt thereof, such as sodium ascorbate. The formulations illustrated in Tables 10-13 of the Examples illustrate oral care solid films comprising sodium ascorbate as a reducing agent. The one or more reducing agents can be present in the oral care solid film in an amount ranging from, for example, about 0.01 wt% to about 20 wt%, about 0.1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, about 3 wt% to about 8 wt%, about 0.5 wt% to about 5 wt%, about 0.5 wt% to about 3 wt%, about 0.5 wt% to about 2 wt%, about 0.5 wt% to about 1.5 wt%, or about 1 wt%, based on the total weight of the oral care solid film.

[0038] Certain embodiments of the disclosure comprise an oral care solid film comprising one or more enzymes, one or more water-soluble polymers, and one or more reducing agents, wherein the one or more enzymes comprise papain, the one or more water soluble polymers comprise pectin, and the one or more reducing agents comprise ascorbic acid or an alkali metal salt thereof, such as sodium ascorbate, as well as applying to the oral cavity of a subject in need thereof the oral care solid film.

[0039] In additional embodiments of the disclosure, the oral care solid film further comprises one or more plasticizers. In certain embodiments, the one or more plasticizers serve to improve flexibility of the oral care solid film. In certain embodiments, the one or more plasticizers comprise glycerin. Papain is commercially available, for example, in a formulation of glycerin and water. As demonstrated in the Examples, and without being bound to a particular theory, it is believed that at least certain concentrations of glycerin inhibit enzyme activity. Thus, in some embodiments, the glycerin is present in the oral care solid film in an amount less than about 30 wt%, less than about 25 wt%, less than about 20 wt%, less than about 10 wt%, or less than about 5 wt%, based on the total weight of the oral care solid film. In some embodiments, the glycerin is present in the oral care solid film in an amount ranging from about 0.01 wt% to about 30 wt%, such as from about 1 wt% to about 30 wt%, about 1 wt% to about 25 wt%, about 5 wt% to about 30 wt%, about 5 wt% to about 25 wt%, about 10 wt% to about 30 wt%, about 10 wt% to about 25 wt%, about 15 wt% to about 30 wt%, about 15 wt% to about 25 wt%, about 20 wt% to about 30 wt%, about 20 wt% to about 25 wt%, about 21 wt% to about 24 wt%, about 22 wt% to about 24 wt%, about 23 wt% to about 24 wt%, or about 23.5 wt%, based on the total weight of the oral care solid film. In further embodiments, the oral care solid film does not comprise glycerin, i.e., the oral care solid film is free of or substantially free of glycerin.

[0040] Other exemplary plasticizers that may be incorporated into the oral care solid films include, for instance, sorbitol, alkylene glycols, poloxamers, block co-polymers, or a combination thereof. In some embodiments, the oral care solid film does not comprise an alkylene glycol, such as polyethylene glycol.

[0041] In some embodiments of the disclosure, the oral care solid film further comprises one or more additional ingredients as known in the art and as disclosed below. These additional ingredients may include, but are not limited to, metal ion sources, fluoride ion sources, anticalculus agents, surfactants, flavoring agents, sweeteners, anti-bacterial agents, colorants, antisensitivity agents, antioxidants, or a combination thereof. Such ingredients would be known to those skilled in the ail of oral care. However, non-limiting examples of these ingredients are provided herein. Suitable components, such as those listed herein, may be included or excluded from the formulations for the oral care solid films depending on the specific combination of other ingredients present.

[0042] The ingredients for use in the oral care solid films should be orally acceptable. As used herein, “orally acceptable” may refer to any ingredient that is present in a composition as described in an amount and form which does not render the composition unsafe for use in the oral cavity.

[0043] In some embodiments, the oral care solid film further comprises one or more metal ion sources, such as a zinc ion source or a copper ion source. For example, in certain embodiments, the oral care solid films comprise a zinc ion source selected from zinc oxide, zinc citrate, zinc lactate, zinc phosphate, and combinations thereof. In certain embodiments, the one or more metal ion sources are present in an amount ranging from about 0.1 wt% to about 5 wt%, such as about 0.2 wt% to about 1 wt%, by weight based on the total weight of the oral care solid film.

[0044] In some embodiments, the oral care solid film further comprises one or more fluoride ion sources. A fluoride ion source may be useful, for example, as an anti-caries agent. The fluoride ion sources may be selected from any fluoride ion source known in the art, including, for example, sodium fluoride, potassium fluoride, stannous fluoride, sodium fluorosilicate, ammonium fluorosilicate, potassium monofluorophosphate, sodium monofluorophosphate, ammonium monofluorophosphate, indium fluoride, amine fluoride such as N'-octadecyltrimethylendiamine- N,N,N'-tris(2-ethanol)-dihydrofluoride (i.e., olaflur) or N-octadeca-9-enylamine hydrofluoride (i.e., dectaflur), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

[0045] The one or more fluoride ion sources may be present in an amount providing a clinically efficacious amount of total soluble fluoride ion to the oral care solid film. In some embodiments, the one or more fluoride ion sources (e.g., sodium fluoride) may be present in the oral care solid film in an amount ranging from about 0.005 wt% to about 5 wt%, such as from about 0.01 wt% to about 0.1 wt%, based on the total weight of the oral care solid film. In certain embodiments, the total fluoride content of the oral care solid film ranges from about 25 ppm to about 25,000 ppm.

[0046] In some embodiments, the oral care solid film further comprises one or more anticalculus agents. Illustrative anticalculus agents include, but are not limited to, phosphates and polyphosphates, polyaminopropane sulfonic acid (AM PS), polyolefin sulfonates, polyolefin phosphates, diphosphonates such as azacycloalkane-2, 2-diphosphonates (e.g., azacycloheptane- 2,2-diphosphonic acid), N-methyl azacyclopentane-2,3-diphosphonic acid, ethane- 1 -hydroxy- 1,1- diphosphonic acid (EHDP) and ethane- 1 -amino- 1,1 -diphosphonate, and phosphonoalkane carboxylic acids. Useful inorganic phosphate and polyphosphate salts include monobasic, dibasicand tribasic sodium phosphates. Soluble pyrophosphates may be useful anti-calculus agents. The pyrophosphate salts can be any of the alkali metal pyrophosphate salts. In certain embodiments, salts include tetra alkali metal pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. Exemplary pyrophosphates may include tetrasodium pyrophosphate (TSPP), tetrapotassium pyrophosphate, sodium tripolyphosphate, tetrapolyphosphate, sodium trimetaphosphate, sodium hexametaphosphate and mixtures thereof. The salts may be useful in both their hydrated and / or unhydrated forms. An effective amount of pyrophosphate salt that may be included in the oral care solid film is generally enough to provide least about 0.1 wt% pyrophosphate ions, e.g., from about 0.1 wt% to about 3 wt%, based on the total weight of the oral care solid film.

[0047] In some embodiments, the oral care solid film further comprises one or more surfactants. Exemplary surfactants include, but are not limited to, anionic, cationic, zwitterionic, and nonionic surfactants, and combinations thereof. One example surfactant is decaglycerol mono- & dioleate, commercially sold as Caprol PGE 860, which is included in the oral care solid films illustrated in Tables 12-13 in the Examples. The surfactant can be included to reduce surface tension in the process of casting the film from a solution or slurry of the film ingredients. The one or more surfactants may be present in the oral care solid film in a combined total amount of, for example, from about 0.01 wt% to about 10 wt% based on the total weight of the oral care solid film.

[0048] In some embodiments, the oral care solid film further comprises one or more flavoring agents. Suitable flavoring agents include essential oils and various flavoring aldehydes, esters, alcohols, and similar materials. Examples of the essential oils include oils of spearmint, peppermint, Wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful are such chemicals as menthol, carvone, and anethole. Additional flavoring agents may include, but are not limited to menthol, artificial vanilla, cinnamon derivatives, and various fruit flavors, spearmint oil, peppermint oil, cinnamon oil, oil of wintergreen (methylsalicylate), clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, cassia oil, and a combination of two or more thereof. The one or more flavoring agents may be present in the oral care solid film in a combined total amount of, for example, from about 0.01 wt% to about 5 wt%, based on the total weight of the oral care solid film.

[0049] In some embodiments, the oral care solid film further comprises one or more sweeteners useful, for example, to enhance taste of the oral care solid film. Sweeteners may include, but arc not limited to, sucralose, maltodextrin, dextrose, polydextrose, sucrose, maltose, dextrin, dried invert sugar, mannose, xylose, ribose, fructose, levulose, galactose, sugar alcohols, such as sorbitol, mannitol, xylitol, maltitol, and isomalt, aspartame, neotame, saccharin and salts thereof (e.g., sodium saccharin), gum arabic, dipeptide-based intense sweeteners, cyclamates, dihydrochalcones, or the like, or combinations thereof. The one or more sweeteners may be present in the oral care solid film in a combined total amount of, for example, from about 0.1 wt% to about 5 wt%, based on the total weight of the oral care solid film.

[0050] In some embodiments, the oral care solid film further comprises one or more antimicrobial agents and / or one or more preservatives, such as methylisothiazolinone (MIT), sodium benzoate, potassium sorbate, benzyl alcohol, and combinations thereof. In another example, the oral care solid film may comprise one or more antibacterial agents selected from halogenated diphenyl ether (e.g., triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea-buckthorn extract), bisguanide antiseptics (e.g., chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, salifluor, other metal ions (e.g., stannous salts, copper salts, iron salts), sanguinarine, propolis and oxygenating agents (e.g., hydrogen peroxide, buffered sodium peroxyborate or peroxycarbonate), phthalic acid and its salts, monoperthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, octapinol, and other piperidino derivatives, nicin preparations, chlorite salts; and combinations of any of the foregoing.

[0051] The one or more antibacterial or preservative agents may optionally be present in the oral care solid film in a combined total amount of, for example, from about 0.01 wt% to about 0.5 wt%, based on the total weight of the oral care solid film.

[0052] In some embodiments, the oral care solid film further comprises one or more antisensitivity agents, e.g., potassium salts such as potassium nitrate, potassium bicarbonate, potassium chloride,potassium citrate, and potassium oxalate; capsaicin; eugenol; strontium salts; chloride salts and combinations thereof. The one or more antisensitivity agents may be present in the oral care solid film in a combined total amount of, for example, from about 1 wt% to about 20 wt%, based on the total weight of the oral care solid film.

[0053] In some embodiments, the oral care solid film further comprises one or more antioxidants. Any orally acceptable antioxidant can be used, including butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, co-enzyme Q10, PQQ, Vitamin A, Vitamin C, Vitamin E, anethole-dithiothione, flavonoids, polyphenols, ascorbic acid, herbal antioxidants, chlorophyll, melatonin, and mixtures thereof.

[0054] Each oral care solid film for use in methods of the disclosure may be packaged as a single dose (e.g., single use strip) or a multi-dose (e.g., roll, stack, etc.) that may be separated by the user / consumer. The oral care solid films may be disposed in or otherwise packaged in a container, such as an airtight container, including a container that is portable and / or disposable. Each container may include any number of doses of the oral care solid film. For example, each container may include a single dose or multiple doses of the oral care solid film.

[0055] The oral care solid films for use in the methods of the disclosure can be prepared by any appropriate technique, such as by methods and procedures known to those skilled in the art. In some embodiments, the ingredients for the oral care solid films are first combined and mixed in any appropriate order in a solution or slurry, for example an aqueous solution or slurry. Films can then be cast from the solution or slurry, with the initial thickness of the films ranging, for example, from about 10 mils to about 50 mils, such as about 35 mils to about 45 mils. Preparing the oral care solid films may include casting the solution or slurry on a substrate before evaporating the water therefrom. The substrate may be a metallic substrate, such as a stainless steel substrate, a non-stick substrate, such as a mylar or TEFLON surface, or the like.

[0056] The cast films can then dried, for example at a temperature of from about 70 °C to about 100 °C, for a time of from about 30 minutes to about 120 minutes, such as from about 45 minutes to about 60 minutes. Drying may be performed at atmospheric pressure or reduced pressure. The final oral care solid film thickness after drying may range from about 2 mils to about 10 mils, for example.

[0057] In the methods of treating and / or preventing dental plaque of the disclosure, the solid film can be applied to the teeth of the subject in need thereof for any period of time and frequencyappropriate to achieve an efficacious effect. As used herein, the term “subject” refers to individuals (c.g., human) to be treated by the methods disclosed herein. Subjects include, but arc not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans. In certain embodiments, the subject is a human who has or is at risk of developing gingivitis, periodontitis, implantitis, mucositis, peri-implant mucositis, aphthous ulcers, irritation, dry mouth, xerostomia, malodor, bleeding, or gingival recession.

[0058] Certain embodiments of the methods of the disclosure comprise applying the oral care solid film to the oral cavity (such as the teeth) of the subject for at least about 2 minutes, at least about 5 minutes, at least about 10 minutes, or at least about 15 minutes. The film can in some embodiments be dissolvable or disintegrable in the subject’s mouth. As used herein, the term or expression “dissolvable” may refer to the ability to disperse into a liquid. For example, a dissolvable oral care solid film may disperse into an aqueous liquid, such as saliva. As used herein, the term or expression “disintegrable” may refer to the ability to decompose into constituent elements, parts, and / or small particles. The ability of the oral care solid film to be dissolvable and / or disintegrable may be provided by one or more components of the oral care solid film, such as the one or more water-soluble polymers and their concentration in the oral care solid film.

[0059] The ingredients of the oral care solid film may be selected such that the film dissolves or disintegrates over time in the presence of saliva such that the subject does not need to manually remove the film from the oral cavity. The methods may include, for example, applying an oral care solid film to the teeth of the subject at least once a day, such as at least twice a day, or such as at least three times a day.

[0060] The examples and other embodiments described herein are exemplary and not intended to be limiting in describing the full scope of this disclosure. Equivalent changes, modifications and variations of specific embodiments, materials, compositions and methods may be made within the scope of the present disclosure, with substantially similar results.EXAMPLES

[0061] In Experiment 1, papain activity was quantified in several pectin films with varying amounts of glycerin using a fluorescent protease assay. This analytical assay is indicative of activity the films are expected to demonstrate in treating plaque on a subject’s teeth. Experiment 2 explored further stabilizing the papain-pectin system with either cysteine or sodium ascorbate asa reducing agent by testing papain activity after dissolution of the films in phosphate-buffered saline (PBS) containing cither of the reducing agents.

[0062] Materials. Papain Concentrate RS 100 was provided by Enzyme Development Corporation (EDC). The approximate percentage of ingredients in RS 100 is 50.0 wt% glycerol, 36.5 wt% water and 13.5 wt% papain.Experiment 1

[0063] Experimental and control film preparation. Three oral care solid films comprising pectin, glycerin and papain were prepared as described in Tables 1-3. The films of Tables 1-3 differ in the amount of glycerin in the films. The film ingredients were first prepared in a solution. The “wt% solution” reports the weight percent of the respective ingredients in the solution. “Grams” reports the weight in grams of the respective ingredients in the solution. Films were then cast from the solution, with the initial thickness of the films reported at either 35 mils for the films in Tables 1 and 2 (1 mil = 0.001 inches) or 30 mils for the film in Table 3. The cast films were then dried at 70 °C, with a target dry film thickness of 6-7 mils. “Solids” reports the weight in grams of the respective ingredients in the dried films. “Film Solids” reports the wt% of the respective ingredients in the dried films. Reference to “casting solids” represents the total weight in grams of the dried film divided by the total weight in grams of the solution and is largely indicative of the loss of water during the drying process.Table 1: Formulation for pectin / low glycerin film comprising papain (LGP)Casting solids = 16.01% Cast film at 35 milsDry at 70 °CTarget 6-7 mil dry film thicknessTable 2: Formulation for pectin / medium glycerin film comprising papain (MGP)Casting solids = 18.05%Cast film at 35 milsDry at 70 °CTarget 6-7 mil dry film thicknessTable 3: Formulation for pectin / high glycerin film comprising papain (HGP)Cast film at 30 milsDry at 70 °CTarget 6-7 mil dry film thickness

[0064] Three corresponding control samples comprising pectin and glycerin, but not papain, were prepared as described in Tables 4-6.Table 4: Formulation for pectin / low glycerin film without papain (LG)Casting solids = 16.01%Cast film at 35 milsTarget 6-7 mil dry film thicknessTable 5: Formulation for pectin / medium glycerin film without papain (MG)Casting solids = 18.05%Cast film at 35 milsTarget 6-7 mil dry film thicknessTable 6: Formulation for pectin / high glycerin film without papain (HG)Casting solids = 20.01%Cast film at 30 milsTarget 6-7 mil dry film thickness

[0065] Experimental procedure. The protease assays were carried out according to the manufacturer protocol with slight modifications. Specifically, papain concentrate (LIQUIPANOL® RS 100, EDC) was used as a source of papain enzyme and was also used for manufacturing films. Trypsin enzyme was only used to confirm the assay performance according to specifications.

[0066] Fluorescent Protease Assay Kit (Thermo Scientific™ Pierce™) uses fluorescein-labeled casein as a substrate for assessing protease activity in a sample by fluorescence resonance energy transfer (FRET). FITC-labeled casein has been labeled using a large molar excess of fluorescein isothiocyanate (FITC). Fluorescence properties of this heavily-labeled, intact protein substrate change dramatically upon digestion by proteases, resulting in a measurable indication of proteolysis. FRET-based measurement detects the decrease in fluorescence quenching (i.e. increased total fluorescence) that occurs as the FITC-Casein substrate is digested into smaller fluorescein-labeled fragments. In this assay, FRET events occur as a result of fluorescence homotransfer in which fluorescein is acting both as the energy “donor” and energy “acceptor.”

[0067] For this assay, black plates with clear bottom were used to measure assay in FRET mode. Standard solutions were prepared with LIQUIPANOL® RS 100. The assay procedure was as follows:

[0068] 1. Add lOOpL of sample (or standard) to each well of a 96-well plate. In addition to the zero- standard, prepare a blank using a buffer similar to that used for the protease sample.

[0069] 2. Add lOOpL of FTC-Casein Working Reagent composed of 5mg / ml of fluorescein thiocarbamoyl-cascin (FTC-Casein) diluted 1:500 in PBS buffer (WR) to all wells of a 96-wcll plate.

[0070] 3. Measure fluorescence in a plate reader using a fluorescein excitation / emission filter set every 10 mins, for 60 mins, at room temperature.

[0071] 4. Subtract the blank from each sample and standard measurement and then prepare a standard curve.

[0072] 5. For FRET, plot the change in relative fluorescence units (RFU) of the standards vs. protease concentration.

[0073] Sample preparation. Films samples were prepared by dissolving a known amount of film in 10 ml of PBS. Subsequently, these stock sample solutions were further diluted to 1:10,000 and 1:15,000 dilutions to match concentrations of papain in the standards.

[0074] Standard curves. The fluorescence measurements were taken every 10 minutes for a 60 minute total duration. Standard curves were generated for every 10 min. time point. The 20 min. and 40 min. time points were selected for monitoring enzyme kinetics based on the linear regression results. FIG. 1 is a graph illustrating the standard curve for the fluorometric assay after 20 minutes of reaction.

[0075] Table 7 reports the results of Experiment 1 at 20 minutes of digestion and 1 : 10,000 dilution. “Film Papain Cone.” refers to the amount of papain detected by the assay. A negative value indicates that papain was not detected and is due to errors and the linear regression that predicted the value to be negative. “Target Papain Cone.” refers to the concentration of papain that is included in the standard to which the concentration of the papain in the film was compared.Table 7: proteolytic activity of papain films in Experiment 1

[0076] Samples LG, MG and HG indicate that pectin did not interfere in the assay readout and confirmed absence of enzymatic activity in samples. Samples LGP and MGP comprising papain retained some enzymatic activity, ranging from about 41% to over 60% activity compared to theoretical concentration of papain standard samples. For the 40 minute timepoint, the trends remain consistent with the analysis for the 20 minute time point. This data illustrates that papain remains active well beyond its immediate application and its enzymatic activity increases as it disperses from the pectin matrix. For oral application, the shorter timepoint of 20 minutes may be most appropriate for analysis to discern the effects of the polymer matrix on the enzyme, if the product were to be applied to the teeth for up to about 10 minutes, for example.Experiment 2

[0077] In this second experiment, film samples prepared as in Experiment 1 were suspended in PBS media and further diluted in PBS containing low, medium, and high concentrations of glycerin and either 1% w / v cysteine (samples labeled LGP C, MGP C, and HGP C) or 1% w / v ascorbate (samples labeled LGP A, MGP A, and HGP A). Table 8 reports the results of Experiment 2 at 20 minutes of digestion and 1:10,000 dilution.Table 8: proteolytic activity of papain films in Experiment 2

[0078] FIG. 2 is a bar graph illustrating papain activity in the dissolved pectin film solutions relative to its target concentration after 20 minutes of reaction in the presence of the reducing agents. This experiment confirmed that papain in the LGP and MGP samples retained its activity, ranging from 30.5% to 32.8%. Notably, once the dissolved samples were further diluted to 1:10,000 and 1:15,000 dilutions in PBS containing either cysteine or sodium ascorbate, papain activity rose drastically in all three film samples. LGP C and MGP C samples diluted in cysteine buffer showed similar activity, 534.5% and 516.0%, respectively, at 1:10,000 dilution. The higher activity percentage at the lower concentrations may be indicative of the presence of inhibitory entities such as glycerin or error due to approximations. The HGP C sample had a slightly less increased activity, 318.7% at 1:10,000 dilution. Samples dissolved in sodium ascorbate had activity of 338.2%, 285.2%, and 105.2% for LGP A, MGP A, and HGP A, respectively.

[0079] Experiment 2 highlights that the presence of glycerin may partially inhibit papain activity. The percentages above 100% may not accurately reflect the level of enzyme activity as their corresponding RFUs lay outside of the concentrations of the standards.

[0080] The drastic difference in activity between freshly prepared standards from the concentrate and samples treated with reducing agents highlights that papain concentrate storage in glycerin causes oxidation over time and reduction in activity. The experiments illustrate that this oxidation is reversible with application of an appropriate reducing agent. The choice of the reducing agent may also be customized, as cysteine and sodium ascorbate did not equally restore the papain activity.

[0081] The experiments described herein illustrate that solid-state enzyme delivery systems as used in the disclosure offer a viable solution for stabilizing enzyme activity. The experiments focused on determining activity of papain after incorporation into pectin films using a fluorescent assay. The results of the study confirmed that papain retained approximately 30-60% of its initial activity. The study also illustrated that the enzymatic activity of papain can be successfully recovered by the addition of a reducing agent, such as cysteine or sodium ascorbate. The results offer a promising solution for disruption of plaque, such as high density plaque that is resistant to mechanical and / or detergent removal.Additional sample preparations

[0082] The samples as shown in Tables 9-13 were prepared analogously to those prepared in Experiment 1. The sample prepared as in Table 9 comprises a higher concentration of papain compared to the sample prepared as in Table 1.Table 9: Formulation for pectin / low glycerin film with papain

[0083] The samples prepared as in Tables 10-11 further comprise sodium ascorbate as a reducing agent. The sample of Tabic 11 comprises a higher concentration of papain than the amount of papain in the sample of Table 10.Table 10: Formulation for pectin / low glycerin film with papain and sodium ascorbateTable 11: Formulation for pectin / low glycerin film with papain and sodium ascorbate

[0084] The samples prepared as in Tables 11-12 further comprise Caprol PGE 860 as a surfactant. The sample of Table 13 comprises a higher concentration of papain than the amount of papain in the sample of Table 12.Table 12: Formulation for pectin / low glycerin film with papain, sodium ascorbate, and Caprol PGE 860Table 13: Formulation for pectin / low glycerin film with papain, sodium ascorbate and Caprol PGE 860

[0085] The present disclosure has been described with reference to exemplary implementations. Although a limited number of implementations have been shown and described, it will be appreciated by those skilled in the ail that changes may be made in these implementations without departing from the principles and spirit of the preceding detailed description. It is intended that the present disclosure be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims

CLAIMSWhat Is Claimed Is:

1. A method of treating and / or preventing dental plaque, oral biofilm, dental calculus, teeth discoloration or oral lesions, which comprises applying to the oral cavity of a subject in need thereof an oral care solid film comprising one or more enzymes and one or more water-soluble polymers.

2. The method of claim 1, which comprises treating and / or preventing dental plaque.

3. The method of any one of the preceding claims, which comprises applying the oral care solid film to the teeth, tongue, gums, cheek, hard palate, soft palate, or lips of the subject.

4. The method of claim 3, which comprises applying the oral care solid film to the teeth of the subject.

5. The method of any one of claims 1-4, wherein the one or more enzymes comprise papain, ficin, bromelain, chymotrypsin, subtilisin A, subtilisin, glucoamylase, amylase, tannase, lipase, lysozyme, glucanase, dextranase, mutanase, glucose oxidase, galactose oxidase, lactose peroxidase, lactoferrin, krillase, or a combination thereof.

6. The method of any one of claims 1-5, wherein the one or more enzymes comprise a proteolytic enzyme.

7. The method of any one of the preceding claims, wherein the proteolytic enzyme is papain.

8. The method of any one of the preceding claims, wherein the one or more enzymes are present in the oral care solid film in an amount ranging from about 0.01 wt% to about 10 wt%, about 0.1 wt% to about 7%, or about 0.5 wt% to about 5 wt%, based on the total weight of the oral care solid film.

9. The method of any one of the preceding claims, wherein the one or more water-soluble polymers comprise pectin, polyvinylpyrrolidone (PVP), polyvinylpyrrolidone / vinyl acetate (PVP / VA), polyethylene glycol, poly vinyl alcohol, hyaluronic acid, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), hydroxycthyl cellulose (HEC), cetyl hydroxycthylccllulosc, carrageenan, cellulose ethers, xanthan gum, pullulan, gum acacia, locust bean gum, dextran, chitosan, or a salt thereof, or a combination thereof.

10. The method of any one of the preceding claims, wherein the one or more water-soluble polymers comprise pectin.

11. The method of any one of the preceding claims, wherein the one or more water-soluble polymers are present in the oral care solid film in an amount ranging from about 30 wt% to about 90 wt%, about 40 wt% to about 80 wt%, or about 50 wt% to about 70 wt%, based on the total weight of the oral care solid film.

12. The method of any one of the preceding claims, wherein the one or more enzymes comprise papain, and the one or more water soluble polymers comprise pectin.

13. The method of any one of the preceding claims, wherein the oral care solid film further comprises one or more reducing agents.

14. The method of claim 13, wherein the one or more reducing agents comprise ascorbic acid or a salt thereof (such as sodium ascorbate), ascorbyl phosphate or a salt thereof, sodium metabisulfite, erythorbic acid or a salt thereof (such as sodium erythorbate), sodium tetrathionate, sodium stannate, ammonium sulfate, vitamin E, vitamin E acetate, a metal gallate, 3,5, -di-tert- butyl-4-hydroxytoluene (BHT), cysteine, or a combination thereof.

15. The method of any one of claims 13-14, wherein the one or more reducing agents comprise ascorbic acid or an alkali metal salt thereof.

16. The method of any one of claims 13-15, wherein the one or more reducing agents are present in the oral care solid film in an amount ranging from about 0.01 wt% to about 20 wt%, about 0.1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, or about 3 wt% to about 8 wt%, based on the total weight of the oral care solid film.

17. The method of any one of claims 13-16, wherein the one or more enzymes comprise papain, the one or more water soluble polymers comprise pectin, and the one or more reducing agents comprise sodium ascorbate.

18. The method of any one of the preceding claims, wherein the oral care solid film further comprises one or more surfactants.

19. The method of any one of the preceding claims, wherein the oral care solid film further comprises one or more plasticizers.

20. The method of claim 19, wherein the one or more plasticizers comprise glycerin.

21. The method of claim 20, wherein the glycerin is present in the oral care solid film in an amount less than about 30 wt%, less than about 25 wt%, less than about 20 wt%, less than about 10 wt%, or less than about 5 wt%, based on the total weight of the oral care solid film.

22. The method of any one of the preceding claims, which comprises applying the oral care solid film to the oral cavity of the subject for at least about 2 minutes, at least about 5 minutes, at least about 10 minutes, or at least about 15 minutes.

23. The method of any one of the preceding claims, wherein the subject is human.

24. The method of any one of the preceding claims, wherein the subject has or is at risk of developing gingivitis, periodontitis, implantitis, mucositis, peri-implant mucositis, aphthous ulcers, irritation, dry mouth, xerostomia, malodor, bleeding, or gingival recession.

25. An oral care solid film comprising one or more enzymes and one or more water-soluble polymers.

26. The oral care solid film of claim 25, wherein the one or more enzymes comprise papain, ficin, bromelain, chymotrypsin, subtilisin A, glucoamylase, amylase, tannase, lipase, lysozyme, glucanase, dextranase, mutanase, glucose oxidase, galactose oxidase, lactose peroxidase, lactoferrin, krillase, or a combination thereof.

27. The oral care solid film of claim 25, wherein the one or more enzymes comprise a proteolytic enzyme.

28. The oral care solid film of claim 27, wherein the proteolytic enzyme is papain.

29. The oral care solid film of any one of claims 25-28, wherein the one or more enzymes are present in the oral care solid film in an amount ranging from about 0.01 wt% to about 10 wt%, about 0.1 wt% to about 7%, or about 0.5 wt% to about 5 wt%, based on the total weight of the oral care solid film.

30. The oral care solid film of any one of claims 25-29, wherein the one or more water- soluble polymers comprise pectin, polyvinylpyrrolidone (PVP), polyvinylpyrrolidone / vinyl acetate (PVP / VA), polyethylene glycol, poly vinyl alcohol, hyaluronic acid, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), cetyl hydroxyethylcellulose, carrageenan, cellulose ethers, xanthan gum, pullulan, gum acacia, locust bean gum, dextran, chitosan, or a salt thereof, or a combination thereof.

31. The oral care solid film of any one of claims 25-30, wherein the one or more water- soluble polymers comprise pectin.

32. The oral care solid film of any one of claims 25-31, wherein the one or more water- soluble polymers are present in the oral care solid film in an amount ranging from about 30 wt% to about 90 wt%, about 40 wt% to about 80 wt%, or about 50 wt% to about 70 wt%, based on the total weight of the oral care solid film.

33. The oral care solid film of any one of claims 25-32, wherein the one or more enzymes comprise papain, and the one or more water soluble polymers comprise pectin.

34. The oral care solid film of any one of claims 25-33, wherein the oral care solid film further comprises one or more reducing agents.

35. The oral care solid film of claim 34, wherein the one or more reducing agents comprise ascorbic acid or a salt thereof (such as sodium ascorbate), ascorbyl phosphate or a salt thereof, sodium metabisulfite, erythorbic acid or a salt thereof (such as sodium erythorbate), sodiumtetrathionate, sodium stannate, ammonium sulfate, vitamin E, vitamin E acetate, a metal gallate, 3,5, -di-tcrt-butyl-4-hydroxytolucnc (BHT), cysteine, or a combination thereof.

36. The oral care solid film of any one of claims 34-35, wherein the one or more reducing agents comprise ascorbic acid or an alkali metal salt thereof.

37. The oral care solid film of any one of claims 34-36, wherein the one or more reducing agents are present in the oral care solid film in an amount ranging from about 0.01 wt% to about 20 wt%, about 0.1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, or about 3 wt% to about 8 wt%, based on the total weight of the oral care solid film.

38. The oral care solid film of any one of claims 34-37, wherein the one or more enzymes comprise papain, the one or more water soluble polymers comprise pectin, and the one or more reducing agents comprise sodium ascorbate.

39. The oral care solid film of any one of claims 25-38, wherein the oral care solid film further comprises one or more surfactants.

40. The oral care solid film of any one of claims 25-39, wherein the oral care solid film further comprises one or more plasticizers.

41. The oral care solid film of claim 40, wherein the one or more plasticizers comprise glycerin.

42. The oral care solid film of claim 41, wherein the glycerin is present in the oral care solid film in an amount less than about 30 wt%, less than about 25 wt%, less than about 20 wt%, less than about 10 wt%, or less than about 5 wt%, based on the total weight of the oral care solid film.

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