Teeth whitening and tooth sensitivity patches or films

Abstract

A tooth whitening and / or tooth sensitivity patch or film comprising: about 1-20 wt.% hydroxyapatite (HAP). A process for manufacturing a tooth whitening patch or film, the process comprising at least the following steps: mixing at least one polyvinylpyrrolidone (PVP) polymer or a combination of polyvinylpyrrolidone (PVP) polymers, wherein the amount of the polyvinylpyrrolidone (PVP) polymer is greater than about 75 wt.% of the film or patch; at least one polycarbophil or a combination of polycarbophils; and water to provide an aqueous tooth whitening solution; applying the aqueous tooth whitening solution to a substrate to provide a substrate carrying the tooth whitening solution; and drying the aqueous tooth whitening solution to provide a tooth whitening film on the substrate, the film having a thickness of about 50 μm to about 500 μm.

Description

Technical Field

[0001] The present invention relates to an orally dissolvable patch or film for tooth whitening and / or tooth sensitivity. In particular, the present invention relates to a thin and orally dissolvable or substantially orally dissolvable patch or film for tooth whitening and / or tooth sensitivity, the patch or film comprising hydroxyapatite in nano and / or non-nano form. Background Art

[0002] Human teeth naturally exhibit a variety of colors, which can be influenced by many factors, such as diet and medications. For example, many foods, such as berries, and beverages, such as tea and red wine, contain pigments that can stain teeth. Tobacco can also darken teeth. Other substances, such as acidic fruits and beverages, can contribute to staining by eroding tooth enamel, softening teeth, and allowing pigments to more easily adhere to them. Therefore, teeth whitening is often used to remove these stains.

[0003] Dentin hypersensitivity (DH) in general is uncomfortable for patients. Several toothpastes are commercially available for the treatment and prevention of DH. However, these products have drawbacks related to the contact time with the sensitive tooth. They are also applied to general areas rather than specific areas of concern within the mouth, and prolonged use may be required before the user notices any benefit.

[0004] Using toothpaste generally requires a sink and a toothbrush, which can be inconvenient at times. Furthermore, whitening toothpaste comes into contact with the oral mucosa and may cause oral allergies or pain.

[0005] Creating a patch containing active ingredients for the treatment of dentin hypersensitivity (DH) that can address issues related to retention time (customizable dissolution time) and targeted application areas. For example, users can place the patch on the affected area to minimize contact with the oral mucosa. Additionally, other ingredients can be incorporated to freshen breath and improve overall oral health.

[0006] White teeth are desirable. However, certain whitening agents, such as hydrogen peroxide (H2O2) and carbamide peroxide, are known to increase the incidence or severity of dentin hypersensitivity (DH). Toothpaste is inconvenient to use and requires users to apply two separate products.

[0007] The applicant has developed a film or patch containing H2O2 and an agent that reduces the severity of dentin hypersensitivity (DH). The benefit to the consumer is whiter teeth with reduced sensitivity.

[0008] It is an object of at least one aspect of the present invention to obviate or at least mitigate one or more of the above-mentioned problems.

[0009] Another object of the present invention is to provide a dissolvable or substantially dissolvable tooth whitening strip or film that reduces and / or minimizes the severity of dentin hypersensitivity (DH).

[0010] Another object of the present invention is to provide a dissolvable or substantially dissolvable tooth whitening strip or film that can be used to whiten teeth and reduce sensitivity.

[0011] It is another object of the present invention to provide an improved method of whitening teeth that reduces and / or minimizes the severity of dentin hypersensitivity (DH).

[0012] It is another object of the present invention to provide an improved cosmetic method of whitening teeth that reduces and / or minimizes the severity of dentin hypersensitivity (DH). Summary of the Invention

[0013] According to a first aspect of the present invention, there is provided a tooth whitening and / or tooth hypersensitivity patch or film, comprising:

[0014] - about 1-20 wt.% hydroxyapatite (HAP).

[0015] Therefore, the present invention provides a tooth whitening and / or tooth hypersensitivity patch or film that overcomes the above-mentioned problems.

[0016] In the present application, wt. % may be defined as the dry weight of the teeth whitening and / or teeth hypersensitivity strip or film.

[0017] A preferred feature of the patch or film is that it prevents degradation of the hydroxyapatite (HAP) during use and when inserted into a person's mouth.

[0018] Hydroxyapatite (HAP) can be in nano and / or non-nano form.

[0019] The hydroxyapatite (HAP) may be in nanocrystalline form.

[0020] Hydroxyapatite (HAP) may be in the form of a paste such as nanoXIM (trademark) paste.

[0021] Hydroxyapatite (HAP) can be hydroxypentacalcium triphosphate, such as Ca 10 (PO4)6(OH)2. Specifically, the present invention provides a thin, dissolvable patch or film that can reduce or prevent dentin hypersensitivity (DH). DH is a common side effect of hydrogen peroxide tooth whitening. However, by incorporating a desensitizing ingredient along with a whitening agent into the film, this adverse effect can be prevented.

[0022] The present invention involves adding a certain range of desensitizing ingredients to a thin patch or film, wherein the desensitizing ingredients are selected from any one or a combination of the following: nano-hydroxyapatite paste; hydroxyapatite powder; potassium oxalate; and / or Vitryxx TM Bioactive glass.

[0023] This document details internal studies of the whitening efficacy of patches containing (nominally) about 6-10 wt.% hydrogen peroxide (e.g., about 6% hydrogen peroxide) and about 6-10 wt.% nano-hydroxyapatite paste (e.g., about 6.5 wt.% nano-hydroxyapatite paste) or about 6-10 wt.% potassium oxalate (e.g., about 6.5 wt.% potassium oxalate). Applicants' standard 6% hydrogen peroxide formulation was used to provide a positive control. Additionally, external whitening study data summarizes the efficacy of hydrogen peroxide patches containing HAP powder versus competitive patches without nano-HAP.

[0024] The hydroxyapatite (HAP) may be in the form of nano-hydroxyapatite (n-HAP), which has a high n-HAP loading.

[0025] In certain embodiments, the loading of n-HAP can be any of the following: greater than about 10 wt.%; greater than about 15 wt.%; or greater than about 20 wt.%.

[0026] Furthermore, the loading of n-HAP may be any of the following: about 5-20 wt.%; about 10-20 wt.%; or about 15-20 wt.%.

[0027] Hydroxyapatite (HAP) (e.g., n-HAP) may be in the form of a powder formulation. The powder formulation may include the following amounts of HAP: about 1-20 wt.%, about 1-10 wt.%, about 5-15 wt.%, about 5-20 wt.%, about 1-15 wt.%.

[0028] The patch formulation may include a whitening agent, such as phthalimidoperoxycaproic acid (PAP) and / or hydrogen peroxide, optionally in combination with one or more polyphosphates, such as sodium tripolyphosphate or sodium hexametaphosphate.

[0029] The tooth whitening and / or tooth hypersensitivity strips or films of the present invention may be placed directly on areas of the teeth affected by dentin hypersensitivity (DH).

[0030] The tooth whitening and / or tooth sensitivity strips or films of the present invention also have the advantage of not requiring tools and providing additional convenience. The formulation can be modified to include whitening actives as well as other oral health actives.

[0031] In addition, the tooth whitening and / or tooth hypersensitivity patch or film of the present invention can be used by changing the dosage and dissolution time to meet the needs.

[0032] Potential embodiments of the present invention can deliver "high" doses of anti-allergic actives in rapidly dissolving compositions.

[0033] Alternatively, another embodiment may include a "low" dose delivered over an extended period of time.

[0034] The dissolvable patch or film may include hydrogen peroxide (ie, H2O2) in the range of about 6-20 wt.%, or preferably, about 6-10 wt.%. Alternatively, other whitening agents may be used, such as phthalimidoperoxycaproic acid (PAP) and / or urea peroxide.

[0035] Additionally, dissolvable patches or films may include any one or a combination of the following: such as Vitryxx TM of sodium calcium phosphosilicate; potassium oxalate; the amino acid arginine and related compounds, such as arginine bicarbonate; potassium nitrate; and various blends that optionally contain a source of fluoride ions or an alternative source of calcium, sodium, potassium and / or phosphate ions, such as calcium phosphate, dicalcium phosphate, tricalcium phosphate, calcium carbonate, calcium silicate, calcium citrate, calcium monofluorophosphate, calcium sulfate, pentasodium triphosphate, sodium hexametaphosphate, sodium metaphosphate, sodium monofluorophosphate, sodium phosphate, sodium polyphosphate, sodium trimetaphosphate, disodium pyrophosphate, tetrasodium pyrophosphate, trisodium phosphate, potassium phosphate, dipotassium phosphate, pentapotassium triphosphate, potassium carbonate, potassium citrate, potassium fluoride, potassium silicate, potassium fluorosilicate, potassium metaphosphate, potassium monofluorophosphate, tetrapotassium pyrophosphate, and tripotassium phosphate.

[0036] The present invention provides a soluble or substantially soluble tooth whitening strip or film comprising hydrogen peroxide (H2O2), wherein the concentration of hydrogen peroxide (H2O2) is about 10 wt.% to 30 wt.% of the strip or film; about 15 wt.% to 30 wt.% of the strip or film; about 10 wt.% to 20 wt.% of the strip or film; or about 10 wt.% to 15 wt.% of the strip or film.

[0037] Teeth whitening strips or films may also include a series of other ingredients, including any one or a combination of the following:

[0038] - one or more polyphosphates;

[0039] - one or more water-soluble film-forming polymers;

[0040] - one or more plasticizers; and / or

[0041] - One or more emulsifiers.

[0042] The film or patch of the present invention may have a thickness of about 50 μm to about 500 μm; about 50 μm to about 250 μm; about 50 μm to about 100 μm; or about 100 μm to about 200 μm.

[0043] The soluble film-forming polymer may be one or more of the group consisting of polyvinyl pyrrolidone, pullulan, pectin, starch, dextrin, chitosan, alginic acid, alginates, polyalkylene oxides and cellulose derivatives.

[0044] Suitable cellulose derivatives include carboxyalkyl cellulose or its salts and hydroxyalkyl cellulose or its salts, wherein the alkyl group of the carboxyalkyl cellulose or hydroxyalkyl cellulose is independently selected from C 1-5 The alkyl group is preferably a methyl group, an ethyl group or a propyl group. The preferred hydroxyalkyl cellulose may be a hydroxypropyl cellulose.

[0045] Preferably, the water-soluble film-forming polymer may be selected from the group consisting of any one of the following or a combination thereof: polyvinyl pyrrolidone, pullulan, pectin, starch, carboxyalkyl cellulose or its salt, hydroxyalkyl cellulose or its salt, wherein the alkyl group is independently selected from C 1-5 Alkyl groups, alginic acid, alginates, polyglycols (wherein the alkylene group has 2 or 3 carbon atoms) and copolymers thereof, polyacrylic acid or its salts, and combinations thereof.

[0046] The water-soluble film-forming polymer can be a polymer in a hydrogen peroxide-polymer complex that can form a tooth bleaching agent. For example, when the water-soluble film-forming polymer is polyvinylpyrrolidone, it can be present as a tooth bleaching agent to form a complex with hydrogen peroxide.

[0047] The total amount of one or more film-forming polymers present in the film or patch can be in an amount of about 40 wt % to about 95 wt %; about 50 wt % to about 95 wt %; about 60 wt % to about 95 wt %; about 50 wt % to about 80 wt %; or about 50 wt % to about 70 wt %.

[0048] Preferably, the one or more film-forming polymers may be present in a total amount of about 50 wt % to about 90 wt %. More preferably, the one or more film-forming polymers may be present in a total amount of about 60 wt % to about 85 wt %. Even more preferably, the one or more film-forming polymers may be present in a total amount of about 65 wt % to about 80 wt %.

[0049] In one embodiment, the one or more plasticizers may be selected from the group consisting of polyols such as glycerol, polyglycol, polyglycol monomethyl ether, monosaccharides, oligosaccharides, sorbitol and sorbitan, wherein the alkylene groups are independently selected from C 1-5The alkylene group is preferably a methylene group, an ethylene group or a propylene group. The preferred polyglycol may be one or both of polyethylene glycol and polypropylene glycol. The preferred polyglycol monomethyl ether may be polyethylene glycol monomethyl ether. The preferred plasticizer may be glycerol.

[0050] The one or more plasticizers may be present in the film or patch in a total amount of about 0.1 wt.% to about 15 wt.%. Preferably, the one or more plasticizers may be present in a total amount of about 1 wt.% to about 12 wt.%. More preferably, the one or more plasticizers may be present in the film in a total amount of about 3 wt.% to about 10 wt.%.

[0051] The tooth whitening / dentin hypersensitivity film may include one or more emulsifiers. In one embodiment, the one or more emulsifiers may be selected from ionic emulsifiers and non-ionic emulsifiers. In another embodiment, the one or more emulsifiers may be selected from the group consisting of fatty acid derivatives, lecithin, and polysorbate.

[0052] Preferably, emulsifier, such as nonionic emulsifier, can be selected from the group comprising saturated fatty acid derivatives, lecithin or polysorbate. Fatty acid can be saturated or unsaturated. More preferably, nonionic emulsifier can comprise at least one unsaturated fatty acid and optional at least one saturated fatty acid, or one or both of the polysorbate, the unsaturated fatty acid such as oleic acid and / or linoleic acid, the saturated fatty acid such as palmitic acid and / or stearic acid.

[0053] More preferred emulsifiers, such as nonionic emulsifiers, can be selected from fatty acids and polysorbates, and the fatty acids can be saturated or unsaturated. More preferably, the emulsifier, such as a nonionic emulsifier, comprises one or both of the following: (i) 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, and (ii) a polysorbate. Polysorbates are polyethoxylated esters of sorbitol, sorbitan, and isosorbide. Preferred saturated fatty acid derivatives include sucrose esters of saturated fatty acids; monoglycerides, diglycerides, or triglycerides of saturated fatty acids; or sorbitan esters of saturated fatty acids.

[0054] One or more emulsifiers may be present in the film in a total amount of about 0.1 wt.% to 10 wt.%. More preferably, one or more emulsifiers are present in a total amount of about 1 wt.% to 5 wt.%, more preferably in a total amount of about 2 wt.% to 4 wt.%.

[0055] In one embodiment, the tooth whitening film may further include water. The water may be present in the film in an amount of less than or equal to about 15 wt.%, particularly in an amount of about 0.1 wt.% to 15 wt.%. Typically, the tooth whitening film may further include water in an amount of about 3 wt.% to 12 wt.%, preferably, in an amount of about 5 wt.% to 10 wt.%.

[0056] In one embodiment, the tooth whitening film may further include one or more optional ingredients selected from the group consisting of colorants, gelling agents, flavoring agents, sweeteners, acidulants, antioxidants, solubility extenders, and chelating agents.

[0057] The gelling agent may be a hydrocolloid binder.

[0058] Other ingredients of the tooth whitening film, such as certain types of water-soluble film-forming polymers like polyvinylpyrrolidone and certain polysaccharides like hydroxypropylcellulose, can exhibit gelling behavior. For the purposes of the present invention, when a gelling agent is present as an additional optional ingredient of the tooth whitening film, it is considered separate from and additional to any other ingredients that may exhibit gelling behavior.

[0059] The flavoring agent may be selected from the group consisting of menthol, peppermint, and alkyl alkanoates, wherein the alkyl group may be linear or branched and may comprise 1 to 8 carbon atoms and the alkanoate group may comprise 1 to 5 carbon atoms.

[0060] The sweetener may be selected from one or more of the group consisting of aspartame, acesulfame K, sucralose, cyclamate, erythritol, mannitol, sorbitol, stevia and / or xylitol.

[0061] The acidifying agent may be phosphoric acid.

[0062] The antioxidant may be selected from one or more of the group consisting of tocopherol (vitamin E), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and ethylenediaminetetraacetic acid or a salt thereof.

[0063] Introducing a small amount (eg, about 1-5 wt. % or about 2-3 wt. %) of polycarbophil (eg, Noveon, a registered trademark) can slow down the dissolution rate of the composition, thereby potentially increasing the whitening effect.

[0064] Noveon (registered trademark) may be Noveon AA-1 polycarbophil USP, which has a Brookfield viscosity of 2,000-12,000 (measured on a Brookfield RVT, 20 rpm, neutralized to pH 7.3-7.8).

[0065] Polycarbophil may include a metal salt of polyacrylic acid cross-linked with ethylene glycol.

[0066] In certain embodiments, polycarbophil may include calcium salt of polyacrylic acid cross-linked with diethylene glycol, and may have a viscosity of, for example, 2,000-12,000 cP for an approximately 0.2% solution.

[0067] Polycarbophil may be in the form of a metal salt, such as polycarbophil calcium. Polycarbophil may be formed as a synthetic polymer of polyacrylic acid cross-linked with diethylene glycol, with calcium as a counter ion, for example.

[0068] The chelating agent may be ethylenediaminetetraacetic acid or a salt thereof. The chelating agent can be used to capture heavy metal ions, thereby preventing the decomposition of the peroxycarboxylic acid.

[0069] Other ingredients may optionally have antimicrobial or antibacterial properties, such as cetylpyridinium chloride or zinc acetate, which generally improve oral health.

[0070] In another embodiment, the tooth whitening film / dentin hypersensitivity film may be a single layer.

[0071] In another embodiment, the tooth whitening film / dentin hypersensitivity film is free of any other layer or layers, such as a barrier layer or a supporting substrate.

[0072] In another embodiment, the film can be used without dental braces and has a thickness in the range of 50 to 250 microns, more preferably, the film has a thickness in the range of 100 to 200 microns, and even more preferably, about 150 microns.

[0073] Preferably, the membrane can be used without orthodontic appliances and has a length of 50 to 70 mm, more preferably about 60 mm. Preferably, the membrane has a width of 10 to 20 mm, more preferably about 15 mm.

[0074] The film can be used without dental braces and has a weight ranging from 60 to 250 mg, preferably from 100 to 200 mg, more preferably about 150 mg.

[0075] In another embodiment, the film can be used with dental braces and has a thickness in the range of 50 to 150 microns, more preferably, the film has a thickness in the range of 60 to 130 microns, and even more preferably, 70 to 125 microns.

[0076] In a second aspect, a process for manufacturing a tooth whitening strip or film / dentin hypersensitivity strip or film is provided, the process comprising at least the following steps:

[0077] - The following ingredients are mixed to provide an aqueous teeth whitening solution / dentin hypersensitivity solution;

[0078] - at least one polyvinylpyrrolidone (PVP) polymer or a combination of polyvinylpyrrolidone (PVP) polymers, wherein the amount of polyvinylpyrrolidone (PVP) polymer is greater than about 35 wt.% of the film or patch;

[0079] - a content of at least about 1-20 wt.% hydroxyapatite (HAP);

[0080] - Optionally, at least one polycarbophil or a combination of polycarbophils;

[0081] -optionally, a source of a tooth whitening agent, such as hydrogen peroxide or phthalimidoperoxycaproic acid (PAP); and

[0082] -water;

[0083] - applying an aqueous teeth whitening solution / dentin hypersensitivity solution to a substrate to provide a teeth whitening solution / dentin hypersensitivity solution-carrying substrate; and

[0084] - drying the aqueous tooth whitening / dentin hypersensitivity solution to provide a tooth whitening / dentin hypersensitivity film on a substrate, the film having a thickness of about 50 μm to about 500 μm.

[0085] Optionally, the process may further comprise adding at least one polycarbophil or a combination of polycarbophils.

[0086] Additionally, the process includes a source of a tooth whitening agent, such as hydrogen peroxide or phthalimidoperoxycaproic acid (PAP).

[0087] In one embodiment, the aqueous tooth whitening solution / dentin hypersensitivity solution comprises greater than 60 wt.% of water (based on the total amount of the tooth whitening solution / dentin hypersensitivity solution, including any water present), preferably 70 wt.% to 85 wt.% of water. Therefore, the aqueous tooth whitening solution / dentin hypersensitivity solution may comprise about 40 wt.% or less of a tooth whitening film / dentin hypersensitivity film-forming component, preferably 15 wt.% to 30 wt.% of a tooth whitening film / dentin hypersensitivity film-forming component.

[0088] In one embodiment, the drying step comprises:

[0089] - Drying the aqueous tooth whitening / dentin hypersensitivity solution in air at a temperature below about 60°C.

[0090] In another embodiment, the aqueous tooth whitening liquid / dentin hypersensitivity liquid is dried in air at a temperature in the range of about 40°C to less than 60°C, preferably in the range of about 40°C to 55°C.

[0091] In another embodiment, drying can be performed at a speed in the range of about 0.2 to 2.0 m / min, preferably, at a speed in the range of about 0.5 to 1.5 m / min, for example, by passing the aqueous tooth whitening solution / dentin hypersensitivity solution on the substrate through a dryer such as an oven, hot air flow, etc.

[0092] In another embodiment, the drying step is performed for about 80 minutes or less, preferably about 35 minutes or less, and more preferably about 25 minutes or less. The drying step may be performed for about at least 8 minutes, preferably about at least 15 minutes, and more preferably about at least 20 minutes. Thus, the drying step may be performed for about 8 to 80 minutes, preferably about 15 to 35 minutes, and more preferably about 20 to 25 minutes.

[0093] In another embodiment, the mixing step is performed under high shear conditions, for example, at a shear rate greater than about 500 s-1 Under the condition of s-1 , up to about 8000 s-1 Preferably, the shear rate range is 1000 s-1 to 4000 s-1 .

[0094] In one embodiment, the mixing step further comprises mixing one or more additional ingredients selected from the group consisting of colorants, gelling agents, flavoring agents, sweeteners, acidulants, antioxidants, and chelating agents.

[0095] In a third aspect, a tooth whitening strip or film / dentin hypersensitivity strip or film obtained by the process of the second aspect and its embodiments is provided.

[0096] In a fourth aspect, a method for bleaching teeth is provided, the method comprising at least the following steps:

[0097] - applying a teeth whitening strip or film according to the first, second or third aspect to one or more teeth of a subject.

[0098] The method may be a cosmetic method, in particular a purely cosmetic method.

[0099] The film or patch may be applied to the front surface of one or more teeth and / or above the front surface of one or more teeth, the chewing surface and / or the back surface of one or more teeth. BRIEF DESCRIPTION OF THE DRAWINGS

[0100] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0101] FIG. 1 shows the brightness (L) values ​​of a series of test batches relative to the number of treatments according to an embodiment of the present invention.

[0102] FIG2 is a table showing a series of compositions according to yet another embodiment of the present invention;

[0103] Tables 3A and 3B in FIG. 3A and FIG. 3B respectively show compositions according to yet another embodiment of the present invention; and

[0104] Table 4 of FIG. 4 shows a series of additional data for the compositions shown in Tables 3A and 3B. DETAILED DESCRIPTION

[0105] The present invention relates to a tooth whitening strip or film. The present invention also relates to a thin, orally dissolvable or substantially dissolvable strip or film comprising hydroxyapatite (e.g., nanoXIM) for use in tooth whitening and / or treating tooth hypersensitivity. The hydroxyapatite may be in nano and / or non-nano form.

[0106] In particular, the present invention relates to dissolvable or substantially dissolvable tooth whitening strips or films, such as those comprising hydrogen peroxide and / or phthalimidoperoxycaproic acid (PAP).

[0107] In a preferred embodiment, the dissolvable or substantially dissolvable tooth whitening strip or film comprises phthalimidoperoxycaproic acid (PAP).

[0108] The present invention also relates to a process for making a dissolvable or substantially dissolvable tooth whitening / dentin hypersensitivity strip or film, and a method of using the strip or film to whiten and / or bleach teeth. The method can be a cosmetic method of whitening and / or bleaching teeth.

[0109] plasticizers

[0110] In the present invention, a plasticizer may be present in the tooth whitening film. Preferably, the plasticizer should be a physiologically acceptable plasticizer.

[0111] The one or more plasticizers may be selected from the group consisting of polyols such as glycerol, alkylene groups independently selected from C 2-5 Alkylene polyglycol, alkylene independently selected from C 2-5Alkylene polyglycol monomethyl ether, monosaccharide, oligosaccharide, sorbitol and anhydrous sorbitan, preferably alkylene is ethylene or propylene. Preferred polyglycol is polyethylene glycol and / or polypropylene glycol. Preferred polyglycol monomethyl ether is polyethylene glycol monomethyl ether.

[0112] The plasticizer may be a hydrophilic plasticizer, for example one or more of the group consisting of polyols, such as glycerol, polyethylene glycol, polyethylene glycol monomethyl ether, propylene glycol, sorbitol and sorbitan. A preferred plasticizer is glycerol.

[0113] The one or more plasticizers may be present in the film in a total amount of about 0.1 wt.% to about 15 wt.%. Preferably, the one or more plasticizers may be present in a total amount of about 1 wt.% to about 12 wt.%. More preferably, the one or more plasticizers may be present in the film in a total amount of about 3 wt.% to about 10 wt.%, or in a range of about 1 to about 5 wt.%.

[0114] emulsifiers

[0115] The tooth whitening film comprises one or more emulsifiers. The one or more emulsifiers can be selected from ionic emulsifiers and / or nonionic emulsifiers.

[0116] Preferably, the nonionic emulsifier is selected from the group consisting of saturated fatty acid derivatives, lecithin or polysorbate. The fatty acid may be saturated or unsaturated. More preferably, the nonionic emulsifier comprises at least one unsaturated fatty acid and optionally at least one saturated fatty acid, or one or both of the polysorbates, the unsaturated fatty acids being oleic acid and / or linoleic acid, and the saturated fatty acids being palmitic acid and / or stearic acid.

[0117] Polysorbates are polyethoxylated sorbitol, sorbitan, and isosorbide esters. Preferred saturated fatty acid derivatives include sucrose esters of saturated fatty acids; mono-, di-, or triglycerides of saturated fatty acids; or sorbitan esters of saturated fatty acids. A preferred emulsifier is sorbitol, such as T80 supplied by Azelis.

[0118] One or more emulsifiers may be present in the film in a total amount of 0.1 to 10 wt %, preferably in a total amount ranging from 2.0 to 2.5 wt %, based on the dry weight of the tooth whitening film.

[0119] Optional Ingredients

[0120] The tooth whitening film may further comprise one or more optional ingredients selected from the group consisting of colorants, gelling agents, flavoring agents, sweeteners, acidulants, antioxidants, antimicrobial / antibacterial agents, and chelating agents.

[0121] The gelling agent can be a hydrocolloid. Typically, the gelling agent can be a hydrocolloid that is also used as a binder. As used herein, the term "hydrocolloid" refers to a hydrophilic polymer that can be of any origin, such as plant, animal, microbial, or synthetic, contains hydrophobic groups, and forms a gel in the presence of water, i.e., a heterogeneous system having a solid hydrocolloid network containing a liquid aqueous phase. The hydrocolloid binder can be selected from natural gums, polyacrylic acids, or polyalkylacrylic acids in which the alkyl group is methyl or ethyl. The alkyl group can be methyl or ethyl, i.e., polymethacrylic acid or polyethylacrylic acid. The natural gum can be selected from alginic acid and its salts, agar, carrageenan, tragacanth gum, and polysaccharide gums. More preferably, when the hydrocolloid gelling agent is a natural gum, it is tragacanth gum, which comprises a mixture of water-soluble polymers and water-insoluble polymers, particularly a mixture of polysaccharides, such as a mixture of tragacanth and tragacanth polymers. The tragacanth polymer may be a polymer of fucose, xylose, arabinose, galacturonic acid, and rhamnose.

[0122] Alternatively, the hydrocolloid binder may be a polymer of acrylic acid or alkylacrylic acid as defined above. High molecular weight polyacrylic acid is also known as carbomer. The polymer of acrylic acid may be cross-linked or uncross-linked.

[0123] Examples of crosslinking agents include pentaerythritol allyl ether, sucrose allyl ether or propylene allyl ether. Crosslinked polymers of acrylic acid are marketed by Lubrizol Corporation under the trade name Carbopol ® For sale.

[0124] Polyacrylic acid can be provided in the form of a salt, such as an ammonium salt, a sodium salt, a potassium salt, a magnesium salt or a calcium salt. Crosslinked polyacrylic acid, such as those crosslinked with divinyl glycol, can be provided in the form of a salt, such as a magnesium salt or a calcium salt, in particular a calcium salt, also known as polycarbophil. Suitable polycarbophils are available from Lubrizol under the trade name Noveon TM For sale.

[0125] The gelling agent may be present in an amount ranging from 0.1 to 10 wt % of the dry weight of the tooth whitening film.

[0126] Flavoring agent can be artificial flavoring agent or natural flavoring agent. Flavoring agent can be selected from the group comprising menthol, peppermint and alkyl alkanoate, wherein alkyl can be straight chain or branched, and can comprise 1 to 8 carbon atoms, and alkanoate group can comprise 1 to 5 carbon atoms. Preferably, the alkyl of alkyl alkanoate has 1,2,5 or 8 carbon atoms, and the alkanoate group of alkyl alkanoate can comprise 1 to 5 carbon atoms, preferably 1,4 or 5 carbon atoms. Preferred alkyl alkanoate is methyl butyrate [apple / pineapple], ethyl butyrate [orange / pineapple], isoamyl acetate [banana / pear], amyl butyrate [pear / apricot], amyl valerate [apple], octyl acetate [orange].

[0127] Peppermint is a common flavoring used in tooth whitening masks. Peppermint flavoring contains menthol and other ingredients such as menthone, menthofuran, cineole, pulegone, and some smaller ingredients.

[0128] Preferably, the flavoring agent is present in a proportion of 0.1 to 10 wt.% of the dry weight of the tooth whitening film, more preferably in a proportion of 1 to 5 wt.% of the dry weight of the tooth whitening film.

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

[0130] Preferably, the sweetener is present in a proportion of 0.01 to 5 wt.% based on the dry weight of the tooth whitening film. More preferably, the acidulant is present in a proportion of 0.05 to 0.5 wt.% based on the dry weight of the tooth whitening film.

[0131] The acidulant may be an inorganic acidulant or an organic acidulant. Phosphoric acid is a preferred inorganic acidulant. Preferred organic acidulants are selected from the group consisting of lactic acid, malic acid, acetic acid and citric acid, and the most preferred organic acidulant is citric acid.

[0132] Preferably, the acidifying agent is present in a proportion of 0.1 to 5% by dry weight of the tooth whitening film. More preferably, the acidifying agent is present in a proportion of 1.0 to 1.5% by dry weight of the tooth whitening film.

[0133] The antioxidant may be one or more selected from tocopherol (vitamin E), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), di-tert-butylhydroxytoluene and ethylenediaminetetraacetic acid or its salt. A preferred antioxidant is ethylenediaminetetraacetic acid (EDTA).

[0134] Preferably, the antioxidant is present in a proportion of 0.01 to 0.5 wt. % based on the dry weight of the tooth whitening film, more preferably in a proportion of 0.05 to 0.15 wt. % based on the dry weight of the tooth whitening film.

[0135] The chelating agent may be ethylenediaminetetraacetic acid or a salt thereof. The chelating agent can be used to capture heavy metal ions, thereby preventing the decomposition of the peroxycarboxylic acid.

[0136] The chelating agent may be present in an amount of 0.1 to 5 wt. % based on the dry weight of the tooth whitening film.

[0137] Preservatives may also be present in the tooth whitening film. Commonly used preservatives may be one or more compounds selected from the group consisting of potassium sorbate, benzoic acid and its salts, propionic acid and its salts, salicylic acid and its salts, and triclosan.

[0138] Preferably, the preservative is present in a proportion of 0.01 to 5 wt. % based on the dry weight of the tooth whitening film. More preferably, the preservative is present in a proportion of 0.05 to 0.5 wt. % based on the dry weight of the tooth whitening film.

[0139] Additionally, the dissolvable patch or film may include any one or a combination of the following: such as Vitryxx TM of calcium sodium phosphosilicate; potassium oxalate; the amino acid arginine and related compounds, such as arginine bicarbonate; potassium nitrate; and various blends that optionally contain a source of fluoride ions or an alternative source of calcium, sodium, potassium and / or phosphate ions, such as calcium phosphate, dicalcium phosphate, tricalcium phosphate, calcium carbonate, calcium silicate, calcium citrate, calcium monofluorophosphate, calcium sulfate, pentasodium triphosphate, sodium hexametaphosphate, sodium metaphosphate, sodium monofluorophosphate, sodium phosphate, sodium polyphosphate, sodium trimetaphosphate, disodium pyrophosphate, tetrasodium pyrophosphate, trisodium phosphate, potassium phosphate, dipotassium phosphate, pentapotassium triphosphate, potassium carbonate, potassium citrate, potassium fluoride, potassium silicate, potassium fluorosilicate, potassium metaphosphate, potassium monofluorophosphate, tetrapotassium pyrophosphate, and tripotassium phosphate.

[0140] The present invention also discloses a process for preparing the tooth film, which does not require the presence of other layers, such as a barrier layer or a supporting substrate.

[0141] The tooth whitening film is prepared from an aqueous tooth whitening solution. The aqueous tooth whitening solution is a mixture of the tooth whitening film components and water. The components are as described in this application.

[0142] The non-peroxide bleaching agent and water-soluble film-forming polymer components of the tooth whitening film can be mixed with water to provide an aqueous tooth whitening solution. Typically, the water is drinking water. Distilled water or deionized water can also be used. Preferably, the components are added to the water under a shear field.

[0143] The mixing step may further comprise adding one or more additional ingredients of the aqueous tooth whitening film. The one or more additional ingredients may be selected from one or more of the group consisting of colorants, gelling agents, flavoring agents, sweeteners, acidulants, antioxidants, and chelating agents.

[0144] Mixing parameters, such as shear force and shear duration, will depend on the scale of the manufacturing process and the tooth whitening film ingredients to be mixed. This, in turn, will influence the choice of equipment used in the mixing step.

[0145] Typically, the mixing step begins by adding any water-soluble film-forming polymer, plasticizer, and optionally, gelling agent, additional polymer, or gum to the water. Typically, any acidulant and any optional additional ingredients, such as colorants, sweeteners, or other low-level additives, are also added at this stage. The water-soluble film-forming polymer and any other polymer components or gums are added sequentially to prevent excessive viscosity early on, i.e., the polymer or gum that produces the lowest viscosity is added first. Typically, any flavoring is mixed in at a later stage to prevent decomposition of any heat-sensitive ingredients or loss of volatile components. On a laboratory scale, non-peroxide bleaching agents, such as peroxycarboxylic acids, particularly complexes of PAP and polysaccharides, such as complexes of PAP and dextrin, may be added near the end of mixing to prevent unnecessary exposure to heat that could lead to degradation. On an industrial scale, heat buildup during mixing is significantly reduced, so non-peroxide bleaching agents can be added at any point during the mixing step.

[0146] For example, these compositions can be mixed in a shear rate range of 1000 to 6000 rpm. For a smaller amount on a laboratory scale, the shear rate may be in the range of 2000 to 6000 rpm, preferably in the range of 3000 to 4000 rpm. For a larger amount on an industrial scale, the shear rate may be in the range of 1500 to 2500 rpm, preferably about 2000 rpm. For a small batch on a laboratory scale, the mixing time may be in the range of 5 to 20 minutes, preferably in the range of 5 to 10 minutes. For a larger amount on an industrial scale, the mixing time may be in the range of 10 to 20 minutes, preferably about 15 minutes.

[0147] Once these ingredients are mixed with water to provide an aqueous teeth whitening solution, it can be applied to a substrate. The aqueous teeth whitening solution can be applied using known film-forming processes such as dipping, spraying, roller casting, extrusion, and injection molding.

[0148] Casting equipment can be used to apply aqueous tooth whitening solutions to a substrate, such as a casting wheel, applicator, mold, or hopper. The aqueous solution can be pumped into the applicator. If necessary, the temperature of the aqueous solution can be maintained constant by a heating element, allowing for careful control of the viscosity of the solution.

[0149] The coating device is used for coating water-based teeth whitening liquid.The ...

[0150] Many different materials can be used for the substrate, such as copper; silver-plated copper; chrome-plated steel; stainless steel; metal coated with polyvinyl alcohol or gelatin; paper, such as silicone-coated paper; or polymer films, such as polyethylene film, polypropylene film, polyester film, such as polyethylene terephthalate (PET) film, in particular siliconized PET film, polytetrafluoroethylene (PTFE) film. Preferably, the substrate comprises paper coated with a release layer, such as silicone film, polyethylene film, polypropylene film, polytetrafluoroethylene (PTFE) film, or polyester film, such as polyethylene terephthalate (PET film), in particular siliconized PET film.

[0151] Then, the aqueous tooth whitening liquid supported on the substrate is dried. Exemplary drying methods include indirect heating, radiant heating and air flow drying.

[0152] In one embodiment, an air inlet stream with no or low moisture content is directed toward the aqueous tooth whitening solution on the substrate, and an air exhaust stream laden with water vapor is removed. The air exhaust stream laden with moisture may be exhausted or sent to a condenser to condense and separate the liquid water.

[0153] The aqueous tooth whitening solution on the substrate can be dried on both sides. This can be achieved by winding the dry tooth whitening film around a series of polishing rollers and directing an air inlet stream to each exposed surface in turn.

[0154] The air intake stream may be at ambient temperature. Alternatively, the air intake stream may be heated. The bleaching agent PAP melts above 75°C and degrades to ε-phthalimidopentanol with the formation of carbon dioxide, so the temperature of the heated air intake stream should be below 60°C. Preferably, the temperature of the heated air intake stream ranges from above ambient temperature to 60°C. More preferably, the temperature of the heated air intake stream ranges from 25°C to 55°C, and even more preferably, from 45°C to 55°C. Heating may be performed using a belt heater with a belt speed ranging from 0.2 to 2.0 m / min, preferably from 0.5 to 1.5 m / min.

[0155] Alternatively, heated rollers or radiant heaters, such as infrared lamps, may be used to dry the aqueous liquid to provide the film. These may heat the tooth whitening liquid supported on the substrate to a temperature in the range of from greater than ambient temperature to about 60°C, preferably to a temperature in the range of from about 25°C to 55°C.

[0156] The drying step may include carrying out the first drying to the first surface of the aqueous tooth whitening liquid supported on the substrate, to provide the first dry tooth whitening film supported on the substrate. The first surface of the aqueous tooth whitening liquid may be the outer surface of the liquid relative to the second surface adjacent to the support. Then, the first dry tooth whitening film can be separated from the substrate. Then, the second surface of the first dry tooth whitening film can be carried out the second drying to provide the second dry tooth whitening film. As previously mentioned, the first drying and the second drying can be carried out independently.

[0157] By this method, a tooth whitening film can be provided, the water content of the film being less than 15 wt.% of the dry weight of the film. Preferably, the water content of the film is in the range of 3-12 wt.% of the dry weight of the film, more preferably, the water content of the film is in the range of 5-10 wt.% of the dry weight of the film, and even more preferably, the water content of the film is in the range of 5-7 wt.% of the dry weight of the film.

[0158] The tooth whitening film can be stored in a sterile package, such as a sealed package. The sealed package can be watertight, more preferably watertight and airtight. The package can be made of a metal foil (such as aluminum foil) or a plastic film coated with a metal layer.

[0159] The tooth whitening film obtainable by the method disclosed herein can be used in a method for bleaching teeth. The method may include at least the following steps:

[0160] - Applying the teeth whitening film obtained herein above to one or more teeth of a subject.

[0161] The method may be a cosmetic method. Preferably, the method is a purely cosmetic method. As used herein, the term "pure cosmetic method" refers to a cosmetic method that does not involve the treatment or prevention of a condition or indication.

[0162] Certain aspects and embodiments of the present invention will now be described by way of example and with reference to the following tables.

[0163] Example

[0164] The present invention can be illustrated as follows.

[0165] Example 1

[0166] Hydroxyapatite (HA) discs: Pretreatment

[0167] Before using the hydroxyapatite (HA) discs in the whitening experiments, they were treated to make them suitable for use.

[0168] The treatment involves forming a thin film layer on the surface of the HA substrate, followed by exposing it to a dye broth.

[0169] Thin film layer formation

[0170] Artificial saliva was prepared using a modified version of WI-82-05-5 Rev 3, in which the amount of each reagent was halved to produce a half-batch (500 ml) of artificial saliva. Porcine gastric mucin (PGM) (1.25 g) was added in four separate additions, each followed by stirring with a magnetic stir bar at 950 rpm for approximately 15 minutes, with the final addition followed by stirring for 90 minutes to produce a turbid, slightly yellowish PGM / artificial saliva mixture solution (concentration 2.5 g / L). HA discs were polished on one side using 240-grit water-abrasive sandpaper, and the color of the polished surface was measured using a colorimeter according to WI-73-03-7 Rev 2. Each disc was placed with the polished side facing up in a Petri dish, into which the PGM / artificial saliva mixture was added. The dishes were covered and placed in an oven at approximately 37°C overnight, for approximately 18 hours. The discs were then removed, patted dry with a paper towel, and the color was measured again before use.

[0171] Staining broth recipe and preparation

[0172] Preparation of staining broth: Nescafé Gold instant (registered trademark) coffee (1 g) was dissolved in boiling water (100 mL) in a 150 mL beaker and stirred at 350 rpm using a magnetic stirring bar for 5 minutes.

[0173] In a 150 mL beaker, add a single Tetley tea bag to 100 mL of boiling water and stir at 350 rpm with a magnetic stir bar for 5 minutes. Add the tea solution and coffee solution to a 500 mL beaker.

[0174] Concentrated blueberry juice (30 mL) and potassium sorbate (0.5 g) were then added to the tea / coffee solution. PGM (0.75 g) was then added to the dye broth in three portions, stirring with a magnetic stir bar at 950 rpm for 15 minutes after each addition, and for 90 minutes after the final addition of PGM.

[0175] Place each HA disc in its own Petri dish, polished side up. Add staining broth to the dish until each disc is completely submerged, taking care not to pour broth vertically onto the surface of the disc. Cover the dish, label it, and place it in an oven at approximately 37°C for 72 hours.

[0176] The benefits of teeth whitening strips

[0177] Process the stained HA discs using the following protocol:

[0178] (Using a disposable pipette) Place one drop of room temperature PGM / artificial saliva mixture on each disc. Place pre-cut tooth whitening strip squares on the discs, covering the surface. Place one drop of PGM / artificial saliva mixture on the strips and spread with a paintbrush. After 5 minutes, add another drop of PGM / artificial saliva mixture and gently scrub the surface of the disc with a paintbrush. Repeat step 4 after 10, 15, and 20 minutes. After 25 minutes, gently scrub the disc with a paintbrush (do not add PGM / artificial saliva mixture at this step). After 30 minutes, wipe the disc with a paper towel to remove any excess whitening strips. Rinse each disc in 100ml of water and then pat dry with a paper towel. Allow the discs to air dry for 1 hour before measuring the color. Color Measurement

[0179] Color was measured using a colorimeter (Minolta Colorimeter CR-400) using Hunter's L, a, and b color scales, where the L value represents the degree of brightness, with 0 being completely black and 100 being completely bright.

[0180] The above steps were repeated to provide a total of 10 treatments.

[0181] Batch preparation

[0182] Developmental batches of approximately 6% H2O2 tooth whitening strips were prepared, comprising approximately 6.5% nano-hydroxyapatite paste (n-HAP) and approximately 6.5% potassium oxalate, as outlined in DEV04861 and DEV04852 (see Figure 1). The nano-hydroxyapatite paste (n-HAP) can be NanoXIM (trademark). These developmental batches were tested against a standard 6% peroxide formulation to provide a positive control for comparison. Two discs were not treated with the whitening strips to serve as negative controls.

[0183] Disc processing

[0184] Two discs were treated with each of the formulations listed above, and Table 1 shows which discs were treated with which formulation. Each formulation was tested by titration with KMnO4.

[0185] Table 1: Summary of batches tested during the whitening trial

[0186]

[0187] Note: Potassium oxalate is also titrated with KMnO4 and the reported value is corrected for 6.5% oxalic acid and should therefore be the correct H2O2 content.

[0188] Figure 1 shows the change in lightness (L value) during the 10 treatments for each batch tested.

[0189] As can be seen in Figure 1, DEV04682 showed the fastest onset of whitening. However, after 10 treatments, the three peroxide lots reached similar endpoints (within ±10%).

[0190] The average L values ​​for discs treated with DEV04861 and DEV04862 were lower than the initial values ​​for the two control samples. This lower initial starting point may explain the high initial whitening rates observed for the two developmental batches, as the whitening effect may be more pronounced on darker samples. After three treatments, the whitening rates of the two developmental samples were consistent with those of the positive control, indicating that the addition of n-HAP and potassium oxalate had no effect on the whitening efficacy of the tested membranes.

[0191] Adding tooth desensitizing ingredients to hydrogen peroxide whitening films had no effect on whitening effectiveness when compared to standard hydrogen peroxide films.

[0192] Both developmental lots performed significantly better than the negative control. In both developmental lots, DEV04862 (potassium oxalate) showed an increased rate of whitening compared to the control lot during the first four treatments. However, after 10 treatments, its performance level was comparable to the control lot. Throughout the study, DEV04861 (n-HAP) performed significantly better than the control lot.

[0193] Example 2

[0194] The applicant has recently developed a new thin, dissolvable film that can reduce / prevent dentin hypersensitivity (DH). DH is a side effect of peroxide tooth whitening. However, by incorporating a desensitizing ingredient along with the whitening agent into the film, it is possible to avoid this undesirable effect.

[0195] The applicant has studied the addition of three potential desensitizing ingredients to the film in the presence and absence of whitening agents. The three desensitizing ingredients studied are: nano-hydroxyapatite (n-HAP) paste; Vitryxx TM Activated glass and potassium oxalate.

[0196] Hydroxyapatite

[0197] n-HAP or HAP powder can be added to oral care products such as toothpaste and mouthwash to treat tooth sensitivity or promote remineralization. The development work was conducted using the applicant's standard 6 wt.% hydrogen peroxide tooth whitening formulation as a starting point. However, the whitening agent, Peroxydone, a polyvinylpyrrolidone-hydrogen peroxide complex, was replaced with pure polyvinylpyrrolidone (PVP). In the initial formulation, xylitol was used instead of sucralose because xylitol promotes mineralization by increasing saliva flow and also has antibacterial properties. Information on the batches produced is listed below:

[0198] Both DEV04835 and DEV04837 attempted to add about 6.5 wt.% of n-HAP paste (e.g., nanoXIM paste provided by Fluidinova). However, upon adding the n-HAP paste, the viscosity of the casting solution increased significantly, reaching a viscosity that made further processing impossible.

[0199] DEV04838 reduced the pectin content to compensate for n-HAP, but the casting solution was still too viscous to process.

[0200] DEV04842 used pullulan instead of pectin. However, the addition of n-HAP paste did not thicken the casting solution, indicating that the specific combination of pectin and n-HAP caused the thickening of the casting solution. The lack of thickening resulted in a casting solution that was too thin to be used.

[0201] DEV04844 Approximately 10 wt.% pectin was added to the formulation used for DEV04842, thickening the formulation sufficiently to allow film production. The quality of the films was good and contained approximately 6.5 wt.% n-HAP paste.

[0202] Since DEV04844 successfully produced high-quality membranes, this formulation was attempted as a base for the addition of hydrogen peroxide.

[0203] DEV04848 replaces PVP with an equivalent amount of peroxydone to a standard 6% peroxide formulation. Patches produced from DEV04848 were tested and found to contain 4.6 wt.% peroxide, which is within the limits specified in the applicant's finished 6 wt.% peroxide product specifications.

[0204] DEV04849 is based on a 10 wt.% peroxide formulation, with n-HAP paste increased to about 10 wt.% to provide a high strength, high protection patch. Due to the high level of Peroxydone required to achieve about 10 wt.% peroxide in the finished film, pullulan is not present in the film.

[0205] DEV04855 attempted to add approximately 6.5% of n-HAP paste to the applicant's non-peroxide tooth whitening formulation. The formulation did not thicken after the addition of n-HAP paste, again demonstrating that n-HAP's thickening properties are more effective when combined with a pectin-based film. The sample was successfully produced and retained.

[0206] Vitryxx TM Bioactive glass and potassium oxalate

[0207] In addition to n-HAP, two other potential ingredients have been investigated for reducing the allergic effects of peroxides: Vitryxx TM Bioactive Glass and Potassium Oxalate. Potassium oxalate and bioactive glass (such as calcium sodium phosphosilicate (CSPS)) have been found to reduce DH.

[0208] In the DEV04848-based formulation, DEV04851 and DEV04852 were each added with approximately 6.5 wt.% Vitryxx. TM Bioactive glass and potassium oxalate were used as an alternative to n-HAP. Both formulations successfully produced high-quality films. However, since neither active caused any thickening of the casting solution, further development may be necessary. Possible next steps include increasing the pectin content to approach that of DEV04835 / DEV04837 or increasing the solids content of the casting solution.

[0209] Since neither ingredient prevented film formation in the formulations tried, they were both considered compatible with the 6% hydrogen peroxide formulation and, therefore, should also be viable options for the 10% peroxide formulation.

[0210] Estimated content range of the formula

[0211] The content range of each developed tooth sensitivity formula is presented in Table 2. As shown in Figure 2.

[0212] Table 2 shows the dry weight (wt. %) of the ingredients used to prepare the tooth allergy films.

[0213] Applicants have developed a thin, dissolvable film comprising a whitening agent and a desensitizing agent that has the potential to limit any tooth sensitivity that may be caused by a whitening regimen.

[0214] Three possible desensitizing agents have been successfully used: nano-hydroxyapatite, Vitryxx TM Bioactive glass and potassium oxalate. These have been combined with about 6-10 wt.% (e.g., 6 wt.% and 10 wt.%) hydrogen peroxide and the applicant's non-peroxide (peracid) tooth whitening system.

[0215] Of the formulations tested to date, DEV04848, DEV04849, DEV04851, DEV04852, and DEV04855 were the most successful and served as strong proof of concept for incorporating desensitizing agents into tooth whitening films.

[0216] Example 3

[0217] The following involves further experiments on the preparation of a tooth whitening (PAP and H2O2) formulation as well as a tooth sensitivity formulation using a non-nano form of HAP.

[0218] The examples in Examples 1 and 2 above involve the use of hydroxyapatite material (n-HAP) having nanometer-sized dimensions. The n-HAP used is provided in an aqueous dispersion.

[0219] In Example 3, the DEV04942-DEV04944 formulations are discussed, neither of which has a nanoform.

[0220] In Figures 3A and 3B, Tables 3A and 3B should be combined to show all ingredients in each development product.

[0221] Additionally, in FIG4 , Tables 3A and 3B present data for the compositions.

[0222] DEV04942-DEV04944

[0223] The DEV04942-DEV04944 formulations were used to evaluate the amount of n-HAP that could be added to a formulation that combines three primary film formers (ie, PVP, pectin, and pullulan).

[0224] The maximum loading of n-HAP included in the formulation was approximately 20.7 wt.%, and the minimum loading was approximately 6.5 wt.%. This experiment showed that there is a finite value for hydroxyapatite dosage, which can be reached if a dilute (e.g., 11 wt.% hydroxyapatite) dispersion is used as the source of hydroxyapatite (3).

[0225] Table 5: Theoretical n-HAP dosage in the developmental formulation

[0226]

[0227] A dry weight of approximately 21 wt.% provides only a theoretical dose of approximately 2 mg of n-HAP per patch. The need to use a relatively large loading of n-HAP paste in the formulation, coupled with the unclear regulatory status of cosmetics containing nanoparticles, led the applicant to re-evaluate the use of n-HAP dispersed pastes and focus on HA powders.

[0228] DEV04947, DEV04951, and DEV04952

[0229] These formulations are generally similar to DEV04942-DEV04944, but n-HAP is replaced with HAP powder (eg, approximately 90 wt.% active HAP). Three different HAP contents are included in these formulations, and the HAP dosage in each formulation is shown in Table 6.

[0230] Table 6: Theoretical HAP dosage in the development formulation

[0231]

[0232] The use of HAP powders with higher active content enables the HPA loading to be reduced in the formulation, which allows the HAP loading to be increased in the formulation.

[0233] DEV05052 and DEV05053

[0234] These formulations were designed to investigate the addition of HAP powder to applicant's non-peroxide tooth whitening strips containing a combination of PAP and polyphosphate.

[0235] DEV05052 included approximately 5% HAP powder and was found to produce extremely brittle dry films. DEV05053 added approximately 5% additional pectin to the formulation of DEV05052, but the addition of pectin had no effect on the brittleness of the cast films.

[0236] These batches indicate that adding concentrated (90 wt.%) HAP sources to applicant's PAP and polyphosphate formulations may not be a simple process.

[0237] R&D and production batch number 20036

[0238] This development extension batch is based on development batch DEV04952. A single 30 kg production batch was prepared and coated. HAP was derived from HAP powder, and approximately 30 m rolls were collected and processed into patches.

[0239] DEV05061, DEV05066, and DEV05068

[0240] Because the addition of HAP powder (e.g., approximately 5 wt.%) was found to cause brittleness in the PAP and polyphosphate patches (DEV05052 / DEV05053), it was decided to incorporate the active ingredients of the PAP and polyphosphate patches into the DEV04952 / 20036 formulations. The HAP powder content in all three formulations was set at approximately 5.3 wt.%.

[0241] The main difference between these formulations is defined by the glycerol content. Films produced with a glycerol loading of approximately 5% (DEV05061) were found to not meet the required quality (uneven drying was observed). Increasing the glycerol content to 7 wt.% and 10 wt.% (DEV05068 and DEV05066, respectively) produced films with satisfactory appearance.

[0242] The formulation described herein demonstrates that it is possible to prepare a tooth whitening strip with polyphosphate and PAP that also contains a desensitizing agent (HAP).

[0243] DEV05067 and DEV05069

[0244] To overcome the brittleness observed in DEV05052 / DEV05053, the glycerol content was increased to 7 wt.% (DEV05069) and 10 wt.% (DEV05067).

[0245] Here, glycerol was added to address the brittleness observed in DEV05052 / DEV05053 and was found to produce patches of acceptable quality.

[0246] DEV05010 / 21012

[0247] HAP powder (e.g., about 3 wt.%) was added to the applicant's hydrogen peroxide formulation for whitening strips. No problems were encountered during the preparation of the development batches.

[0248] Scaling up this formulation, a single batch of 30 kg provides approximately 100 meters of roll material for further processing into patches.

[0249] These developments demonstrate the ability to add HAP powder to hydrogen peroxide teeth whitening strips.

[0250] DEV05081 and DEV05082

[0251] The purpose of these formulations was to investigate the upper limit of HPA powder loading that could be easily incorporated into PAP and polyphosphate formulations.

[0252] Both formulations can maintain approximately 10.6 wt.% of the dry weight of the HAP powder. If necessary, further modification of the formulation can maintain up to approximately 20 wt.% of the dry weight of the HAP powder.

[0253] In vitro testing

[0254] Two external in vitro tests were commissioned for this work. The first was a whitening study to investigate whether the addition of hydroxyapatite had an impact on whitening efficacy. It was found that DEV05010 strips containing approximately 3 wt.% HAP powder exhibited whitening efficacy comparable to a market-leading HAP-free hydrogen peroxide teeth whitening product.

[0255] In fact, the HAP-containing patch was more effective than the market-leading competitor after treatments 1, 3, and 7. Equal efficacy was observed with the competitor at treatments 10 and 14 (Table 7).

[0256] Table 7: R20 whitening values ​​of the applicant's HAP-containing hydrogen peroxide patch and the leading hydrogen peroxide competitor patch on the market.

[0257]

[0258] A second in vitro study evaluated whether the hydraulic conductivity test could differentiate the ability of two whitening strips to occlude dentinal tubules, whose formulations differed only in the presence or absence of hydroxyapatite. These results are shown in Table 8.

[0259] deal with

[0260] Table 8: Whitening patch formula grouping

[0261]

[0262] method

[0263] Dentin discs were cut from the unrestored, caries-free coronal portions of human molars. A diamond wire saw (approximately 550 µm thick) was used, with all cuts perpendicular to the longitudinal axis of each tooth. Three discs that passed baseline criteria were used for each treatment group (n = 3).

[0264] The discs were sonicated in deionized water for 5 minutes, rinsed in deionized water for 30 seconds, etched in 10% (w / w) citric acid for 2 minutes, rinsed in deionized water for 30 seconds, and then patted dry with absorbent paper towels. The etched discs were stored in deionized water.

[0265] Discs were randomly selected and secured within the microfluidic cell, taking care to eliminate any bubbles or debris. A perfusion solution (Earle's balanced salt solution) was forced through the disc using a digital pressure controller via a digital flow sensor at a constant pressure of 100 mbar. Average flow rates were measured over 5 minutes and recorded using direct data export to Microsoft Excel. For baseline measurements, an average flow rate range of 4 to 15 µL / min was considered acceptable. Each disc that passed the baseline flow standard was randomly assigned to a treatment group and underwent the following treatment regimen.

[0266] Artificial saliva was injected into the flow cell and the reagents used were listed in Table 9.

[0267] Table 9: Artificial saliva reagents

[0268]

[0269] The whitening strip was gently folded and completely immersed in the injected cells, allowing it to sit for 30 minutes. Saliva and residue from the strip were then rinsed from the cells with deionized water. As before, the average flow rate was recorded for 5 minutes after application, and the ability of the test product to occlude dentinal tubules was calculated.

[0270] exist

[0271] Baseline

[0272] Post-application of whitening patches

[0273] Measure the flow rate (µL / min) for each of the three disks in each treatment group.

[0274] For the flow rate of each of the three disks in each treatment group, the percent reduction in flow rate at each time point was calculated as follows:

[0275]

[0276] result

[0277] Table 10 presents the average percentage reduction in dentin microfluidic flow rate for each whitening strip formulation.

[0278] Table 10: Average flow rate reduction percentage

[0279]

[0280] Both whitening strip formulations resulted in a decrease in the flow rate of the perfusate through the dentinal tubules. The data suggest that some mechanical occlusion occurs when the components of both formulations are released from the whitening strips.

[0281] A higher mean percentage reduction in microfluidic flow rate was achieved with the hydroxyapatite-impregnated whitening strip 21021B (46%) compared to the unimpregnated strip 21019B (38%). These data support the theory that the inclusion of hydroxyapatite in the formulation aids in occluding the dentinal tubules of the test product.

[0282] Therefore, the applicant has found that it is possible to have

[0283] - n-HAP formulations with higher n-HAP loadings (e.g., up to about 20.7 wt.%)

[0284] - HAP powder formulations ranging from approximately 1.1 to 10.6 wt.%

[0285] - HAP powder formulations containing whitening agents (e.g. PAP / H2O2 + P3).

[0286] Many modifications and other embodiments of the present invention will occur to those skilled in the art having the benefit of the teachings presented in the foregoing description; and it will be apparent to those skilled in the art that changes and modifications may be made to the present invention without departing from the scope of the appended claims. Therefore, it should be understood that the present invention is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are used herein, they are used for general descriptive purposes only and not for purposes of limitation.

Claims

1. A tooth whitening and / or tooth hypersensitivity patch, comprising: 1-20 wt.% hydroxyapatite (HAP); at least one polyvinylpyrrolidone (PVP) polymer or a combination of polyvinylpyrrolidone (PVP) polymers, wherein the amount of the PVP polymer is greater than 35 wt.% of the patch; at least one polycarbophil or a combination of polycarbophils, wherein the amount of polycarbophil is 1-5 wt.% of the patch; and Phthalimidoperoxycaproic acid (PAP), wherein the concentration of the phthalimidoperoxycaproic acid (PAP) is 0.01 wt.% to 5 wt.% of the patch; Wherein, the patch has a thickness of 50 μm to 500 μm.

2. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The teeth whitening strips are dissolvable in the oral cavity.

3. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The amount of the hydroxyapatite (HAP) ranges from 1 wt.% to 15 wt.% of the teeth whitening strip.

4. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The tooth whitening strip includes hydrogen peroxide (H2O2), and the concentration of hydrogen peroxide (H2O2) is 10 wt.% to 30 wt.% of the tooth whitening strip.

5. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The phthalimidoperoxycaproic acid (PAP) has a concentration of 0.02 wt. % to 2 wt. % of the teeth whitening strip.

6. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: Also included is one or more polyphosphates.

7. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The tooth whitening strips may include a series of other ingredients, including any one or a combination of the following: - one or more water-soluble film-forming polymers; - one or more plasticizers; - one or more emulsifiers; - a source of chloride; and / or - one or more sources of calcium ions, sodium ions, potassium ions, and / or phosphate ions.

8. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The teeth whitening strip has a thickness of 50 μm to 250 μm.

9. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The soluble film-forming polymer is one or more of the group consisting of pullulan, pectin, starch, dextrin, chitosan, alginic acid, alginates, and cellulose derivatives.

10. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: Hydroxyapatite (HAP) is available in the form of nanocrystals, powder, or paste.

11. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: Hydroxyapatite (HAP) is a form of hydroxypentacalcium triphosphate.

12. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The hydroxyapatite (HAP) is in the form of nano-hydroxyapatite (n-HAP) with a high n-HAP loading, with the loading of n-HAP being as high as 20 wt.%.

13. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The hydroxyapatite (HAP) is in the form of nano-hydroxyapatite (n-HAP), and the loading amount of n-HAP is 5-20 wt.%.

14. The tooth whitening and / or tooth hypersensitivity patch according to claim 1, characterized in that: The hydroxyapatite (HAP) is in the form of a powder formulation comprising 1-20 wt.% of HAP.

15. A process for manufacturing a tooth whitening strip, the process comprising at least the following steps: - The following ingredients are mixed to provide an aqueous teeth whitening solution; - at least one polyvinylpyrrolidone (PVP) polymer or a combination of polyvinylpyrrolidone (PVP) polymers, wherein the amount of polyvinylpyrrolidone (PVP) polymer is greater than 35 wt.% of the tooth whitening strip; -1-20wt.% hydroxyapatite (HAP); - at least one polycarbophil or a combination of polycarbophils, wherein the amount of polycarbophil is 1-5 wt.% of the tooth whitening strip; and - phthalimido peroxycaproic acid (PAP), wherein the phthalimido peroxycaproic acid (PAP) has a concentration of 0.01 wt.% to 5 wt.% of the tooth whitening strip; -water; - applying an aqueous teeth whitening solution to a substrate to provide a substrate carrying the teeth whitening solution; - drying the aqueous teeth whitening liquid to provide a teeth whitening strip on a substrate, the strip having a thickness of 50 μm to 500 μm.

Images