Use of oxalic acid compositions in dental care

Abstract

The invention relates to the application of liquid compositions comprising oxalic acid or a salt thereof to tooth enamel, a method of preventing or treating a disorder in dental enamel using such liquid compositions, and a kit comprising such liquid compositions.

Description

[0001] P5528PC00

[0002] USE OF OXALIC ACID COMPOSITIONS IN DENTAL CARE

[0003] TECHNICAL FIELD

[0004] This invention relates to the application of liquid compositions comprising oxalic acid or a salt thereof to tooth enamel.

[0005] BACKGROUND

[0006] All mammalian teeth have the same general structure and contain three layers: an outer layer of enamel, a middle layer of dentin, and an inner layer of pulp.

[0007] Disorders of dental enamel are well known in the art, including erosive tooth wear. Erosive tooth wear is a condition which involves the softening of dental enamel by acidic substances. The acidic substances may be of intrinsic and / or extrinsic origin. The most common intrinsic acid is gastric acid. Extrinsic acids may come from a variety of sources. Sources of dietary extrinsic acids are well known and include fresh fruit, as well as carbonated soft drinks, sports drinks, alcoholic beverages (such as dry wine, cider and alcopops).

[0008] Repeated and prolonged contacts with acidic substances not only cause softening of the enamel but can also lead to overall loss of tooth structure.

[0009] The softened tooth enamel is further left susceptible to mechanical impact. The combination of chemical-mechanical enamel loss may eventually expose the dentin layer. Exposure of the dentin layer may be undesirable for a number of reasons. For example, dentin is typically a different colour to enamel (e.g. dentine may be more yellow than enamel) in a patient. The patient may wish to avoid exposure of the dentin for aesthetic or cosmetic reasons.

[0010] Exposure of dentine also typically leads to dentin hypersensitivity. Hypersensitivity of a tooth occurs when the enamel is worn away or there is less gum around the tooth, causing the dentin layer to be exposed. Dentin is chemically similar but structurally different to enamel. Specifically, dentin contains tubules running from the outer surface to the pulp. These tubules contain fluid that is usually still when the dentin is covered by enamel, gum or bone. Without being bound by theory, it is believed that if the tubules are exposed, the fluid can be moved by various stimuli including cold (e.g. drinks, air), heat (e.g. food and / or drinks), pressure changes (e.g. tooth brushing) and chemical changes (e.g. food and / or drinks). It is believed that this movement is picked up by the nerve endings in the pulp that transmit a pain signal. There is therefore a desire to prevent or reduce erosion of dental enamel for therapeutic reasons. Preferably, there is a desire to prevent or reduce erosive tooth wear in a patient. P5528PC00

[0011] It is often difficult to avoid exposing dental enamel to intrinsic and extrinsic acids for health and / or social reasons. For example, reducing acid exposure, although effective at reducing erosive tooth wear progression, is difficult. In some cases of heavy fruit consumption, it is also undesirable e.g. if a patient is not getting enough fibre / vitamins from vegetables for health reasons, it is undesirable to ask them to alter fruit pattern consumption. Gastric reflux can be asymptomatic and is it undesirable to ask a patient to go on medication to reduce the exposure of gastric acids to their teeth. Vomiting eating disorders are even more difficult to manage. Therefore, there is a desire to prevent or reduce the harm these acids cause on the dental enamel.

[0012] Enamel is predominantly made of crystals of a mineral called hydroxyapatite. These crystals can dissolve if surrounded by intrinsic and / or extrinsic acids, meaning that if teeth are in contact with acid for too long, the top layer could disappear completely or in part. Without wishing to be bound by theory, it is believed that this happens via a mechanism known as 'demineralisation' where the acid causes minerals such as calcium and phosphorus to be released from the hydroxyapatite (known as "etching"), and thus making the resulting crystal more soluble than the "un-etched" hydroxyapatite. Mineral leaching can extend up to about 50 microns into the enamel when exposed to such intrinsic and / or extrinsic acids.

[0013] Fluorides are customarily used in oral care products such as toothpastes, dental gels or mouthwashes. It is known that fluoride ions, optionally in combination with sodium or stannous ions, such as in the form of sodium or stannous fluoride, are beneficial in preventing erosive tooth wear of the enamel.

[0014] The mechanisms by which conventional fluorides such as sodium fluoride and amine fluoride prevent erosive demineralisation is through the formation of a calcium fluoride layer on the surface and incorporation of the fluoride within the hydroxyapatite structure to form fluorapatite which is more stable and can make enamel more resistant to further acidic challenges. The calcium fluoride layer acts as a physical barrier to the acids, and as a reservoir of calcium and fluoride ions that can be released during an acid attack. Conventional fluoride products can therefore potentially slow the progression of tooth wear. It is thought, however, that under the conditions of an acidic attack, the protection of a calcium fluoride layer is short lived.

[0015] There is therefore a desire to provide a method of treating dental enamel to prevent or mitigate the effects of acid wear which has a long-lasting effect.

[0016] Oxalate salts have been known for the treatment of dentin hypersensitivity since the late 1970s. It has been shown that oxalates form precipitates within dentin tubules that block dentinal fluid flow (Journal of dental research vol. 90,3 (2011), 304-10). P5528PC00

[0017] In 2004, Hannig et al (Archives of Oral Biology, 2005(50), 541-552) studied the erosive effects of different acids on bovine enamel, including citric acid, maleic acid, lactic acid, tartaric acid, phosphoric acid, oxalic acid, acetic acid and hydrochloric acid. The authors observed that oxalic acid displayed non-linear kinetics for erosive phosphate dissolution, and concludes that oxalic acid is a cause of enamel erosion, rather than being useful in the prevention or mitigation thereof.

[0018] SUMMARY OF THE INVENTION

[0019] Aspects of the invention relate to a liquid composition comprising oxalic acid or a salt thereof. It has been found that such a liquid can be used to prevent or treat disorders in dental enamel.

[0020] A first aspect of the invention provides a liquid composition comprising oxalic acid or a salt thereof for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0021] A second aspect of the invention relates to a method of preventing or treating a disorder in dental enamel of a patient, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0022] A third aspect of the invention provides a method of cosmetic treatment of dental enamel, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0023] A fourth aspect of the invention provides a kit comprising: a) liquid composition comprising oxalic acid or a salt thereof; and bl) a container containing the liquid composition and bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b2) a package containing a container, the container comprising the liquid composition, and the package bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b3) a package containing a container and a leaflet, the container comprising the liquid composition, and the leaflet bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0024] As explained above, exposure of dental enamel to intrinsic and / or extrinsic acids causes demineralisation of the enamel. P5528PC00

[0025] In contrast, oxalic acid acts as a protective agent for enamel. Specifically, it is understood that upon initial contact, oxalic acid causes minerals such as calcium and phosphorus to be released from the hydroxyapatite, but then causes mineral-doped hydroxyapatite to be incorporated into the surface of the enamel, which is less soluble than the "unetched" hydroxyapatite. For example, the mineral doped hydroxyapatite may be doped with minerals such as calcium, phosphorus, fluoride, stannous (tin), titanium, silver, zinc, and combinations thereof.

[0026] Thus, oxalic acid causes a physical and structural change to the enamel. The initial mineral etching by oxalic acid is understood to extend a smaller distance into the enamel surface than other acids, at which point mineral-doped hydroxyapatite is formed on the enamel to prevent further mineral release and / or to reduces the ability of the acids to penetrate the enamel surface.

[0027] Stable calcium oxalate crystals then form on the surface of the dental enamel, thereby reducing or preventing demineralisation of the dental enamel,

[0028] While applying an oxalate salt (as opposed to oxalic acid) to dental enamel does cause deposits of stable calcium oxalate crystals on the surface of the dental enamel, thereby reducing or preventing demineralisation of the dental enamel, it is understood that these deposits can subsequently be removed from the enamel, for example, by exposure to further intrinsic and / or extrinsic acids.

[0029] Therefore, it is understood that the protective effect of oxalic acid on dental enamel is superior to and longer lasting than that of oxalate salts, particularly when in the presence of minerals which can be incorporated into the hydroxyapatite structure.

[0030] Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of the words, for example "comprising" and "comprises", mean "including but not limited to", and do not exclude other components, integers or steps. Moreover the singular encompasses the plural unless the context otherwise requires: in particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0031] Preferred and optional features of each aspect of the invention may be as described in connection with any of the other aspects. Within the scope of this application it is expressly intended that the various aspects, embodiments, examples and alternatives set out in the preceding paragraphs, in the claims and / or in the following description and drawings, and in particular the individual features thereof, may be taken independently or in any combination. That is, all embodiments and / or features of any embodiment can be combined in any way and / or combination, unless such features are incompatible. P5528PC00

[0032] BRIEF DESCRIPTION OF THE DRAWINGS

[0033] One or more embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0034] Figure 1 shows the results of step height formation of dental enamel exposed to five different groups: stannous fluoride, 0.76% oxalic acid, IM oxalic acid, potassium oxalate, and a control (water).

[0035] Figure 2 shows SEM images of enamel and dentin of the teeth exposed to five different formulations: stannous fluoride, 0.76% oxalic acid, IM oxalic acid, potassium oxalate, and a control (water).

[0036] DETAILED DESCRIPTION

[0037] Liquid Composition

[0038] Aspects of the invention relate to a liquid composition. The liquid composition comprises oxalic acid or a salt thereof.

[0039] It will be appreciated that a liquid composition which comprises oxalic acid or salt thereof includes a liquid composition which comprises oxalic acid (H2C2O4), or either of its conjugate bases, hydrogen oxalate (HC2O4) or oxalate (C2O42), or any mixture thereof. An appropriate counterion will be present when hydrogen oxalate or oxalate is present in the liquid composition. Preferably, the liquid composition comprises oxalic acid.

[0040] Examples of salts for use in the invention include a magnesium salt, a calcium salt, a lithium salt, a sodium salt, a zinc salt, a manganese salt, an iron salt and combinations thereof. Thus, the oxalate salt may be calcium oxalate, dilithium oxalate, disodium oxalate, magnesium oxalate etc., and combinations thereof. It will be appreciated that the salt may be a biocompatible salt, that is, a salt which is able to be in contact with dental substrates without producing adverse effect on the patient. The salt of oxalic acid is preferably a pharmaceutically acceptable salt.

[0041] In certain embodiments, the salt is not a potassium salt. For example, in certain embodiments, the salt is not dipotassium oxalate.

[0042] The oxalic acid or salt thereof may be present in any concentration in the liquid composition.

[0043] For example, the oxalic acid or salt thereof, preferably the oxalic acid, may be present in the composition in an amount of at least 0.01M, at least 0.1M, at least 0.2M, at least 0.5M at least IM, at least 2M, at least 5M, at least 7M, at least 10M, at least 20M or at least 30M. P5528PC00

[0044] The oxalic acid or salt thereof, preferably the oxalic acid, may be present in the composition in an amount of up to IM, up to 2M, up to 3M, up to 4M, up to 5M, up to 10M, up to 20M, up to 30M, up to 40M, up to 50M, up to 75M, or up to 100M.

[0045] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the oxalic acid or salt thereof may be combined. For example, the oxalic acid or salt thereof may be present in the composition in an amount of from 0.01 to 100M, such as from 0.1 to 100M, for example from IM to 100M, such as IM to 75M, for example from 2M to 50M, such as from 5M to 40M. Other ranges may include 0.01M to 5M, for example from 0.1M to 3M, such as from 0.5M to 2M.

[0046] The liquid composition is preferably an aqueous composition. Preferably, the liquid composition comprises at least about 50wt% of water, such as at least 70% by weight of water.

[0047] The liquid composition may comprise ethanol. When present, the ethanol may be present in an amount of from about 1 to 15 wt% of the liquid composition.

[0048] The liquid composition may comprise an additive selected from the group consisting of calcium, phosphorus, fluoride, stannous (tin), zinc, titanium, silver and combinations thereof.

[0049] Mouthwash

[0050] The liquid composition may be suitable for use as a mouthwash. A mouthwash is also commonly referred to as a mouthrinse, and the terms may be used interchangeably.

[0051] Typically, mouthwashes are applied to the mouth of a patient, e.g. by pouring, whereafter the patient circulates the mouthwash in the oral cavity to contact the mouthwash with the teeth of the patient, e.g. by swirling, gurgling etc. In this way, the active component(s) of the mouthwash impart their properties to the teeth and oral cavity in general. The patient is instructed to avoid swallowing the mouthwash liquid during and usually after application to the oral cavity by expelling the mouthwash, e.g. by spitting the mouthwash out.

[0052] Therefore, it will be appreciated that the liquid composition may be applied to the dental enamel of the patient by carrying out the following steps: a) circulating (such as by swirling or gurgling) the liquid composition in a dental cavity of the patient, thereby contacting the liquid composition with the dental enamel for a time sufficient to impart the desired effect to the dental enamel; b) subsequently expelling the liquid composition from the oral cavity (such as by spitting). P5528PC00

[0053] The time sufficient to impart the desired effect to the dental enamel may be at least 10 seconds, such as at least 20 seconds.

[0054] The time sufficient to impart the desired effect to the dental enamel may be up to 120 seconds, such as up to 60 seconds, for example up to 40 seconds.

[0055] It will be appreciated that any of the lower limits and any of the upper limits for these times may be combined. For example, the time sufficient to impart the desired effect to the dental enamel may be from 10 seconds to 120 seconds, such as from 20 seconds to 60 seconds, for example from 20 seconds to 40 seconds. Exemplary times include 20 seconds, 30 seconds and 40 seconds, preferably 30 seconds.

[0056] It will also be appreciated that the desired effect will depend on the intended use of the liquid composition. For example, for therapeutic applications, the desired effect may be the prevention or treatments of a disorder in dental enamel of a patient, such as erosive tooth wear. For cosmetic applications, the desired effect may be the prevention, retardation or reduction of tooth discoloration. It will also be appreciated that the desired effect may be the reduction or prevention of demineralisation of the dental enamel.

[0057] The liquid composition may comprise ethanol. When present, the ethanol may be present in an amount of from about 1 to 15 wt% of the liquid composition.

[0058] The liquid composition may have a pH which is physiologically acceptable. Such pH may typically be in the range of about 3.0 to about 6.0, preferably about 4.0 to about 5.0, more preferably about 4.3 to about 4.6. If necessary, the pH of the liquid composition may be adjusted to the desired value by adding acid (such as lactic acid) or base (such as sodium benzoate).

[0059] The liquid composition may comprise fluoride ions. The fluoride ions may be used in the form of any fluoride ion source customarily employed in oral care compositions, such as stannous fluoride, sodium fluoride, sodium monofluorophosphate and amine fluoride. When present, the liquid composition may comprise from 100 to 2000 ppm, preferably 200 to 1000 ppm dissolved fluoride ions.

[0060] The liquid composition may comprise dissolved tin. The term "dissolved tin" is intended to encompass all ionic or non-ionic tin species in the formal oxidation states +11 and / or +IV and being dissolved in the liquid composition. Examples of dissolved tin species include hydrated stannous ions, stannous hydroxide, soluble ionic or nonionic complexes of stannous and / or stannic ions with ligands, and ionic hydroxo complexes of stannous and / or stannic ions. Exemplary species include stannous chloride, stannous fluoride, stannous hydroxide, and stannous sulphate. Preferably 60 mol% or more, more preferably 75 mol% or more of the content of dissolved tin is tin in the formal oxidation state +11. The content P5528PC00 of dissolved tin in the liquid composition may be from about 100 to 2000 ppm, preferably from about 150 to 1000 ppm, more preferably about 500 to 900 ppm.

[0061] The liquid composition may comprise zinc. The zinc may be used in the form of any zinc source customarily employed in oral care compositions, such as zinc chloride, zinc lactate, zinc acetate, zinc citrate, zinc phenolsulphonate, zinc glycinate, zinc sulphate, zinc gluconate and combinations thereof. When present, the liquid composition may comprise zinc in an amount of from 100 to 2000 ppm, preferably from 200 to 1000 ppm. Preferably the zinc is dissolved zinc.

[0062] The liquid composition may comprise titanium. The titanium may be used in the form of any titanium source customarily employed in oral care compositions, such as titanium dioxide, titanium tetrafluoride and combinations thereof. When present, the liquid composition may comprise titanium in an amount of from 0.1 to 4wt%, preferably from 0.5 to lwt%. Preferably the titanium is dissolved titanium.

[0063] The liquid composition may comprise silver. The silver may be used in the form of any silver source customarily employed in oral care compositions, such as silver (e.g. colloidal silver), silver diamine fluoride (SDF), and combinations thereof. When present, the liquid composition may comprise silver in an amount of from 10 to 2000 ppm, preferably from 50 to 1000 ppm. Colloidal silver encompasses silver particles suspended in the liquid composition, where the silver particles may have a maximum diameter in the range of from 1 to 1000 nm, preferably in the range of from 1 to 500 nm.

[0064] The liquid composition may comprise calcium. The calcium may be used in the form of any calcium source customarily employed in oral care compositions, such as calcium fluoride, calcium phosphate, calcium carbonate, calcium silicate, calcium glycerophosphate, calcium lactate, calcium gluconate and combinations thereof. When present, the liquid composition may comprise calcium in an amount of from about 100 to 500ppm, preferably from about 150 to 300ppm. Preferably the calcium is dissolved calcium.

[0065] The liquid composition may comprise phosphorus. The phosphorus may be used in the form of any phosphorus source customarily employed in oral care compositions, such as phosphates (e.g. calcium phosphate, zinc phosphate, sodium phosphate, and combinations thereof). When present, the liquid composition may comprise phosphorus in an amount of from about 150 to lOOOppm, preferably from about 200 to 600ppm. Preferably the phosphorus is dissolved phosphorus.

[0066] The liquid composition may comprise an organic acid and / or salt thereof, either as part of a buffering system intended to achieve the above mentioned physiologically acceptable pH, or as a complexing agent for dissolved tin species, if present. The organic acid, if present, is preferably a carboxylic acid, and is dissolved in the liquid composition. When organic acid is P5528PC00 present, it may be present in an amount of 0.01 to 10wt%, preferably 0.05 to 5wt% of the liquid composition.

[0067] Further optional components in the liquid composition include flavourings and cooling flavours, sweeteners, antibacterial agents, preservatives, emulsifiers or solubilisers, thickeners, thixotropic agents, stabilisers, and combinations thereof.

[0068] Exemplary flavourings and cooling flavours include coumarin, vanillin, ethereal oils (such as peppermint oil, spearmint oil, aniseed oil, menthol, anethol and citrus oil) or other essences (such as apple, eucalyptus and spearmint essence). The flavourings and cooling flavours may be present in 0.01 to 0.5wt%, preferably 0.03 to 0.3wt%, of the liquid composition.

[0069] Exemplary sweeteners include artificial sweeteners such as saccharin, acesulfam, neotam, cyclamate and sucralose, natural high-intensity sweeteners such as thaumatin, stevioside and glycyrrhizin, and sugar alcohols, such as glycerol, erythritol, threitol, arabitol, xylitol, ribitol, sorbitol, maltitol and mannitol. The sweetener may be present in an amount of from 0.001 to 0.2wt%, preferably 0.005 to 0.1wt%, of the liquid composition.

[0070] Exemplary antibacterial agents and / or preservatives include chlorhexidine, triclosan, quaternary ammonium compounds (such as benzalkonium chloride), parabens (such as methyl or propyl paraben) or sodium benzoate. The amount of antimicrobial agent and / or preservative may be from about 0.01 to about 0.5wt%, preferably 0.05 to 0.1wt%, of the liquid composition.

[0071] Exemplary emulsifiers or solubilisers include neutral surfactants (such as polyoxyethylene hydrogenated castor oil or fatty acids of sugars), anionic surfactants (such as sodium lauryl sulphate), cationic surfactants (such as ammonium cations) or zwitterionic surfactants. The surfactants or solubilisers may be present in an amount of from 0.1 to 2wt%, preferably 0.2 to 1.5wt%, of the liquid composition.

[0072] Exemplary thickeners include propylene glycol, cocamidopropyl betaine, glycerin, tetrapotassium or tetrasodium pyrophosphate, titanium dioxide and xanthan gum. The thickeners may be present in an amount of from 0.1 to 5wt%, preferably 0.2 to 3wt%, of the liquid composition.

[0073] Exemplary thixotropic agents include soluble grades of hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC) or mucins. Exemplary stabilisers include polyvinylpyrrolidone (PVP).

[0074] The liquid composition may be suitable for daily application. For example, the liquid composition may be applied once a day, twice a day, three times a day four times a day or more. Preferably, the liquid composition is applied one, two or three times a day. P5528PC00

[0075] Each portion of liquid composition which may be applied may be from 5 to 50ml, for example 10 to 30 ml. In other words, for application three times daily, three portions would be applied.

[0076] The liquid composition may comprise the oxalic acid or salt thereof in an amount of at least 0.01M, at least 0.1M, at least 0.2M, at least 0.5M or at least IM.

[0077] The oxalic acid or salt thereof may be present in the liquid composition in an amount of up to 2M, up to 3M, up to 4M or up to 5M.

[0078] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the oxalic acid or salt thereof may be combined. For example, the oxalic acid or salt thereof may be present in the liquid composition in an amount of from 0.01 to 5M, such as from 0.1 to 4M, for example from 0.2M to 3M, such as from 0.5 to 3M.

[0079] Professional product

[0080] The liquid formulation may comprise a high concentration of the oxalic acid or salt thereof, preferably oxalic acid, meaning that it may be more suited for application by a dental professional as opposed to being a consumer product, such as a mouthwash.

[0081] For example, the liquid composition may comprise the oxalic acid or salt thereof, preferably oxalic acid, in an amount of at least 5M, at least 7M, at least 10M, at least 20M, or at least 30M.

[0082] The oxalic acid or salt thereof, preferably the oxalic acid, may be present in the liquid composition in an amount of up to 10M, up to 20M, up to 30M, up to 40M, up to 50M, up to 75M, or up to 100M.

[0083] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the oxalic acid or salt thereof may be combined. For example, the oxalic acid or salt thereof may be present in the composition in an amount of from 5M to 100M, such as 5M to 75M, for example from 10M to 50M, such as from 20M to 40M.

[0084] It will be appreciated that the liquid composition may be applied by a dental professional.

[0085] The liquid composition may be applied to the dental enamel by any appropriate method, including by a swab (such as a cotton swab), a brush (such as a microbrush), or as droplets (such as a by spray or pipette).

[0086] At higher concentrations, the liquid composition may need to be applied less often than a liquid composition comprising lower concentrations (e.g. liquid compositions suitable for use as a mouthwash). For example, the liquid composition may be applied one or more, two or more, or three or more times in a year. P5528PC00

[0087] It will also be appreciated that the liquid composition may be applied four or less, three or less, or two or less times in a year.

[0088] Any of the lower limits and any of the upper limits of these ranges may be combined. For example, the liquid composition may be applied 1 to 4 times in a year, 1-3 times in a year, 2-3 times in a year.

[0089] It will also be appreciated that the liquid composition may be applied 1 time in a year, 2 times in a year, three times in a year or four times in a year.

[0090] Preventing or treating a disorder in dental enamel

[0091] Aspects of the invention relate to therapeutic use of a liquid composition comprising oxalic acid or a salt thereof for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0092] A first aspect of the invention provides a liquid composition comprising oxalic acid or a salt thereof for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0093] A second aspect of the invention relates to a method of preventing or treating a disorder in dental enamel of a patient, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0094] The liquid composition may be as described above. Preferably, the liquid composition may be suitable for use as a mouthwash or as a professional product as described above and may be used according to the indications set out above.

[0095] It will be appreciated that the disorder in the dental enamel may be erosive tooth wear.

[0096] The liquid compositions may be for use in a patient in need thereof. The patient is preferably a human. Thus, the dental enamel is preferably human dental enamel.

[0097] The liquid composition may be used on patients who do not yet have a disorder of the dental enamel, i.e. as a preventative measure against the disorder. Alternatively, the liquid compositions may be used on patients who already have a disorder of the dental enamel, i.e. in order to slow down a further progression of the disorder.

[0098] The most common source of intrinsic acids is stomach acid. Stomach acid may come into contact with dental enamel for a number of different reasons.

[0099] Reflux is the passive or effortless movement of regurgitated acid into the mouth and when this occurs regularly over a prolonged period, it is referred to as gastro-oesophageal reflux disease (GORD). Thus, the intrinsic acid may be as a result of GORD. P5528PC00

[0100] Persistent spontaneous or self-induced vomiting often results in dental erosion. The medical conditions associated most frequently with persistent vomiting include eating disorders, pregnancy, alcoholism and cyclic vomiting syndrome. Thus, the intrinsic acid may be as a result of persistent spontaneous or self-induced vomiting, preferably associated with eating disorders, pregnancy, alcoholism or cyclic vomiting syndrome.

[0101] Consequently, the patient may have gastro-oesophageal reflux disease, or a disorder associated with persistent vomiting selected from an eating disorder, alcoholism and cyclic vomiting syndrome, or the patient may be pregnant and suffer from persistent vomiting.

[0102] Cosmetic method

[0103] A third aspect of the invention provides a method of cosmetic treatment of dental enamel, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0104] The liquid composition may be as described above. Preferably, the liquid composition may be suitable for use as a mouthwash or as a professional product as described above and may be used according to the indications set out above.

[0105] Preferably, the cosmetic treatment is the prevention, retardation or reduction of tooth discoloration. This may be achieved by preventing, retarding or reducing demineralisation of at least a part of the dental enamel.

[0106] Preferably, the cosmetic method does not comprise the step of applying sodium hypochlorite to the dental enamel. Preferably, the cosmetic method is not a method of whitening the dental enamel.

[0107] Preferably the dental enamel is human dental enamel.

[0108] Kit

[0109] As set out above, aspects of the invention relate to the use of a liquid composition comprising oxalic acid or a salt thereof in a method of preventing or treating a disorder in dental enamel of a patient.

[0110] For this purpose, they may suitably be provided as a kit containing the liquid composition and human- readable indications disclosing to the subject using the composition that the composition is for use, or efficacious, against a disorder in dental enamel of a patient. These indications may be directly printed on the container comprising the composition (such as a mouthrinse bottle), or they may be printed on a label wrapped or adhered onto the container. They may also be printed on a package, such as a cardboard box, enclosing the container. Finally, they may be printed on a leaflet (a package insert), to be included into the kit. P5528PC00

[0111] Thus, the fourth aspect of the invention provides a kit comprising: a) liquid composition comprising oxalic acid or a salt thereof; and bl) a container containing the liquid composition and bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b2) a package containing a container, the container comprising the liquid composition, and the package bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b3) a package containing a container and a leaflet, the container comprising the liquid composition, and the leaflet bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0112] The liquid composition may be as described above. Preferably, the liquid composition may be suitable for use as a mouthwash or as a professional product as described above and may be used according to the indications set out above.

[0113] It will be appreciated that the disorder in the dental enamel may be erosive tooth wear.

[0114] The patient is preferably a human. Thus, the dental enamel is preferably human dental enamel.

[0115] EXAMPLES

[0116] Example 1

[0117] Materials and Methods

[0118] 1. Teeth collection

[0119] Human molar enamel samples (n=50) were obtained from Guy's Hospital oral surgery department with informed consent (REC ref 12 / LO / 1836) by a good clinical practice trained individual. Following disinfection by placing in 5% sodium hypochlorite solution, the buccal surfaces of the teeth were sectioned using a water-cooled diamond watering blade (XL 12205, Benetec Ltd., London, UK) and circular saw (Isomet 1000; Buehler, Coventry, UK) at a speed of 300 rpm and 150 g of force. All the teeth slabs were fully embedded in cold cure acrylic resin (Oracryl; Bracon, East Sussex, UK).

[0120] 2. Sample preparation

[0121] Using successively finer silicon-carbide discs (Versocit, Struers A / S, Copenhagen, Denmark) of grit 500, 1200, 2000, and 4000 for 5s, 25s, 30s and 60s, enamel samples were polished using a water-cooled rotating polishing machine at constant pressure of 10 Newton and 150 RPM and (Laboforce-100, Struers ApS, Ballerup, Denmark). To eliminate the smear layer, P5528PC00 samples were then ultrasonicated (GP-70, Nusonics, Lakewood, USA) for five minutes in 100 milliliters of deionized water (pH 5.8), cleaned with an alcohol swab, and allowed to air dry for a full day at room temperature.

[0122] To verify flatness tolerance ±0.2pm, 5% of samples were scanned with the white light profilometer (XYRIS 4000 WL). Initially they did not meet this tolerance level and they were repolished repeating the above protocol until the desired flatness tolerance was achieved. The samples are split into 1:3 ratios using PVC adhesive tape, leaving two protected reference zones and an exposed enamel window of 1 mm x 3 mm. The samples were then randomly assigned into each of the solution groups of commercial stannous fluoride (225 ppm F) mouthrinse (PerioMed, 3M ESPE, MI, USA) commercial 1.4% potassium oxalate mouthrinse (Listerine Advanced Defense Sensitive, Johnson and Johnson, USA), 1 molar oxalic acid solution and 0.76% oxalic acid solution and control (distilled water) group.

[0123] 3. Citric acid and oxalic Acid preparation

[0124] To prepare a 0.3% citric acid solution, 3.0g of anhydrous citric acid powder (Sigma Aldrich, Poole, Dorset UK) was added to IL of deionized water. The pH of the solution was then adjusted to 3.2 using 0.1M sodium hydroxide buffer (4g 99% NaOH in IL of deionized water; 18.0 ml volume of sodium hydroxide needed to raise the solution's pH to 7, which determined the titratable acidity.

[0125] Formulation of 0.76% oxalic acid solution was completed by adding 7.6 g of oxalic acid to IL of deionized water. As the molar mass of oxalic acid (C2H2O4,) is 90.03 g / mol, a solution of IM oxalic acid was made by adding 22.5 grams of oxalic acid to 250 milliliters of deionized water.

[0126] Experiment protocol

[0127] Each group (n = 10) was submerged in 100ml of the allocated solution in an orbital shaker operating at a speed of 62.5rpm for about 10 minutes. After that, all samples were immersed in deionised water (pH 5.8) for 1 minute. Each group was then immersed in 100ml 0.3% citric acid under agitation in an orbital shaker (62.5rpm) for 10 minutes. Afterwards, all samples were again immersed in deionised water (pH 5.8) for 1 minute. This was repeated 3 times for a total acid exposure time of 30 mins. Samples were then allowed to dry overnight.

[0128] Measurement and Data Analysis

[0129] 1. Laser Profilometry (Quantitative Analysis)

[0130] Tape was removed from all samples to expose reference areas on both sides of the 1mm eroded enamel sample. A 2 pm laser spot-sized red light confocal scanning (Taicaan, XYRIS P5528PC00

[0131] 2000, UK) was used to perform profilometric measurements. The instrument was operated in medium precision mode, providing a vertical (z-axis) resolution of 0.01 pm. During the measurements, a raster scanning technique was employed with an x,y scanning interval of 10 pm. The resulting surface topography data were analyzed to determine the mean 3D step height. This analysis was performed using surface metrology software (BEX, Taicaan Technologies, Southampton, UK) in accordance with the ISO 5436-1 standard protocol.

[0132] 2. Scanning Electron Microscopy (Qualitative analysis)

[0133] Qualitative characteristics of the enamel were explored using scanning electron microscopy (SEM). Two randomly selected samples from each group underwent surface SEM. Carbon tapes were used to mount the selected samples and next placed into a Leica EM ACE600 (Leica Microsystems UK Ltd, Milton Keynes, United Kingdom). After that, each mounted sample was sputter coated with a 6nm of gold to avoid electron charging of the surface and put into a benchtop SEM (JCM-7000 NeoScope Benchtop SEM, JEOL LTD, Hertfordshire, UK). Imaging was performed with 10 kV and 1400x magnification.

[0134] 3. Energy dispersive X-ray spectroscopy (EDS)

[0135] Using the same SEM machine, EDS element analysis was carried out on the samples after SEM examination. EDS analysis was performed by point analysis, where randomly placed dots on enamel samples were selected for the elemental investigation. Focused element peaks were carbon, calcium, phosphorus, and oxygen. Other recorded peaks included magnesium, potassium, and tin. Data tables containing the mass percentage and atom percentage of peak elements were collected for each sample.

[0136] Statistical analysis

[0137] The primary outcome was profilometric step height. Using observed differences and standard deviations between stannous fluoride and the water control according to O'Toole et al. (J Dent., 2015, 43(12), 1498-503) to get the effect size, 80% power and 5% alpha, a sample size of 6 per group was deemed necessary to achieve statistical power. As there are no studies on oxalic acid and erosion, we increased this to 10 per group. Data were analysed in IBM SPSS Statistics version 29.0.0 (Armonck, USA).

[0138] Normality tests were performed to decide whether parametric or non-parametric tests would be used. Normality was assessed statistically using Shapiro wilks and visually using histograms. The data exhibited normal distribution and were represented using means and standard deviations. Differences between means were therefore assessed using a one-way ANOVA with Tukey's post hoc analysis. The threshold for statistical significance was set as P < 0.05. P5528PC00

[0139] Results

[0140] 1. Step height

[0141] In the control water group, the mean step height (SD) was 8.43 pm (0.89). For the oxalic acid groups, 0.76% OA produced a mean step height of 2.13 pm (0.55), while the IM OA produced a step height of 2.36 pm (0.75). Potassium oxalate group had a step height of 2.28 pm (0.74). For the SnF2group, the mean step height was 2.99 pm (0.76). These results are shown in Figure 1.

[0142] Differences between means were found to be significant (p<0.001) in one-way ANOVA. Post hoc analysis demonstrated a statistical difference between the water control and all other groups (p<0.001). However, no differences were observed between treatment groups.

[0143] 2. SEM Imaging

[0144] SEM images of the enamel are shown in Figure 2. In the 0.76% OA group, the enamel surface is blocked completely by a heavy crystal-like deposition seen across the enamel layer. Similarly, crystalline depositions can also be seen in IM OA group. In stannous fluoride group, the enamel prisms are dissolved revealing a honeycomb appearance characteristic of surface enamel erosion with no deposits. In potassium oxalate group, crystal formations resembling the ones in OA groups are observed covering the enamel surface. In the water group, a honeycomb appearance is observed, characterized by the loss of enamel rods and exposure of interrod substance.

[0145] 3. EDS Analysis

[0146] The 0.76% OA group showed levels of calcium (30.90±0.27 mass %, 14.29±0.12 atom %); However, no phosphorous peaks were picked up by the EDS elemental examination. In the 0.1M oxalic acid group, calcium percentages were (65.48±0.60 mass %, 47.47±0.43 atom %) and the phosphate levels were (15.51±0.20 mass %, 14.55±0.18 atom %). A small amount of sodium was also present with a mass % of 0.24±0.02 and atom % of 0.30±0.03. The calcium to phosphate ratio was calculated to be 3.26. The Stannous fluoride group revealed calcium amounts of 30.76±0.25 mass % and 16.59±0.14 atom %, phosphorous of 14.82±0.12 mass % and 10.35±0.08 atom %, which in return gave atomic Ca / P ratio of 1.6. Also, tin was captured with 3.89±0.12 mass % and 0.71±0.02 atom %, in addition to minute amounts of sodium and magnesium. For the potassium oxalate group, mass and atomic percentages of calcium were found to be 43.13±0.43 and 22.36±0.22 respectively, in addition to small amounts of sodium. Phosphorous on the other hand was not detected in the EDS analysis of this potassium oxalate coated enamel sample. Lastly, distilled water group had calcium percentages of 30.88±0.30 mass and 15.82±0.15 atom. Phosphorous P5528PC00 had 16.45±0.15 percent mass and 10.90±0.10 percent atom, thus giving a Ca / P ratio of

[0147] 1.45. Minuscule amounts of sodium and chlorine were recorded.

[0148] Discussion

[0149] Oxalic acid application on enamel did not result in significantly greater step height formation compared to stannous fluoride application after erosive challenges therefore our null hypothesis was accepted. This is remarkable given that stannous fluoride is considered to be the gold standard topical agent against erosive tooth wear.

[0150] Results showed that oxalic acid groups along with the potassium oxalate and stannous fluoride showed significant reduction in enamel loss when compared to the control water group (p<0.001) after the erosive challenge took place when compared to the control water. This suggests that the oxalic acid in its 2 concentrations (0.76% and IM) and the potassium oxalate rinse exhibited comparable anti-erosive properties similar to the well- documented effects of stannous fluoride. The lowest step height 2.13 (0.55) microns was seen in the 0.76% Oxalic acid group. No surface protection was seen on the SnF2 group.

[0151] No crystals were viewed in SnF2treated samples and the SEM captured a common honeycomb appearance of eroded enamel with the absence of any deposited structure on enamel surface. The image of stannous fluoride samples resembled the image taken of enamel treated with water, with the distinguishing factor between the two groups being the vertical height loss observed under laser profilometer.

[0152] Under SEM imaging, crystalline-like structures were seen formed on the surface of enamel treated with the two oxalic acid concentrates and 1.4% potassium oxalate groups. When comparing the elemental analysis results, phosphorus was not captured in the 0.76% OA and potassium oxalate groups. When viewing the SEM images in Figure 2, it can clearly be seen that the enamel surface is completely blocked by the formed crystalline structures that it attributed to the formation of calcium oxalate salts. This can also explain why the measured calcium levels are high (30.90±0.27 and 43.13±0.43 weight % for group 1 and group 4 respectively). Similarly, the IM OA group showed excessive calcium levels in the EDS findings; however, phosphorous elements were also captured. This is due to the fact that, in contrast to the other two groups, the crystalline structures shown in the SEM image did not entirely obscure the enamel surface. The Ca / P ratio of enamel treated with potassium oxalate group was 3.26, which is above the normal Ca / P ratio for enamel (1.63) and hydroxyapatite (1.67).

[0153] As mentioned above, stannous fluoride samples showed efficient reduction in step height (2.99 pm ±0.76) when compared to control water group (p<0.001). The development of the less acid soluble fluorapatite Ca5(PO4)3F was considered to be one of the primary factors to properly influenced this outcome. EDS, however, did not spot any fluorine peaks in the P5528PC00 elements on the surface. This was believed to be due to the relatively mild acid-challenge of the experiment. Another noteworthy observation is that the stannous fluoride-treated enamel showed no signs of precipitation.

[0154] Conclusions It was concluded from this study that:

[0155] 1. Oxalic acid, stannous fluoride and potassium oxalate resulted in statistically significant reduction in step height on enamel surface after erosive challenges when compared to the water control group.

[0156] 2. SEM imaging demonstrated that enamel treated with oxalic acid and potassium oxalate formed an acid-resistant crystalline layer that almost fully blocked the enamel prisms. In contrast, no such layers were observed on enamel surfaces treated with stannous fluoride.

[0157] 3. Elemental analysis using EDS on oxalic acid and oxa late-treated groups indicated prominent calcium peaks and elevated Ca / P ratios, suggesting the presence of a calcium-rich protective layer that obscured the enamel surface on oxalic acid / oxalate groups.

[0158] P5528PC00

[0159] NUMBERED EMBODIMENTS

[0160] The following numbered statements are not claims, but instead describe particular aspects and features of the invention.

[0161] 1. A liquid composition comprising oxalic acid or a salt thereof for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0162] 2. A method of preventing or treating a disorder in dental enamel of a patient, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0163] 3. The liquid composition for use according to embodiment 1, or the method of embodiment 2, wherein the disorder is erosive tooth wear.

[0164] 4. The liquid composition for use according to embodiment 1 or 3, or the method of embodiments 2 or 3, wherein the patient is a human.

[0165] 5. The liquid composition for use according to embodiment 1 or 3-4, or the method according to embodiment 2-4, wherein the patient has gastro-oesophageal reflux disease, or a disorder associated with persistent vomiting selected from an eating disorder, alcoholism and cyclic vomiting syndrome, or wherein the patient is pregnant and suffering from persistent vomiting.

[0166] 6. A method of cosmetic treatment of dental enamel, the method comprising contacting a liquid composition comprising oxalic acid or a salt thereof with the dental enamel.

[0167] 7. The method of embodiment 6, wherein the cosmetic treatment is the prevention, retardation or reduction of tooth discoloration.

[0168] 8. The method of embodiment 6 or 7, wherein the dental enamel is human dental enamel.

[0169] 9. The liquid composition for use according to embodiment 1 or 3-5, or the method according to embodiments 2-8, wherein the liquid composition is an aqueous composition, preferably wherein the liquid composition comprises at least 50wt% of water, more preferably at least 70% by weight of water.

[0170] 10. The liquid composition for use according to embodiment 1, 3-5 or 9, or the method according to embodiments 2-9, wherein the liquid composition comprises ethanol, preferably from about 1 to 15wt% of ethanol.

[0171] 11. The liquid composition for use according to embodiment 1, 3-5 or 9-10, or the method according to embodiments 2-10, wherein the liquid composition comprises oxalic acid. P5528PC00

[0172] 12. The liquid composition for use according to embodiment 1, 3-5 or 9-11, or the method according to embodiments 2-11, wherein the salt is a pharmaceutically acceptable salt.

[0173] 13. The liquid composition for use according to embodiment 1, 3-5 or 9-12, or the method according to embodiments 2-12, wherein the salt is selected from a magnesium salt, a calcium salt, a lithium salt, a sodium salt, a zinc salt, a manganese salt, an iron salt and combinations thereof.

[0174] 14. The liquid composition for use according to embodiment 1, 3-5 or 9-13, or the method according to embodiments 2-13, wherein the salt is not a potassium salt.

[0175] 15. The liquid composition for use according to embodiment 1, 3-5 or 9-14, or the method according to embodiments 2-14, wherein the salt is not dipotassium oxalate

[0176] 16. The liquid composition for use according to embodiment 1, 3-5 or 9-15, or the method according to embodiments 2-15, wherein the liquid composition comprises at least 0.01M of oxalic acid or the salt thereof.

[0177] 17. The liquid composition for use according to embodiment 1, 3-5 or 9-16, or the method according to embodiments 2-16, wherein the liquid composition comprises at least 0.1M of oxalic acid or the salt thereof.

[0178] 18. The liquid composition for use according to embodiment 1, 3-5 or 9-17, or the method according to embodiments 2-17, wherein the liquid composition comprises at least IM of oxalic acid or the salt thereof.

[0179] 19. The liquid composition for use according to embodiment 1, 3-5 or 9-18, or the method according to embodiments 2-18, wherein the liquid composition comprises up to 5M of oxalic acid or the salt thereof.

[0180] 20. The liquid composition for use according to embodiment 1, 3-5 or 9-15, or the method according to embodiments 2-15, wherein the liquid composition comprises at least 5M of oxalic acid or the salt thereof.

[0181] 21. The liquid composition for use according to embodiment 1, 3-5, 9-15 or 20, or the method according to embodiments 2-15 or 20, wherein the liquid composition comprises at least 10M of oxalic acid or the salt thereof.

[0182] 22. The liquid composition for use according to embodiment 1, 3-5, 9-15, 20 or 21, or the method according to embodiments 2-15 or 20-21, wherein the liquid composition comprises up to 100M of oxalic acid or the salt thereof. P5528PC00

[0183] 23. The liquid composition for use according to embodiment 1, 3-5, 9-15, or 20-22, or the method according to embodiments 2-15 or 20-22, wherein the liquid composition comprises up to 50M of oxalic acid or the salt thereof.

[0184] 24. The liquid composition for use according to embodiments 1, 3-5 or 9-19, wherein the liquid composition is suitable for use as a mouthwash.

[0185] 25. The liquid composition for use according to embodiment 1, 3-5, 9-19 or 24, wherein the liquid composition is applied to the dental enamel once a day, twice a day, three times a day, four times a day, or more, preferably one, two or three times a day.

[0186] 26. The liquid composition for use according to embodiment 1, 3-5, 9-15, or 20-23, wherein the liquid composition is applied by a dental professional.

[0187] 27. The liquid composition for use according to embodiment 1, 3-5, 9-15, 20-22 or 26, wherein the liquid composition is applied to the enamel by a swab, brush, or as droplets.

[0188] 28. The liquid composition for use according to embodiment 1, 3-5, 9-15, 20-22 or 26-27, wherein the liquid composition is applied one or more, two or more, or three or more times in a year, preferably 1 time in a year, 2 times in a year, three times in a year or four times in a year.

[0189] 29. The liquid composition for use according to embodiments 1, 3-5, or 9 to 28, or the method according to embodiments 2 to 23, wherein the liquid composition comprises dissolved tin, preferably wherein the content of dissolved tin in the liquid composition is from about 100 to 2000 ppm, preferably from about 150 to 1000 ppm, more preferably from about 500 to 900 ppm.

[0190] 30. The liquid composition for use according to embodiment 29 or the method of embodiment 29, wherein the dissolved tin is selected from hydrated stannous ions, stannous hydroxide, soluble ionic or nonionic complexes of stannous and / or stannic ions with ligands, ionic hydroxo complexes of stannous and / or stannic ions, and combinations thereof, preferably wherein the dissolved tin is selected from stannous chloride, stannous fluoride, stannous hydroxide, stannous sulphate, and combinations thereof.

[0191] 31. The liquid composition for use according to embodiments 1, 3-5, or 9 to 30, or the method according to embodiments 2 to 23 or 29-30, wherein the liquid composition comprises fluoride ions, preferably wherein the content of fluoride ions in the liquid composition is from 100 to 2000 ppm, more preferably from 200 to 1000 ppm.

[0192] 32. The liquid composition for use according to embodiments 1, 3-5, or 9 to 31, or the method according to embodiments 2 to 23 or 29-31, wherein the liquid composition comprises zinc, preferably dissolved zinc, optionally wherein the liquid composition P5528PC00 comprises zinc chloride, zinc lactate, zinc acetate, zinc citrate, zinc phenolsulphonate, zinc glycinate, zinc sulphate, zinc gluconate or combinations thereof, and / or wherein the liquid composition comprises zinc in an amount of from 100 to 2000 ppm, preferably from 200 to 1000 ppm.

[0193] 33. The liquid composition for use according to embodiments 1, 3-5, or 9 to 32, or the method according to embodiments 2 to 23 or 29-32, wherein the liquid composition comprises titanium, optionally wherein the liquid composition comprises titanium dioxide, titanium tetrafluoride or combinations thereof, and / or wherein the liquid composition comprises titanium in an amount of from 0.1 to 4wt%, preferably from 0.5 to lwt%.

[0194] 34. The liquid composition for use according to embodiments 1, 3-5, or 9 to 33, or the method according to embodiments 2 to 23 or 29-33, wherein the liquid composition comprises silver, optionally wherein the liquid composition comprises silver (e.g. colloidal silver), silver diamine fluoride (SDF), or combinations thereof, and / or the liquid composition comprises silver in an amount of from 10 to 2000 ppm, preferably from 50 to 1000 ppm.

[0195] 35. The liquid composition for use according to embodiments 1, 3-5, or 9 to 34, or the method according to embodiments 2 to 23 or 29-34, wherein the liquid composition comprises calcium, preferably dissolved calcium, optionally wherein the liquid composition comprises calcium fluoride, calcium phosphate, calcium carbonate, calcium silicate, calcium glycerophosphate, calcium lactate, calcium gluconate or combinations thereof, and / or the liquid composition comprises calcium in an amount of from about 100 to 500ppm, preferably from about 150 to 300ppm.

[0196] 36. The liquid composition for use according to embodiments 1, 3-5, or 9 to 35, or the method according to embodiments 2 to 23 or 29-35, wherein the liquid composition comprises phosphorus, preferably dissolved phosphorus, optionally wherein the liquid composition comprises one or more phosphates (e.g. calcium phosphate, zinc phosphate, sodium phosphate, and combinations thereof), and / or the liquid composition comprises phosphorus in an amount of from about 150 to lOOOppm, preferably from about 200 to 600ppm.

[0197] 37. The method according to embodiment 2-19 or 29-36, wherein the method involves the steps of: a) contacting the liquid composition with the dental enamel involves circulating (such as by swirling or gurgling) the liquid composition in a dental cavity of the patient, thereby contacting the liquid composition with the dental enamel for a time sufficient to impart the desired effect to the dental enamel; P5528PC00 b) subsequently expelling the liquid composition from the oral cavity (such as by spitting).

[0198] 38. The method according to embodiments 2-19 or 29-37, wherein the step of applying the liquid composition to the dental enamel is carried out once a day, twice a day, three times a day, four times a day, or more, preferably one, two or three times a day.

[0199] 39. The method according to embodiments 2-19 or 29-36 or 38, wherein the step of applying the liquid composition to the dental enamel is carried out by a dental professional.

[0200] 40. The method according to embodiments 2-19 or 29-36 or 38-39, wherein the step of applying the liquid composition to the dental enamel is by a swab, brush, or as droplets.

[0201] 41. The method according to embodiments 2-19 or 29-36 or 38-40, wherein the step of applying the liquid composition to the dental enamel is carried out one or more, two or more, or three or more times in a year, preferably 1 time in a year, 2 times in a year, three times in a year or four times in a year.

[0202] 42. A kit comprising: a) liquid composition comprising oxalic acid or a salt thereof; and bl) a container containing the liquid composition and bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b2) a package containing a container, the container comprising the liquid composition, and the package bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b3) a package containing a container and a leaflet, the container comprising the liquid composition, and the leaflet bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient.

[0203] 43. The kit according to embodiment 42, wherein the disorder is erosive tooth wear.

[0204] 44. The kit according to embodiment 42-43, wherein the patient is a human. P5528PC00

[0205] 45. The kit according to embodiment 42-44, wherein the liquid composition is as defined in any of embodiments 9 to 23 or 29-36.

[0206] 46. The kit according to embodiments 42-44, wherein the liquid composition is as defined in any of embodiments 9 to 19 or 29-36, and wherein the human-readable indications disclose that the liquid composition is to be applied as a mouthwash.

[0207] 47. The kit according to embodiments 42-44 or 46, wherein the liquid composition is as defined in any of embodiments 9 to 19 or 29-36, and wherein the human-readable indications disclose that the liquid composition is to be applied to the dental enamel once a day, twice a day, three times a day, four times a day, or more, preferably one, two or three times a day.

[0208] 48. The kit according to embodiments 42-44, wherein the liquid composition is as defined in any of embodiments 9-15, 20-23 or 29-36, and wherein the human-readable indications disclose that the liquid composition is to be applied by a dental professional.

[0209] 49. The kit according to embodiments 42-44 or 48, wherein the liquid composition is as defined in any of embodiments 9-15, 20-23 or 29-36, and wherein the human-readable indications disclose that the liquid composition is to be applied to the enamel by a swab, brush or as droplets.

[0210] 50. The kit according to embodiments 42-44 or 48-49, wherein the liquid composition is as defined in any of embodiments 9-15, 20-23 or 29-36, and wherein the human-readable indications disclose that the liquid composition is to be applied one or more, two or more, or three or more times in a year, preferably 1 time in a year, 2 times in a year, three times in a year or four times in a year.

[0211] 51. The kit according to embodiments 42-50 wherein the human-readable indications disclose that the patient has gastro-oesophageal reflux disease, or a disorder associated with persistent vomiting selected from an eating disorder, alcoholism and cyclic vomiting syndrome, or that the patient is pregnant and suffering from persistent vomiting.

Claims

P5528PC00CLAIMS1. A liquid composition comprising oxalic acid for use in a method of preventing or treating a disorder in dental enamel of a patient.

2. The liquid composition for use according to claim 1, wherein the disorder is erosive tooth wear.

3. The liquid composition for use according to claim 1 or 2, wherein the patient is a human.

4. The liquid composition for use according to claims 1-3, wherein the patient has gastro- oesophageal reflux disease, or a disorder associated with persistent vomiting selected from an eating disorder, alcoholism and cyclic vomiting syndrome, or wherein the patient is pregnant and suffering from persistent vomiting5. The liquid composition for use according to claims 1-4, wherein the liquid composition is an aqueous composition, preferably wherein the liquid composition comprises at least 50wt% of water, more preferably at least 70% by weight of water.

6. The liquid composition for use according to claims 1-5, wherein the liquid composition comprises at least 0.1M of oxalic acid, preferably at least IM of oxalic acid.

7. The liquid composition for use according to claims 1-6, wherein the liquid composition comprises dissolved tin, preferably wherein the content of dissolved tin in the liquid composition is from about 100 to 2000 ppm, preferably from about 150 to 1000 ppm, more preferably from about 500 to 900 ppm.

8. The liquid composition for use according to claim 7, wherein the dissolved tin is selected from hydrated stannous ions, stannous hydroxide, soluble ionic or nonionic complexes of stannous and / or stannic ions with ligands, ionic hydroxo complexes of stannous and / or stannic ions, and combinations thereof, preferably wherein the dissolved tin is selected from stannous chloride, stannous fluoride, stannous hydroxide, stannous sulphate, and combinations thereof.

9. The liquid composition for use according to claims 1-8, wherein the liquid composition comprises fluoride ions, preferably wherein the content of fluoride ions in the liquid composition is from 100 to 2000 ppm, more preferably from 200 to 1000 ppm.

10. The liquid composition for use according to claims 910, wherein the liquid composition comprises zinc, preferably dissolved zinc, optionally wherein the liquid composition comprises zinc chloride, zinc lactate, zinc acetate, zinc citrate, zinc phenolsulphonate, zinc glycinate, zinc sulphate, zinc gluconate or combinations thereof, and / or wherein the25P5528PC00 liquid composition comprises zinc in an amount of from 100 to 2000 ppm, preferably from 200 to 1000 ppm.

11. The liquid composition for use according to claims 1-10, wherein the liquid composition comprises titanium, optionally wherein the liquid composition comprises titanium dioxide, titanium tetrafluoride or combinations thereof, and / or wherein the liquid composition comprises titanium in an amount of from 0.1 to 4wt%, preferably from 0.5 to lwt%.

12. The liquid composition for use according to claims 1-11, wherein the liquid composition comprises silver, optionally wherein the liquid composition comprises silver (e.g. colloidal silver), silver diamine fluoride (SDF), or combinations thereof, and / or the liquid composition comprises silver in an amount of from 10 to 2000 ppm, preferably from 50 to 1000 ppm.

13. The liquid composition for use according to claims 1-12, wherein the liquid composition comprises calcium, preferably dissolved calcium, optionally wherein the liquid composition comprises calcium fluoride, calcium phosphate, calcium carbonate, calcium silicate, calcium glycerophosphate, calcium lactate, calcium gluconate or combinations thereof, and / or wherein the liquid composition comprises calcium in an amount of from about 100 to 500ppm, preferably from about 150 to 300ppm.

14. The liquid composition for use according to claims 1-13, wherein the liquid composition comprises phosphorus, preferably dissolved phosphorus, optionally wherein the liquid composition comprises one or more phosphates (e.g. calcium phosphate, zinc phosphate, sodium phosphate, and combinations thereof), and / or the liquid composition comprises phosphorus in an amount of from about 150 to lOOOppm, preferably from about 200 to 600ppm.

15. The liquid composition for use according to claims 1-14, wherein the liquid composition is suitable for use as a mouthwash.

16. The liquid composition for use according to claims 1-15, wherein the liquid composition is for application to the dental enamel once a day, twice a day, three times a day, four times a day, or more, preferably one, two or three times a day.

17. A kit comprising: a) liquid composition comprising oxalic acid; and bl) a container containing the liquid composition and bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, orP5528PC00 b2) a package containing a container, the container comprising the liquid composition, and the package bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient, or b3) a package containing a container and a leaflet, the container comprising the liquid composition, and the leaflet bearing human-readable indications disclosing that the liquid composition is for use in a method of preventing or treating a disorder in dental enamel of a patient.

18. The kit according to claim 17, wherein the disorder is erosive tooth wear.

19. The kit according to claims 17 or 18, wherein the patient is a human.

20. The kit according to claims 17-19, wherein the liquid composition is as defined in any of claims 6 to 14.

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