COMPOSITIONS AND METHODS TO PROMOTE MINERALIZATION.
Patent Information
- Application Number
- MX2021011093
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-10-14
- Filing Date
- 2021-09-13
- Publication Date
- 2026-02-25
- Estimated Expiration
- 2040-03-13
AI Technical Summary
Current methods for remineralizing hypomineralized dental enamel, such as those caused by dental caries or fluorosis, are limited by the propensity of amorphous calcium phosphate and calcium fluoride phosphate complexes to form gels at high concentrations, reducing their bioavailability and slowing the remineralization process.
The use of high concentrations of stabilized amorphous calcium phosphate (ACP) and/or amorphous calcium fluoride phosphate (ACFP) in liquid form, combined with heating the tooth surface or subsurface to temperatures above 37°C, to enhance mineralization.
This approach allows for faster and more extensive remineralization of dental lesions by ensuring higher concentrations of ACP and ACFP penetrate and mineralize the tooth surface effectively, overcoming the limitations of gel formation and enhancing the remineralization process.
Abstract
Description
This application claims priority over Australian provisional applications 2019900834 and 2019903859, the contents of which are incorporated herein in full by reference. FIELD OF INVENTION The present invention relates to compositions for uses including the mineralization of a tooth surface, particularly dental enamel. Methods are also provided for mineralizing hypomineralized lesions (including subsurface lesions) in dental enamel caused by various means, including dental caries, dental erosion, and fluorosis. BACKGROUND OF THE INVENTION Common causes of hypomineralized lesions are caries and fluorosis. Dental caries results from the demineralization of the hard tooth tissue, usually due to the fermentation of dietary sugars by odontopathogenic bacteria in dental plaque. Furthermore, restored tooth surfaces may be more susceptible to decay around the restoration margins. Dental erosion or corrosion is the loss of tooth minerals due to dietary or regurgitated acids. Tooth sensitivity results from the exposure of dentinal tubules through the loss of the protective mineralized layer, cementum. Dental calculus is the unwanted accumulation of calcium phosphate minerals on the tooth surface. All of these conditions—dental caries, dental erosion, tooth sensitivity, and dental calculus—are therefore related to imbalances in calcium phosphate levels. Enamel fluorosis (mottled enamel) has been recognized for nearly a century; however, the etiological role of fluoride was not identified until 1942. The characteristic appearance of fluorosis can be distinguished from other enamel disorders. The clinical features of fluorotic enamel lesions (FELs) represent a continuum ranging from fine opaque lines following the perikymata to white, chalky enamel. The presence of a comparatively highly mineralized outer enamel surface and a hypomineralized subsurface in the fluorotic lesion stimulates the incipient carious lesion of the enamel "white spot." As severity increases, both the depth of enamel involved in the lesion and the degree of hypomineralization increase. The development of fluorosis is highly dependent on the dose, duration, and timing of fluoride exposure and is thought to be related to elevated serum fluoride concentrations.Calcium lesions of white spots can also form on the developing teeth of children, such as after antibiotic treatment or fever. Such lesions indicate areas of hypomineralization (i.e., very little mineralization) of the tooth enamel. ML / I / uo I ουο Depending on the severity of the lesion, fluorosis has been clinically treated by restorative replacement or microabrasion of the external enamel. These treatments are unsatisfactory because they involve restorations or the removal of tooth structure. What is desired is a treatment that mineralizes the hypomineralized enamel to produce a natural appearance and structure. Specific complexes of casein phosphopeptides and amorphous calcium phosphate (CPP-ACP, commercially available as Recaldent™) have been shown to remineralize subsurface enamel lesions in vitro and in situ. WO 98 / 40406, issued by the University of Melbourne (the contents of which are incorporated herein by reference), describes amorphous calcium phosphate complexes (CPP-ACP) and amorphous calcium fluoride phosphate complexes (CPP-ACFP) stabilized with casein phosphopeptides (CPP), which have been produced at alkaline pH. Such complexes have been shown to prevent enamel demineralization and promote remineralization of subsurface enamel lesions in animal and human in situ caries models. Improved amorphous calcium phosphate-casein phosphopeptide (CPP-ACP) complexes and CPP-stabilized amorphous calcium fluoride phosphate (CPP-ACFP) complexes, including preferred complexes formed at pH 5 to 6.5, have also been described in WO2006 / 056013 and WO2006 / 135982. Casein-like peptides (CPPs) that are active in complex formation do so whether or not they are part of a full-length casein protein. Examples of active CPPs that can be isolated after tryptic digestion of full-length casein are specified in U.S. Patent No. 5,015,628 and include the peptides BosaS2-casein X-5P (f59-79), Bosp-casein X-4P (f1-25), BosaS2-casein X-4P (f46-70), and Bosas2-casein X-4P (f1-21). While CPP-ACP and CPP-ACFP complexes are effective in remineralizing hypomineralized enamel, current manufacturing methods limit the amount of CPP-ACP or CPP-ACFP that can be used in liquid form due to the complexes' tendency to crosslink and form a gel. Gel formation reduces the activity (bioavailability) of the ions required for remineralization of the enamel subsurface lesion. This is a significant clinical limitation, as remineralization is a slow process and can take several months at CPP-ACP or CPP-ACFP concentrations of 10% to achieve noticeable remineralization. There is a need to provide improved or alternative treatments for hypomineralized lesions. Reference to any prior art in the specification is not an acknowledgment or suggestion that this prior art forms part of the common knowledge in any jurisdiction or that it may reasonably be expected that this prior art would be understood, considered relevant and / or combined with other pieces of prior art by a person skilled in the art. BRIEF DESCRIPTION OF THE INVENTION MA / I / UO 1090 In one aspect, the present invention provides a method for mineralizing a dental surface or subsurface comprising contacting the dental surface or subsurface with stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP), and simultaneously or subsequently heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In another aspect, the present invention provides a method for mineralizing a dental surface or subsurface comprising contacting the dental surface or subsurface with a liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP). In another aspect, the present invention provides a method for mineralizing a dental surface or subsurface comprising contacting the dental surface or subsurface with a liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP), and simultaneously or subsequently heating the dental surface or subsurface to which the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In a further aspect of the present invention, a method for remineralizing a dental lesion is provided, the method comprising: To bring the hypomineralized dental surface or subsurface into contact with a liquid composition comprising at least 40% w / w amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP) stabilized with phosphopeptides (PP) at a pH greater than or equal to pH 5, but less than or equal to pH 9, thereby remineralizing the dental lesion. Preferably, the liquid composition has a pH greater than or equal to pH 6, but less than or equal to pH 8, for example, greater than or equal to pH 7, but less than or equal to pH 8. In any aspect of the invention, the method comprises heating the dental surface or subsurface to which stabilized ACP and / or ACFP has been or is being applied (e.g., in a liquid composition) to a temperature greater than or equal to 40°C, greater than or equal to 45°C, greater than or equal to 50°C, greater than or equal to 55°C, greater than or equal to 60°C or greater than or equal to 65°C. In any aspect of the invention, the method comprises heating the dental surface or subsurface to which stabilized ACP and / or ACFP has been or is being applied (e.g., in a liquid composition) to a temperature greater than 37°C, but equal to or less than 65°C, greater than 40°C, but equal to or less than 65°C, greater than 45°C, but equal to or less than 65°C, greater than 50°C, but equal to or less than 65°C, greater than 55°C, but equal to or less than 65°C, greater than 60°C, but equal to or less than 65°C. MA / t / ZUZ I / uo I ουο In any aspect of the present invention, the liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (AGP) and / or amorphous calcium fluoride phosphate (ACFP) comprises more than or equal to 25% w / v, more than or equal to 30% w / v, greater than or equal to 35% w / v, greater than or equal to 40% w / v, greater than or equal to 45% w / v, greater than or equal to 50% w / v, greater than or equal to 55% w / v, greater than or equal to 60% w / v, greater than or equal to 65% w / v of stabilized AGP and / or ACFP, greater than or equal to 70% w / v of stabilized ACP and / or ACFP, or greater than or equal to 75% w / v of stabilized ACP and / or ACFP. In any aspect of the present invention, the liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP) comprises more than 20% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 25% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 30% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 35% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 40% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 45% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 50% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 55% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP,More than 60% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP; more than 65% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP; more than 70% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP; or more than 75% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP. In any aspect of the present invention, the liquid composition comprises more than 40% w / w of phosphopeptide (PP) stabilized ACP and / or ACFP, more than 45% w / w, more than 50% w / w of stabilized ACP and / or ACFP, more than 55% w / w of stabilized ACP and / or ACFP, more than 60% w / w of stabilized ACP and / or ACFP, more than approximately 65% w / w of stabilized ACP and / or ACFP, more than approximately 70% w / w of stabilized ACP and / or ACFP, or more than approximately 75% w / w of stabilized ACP and / or ACFP. In any aspect of the present invention, the liquid composition comprises more than 40% w / w of phosphopeptide (PP) stabilized ACP and / or ACFP, more than 40% w / w of stabilized ACP and / or ACFP but less than 80% w / w of stabilized ACP and / or ACFP, more than 45% w / w of stabilized ACP and / or ACFP but less than 80% w / w of stabilized ACP and / or ACFP, more than 50% w / w of stabilized ACP and / or ACFP but less than 80% w / w of stabilized ACP and / or ACFP, more than 55% w / w of stabilized ACP and / or ACFP but less than 80% w / w of stabilized ACP and / or ACFP, more than 60% w / w of stabilized ACP and / or ACFP but less than 80% w / w of ACP and / or ACFP stabilized, more than 65% w / w stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP, more than 70% w / w stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP, or more than 75% w / w stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP. MA / I / uo I ουο In any case, the liquid composition is degassed. Degassing can be accomplished by any method that creates a negative pressure above the liquid composition. Exemplary methods involve a vacuum pump or system, for example, a venturi vacuum water system. In any aspect of the present invention, the stabilized amorphous calcium phosphate (ACP) and / or the amorphous calcium fluoride phosphate (ACFP) is stabilized with phosphopeptides. Preferably, the phosphopeptide (as defined below) is a casein phosphopeptide. In any respect, the calcium ion content of the stabilized ACP or ACFP complex is greater than approximately 30 moles per mole of PP. Preferably, the calcium ion content is in the range of approximately 30 to 100 moles of calcium per mole of PP. More preferably, the calcium ion content is in the range of approximately 30 to approximately 50 moles of calcium per mole of PP. In a preferred embodiment of each aspect of the invention, the phosphopeptide-stabilized ACP or ACFP complex in the composition has tightly bound and weakly bound calcium, wherein the bound calcium in the complex is less than the tightly bound calcium in an ACP or ACFP complex formed at pH 7.0. Optionally, the ACP or ACFP is predominantly in a basic form. In any respect, the stabilized ACP complex is a stannous (PP) associated phosphopeptide ACP complex, and the stabilized ACFP complex is an amorphous calcium fluoride phosphate (ACFP) complex stabilized with stannous (PP) associated phosphopeptide. In any respect, the ACP and / or ACFP complex is in the form of an ACP and / or ACFP complex stabilized with casein phosphopeptides. Preferably, the ACP phase is primarily (i.e., >50%) a basic phase, where the ACP predominantly comprises the species Ca2+, PO43-, and OH-. The basic phase of ACP may have the general formula [Ca3(PO4)2] x[Ca2(PO4)(OH)] where x > 1. Preferably x = 1–5. More preferably, x = 1, i.e., the two components of the formula are present in equal proportions. Accordingly, in one embodiment, the basic phase of ACP has the formula Ca3(PO4)2Ca(PO4)(OH). Preferably, the ACFP phase is primarily (i.e., >50%) basic phase, in which the ACFP predominantly comprises the species Ca2+, P4 3-, and F'. The basic phase of ACFP may have the general formula [Ca3(PO4)2]x[Ca2(PO4)F]y where x ≠ 1 when y = 1 or where y ≠ 1 when x = 1. Preferably, y = 1 and x = 1-3. More preferably, y = 1 and x = 1, i.e., the two components of the formula are present in equal proportions. Accordingly, in one embodiment, the basic phase of ACFP has the formula Ca3(PO4)2Ca2(PO4)F. In one embodiment, the ACP complex consists essentially of phosphopeptides, calcium, phosphate, and hydroxide ions, and water. Preferably, the complex also includes stannous ions. In one embodiment, the ACFP complex consists essentially of phosphopeptides, calcium, phosphate, fluoride, and hydroxide ions, and water. Preferably, the complex also includes stannous ions. In one aspect, the present invention provides a method for treating fluorosis that ML / t / ZUZ I / uo 1 ouo comprises contacting a fluorotic lesion, preferably in the dental enamel, with stabilized ACP and / or ACFP, and simultaneously or subsequently, heating the fluorotic lesion to which the stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In another aspect, the invention provides a method for treating fluorosis comprising bringing a fluorotic lesion, preferably in dental enamel, into contact with a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP. In another aspect, the invention provides a method for treating fluorosis comprising bringing a fluorotic lesion, preferably in dental enamel, into contact with a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, and simultaneously or subsequently heating the fluorotic lesion to which the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In one aspect, the present invention provides a method for treating dental caries comprising contacting a caries lesion with stabilized ACP and / or ACFP, and simultaneously or subsequently, heating the caries lesion to which the stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In another aspect, the present invention provides a method for treating dental caries comprising contacting a caries lesion with a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP. In another aspect, the present invention provides a method for treating dental caries comprising contacting a caries lesion with a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, and simultaneously or subsequently heating the caries lesion to which the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C. In any aspect of the present invention, a method, use, or composition of the invention may be employed to treat dental erosion. In this aspect, a lesion in the dental enamel caused by erosion is brought into contact with stabilized ACP and / or ACFP or a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP. In any aspect of the present invention, a method, use, or composition of the invention may be employed to reduce white spot lesions. In this respect, a white spot lesion, ML / t / ZUZ I / UO IOUÓ preferably in dental enamel, comes into contact with stabilized ACP and / or ACFP or a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP. In any aspect of the present invention, a method, use, or composition of the invention may be employed to remineralize a lesion in dental enamel or dentin. In this aspect, the lesion, preferably in dental enamel, is brought into contact with stabilized ACP and / or ACFP or a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP. In any aspect of the present invention, the liquid composition comprises equal to or greater than approximately 40% w / v of stabilized ACP. In any aspect of the present invention, the liquid composition comprises equal to or greater than approximately 50% w / v of ACFP. In any aspect of the present invention, the dental surface or subsurface, or the lesion (e.g., fluorosis, caries, white spot, or erosion), can be heated to a temperature equal to or greater than approximately 45°C. Preferably, the temperature does not exceed 65°C. In any aspect of the invention, the pH of the liquid composition is less than or equal to 6. Preferably, the pH is equal to or less than 5.5. Alternatively, the pH of the liquid composition is greater than or equal to pH 5, but less than or equal to pH 9, preferably greater than or equal to pH 6, but less than or equal to pH 8, most preferably greater than or equal to pH 7, but less than or equal to pH 8. In one embodiment, when the w / v percentage of stabilized ACP and / or ACFP is greater than 20% w / v but less than 40% w / v, the pH of the liquid composition is between approximately 5 and approximately 8, preferably between approximately 5 and approximately 7. In another embodiment, when the w / v percentage of stabilized ACP and / or ACFP is greater than 40% w / v, the pH of the liquid composition is less than or equal to 6. Preferably, the pH is equal to or less than 5.5. In any aspect of the invention described herein, a dental health professional applies stabilized ACP or ACFP, a liquid composition comprising stabilized ACP or ACFP and / or heat to the mouth, tooth or lesion. In any aspect of the present invention, the dental surface or subsurface, or the lesion (e.g., fluorosis, caries, white spot or caused by erosion), can be heated for approximately 1 to 60 minutes, or for approximately 1 to 30 minutes. Preferably, the stabilized ACP and / or ACFP or the liquid composition comprising stabilized ACP and / or ACFP are brought into contact with the tooth surface for a period of approximately 1 minute to 2 hours, or 5 minutes to 60 minutes, or approximately 10 minutes. In any respect, the dental surface or subsurface, or the lesion, requires such treatment. Therefore, the invention includes, in addition to the steps of any method described herein, a step of identifying a subject suffering from fluorosis, dental caries, dentin hypersensitivity, or dental calculus; a white spot lesion; a fluorotic lesion; a carious lesion; or a lesion caused by erosion. ΜΛ / t / ZUZ I / uo I ουο dental. In another aspect, the present invention provides a liquid composition comprising more ML / I / uo I ouo of 20% w / v of stabilized ACP and / or ACFP. Preferably, the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP comprises more than or equal to 25% w / v, more than or equal to 30% w / v, more than or equal to 35% w / v, more than or equal to 40% w / v, more than or equal to 45% w / v, more than or equal to 50% w / v stabilized ACP and / or ACFP, more than or equal to 55% w / v stabilized ACP and / or ACFP, more than or equal to 60% w / v stabilized ACP and / or ACFP, more than or equal to 65% w / v stabilized ACP and / or ACFP, more than or equal to 70% w / v of stabilized ACP and / or ACFP, or more than or equal to 75% w / v of stabilized ACP and / or ACFP. In this aspect of the present invention, the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 25% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 30% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 35% w / v of stabilized ACP and / or ACFP, but less than 80% w / v stabilized ACP and / or ACFP, more than 40% w / v stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 45% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 50% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 55% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 60% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 65% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, more than 70% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP, or more than 75% w / v of stabilized ACP and / or ACFP, but less than 80% w / v of stabilized ACP and / or ACFP. In this aspect of the present invention, the liquid composition comprises more than 40% w / w of ACP and / or ACFP stabilized, more than 45% w / w, more than 50% w / w of ACP and / or ACFP stabilized, more than 55% w / w of ACP and / or ACFP stabilized, more than 60% w / w of ACP and / or ACFP stabilized, more than approximately 65% w / w of ACP and / or ACFP stabilized, more than approximately 70% w / w of ACP and / or ACFP stabilized, or more than approximately 75% w / w of ACP and / or ACFP stabilized. In this respect, the liquid composition comprises more than 40% w / w of ACP and / or ACFP, more than 40% w / w of ACP and / or ACFP stabilized with phosphopeptides (PP), but less than 80% w / w of ACP and / or ACFP stabilized, more than 45% w / w of stabilized ACP and / or ACFP, but less than 80% w / w of stabilized ACP and / or ACFP, more than 50% w / w of stabilized ACP and / or ACFP, but less than 80% w / w of stabilized ACP and / or ACFP, more than 55% w / w of stabilized ACP and / or ACFP, but less than 80% w / w of stabilized ACP and / or ACFP, more than 60% w / w of stabilized ACP and / or ACFP, but less than 80% w / w of stabilized ACP and / or ACFP, more than 65% w / w of stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP, more than 70% w / w stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP, or more than 75% w / w stabilized ACP and / or ACFP, but less than 80% w / w stabilized ACP and / or ACFP. In any aspect as described herein, the liquid composition may further comprise fluoride ions, preferably free fluoride ions. The fluoride ions may be present in the liquid composition at a concentration in the range of approximately 200 ppm to 50,000 ppm. In a preferred embodiment, the fluoride ions are at a concentration in the range of approximately 2,600 ppm to approximately 10,000 ppm. In a further preferred embodiment, the fluoride ions in the liquid composition are at a concentration of approximately 8,200 ppm or approximately 6,500 ppm. The fluoride ions may be present in the liquid composition at any ppm described herein, particularly in the Examples. In any embodiment, the fluoride ions are at a concentration of approximately 2,600 ppm, 3,900 ppm, 5,200 ppm, 6,500 ppm, or 7,800 ppm.Typically, fluoride ions are at a concentration of approximately 2,600 ppm for ACP or ACFP stabilized at 20% w / v, approximately 3,260 ppm for ACP or ACFP stabilized at 25% w / v, approximately 3,900 ppm for ACP or ACFP stabilized at 30% w / v, approximately 4,890 ppm for ACP or ACFP stabilized at 38%, 5,200 ppm for ACP or ACFP stabilized at 40% w / v, 6,500 ppm for ACP or ACFP stabilized at 50% w / v, approximately 8,200 ppm for ACP or ACFP stabilized at 63% w / v and approximately 9,900 ppm for ACP or ACFP stabilized at 75% w / v. In another embodiment, fluoride ions are at a concentration of approximately 5,200 ppm for 40% w / w CPP-ACP and approximately 7,800 ppm for 60% w / w CPP-ACP. Preferably, the stabilized ACP and / or ACFP are stabilized with phosphopeptides. Preferably, the phosphopeptide is a casein phosphopeptide. Any composition described in this document may be used in any of the methods described herein. The composition is a physiologically acceptable composition as described herein. In another aspect, the present invention provides a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP for use in: • the mineralization of a tooth surface or subsurface, or any lesion as described in this document; or • the treatment or prevention of one or more of each dental caries, dental erosion, white spot lesions, and fluorosis. In an additional aspect, the use of a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP is provided in the manufacture of a composition or drug for the mineralization of a dental surface or subsurface, or treatment and / or prevention of one or more of the dental caries, dental erosion and fluorosis. In an additional aspect, the use of an amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP) stabilized with phosphopeptide (PP) is provided in the manufacture of a product comprising or consisting of a liquid composition for remineralizing a dental surface or subsurface. MA / t / ZUZ! / UO I Oyó liquid composition comprising at least 40% w / w of said amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP) stabilized with phosphopeptides (PP) at a pH greater than or equal to pH 5 but less than or equal to pH 9. In one embodiment, the product is a cosmetic product. The invention also relates to a kit for the treatment or prevention of one or more dental caries, fluorosis, and dental erosion, or mineralization of a surface or subsurface or dental lesion as described herein, comprising (a) a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, and (b) a heat source. Desirably, the kit further includes instructions for its use in any of the methods or applications described herein. The instructions may describe the use of the kit to treat or prevent one or more of each dental caries, dental erosion, and fluorosis. In one embodiment, the liquid composition is present in quantities suitable for the treatment of a patient. Preferably, the stabilized ACP and / or ACFP are stabilized with phosphopeptides (PP). Preferably, the phosphopeptide (as defined below) is a casein phosphopeptide.Preferably, the ACP or ACFP is in the form of an ACP or ACFP complex stabilized with casein phosphopeptide. The composition or kit of the invention may further include a source of fluoride ions. The fluoride ions may be derived from any suitable source. A source of fluoride ions may include free fluoride ions or fluoride salts. Examples of sources of fluoride ions include, but are not limited to, the following: sodium fluoride, sodium monofluorophosphate, stannous fluoride, sodium silicofluoride, silver fluoride, amine fluoride, or any metal ion fluoride salt. A source of fluoride ions may be hypofluorite. These sources of fluoride ions may be provided in solution (usually an aqueous solution) or in suspension. In another aspect, the present invention provides a method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of: Mix a solvent and a powder comprising or consisting of stabilized ACP and / or ACFP, and maintain the pH below 7. Preferably, the pH is maintained at, or below, 6, preferably the pH is maintained at, or below, 5.5. In another aspect, the present invention provides a method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of: Mix a solvent and a powder comprising or consisting of stabilized ACP and / or ACFP, and reduce the pH below 7. Preferably, the pH is reduced to, or below, 6, preferably 5.5. Normally, the pH is kept below 7, more preferably the pH is kept at, or below, 6, even more preferably 5.5. In another aspect, the present invention provides a method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process ΜΛ / t / ZUZ I / uo I ουο comprises or consists of: Mixing a solution containing fluoride and a powder comprising or consisting of stabilized AGP and / or ACFP, and adjusting the pH between 6.5 and 8. Preferably, the pH is adjusted to approximately pH 7.8. Preferably, the pH is adjusted with HCl. In this respect, the method also includes the step of mixing the solution for at least approximately 10 minutes, at least approximately 20 minutes, or at least approximately 30 minutes after adjusting the pH. In this respect, the method also includes the step of degassing the liquid composition. In any respect, the step of mixing a solvent and a powder comprising or consisting of PP-stabilized ACP and / or ACFP comprises adding the solvent to the powder. Alternatively, the step comprises adding the powder to the solvent. In any method or process for preparing a liquid composition as described herein, the method or process further comprises the step of degassing the liquid composition. Degassing may be carried out by any method that creates a negative pressure above the liquid composition, including the methods described herein. In any method or process for preparing a liquid composition as described in this document, the method or process further comprises a step of mixing the liquid composition with a solution comprising fluoride ions. In another aspect, the present invention provides a method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of the steps described in Example 2 or 4 of this document. In any respect, the present invention provides a method or process further comprising the following steps for preparing a powder comprising or consisting of stabilized ACP and / or ACFP: mixing one or more solutions comprising phosphopeptides, calcium ions, phosphate ions, hydroxide ions, and optionally fluoride ions, while maintaining the pH at approximately 7.0 or higher, preferably around 9, to form a solution comprising stabilized ACP and / or ACFP, and drying the solution comprising stabilized ACP and / or ACFP, thereby forming a powder comprising or consisting of stabilized ACP and / or ACFP. Preferably, the drying is by spray drying or drip drying. In one modality, the method or process also includes the following steps: filter the solution comprising stabilized ACP and / or ACFP, prior to drying, to form a retentate, wherein the retentate is subsequently dried to form a powder comprising or consisting of stabilized ACP and / or ACFP. In another aspect, the present invention provides a method or process for preparing a MA / I / uo i ouo liquid composition comprising at least 40% w / v of stabilized ACP and / or ACFP, the method or process comprises or consists of: Mix a solvent and a powder comprising or consisting of ACP stabilized with PP and / or ACFP, and reduce the pH below 9, preferably 8. Preferably, the solvent comprises fluoride. In this respect, the method also includes a step of stirring the liquid composition after the pH has been reduced. Preferably, the stirring takes place for at least 5, 10, 15, 20, 25, or 30 minutes. In this respect, the liquid composition is degassed to remove trapped air bubbles, preferably by placing the solution under vacuum, most preferably for 24 hours. In another aspect, the present invention provides a method or process for preparing a liquid composition comprising at least 40% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of the steps described in Example 4 of this document. In any method or process for preparing a liquid composition comprising more than 20% w / v or more than 40% w / w of stabilized ACP and / or ACFP, the solvent is water. In any method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the pH is reduced or maintained using 1-10 M HCl or 11 M HCl. In any respect, the method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP may be for preparing a liquid composition comprising equal to or greater than 25% w / v, 30% w / v, 35% w / v, 40% w / v, 45% w / v, 50% w / v, 55% w / v, 60% w / v, 65% w / v, 70% w / v, 75% w / v, or 80% w / v of stabilized ACP and / or ACFP. In any method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the stabilized ACP or ACFP is CPP-ACP or CPP-ACFP as described herein. In any method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the liquid composition is used in any dental treatment method, preferably those described in this document (e.g., mineralization of a dental surface or subsurface). In another aspect, the present invention provides a liquid composition comprising more than 20% w / v of ACP and / or ACFP prepared by a method or process described herein. Additional aspects of the present invention and other additional embodiments of the aspects described in the preceding paragraphs will become evident from the following description, given by way of example and with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE FIGURES MA / t / ZUZ I / uo I ουο Figure 1. Effect of Temperature on Remineralization of Subsurface Lesions of the enamel in vitro. Figure 2. Remineralization by high concentrations of CPP-ACP in the presence of fluoride. Figure 3. Remineralization by high concentrations of CPP-ACP. DETAILED DESCRIPTION OF THE MODALITIES It is also understood that the invention disclosed and defined in this description extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All these different combinations constitute various alternative aspects of the invention. Additional aspects of the present invention and other additional embodiments of the aspects described in the preceding paragraphs will become evident from the following description, given by way of example and with reference to the accompanying drawings. Detailed reference will now be made to the embodiments of the invention. Although the invention will be described in conjunction with the embodiments, it is understood that the invention is not intended to be limited to those described. On the contrary, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the scope of the present invention as defined in the claims. A person skilled in the art will recognize many methods and materials similar or equivalent to those described herein that could be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described. All patents and publications cited herein are incorporated in their entirety by reference. For the purposes of interpreting this description, terms used in the singular will also include the plural and vice versa. As used in this document, except where the context requires otherwise, the term "comprises" and variations of the term, such as "comprises," "understands," and "understood," are not intended to exclude additives, components, whole numbers, or additional steps. As used in this document, except where the context requires otherwise, "comprises" and "includes" may be used interchangeably. One aspect of an invention described herein is based on the surprising finding that it is possible to achieve a composition with a high concentration of stabilized ACP and / or ACFP while still maintaining a liquid state (i.e., not forming a gel). Prior to the present invention, it was thought that high concentrations of phosphopeptide-stabilized ACP and / or ACFP would result in the composition forming a gel or paste, and all liquid compositions described to date had relatively low concentrations of phosphopeptide-stabilized ACP and / or ACFP. The unexpected property of a high-concentration composition of phosphopeptide-stabilized ACP and / or ACFP that maintains a liquid state The liquid ML / I / uo i ouo, applied before application to a dental surface or subsurface, allows for faster penetration into a hypomineralized site. While not linked to any specific theory or mode of action, it is believed that a higher concentration of stabilized ACP and / or ACFP can be achieved within the lesion, resulting in faster and more extensive remineralization. This provides the advantage that a dental professional can apply the high-concentration liquid composition directly to a lesion, enabling more extensive remineralization compared to at-home application of low-concentration compositions such as pastes or mousses. Furthermore, an independent aspect of an invention described herein is based on the surprising finding that heating the dental surface or subsurface at the same time as or after the application of stabilized ACP and / or ACFP increases the degree of mineralization, even up to relatively high temperatures. Finally, a combination of both high-concentration liquid compositions with heating of the tooth surface to which the stabilized ACP and / or ACFP has been or is being applied, provides extensive and rapid remineralization. Any heat source may be used in a method or use of the invention to heat the dental surface or subsurface. Heat sources that emit light or radiation and are suitable for use in dental applications are known in the art. Specific examples include dental curing lights, for example, a 10 W high-power blue LED such as the X-Cure from Guilin Woodpecker Medical Instrument Co. Ltd. As used here, % w / v can be taken as equivalent to g / 100 mL As used herein, stabilized ACP or ACFP and stabilized ACP complex or ACFP are used interchangeably. A stabilized ACP or ACFP complex as described in the current description may be the closed complexes shown in Figure 2 of Cross et al., 2007. A stabilized ACP or ACFP as referred to herein includes a stabilized ACP or ACFP as described in document WO2006 / 056013 (PCT / AU2005 / 001781), the contents of which are incorporated by reference. In a preferred embodiment, the phosphopeptide-stabilized amorphous calcium phosphate complex (ACP) or amorphous calcium fluoride phosphate (ACFP) has both strongly and weakly bound calcium, wherein the bound calcium in the complex is less than the strongly bound calcium in an ACP or ACFP complex formed at pH 7.0. Optionally, the ACP or ACFP is predominantly in a basic form. A stabilized ACP or ACFP complex as referred to herein includes a stabilized ACP or ACFP complex formed at a pH below 7.0. Preferably, the complex forms at a pH in the range of approximately 5.0 to, but below, 7.0. More preferably, the complex forms in a pH range of approximately 5.0 to approximately 6.0. In one embodiment ML / I / uo I ouo preferably, the complex is formed at a pH of approximately 5.5. Preferably, the AGP or ACFP in the complex is predominantly in basic form. A stabilized PCA can be produced by a method comprising the following steps: (i) obtaining a solution comprising at least one phosphopeptide and; (ii) mixing solutions comprising calcium ions, phosphate ions and hydroxide ions, while maintaining the pH between approximately 5.5 and 9. In one mode, the pH is maintained at approximately 7.0 or less. A stabilized ACFP can be produced by a method comprising the following steps: (i) obtaining a solution comprising at least one phosphopeptide and; (ii) mixing solutions comprising calcium ions, phosphate ions, hydroxide ions and fluoride ions, while maintaining the pH between approximately 5.5 and 9. In one mode, the pH is maintained at approximately 7.0 or less. An amorphous calcium phosphate (ACP) complex stabilized with phosphopeptide or amorphous calcium fluoride phosphate (ACFP) may also include a complex in which the ACP in the complex has tightly bound and weakly bound calcium, wherein the tightly bound calcium in the complex is less than the tightly bound calcium in an ACP or ACFP complex formed at pH 7.0 and the ACP or ACFP is predominantly in a basic form, obtainable or obtained by a method comprising: a) mixing a first solution comprising calcium ions, a second solution comprising phosphate ions and optionally a third solution comprising fluoride ions, in a solution comprising phosphopeptides and a solvent having a pH of approximately 5 to, but below, 7; and b) maintain the pH of the solution from approximately 5.0 to, but below, 7.0 during mixing by adding hydroxide ions. The tightly and weakly bound calcium and phosphate in ACP or ACFP can be determined by analytical ultrafiltration. Briefly, a solution of phosphopeptide, calcium, phosphate, and optionally fluoride, mixed while maintaining the pH at approximately 7.0 or below, can first be filtered through a 0.1 µm filter to remove free calcium and phosphate that are not associated with the complexes. This free calcium and phosphate is present in the filtrate and is discarded. Any free calcium or phosphate that is not associated in any way with the complexes would not be bioavailable, i.e., supplied by the phosphopeptide to the tooth. The retentate from the 0.1 µm filtrate can be further analyzed by centrifugation through a 3000 mW cut filter at 1000 g for 15 min. The resulting filtrate contains calcium and phosphate that is weakly bound or associated with the complexes.Due to this centrifugal force, calcium and phosphate that are not tightly bound to the complexes are released and move into the filtrate. The Ca and Pi that are tightly bound in the complexes are retained in the retentate. The amount of tightly bound Ca and Pi in the retentate can then be determined by subtracting the amount of Ca and Pi in the filtrate from the total amount of Ca. MA / I / uo I ouo and Pi in the retentate of the filtration of 0.1 mieras. A stabilized ACP or ACFP complex as referred to herein includes a stabilized ACP or ACFP complex as described in document WO2006 / 135982 (PCT / AU2006 / 000885) the contents of which are incorporated by reference. A phosphopeptide or phosphoprotein (PP) complex supercharged with stabilized amorphous calcium phosphate (ACP) or stabilized amorphous calcium fluoride phosphate (ACFP). The complex can form at any pH (e.g., 3–10). Preferably, the phosphopeptide includes the sequence -ABC-, where A is a phosphoamino acid, preferably phosphoserine, B is any amino acid including a phosphoamino acid, and C is glutamic acid, aspartic acid, or a phosphoamino acid. The phosphoamino acid can be phosphoserine. The PP is overloaded with calcium and phosphate ions. The calcium ions can be in the range of 30–1000 moles of Ca per mole of PP, or in the range of 30–100 or 30–50 moles of Ca per mole of PP. In another form, the mole of Ca per mole of PP is at least 25, 30, 35, 40, 45 or 50. The amorphous calcium phosphate complex stabilized with phosphopeptide or phosphoprotein (PP) or stabilized amorphous calcium fluoride phosphate may have a calcium ion content greater than approximately 30 moles of calcium per mole of PP. In a preferred embodiment, the calcium ion content is in the range of approximately 30 to 100 moles of calcium per mole of PP. More preferably, the calcium ion content is in the range of approximately 30 to approximately 50 moles of calcium per mole of PP. The stabilized amorphous calcium phosphate (ACP) complex or the stabilized amorphous calcium fluoride phosphate (ACFP) complex with phosphopeptide or phosphoprotein (PP) can be produced by a method comprising the steps of: (i) obtaining solutions comprising calcium, inorganic phosphate and fluoride (optional); and (ii) mixing (i) with a solution comprising PP-ACP. In a preferred form, PP is casein phosphopeptide (CPP). The PP-stabilized ACP and / or ACFP complex may further include at least an equal amount by weight of calcium phosphate. Preferably, the calcium phosphate is CaHPO4. Preferably, the calcium phosphate (e.g., CaHPO4) is dry-mixed with the PP-stabilized ACP and / or ACFP complex. In a preferred embodiment, the ratio of PP-ACP and / or PP-ACFP complex to calcium phosphate is approximately RISO, more preferably approximately 1:1-25, more preferably approximately 1:5-15. In one embodiment, the ratio of PP-ACP and / or PP-ACFP complex to calcium phosphate is approximately 1:10. The oral care formulation that includes an amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP) complex stabilized with phosphopeptide or phosphoprotein (PP) having a calcium ion content greater than approximately 30 moles of calcium per mole of PP when used in the oral cavity can be produced by a method that includes the following steps: (i) obtaining a powder that includes a PP-ACP and / or PP-ACFP complex; (i) dry mix with an effective amount of calcium phosphate; and ΜΛ / I / uo i ουο (iii) formulate the dry mixture of PP-ACP and / or PP-ACFP and calcium phosphate into an oral care formulation. Preferably, the form of calcium phosphate for dry mixing is any soluble calcium phosphate that includes, but is not limited to, CaHPO4, Ca2HPO4 and calcium lactate. A composition as described herein may also include free fluoride ions. The fluoride ions may be derived from any suitable source. A source of fluoride ions may include free fluoride ions or fluoride salts. Examples of sources of fluoride ions include, but are not limited to, the following: sodium fluoride, sodium monofluorophosphate, stannous fluoride, sodium silicofluoride, and amine fluoride. These may be provided in solution (usually an aqueous solution) or in suspension. Fluoride ions are preferably present in the composition in an amount greater than 1 ppm. More preferably, the amount is greater than 3 ppm. In another embodiment, it is preferably greater than ppm. In the typical embodiments described below, the amount may be several hundred or thousands of ppm. Normally, free fluoride ions are in the range of 1,000 ppm to 50,000 ppm F. ppm F may be any amount or concentration described in this document. Fluoride content is generally measured as ppm in oral compositions in the manner commonly used in the art. When fluoride is derived from a source with stabilized ACP, ppm refers to the fluoride concentration in that source, usually a bioavailable fluoride solution or suspension. A stannous ACP or ACFP complex, as referred to in this document, includes any of those described in PCT / AU2014 / 050447, the content of which is incorporated in full by reference. A composition as described herein for use in a method of using the invention may include an ACP or ACFP complex associated with stannous fluoride. The composition may include 2% CPP-ACP and 290 ppm fluoride, with 220 ppm of fluoride as stannous fluoride and 70 ppm as sodium fluoride. Phosphopeptide, in the context of this invention, means an amino acid sequence in which at least one amino acid is phosphorylated. Preferably, the phosphopeptide includes one or more of the amino acid sequence ABC, where A is a phosphoamino residue, B is any amino acyl residue including a phosphoamino residue, and C is selected from a glutamyl, aspartyl, or phosphoamino residue. Any of the phosphoamino residues may independently be a phosphoseryl residue. B is desirably a residue whose side chain is neither relatively large nor hydrophobic. It may be Gly, Ala, Val, Met, Leu, He, Ser, Thr, Cys, Asp, Glu, Asn, Gln, or Lys. In another embodiment, at least two of the phosphoamino acids in the sequence are preferably contiguous. Preferably, the phosphopeptide includes the sequence ABCDE, where A, B, C, D, and E are independently phosphoserine, phosphothreonine, phosphotyrosine, phosphohistidine, glutamic acid, or aspartic acid, and ML / t / ZUZ I / UO IOUÓ at least two, preferably three, of A, B, C, D and E are a phosphoamino acid. In a preferred embodiment, the phosphoamino acid residues are phosphoserine, most preferably three contiguous phosphoserine residues. It is also preferred that D and E be independently glutamic or aspartic acid. In one embodiment, the ACP or ACFP is stabilized by a casein phosphopeptide (CPP), which is in the form of intact casein or a casein fragment, and the complex formed preferably has the formula [CPP(ACP)8]n[(CPP)(ACFP)8]n where n is equal to or greater than 1, for example, 6. The complex formed can be a colloidal complex, where the core particles aggregate to form large colloidal particles (for example, 100 nm) suspended in water. Therefore, the PP can be either a casein protein or a phosphopeptide. The PP can be of any source; it may be present within a larger polypeptide, including a full-length casein polypeptide, or it may be isolated by tryptic or other enzymatic or chemical digestion of casein, or other phosphoamino acid-rich proteins such as phosphitin, or by chemical or recombinant synthesis, provided it comprises the sequence -ABC- or ABCDE as described above. The sequence flanking this core sequence can be any sequence. However, flanking sequences at asi(59-79), β(1-25), aS2(46-70), and aS2(1-21) are preferred. The flanking sequences may optionally be modified by deletion, addition, or conservative substitution of one or more residues. The amino acid composition and sequence of the flanking region are not critical. Table 2 shows examples of such conservative substitutions. ML / t / ZUZ I / UO IOUÓ TABLE A ML / t / ZUZ I / UO 1090 Original Residue Conservative Substitution Exemplar Preferred Conservative Substitution Ala Val, Leu, lie Val Asn Gln Lys His Phe Gln Gln Asn Asn Gly Pro Pro He Leu. Val, Met. Ala, Phe Leu Leu lie, Val. Met, Ala. Phe lie Lys Arg. Gln, Asn Arg Phe Leu. Val, lie, Ala Leu Pro Gly Gly Ser Thr Thr Val He, Leu. Met, Phe, Ala Leu Asp Glu Glu Thr Ser Ser Trp Tyr Tyr Tyr Trp Phe Thr Ser Phe Flanking sequences may also include amino acid residues of non-natural origin. Commonly found amino acids not encoded by the genetic code include: 2-aminoadipic acid (Aad) for Glu and Asp; 2-aminopimelic acid (Apm) for Glu and Asp; 2-aminobutyric acid (Abu) for Met, Leu and other aliphatic amino acids; 2-aminoheptanoic acid (Ahe) for Met, Leu and other aliphatic amino acids; 2-aminoisobutyric acid (Aib) for Gly; cyclohexylalanine (Cha) for Val, and Leu e lie; homoarginine (Har) for Arg and Lys; 2,3-diaminopropionic acid (Dpr) for Lys, Arg and His; N-ethylglycine (EtGly) for Gly, Pro and Ala; N-ethylasparygin (EtAsn) for Asn and Gln; hydroxylysine (Hyl) for Lys; allohydroxylysine (AHyl) for Lys; 3-(and 4) hydroxyproline (3Hyp, 4Hyp) for Pro, Ser and Thr; aloisoleucine (Alie) for lie, Leu and Val; p-amidinophenylalanine for Ala; N-methylglycine (MeGly, sarcosine) for Gly, Pro, Ala. N-methylisoleucine (Melle) for He; Norvaline (Nva) for Met and other aliphatic amino acids; Norleucine (Nle) for Met and other aliphatic amino acids; Ornithine (Orn) for Lys, Arg and His; Citrulline (Cit) and methionine sulfoxide (MSO) for Thr, Asn and Gln; N-methylphenylalanine (MePhe), trimethylphenylalanine, halo (F, Cl, Br and I) phenylalanine, trifluorylphenylalanine, para Phe. In one modality, PP is one or more selected phosphopeptides from the group that consists of asi (59-79) [1], β (1-25) [2], as2(46-70) [3] and as2 (1-21) [4]: [1] Gln59-Met-Glu-Ala-Glu-Ser(P)-lle-Ser(P)-Ser(P)-Se(P)-Glu-Glu-lle-Val-Pro-Asn-Ser(P)-ValGlu-GIn-Lys79(SEQ ID NO: 1) asi (59-79) [2] Arg1-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-lle-Val-Glu-Ser(P)-Leu-Ser(P)-Ser(P) -Ser(P) -Glu -Glu-Ser-lle-Thr-Arg25 (SEC ID NO: 2) β (1-25) [3] Asn46-Ala-Asn-Glu-Glu-Glu-Tyr-Ser-lle-Gly-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ser(P)-Ala-Glu-ValAla-Thr-Glu-Glu-Val-Lys70(SEQ ID NO: 3) as2(46-70) [4] Lys1-Asn-Thr-Met-Glu-His-Val-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-Ser-lle-lle-Ser(P)-Gln-Glu-ThrTyr -Lys21(SEQ ID NO: 4) as2(1 -21). In certain preferred embodiments of the invention, a liquid composition may be a mouthwash, rinse, or spray. In such a preparation, the vehicle is generally a mixture of water and alcohol, desirably including a humectant as described below. Generally, the weight ratio of water to alcohol is in the range of approximately 1:1 to approximately 20:1. The total amount of water and alcohol mixture in this type of preparation is generally in the range of approximately 70 to approximately 99.9% by weight of the preparation. The alcohol is generally ethanol or isopropanol. Ethanol is preferred. It is understood that, as is conventional, oral preparations will normally be sold or otherwise distributed in appropriately labeled containers. Therefore, a bottle of mouthwash will have a label describing it, essentially, as a mouthwash and with instructions for its use. Organic surfactants may be used in the compositions of the present invention to achieve increased prophylactic action, helping to achieve total and complete dispersion of the active agent MA / t / ZUZ! / UO 10^0 throughout the oral cavity and make the present compositions more cosmetically acceptable. The organic surfactant is preferably anionic, non-ionic, or ampholytic in nature and preferably does not interact with the active agent. It is preferred to use a detergent material as the surfactant that imparts detergent and foaming properties to the composition.Suitable examples of anionic surfactants are water-soluble salts of monosulfates of higher fatty acid monoglycerides, such as the sodium salt of monosulfated fatty acid monoglyceride of hydrogenated coconut oil, higher alkyl sulfates such as sodium lauryl sulfate, alkyl and aryl sulfonates such as sodium dodecylbenzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxypropanesulfonate, and substantially saturated higher aliphatic acylamides of lower aliphatic aminocarboxylic acid compounds, such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the like. Examples of the latter amides mentioned are N-lauroyl sarcosine and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine, which must be substantially free of soap or similar higher fatty acid material.The use of these sarconite compounds in the oral compositions of the present invention is particularly advantageous since these materials exhibit a marked prolonged effect in inhibiting acid formation in the oral cavity due to carbohydrate decomposition, in addition to exerting some reduction in the solubility of tooth enamel in acidic solutions.Examples of water-soluble nonionic surfactants suitable for use are condensation products of ethylene oxide with various hydrogen-containing reactive compounds that react with them having long hydrophobic chains (e.g., aliphatic chains of approximately 12 to 20 carbon atoms), whose condensation products (ethoxamers) contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g., sorbitan monostearate), and polypropylene oxide (e.g., pluronic materials). The surfactant is generally present in an amount of approximately 0.1–5% by weight. It is worth noting that the surfactant can help dissolve the active agent of the invention and, therefore, decrease the amount of solubilizing wetting agent required. Various other materials may be incorporated into the oral preparations of this invention, such as bleaching agents, preservatives, silicones, chlorophyll compounds, and / or ammoniacal materials such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, when present, are incorporated into the preparations in quantities that do not substantially and adversely affect the desired properties and characteristics. Any suitable flavoring or sweetening material may also be used. Examples of suitable flavoring constituents are flavoring oils, for example, spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange oils, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, xylitol, and sodium cyclamate. MA / I / UO 1090 perillartin, AMP (aspartyl phenylalanine methyl ester), saccharin, and the like. Suitablely, flavoring and sweetening agents may each or together comprise approximately 0.1% to 5% more of the preparation. In another embodiment, the compositions of the invention described herein do not include a phosphate buffer and / or a calcium chelator. For example, any toothpaste described herein may not include a phosphate buffer and / or a calcium chelator. In one embodiment of the present invention, a composition is provided, wherein the composition does not include a phosphate buffer and / or calcium chelator. In another embodiment, the compositions of the invention as described herein do not include a viscosity regulator or a viscosity regulator at 0.5 to 50%. In another embodiment, the compositions of the invention as described herein do not include sodium carboxymethylcellulose or sodium carboxymethylcellulose at 0.1 to 10% having the degree of esterification of 0.7 to 1.0. In one modality, the active components of the composition consist essentially of stabilized ACP or ACFP complexes. It shall be clearly understood that, although this description refers specifically to applications in humans, the invention is also useful for veterinary purposes. Therefore, in all respects, the invention is useful for domestic animals such as cattle, sheep, horses, and poultry; for companion animals such as dogs and cats; and for zoo animals. The invention also provides a kit comprising stabilized amorphous calcium phosphate (ACP) and / or stabilized amorphous calcium phosphate fluoride (ACFP), said kit being adapted for use in the methods described above. The invention also provides a kit comprising a liquid composition as described herein. In any case, the kit may also include a label or leaflet with instructions for its use in any method described herein. The kit may include: - a container containing a composition comprising stabilized amorphous calcium phosphate (ACP) and / or stabilized amorphous calcium phosphate fluoride (ACFP); - a label or leaflet with instructions for use. In certain modalities, the kit may contain one or more additional active ingredients or components for the treatment or prevention of a disease or condition as described herein. The kit may comprise a container and a label or leaflet on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, blister packs, etc. The containers may MA / E / ZuZ / UO I Oyó can be formed from a variety of materials such as glass or plastic. The container holds a therapeutic composition that is effective in treating the condition and may have a sterile access port (for example, the container may be an intravenous solution bag or a vial that has a stopper that can be pierced by a hypodermic injection needle). The label or package insert indicates that the composition is used to treat the condition of choice. In one modality, the label or package insert includes instructions for use and indicates that the therapeutic composition can be used for the treatment of the given condition. The kit may comprise (a) a liquid composition as described herein; and (b) a second container with a second active ingredient. The kit in this embodiment of the invention may further comprise a package insert stating that the composition and another active ingredient may be used to treat a condition as described herein. Alternatively or additionally, the kit may further comprise a second (or third) container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and dextrose solution. It may further include other commercially and user-desirable materials, including additional buffers, diluents, filters, needles, and syringes. It is also understood that the invention disclosed and defined in this description extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All these different combinations constitute various alternative aspects of the invention. The invention will now be described in more detail with reference to the following non-limiting examples. EXAMPLES Example 1 Effect of Temperature on Remineralization of Enamel Subsurface Lesions. The aim of these experiments was to determine the effect of temperature on the remineralization of enamel subsurface lesions using an in vitro model. The solutions were prepared using CPP-ACP and, optionally, NaF, to produce CPP-ACP at 1.0% w / v pH 5.5 or CPP-ACFP at 1.0% w / v pH 5.5. Five different temperatures tested: (i) 25°C, (ii) 35°C, (iii) 45°C, (iv) 55°C and (v) 65°C. Subsurface demineralized lesions of human dental enamel were prepared in third molar enamel blocks using the Reynolds method (J. Dent. Res. 1997, 76(9):1587-95). Half of the blocks were kept as a control and the other half were remineralized by suspending them individually in 1.0% CPP-ACP + 725ppm F for 14 days at five different temperatures (25, 35, 45, 55 and 65°C). After remineralization, the enamel blocks were embedded, sectioned, and subjected ML / t / ZUZ I / uo I ouo a cross-sectional microradiography and densitometric image analysis as described above by Reynolds (1997, J Dent Res, supra) to determine the percentage of mineral content gain (% Remineralization). Figure 1 shows the direct correlation between the increase in temperature and the increase in the amount of remineralization. Table 1: Results of the Effect of Temperature on the Remineralization of Enamel Subsurface Lesions ML / t / ZUZ I / uo i ουο LDd LDd-LDr AZd ΔΖά-ΔΖτ %R 25°C 110.62 ± 10.11 10.16 ±3.29 3138.78 ± 568.20 856.66 ± 160.90abc 27.30 ± 1.36abcd 35°C 107.28 ±6.38 11.85 ±4.43 2703.38 ± 610.76 dp 844.06 ± 194.21 31.30 ± 1 14aef9 45°C 102.79 ±7.62 18.10 ±2.63 2462.15 ± 139.28 872.76 ± 57.50a#f 35.44b ± 0.94beh 55°C 108.76 ±5.36 17.24 ± 10.81 3853.07 ± 429.12 1528.36 ± 166.34bd# 39.67d ± 1 01cf 65°C 107.89 ±9.70 21.03 ± 6.34 3625.38 ± 989.41 cpf 1514.64 ± 394.85 41.73 ±3.52d9b treatment effect > 0.05 >0.05 > 0.05 < 0.0001 < 0.0001 LDd ANOVA using untransformed data LDd-LDr ANOVA using untransformed data - (LDd removed from model because its effect was negligible in the model (p > 0.05) Kruskal-Wallis Zd test with paired comparisons using a Bonferroni correction Zd-Zr ANCOVA using square root transformed data with post hoc pairwise comparisons using a Sidak fit. Zd as a covariate retained in the model, as it had a highly significant effect (p < 0.0001). fp < 0.01; ad < 0.001; bce < 0.0001; #p = 0.051 (approaching significance). Note: 25°C vs 35°C p = 0.071; 35°C vs 45°C p = 0.085 (approaching significance). %R ANOVA using logarithmically transformed data with post hoc Sidak multiple comparison tests. Zd as a covariate removed from the model, as it had an insignificant effect (p > 0.05). ae < 0.05; h < 0.0001; bcdf9 < 0.0001; Note: 45°C vs 55°C p = 0.065 (approaching significance) It should be noted that ANOVA gives the same result as ANCOVA when the covariate is removed. Example 2 The following describes a method for producing high concentration liquid compositions comprising CPP-ACP or CPP-ACP with free fluoride. Stock solutions of 3.25 M CaCF and 1.25 M NaH₂PO₄ (pH 5.5) were added in approximately thirty aliquots to a 10–15% w / v tryptic casein digest until just before precipitation or gelation (typically yielding a final concentration of approximately 78 mM Ca²⁺ and 48–76 mM inorganic phosphate). The solutions were added slowly (i.e., less than approximately 1% by volume per minute) with thorough mixing. An aliquot of the phosphate solution was added first, followed by an aliquot of the calcium solution. The pH of the bulk solution was maintained at 9.0 using 1–10 M NaOH with thorough mixing. The sodium hydroxide solution was added automatically using pH statistics, with the addition of hydroxide ions typically following each addition of calcium ions.Once the addition of calcium, phosphate, and hydroxide ions was complete, the solution was filtered through a 0.1 µm filter to concentrate it 1–2 times. The retentate was then washed with 1–2 volumes of water to remove salts and inactive (and bitter-tasting) peptides. The prepared CPP-ACP solutions were then spray-dried or freeze-dried to produce a white powder. This dry powder was then added to water to form 20% to 75% w / v CPP-ACP solutions at pH 5.5 by adding 1–10 M HCl, or with added NaF to produce 3260 ppm F for 25% w / v, 4890 ppm F. F for 38%, 6520ppm F for 50% w / v, 8151ppm F for 63% CPP-ACP and 9,880 ppm F for 75% CPP-ACP at pH 5.5. The 75% w / v solution was prepared by adding 75 g of CPP-ACP powder to 20 mL of water at a small rate (0.5 g / min) while maintaining the pH at 5.5 by adding 10 M HCl. The solution was thoroughly mixed after each addition to ensure dispersion. A concentrated NaF solution (0.95 M) was added along with 10 M HCl to ensure a final addition of 52 mmol of F. The CPP-ACP powder, NaF, and HCl were added to the water for 2–3 hours to a final volume of 100 mL. This produced a highly viscous 75% w / v CPP-ACP solution containing 9,880 ppm F at pH 5.5. Example 3 Remineralization by CPP-ACFP and CPP-ACP in vitro at high concentrations. The aim of these experiments was to compare remineralization by CPP-ACP + fluoride (F) and CPP-ACP at high concentrations (e.g., 20% w / v, 25% w / v, 30% w / v, 38% w / v, 40% w / v, 50% w / v and 63% w / v). Subsurface demineralized lesions of human dental enamel were prepared in third molar enamel blocks. Half of the blocks were kept as controls, and the other half were treated as follows: Each enamel sample was pretreated with 1M NaOH (5 ml) for 5 min at 45°C and then washed with water for 10 sec / patted dry; Remineralized by suspending them individually in one of the following remineralization solutions: ML / t / ZUZ I / uo I ουο Liquid compositions of CPP-ACP + F at 25% w / v, 38% w / v, 50% w / v and 63% w / v of CPP-ACP; or Liquid compositions of CPP-ACP alone (without fluoride) at 20% w / v, 30% w / v, 40% w / v and 50% w / v of CPP-ACP, for 4 hours at 45°C. The fluoride content for the liquid compositions of CPP-ACP + F is as shown in Table 2, specifically 3,260 ppm F for 25% w / v, 4,890 ppm F for 38% w / v, 6,520 ppm F for 50% w / v and 8,151 ppm F for CPP-ACP at 63% w / v, respectively. The enamel block was removed and combined with its control for inlay, sectioning and cross-sectional microradiography and densitometric image analysis to determine the percentage of mineral content gain (% Remineralization). Table 2 Results of Remineralization by CPP-ACP + F and CPP-ACP in vitro at high concentrations. ML / t / ZUZ I / UO IOUÓ Treatment LDd (pm) AZd (vol. pm) AZd-AZr (vol. pm) %R 25% w / v CPP-ACP + 3260ppmF 114.73 ± 8.80 3021.30 ± 578.92 389 30 ± 71.06 13.05 ± 2.09 20% w / v CPP-ACP 102.51 ±6.30 2826.42 ± 349.81 234 83 ± 59.38 8.30 ±2.24 38% w / v CPP-ACP + 4890ppmF 102.04 ±9.06 2692.09 ± 448.70 515 01 ± 121.81 18.92 ±2.27 30% w / v CPP-ACP 104.02 ±9.48 3041.59 ±536.66 438 07 ±65.16 14.43 ± 1.28 50% w / v CPP-ACP + 6520ppmF 112.45 ±7.76 3145.51 ±534.90 822 27 ±181.33 25.81 ± 1.42 40% w / v CPP-ACP 99.24 ± 6.87 2794.54 ± 501.81 458 38 ± 63.67 16.34 ± 1.47 63% w / v CPP-ACP + 8151ppmF 118.05 ± 10 67 3139.87 ±218.49 859 84 ±115 10 27.21 ±2.14 50% w / v CPP-ACP 104.00 ±7.79 2691.53 ±745.94 375 62 ± 129.73 13.98 ±3.72 The levels of enamel subsurface remineralization in just 4 hours are the highest level of remineralization reported in such a short exposure time and have been achieved by the novel preparation of liquid compositions containing high concentration CPP-ACP (F) and the novel use of temperature to facilitate remineralization. Example 4 The following describes a method for producing high concentration liquid compositions comprising CPP-ACP or CPP-ACP with free fluoride. 30 g of CPP-ACP powder (commercial Recaldent) was added to 19.5 g of a 20,000 ppm F (NaF) solution, to which 0.5 g of an 11 M HCl solution was added to give a final weight of 50 g (therefore, this final solution is 60% w / w CPP-ACP with 7,800 ppm F at pH 7.8 or 75% w / v CPP-ACP containing 10,000 mg / l F at pH 7.8). With careful stirring (approximately 30 min), a homogeneous, highly viscous, but stable solution with a pH of 7.8 was prepared. This solution was then degassed to remove trapped air bubbles by placing the solution under vacuum for 24 hours. The viscous, stable, and safe solution (pH neutral) is easy to apply in dental surgery and is more concentrated, thus producing a better effect over a longer period. The composition is still in liquid form, so it can be applied to the tooth surface with a microbrush.
Claims
1. A method for mineralizing a dental surface or subsurface comprising contacting the dental surface or subsurface with stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP), and simultaneously or subsequently, heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C.
2. A method for mineralizing a tooth surface or subsurface comprising contacting the tooth surface or subsurface with a liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP).
3. A method for mineralizing a tooth surface or subsurface comprising contacting the tooth surface or subsurface with a liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium fluoride phosphate (ACFP), and simultaneously or subsequently heating the tooth surface or subsurface to which the liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP has been or is being applied to a temperature above 37°C.
4. A method according to claim 1 or 3, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature greater than or equal to 40°C.
5. A method according to claim 4, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature greater than or equal to 45°C.
6. A method according to claim 5, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature greater than or equal to 50°C.
7. A method according to claim 6, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP MA / t / ZUZ I / uo I ouo has been or is being applied to a temperature greater than or equal to 55°C.
8. A method according to claim 7, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature greater than or equal to 60°C.
9. A method according to claim 8, wherein the method comprises heating the dental surface or subsurface to which the stabilized ACP and / or ACFP has been or is being applied to a temperature greater than or equal to 65°C.
10. A method according to claim 2 or 3, wherein the liquid composition comprises more than 25% w / v of stabilized ACP and / or ACFP.
11. A method according to claim 10, wherein the liquid composition comprises more than 30% w / v of stabilized ACP and / or ACFP.
12. A method according to claim 11, wherein the liquid composition comprises more than 35% w / v of stabilized ACP and / or ACFP.
13. A method according to claim 12, wherein the liquid composition comprises more than 40% w / v of stabilized ACP and / or ACFP.
14. A method according to claim 13, wherein the liquid composition comprises more than 45% w / v of stabilized ACP and / or ACFP.
15. A method according to claim 14, wherein the liquid composition comprises more than 50% w / v of stabilized ACP and / or ACFP.
16. A method according to claim 15, wherein the liquid composition comprises more than 55% w / v of stabilized ACP and / or ACFP.
17. A method according to claim 16, wherein the liquid composition comprises more than 60% w / v of stabilized ACP and / or ACFP.
18. A method according to claim 17, wherein the liquid composition comprises more than 65% w / v of stabilized ACP and / or ACFP.
19. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 40% w / w of stabilized ACP and / or ACFP.
20. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 45% w / w of stabilized ACP and / or ACFP.
21. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 50% w / w of stabilized ACP and / or ACFP.
22. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 55% w / w of stabilized ACP and / or ACFP.
23. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 60% w / w of stabilized ACP and / or ACFP.
24. A method according to any of claims 1 to 18, wherein the liquid composition comprises more than 65% w / w of stabilized ACP and / or ACFP.
25. A method according to any of claims 1 to 24, wherein the stabilized ACP and / or ACFP are stabilized with phosphopeptides.
26. A method according to claim 25, wherein the suspension comprises:
27. A method according to any of claims 1 to 26, wherein the dental surface or subsurface is a fluorotic lesion.
28. A method according to any of claims 1 to 26, wherein the dental surface or subsurface is a white spot lesion.
29. A method according to any one of claims 1 to 26, wherein the tooth surface or subsurface is a carious lesion.
30. A method according to any one of claims 1 to 26, wherein the tooth surface or subsurface is a lesion caused by erosion.
31. A liquid composition comprising more than 20% w / v of stabilized amorphous calcium phosphate (ACP) and / or amorphous calcium phosphate fluoride (ACFP). MA / I / uo I ouo 32. A liquid composition according to claim 31, wherein the composition comprises more than 25% w / v of stabilized ACP and / or ACFP.
33. A liquid composition according to claim 31, wherein the composition comprises more than 30% w / v of stabilized ACP and / or ACFP.
34. A liquid composition according to claim 31, wherein the composition comprises more than 35% w / v of stabilized ACP and / or ACFP.
35. A liquid composition according to claim 31, wherein the composition comprises more than 40% w / v of stabilized ACP and / or ACFP.
36. A liquid composition according to claim 31, wherein the composition comprises more than 45% w / v of stabilized ACP and / or ACFP.
37. A liquid composition according to claim 31, wherein the composition comprises more than 50% w / v of stabilized ACP and / or ACFP.
38. A liquid composition according to claim 31, wherein the composition comprises more than 55% w / v of stabilized ACP and / or ACFP.
39. A liquid composition according to claim 31, wherein the composition comprises more than 60% w / v of stabilized ACP and / or ACFP.
40. A liquid composition according to claim 31, wherein the composition comprises more than 65% w / v of stabilized ACP and / or ACFP.
41. A liquid composition according to claim 31, wherein the composition comprises more than 70% w / v of stabilized ACP and / or ACFP.
42. A liquid composition according to claim 31, wherein the composition comprises more than 75% w / v of stabilized ACP and / or ACFP.
43. A liquid composition according to claim 31, wherein the liquid composition comprises more than 40% w / w of stabilized ACP and / or ACFP.
44. A liquid composition according to claim 31, wherein the liquid composition comprises more than 45% w / w of stabilized ACP and / or ACFP.
45. A liquid composition according to claim 31, wherein the liquid composition comprises more than 50% w / w of stabilized ACP and / or ACFP.
46. A liquid composition according to claim 31, wherein the liquid composition comprises more than 55% w / w of stabilized ACP and / or ACFP.
47. A liquid composition according to claim 31, wherein the liquid composition comprises more than 60% w / w of stabilized ACP and / or ACFP.
48. A liquid composition according to claim 31, wherein the liquid composition comprises more than 65% w / w of stabilized ACP and / or ACFP.
49. A liquid composition according to any of claims 1 to 4, wherein said buffer further comprises potassium ions.
50. A liquid composition comprising more than 20% w / v of amorphous calcium phosphate (ACP) and / or stabilized amorphous calcium fluoride phosphate (ACFP) for use in: • the mineralization of a dental surface or subsurface, or any lesion as described herein; or • the treatment or prevention of one or more of each dental caries, dental erosion, white spot lesions and fluorosis.
51. Use of a liquid composition comprising more than 20% w / v of amorphous calcium phosphate (ACP) and / or stabilized amorphous calcium fluoride phosphate (ACFP) in the manufacture of a composition or medicament for the mineralization of a dental surface or subsurface, or treatment and / or prevention of one or more of the dental caries, dental erosion and fluorosis.
52. A kit for the treatment or prevention of one or more dental caries, fluorosis and dental erosion, or mineralization of a surface or subsurface or dental lesion as described herein, comprising a liquid composition comprising more than 20% w / v of amorphous calcium phosphate (ACP) and / or stabilized amorphous calcium fluoride phosphate (ACFP).
53. A kit according to claim 52, the kit further comprising a heat source.
54. A method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of: mixing a solvent and a powder comprising or consisting of stabilized ACP and / or ACFP, and maintaining the pH below 9, preferably below 8 or 7.
55. A method or process for preparing a liquid composition comprising more than 20% w / v of stabilized ACP and / or ACFP, the method or process comprising or consisting of: mixing a solvent and a powder comprising or consisting of stabilized ACP and / or ACFP, and reducing the pH below 9, preferably the pH is reduced to, or below, 7, 6, preferably 5.
5.
56. A method or process according to claim 42 or 43, wherein the pH is maintained at or below 6, preferably the pH is maintained at or below 5.
5.
57. A method or process further comprising the following steps for preparing a powder comprising or consisting of stabilized ACP and / or ACFP: mixing one or more solutions comprising phosphopeptides, calcium ions, phosphate ions, hydroxide ions and optionally fluoride ions, while maintaining the pH at approximately 7.0 or more, preferably around 9, to form a solution comprising stabilized ACP and / or ACFP, and drying the solution comprising stabilized ACP and / or ACFP, thereby forming a powder comprising or consisting of stabilized ACP and / or ACFP.
58. A method or process according to claim 57, wherein the drying is by spray drying or freeze-drying.
59. A method or process according to claim 57 or 58, further comprising the step of filtering the solution comprising stabilized ACP and / or ACFP, prior to drying, to form a retentate, wherein the retentate is subsequently dried to form a powder comprising or consisting of