Cationic ACP gel formed in situ for the treatment of dental alenia

Abstract

A gel composition comprising immediate formation of cationic amorphous calcium phosphate (ACP) for the treatment of dentin hypersensitivity, methods of using the composition, and systems for making the gel composition.

Description

Technical Field

[0001] The present disclosure generally relates to compositions for treating dentin hypersensitivity, related oral health care methods, and systems for preparing such compositions. Background Art

[0002] Tooth and gum sensitivity are areas of particular concern in oral health care, often the most prominent problem after tooth decay. This concern is growing as more and more people use teeth whitening products.

[0003] Dentin hypersensitivity is characterized by intense, short pain from exposed dentin, usually in response to external stimuli such as clinical, thermal, tactile, evaporative, or osmotic stimulation. It often develops when dentin is exposed to the oral environment due to gingival recession or enamel loss.

[0004] The most widely accepted explanation for dentin hypersensitivity is provided by the fluid dynamic theory, which suggests that nerve stimulation due to movement of dentinal fluid is the cause of hypersensitivity. When the dentinal tubules are exposed to the oral environment, fluid movement through the dentinal tubules can be sensed by the internal dental nerves. Activation of the dental nerve fibers may cause the sensation of intense pain. A relationship between dentin hypersensitivity and patency of the dentinal tubules has been established in vivo, and occlusion of the tubules has been found to reduce this sensitivity.

[0005] In general, the techniques and materials developed for the treatment of dentin hypersensitivity can be divided into two treatment categories: Treatment I and Treatment II, which are described below.

[0006] Treatment I works by desensitizing the dental nerve via potassium salts such as potassium nitrate, potassium citrate, potassium chloride, which depolarize the excited nerve fibers, numbing the pain. This treatment usually provides short-term relief from dentin hypersensitivity.

[0007] Treatment II is based on closing the dentinal tubules by plugging them or coating the sensitive dentinal areas with a thin protective layer of material. The occlusion of the open tubules blocks the hydrodynamic mechanism. Treatment II can provide a relatively long-term solution.

[0008] Most of the available products and methods for treating dentin hypersensitivity work by blocking the dentinal tubules and preventing the flow of dentinal fluid. Examples of such materials and methods include the application of specific dentifrices, dentin adhesives, some antimicrobial agents, aldehydes, resin suspensions, fluoride rinses, fluoride varnishes, amorphous calcium phosphate (ACP), strontium fluoride, oxalates, Nd-YAG laser application, bioactive glass, casein phosphopeptides, and Portland cement.

[0009] Generally speaking, existing products and methods for treating dentin hypersensitivity suffer from one or more of the problems or disadvantages described below.

[0010] Existing products generally provide insufficient blocking of open tubules in terms of depth of the tubules and area coverage of the openings on the dentin surface. Existing products generally allow the active blocking ingredients to diffuse and / or disperse slowly into the open dentin tubules. For example, in products that use arginine bicarbonate-calcium carbonate complexes to block dentin tubules, arginine binds to the tooth surface and absorbs calcium ions and phosphate ions from saliva. Since calcium carbonate has a low solubility in water to generate calcium ions and the diameter of tooth dentin tubules is approximately 5 μm, it takes time to establish an effective blockage with the compound formed by calcium ions and phosphate ions within the dentin tubules.

[0011] Existing products offer weak or low affinity for dentin and provide unstable remineralization and low efficiency of occlusion of dentinal tubules. For example, calcium and phosphate ions may be released from preformed amorphous calcium phosphate (ACP) gels in the presence of saliva to accelerate the absorption of these bioavailable ions, but the resulting compound lacks stability and has low affinity for dentin within dentinal tubules.

[0012] Existing products provide hypersensitivity relief only for a limited time. For example, it is reported that a composition of arginine, bicarbonate, and calcium carbonate is polished onto sensitive teeth after scaling and root planing procedures in a dental office, and the reported sensitivity relief lasts for at least 28 days with a single treatment (D. Cummins, Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief, J Clin Dent. 2009; 20(1): 1-9).

[0013] Existing products and methods are inconvenient, expensive and / or uncomfortable to treat. Many existing dentin hypersensitivity treatments require a dental office visit.

[0014] In view of the foregoing, there remains a continuing need for improved products and techniques for treating dentin hypersensitivity. Summary of the invention

[0015] In accordance with implementations and embodiments described herein that address this need, compositions and methods for treating dentin hypersensitivity, and systems for preparing such compositions, are provided.

[0016] The present disclosure relates to a composition for treating dentin hypersensitivity, the composition comprising a first component and a second component. The first component comprises a pH-sensitive rheology-modified polymer, a calcium ion source, and an acidulant. The pH of the first component is in the range of about 2.0 to about 6.5. The second component comprises a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizing agent. The pH of the second component is in the range of about 9.5 to about 14.0. The first component and the second component are combined into a mixture, for example, via a mixing top or a mixing chamber, and when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, the mixture instantly produces a cationic amorphous calcium phosphate (ACP) gel composition. The purpose of the subject matter of the present invention is to provide an ACP relief gel formed instantly, comprising cationic amino acids, proteins and / or peptides, which provides a stronger affinity for dentin than existing products and forms better closed aggregates to more effectively treat dentin hypersensitivity.

[0017] In some embodiments, the pH sensitive rheology modifying polymer can be selected from a hydrophobically modified alkali soluble emulsion (HASE) polymer of polyacrylic acid, an alkali soluble emulsion (ASE) polymer of polyacrylic acid, and a polymer having one or more acidic groups selected from the group consisting of carboxylic acid, sulfonic acid, and phosphoric acid, and capable of thickening a composition comprising water when the pH of the composition is increased from an acidic value to an alkaline value within a pH range of about 7.0 to about 12.0.

[0018] In some embodiments, the calcium ion source is a calcium salt of nitrate, a calcium salt of aspartic acid, a calcium salt of glutamic acid, or a water-soluble calcium salt of other suitable acids. In some embodiments, the acidulant is phosphoric acid or other acids compatible with the ingredients of the first component. In other embodiments, the phosphate ion source is disodium phosphate, monosodium phosphate, or other suitable alkaline water-soluble phosphates. In some embodiments, the positively charged basic amino acid is arginine, lysine, histidine, or a combination thereof. In some embodiments, the cationic peptide is a water-soluble peptide that is positively charged at a neutral pH and is nontoxic to the user. In some embodiments, the alkalizing agent is sodium hydroxide, potassium hydroxide, or other suitable alkaline compounds. In a further embodiment, the viscosity of the cationic ACP gel formed instantly is greater than about 5,000 cP.

[0019] The subject matter disclosed herein further relates to an oral care method for treating dentin hypersensitivity, comprising providing a first component and a second component. The first component comprises a pH-sensitive rheology-modified polymer, a calcium ion source, and an acidulant. The pH of the first component is in the range of about 2.0 to about 6.5. The second component comprises a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizing agent. The pH of the second component is in the range of about 9.5 to about 14.0. The method further comprises separately accommodating the first component and the second component, distributing the first component and the second component in a mixing top or mixing chamber, thereby combining the first component and the second component into a mixture, and when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, the mixture instantly forms an ACP gel composition, and the instantly formed cationic ACP gel composition is applied to the dentin surface of the user's teeth.

[0020] In some embodiments, the pH of the first component is in the range of about 2.5 to about 4.5. In some embodiments, the pH of the second component is in the range of about 10.5 to about 12.5. In further embodiments, the pH of the instant-formed cationic ACP gel composition ranges from about 7.0 to about 9.5.

[0021] The subject matter described herein further includes a system for preparing a composition for treating dentin hypersensitivity, the system comprising a dosing device and a dispensing device. The dosing device comprises a first compartment and a second compartment, the first compartment containing a first component, the first component comprising a pH-sensitive rheology-modified polymer, a calcium ion source, and an acidulant, and wherein the pH of the first component is in the range of about 2.0 to about 6.5, the second compartment containing a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and a second component of an alkalizer, and wherein the pH of the second component is in the range of about 9.5 to about 14.0. The dispensing device is configured to receive the first component and the second component into a mixing top or mixing chamber, and combine the first component and the second component into a mixture, and when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, the mixture instantly produces an ACP gel composition, and wherein the dispensing device has an opening to apply the cationic ACP gel composition to the dentin surface of the user's teeth.

[0022] In certain embodiments, dispensing device is suitable for dispensing the cation ACP gel composition as the viscous gel of viscosity greater than about 5,000cP.In other embodiments, dosing device comprises a plurality of compartments, each compartment comprises one or more compatible ingredients of the first component and / or one or more compatible ingredients of the second component, and wherein the content of a plurality of compartments is dispensed in mixing top or mixing chamber to form cation ACP gel composition.In certain embodiments, the composition for each compartment is supplied with the form of cartridge.In a further embodiment, dispensing device can comprise double barrel syringe, double chamber bottle or a kind of form dispensing device, and the dispensing device of this form can be dispensed in the shared mixing top with two independent components, to form cation amorphous calcium phosphate gel composition.

[0023] These and other aspects of the disclosure will be apparent from and elucidated with reference to the embodiments described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is a perspective view of an exemplary system using a double barrel syringe and a mixing tip to form an instant cationic ACP gel composition.

[0025] Figure 2 is a simplified elevation view of an exemplary system using a dual chamber bottle and a mixing top to form an instant cationic ACP gel composition.

[0026] Figure 3 is a schematic diagram of an exemplary system in which the dosing device comprises three compartments.

[0027] Figure 4 is a high level flow chart of an exemplary method for treating dentin hypersensitivity. DETAILED DESCRIPTION

[0028] Disclosed are compositions for treating dentin hypersensitivity, methods for preparing such compositions, and systems for preparing the compositions. The disclosed compositions include instant-forming cationic amorphous calcium phosphate (ACP) gels that have several advantages over currently available ACP gels that are not cationic and / or not instant-forming.

[0029] As is well known, dentin or the tooth surface is negatively charged in nature. Chemically, dentin is composed of about 20% organic material, about 75% inorganic material, and about 5% water by weight. The organic material is primarily collagen, which acts as a binder in the dentin structure. The inorganic material includes calcium phosphate.

[0030] In healthy teeth, saliva effectively reduces dentin hypersensitivity naturally by supplying and transporting calcium and phosphate ions to the open dentinal tubules to gradually seal them and form a surface protective layer composed of sialoglycoproteins and precipitates of calcium phosphate. For people with dentin hypersensitivity, the affected tooth dentin exposes many microtubules with a diameter of about 5 μm. The microtubules allow small molecular-sized fluids or particles to migrate inside the dentin structure. It is very beneficial to have a composition of a dentin sealing material that is close to or similar to the natural composition of dentin, that is, the composition is made of calcium phosphate; amino acids, peptides or proteins; and water. Therefore, a cationically charged, instantly formed ACP gel is needed in terms of freshness, binding affinity, and sealing efficiency of dentinal tubules.

[0031] As disclosed herein, a composition for treating dentin hypersensitivity includes a first component and a second component, the first component including a pH-sensitive rheology-modifying polymer / pH-induced rheology-modifying polymer, a calcium ion source, and an acidifier, and the second component including a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizer. The pH of the first component is in the range of about 2.0 to about 6.5. The pH of the second component is in the range of about 9.5 to about 14.0. The first component and the second component are combined into a mixture via a mixing top or a mixing chamber, whereby when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, a cationic ACP gel composition is produced instantly. A new instant gelling method is disclosed, which uses pH manipulation to produce a fresh cationic charged ACP gel in an instant gelling manner. By using the methods, systems, and compositions disclosed herein, not only the problems of the prior art are solved, but also a longer dentin hypersensitivity relief effect can be achieved in a natural, convenient and cost-effective manner.

[0032] As used herein, the terms "instant" and "instantly" refer to a short time, typically less than about 5 seconds, from mixing the components to the formation of the finished gel.

[0033] As used herein, the term "gel" refers to a homogeneous solid aqueous gel-like material, such as a hydrogel having a water-swellable polymeric matrix that can absorb large amounts of water.

[0034] The term "acidifier" refers to one or more compounds which, when dissolved or dispersed in neutral water at pH 7, causes the pH of the water to be below 7. It may refer to a Bronsted acid or an Arrhenius acid.

[0035] The term "alkalizing agent" refers to one or more compounds which, when dissolved or dispersed in neutral water at a pH of 7, cause the pH of the water to be above 7.

[0036] As used herein, the term "pH manipulation" refers to a formulation strategy achieved by a change in the pH of the mixture when a pH sensitive thickener is used in a multi-component composition. pH manipulation is performed by raising the pH of the final mixture to an alkaline pH, particularly a pH of about 7.0 to about 12.0, when a predetermined amount of one acidic component is mixed with a pH sensitive thickener via a mixing head or in a mixing chamber with an amount of another alkaline component. During mixing, the acidic pH sensitive thickener molecules will be deprotonated and instant thickening ability will result from the electrostatic repulsion between the charges present on the deprotonated polymer chains. The use of uncrosslinked HASE polymers and / or ASE polymers in component form allows for rapid gel formation in the mixture, which can be instantaneous.

[0037] The term "thickening" refers to an increase in the viscosity of a composition. A pH-sensitive thickener is capable of increasing the viscosity of a composition when the composition is subjected to an increase in pH, such as, in particular, a composition pH in the range of 7.0 to 12.0. The thickener is compatible with one or more of basic amino acids / peptides, phosphate ions, calcium ions, and / or acidic amino acids.

[0038] Mechanistically, when the pH of the acidic component containing a pH-sensitive rheology-modifying polymer (such as a hydrophobically modified alkali-soluble emulsion (HASE) polymer or other alkali-swellable acrylic acid (ASE) polymer) exceeds pH 7.0 and is below pH 12.0, it can instantly thicken after neutralization with a basic component of phosphate ions and basic amino acids or cationic peptides, and the final mixture becomes a cationic gel with a large amount of calcium ions and phosphate ions and some instantly formed ACP nanoparticles. For use on the human body, it is expected that the pH of the resulting cationic ACP gel is about 7.0 to about 9.5.

[0039] As pH sensitive rheology modifiers, when the acid groups of the HASE polymers are neutralized / deprotonated by an inorganic base or an organic amine, the HASE polymers first swell due to charge-charge repulsion and thus instantly thicken in response to an increase in pH. As these polymers swell, the pendant hydrophobic groups are then released to bind to each other and / or other available hydrophobic groups in the system. This phenomenon creates a network structure that results in a significant increase in viscosity, which further enhances the gelling effect and stabilizes and disperses any particles that may be present in the composition.

[0040] In an exemplary embodiment, the pH sensitive thickener may include one or more polymers, each of which has an acidic group. Such acidic groups are in protonated form at a first acidic pH and in deprotonated form at a final mixture pH in the range of about 7.0 to about 12.0. Deprotonation provides charged sites responsible for polar interactions for thickening.

[0041] The disclosed subject matter utilizes the interaction principle of pH sensitive thickening polymers and charged particles in physics: opposites attract, and likes repel. It also utilizes the chemical properties of the cationic charge of calcium salts of aspartic acid or glutamic acid, or lysine, arginine, and histidine, which are readily soluble in water at neutral pH.

[0042] The disclosed subject matter relates to a system for preparing a composition for treating dentin hypersensitivity, the system comprising a dosing device and a dispensing device. The dosing device comprises at least two compartments. Figure 1 and Figure 2 An example of an embodiment of a dosing device using two compartments is shown in the . The first compartment includes a first component of a pH-sensitive rheology-modified polymer, a calcium ion source, and an acidulant. The second compartment includes a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and a second component of an alkalizer. The dispensing device is configured to receive the first component and the second component into a mixing top or mixing chamber, and when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, the individual components can be combined or mixed in the mixing top or mixing chamber to instantly form a mixture of a cationic ACP gel composition. The resulting mixture is freshly prepared on site and can be removed from the chamber via an opening and applied to the dentin surface of the user's teeth.

[0043] In an exemplary embodiment, the cationic ACP gel composition can be formed by combining predetermined amounts of two components (Part 1 and Part 2), as described below.

[0044] Table 1

[0045]

[0046]

[0047] The two-part system in solution form has the following benefits. Calcium salts, such as calcium nitrate salts, are soluble in acidic environments but unstable under alkaline conditions. Phosphates, such as disodium phosphate, are very soluble under strongly alkaline conditions but are less soluble under neutral pH. When the two parts are mixed in appropriate proportions and conditions, the formation of ACP begins near neutral pH and accelerates with increasing pH because the solubility of ACP under neutral or weakly alkaline pH conditions is very poor. In addition, basic amino acids such as arginine, lysine, and histidine are water-soluble and positively charged in neutral or near-neutral pH environments.

[0048] Part 1 and Part 2 may be in liquid form, either as a solution or as an emulsion. Mixing may be achieved by using a mixing tip, as described below. Figure 1 further discussed, or by using a mixing chamber, as described below with reference to Figure 2 Further discussed. By using both Part 1 and Part 2 in liquid form, mixing of the components is easier, the ingredients of the components are mixed more evenly, and a faster viscosity increase is provided. In some embodiments, the viscosity of the resulting cationic ACP gel composition is greater than 5000 cP, preferably greater than 10000 cP.

[0049] Figure 1 An embodiment is shown, wherein the system 10 comprises a dosing device 12 and a dispensing device 14. The dosing device 12 comprises a dual reservoir, each of which contains fluid components in a desired mixing ratio. The dosing device 12 consists of a double barrel syringe 16, wherein one barrel 26 contains Part 1 and the other barrel 28 contains Part 2. The dispensing device 14 has a mixing tip 18, wherein Part 1 and Part 2 are mixed to form an instant cationic ACP gel composition.

[0050] This system allows the alkaline component and the acidic component to be stored separately before use. It allows for component stability and avoids premature reaction or combination of the ingredients of the two separate components before reaching the target area. When desired, the alkaline component and the acidic component can be mixed and gelled from a single unit at a joint mixing point or mixing chamber before starting application.

[0051] Figure 2Another embodiment is shown, wherein system 100 includes dosing device 112 and dispensing device 114. Dosing device 112 includes double chamber bottle 120, and each chamber 122,124 accommodates fluid components in required mixing ratio. These components are separated by wall 126, and each chamber 122,124 includes pipeline 126,128, to distribute the contents of each chamber 122,124 to dispensing device 114, and this dispensing device includes mixing top 126, forms instant cationic ACP gel composition in this mixing top. Viscous gel can be applied on the user's teeth or applied on the exposed dentin surface.

[0052] Alternatively, the dosing system may include a pump or vacuum device to simultaneously draw fluid from each compartment, for example via separate suction tubes, and discharge the fluid into a common mixing chamber and thereafter discharge the instantaneously formed gel contents into the application area.

[0053] In other embodiments, the cationic ACP gel composition can be formed by combining predetermined amounts of multiple components, such as three, four, or more. Figure 3 is a diagram of a system in which the dosing device includes three compartments. The first compartment may include, for example, Part 1 as described above. The second compartment may include Part 2 as described above. The third compartment may include one or more spices and / or other functional ingredients or inert ingredients. The contents of the three compartments are combined in a blending chamber or a mixing chamber. The resulting cationic ACP gel composition can be removed from the chamber via a dispensing pump and applied to the tooth area to be treated.

[0054] In some embodiments, the dispensing system can be designed to work similar to a soda fountain with multiple components. Such a system can accurately control the dosage of each component and / or ingredient. In some embodiments, each component / ingredient can be supplied in cartridge form or as a replaceable container to facilitate dosage control, replacement, modification, or product selection during application.

[0055] The composition can be prepared on-site, i.e., at the point of use shortly before application, to maintain freshness and effectiveness. In some embodiments, the instant-forming cationic ACP gel can be applied directly to exposed dentin to relieve dentin hypersensitivity, for example, by massaging the composition directly onto the exposed dentin for 1 to 2 minutes to help diffuse and / or disperse into the dentin microtubules. In some embodiments, this can be repeated once or twice a day to achieve the desired effect.

[0056] The present subject matter will be more readily understood by reference to the following detailed description of ingredients and formulations, which description is intended to illustrate the disclosure rather than to limit the scope of the disclosure.

[0057] As described above, the cationic ACP gel composition can be made from two components, Part 1 and Part 2. The combination of these components provides more effective allergy relief than ACP alone.

[0058] For the pH sensitive polymer used in Part 1, there are a number of non-hazardous, pH sensitive rheology modifying polymers that are suitable. These polymers are provided in an uncrosslinked form and thicken the composition substantially only at an alkaline pH. Such polymers include: HASE polymers; acrylic acid ASE copolymers, such as those sold under the trade name The invention relates to a series of commercially available polymers such as those sold as acrylate copolymers; acrylate copolymers; and polymers having one or more acidic groups selected from the group consisting of carboxylic acids, sulfonic acids, and phosphoric acids and capable of thickening a composition comprising water as the pH of the composition is increased from acidic values ​​to alkaline values ​​within the pH range of about 7.0 to about 12.0.

[0059] An example of a suitable acrylic ASE copolymer in the series is 940NF polymer. 1% The pH of 940NF solution is about 2.5-3.0, and the viscosity is well below 1500 cP at this pH. However, at pH 7.5-10.0, the viscosity of a 0.5% dispersion is 40000 cP-60000 cP. 1% neutralized 940NF polymer cement forms a hard gel. 940NF and other suitable The preferred dosage of polymer is between 0.5% and 3.0% solid polymer levels.

[0060] Another suitable example is a HASE polymer synthesized from an acid / acrylate copolymer backbone and including an ethoxylated hydrophobic agent. An example of a HASE polymer is ACULYN TM 28. At pH 7.0-pH 12, 5% (wt.) ACULYN TM 28 doses can form highly viscous gels with viscosities exceeding 100,000 Cp, and at pH 3.0, for 100% ACULYN TM 28, showing very low viscosity, i.e. less than 30 Cp. In some embodiments, from a cost-effectiveness perspective, ACULYN TM Preferred dosage levels of 28 and other HASE polymers may be between 1%-10% levels.

[0061] The calcium ion source in Part 1 may include calcium salts of nitric acid, aspartic acid, glutamic acid or other suitable acids, such as calcium nitrate, calcium aspartate, or calcium glutamate, as long as it remains soluble in aqueous solution at pH 2.0-6.0. The preferred dosage range of the calcium salt is 0.5%-1.5% w / w.

[0062] The phosphate ion source in Part 2 may include disodium phosphate, monosodium phosphate, or other alkaline water-soluble non-toxic phosphates may be used in the formulation of Part 2. The preferred dosage range is 0.5%-1.5% w / w.

[0063] The positively charged basic amino acids and / or cationic peptides in Part 2 include three basic amino acids, lysine, arginine and histidine, which have basic side chains at neutral pH. Table 2 shows their pKa1 (α-carboxyl), pKa2 (α-ammonium ion), pKa3 (side chain R group) and isoelectronic point PI. Basic amino acids are positively charged under neutral pH conditions. In particular, arginine and lysine have 100% positively charged basic side chains between pH 6.5-8.0, which makes these amino acids particularly suitable. Depending on which basic amino acid is used in the composition, it is feasible to have a strongly positively charged basic amino acid near neutral pH. Among the available two optical isomers D (-) and L (+) of lysine, arginine or histidine, the L-type of lysine, arginine or histidine is preferred. The preferred dosage range of each basic amino acid is 6-12% w / w. In formulation, when the relevant basic amino acids are used in Part 2, the pH of the Part 2 solution should be away from the PI value. The pKa1, pKa2, pKa3, and PI of lysine, arginine, and histidine are listed in Table 2 below, respectively.

[0064] Table 2

[0065]

[0066] The above basic amino acids can also be formulated as functional agents of Part 1 when the pH of the Part 1 solution is not highly acidic and the basic amino acids remain soluble and compatible in Part 1.

[0067] For the positively charged peptide in Part 2, any commercially available acidic water-soluble peptide that is positively charged at neutral pH and non-toxic can be used. The preferred dosage range of the positively charged peptide is 6-12% w / w.

[0068] In Part 1, a pH acidifier may be used, such as phosphoric acid or other acids compatible with all ingredients in Part 1. In Part 2, an alkalizer may be used, such as sodium hydroxide, potassium hydroxide, as long as they are compatible with all ingredients in Part 2.

[0069] Flavoring agents that can be used in Part 1 and Part 2 are substances that trigger taste and / or smell. They are used to improve the perception and experience of consumers in the treatment of dentin hypersensitivity. Generally speaking, mint flavors such as peppermint oil and spearmint oil are used to give dental products a clean and fresh feeling. Sweeteners such as xylitol or artificial sweeteners such as saccharin sodium and sucralose can also be used. A generally preferred flavoring agent is natural peppermint oil. As long as the flavoring ingredients are compatible with the other ingredients in Part 1 and / or Part 2, the flavoring ingredients can be used at a minimum dosage level if the application and user require.

[0070] Potassium salts can be added to Part 1 and / or Part 2 as a rapid temporary dentin hypersensitivity desensitizer. Potassium-based salts can depolarize excited nerve fibers and numb pain. Examples of suitable potassium salts include potassium nitrate, potassium citrate, and potassium chloride.

[0071] Other functional chemicals or inert chemicals can be added to Part 1 and Part 2. Depending on the other functions required by the product, functional agents such as solvents, such as propylene glycol, and nonionic and amphoteric surfactants, fluorides, etc. can be formulated in Part 1 and / or in Part 2 to provide some desired functions for the composition and desensitization application.

[0072] Table 3 below shows an exemplary composition formula for instant formation of cationic amino acid-based ACP gels. Other formulations can be easily developed according to the formulation methods disclosed in the present disclosure.

[0073] Table 3 Part A

[0074]

[0075]

[0076] Section B

[0077]

[0078] The mixing ratio of Part A and Part B in Table 3 is 1:1 (v / v) to produce an instant, on-site formed cationic arginine ACP gel having a pH range of about 6.5 to about 9.5 for dental treatment of hypersensitive teeth. Generally, the gel is stable for at least 2 hours at a temperature range of about 0°C to about 40°C.

[0079] The disclosed subject matter further provides oral healthcare methods for treating dentin hypersensitivity. Figure 42 is a high-level flow chart of a method 200 for treating dentin hypersensitivity. The method 200 includes providing a first component and a second component. The first component includes a pH-sensitive rheology-modified polymer, a calcium ion source, and an acidulant. The pH of the first component is in the range of about 2.0 to about 6.5. The second component includes a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizing agent. The pH of the second component is in the range of about 9.5 to about 14.0. The method further includes separately accommodating the first component and the second component, distributing the first component and the second component in a mixing top or mixing chamber, thereby combining the first component and the second component into a mixture, when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, the mixture instantly forms a cationic ACP gel composition, and applying the instantly formed cationic ACP gel composition to the dentin surface of the user's teeth.

[0080] In some embodiments, the composition can be used as a therapeutic gel product in a dental clinic. In other embodiments, the composition can also be manufactured as a sensitivity relief toothpaste for "take-home" or retail type products for the treatment of dentin hypersensitivity. In further embodiments, due to the same mechanism and strong affinity for tooth enamel, the composition can be used to treat tooth decay. In addition, the present disclosure can be used to produce artificial dentin tissue or artificial tooth materials.

[0081] Compared with conventional methods and products, the composition according to the disclosed subject matter can quickly introduce a large amount of water-soluble calcium ions and phosphate ions from non-salivary sources into dentin, and accelerate the formation of calcium phosphate compounds, which are considered to be the pillars of the internal closure of dentinal tubules. In a short period of time, the disclosed composition produces a strong closure of dentinal tubules through dentin, positively charged amino acids / peptide reagents, and strong binding complexes between calcium ions and phosphate ions or formed ACP particles. These reactions deposit dentin-like minerals as a solid plug in the dentinal tubules and form a protective layer on the surface of the dentin. Since calcium phosphate is chemically more resistant to acid erosion than calcium carbonate in the closure of dentinal tubules, the disclosed subject matter is superior to existing products in terms of the duration of relieving dentin hypersensitivity.

[0082] Those skilled in the art will appreciate that changes, modifications and alterations may be made to the disclosed examples without departing from the scope of the invention as described herein. The invention may appear in the form of various components and component arrangements, and in the form of various techniques, methods, or procedures and step arrangements.

[0083] Although the present invention has been described in detail for purposes of illustration based on what are presently considered to be the most practical and preferred embodiments, it should be understood that such details are provided for that purpose only and that the present invention is not limited to the disclosed embodiments, but rather is intended to cover modifications and equivalent arrangements within the spirit and scope of the appended claims. For example, it should be understood that the present invention contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

[0084] As defined and used herein, all definitions should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0085] Unless expressly indicated to the contrary, as used herein in the specification and in the claims, the indefinite articles "a" and "an" are to be understood to mean "at least one". Furthermore, singular references do not exclude plural references. Thus, references to "a", "an", "first", "second" etc. do not exclude a plurality.

[0086] As used herein in the specification and in the claims, the phrase "and / or" should be understood to mean "either or both" of the elements so combined (i.e., elements present in combination in some cases and separately in other cases). Multiple elements listed with "and / or" should be interpreted in the same manner, i.e., "one or more" of the elements so combined. In addition to the elements specifically identified by the "and / or" clause, other elements may optionally be present, whether related or unrelated to those elements specifically identified.

[0087] As used herein in the specification and in the claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" should be interpreted as inclusive, i.e., including at least one element, but also including more than one element, including many elements or a series of elements, and optionally including additional unlisted items. Only when the opposite terms are clearly indicated, such as "only one of..." or "exactly one of...", or when used in the claims, "consisting of...", it means to include exactly one element in many elements or a series of elements. In general, the term "or" as used herein should be interpreted as indicating an exclusive alternative (i.e., "one or the other, but not both"), provided that there is an exclusive term in front, such as "either", "one of...", "only one of...", or "exactly one of...".

[0088] It should also be understood that in any method claimed herein that includes more than one step or action, the order of the steps or actions of the method is not necessarily limited to the order in which the steps or actions of the method are described unless explicitly indicated to the contrary.

[0089] In the claims, as well as in the above description, all transitional phrases, such as "includes," "comprising," "carrying," "having," "containing," "involving," "holding," "composed of," etc., are to be construed as open-ended, i.e., meaning including, but not limited to,

Claims

1. A composition for treating dentin hypersensitivity, comprising: a first component comprising a pH sensitive rheology modifying polymer, a source of calcium ions, and an acidulant, and wherein the pH of the first component is in the range of about 2.0 to about 6.5; a second component comprising a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizing agent, and wherein the pH of the second component is in the range of about 9.5 to about 14.0; and The first component and the second component are combined into a mixture, wherein a cationic amorphous calcium phosphate gel composition is instantly produced when the pH of the mixture reaches a pH range of about 7.0 to about 9.

5.

2. The composition of claim 1, wherein the first component and the second component are combined into a mixture via a mixing tip or a mixing chamber.

3. The composition of claim 1, wherein the pH sensitive rheology modifying polymer is selected from the group consisting of hydrophobically modified alkali-soluble emulsion polymers of polyacrylic acid, alkali-soluble emulsion polymers of polyacrylic acid, and polymers having one or more acidic groups selected from the group consisting of carboxylic acid, sulfonic acid, and phosphoric acid and capable of thickening a composition comprising water when the pH of the composition is increased from an acidic value to an alkaline value within a pH range of about 7.0 to about 12.

0.

4. The composition of claim 1, wherein the calcium ion source is a calcium salt of nitrate, a calcium salt of aspartic acid, a calcium salt of glutamic acid, or a water-soluble calcium salt of other suitable acids.

5. The composition of claim 1, wherein the acidulant is phosphoric acid, or other acids compatible with the ingredients of the first component.

6. The composition of claim 1, wherein the phosphate ion source is disodium phosphate, monosodium phosphate, or other suitable alkaline water-soluble phosphates.

7. The composition of claim 1, wherein the positively charged basic amino acid is arginine, lysine, histidine, or a combination thereof.

8. The composition of claim 1, wherein the cationic peptide is a water-soluble peptide that is positively charged at neutral pH and is non-toxic to the user.

9. The composition of claim 1, wherein the alkalizing agent is sodium hydroxide, potassium hydroxide, or other suitable alkaline compounds.

10. The composition of claim 1, wherein the viscosity of the cationic amorphous calcium phosphate gel formed instantaneously is greater than about 5,000 cP.

11. An oral health care method (200) for treating dentin hypersensitivity, comprising: providing a first component, the first component comprising a pH sensitive rheology modifying polymer, a calcium ion source, and an acidulant, and wherein the pH of the first component is in the range of about 2.0 to about 6.5; providing a second component, the second component comprising a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and an alkalizing agent, and wherein the pH of the second component is in the range of about 9.5 to about 14.0; separately accommodating the first component and the second component; dispensing the first component and the second component in a mixing top or mixing chamber, thereby combining the first component and the second component into a mixture that instantly forms a cationic amorphous calcium phosphate gel composition when the pH of the mixture reaches a pH range of about 7.0 to about 9.5; as well as The instantaneously formed cationic amorphous calcium phosphate gel composition is applied to the dentin surfaces of the user's teeth.

12. The oral care method of claim 11, wherein the pH of the first component is in the range of about 2.5 to about 4.

5.

13. The oral care method of claim 11, wherein the pH of the second component is in the range of about 10.5 to about 12.

5.

14. The oral care method of claim 11, wherein the pH of the instantaneously formed cationic amorphous calcium phosphate gel composition ranges from about 7.0 to about 9.

5.

15. A system (10, 100) for preparing a composition for treating dentin hypersensitivity, comprising: A dosing device (12, 112), the dosing device comprising: a first compartment comprising a first component, the first component comprising a pH sensitive rheology modifying polymer, a calcium ion source, and an acidulant, and wherein the pH of the first component is in the range of about 2.0 to about 6.5, and a second compartment comprising a phosphate ion source, a positively charged basic amino acid and / or a cationic peptide, and a second component of an alkalizing agent, and wherein the pH of the second component is in the range of about 9.5 to about 14.0; and A dispensing device (14, 114) is configured to receive the first component and the second component into a mixing tip (18) or a mixing chamber (122, 124), and to combine the first component and the second component into a mixture, wherein the mixture instantly produces a cationic amorphous calcium phosphate gel composition when the pH of the mixture reaches a pH range of about 7.0 to about 9.5, and wherein the dispensing device has an opening for applying the cationic amorphous calcium phosphate gel composition to the dentin surface of the user's teeth.

16. The system of claim 15, wherein the dispensing device is adapted to dispense the cationic amorphous calcium phosphate gel composition as a viscous gel having a viscosity greater than about 5,000 cP.

17. system according to claim 15, wherein said dosing device comprises a plurality of compartments, each compartment comprises one or more compatible ingredients of said first component and / or one or more compatible ingredients of said second component, and wherein the contents of said plurality of compartments are dispensed into said mixing top or said mixing chamber to form said cationic amorphous calcium phosphate gel composition.

18. The system of claim 15, wherein the ingredients for each compartment are supplied in cartridge form.

19. system according to claim 15, wherein said dispensing device comprises a double barrel syringe, a double chamber bottle or a form of dispensing device, and said form of dispensing device can distribute two separate components into a common mixing top to form said cationic amorphous calcium phosphate gel composition.

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