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    • 专利摘要:
    surface-reacted calcium carbonate; and, oral care composition. The present invention relates to surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid. said calcium carbonate and oral compositions containing the same can be used as a medicine and especially in the treatment of dentin hypersensitivity.
    公开号:BR112016021680B1
    申请号:R112016021680-6
    申请日:2015-03-20
    公开日:2021-06-01
    发明作者:Daniel E. Gerard；Tanja Budde；Joachim Schoelkopf；Patrick A. C. Gane
    申请人:Omya International Ag；
    IPC主号:
    专利说明:

    [001] The present invention relates to novel desensitizing agents for hypersensitive teeth and oral care compositions including such agents and their use.
    [002] Dentin is calcified tissue of the body and together with enamel, cement and pulp is one of the four main components of teeth. This is usually covered with enamel at the crown and cement at the root and surrounds the entire pulp. Dentin consists of microscopic channels, called dental tissues, that radiate through the pulp to the outer cement or enamel boundary.
    [003] Dentin hypersensitivity is a common clinical condition usually associated with exposed dentin surfaces. Many diseases, including physiological wear and enamel hypoplasia, wedge-shaped defects, and gingival recession, can lead to exposed dentin. This can affect patients of any age group and most commonly affects the canines and premolars of both arches. Dentin hypersensitivity is characterized by short sharp pain typical of exposed dentin that is caused by thermal, evaporative, tactile, osmotic, or chemical stimuli.
    [004] Currently, the most widely accepted mechanism of dentin hypersensitivity is the hydrodynamic theory advanced by Brãnnström in the 1960s. According to said theory, dentin hypersensitivity occurs when external stimulus such as temperature or a change in physical pressure or osmotic contact the exposed dentin and trigger a change in dentinal fluid flow. The resulting pressure change across the dentin activates the inner nerve fibers causing immediate pain. Therefore, a method to treat dentin hypersensitivity is based on occlusion of dentinal tubules with materials, reducing dentin permeability and reducing or preventing fluid flow in dentin due to external stimuli.
    [005] Oral compositions for treating hypersensitive teeth which comprise bioactive glass and one or more bioadhesive active components are described in WO 2010/115041. EP 2 578 272 A1 relates to a formulation for oral teeth comprising a plurality of calcium ion carriers and a plurality of calcium containing particulates, wherein the calcium containing particulates are carried by the calcium ion carriers. The effects of hydroxyapatite-containing dentifrice on dentinal tubule occlusion are studied in Yuan et al., PLOS ONE 2012, 7(12), 1-8. However, all of these occluding agents can lead to a complete blockage of the dentinal tubules, which must cut off the flow of nutrients that are supplied daily to each by the artery that follows the nerve and vein in the root canal and keeps teeth alive and healthy. .
    In view of the foregoing, there is a continuing need for agents that are useful in the treatment of dentin hypersensitivity.
    [007] Consequently, it is an object of the present invention to provide a desensitizing agent that can be used in the treatment of dentin hypersensitivity. In particular, it is desirable to provide a desensitizing agent that is easy to apply, can provide immediate relief, and is consistently effective. It is also desirable to provide a desensitizing agent that is non-toxic, non-irritating to the pulp and painless on application.
    [008] It is also an object of the present invention to provide a desensitizing agent that can migrate into dentin tubules easily and remain in the tubules and effectively occlude the tubules for a long period after application. It is also desirable to provide a desensitizing agent that allows a diffuse flow of nutrients into the dentin tubules without allowing for hydrodynamic flow, which can cause pain. Furthermore, it is desirable to provide a desensitizing agent that is more resistant to acid challenge.
    [009] The foregoing and other objectives are resolved by matter as defined herein in the independent claims.
    [0010] According to one aspect of the present invention, a surface-reacted calcium carbonate for use as a medicine is provided, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with dioxide of carbon and at least one acid.
    [0011] According to another aspect of the present invention, surface-reacted calcium carbonate for use in the treatment of dentin hypersensitivity is provided, wherein the surface-reacted calcium carbonate is a natural or natural calcium carbonate reaction product. synthetic with carbon dioxide and at least one acid.
    [0012] According to yet another aspect of the present invention, an oral care composition for use as a medicine is provided, which comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a product of reaction of natural or synthetic calcium carbonate with carbon dioxide and at least one acid.
    According to yet another aspect of the present invention, an oral care composition for use in treating dentin hypersensitivity is provided which comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid.
    [0014] According to yet another aspect of the present invention, an oral care composition comprising a surface-reacted calcium carbonate is provided, wherein the surface-reacted calcium carbonate is a natural calcium carbonate reaction product or synthetic with carbon dioxide and at least one acid and wherein the surface-reacted calcium carbonate is in the form of particles having a top-cut particle size determined by volume (dgs) equal to or less than 6 µm.
    Advantageous embodiments of the present invention are defined in the corresponding sub-claims.
    [0016] According to an embodiment, the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, preferably the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, oxalic acid and mixtures thereof and more preferably the at least one acid is phosphoric acid.
    [0017] According to an embodiment, the surface-reacted calcium carbonate is in the form of particles having a volume mean grain diameter (W50) equal to or less than 3 µm, preferably from 1.5 to 2.9 µm , more preferably from 1.7 to 2.7 µm and more preferably from 2.2 to 2.6 µm and/or a top cut particle size determined by volume (dg$) equal to or less than 6 µm, preferably from 3.5 to 5.5 µm and more preferably from 4.5 to 5 µm. According to another embodiment, the surface-reacted calcium carbonate is in the form of particles having a specific surface area of 5 m 2 /g to 200 m 2 /g, more preferably 20 m 2 /g to 80 m 2 /g and even more preferably 30 m 2 /ga 60 m2/g, measured using nitrogen and the BET method in accordance with ISO 9277.
    [0018] According to an embodiment, at least one active agent is associated with the surface-reacted calcium carbonate, preferably the active agent is at least one additional desensitizing agent and more preferably the at least one additional desensitizing agent is selected from the group consisting of potassium nitrate, gluteraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, strontium acetate, arginine, hydroxyapatite, sodium calcium phosphosilicate, sodium oxalate potassium, calcium phosphate, calcium carbonate, bioactive glasses and mixtures thereof.
    [0019] According to one embodiment, the surface-reacted calcium carbonate is obtained by a process comprising the steps of: a) providing a suspension of natural or synthetic calcium carbonate, b) adding at least one acid having a value of pKa of 0 or less at 20°C or having a pKa value of 0 to 2.5 at 20°C to the suspension from step a) and c) treating the suspension from step a) with carbon dioxide before, during or after the step b).
    [0020] According to another modality, the surface-reacted calcium carbonate is obtained by a process comprising the steps of: A) providing a natural or synthetic calcium carbonate, B) providing at least one water-soluble acid, C) providing gaseous CO2, D) contacting said natural or synthetic calcium carbonate from step A) with the at least one acid from step B) and with the CO2 from step C), characterized in that: i) the at least one acid from step B) has a pKa greater than 2.5 and less than or equal to 7 at 20°C, associated with the ionization of its first available hydrogen, and a corresponding anion is formed on the loss of its first available hydrogen capable of form a water-soluble calcium salt and ii) proceed by contacting the at least one acid with natural or synthetic calcium carbonate, at least one water-soluble salt, which, in the case of a hydrogen-containing salt, has a pKa greater than 7 a 20°C, associated with the ionization of the first available hydrogen and the salt anion that is cap z to form water-insoluble calcium salts is additionally provided.
    According to an embodiment, the oral care composition comprises from 1 to 20% by weight, preferably from 1.5 to 15% by weight, more preferably from 2 to 10% by weight of the surface-reacted calcium carbonate , based on the total weight of the composition. According to another embodiment, the oral care composition is a toothpaste, a dental powder or a mouthwash and preferably the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with calcium dioxide. carbon and phosphoric acid.
    [0022] According to an embodiment, the oral care composition comprises at least one additional desensitizing agent, preferably selected from the group consisting of potassium nitrate, gluteraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, strontium acetate, arginine, hydroxyapatite, sodium calcium phosphosilicate, potassium oxalate, calcium phosphate, calcium carbonate, bioactive glasses and mixtures thereof. According to another embodiment, the oral care composition comprises a bioadhesive polymer, preferably selected from the group consisting of hydroxyethyl methacrylate, PEG/PPG copolymers, polyvinylmethylether/maleic anhydride copolymers, polyvinylpyrrolidone (PVP), crosslinked PVP, gum lacquer, polyethylene oxide, methacrylates, acrylate copolymers, methacrylic copolymers, vinylpyrrolidone/vinyl acetate copolymers, polyvinyl caprolactam, polylactics, silicone resins, silicone adhesives, chitosan, milk proteins (casein), amelogenin, ester gum and combinations thereof.
    [0023] According to one embodiment, the surface-reacted calcium carbonate has a radioactive dentin abrasion (RDA) value of less than 70, preferably less than 50 and more preferably less than 35. According to another embodiment, the oral care composition has a pH between 7.5 and 10, preferably between 8 and 9.
    [0024] It is to be understood that for the purpose of the present invention, the following terms have the following meaning.
    [0025] For the purpose of the present invention, an "acid" is defined as Brpnsted-Lowry acid, that is, it is a supplier of H}O+ ion. An “acid salt” is defined as an HsO+ ion supplier, eg a hydrogen-containing salt that is partially neutralized by an electropositive element. A “salt” is defined as an electrically neutral ionic compound formed from anions and cations. A “partially crystalline salt” is defined as a salt that, in XRD analysis, exhibits an essentially distinct diffraction pattern.
    [0026] According to the present invention, pKa is the symbol that represents the dissociation constant of acid with a given ionizable hydrogen in a given acid and is indicative of the natural degree of dissociation of this hydrogen from this acid in equilibrium in water at a given temperature. Such pKa values can be observed in reference textbooks such as Harris, D.C. "Quantitative Chemical Analysis: 3rd Edition", 1991, W.H. Freeman & Co. (USA), ISBN 0-7167-2170-8.
    [0027] In the meaning of the present invention, the "radioactive dentin abrasion (RDA)" is a measure of the erosive effect of abrasives in toothpaste on tooth dentin. This involves using standardized abrasives against the test sample. Determination of this value is accomplished by determining activity while cleaning spent dentin that is radioactively labeled by mild neutron irradiation. The values obtained depend on the size, quantity and surface structure of the abrasive used in toothpaste. The RDA value is given by DIN EN ISO 11609 standards.
    [0028] "Grinded calcium carbonate" (GCC) in the meaning of the present invention is a calcium carbonate obtained from natural sources such as limestone, marble, dolomite or chalk processed through a wet and/or dry treatment grinding, evaluation and /or fractionation, for example, by a cyclone or classifier.
    [0029] "Precipitated calcium carbonate" (PCC) in the meaning the present invention is a synthesized material, obtained by precipitation following the reaction of carbon dioxide and lime in an aqueous, semi-dry or humid environment or by precipitation from an ion source of calcium and carbonate in water. PCC can be in vateritic, calcitic or aragonitic form.
    [0030] For the purpose of the present invention, a "surface-reacted calcium carbonate" is a material comprising calcium carbonate and a calcium salt other than insoluble, at least partially crystalline carbonate, preferably extending from the surface of at least part of the calcium carbonate. The calcium ions which form said at least partially crystalline non-carbonate calcium salt largely originate from the starting potassium carbonate material which also serves to form the reacted calcium carbonate in the surface core. Such salts can include OH' anions and/or crystalline water.
    [0031] In the meaning of the present invention, "water-insoluble" materials are defined as materials that, when mixed with deionized water and filtered into a filter having a pore size of 0.2 µm at 20°C to recover the filtrate liquid, provides less than or equal to 0.1 g of solid material recovered following the evaporation at 95 to 100°C of 100 g of said liquid filtrate. "Water-soluble" materials are defined as materials which lead to recovery greater than 0.1 g of recovered solid material following the evaporation at 95 to 100°C of 100 g of said liquid filtrate.
    [0032] Throughout this document, the "particle size" of a calcium carbonate and other materials is described by its particle size distribution. The dx value represents the relative diameter at which x wt% of the particles have smaller diameters than dx. This means that the c/20 value is the particle size where 20% by weight of all the particles are smaller and the dis value is the particle size where 75% by weight of all the particles are smaller. The dso value is thus the average particle size by weight, i.e. 50% by weight of all grains are larger or smaller than the particle size. For the purpose of the present invention, particle size is specified as the weight average particle size of dso unless otherwise indicated. To determine the weight average particle size of the value of a Sedigraph can be used. For the purpose of the present invention, the "particle size" of surface-reacted calcium is described as particle size distributions determined by volume. To determine the volume-determined particle size distribution, for example, volume mean grain diameter (e/50) or top cut particle size determined by volume (^s) of surface-reacted calcium carbonate , a Malvern Mastersizer 2000 can be used. The particle size distribution determined by weight can correspond to the particle size determined by volume if the density of all particles is equal.
    [0033] A "specific surface area (SSA)" of a calcium carbonate in the meaning of the present invention is defined as the surface area of the calcium carbonate divided by its mass. As used here, specific surface area is measured by nitrogen gas adsorption using BET isotherm (ISO 9277:2010) and is specified in m2/g.
    [0034] An "oral care composition" in the meaning of the present invention refers to a composition suitable for use in the mouth and for veterinary and/or human applications, but especially for use in human mouth applications.
    [0035] For the purpose of the present invention, the term "viscosity" or "Brookfield viscosity" refers to Brookfield viscosity. Brookfield viscosity is for this purpose measured by a Brookfield viscometer (Typ RVT) at 20°C ± 2°C at 100 rpm using an appropriate shaft and is specified in mPa-s.
    [0036] A "suspension" or "paste" in the meaning of the present invention comprises insoluble solids and water and optionally additional additives and usually contains large amounts of solids and thus is more viscous and may be of higher density. higher than the liquid from which it is formed.
    [0037] When the term “comprising” is used in this descriptive report and claims, it does not exclude other elements. For purposes of the present invention, the term "consisting of" is considered to be a preferred embodiment of the term "comprising of". If, below, a group is defined to comprise at least a number of embodiments, this is also to be understood to describe a group, which preferably consists only of these embodiments.
    [0038] Where an indefinite or definite article is used when referring to a singular name, for example "a", "an" or "the", includes a plural of that name unless something is specifically stated.
    [0039] Terms such as "obtainable" or "definable" and "obtained" or "defined" are used interchangeably. This, for example, means that, unless the context clearly dictates otherwise, the term "obtained" does not mean to indicate that, for example, a modality must be obtained, for example, by the sequence of steps that follow the term " obtained" although such a limited understanding is always encompassed by the terms "obtained" or "defined" as a preferred embodiment.
    [0040] According to the present invention, a surface-reacted calcium carbonate is used as a medicine. Surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid.
    [0041] In the following, the details and preferred modalities of the inventive surface-reacted calcium carbonate will be presented in more detail. It should be understood that these technical details and modalities also apply to the inventive method for producing surface-reacted calcium carbonate as well as the inventive compositions comprising surface-reacted calcium carbonate.
    [0042] According to the present invention, the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid.
    [0043] Natural (or ground) calcium carbonate (GCC) is understood to be a naturally occurring form of calcium carbonate, mined from sedimentary rocks such as limestone or chalk or from metamorphic marble rocks. Calcium carbonate is known to exist primarily as the three types of crystalline polymorphs: calcite, aragonite and vaterite. Calcite, the most common crystalline polymorph, is considered to be the most stable crystalline form of calcium carbonate. Less common is aragonite, which has a distinct or clustered needle orthorhombic crystal structure. Vaterite is the rarest calcium carbonate polymorph and is generally unstable. Natural calcium carbonate is almost exclusively of the calcitic polymorph, which is said to be trigonal-rhombohedric and represents the most stable of the calcium carbonate polymorphs. The term "source" of calcium carbonate in the meaning of the present invention refers to the naturally occurring mineral from which calcium carbonate is obtained. The calcium carbonate source may further comprise naturally occurring components such as magnesium carbonate, aluminum silicate etc.
    [0044] According to an embodiment of the present invention, natural calcium carbonate is selected from the group consisting of marble, chalk, dolomite, limestone and mixtures thereof.
    [0045] According to an embodiment of the present invention the GCC is obtained by dry grinding. According to another embodiment of the present invention the GCC is obtained by wet grinding and, optionally, subsequent drying.
    [0046] In general, the crushing step can be performed with any conventional crushing device, for example, under conditions such that crushing results predominantly from impacts with a secondary body, that is, in one or more of: a mill ball mill, a rod mill, a vibrating mill, a roller crusher, a centrifugal impact mill, a vertical pearl mill, a friction mill, a pin mill, a hammer mill, a pulverizer, a shredder, a chopper, knife cutter or other such equipment known to skilled man. In this case, the calcium carbonate containing mineral material comprises a wet crushed calcium carbonate containing mineral material, the grinding step can be carried out under conditions such that the autogenous grinding takes place and/or by horizontal ball mill and/or other such processes known by the qualified person. The wet processed crushed calcium carbonate containing mineral material thus obtained can be washed and dehydrated by well known processes, for example by flocculation, filtration or forced evaporation before drying. The subsequent drying step can be carried out in a single step, such as spray drying, or in at least two steps. It is also common for such mineral material to undergo a beneficiation step (such as a flotation, bleaching or magnetic separation step) to remove impurities.
    [0047] "Precipitated calcium carbonate" (PCC) in the meaning of the present invention is a synthesized material, generally obtained by precipitation following the reaction of carbon dioxide and lime in an aqueous environment or by precipitation from a source of calcium ion or of carbonate in water or by precipitation of calcium or carbonate ions, eg, CaCk and Na2CO3, out of solution. Still possible ways to produce PCC are the caustic soda process or the Solvay process where PCC is a by-product of ammonia production. Precipitated calcium carbonate exists in three primary crystal forms: calcite, aragonite and vaterite and there are many different polymorphs (crystalline habits) for each of these crystal forms. Calcite has a trigonal structure with typical crystalline habits such as scalenehedric (S-PCC), rhombohedral (R-PCC), prismatic hexagonal, pinachoidal, colloidal (C-PCC), cubic and prismatic (P-PCC) . Aragonite is an orthorhombic structure with crystal habits typical of double hexagonal prismatic crystals, as well as a diverse classification of chisel-shaped, curved-blade, fine elongated prismatic, tree-branched, and coral- or worm-like crystals. Vaterite belongs to the hexagonal crystal system. The PCC slurry obtained can be mechanically dehydrated and dried.
    [0048] According to an embodiment of the present invention, the synthetic calcium carbonate is precipitated calcium carbonate, preferably comprising aragonitic, vateritic or calcitic mineralogical crystal forms or mixtures thereof.
    [0049] According to an embodiment of the present invention, the natural or synthetic calcium carbonate is ground prior to treatment with carbon dioxide and at least one acid. The crushing step can be carried out with any conventional crushing device, such as a crushing mill known to the skilled person.
    [0050] According to an embodiment of the present invention, the natural or synthetic calcium carbonate is in the form of particles having a weight-average particle size equal to or less than 3 µm, preferably from 1.5 to 2. 9 µm, more preferably from 1.7 to 2.7 µm and most preferably from 2.2 to 2.6 µm. According to a further embodiment of the present invention, the natural or synthetic calcium carbonate is in the form of particles having a top cut particle size dw equal to or less than 6 µm, preferably from 3.5 to 5.5 µm and more preferably from 4.5 to 5.0 µm.
    [0051] Preferably, the surface-reacted calcium carbonate to be used in the present invention is prepared as an aqueous suspension having a pH, measured at 20°C, greater than 6.0, preferably greater than 6.5, more preferably greater than 7.0, even more preferably greater than 7.5.
    [0052] In a preferred process for preparing the surface-reacted aqueous suspension of calcium carbonate, the finely divided natural or synthetic calcium carbonate, such as by grinding or not, is suspended in water. Preferably, the pulp has a natural or synthetic calcium carbonate content within the range of 1 wt% to 90 wt%, more preferably 3 wt% to 60 wt% and even more preferably 5 wt% to 40 wt%. % by weight, based on the weight of the paste.
    [0053] In a next step, at least one acid is added to the aqueous suspension containing the natural or synthetic calcium carbonate. The at least one acid can be any strong acid, medium strong acid or weak acid or mixtures thereof, generating HsO+ ions under the conditions of preparation. According to the present invention, the at least one acid can also be an acid salt, which generates H3O+ ions under the conditions of preparation.
    According to one embodiment, the at least one acid is a strong acid having a pKa of 0 or less at 20°C. According to another embodiment, the at least one acid is a medium strong acid having a pKa value of 0 to 2.5 at 20°C. If the pKa at 20°C is 0 or less, the acid is preferably selected from sulfuric acid, hydrochloric acid, or mixtures thereof. If the pKa at 20°C is from 0 to 2.5, the acid is preferably selected from H2SO3, H3PO4, oxalic acid or mixtures thereof. The at least one acid can also be an acid salt, for example HSÜ4- or H2PO4, being at least partially neutralized by a corresponding cation, such as Li+, Na+ or K+ or HPC>42', being at least partially neutralized by a corresponding cation such as Li+, Na+' K+, Mg2+ or Ca2+. The at least one acid can also be a mixture of one or more acids and one or more acid salts.
    [0055] According to yet another embodiment, the at least one acid is a weak acid having a pKa value of greater than 2.5 and less than or equal to 7 when measured at 20°C, associated with the ionizing the first available hydrogen and having a corresponding anion formed on the loss of its first available hydrogen, which is capable of forming water-soluble calcium salts. According to the preferred embodiment, the weak acid has a pKa value of 2.6 from 5 to 20°C and more preferably, the weak acid is selected from the group consisting of acetic acid, formic acid, propanoic acid and mixtures thereof .
    [0056] In the case, a weak acid is used, after adding said acid to the aqueous suspension containing the natural or synthetic calcium carbonate, at least one water-soluble salt, which in the case of a hydrogen containing salt has a pKa greater than 7, when measured at 20°C, associated with the ionization of the first available hydrogen, and the salt anion that is capable of forming water-insoluble calcium salts is additionally added. The cation of said water-soluble salt is preferably selected from the group consisting of potassium, sodium, lithium and mixtures thereof. In a more preferred embodiment, said cation is sodium. Note that depending on the charge of the anion, more than one of said cations may be present to provide an electrically neutral ionic compound. The anion of said water-soluble salt is preferably selected from the group consisting of phosphate, dihydrogen phosphate, monohydrogen phosphate, oxalate, silicate, mixtures thereof and hydrates thereof. In a more preferred embodiment, said anion is selected from the group consisting of phosphate, dihydrogen phosphate, monohydrogen phosphate, mixtures thereof and hydrates thereof. In a more preferred embodiment, said anion is selected from the group consisting of dihydrogen phosphate, monohydrogen phosphate, mixtures thereof and hydrates thereof. The addition of water-soluble salt can be carried out dropwise or in one step. In the case of addition to drops, this addition preferably takes place within a time period of 10 minutes. It is more preferred to add said salt in one step.
    [0057] According to an embodiment of the present invention, the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures of the same. Preferably the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, oxalic acid, FhPCV, being at least partially neutralized by a corresponding cation such as Li+, Na+ or K+, HPO42' , being at least partially neutralized by a corresponding cation, such as Li+, Na+> K+, Mg2+ or Ca2+ and mixtures thereof, more preferably the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, oxalic acid or mixtures thereof and most preferably the at least one acid is phosphoric acid. Without being bound by any theory, the inventors believe that the use of phosphoric acid can be beneficial in therapy, especially in the treatment of dentin hypersensitivity.
    [0058] The at least one acid can be added to the suspension as a concentrated solution or a more dilute solution. Preferably, the molar ratio of the at least one acid to natural or synthetic calcium carbonate is from 0.05 to 4, more preferably from 0.1 to 2.
    [0059] As an alternative, it is also possible to add the at least one acid to the water before the natural or synthetic calcium carbonate is suspended.
    [0060] According to the present invention, surface-reacted calcium carbonate is obtained by treating natural or synthetic calcium carbonate with carbon dioxide. Carbon dioxide can be formed in situ by acid treatment and/or can be supplied from an external source. If a strong acid such as sulfuric acid or hydrochloric acid or medium strong acid such as phosphoric acid is used for acid treatment of natural or synthetic calcium carbonate, carbon dioxide is automatically formed. Alternatively or additionally, carbon dioxide can be supplied from an external source.
    [0061] According to an embodiment, surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid, wherein the carbon dioxide is formed in situ as a result of contacting the at least one acid with natural or synthetic calcium carbonate and/or is supplied from an external source.
    [0062] Acid treatment and carbon dioxide treatment can be carried out simultaneously which is the case when a strong acid or medium strong acid is used. It is also possible to carry out the first acid treatment, for example with a medium strong acid having a pKa in the range of 0 to 2.5 at 20°C, where carbon dioxide is formed in situ and in this way the carbon dioxide treatment will automatically be carried out simultaneously with the acid treatment, followed by additional treatment with carbon dioxide supplied from an external source.
    [0063] Preferably, the concentration of carbon dioxide gas in the suspension is, in terms of volume, such that the ratio (volume of suspension):(volume of CO2 gas) is from 1:0.05 to 1:20, still more preferably from 1:0.05 to 1:5.
    [0064] In a preferred embodiment, the acid treatment step and/or the carbon dioxide treatment step are repeated at least once, more preferably several times. According to one embodiment, the at least one acid is added over a time period of at least 30 minutes, preferably at least 45 minutes and more preferably at least 1 h.
    [0065] Subsequent to treatment with acid and treatment with carbon dioxide, the pH of the aqueous suspension, measured at 20°C, naturally reaches a value greater than 6.0, preferably greater than 6.5, more preferably greater than than 7.0, even more preferably greater than 7.5, thereby preparing the surface-reacted calcium carbonate as an aqueous suspension having a pH greater than 6.0, preferably greater than 6.5, more preferably greater than 7.0, even more preferably greater than 7.5. If the aqueous suspension is allowed to reach equilibrium, the pH is greater than 7. A pH greater than 6.0 can be adjusted without adding a base when stirring of the aqueous suspension is continued for a sufficient period of time, preferably from 1 hour to 10 hours, more preferably 1 to 5 hours.
    [0066] Alternatively, before reaching equilibrium, which occurs at a pH greater than 7, the pH of the aqueous suspension can be increased to a value greater than 6 by adding the base subsequent to the carbon dioxide treatment. Any conventional base such as sodium hydroxide or potassium hydroxide can be used.
    [0067] Further details on the preparation of surface-reacted natural calcium carbonate are described in WO 00/39222 and US 2004/0020410, wherein surface-reacted natural calcium carbonate is described as a filler for papermaking. The preparation of surface-reacted calcium carbonate with weak acids is surface-reacted is described in EP 2 264 108. The preparation of surface-reacted calcium carbonate and its use in purification processes is described in EP 1 974 806, EP 1 982 759, and EP 1 974 807. The use of surface-reacted calcium carbonate as the carrier for the controlled release of active agents is described in WO 2010/037753.
    [0068] Similarly, precipitated surface-reacted calcium carbonate is obtained. As can be seen in detail from EP 2 070 991, the precipitated calcium carbonate reacted on the surface is obtained by contacting the precipitated calcium carbonate with HsO+ ions and in anions being solubilized in an aqueous medium and being able to form calcium salts insoluble in water, in an aqueous medium to form a surface-reacted precipitated calcium carbonate slurry, wherein said surface-reacted precipitated calcium carbonate comprises an at least partially crystalline insoluble calcium salt of said surface-formed anion less part of the precipitated calcium carbonate.
    [0069] Said solubilized calcium ions correspond to an excess of solubilized calcium ions in relation to the solubilized calcium ions naturally generated in the dissolution of calcium carbonate precipitated by H3O+ ions, where said HsO+ ions are provided only in the form from a counterion to the anion, that is, through the addition of the anion in the form of an acid or an acidic salt other than calcium and in the absence of any additional calcium ion or calcium ion generating source.
    [0070] Said excess solubilized calcium ions is preferably provided by adding a neutral calcium salt or soluble acid or by adding an acid or a salt other than neutral calcium or acid which generates a neutral calcium salt or soluble acid in situ.
    [0071] Said HβO+ ions can be provided by the addition of an acid or an acid salt of said anion or the addition of an acid or acid salt that simultaneously serves to provide all or part of said excess of solubilized calcium ions .
    [0072] According to an embodiment of the present invention, the surface-reacted calcium carbonate is obtained by a process comprising the steps of: a) providing a suspension of natural or synthetic calcium carbonate, b) adding at least one acid having a pKa value of 0 or less at 20°C or having a pKa value of 0 to 2.5 at 20°C to the suspension from step a) and c) treating the suspension from step a) with carbon dioxide before, during or after step b).
    [0073] According to an embodiment, at least one acid having a pKa value of 0 or less at 20°C is added in step b) to the suspension of step a). According to another embodiment, at least one acid having a pKa value of 0 to 2.5 at 20°C is added in step b) to the suspension of step a).
    [0074] The carbon dioxide used in step c) can be formed in situ by the acid treatment of step b) and/or can be supplied from an external source.
    [0075] According to an embodiment of the present invention, the surface-reacted calcium carbonate is obtained by a process comprising the steps of: A) providing a natural or synthetic calcium carbonate, B) providing at least one soluble acid in water, C) provide gaseous CO2, D) contact said natural or synthetic calcium carbonate from step A) with the at least one acid from step B) and with the CO2 from step C), characterized in that: i) the at least one acid from step B) has a pKa greater than 2.5 and less than or equal to 7 at 20°C, associated with the ionization of its first available hydrogen, and a corresponding anion is formed on the loss of its first hydrogen available capable of forming a water-soluble calcium salt and ii) following contact of the at least one acid with natural or synthetic calcium carbonate, at least one water-soluble salt, which in the case of a hydrogen-containing salt has a higher pKa than 7 to 20°C, associated with the ionization of the first available hydrogen and the anion No salt which is capable of forming water-insoluble calcium salts is additionally provided.
    [0076] The surface-reacted calcium carbonate can be kept in suspension, further optionally stabilized by a dispersant. Conventional dispersants known to the skilled person can be used. A preferred dispersant is polyacrylic acid.
    [0077] Alternatively, the aqueous suspension described above can be dried, thereby obtaining the solid (i.e., dry or containing so little water that it is not in a fluid form) calcium carbonate reacted on the natural or synthetic surface in the form of granules or a powder.
    [0078] According to an embodiment of the present invention, the surface-reacted calcium carbonate has a specific surface area of 5 m2/g to 200 m2/g, more preferably 20 m2/g to 80 m2/g and even more preferably 30 m2/g to 60 m2/g, measured using nitrogen and the BET method in accordance with ISO 9277.
    [0079] The particle size of the surface-reacted calcium carbonate can be adapted with respect to the dentin tubules to be treated. For example, in the case of a human molar, where dentin tubules typically have a diameter between 3 and 2 µm, the surface-reacted calcium carbonate particles may have a volume mean grain diameter ( (/50) equal to or less than 3 µm.
    [0080] According to an embodiment of the present invention, the surface-reacted calcium carbonate is in the form of particles having a volume mean grain diameter (i/50) equal to or less than 3 µm, preferably of 1, 5 to 2.9 µm, more preferably from 1.7 to 2.7 µm and most preferably from 2.2 to 2.6 µm. According to another embodiment of the present invention, the surface-reacted calcium carbonate is in the form of particles having a top-cut particle size determined by volume (Wgs) equal to or less than 6 µm, preferably 3, 5 to 5.5 µm and more preferably from 4.5 to 5 µm. According to a preferred embodiment of the present invention, the surface-reacted calcium carbonate is in the form of particles having volume mean grain diameter (0Z50) equal to or less than 3 µm, preferably from 1.5 to 2.9 µm , more preferably from 1.7 to 2.7 µm and more preferably from 2.2 to 2.6 µm and having a top cut particle size determined by volume (<7g8) equal to or less than 6 µm, preferably from 3.5 to 5.5 µm and more preferably from 4.5 to 5 µm. Volume mean grain diameter (0Z50) and volume determined top cut particle size (1/98) can be determined by laser diffraction measurements, for example using a Malvern Mastersizer 2000.
    [0081] According to an embodiment of the present invention, the surface-reacted calcium carbonate comprises an insoluble, at least partially crystalline calcium salt of an anion of the at least one acid, which is formed on the surface of the natural calcium carbonate or synthetic. According to an embodiment, the insoluble, at least partially crystalline calcium salt of an anion of the at least one acid covers the surface of the natural or synthetic calcium carbonate at least partially, preferably, completely. Depending on the at least one acid used, the anion can be sulfate, sulfite, phosphate, citrate, oxalate, acetate, formate and/or chloride.
    [0082] According to a preferred embodiment, the surface-reacted calcium carbonate is a reaction product of natural calcium carbonate and at least one acid, preferably phosphoric acid.
    [0083] The surface-reacted calcium carbonate is also able to associate and transport an active agent. The association is preferably a surface adsorption of the reacted calcium carbonate on the surface particles, either the outer or inner surface of the particles, or an absorption on the particles, which is possible due to porosity.
    [0084] In this regard, it is believed that because of the intra- and interpore structure of the surface-reacted calcium carbonate, this material is a superior agent for releasing previously absorbed ad/during time relative to common materials having specific surface areas similar.
    [0085] The surface-reacted calcium carbonate may have an intraparticle porosity within the range of 5% by volume to 50% by volume, preferably from 20% by volume to 50% by volume and more preferably from 30% by volume to 50% by volume, calculated from measurement by mercury porosimetry. From the bimodal derived distribution curve, the lowest point between the peaks indicates the diameter where the intra and interparticle pore volumes can be separated. The pore volume in diameters greater than this diameter is the pore volume associated with the interparticle pores. The total pore volume minus this interparticle pore volume gives the intraparticle pore volume from which the intraparticle porosity can be calculated, preferably as a fraction of the solid material volume, as described in Transport in Porous Media (2006 ) 63: 239-259.
    [0086] Further details regarding the porosity of surface-reacted calcium carbonate and its use as the agent for releasing materials can be found in WO 2010/037753.
    [0087] In this way, in general, any agent that fits in the intra- and/or interparticle pores of the surface-reacted calcium carbonate carrier is suitable to be transported by the surface-reacted calcium carbonate carriers according to the invention . For example, active agents such as those selected from the group comprising pharmaceutically active agents, biologically active agents, disinfecting agents, preservatives such as triclosan, flavoring agents, surfactants such as defoamers or additional desensitizing agents can be used. According to one embodiment, at least one active agent is associated with the surface-reacted calcium carbonate. According to a preferred embodiment the active agent is at least one additional desensitizing agent, preferably selected from the group consisting of potassium nitrate, gluteraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, fluoride stannous, strontium chloride, strontium acetate, arginine, hydroxyapatite, sodium calcium phosphosilicate, potassium oxalate, calcium phosphate, calcium carbonate, bioactive glasses and mixtures thereof.Oral care composition
    [0088] The oral care composition for use in accordance with the present invention comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid.
    [0089] According to an embodiment of the present invention, the composition comprises from 1 to 20% by weight, preferably from 1.5 to 15% by weight, more preferably from 2 to 10% by weight of the calcium carbonate reacted in the surface, based on the total weight of the composition.
    [0090] The surface-reacted calcium carbonate may consist of only one type of surface-reacted calcium carbonate or it may be a mixture of two or more types of surface-reacted calcium carbonate. The oral care composition of the present invention may contain the surface-reacted calcium carbonate only as the desensitizing agent. Alternatively, the oral care composition of the present invention may contain the surface-reacted calcium carbonate in combination with at least one additional desensitizing agent. According to one embodiment, the oral care composition comprises at least one additional desensitizing agent. Preferably, the additional desensitizing agent is selected from the group consisting of potassium nitrate, gluteraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, strontium acetate, arginine , hydroxyapatite, sodium calcium phosphosilicate, potassium oxalate, calcium phosphate, calcium carbonate, bioactive glasses and mixtures thereof.
    [0091] According to an embodiment, the additional desensitizing agent has a weight average particle size of 0.1 to 100 µm, preferably 0.5 to 50 µm, more preferably 1 to 20 µm and more preferably from 2 to 10 µm.
    The at least one additional desensitizing agent may be present in the oral care composition in an amount from 1 to 20% by weight, preferably from 1.5 to 15% by weight, more preferably from 2 to 10% by weight, based on the total weight of the composition.
    According to an embodiment, the oral care composition of the present invention comprises from 1 to 20% by weight of the surface-reacted calcium carbonate and from 1 to 20% by weight of an additional desensitizing agent, based on weight total composition.
    [0094] The oral care composition of the present invention can be, for example, a toothpaste, a dental powder, a varnish, an adhesive gel, a cement, a resin, a spray, a foam, a balm, a carrier composition in a mouthband or adhesive buccal patch, a chewable tablet, a chewable lozenge, a chewable gum, a lozenge, a drink or a mouthwash. According to one embodiment of the present invention, the oral care composition is a toothpaste, a toothpaste or a mouthwash, and preferably a toothpaste.
    [0095] According to a preferred embodiment, the oral care composition is a toothpaste, a dental powder or a mouthwash and the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with calcium dioxide. carbon and phosphoric acid. According to another preferred embodiment, the oral care composition is a toothpaste, a dental powder or a mouthwash and the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and phosphoric acid, wherein the surface-reacted calcium carbonate is in the form of particles having a volume mean grain diameter ( (/50) equal to or less than 3 µm, preferably from 1.5 to 2.9 µm, plus preferably from 1.7 to 2.7 µm and more preferably from 2.2 to 2.6 µm, and/or having a top cut particle size determined by volume (d^) equal to or less than 6 µm, preferably from 3.5 to 5.5 µm and more preferably from 4.5 to 5 µm.
    [0096] The surface-reacted calcium carbonate may consist of one type of surface-reacted calcium carbonate or may be a mixture of two or more types of surface-reacted calcium carbonate. According to an embodiment, the surface-reacted calcium carbonate has a radioactive dentin abrasion (RDA) value of less than 70, preferably less than 50 and more preferably less than 35. According to an embodiment of the present invention, the oral care composition is a toothpaste for sensitive teeth and/or infant teeth and preferably the surface-reacted calcium carbonate has an RDA of less than 50 and more preferably less than 35.
    [0097] According to an embodiment of the present invention, the oral care composition has a pH between 7.5 and 10, preferably between 8 and 9.
    [0098] According to an embodiment of the present invention, the oral care composition comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with dioxide of carbon and at least one acid and wherein the surface-reacted calcium carbonate is in the form of particles having a top-cut particle size determined by volume (t/g) equal to or less than 6 µm.
    [0099] In addition to the surface-reacted calcium carbonate and the optional additional desensitizing agent, the oral care composition may further comprise bioadhesive polymers, fluoride compounds, surfactants, binders, humectants, remineralizers, flavoring agents, sweetening agents and/or water .
    [00100] According to an embodiment of the present invention, the oral care composition comprises a bioadhesive polymer. The bioadhesive polymer can include any polymer that promotes adhesion of calcium carbonate reacted on the tooth or tooth surface and remains on the tooth or tooth surface for an extended period of time, eg, 1 hour, 3 hours, 5 hours, 10 hours, 24 hours. In certain embodiments, the bioadhesive polymer can become more adhesive when the oral care composition is moistened with, for example, water or saliva. In other embodiments, the bioadhesive polymer is a material or combination of materials that enhance retention of the active ingredient on the surface of the teeth or tooth to which the composition is applied. Such bioadhesive polymers include, for example, hydrophilic organic polymers, hydrophobic organic polymers, silicone gums, silicas and combinations thereof. According to one embodiment, the bioadhesive polymer is selected from the group consisting of hydroxyethyl methacrylate, PEG/PPG copolymers, polyvinylmethylether/maleic anhydride copolymers, polyvinylpyrrolidone (PVP), crosslinked PVP, shellac, polyethylene oxide, methacrylates, acrylate copolymers, methacrylic copolymers, vinylpyrrolidone/vinyl acetate copolymers, polyvinyl caprolactam, polylactics, silicone resins, silicone adhesives, chitosan, milk proteins (casein), amelogenin, ester gum and combinations thereof.
    Examples of suitable fluoride compounds are sodium fluoride, stannous fluoride, sodium monofluorophosphate, potassium fluoride, stannous potassium fluoride, sodium fluorostannate, stannous chlorine fluoride and amine fluoride. Fluoride compounds can be added in an amount of 0.1 to 2% by weight, based on the total weight of an oral care composition. Good results can be achieved by using an amount of fluoride compound to provide available fluoride ion in the range of 300 to 2000 ppm in the oral care composition, preferably about 1450 ppm.
    [00102] Suitable surfactants are generally anionic organic synthetic surfactants over a wide pH range. Representative of such surfactants used in the range of about 0.5 to 5% by weight, based on the total weight of the oral care composition, are water-soluble salts of C10-Cis alkyl sulfates, such as sodium lauryl sulfate. from sulfonated fatty acid monoglycerides, such as sodium monoglyceride sulfonates, from taurine fatty acid amides, such as sodium N-methyl-N-palmitoyltauride, and from fatty acid esters of isethionic acid and aliphatic acylamides, such as N sarcosinate -lauroyl sodium. However, surfactants obtained from natural sources such as cocamidopropyl betaine can also be used.
    Suitable binding agents or thickeners providing the desired consistency are, for example, hydroxyethylcellulose, sodium carboxymethylcellulose, natural gums such as karaya gum, arabic gum, gum tragacanth, xanthan gum or cellulosic gum, colloidal silicates or finely divided silica. Generally, from 0.5 to 5% by weight, based on the total weight of the oral care composition, can be used.
    [00104] Various humectants known to the skilled person can be used, such as glycerin, sorbitol and other polyhydric alcohols, for example, in an amount of 20 to 40% by weight, based on the total weight of the oral care composition. Examples of suitable flavoring agents include oil of wintergreen, oil of peppermint, oil of mint, oil of cloves, oil of sassafras and others. Saccharin, aspartame, dextrose or levulose can be used as sweetening agents, for example, in an amount of 0.01 to 1% by weight, based on the total weight of the oral care composition. Preservatives such as sodium benzoate may be present in an amount of 0.01 to 1% by weight, based on the total weight of the oral care composition. Colorants such as titanium dioxide can also be added to the oral care composition, for example, in an amount of 0.01 to 1% by weight, based on the total weight of the oral care composition.
    [00105] The oral care composition of the present invention may also contain a material selected from the group consisting of silica, precipitated silica, alumina, aluminosilicate, metaphosphate, calcium triphosphate, calcium pyrophosphate, ground calcium carbonate, precipitated calcium carbonate , sodium bicarbonate, bentonite, kaolin, aluminum hydroxide, calcium hydrogen phosphate, hydroxylapatite and mixtures thereof. According to one embodiment, the oral care composition contains a material being selected from ground calcium carbonate and/or precipitated silica. According to another embodiment, the oral care composition contains a material being selected from the group consisting of ground calcium carbonate, precipitated calcium carbonate, aluminum hydroxide, calcium hydrogen phosphate, silica, hydroxylapatite and mixtures thereof. According to a preferred embodiment of the present invention, the oral care composition comprises surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and hair. minus one acid and calcium carbonate, preferably ground calcium carbonate and/or precipitated calcium carbonate.
    [00106] According to an embodiment of the present invention, the oral care composition is a toothpaste. Toothpaste can be produced by a method comprising the following steps: I) providing a mixture of water and a humectant and optionally at least one of a thickener, a preservative, a fluoride and a sweetener, II) adding a carbonate of surface-reacted calcium and, optionally, a dye, to the mixture of step I), wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid, III) adding a surfactant to the mixture from step II) and IV) optionally adding a flavoring agent to the mixture from step III).
    [00107] However, a toothpaste of the present invention can also be produced by any other method known to the skilled person. Therapeutic use
    [00108] It has been observed that surface-reacted calcium carbonate can be used in therapy and especially in dental therapy. According to the present invention, a surface-reacted calcium carbonate for use as a medicine is provided, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least an acid. According to another aspect of the present invention, an oral care composition for use as a medicine is provided, which comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of calcium carbonate. natural or synthetic calcium with carbon dioxide and at least one acid.
    [00109] According to an embodiment, the surface-reacted calcium carbonate of the present invention or the oral care composition of the present invention is used in the treatment of dentin hypersensitivity.
    [00110] The inventors of the present invention have surprisingly found that surface-reacted calcium carbonate is useful in therapy, for example dental therapy, and especially in the treatment of dentin hypersensitivity. Surface-reacted calcium carbonate differs from conventional calcium carbonate in several respects. For example, different conventional calcium carbonate, surface-reacted calcium carbonate comprises a porous, placoid or lamellar surface structure (See figures 1 and 2). Without being bound by any theory, it is believed that due to its porous, placoid or lamellar surface structure, surface-reacted calcium carbonate can occlude dentin tubules without cutting off the diffuse flow of nutrients into the dentin tubules. It is also believed that due to its special surface-structure, surface-modified calcium carbonate can connect to dentin tubules by an oscillating mechanism due to its lamellar surface structure and thus can remain within the tubules. for a long period of time. In addition, surface treatment makes the surface-reacted calcium carbonate more resistant against acids. Therefore, surface-reacted calcium carbonate is more stable under acidic conditions, for example, during consumption of acidic beverages such as soft drinks or acidic dishes such as salads with vinegar-based seasonings.
    [00111] The surface-reacted calcium carbonate of the present invention and/or oral compositions comprising the same can be used in professional treatment, office treatment or in home treatment.
    [00112] According to an embodiment, surface-reacted calcium carbonate for use in treating dentin hypersensitivity is used in a method comprising administering to at least one tooth of a patient, at least a therapeutically effective amount of calcium carbonate reacted on the surface at least once a day, preferably twice a day and more preferably three times a day. A "therapeutically effective" amount of surface-reacted calcium carbonate is an amount that is sufficient to have the desired therapeutic or prophylactic effect on the human patient to which the active agent is administered, without undue adverse side effects (such as toxicity, irritation or allergic response), provided with a reasonable risk/benefit ratio when used in the manner of this invention. The specific effective amount will vary with such factors as the particular condition being treated, the patient's physical condition, the nature of concurrent therapy (if any), the specific dosage form, the oral care composition used, and the desired dosage regimen .
    [00113] According to an embodiment, the oral composition for use in treating dentin hypersensitivity is used in a method comprising applying a composition to at least one tooth of a patient for an effective amount of time, preferably the composition stays on at least one tooth for at least 1 minute, at least 15 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 12 hours, or at least 24 hours.
    [00114] The scope and interest of the present invention will be better understood based on the following figures and examples which are intended to illustrate certain embodiments of the present invention and are not limiting. Description of the figure:
    [00115] Figure 1 shows a scanning electron microscope (SEM) micrograph of the calcium carbonate reacted on the surface prepared according to Example 1.
    [00116] Figure 2 shows an SEM micrograph of the surface-reacted calcium carbonate prepared according to Example 2.
    [00117] Figure 3 shows an SEM micrograph of an untreated bovine tooth neck sample with open dentin tubules.
    [00118] Figure 4 shows an SEM micrograph of the bovine tooth neck sample that was treated with the surface-reacted calcium carbonate from Example 1.
    [00119] Figure 5 shows an SEM micrograph of the bovine tooth neck sample that was treated with the surface-reacted calcium carbonate from Example 3.
    Figure 6 shows an SEM micrograph of the bovine tooth neck sample that was treated with the surface-reacted calcium carbonate from Example 3 and a 0.2 M acetic acid solution.
    [00121] Figure 7 shows an SEM micrograph of the bovine tooth neck sample that was treated with a ground calcium carbonate (comparative example).
    [00122] Figure 8 shows an SEM micrograph of the bovine tooth neck sample that was treated with a ground calcium carbonate (comparative example) and a 0.2 M acetic acid solution. Examples1. measurement methods
    [00123] In the following measurement methods implemented in the examples are described. Particle size distribution
    [00124] The particle size distribution of surface reacted particles other than calcium carbonate, eg ground calcium carbonate, was measured using a Sedigraph 5100 from the company Micromeritics, USA. The method and instrument are known to that skilled person and are commonly used to determine the grain size of fillers and pigments. The measurement was carried out in an aqueous solution comprising 0.1% by weight Na4P2θ7. The samples were dispersed using a high speed supersonic stirrer. For measuring the dispersed samples, none of the additional dispersing agents were added.
    [00125] The volume mean grain diameter ( de/50) of surface-reacted calcium carbonate was determined using a Malvern Mastersizer 2000 Laser Diffraction System (Malvern Instruments Plc., Great Britain). Scanning Electron Microscope (SEM) Micrographs
    [00126] The prepared surface-reacted calcium carbonate and tooth neck samples were examined by a Sigma VP field emission scanning electron microscope (Carl Zeiss AG, Germany) and a secondary variable pressure electronic detector (VPSE) with a chamber pressure of about 50 Pa. Specific Surface Area (SSA)
    [00127] The specific surface area is measured by means of a BET method according to ISO 92T1 using nitrogen, following conditioning of the sample by heating to 250°C for a period of 30 minutes. Prior to such medications, the sample is filtered into a Büchner funnel, rinsed with deionized water and dried overnight at 90 to 100°C in an oven. Subsequently the dry cake is crushed completely in a pestle and the resulting powder placed on a moisture balance at 130°C under constant weight to be reached. Solid content of an aqueous suspension
    [00128] The solids content of the suspension (also known as “dry weight”) was determined using an MJ33 Moisture Analyzer from the company Mettler-Toledo, Switzerland, with the following settings: drying temperature 160°C, automatic shut-off if the mass does not change more than 1 mg in a period of 30 seconds, standard drying 5 to 20 g of the suspension. 2. ExamplesExample 1 - Preparation of surface-reacted calcium carbonate
    [00129] In a mixing vessel, 7 liters of an aqueous suspension of ground calcium carbonate was prepared by adjusting the solids content of a ground calcium carbonate having a particle size distribution of 90% by weight below 2 µm , based on the total weight of the ground calcium carbonate, (commercially available from Omya AG, Switzerland) such that a solids content of 15% by weight, based on the total weight of the aqueous suspension, is obtained.
    [00130] 232 g of phosphoric acid was added in the form of an aqueous solution containing 30% by weight phosphoric acid to said suspension in a period of 30 minutes at a temperature of 70°C. After addition of acid, the slurry was stirred for an additional 5 minutes, before removal from the container.
    [00131] The resulting surface-reacted calcium carbonate has a volume mean grain diameter (4/50) of 2.7 µm, as measured by laser diffraction (Malvern Mastersizer 2000) and specific surface area of 51, 0 m 2 /g.
    [00132] The SEM micrograph of surface-reacted calcium carbonate having a porous, placoid or lamellar surface structure is shown in figure 1. Example 2 - Preparation of surface-reacted calcium carbonate
    [00133] In a mixing vessel, 7 liters of an aqueous suspension of ground calcium carbonate was prepared by adjusting the solids content of a ground calcium carbonate having a particle size distribution of 90% by weight below 2 µm , based on the total weight of the ground calcium carbonate, (commercially available from Omya AG, Switzerland) such that a solids content of 20% by weight, based on the total weight of the aqueous suspension, is obtained.
    [00134] 320 g of phosphoric acid was added in the form of an aqueous containing 30% by weight of phosphoric acid to said suspension over a period of 60 minutes at a temperature of 70°C. After addition of acid, the slurry was stirred for an additional 5 minutes, before removal from the container.
    [00135] The resulting surface-reacted calcium carbonate has a volume mean grain diameter (t/50) of 2.4 µm, as measured by laser diffraction (Malvern Mastersizer 2000) and the specific surface area of 48, 8 m2/g.
    [00136] The SEM micrograph of surface-reacted calcium carbonate having a porous, placoid or lamellar surface structure is shown in figure 2. Example 3 - Preparation of surface-reacted calcium carbonate
    [00137] In a mixing vessel, 7 liters of an aqueous suspension of ground calcium carbonate was prepared by adjusting the solid content of a ground calcium carbonate having a particle size distribution of 90% by weight below 2 µm , based on the total weight of the ground calcium carbonate, (commercially available from Omya AG, Switzerland) such that a solids content of 20% by weight, based on the total weight of the aqueous suspension, is obtained.
    [00138] 320 g of phosphoric acid was added in the form of an aqueous solution containing 30% by weight of phosphoric acid to said suspension in a period of 60 minutes at a temperature of 85°C. After addition of acid, the slurry was stirred for an additional 5 minutes, before removal from the container.
    [00139] The resulting surface-reacted calcium carbonate has a volume mean grain diameter (t/50) of 2.1 µm, as measured by laser diffraction (Malvern Mastersizer 2000) and specific surface area of 20, 2 m2/g. Example 4 - Surface-reacted calcium carbonate tooth treatment
    [00140] The crown section of a bovine molar was separated from the tooth neck by a saw. Subsequently, the following grinding or polishing steps were carried out on the tooth neck using a Buehler Phoenix 4000 polishing machine (Buehler GmbH, Germany):
    [00141] First, the tooth neck was ground parallel to its longitudinal axis until the dentin layer was reached (grinding wheel: Ultraprep 20 μm, speed: 300 rpm, water-cooling). Subsequently, the pre-crushed surface was polished for 30 s (crushing wheel: Apex, speed: 300 rpm, water-cooling). Finally, the polished surface was further polished by 120 with a polishing cloth (perforated Texmet, speed: 150 rpm, no water-cooling).
    [00142] The polished tooth neck was soaked for 2 min in a 15% EDTA solution and rinsed with tap water.
    The prepared tooth neck sample was soaked in the surface-reacted calcium carbonate suspensions of Example 1, 2 or 3 for 60 s and the tooth surface was brushed for 30 s with a toothbrush. Subsequently, the tooth sample was rinsed with tap water.
    [00144] Tooth neck samples before and after treatment with surface-reacted calcium carbonate were glued into SEM sample containers and examined by a Sigma VP field emission scanning electron microscope (Carl Zeiss AG, Germany) and a secondary electronic variable pressure detector (VPSE) with a chamber pressure of about 50 Pa.
    [00145] Figure 3 shows scanning electron microscope (SEM) micrographs of the untreated tooth neck sample and figure 4 shows an SEM micrograph of a tooth neck sample that has been treated with the calcium carbonate suspension reacted on the surface of Example 1. While the open dentin tubules are clearly visible in the untreated sample shown in figure 3, figure 4 evidences that the dentin tubules were effectively closed by treatment with the inventive surface-reacted calcium carbonate suspension. Example 5 - Resistance to acid challenge
    [00146] The bovine tooth neck sample was prepared by treating a bovine tooth neck sample with surface-reacted calcium carbonate from Example 3 according to the procedure in Example 4. The obtained tooth neck sample was soaked. for 10 s in a 0.2 M acetic acid solution. Subsequently, the toothpaste sample was rinsed with tap water.
    [00147] As a comparative example, the bovine tooth neck sample was prepared as described in Example 4, but by using a ground calcium carbonate from Avenza-Carrara, Italy (average particle size by weight dso = 2.6 µm , commercially available from Omya AG, Switzerland) instead of surface-reacted calcium carbonate.
    [00148] Tooth neck samples before and after treatment with acetic acid were pasted into an SEM sample container and examined by a Sigma VP field emission scanning automatic microscope (Carl Zeiss AG, Germany) and an electronic detector variable pressure secondary (VPSE) with a chamber pressure of about 50 Pa.
    [00149] Figure 5 shows a scanning electron microscope (SEM) micrograph of a tooth neck sample being treated with the inventive surface-reacted calcium carbonate from Example 5 prior to acid treatment and figure 6 shows an SEM micrograph of such a tooth neck sample after acid treatment. Figure 7 shows a scanning electron microscope (SEM) micrograph of a tooth neck sample being treated with the comparative ground calcium carbonate prior to acid treatment and Figure 8 shows an SEM micrograph of such a tooth neck sample after acid treatment. While the closed dentin tubules are clearly visible to the inventive sample in figure 5, figure 7 evidences that using the comparative ground calcium carbonate the dentin tubules are partially closed or not fully closed. Furthermore, it can be deduced from Figure 8 that the comparative ground calcium carbonate was removed from the tooth surface and dentin tubules almost completely by the acid treatment. In contrast, the inventive sample shown in Figure 6 shows that the dentin tubules are still closed by the inventive reacted calcium carbonate on the surface after acid treatment. These results demonstrate that the inventive surface-reacted calcium carbonate is resistant to an acid challenge from the typical beverage or dish that may be consumed following use of the product.
    权利要求:
    Claims (17)
    [0001]
    1. Surface-reacted calcium carbonate for use as a medicine, characterized by the fact that surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid, the hair. at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, the molar ratio of the at least one acid to the carbonate of natural or synthetic calcium is 0.05 to 4, and carbon dioxide is formed in situ by acid treatment and/or is supplied from an external source.
    [0002]
    2. Surface-reacted calcium carbonate for use in the treatment of dentin hypersensitivity, characterized by the fact that surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid , the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, the molar ratio of the at least one acid to natural or synthetic calcium carbonate is 0.05 to 4, and carbon dioxide is formed in situ by acid treatment and/or is supplied from an external source.
    [0003]
    3. Surface-reacted calcium carbonate for use according to claim 1 or 2, characterized in that the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, oxalic acid and mixtures thereof and most preferably the at least one acid is phosphoric acid.
    [0004]
    4. Surface-reacted calcium carbonate for use according to any one of claims 1 to 3, characterized in that the surface-reacted calcium carbonate is in the form of particles having an equal volume mean grain diameter (D50) at or less than 3 µm, preferably from 1.5 to 2.9 µm, more preferably from 1.7 to 2.7 µm and most preferably from 2.2 to 2.6 µm and/or a cut-off particle size of top determined by volume (D98) equal to or less than 6 µm, preferably from 3.5 to 5.5 µm and more preferably from 4.5 to 5 µm.
    [0005]
    5. Surface-reacted calcium carbonate for use according to any one of claims 1 to 4, characterized in that the surface-reacted calcium carbonate is in the form of particles having a specific surface area of 5 m2/g at 200 m2/g, more preferably 20 m2/g to 80 m2/g and even more preferably 30 m2/g to 60 m2/g, measured using nitrogen and the BET method in accordance with ISO 9277.
    [0006]
    6. Surface-reacted calcium carbonate for use according to any one of claims 1 to 5, characterized in that at least one active agent is associated with the surface-reacted calcium carbonate, preferably the active agent is at least one additional desensitizing agent and more preferably the at least one additional desensitizing agent is selected from the group consisting of potassium nitrate, gluteraldehyde, silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, chloride strontium, strontium acetate, arginine, hydroxyapatite, sodium calcium phosphosilicate, potassium oxalate, calcium phosphate, calcium carbonate, bioactive glasses and mixtures thereof.
    [0007]
    7. Surface-reacted calcium carbonate for use according to any one of claims 1 to 6, characterized in that the surface-reacted calcium carbonate is obtained by a process comprising the steps of: a) providing a suspension of natural or synthetic calcium carbonate, b) adding at least one acid having a pKa value of 0 or less at 20°C or having a pKa value of 0 to 2.5 at 20°C to the suspension of step a) and c) treating the suspension from step a) with carbon dioxide before, during or after step b).
    [0008]
    Surface-reacted calcium carbonate for use according to any one of claims 1 to 7, wherein the surface-reacted calcium carbonate is obtained by a process comprising the steps of: A) providing a natural calcium carbonate or synthetic, B) provide at least one water-soluble acid, C) provide gaseous CO2, D) contact said natural or synthetic calcium carbonate from step A) with the at least one acid from step B) and with the CO2 from step C), characterized by the fact that: E) the at least one acid from step B) has a pKa greater than 2.5 and less than or equal to 7 at 20°C, associated with the ionization of its first available hydrogen and a corresponding anion is formed on the loss of its first available hydrogen capable of forming a water-soluble calcium salt eF) ) keeps contacting the at least one acid with natural or synthetic calcium carbonate, at least one water-soluble salt, which , in case a hydrogen-containing salt has a pKa greater than 7 at 20°C, assoc combined with the ionization of the first available hydrogen and the salt anion which is capable of forming water-insoluble calcium salts is additionally provided.
    [0009]
    9. Oral care composition for use as a medicine, characterized in that it comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide. carbon and at least one acid, the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, the molar ratio The at least one acid to natural or synthetic calcium carbonate is 0.05 to 4, and carbon dioxide is formed in situ by acid treatment and/or is supplied from an external source.
    [0010]
    10. Oral care composition for use in the treatment of dentin hypersensitivity, characterized in that it comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a natural or synthetic calcium carbonate reaction product with carbon dioxide and at least one acid, the at least one acid is selected from the group consisting of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, the molar ratio of at least one acid to natural or synthetic calcium carbonate is 0.05 to 4, and carbon dioxide is formed in situ by acid treatment and/or is supplied from an external source.
    [0011]
    11. Oral care composition for use according to claim 9 or 10, characterized in that the oral care composition comprises from 1 to 20% by weight, preferably from 1.5 to 15% by weight, more preferably from 2 to 10% by weight of the surface-reacted calcium carbonate, based on the total weight of the composition.
    [0012]
    12. Oral care composition for use according to any one of claims 9 to 11, characterized in that the oral care composition is a toothpaste, a dental powder or a mouthwash and wherein preferably calcium carbonate Surface-reacted is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and phosphoric acid.
    [0013]
    13. Oral care composition for use according to any one of claims 9 to 12, characterized in that the oral care composition comprises at least one additional desensitizing agent, preferably selected from the group consisting of potassium nitrate, gluteraldehyde , silver nitrate, zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, strontium acetate, arginine, hydroxyapatite, sodium calcium phosphosilicate, potassium oxalate, calcium phosphate, calcium carbonate calcium, bioactive glasses and mixtures thereof.
    [0014]
    14. Oral care composition for use according to any one of claims 9 to 13, characterized in that the oral care composition comprises a bioadhesive polymer, preferably selected from the group consisting of hydroxyethyl methacrylate, PEG/PPG copolymers , polyvinylmethylether/maleic anhydride copolymers, polyvinylpyrrolidone (PVP), crosslinked PVP, shellac, polyethylene oxide, methacrylates, acrylate copolymers, methacrylic copolymers, vinylpyrrolidone/vinyl acetate copolymers, polyvinyl caprolactam adhesives, polylactic resins, silicones silicone, chitosan, milk proteins (casein), amelogenin, ester gum and combinations thereof.
    [0015]
    15. Oral care composition for use according to any one of claims 9 to 14, characterized in that the surface-reacted calcium carbonate has a radioactive dentin abrasion (RDA) value of less than 70, preferably less than 50 and more preferably less than 35.
    [0016]
    16. Oral care composition for use according to any one of claims 9 to 15, characterized in that the oral care composition has a pH between 7.5 and 10, preferably between 8 and 9.
    [0017]
    17. Oral care composition, characterized in that it comprises a surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid and in which the surface-reacted calcium carbonate is in the form of particles having a top-cut particle size determined by volume (d98) equal to or less than 6 µm, wherein the at least one acid is selected from the group that consists of hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid and mixtures thereof, the molar ratio of at least one acid to natural or synthetic calcium carbonate is 0, 05 to 4, and carbon dioxide is formed in situ by acid treatment and/or is supplied from an external source.
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    同族专利:
    公开号 | 公开日
    ES2777504T3|2020-08-05|
    US20170157171A1|2017-06-08|
    RU2674030C2|2018-12-04|
    EP2921173A1|2015-09-23|
    ZA201607255B|2018-05-30|
    JP2017508812A|2017-03-30|
    TW201536336A|2015-10-01|
    US10463693B2|2019-11-05|
    JP6352520B2|2018-07-04|
    CA2941527C|2018-07-03|
    TWI615154B|2018-02-21|
    EP3119408B1|2019-12-18|
    IL247634A|2020-06-30|
    IL247634D0|2016-11-30|
    BR112016021680A2|2018-12-04|
    PL3119408T3|2020-06-29|
    AU2015233384B2|2017-08-03|
    KR20160134795A|2016-11-23|
    CN106132421A|2016-11-16|
    CL2016002258A1|2017-02-10|
    US20200061105A1|2020-02-27|
    CA2941527A1|2015-09-24|
    MX361430B|2018-12-06|
    CN106132421B|2021-01-29|
    SG11201607509RA|2016-10-28|
    WO2015140308A1|2015-09-24|
    DK3119408T3|2020-03-16|
    UY36035A|2015-10-30|
    EP3119408A1|2017-01-25|
    RU2016141139A|2018-04-24|
    AU2015233384A1|2016-09-22|
    MX2016011700A|2017-04-25|
    AR099786A1|2016-08-17|
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    法律状态:
    2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2020-10-20| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
    2021-02-17| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]|
    2021-02-23| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-04-27| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-01| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 20/03/2015, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    EP14161064.2A|EP2921173A1|2014-03-21|2014-03-21|Surface-reacted calcium carbonate for desensitizing teeth|
    EP14161064.2|2014-03-21|
    PCT/EP2015/055962|WO2015140308A1|2014-03-21|2015-03-20|Surface-reacted calcium carbonate for desensitizing teeth|
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