A composition comprising a phosphinic acid or salt thereof and a carrier system

Abstract

This invention relates to a composition comprising phosphonic acid or its salt and a carrier system, oral care products comprising the composition, and the use thereof, particularly toothpaste or mouthwash.

Description

[0001] This invention relates to a composition comprising phosphonic acid or its salt and a carrier system, oral care products comprising the composition, and the use thereof, particularly toothpaste or mouthwash.

[0002] The importance of dental care is constantly increasing, largely due to the rise in carbohydrate-rich diets globally. Beyond aesthetics, there is a growing emphasis on preventative care, particularly regarding reducing or even preventing plaque, cavities, and halitosis, as well as maintaining healthy gums.

[0003] In particular, healthy gums are characterized by surrounding the teeth in the neck region. In this context, the gums encircle the tooth neck, thus sealing the interface between the teeth and the jawbone within the oral cavity. Therefore, the gums, in particular, function to protect the teeth and hold them in place.

[0004] Natural teeth consist of a crown, neck, and root, each composed of multiple layers. In healthy teeth, only the outer enamel (dental enamel) is visible, surrounding the dentin and deeper layers. Enamel is very hard, allowing you to bite or grind food without damaging the tooth. It is approximately 97 wt.% composed of hydroxyapatite (HAP), which has the molecular formula Ca5(PO4)3(OH). Dentin is also considered the hardest tooth tissue and is composed of about two-thirds hydroxyapatite. In addition to hydroxyapatite, dentin also contains proteins (such as collagen) and water, which is why it is softer than enamel.

[0005] As is well known, saliva contains bioavailable forms of calcium. 2+ and PO4 3- Ion supersaturation leads to remineralization. However, remineralization induced by saliva is not only slow, but also clearly insufficient to protect people from tooth decay and / or remineralization of existing dental lesions without the addition of mineralizing additives.

[0006] Dental diseases such as tooth decay can be caused by the formation of bacterial microfilms and / or bacterial inflammation. Although tooth decay is often preventable with preventative care, it remains one of the most common chronic diseases among children and adults worldwide, and there is an urgent need for products that prevent and treat the teeth affected by tooth decay.

[0007] Dental caries is considered a multifactorial disease, with the involvement of microorganisms, particularly affecting tooth enamel and dentin. In the first step, deposits, also known as pellicles, can form on the tooth surface by salivary proteins and other substances. The rougher the tooth surface, the easier it is for these deposits to form or adhere to it. Over time, this pellicle then forms a membrane several micrometers thick, covering the tooth surface. Bacteria can then multiply and spread on this membrane. This membrane can be considered a biofilm.

[0008] Bacteria can produce organic acids such as gluconic acid and lactic acid from low-molecular-weight carbohydrates commonly found in today's foods. Both these organic acids produced by bacteria and dietary acids (such as glycosides) can lead to the erosion of hard tooth tissues.

[0009] Among other things, calcium phosphate in the enamel dissolves. If this process is not stopped or preferably even reversed, it can lead to demineralization of the enamel and optionally the dentin. Structural defects of the tooth caused in this way are called caries, and caries of the dentin layer, for example, can be identified by yellow to brown discoloration of the corresponding area of ​​the tooth. While caries affecting only the enamel can often be mitigated or eliminated by remineralization of the enamel, caries affecting layers other than the enamel usually requires removal of the damaged portion of the tooth and filling the resulting cavity (caries) with a filling material.

[0010] In summary, the formation of dental caries can be promoted by the interaction of the following factors: - Specific bacteria that attach to the surface membrane - Poor tooth quality or poor tooth mineral quality Dental plaque - Foods containing low-molecular-weight carbohydrates - time.

[0011] Therefore, one way to prevent tooth decay is to ingest calcium phosphate compounds, especially hydroxyapatite, to improve tooth quality. In addition, there are various other methods, all aimed at preventing tooth decay to avoid the aforementioned treatments. Currently, the standard for tooth decay prevention is considered to be the use of fluoride dental care products. A review article in JM Ten Cate: "Contemporary perspective on the use of fluoride products in caries prevention," British Dental Journal, February 23, 2013, vol. 214, no. 4, pp. 161-167, describes the use and mechanism of action of fluoride dental care products such as toothpaste and mouthwash.

[0012] Regarding fluoride dental care products, it is particularly noted that the reduction of tooth decay is achieved through the regular use of fluoride dental care products. The model here assumes that fluoride accelerates the natural remineralization process in saliva.

[0013] Various fluoride compounds, such as sodium fluoride, stannous fluoride, amine fluoride, and sodium monofluorophosphate, are suitable sources of fluoride for the aforementioned dental care products. JM ten Cate: "The Need for Antibacterial Approaches to Improve Caries Control," Adv Dent Res 21:8-12, August 2009, pp.8-12, describes how fluoride alone may not be sufficient for adequate caries prevention because, as mentioned above, bacteria also play a decisive role in caries formation. For this reason, caries prevention compositions containing one or more antimicrobial substances in addition to fluoride are being considered. One such substance is chlorhexidine (CHX), whose antimicrobial properties in the oral cavity have been investigated in numerous studies.

[0014] However, the use of fluoride in dental care products is controversial due to concerns about negative side effects. One example is dental fluorosis, caused by excessive fluoride intake during tooth formation. Acute toxic effects include nausea, vomiting, and diarrhea. Other examples include bone fluorosis, characterized by thickening of the outer layer of bone and associated loss of bone elasticity and toughness, and enamel fluorosis, which appears as white enamel patches on the tooth surface. Furthermore, ingestion of high doses of dental care products has been reported to cause acute fluoride poisoning, especially in children, and can sometimes be fatal. A recent evaluation of in vivo studies by the U.S. Department of Health and Human Services' National Toxicology Program clearly found that the more fluoride a mother was exposed to during pregnancy, the lower her child's IQ.

[0015] Furthermore, the WHO has not established recommended daily fluoride intake levels because fluoride is not considered an essential micronutrient. Therefore, there are neither diagnostic criteria nor supporting evidence of clinical symptoms attributable to 'fluoride deficiency'.

[0016] In dental care, particularly for caries prevention, the use of antimicrobial agents such as chlorhexidine is controversial. It has been reported that the effects of caries prevention are not always reproducible and occur only in a limited number of cases. Furthermore, the antimicrobial effect of chlorhexidine is not limited to caries-causing bacteria in the oral cavity but also includes beneficial bacteria. In addition, long-term use of chlorhexidine-containing products can lead to undesirable side effects such as tooth discoloration and taste disturbances.

[0017] Biomimetic toothpastes and mouthwashes containing artificial enamel (which may contain the active ingredient hydroxyapatite) are also known. Hydroxyapatite-based products can reduce initial bacterial colonization on the enamel surface without possessing antimicrobial properties that could disrupt the oral microbial balance. Furthermore, these products are designed to promote remineralization and repair micro-defects in the enamel, as well as form a protective layer.

[0018] Furthermore, biomimetic dental care products based on the use of hydroxyapatite are also known. For example, WO 2018 / 024649A1, DE 10 2017 009 626 A1 and DE 10 2018 102 365 describe oral care compositions containing synthetic hydroxyapatite, wherein, as described above, hydroxyapatite is a bioactive and biocompatible material having a chemical composition similar to that of hydroxyapatite in human tooth enamel.

[0019] Given the aforementioned limitations of both the body's salivary homeostasis mechanisms and fluoride-based methods for caries prevention and remineralization, there is a need for alternative oral care compositions that are at least as effective as fluoride in promoting mineralization, while avoiding the unwanted side effects associated with fluoride use.

[0020] In addition, there is still a need for compositions and oral care products for the treatment or prevention of various diseases that damage teeth.

[0021] Furthermore, when using the provided compositions and oral care products, the oral cavity's ecological balance should not be significantly disturbed, and / or there should be no risk of tooth discoloration or taste disturbance.

[0022] Therefore, the object of the present invention is to produce a composition, and particularly an oral care product, especially toothpaste or mouthwash, having one or more biomimetic or bio-inspired active ingredients, specifically for the prevention of tooth decay, which avoids the disadvantages of the prior art described above.

[0023] Specifically, a composition or oral care product, particularly toothpaste or mouthwash, is provided that mineralizes existing minor caries and / or repairs microscopic defects in tooth enamel. Furthermore, it should be able to apply a protective layer to teeth and / or seal open dentinal tubules. To this end, the aforementioned effects should be achieved while avoiding the disadvantages that may be associated with the use of fluoride. In addition, it should advantageously reduce bacterial adhesion to tooth enamel without significantly disrupting the oral cavity's ecological balance and / or posing a risk of tooth discoloration or taste disturbance. The composition, and particularly the oral care product, should also not irritate the oral mucosa.

[0024] These objectives are achieved by compositions according to the invention, and particularly by oral care products according to the invention, comprising hypophosphonic acid and / or hypophosphonates, especially calcium hypophosphite (Ca(H2PO2)2). Furthermore, at least one compound selected from the group consisting of remineralizing agents, antibacterial agents, moisturizing or conditioning agents, desensitizing agents, and cleansing agents may also be included.

[0025] Therefore, a first aspect of the present invention relates to a composition, particularly an oral care product, comprising: (A) Phosphocyanic acid and / or phosphite salts, particularly calcium hypophosphite (Ca(H2PO2)2), and (B) A carrier system having a pH value between 3.0 and 9.0.

[0026] Hypophosphonic acid, also known as hypophosphoric acid, is a type of phosphoric acid with the molecular formula H3PO2. Its salts are called hypophosphonates or hypophosphites. According to the present invention, salts of hypophosphonic acid are preferred. Divalent salts of hypophosphonic acid are particularly preferred, with calcium hypophosphite (Ca(H2PO2)2) being particularly preferred.

[0027] Preferably, the composition according to the invention comprises a phosphonate, and particularly calcium hypophosphite, in each case in an amount of 0.00001 to 40.0 wt.%, preferably 0.0001 to 20.0 wt.%, more preferably 0.001 to 15 wt.%, more preferably 0.01 to 15 wt.%, particularly preferably 0.1 to 8 wt.%, and particularly 2.5 wt.%, based on the total weight of the composition.

[0028] In the compositions according to the invention, calcium hypophosphite is preferably present in a dissolved or predominantly dissolved state, and more preferably in a completely dissolved state. The solubility of calcium hypophosphite in water is known to be approximately 154 g / L (Robertson, DSMagnesium or calcium hypophosphite could be a treatment for obesity inhumans. Med. Hypotheses 2006, 66, 439-440). Therefore, it is preferred that all calcium hypophosphite in the compositions according to the invention is present in a dissolved state, with a concentration of at most 154 g / L. Preferably, the compositions according to the invention comprise dissolved calcium hypophosphite, particularly at a concentration of 0.0001 to 154 g / L, more preferably 0.001 to 154 g / L, even more preferably 0.01 to 150 g / L, even more preferably 0.1 to 150 g / L, particularly preferably 1 to 80 g / L, and particularly 25 g / L.

[0029] The carrier system according to the invention comprises at least one substance selected from remineralizing agents, antibacterial agents, moisturizing or conditioning agents, desensitizing agents, and abrasives. Furthermore, the carrier system according to the invention may also comprise any mixture of these substances.

[0030] A particularly preferred embodiment provides a support system comprising at least one calcium phosphate. Generally, calcium phosphate, also known as tricalcium orthophosphate or tricalcium phosphate (Ca3(PO4)2), is the calcium salt of orthophosphate and belongs to the phosphate group. The term tricalcium phosphate is sometimes used for the very similar compound pentacalcium triphosphate (Ca5(PO4)3·OH) (=hydroxyapatite).

[0031] According to the present invention, in addition to calcium hypophosphite, at least one calcium phosphate compound is preferably present, preferably in particulate form, and selected from the group consisting of: monocalcium phosphate monohydrate (MCPM), anhydrous monocalcium phosphate (MCPA), dicalcium phosphate dihydrate (DCPD, calcium phosphate), anhydrous dicalcium phosphate (DCPA, triclinic calcium phosphate), octacalcium phosphate (OCP), and α-tricalcium phosphate (α-TCP). β-Tricalcium phosphate (β-TCP), amorphous calcium phosphate (ACP; also known as CPP-ACP complex = casein phosphopeptide-amorphous calcium phosphate), amorphous calcium phosphate (ACP), calcium-deficient hydroxyapatite (CDHA), hydroxyapatite (HA or HAP), tetracalcium phosphate (TTCP), and calcium pyrophosphate, preferably selected from the group consisting of: monocalcium phosphate monohydrate (MCPM), anhydrous monocalcium phosphate (MCPA), dicalcium phosphate dihydrate (DCPD, permeapatite), anhydrous dicalcium phosphate (DCPA, triclinic calcium phosphate), octacalcium phosphate (OCP), amorphous calcium phosphate (ACP; also known as CPP-ACP complex = casein phosphopeptide-amorphous calcium phosphate), amorphous calcium phosphate (ACP), calcium-deficient hydroxyapatite (CDHA), hydroxyapatite (HA or HAP), and tetracalcium phosphate (TTCP), and any mixtures of these compounds. Hydroxyapatite is particularly preferred. At least one calcium phosphate compound can exist in different crystal forms, including mixtures of these crystal forms, wherein a predominantly globular crystal form is preferred over a predominantly acicular crystal form (e.g., needle-shaped crystals). They can also exhibit different crystal and aggregate sizes, exist in mixed forms, and have different degrees of crystallinity, also in mixed forms.

[0032] According to the invention, hydroxyapatite is particularly preferred. However, depending on the intended use of the compositions described herein, embodiments that do not contain any other calcium phosphate compounds besides calcium hypophosphite, and particularly do not contain hydroxyapatite, are also preferred according to the invention.

[0033] Hydroxyapatite is also known as hydroxyapatite. Therefore, these terms can be used interchangeably in this document. It is a phosphate mineral that crystallizes in a hexagonal crystal system. Furthermore, hydroxyapatite is a member of the apatite group and forms a mixed batch with chlorapatite and fluorapatite.

[0034] For example, DE 10 2016 114 189.5 describes Ca5(PO4)3(OH) suitable for use according to the invention. The Ca5(PO4)3(OH) used according to the invention is preferably produced synthetically. This means that the Ca5(PO4)3(OH) used according to the invention is preferably not obtained by calcining organic components from animal materials such as bone.

[0035] According to the present invention, compositions or oral care products each comprising calcium hypophosphite and hydroxyapatite are particularly preferred.

[0036] The calcium phosphate compounds used according to the invention can exist in pure form, in the form of substituted compounds, and as mixtures thereof. According to the invention, a pure form exists when the ions contained in each calcium phosphate compound are substituted by one or more other ions in each case by less than 1%, preferably less than 0.5%, and even more preferably less than 0.1%. For example, in pure hydroxyapatite, Ca... 2+ Ions are, for example, Mg 2+ or Zn 2+ The amount of the substitute is less than 1%, preferably less than 0.5%, and even more preferably less than 0.1%.

[0037] Furthermore, it is preferred that the calcium phosphate compound is free from any doping, such as zinc carbonate doping. However, doped calcium phosphate compounds may also be used.

[0038] X-ray diffraction based on volume of calcium phosphate compounds 50 The value is from 1.0 nm to 100.0 µm, preferably from 10 nm to 10.0 µm, more preferably from 50 nm to 1 µm, and particularly preferably from 100 nm to 5500 nm, wherein X is based on the volumetric particle size distribution. 50 The value is measured by laser diffraction. The aspect ratio (length to width ratio) of the maximum length of the calcium phosphate compound particles, as determined by transmission electron microscopy (TEM) images, is preferably in the range of 1-20, more preferably 2-15, and even more preferably 4-10.

[0039] For this purpose, the calcium phosphate compound sample was first sonicated for 9 minutes in an ultrasonic homogenizer with an energy output of 96 W, and then sonicated for another 3 minutes in a sample preparation apparatus. Subsequently, particle size distribution was measured (laser diffraction) in a particle size analyzer at a temperature of 25℃ ± 0.3℃, and the corresponding values ​​were calculated according to Mie theory. Only commercially available instruments were used.

[0040] In a preferred embodiment of the invention, the calcium phosphate compound is Ca5(PO4)3(OH) and has a hexagonal lattice, wherein the length of the α-axis is 0.930 to 0.950 nm, preferably 0.933 to 0.948 nm, particularly preferably 0.936 to 0.945 nm; and the length of the c-axis is 0.680 to 0.700 nm, preferably 0.682 to 0.696 nm, particularly preferably 0.685 to 0.692 nm. The lengths of the α-axis and c-axis are determined by Rietveld analysis of the corresponding X-ray powder diffraction patterns. The X-ray powder diffraction patterns themselves are obtained by measurements using a conventional powder diffractometer under conventional settings.

[0041] In a preferred embodiment of the invention, at least one calcium phosphate compound exists in aggregate form. In this context, aggregation is understood to mean that molecules or particles combine to form a larger entity, i.e., an aggregate. This combination or aggregate is caused and held together by various forces and / or various types of bonds such as ionic bonds, van der Waals forces, intermolecular forces, or other types of chemical bonds. The degree of aggregation, as well as the size of the aggregate, can be determined using scanning electron microscopy.

[0042] The compositions or oral care products according to the invention comprise a calcium phosphate compound, wherein the amount of the calcium phosphate compound is 0.01 to 80 wt.%, preferably 0.1 to 20 wt.%, particularly preferably 1 to 10 wt.%, and especially 1 to 5 wt.%, based on the total weight of the oral care product. For mouthwash, the preferred amount of the calcium phosphate compound is 1 to 5 wt.%, and for toothpaste, the preferred amount is 10 to 20 wt.%, in each case based on the total weight.

[0043] In addition to calcium hypophosphite and / or hydroxyapatite, the compositions or oral care products according to the invention may also contain at least one other calcium compound, preferably selected from the group consisting of: calcium carbonate, calcium chloride, calcium bromide, calcium nitrate, calcium acetate, calcium gluconate, calcium lactate, calcium tartrate and their hydrates and mixtures thereof, preferably calcium carbonate.

[0044] The carrier system according to the invention preferably has a viscosity in the range of 0 to 150,000 mP. . Between s (mPas).

[0045] In embodiments of the invention relating to pastes, and particularly toothpaste, the viscosity is preferably in the range of 0-150,000 mPas, more preferably between 5,000-120,000 mPas, and particularly preferably in the range of 10,000-90,000 mPas (in each case, determined 0-4 days after manufacture).

[0046] In embodiments of the invention relating to solutions, and particularly mouthwashes, the viscosity is preferably in the range of 0-1,000 mPas, more preferably between 0-500 mPas, and particularly preferably in the range of 10-150 mPas (in each case, determined 0-4 days after manufacture).

[0047] All viscosity data are based on measurements taken in a flat-plate geometry using a Haake RheoStress1 rheometer (ThermoFisher Scientific) at 20°C and shear rates of 10 / s (toothpaste) and 50 / s (mouthwash) in accordance with DIN 53019-1:2008-09.

[0048] The carrier system according to the invention has a pH value between 3.0 and 9.0. The pH value is preferably in the range of 4.0 to 8.0, and particularly between 5.0 and 7.0.

[0049] pH adjusters can be used to adjust the pH value. A pH adjuster is a substance that can adjust the pH value within a specific range, preferably from pH 5.5 to 8.0.

[0050] Examples of pH adjusters include acetic acid, acetates, lactic acid, lactate, malic acid, malate, fumaric acid, citric acid, citrate, tartaric acid, tartrate, orthophosphate, diphosphate, triphosphate and polyphosphate, hydrochloric acid, chloride, sulfuric acid, sulfate, hydroxide, oxide, adipic acid, adipic acid salt, gluconic acid, gluconate, phosphoric acid, calcium carbonate or their hydrates. A preferred example of a pH adjuster that can be added when a lower pH is desired is phosphoric acid (H3PO4).

[0051] In the context of this invention, it has been unexpectedly discovered that calcium hypophosphate effectively remineralizes tooth enamel and dentin, protecting them from tooth decay. In particular, it is also effective in remineralizing chalky teeth and / or teeth affected by fluoride poisoning. Unexpectedly, the remineralization effect is significantly higher than that of other calcium compounds. Furthermore, it has been unexpectedly discovered that calcium hypophosphate possesses significant antimicrobial properties against bacteria that cause tooth decay and periodontitis, and is also effective in preventing tooth sensitivity.

[0052] Surprisingly, a synergistic effect was found when combined with hydroxyapatite. The addition of calcium hypophosphite unexpectedly and significantly increased the remineralization properties of the active ingredient, hydroxyapatite.

[0053] A composition comprising calcium hypophosphite, hydroxyapatite, and additional antibacterial substances is particularly preferred.

[0054] The composition comprising calcium hypophosphite, hydroxyapatite, and moisturizing or conditioning substances as described herein is a preferred embodiment of the invention.

[0055] The composition comprising calcium hypophosphite, hydroxyapatite, and a cleaning agent as described herein represents a preferred embodiment of the invention.

[0056] During the teeth cleaning process, cleaning agents, typically used in conjunction with a toothbrush, remove plaque and harmful bacteria from the tooth surface and provide a whitening effect. Toothpaste contains abrasives or cleaning agents in amounts up to 15% or more based on the total weight of the toothpaste. Examples of abrasives are chalk, marble powder, and / or silicate compounds such as silica. The most commonly used abrasives globally are polysilicic acid (hydrated silica / silica) and calcium carbonate. A drawback is that, with the exception of calcium phosphate compounds (such as hydroxyapatite), all types of cleaning agents are exogenous and do not correspond to the natural tooth mineral (hydroxyapatite). For example, cleaning agents with high relative hardness can cause irreparable damage to hard tooth tissue. If the cleaning agent has too low a hardness, the overall cleaning performance of the toothpaste formulation may be too low to effectively remove plaque during brushing (increasing the risk of cavities and periodontitis).

[0057] The composition comprising calcium hypophosphite, hydroxyapatite, and gingival care substances as described herein constitutes a preferred embodiment of the invention.

[0058] The above-mentioned active ingredients and groups of active ingredients can be combined with calcium hypophosphite, and in particular calcium hypophosphite and hydroxyapatite, freely and independently.

[0059] Anionic, nonionic, cationic, and zwitterionic surfactants can be used as surfactants, but nonionic surfactants are often avoided due to their adverse effects on antibacterial compounds; cationic and zwitterionic surfactants are also often avoided because they can stain or darken teeth. Therefore, anionic surfactants are preferred as cleaning components in compositions or oral care products, wherein sodium lauryl sulfate and other higher alkyl sulfates having 10 to 18 carbon atoms in the alkyl residue are preferred, although other known sulfonated and sulfonated surfactants may also be used in whole or in part.

[0060] Preferably, the composition or oral care product contains at least one surfactant selected from the group consisting of taurine salts, glycine salts, sarcosinate salts and quaternary ammonium compounds, preferably sodium methylcocoyl taurate, sodium cocoyl glycinate, sodium lauroyl sarcosinate, benzalkonium chloride, cetylpyridinium chloride, or any mixture thereof.

[0061] Preferably, the composition or oral care product contains less than 10 wt.% poloxamer, also known as pluronic acid, a nonionic surfactant. Particularly preferred is that the composition or oral care product is substantially free of pluronic acid. "Substantially free" in this application means "<10 ppm".

[0062] Preferably, the composition or oral care product contains no more than 10.0 wt.% calcium gluconate.

[0063] In a preferred embodiment of the invention, the composition or oral care product contains a peroxide, preferably in an amount of 0.00001-40 wt.%, more preferably 0.0001-6 wt.%, and particularly preferably 0.001-0.1 wt.%. In this case, the peroxide is preferably selected from the group consisting of hydrogen peroxide, urea peroxide, sodium percarbonate, and calcium peroxide, and any mixture thereof; particularly preferred are hydrogen peroxide or urea peroxide.

[0064] In a preferred embodiment of the invention, the composition or oral care product contains about 0.1 wt.%, particularly preferably 0.1 wt.%, of hydrogen peroxide.

[0065] In other preferred embodiments of the invention, the composition or oral care product contains less than 0.1% hydrogen peroxide, and is particularly preferred to be substantially free of hydrogen peroxide.

[0066] As described herein, aspects of the invention relate to an oral care product comprising the composition described herein. The oral care product is preferably toothpaste, oral gel, or mouthwash. The terms "composition according to the invention" and "oral care product" are used interchangeably herein, provided that the composition according to the invention is intended for oral use or buccal application.

[0067] The compositions according to the invention are preferably intended for external application, particularly in the oral cavity.

[0068] Toothpaste, also known as dental cream, is used in conjunction with a toothbrush to mechanically clean teeth and gums, and is a soft or semi-solid composition for oral use. Oral gels are used in the same manner but have a gel-like composition. Mouthwash, also known as mouthwash, is a liquid preparation that can be used, in particular, for the prevention of tooth decay and other oral diseases. Oral care products according to the invention are available for use on teeth and / or for rinsing clean. Compositions according to the invention can also be present as dental varnishes or polishing pastes.

[0069] However, since sodium lauryl sulfate can also irritate mucous membranes at concentrations exceeding 1.0% by weight, oral care products according to the invention may also be free of sodium lauryl sulfate and, instead, free of surfactants, or contain other surfactants that cause less mucous membrane irritation than sodium lauryl sulfate, such as taurine salts (preferably sodium methylcocoyl taurate), glycinates (preferably sodium cocoyl glycinate), sarcosinates (preferably sodium lauroyl sarcosinate), or quaternary ammonium compounds (preferably benzalkonium chloride or cetylpyridinium chloride). Specifications for each surfactant also include all its variants (different alkyl chains, branches in the alkyl chain, anti-charge ions, etc.). Surfactants are important for toothpaste because they help distribute the active ingredients in the oral cavity during brushing. Surfactants are also important for consumer convenience.

[0070] Furthermore, it has been unexpectedly found that the oral care products according to the invention advantageously mineralize smaller caries lesions and / or repair minor defects in enamel, especially in patients with dry mouth / low saliva production. Additionally, the compositions according to the invention can be used to form a protective layer on teeth, and it has also been found that tooth enamel exhibits favorable solubility and acid resistance after application of the compositions according to the invention. Furthermore, the compositions of the invention can omit antimicrobial substances (such as chlorhexidine) as excipients. This ensures excellent caries prevention without, for example, interfering with / disrupting the bacterial balance in the oral cavity and without the risk of unpleasant side effects.

[0071] Furthermore, it has been unexpectedly found that the oral care product according to the invention prevents tooth decay and is also capable of remineralizing lesions down to deeper layers of the tooth (particularly the enamel). Additionally, the oral care product according to the invention can be used to apply a protective layer to the teeth and exposed dentin, and particularly to seal open dentinal tubules. Furthermore, it has been found that after application, the enamel exhibits a significant reduction or is no longer detectable in structural damage. Moreover, this oral care product completely eliminates the need for fluoride. This ensures the aforementioned positive aspects without, for example, interfering with / disrupting the bacterial balance in the oral cavity and without the risk of adverse side effects that may occur when using fluoride-containing oral care products (see above). The subject of this invention is an oral care product for the mineralization and remineralization of teeth, particularly enamel and dentin, and, in the case of so-called mineralization defects, non-mineralized tooth components. For example, this includes "molar incisor hypomineralization" (MIH, also known as "chalky teeth"). Alternatively, chalky teeth are also referred to in the art as "molar hypomineralization" (MH). Therefore, these terms can be used interchangeably in this article.

[0072] The oral care product according to the present invention is intended for daily use, applied 1-3 times daily.

[0073] In the case of oral care products in the form of oral gels, spitting is not required, but absorption can occur over a longer period of time, preferably between 5 minutes and 12 hours, and most preferably between 10 minutes and 1 hour. Due to its gel composition, the direct adhesion of calcium hypophosphite to the teeth (enamel, dentin, cementum) is supported, allowing for direct contact between calcium hypophosphite and the teeth over a longer period, thereby achieving a high remineralization rate. The oral gel according to the invention is preferably used 1-3 times daily, particularly preferably once daily. It is preferably used at night. In other embodiments, it may also be applied once a week.

[0074] Oral care products may also be substantially free (preferably free) of fluoride and / or tin salts and / or chlorhexidine and / or triclosan. "Free" in the context of this invention means that compositions according to the invention may contain unavoidable impurities of substances designated as "free". "Substantially free" in the context of this application means "<10 ppm".

[0075] The oral care products according to the present invention can be used for tooth remineralization and protection.

[0076] It has been found that the oral care products according to the present invention can be used to treat and / or prevent a variety of dental diseases.

[0077] In a preferred embodiment of the invention, the oral care product according to the invention can be used to treat (dental) diseases / conditions selected from dental caries, tooth erosion, tooth wear, abrasion, bruxism, hypomineralization of molars and incisors (MIH; chalky teeth), hereditary enamel hypoplasia, dentinogenesis imperfecta, and fluoride poisoning.

[0078] The term dental caries is familiar to those skilled in the art. Dental caries is generally understood as a destructive disease of the hard tooth tissues, enamel, and dentin.

[0079] Tooth erosion refers to damage to the hard tissues of teeth caused by acid. In other words, defects in the enamel and / or dentin are caused by tooth erosion, which can lead to irreversible damage if treated too late.

[0080] (Tooth) wear refers to the loss of hard tooth tissue due to friction. Abrasion is a subtype of wear, namely the loss of hard tooth tissue due to reflexive contact between teeth.

[0081] Bruxism is an unconscious grinding or clenching of the teeth, usually at night, but also during the day. This not only wears down the teeth, but also the periodontal tissues and masticatory muscles.

[0082] Mineral hypomineralization of molars and incisors (MIH), also known as "chalky teeth," is a disorder of enamel formation, that is, structural damage to the enamel.

[0083] Hereditary enamel hypoplasia is considered a genetic disorder that causes enamel formation disorders. Therefore, teeth have an increased risk of tooth decay and are particularly sensitive to temperature.

[0084] Dentinogenesis imperfecta is an autosomal dominant inherited dental malformation / structural disorder, affecting approximately 1 in 8,000 people, and causing severe tooth wear.

[0085] (Dental) fluoride poisoning (also known as dental fluorosis) is a non-inflammatory disease (“mottled teeth”) caused by excessive fluoride intake, particularly during individual tooth development. It has been found that use according to the invention can prevent the aforementioned (dental) disease and / or at least significantly slow its progression and / or achieve complete repair of tooth material, particularly hard tooth tissue. In particular, it has been found that by use according to the invention or after its application, tooth enamel exhibits a significant reduction or no longer detectable structural damage.

[0086] In a preferred embodiment, the oral care product according to the invention can be used for both cosmetic and medical purposes. This means, for example, that it can be used not only to treat the aforementioned (dental) conditions, but also for cosmetic purposes, such as improving the appearance of teeth.

[0087] In a preferred embodiment, the oral care product according to the invention is used by people of all ages, including children, preferably children aged 6 months to 14 years, and particularly children aged 10 months to 12 years.

[0088] In a preferred embodiment, the Ca5(PO4)3(OH) contained in the oral care product according to the present invention is the only apatite component in the oral care product.

[0089] In a preferred embodiment, the oral care product according to the invention comprises 0.01 to 80 wt.%, preferably 0.2 to 40 wt.%, more preferably 0.5 to 30 wt.%, and particularly 1.0 to 20 wt.% of a calcium phosphate compound. In a preferred embodiment, the oral care product according to the invention may contain 1 wt.%, 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.%, 15 wt.%, 20 wt.%, or 25 wt.% of a calcium phosphate compound.

[0090] Preferably, the composition comprises one or more pharmaceutical or cosmetic ingredients, such as xylitol, antimicrobial substances, pH adjusters, abrasives, flavoring agents, and humectants, particularly xylitol, pH adjusters, abrasives, and flavoring agents.

[0091] Xylitol can minimize the number of cariogenic bacteria and inhibit their growth. Furthermore, xylitol stimulates saliva production. Increased saliva production leads to an increase in phosphate levels. This phosphate can react with calcium (ions) in the oral care product according to the invention to form hydroxyapatite. The oral care product according to the invention may contain xylitol in an amount of 0.01 to 15 wt.%, preferably 1.0 to 10.0 wt.%, particularly about 7.0 wt.%, based on the total weight of the oral care product. In addition to xylitol, the oral care product according to the invention may also contain other sugar alcohols, such as sorbitol.

[0092] Antimicrobial substances are substances capable of killing microorganisms such as bacteria or significantly reducing their proliferation. In addition to antimicrobial substances that provide non-specific defense against bacteria and fungi, there are also substances that act only against specific bacteria. For example, the use of antimicrobial substances can also address halitosis. Preferably, the antimicrobial substance may be included in the oral care product according to the invention at an amount of 0.01 to 2.0 wt.%, preferably 0.05 to 1.0 wt.%.

[0093] In another preferred embodiment, the oral care product according to the invention comprises a pH adjuster, the amount of which is 0.05 to 3.0 wt.%, more preferably 0.1 to 2.5 wt.%, and particularly preferably 0.2 to 1.5 wt.%, based on the total weight of the oral care product in each case.

[0094] In a preferred embodiment, the oral care product according to the invention comprises one or more flavoring agents capable of providing a desired flavor. One or more of these flavoring agents may be natural flavoring agents, natural equivalent flavoring agents, synthetic flavoring agents, and / or mixtures thereof.

[0095] Flavoring agents may be included in the oral care product according to the invention, preferably in an amount of 0 to 5 wt.%, preferably 0.1 to 3 wt.%, based on the total weight of the oral care product according to the invention.

[0096] A humectant is an additive that prevents the oral care product according to the invention from drying out by incorporating added water during manufacturing (i.e., preventing evaporation) or by absorbing moisture from the air during storage. Examples of humectants are glycerin, propane-1,2-diol, hexane-1,2-diol, egg yolk, aloe vera gel, honey, molasses, and especially glycerin and hexane-1,2-diol. Preferably, the humectant may be included in the oral care product according to the invention, in an amount of 0 to 25 wt.%, preferably 0.1 to 20 wt.%, based on the total weight of the oral care product according to the invention.

[0097] In a preferred embodiment, the oral care product according to the present invention comprises: - 0.01 to 80 wt.%, preferably 0.2 to 40 wt.%, more preferably 0.5 to 30 wt.%, particularly 1.01 to 20 wt.% of a calcium phosphate compound, preferably hydroxyapatite, - 0.00001 to 30.0 wt.%, preferably 0.0001 to 10.0 wt.%, and particularly preferably 0.0005 to 5.0 wt.%, especially 2.5 wt.% of calcium hypophosphate. - 0.3 to 3 wt.% of a surfactant, preferably about 1.0 wt.% of sodium cocoyl glycinate or sodium methyl cocoyl taurate. - 0.5 to 15 wt.%, preferably 1 to 10 wt.%, particularly about 7.0 wt.% of xylitol, - 0 to 2.0 wt.%, preferably 0.01 to 2.0 wt.%, more preferably 0.05 to 1.0 wt.%, of antimicrobial substances, particularly cetylpyridinium chloride and / or zinc chloride, - 0 to 5 wt.%, preferably 0.3 to 2.0 wt.%, of a pH adjuster, particularly phosphoric acid. - 0 to 5 wt.%, preferably 0.1 to 3 wt.%, of flavoring agent. - 0 to 25 wt.%, preferably 0.1 to 20 wt.%, of a humectant, particularly glycerin and / or hexane-1,2-diol. The figures expressed in wt.% refer to the total weight of the oral care products. The remainder is distilled water, if necessary.

[0098] If the oral care product is in the form of an oral gel, it contains a gelling agent, which is composed of synthetic and / or natural polymer materials.

[0099] Advantageously, the gelling agent is selected from the group consisting of cellulose and cellulose derivatives, such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, agarose, agar, pectin, sclerotium gum, xanthan gum, guar gum, carrageenan, alginate, polyvinyl alcohol, polyvinylpyrrolidone, and mixtures thereof.

[0100] Preferably, such oral gel contains a gelling agent in an amount of 1.0 to 4.0 percent by weight based on the total weight of the oral gel in each case, particularly preferably 1.5 to 3.0 percent by weight and particularly about 2.0 percent by weight.

[0101] Other aspects of the invention relate to the use of the compositions described herein for the treatment of skin diseases. In this embodiment, the compositions according to the invention particularly preferably comprise a divalent salt of hypophosphonic acid, particularly calcium hypophosphite (Ca(H2PO2)2), but without hydroxyapatite.

[0102] It is particularly preferred for use in the treatment of skin diseases, as well as diseases of mucous membranes, hair and / or nails.

[0103] Topical application is preferred. Topical application may be in the form of, for example, ointment, cream, solution, or drops.

[0104] Therefore, topical treatments for the skin and scalp are particularly preferred.

[0105] Example The present invention is illustrated by the following examples.

[0106] Embodiments of the composition of the oral care product in toothpaste form according to the present invention (in wt.%):

[0107] Study 1: Remineralizing tooth enamel with toothpaste (in situ) The experimental design is similar to: K. Najibfard, K. Ramalingam, I. Chedjieu, BT Amaechi, Remineralization of early caries by a nano-hydroxyapatite dentifrice, J. Clin. Dent. 22 (2011) 139-43.

[0108]

[0109] result:

[0110] Study 2: Remineralizing tooth enamel with mouthwash (in vitro) The experimental design is similar to: P. Tschoppe, DL Zandim, P. Martus, AM Kielbassa, Enamel anddentine remineralization by nano-hydroxyapatite toothpastes, J. Dent. 39(2011) 430-437.

[0111] (Modification compared to the cited literature: Instead of toothpaste, this paper tests different mouthwashes.)

[0112] result:

[0113] Study 3: Remineralization of chalky teeth with toothpaste (MIH) (in vitro) The experimental design is similar to: BT Amaechi, R. Farah, JA Liu, TS Phillips, BI Perozo, Y.Kataoka, F. Meyer, J. Enax, Remineralization of molar incisorhypomineralization (MIH) with a hydroxyapatite toothpaste: an in-situ study, BDJ Open 8 (2022) 33.

[0114]

[0115] result:

[0116] Study 4: The effectiveness of toothpaste for sensitive teeth (in vivo) The experimental design is similar to: G. Orsini, M. Procaccini, L. Manzoli, F. Giuliodori, A. Lorenzini, A.Putignano, A double-blind randomized-controlled trial comparing the desensitizing efficacy of a new dentifrice containing carbonate / hydroxyapatite nanocrystals and a sodium fluoride / potassium nitratedentifrice, J. Clin. Periodontol. 37 (2010) 510-517.

[0117]

[0118] result:

[0119] This invention is summarized in the following terms: 1. A composition comprising: (A) Phosphinoic acid and / or at least one phosphoate, and (B) A carrier system having a pH value between 3.0 and 9.0.

[0120] 2. The composition according to Clause 1, wherein the carrier system (B) has a viscosity between 0 and 150,000 mP.s.

[0121] 3. The composition according to clause 1 or 2, wherein the carrier system (B) comprises at least one calcium phosphate.

[0122] 4. The composition according to any one of the preceding clauses, wherein the carrier system (B) comprises hydroxyapatite.

[0123] 5. The composition according to any one of the preceding clauses, wherein the pH value is in the range of 4 to 7.

[0124] 6. The composition according to any one of the preceding clauses, wherein the phosphonate (A) is divalent.

[0125] 7. The composition according to any one of the preceding clauses, wherein the hypophosphite (A) is a calcium salt, namely calcium hypophosphite, particularly dissolved calcium hypophosphite.

[0126] 8. The composition according to any one of the preceding clauses, wherein the composition comprises 0.00001 to 40.0 wt.%, particularly 0.001 to 20 wt.%, preferably 0.01 to 15 wt.%, particularly preferably 0.1 to 8 wt.% of calcium hypophosphate.

[0127] 9. The composition according to any one of the preceding clauses, wherein the composition is designed for external application.

[0128] 10. The composition according to any one of the preceding clauses, wherein the carrier system (B) comprises a gelling agent, particularly cellulose and / or xanthan gum or a corresponding derivative.

[0129] 11. The composition according to any one of the preceding clauses, wherein the composition is provided for rinsing after application.

[0130] 12. The composition according to any one of the preceding clauses, wherein the composition is provided for remaining on the teeth after application.

[0131] 13. The composition according to any one of the preceding clauses, wherein the composition comprises one or more organic acids.

[0132] 14. The composition according to any one of the preceding clauses, wherein the composition comprises xylitol.

[0133] 15. The composition according to any one of the preceding clauses, wherein the composition comprises at least one surfactant, said surfactant being derived from the group consisting of taurine salts, sarcosine salts, glycine salts, and alkyl sulfates or mixtures thereof.

[0134] 16. The composition according to any one of the preceding clauses, wherein the composition is substantially free of fluorides.

[0135] 17. The composition according to any one of the preceding clauses, wherein the composition comprises menthol and / or menthol derivatives.

[0136] 18. The composition according to any one of the preceding clauses, wherein the composition comprises silica cleaner, calcium carbonate and / or calcium phosphate.

[0137] 19. The composition according to any one of the preceding clauses, wherein the composition comprises an antimicrobial substance.

[0138] 20. The composition according to any one of the preceding clauses, wherein the composition comprises a gingival care additive.

[0139] 21. Use of the composition according to any one of the preceding clauses for the prevention and / or treatment of dental and / or gingival diseases.

[0140] 22. Use of the composition as described in Clause 21 for the treatment of chalky teeth and / or fluoride poisoning.

[0141] 23. Use of the composition as described in Clause 21 or 22 for the prevention and / or treatment of dental caries.

[0142] 24. Use of the composition according to any one of the preceding clauses for the prevention and / or treatment of tooth sensitivity.

[0143] 25. Use of the composition according to any one of the preceding clauses for teeth whitening.

[0144] 26. Use of the composition according to any one of the preceding clauses for remineralizing teeth.

[0145] 27. Use of the composition according to any one of the preceding clauses for the purpose of protecting teeth from erosion, particularly from exposure to one or more acids.

[0146] 28. The composition according to any one of clauses 1 to 20 is used for the treatment of skin diseases, particularly for topical treatment of the skin and scalp.

[0147] 29. An oral care product comprising the composition according to any one of clauses 1 to 20.

[0148] 30. The oral care product as described in Clause 29, wherein the oral care product is toothpaste, mouthwash, oral gel, dental varnish, or polishing paste.

Claims

1. A composition comprising: (A) Phosphinoic acid and / or at least one phosphoate, and (B) A carrier system having a pH value between 3.0 and 9.

0.

2. The composition according to claim 1, wherein, The carrier system (B) has a viscosity ranging from 0 to 150,000 mP. . Between s.

3. The composition according to claim 1 or 2, wherein, The carrier system (B) contains at least one calcium phosphate and / or hydroxyapatite.

4. The composition according to any one of the preceding claims, wherein, The pH value is in the range of 4 to 7.

5. The composition according to any one of the preceding claims, wherein, The hypophosphite (A) is divalent, and the hypophosphite (A) is preferably a calcium salt, namely calcium hypophosphite, especially dissolved calcium hypophosphite.

6. The composition according to any one of the preceding claims, wherein, The composition comprises 0.00001 to 40.0 wt.%, particularly 0.001 to 20 wt.%, preferably 0.01 to 15 wt.%, and particularly preferably 0.1 to 8 wt.% of calcium hypophosphate.

7. The composition according to any one of the preceding claims, wherein, The composition is designed for external application and is preferably provided for rinsing after application or leaving on the teeth.

8. The composition according to any one of the preceding claims, wherein, The carrier system (B) comprises a gelling agent, particularly cellulose and / or xanthan gum or corresponding derivatives, and / or The composition comprises one or more organic acids and / or xylitol and / or at least one surfactant, wherein the surfactant is derived from the group consisting of taurine salts, sarcosine salts, glycine salts and alkyl sulfates or mixtures thereof.

9. The composition according to any one of the preceding claims, wherein the composition is substantially free of fluorides.

10. The composition according to any one of the preceding claims, wherein the composition comprises menthol and / or menthol derivatives. Silica cleaner, calcium carbonate and / or calcium phosphate, Antimicrobial substances, and / or Gum care additives.

11. Use of the composition according to any one of the preceding claims for the prevention and / or treatment of dental and / or gingival diseases.

12. Use of the composition according to claim 11 for the treatment of chalky teeth and / or fluoride poisoning and / or for the prevention and / or treatment of dental caries and / or tooth sensitivity.

13. Use of the composition according to any one of the preceding claims for the remineralization and / or whitening and / or protection of teeth from erosion, particularly due to exposure to one or more acids.

14. The composition according to any one of claims 1 to 10 is used for the treatment of skin diseases, particularly for topical treatment of the skin and scalp.

15. An oral care product comprising the composition according to any one of claims 1 to 10, wherein, The oral care product is preferably toothpaste, mouthwash, oral gel, dental varnish, or polishing paste.

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