COMPOSITIONS FOR ORAL CARE.

Abstract

This description covers oral care compositions comprising vitamin D, or a derivative thereof; an alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group; and an orally acceptable carrier. Methods for preparing and using these compositions are also described.

Description

ORAL CARE COMPOSITIONS BACKGROUND Periodontal disease results from initial colonization by key pathogens, such as Porphyromonas gingivalis, leading to bacterial dysbiosis and an inflammatory response. Ultimately, this inflammation causes the bone and tooth loss characteristic of periodontal disease. Epidemiological studies have indicated an association between vitamin D deficiency and both chronic and aggressive periodontitis. This may be due to the recently identified relationship between vitamin D and the expression of innate immune mediators and proinflammatory cytokines. The development and validation of a cell-based screening assay to identify LL-37 inducers was described by F. Nylén et al. in Innate Immunity 2014, vol. 20, ed. 4, pp. 364–376. Innate immunity, our first line of defense against pathogens, relies heavily on the production of antimicrobial peptides (AMPs). These peptides exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs include defensins (α and β families) and cathelicidin, LL-37. Bacterial resistance to antibiotics is a growing concern, and new antimicrobial strategies are urgently needed. Therefore, the concept of strengthening immune defenses against infectious microbes by inducing AMP expression may represent novel or complementary pharmaceutical interventions in the treatment or prevention of infections.A robust cell-based indicator assay for LL-37 expression, which serves as a marker of a healthy epithelial barrier, was developed and validated. This indicator assay can be a powerful tool for high-throughput screening tests. Topical vitamin D and oral ubiquinol supplement compositions are described in U.S. Patent No. 9,877,929. A topical vitamin D and ubiquinol supplement composition useful for treating oral inflammation and reducing oxidative stress comprises: a vitamin D and ubiquinol supplement mixture in an aqueous emulsion containing: spilanthes extract, stabilizing compositions for ubiquinol, and transoral mucosal absorption facilitators for the supplement mixture; wherein the emulsion forms a mucoadhesive gel in the presence of saliva, affecting the passive diffusion through the oral mucosa of the supplement mixture, and the spilanthes extract regulating: in vivo availability and immune response of the supplement mixture, and maintaining adequate levels of circulating vitamin D and adjuvantly administered ubiquinol, while minimizing the risk of hypercalcemia. / racnn / zznz / E / YiAi The fluoride-free toothpaste derived from a dietary supplement, and methods of manufacture and use thereof, are described in U.S. Patent Application Publication No. 20180110729. This publication provides a shelf-stable fluoride-free toothpaste composition enriched with a dietary supplement containing both oil-soluble and water-soluble vitamins. The dietary supplement is incorporated into the toothpaste and contains a water-soluble vitamin portion comprising at least one water-soluble vitamin and an oil-soluble vitamin portion comprising at least one oil-soluble vitamin, carrier oil, and an emulsifier.The toothpaste was formulated so that oral application will result in the systemic administration of at least one portion of the dietary supplement to reach an RDI threshold of 2% even when 3 or fewer portion sizes are applied orally. Oral care formulations comprising vitamin D are described in U.S. Patent Application Publication No. 20190076343. The publication describes an oral care product comprising at least one of the following: phytomenadione (vitamin Ki), menaquinone (vitamin K2), vitamin C, selenium, ubiquinone (Coenzyme Q10), Astragalus, Ginseng, Schisandra, adaptogenic herbs, cannabidiol, or similar ingredients. The oral care product is intended to rebalance microbial homeostasis in the mouth, or to establish and maintain a healthy oral microbiome. Vitamin D and the intracrinology of innate immunity are described in M. Hewison, Molec. Cellular Endocrinology, 2010, vol. 321, ed. 2, pp. 103-111. An immunomodulatory role for vitamin D was first proposed before 1985, based on two key observations. First, monocytes / macrophages from patients with the granulomatous disease sarcoidosis were shown to constitutively synthesize the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), from the precursor 25-hydroxyvitamin D (25OHD). Second, the 1,25(OH)2D receptor (vitamin D receptor, VDR) is detectable on proliferative activated lymphocytes. These observations suggested a mechanism by which 1,25(OH)2D produced by monocytes could act on adjacent To B lymphocytes, but the impact of such a system on normal regulation of the immune system was uncertain.In fact, only in recent years has a much clearer picture emerged of the role of vitamin D as a determinant of immune responsiveness. Two concepts have driven this shift. First, innate immunity studies have demonstrated that the intracrine induction of antimicrobial activity by vitamin D is a fundamental component of the monocyte / macrophage response to infection. Second, it is now clear that suboptimal vitamin D status is a common feature in many populations worldwide, with the potential to compromise monocyte / macrophage metabolism of 25OHD and the subsequent actions of 1,25(OH)2D. The publication described the details of these new developments with specific reference to the metabolic and signaling mechanisms associated with vitamin D regulation of innate immunity and the implications for human disease. The association between serum 25-hydroxyvitamin D concentrations and gingival inflammation was proposed in T. Dietrich et al., Am. J. Clin. Nutr. 2005, vol. 82, ed. 3, pp. 575-580. Data from 77,503 gingival units (teeth) in 6,700 never-smokers aged 13 to >90 years from the third National Health and Nutrition Examination Survey were analyzed. Multiple logistic regression models adjusted for site- and subject-specific covariates included age, sex, race / ethnicity, income, body mass index, diabetes, oral contraceptive use and hormone replacement therapy among women, vitamin C intake, missing teeth, full crown coverage, presence of calculus, frequency of dental visits, and dental examiner and survey phase. Generalized estimating equations were used to account for correlated observations within subjects.Compared with sites in subjects in the lowest 25(OH)D quintile, sites in subjects in the highest 25(OH)D quintile were 20% (95% CI; 8%, 31%) less likely to gingival probing bleeding (P for trend < 0.001). The association appeared to be linear across the 25(OH)D range, was consistent across all racial and ethnic groups, and was similar between men and women, as well as between users and non-users of vitamin and mineral supplements. It has been concluded that vitamin D may reduce susceptibility to gingival inflammation through its anti-inflammatory effects and that gingivitis may be a useful clinical model for evaluating the anti-inflammatory effects of vitamin D. The effects of one year of vitamin D and calcium supplementation on chronic periodontitis were described in M. N. García et al., Journal of Periodontology, 2011, vol. 82, no. 1, pp. 25-32. Fifty-one patients enrolled in maintenance programs at two dental clinics were recruited. Of these, 23 were receiving vitamin D (>400 µU / day) and calcium supplementation (>1000 mg / day), and 28 were not. All subjects had at least two interproximal sites with >3 mm of clinical attachment loss. For mandibular posterior teeth, the gingival index, plaque index, probing depth, attachment loss, bleeding on probing, calculus index, and furcation involvement were assessed. Posterior bitewing radiographs with photostimulable phosphor were taken to evaluate the alveolar bone. Daily intake of vitamin D and calcium was calculated using nutritional analysis.Data were collected at baseline, 6 months, and 12 months. Total daily intakes of calcium and vitamin D were 1769 mg (95% confidence interval, 1606 to 1933) and 1049 IU (781 to 1317) in the drug group, and 642 mg (505 to 779) and 156 IU (117 to 195) in the non-drug group, respectively (P < 0.001 for both). Clinical parameters of periodontal health improved over time in both groups (P < 0.001). When clinical measurements were considered collectively, the differences between supplement recipients and non-recipients had the following P-values: at baseline (P = 0.061), 6 months (P = 0.049), and 12 months (P = 0.114). After adjustment for covariates, the P-values ​​for the effect of supplementation were as follows: baseline (P = 0.028); 6 months (P = 0.034); and 12 months (P = 0.058).Calcium and vitamin D supplementation (<1000 µU / day) had a modest positive effect on periodontal health, and consistent dental care improved clinical parameters of periodontal disease, independent of these supplements. Our findings support the possibility that vitamin D may have a positive impact on periodontal health and confirm the need for randomized clinical trials on the effects of vitamin D on periodontitis. V. Nizet and R.L. Gallo analyzed cathelicidins and innate defense against invasive bacterial infection in Scand. J. Infect. Dis. 2003, vol. 35, ed. 9, pp. 670-676. Cathelicidins are small cationic peptides that possess broad-spectrum antimicrobial activity. These genetically encoded “natural antibiotics” are produced by several mammalian species on epithelial surfaces and within the granules of phagocytic cells. Since their discovery more than a decade ago, it has been speculated that cathelicidins function within the innate immune system, contributing to the host’s first line of defense against a variety of microorganisms. Consequently, cathelicidins have attracted the interest of basic researchers in the diverse fields of cell biology, immunology, protein chemistry, and microbiology.A growing body of experimental research now appears to confirm and expand upon the biological importance of these fascinating molecules. This article reviews the latest advances in our understanding of cathelicidin antimicrobial peptides, with particular emphasis on their role in defense against invasive bacterial infection and their associations with human diseases. Calcitriol derivatives and their uses are described in U.S. Patent No. 5,952,317. Calcitriol can therefore be regulated to provide controlled release of vitamin D in vivo over time by changing or modifying the hydrolyzable groups. Structurally, the key feature of modified vitamin D compounds with desirable biological attributes is that they are derivatives of 25-dihydroxyvitamin D3, or derivatives of 25-dihydroxyvitamin D analogues, in which a hydrolyzable group is attached to the hydroxyl group at carbon 25 and, optionally, to any of the other hydroxyl groups present in the molecule. Depending on various structural factors, e.g.The type, size, and structural complexity of the attached group suggest that these derivatives are hydrolyzed to 25-dihydroxyvitamin D3, or to a 25-dihydroxyvitamin D3 analogue, at different rates in vivo, thus providing a slow release of the biologically active vitamin D compound (i.e., 1,25-dihydroxyvitamin D3 or an analogue thereof) in the body. The slow-release in vivo activity profiles of such compounds can be further modulated by the use of mixtures of derivatives (e.g., mixtures of different 1,25-dihydroxyvitamin D3 derivatives, or different derivatives of 1,25-dihydroxyvitamin D analogues) or by the use of mixtures consisting of one or more vitamin D derivatives together with chemically modified molecules derived from 1,25(OH)2D3. Whole-molecule modifications have been made to obtain analogues with the desired properties. The use of 1,25-dihydroxyvitamin D3 analogs as immunomodulatory agents has been analyzed by C. Mathieu and L. Adorini in Trends in Molecular Medicine. The active form of vitamin D, 1,25-dihydroxyvitamin D3 (i.e., 1,25(OH)2D3), is a seco-steroid hormone that regulates calcium and bone metabolism, controls cell proliferation and differentiation, and exerts immunoregulatory activities. This range of functions has been exploited clinically to treat a variety of conditions, from secondary hyperparathyroidism and osteoporosis to autoimmune diseases such as psoriasis. Recent advances in understanding the functions of 1,25(OH)2D3 and novel insights into the mechanisms of its immunomodulatory properties suggest broader applicability of this hormone in the treatment of autoimmune diseases and allograft rejection. Although much progress has been made in the technique of formulating oral care compositions with respect to improving their ability to treat diseases, many more challenges remain. BRIEF DESCRIPTION OF THE INVENTION The present invention relates to an oral care composition comprising: vitamin D, or a derivative thereof. Certain embodiments of the present invention may further comprise a humectant (e.g., sorbitol). In some embodiments, the sorbitol is in the form of a sorbitol solution. The sorbitol solution is a liquid aqueous wetting vehicle comprising sorbitol. In some embodiments, the sorbitol solution is a sorbitol syrup. In some embodiments, the sorbitol solution comprises from about 30% to about 80% by weight of the oral care composition. Sorbitol is a sugar alcohol with a sweet taste that the human body metabolizes slowly. Sorbitol can be obtained by reducing glucose, which changes the aldehyde group to a hydroxyl group. In some embodiments, the compositions of the present invention comprise an abrasive. In some embodiments, the abrasive comprises silica. The silica particle may be prepared by any means known or to be developed in the art, and may be surface-modified, if desired, to increase the particle's ability to adhere to a tooth surface. In one embodiment, the silica comprises precipitated silica. Precipitated silica is an amorphous form of silica (silicon dioxide, SiO2), which is a white powder material. In one embodiment, the silica comprises fumed silica. Examples of silica include ZEODENT® silica, SYLODENT® silica, Tixosll® silica, and SORBOSIL silica. In some embodiments, the compositions of the present invention comprise thickening silica. In some embodiments, the weight ratio of the thickening silica to the abrasive silica is between 1:4 and 1:0.25. In one embodiment, vitamin D is selected from the group consisting of: vitamin D1, ergocalciferol, lumisterol, vitamin D2, vitamin D3, cholecalciferol, vitamin D4, 22-dihydroergocalciferol, vitamin D5, sitocalciferol, calcitriol, vitamin D compounds with hydroxyl groups at carbon positions 1, 3, and 25, 1α,25-dihydroxyvitamin D3 esters, 1,25-dihydroxyvitamin D3 esters, 1,25(OH)2D3, 1,25(OH)2D3 analogues, 25(OH)D3, 25(OH)D3 analogues, and mixtures thereof. In certain embodiments, vitamin D is cholecalciferol. Vitamin D3 is cholecalciferol, also known as cholecalciferol. Cholecalciferol is a type of vitamin D produced by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement. Cholecalciferol is used to treat conditions associated with vitamin D deficiency, familial hypophosphatemia, hypoparathyroidism (which causes low blood calcium levels), and Fanconi syndrome. Cholecalciferol is produced in the skin following exposure to UV-B light (approximately 280-315 nm). In the liver, cholecalciferol is converted to calcifediol, or 25-hydroxyvitamin D, which is then converted in the kidneys to calcitriol, or 1,25-dihydroxyvitamin D. One of the actions of cholecalciferol is to increase calcium absorption in the intestines. The present invention provides an oral care composition that can be used to prevent a pathological condition by reinforcing the antimicrobial peptides (AMPs) of the host tissue in the oral cavity. Antimicrobial peptides, also called host defense peptides, play an important role in the innate immune response found in all forms of life. Such peptides can be potent, broad-spectrum antibiotics that show potential as novel therapeutic agents. The present invention also relates to a method for strengthening the host tissue antimicrobial peptide in the oral cavity by applying toothpaste to a portion of the oral cavity. i racnn / zznz / E / YiAi Data demonstrate that topical application of the active form of vitamin D (1,25(OH)2D3) to gingival epithelial cells (GECs) induces enhanced expression of antimicrobial peptide protein (LL-37) and thus helps maintain innate defense in oral gingival cells. The data also show that GECs are capable of converting the inactive form to the active form. Therefore, it is hypothesized that topical application of both inactive and active vitamin D directly to GECs may have a general therapeutic effect on the etiology and development of periodontal disease. In some embodiments, the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof. BRIEF DESCRIPTION OF THE FIGURES Figure 1 illustrates the LL-37 induction provided by certain embodiments of the present invention. Figure 2 illustrates the induction of CYP24A1 provided by certain embodiments of the present invention. Figure 3A and Figure 3B illustrate the benefits provided by certain embodiments of the present invention in a tissue model. DETAILED DESCRIPTION For illustrative purposes, the principles of the present invention are described by reference to various illustrative embodiments thereof. Although certain embodiments of the invention are specifically described herein, a person skilled in the art will readily recognize that the same principles are equally applicable and may be employed in other embodiments. Before explaining in detail the embodiments of the present invention that are described, it should be understood that the invention is not limited in its application to the details of any particular embodiment shown. The terminology used herein is for descriptive purposes and not for limitation. As used herein and in the appended claims, the singular forms “a,” “one,” and “the” include plural reference unless otherwise dictated by the context. The singular form of any class of ingredients refers not only to a single chemical species within that class but also to a mixture of such chemical species; for example, the term “vitamin D” in the singular form may refer to a mixture of compounds, each of which is also considered a vitamin D. The terms “a,” “one or more,” and “at least one” may be used interchangeably herein. The terms “comprising,” “including,” and “having” may be used interchangeably. The term “includes” should be construed as including, but not limited to. The term “including” should be construed as including, but not limited to. Abbreviations and symbols as used in this description, unless otherwise indicated, have their ordinary meanings. The abbreviation "% by weight" means percentage by weight. The symbol μI refers to a microliter or 10⁻⁶ liters. The symbol ° refers to a degree, which includes a degree of an angle and degrees Celsius. When referring to chemical structures and names, the symbols C, H, and O stand for carbon, hydrogen, and oxygen, respectively. The symbols and = stand for single and double bonds, respectively. The abbreviations “di”, “mo”, “ppm”, “PBS”, “cDNA”, “RNA”, “qPCR”, “GAPDH”, “USP”, “EP”, “FD&C”, “pH” stand for “days”, “months”, “parts per million”, “phosphate-buffered saline”, “complementary deoxyribonucleic acid”, “ribonucleic acid”, “quantitative polymerase chain reaction”, “glyceraldehyde-3-phosphate dehydrogenase”, “United States Pharmacopeia”, “European Pharmacopoeia”, “food, drug and cosmetics”, and the negative logarithm of the molar concentration of hydronium ions, respectively. For ease of reading, vitamin D1, vitamin D2, vitamin D3, vitamin D4, and vitamin D5 are typeset as vitamin D1, vitamin D2, vitamin D3, vitamin D4, and vitamin D5, respectively. The term "approximately" when referring to a number means any number within a 10% range of the number. For example, the phrase "approximately 0.050% by weight" refers to a number between 0.04500% and 0.05500% by weight, which includes 0.04500% and 0.05500%. As used throughout the description, intervals are used as shorthand to describe each and every value that falls within the interval. Any value within the interval can be selected as the interval term. The term "mixture" should be interpreted broadly. It refers to a mixture of ingredients. The mixture may be solid, liquid, or semisolid. If a mixture is a liquid, it may be a solution, an emulsion, a dispersion, a mixture exhibiting the Tyndall effect, or any other homogeneous mixture. In one form, the mixture is stable in storage. When referring to a list of ingredients, unless specifically stated otherwise, the term "mixture" refers to a mixture of the aforementioned ingredients with each other, a mixture of any of the aforementioned ingredients with other ingredients not mentioned above, and a mixture of several of the aforementioned ingredients with other ingredients not mentioned above.For example, the term “mixture” in the phrase “the fluoride source is selected from the group consisting of stannous fluoride, sodium fluoride, amine fluoride, sodium monofluorophosphate, and mixtures thereof” refers to any of the following: a mixture of stannous fluoride and sodium fluoride; or a mixture of stannous fluoride and amine fluoride; or a mixture of stannous fluoride and sodium monofluorophosphate; or a mixture of sodium fluoride and amine fluoride; or a mixture of sodium fluoride and sodium monofluorophosphate; or a mixture of amine fluoride and sodium monofluorophosphate; or a mixture of stannous fluoride and any other fluoride source; or a mixture of sodium fluoride and any other fluoride source; or a mixture of amine fluoride and any other fluoride source; or a mixture of sodium monofluorophosphate and any other fluoride source, and other combinations thereof. Any member in a list of species used to illustrate or define a genus may be mutually different from, overlap with, a subset of, equivalent to, nearly equal to, or identical to any other member of the species list. Furthermore, unless explicitly stated, such as when listing a Markush group, the list of species defining or illustrating the genus is open-ended, and it is understood that other species may exist that define or illustrate the genus as well as, or better than, any other species on the list. All references cited in this description are incorporated herein in full. In case of conflict between a definition in this description and that in a cited reference, this description prevails. The present invention relates to an oral care composition comprising, in a significant part, vitamin D, or a derivative thereof. In some embodiments, the present invention provides oral care compositions further comprising a humectant (e.g., sorbitol or glycerin and the like). In some embodiments, the humectant comprises from about 30% to about 80% by weight of the oral care composition. In other embodiments, the humectant comprises from about 40% to about 70% by weight of the oral care composition. In still other embodiments, the humectant comprises from about 50% to about 60% by weight of the oral care composition. In some embodiments, the oral care compositions of the present invention comprise from about 10% by weight to about 70% by weight of water, optionally from about 15% by weight to about 65% by weight, or from about 20% by weight to about 60% by weight, or from about 25% by weight to about 55% by weight, or from about 30% by weight to about 50% by weight, or from about 35% by weight to about 45% by weight of water. i racnn / zznz / E / YiAi In some embodiments, the compositions of the present invention comprise an abrasive. In some embodiments, the abrasive comprises silica. In some embodiments, the silica particle may be prepared by any means known or to be developed in the art, and may be surface-modified, if desired, to increase the particle's ability to adhere to a tooth surface. Examples may be found in, e.g., U.S. Patent Application Publication No. 20070104660, the contents of which are incorporated herein by reference. The silica particle is present in the composition in an amount of 5% or more by weight of the total composition. Alternatively, the silica particle may be present in an amount of 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, or 25% by weight. In some forms, silica comprises precipitated silica. Precipitated silica is an amorphous form of silica (silicon dioxide, SiOs), which is a white, powdery material. Precipitated silica can be produced by precipitation from a solution containing silicate salts. In some embodiments, the oral care compositions of the present invention comprise a thickening agent (e.g., fumed silica). Other thickening agents known to the art may also be suitable for use in the compositions of the present invention. In some forms, the particle size of fumed silica ranges from approximately 5 nm to approximately 50 nm. In some forms, the fumed silica particles are non-porous and have a surface area of ​​50–600 m² / g. In other forms, the fumed silica has a density of 160–190 kg / m³. Examples of silica include ZEODENT® 105-High, ZEODENT® 103, ZEODENT® 113, ZEODENT® 115, ZEODENT® 116, ZEODENT®117, ZEODENT® 120, ZEODENT® 124, ZEODENT® 153, ZEODENT® 163, ZEODENT® 165, ZEODENT® 167, ZEODENT® 168, ZEODENT® 203, ZEODENT®9175, marketed by Evonik; SYLODENT® 750 silica, SYLODENT® 753 silica, SYLODENT® 756 silica, SYLOBLANC® 81 silica, SYLODENT® SM 850C silica, SYLOBLANC® 82 silica, SYLODENT® SM 500T silica, SYLODENT® SM 614T silica, marketed by WR Grace; Tixosil® 63, Tixosil® 73, Tixosil® SoftClean™, Tixosil® 331, Tixosil® 43, marketed by Solvay; SORBOSIL AC33, SORBOSIL AC43, SORBOSIL BFG10, SORBOSIL BFG50, SORBOSIL BFG51, SORBOSIL BFG52, SORBOSIL BFG54, SORBOSIL CBT60S, SORBOSIL CBT70, SORBOSIL BFG100, marketed by PQ Corporation. In some embodiments, the silica comprises Sorbosil AC43 silica, marketed by PQ Corporation. In one embodiment, the AC43 silica has properties including an average particle size of 2.7-4.0 microns (as determined by MALVERN MASTERSIZER), a sieve residue of +45 pm, a moisture loss at 105 °C of 8.0% max., a loss on ignition at 1000 °C of 14.0% max., and a pH of 5.5 to 7.5 in aqueous suspension. In one embodiment, thickening silica is a synthetic amorphous precipitated material with high surface area and internal pore volume to provide water absorption of approximately 50 ml or more / 20 grams of silica and oil absorption of approximately 200 ml or more / 100 g of silica (according to ASTM D281). Examples of thickening silicas that can be used include Zeodent® 165, Zeodent® 163, and Zeodent® 153; Aerosil® 200 and Sident® 22S (marketed by Evonik); Sylodent® 15 and Perkasil® SM 660 (marketed by W.R. Grace & Co.); and MFIL® (marketed by Madhu Silica). India) and Tixocil 43B (marketed by Rhodia). In one embodiment, the silica particles suitable for oral care compositions of the invention include silica particles with, for example, a particle size distribution of 3 to 4 microns, or alternatively, a particle size distribution of 5 to 7 microns, alternatively, a particle size distribution of 3 to 5 microns, alternatively, a particle size distribution of 2 to 5 microns, or alternatively, a particle size distribution of 2 to 4 microns. In one modality, a silica particle has a particle size of 2.0 microns. In one embodiment, a silica particle has a particle size of 2.5 microns. In another embodiment, a silica particle has a particle size of 3.0 microns. In another embodiment, a silica particle has a particle size of 3.5 microns. In another embodiment, a silica particle has a particle size of 4.0 microns. In another embodiment, a silica particle has a particle size of 5.0 microns. In one aspect of the invention, the silica particle size is a medium particle size. In another aspect, the silica particle size is an average (medium) particle size. In one embodiment, the silica particle comprises at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% of the total silica particles in a composition containing silica particles.In one aspect of the invention, the silica particles have a porosity of less than approximately 0.45 cc / g in pores of approximately 600 Angstroms or smaller. In some embodiments, the present invention relates to an oral care composition comprising vitamin D, or a derivative thereof. In some embodiments, the vitamin D, or a derivative thereof, is selected from the group consisting of: vitamin D1, ergocalciferol, lumisterol, vitamin D2, vitamin D3, cholecalciferol, vitamin D4, 22-dihydroergocalciferol, vitamin D5, sitocalciferol, calcitriol, vitamin D compounds with hydroxyl groups at carbon positions 1, 3, and 25, esters of 1α,25-dihydroxyvitamin D3, esters of 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, 1,25(OH)2D3 analogues, 25(OH)D3, 25(OH)D3 analogues, and mixtures thereof. In some forms, vitamin D, or a derivative thereof, is selected from the group consisting of vitamin D1, ergocalciferol, lumisterol, vitamin D2, vitamin D3, cholecalciferol, vitamin D4, 22-dihydroergocalciferol, vitamin D5, sitocalciferol, calcitriol, and mixtures thereof.In other forms, vitamin D, or a derivative thereof, is cholecalciferol. In some forms, vitamin D, or a derivative thereof, is one of a group of fat-soluble seco-steroids that can be used to increase intestinal absorption of calcium, magnesium, and phosphate, and have multiple other biological effects. The main natural source of the vitamin is the synthesis of cholecalciferol in the skin from cholesterol through a chemical reaction that depends on sun exposure (specifically radiation at approximately 280–315 nm). In certain forms, vitamin D, or a derivative thereof, refers to compounds including: vitamin D1, vitamin D2, vitamin D3, vitamin D4, vitamin D5, vitamin D compounds with hydroxyl groups at carbon positions 1, 3 and 25, 1α,25dihydroxyvitamin D3 esters, 1,25-dihydroxyvitamin D3 esters, 1,25(OH)2D3, 1,25(OH)2D3 analogues, 25(OH)D3, 25(OH)D3 analogues and mixtures thereof. The term “vitamin D” in one modality means any one of the compounds vitamin D1, vitamin D2, vitamin D3, vitamin D4, vitamin D5 or any combination thereof. Vitamin D1 is a mixture of the molecular compounds ergocalciferol and lumisterol. In one formulation, vitamin D1 is a 1:1 mixture of ergocalciferol and lumisterol. Vitamin D2 is, or comprises, ergocalciferol, or calciferol. Vitamin D2 is a type of vitamin D found in food and used as a dietary supplement to prevent and treat vitamin D deficiency. This vitamin D deficiency can result from poor absorption by the intestines or from liver disease. Vitamin D2 can also be used for low blood calcium levels due to hypoparathyroidism. Ergocalciferol has the formula i racnn / zznz / E / YiAi i racnn / zznz / E / YiAi Vitamin D3 is, or comprises, cholecalciferol, also known as L-cholecalciferol. Cholecalciferol is a type of vitamin D produced by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement. Cholecalciferol is used to treat diseases associated with vitamin D deficiency (including rickets), familial hypophosphatemia, hypoparathyroidism causing low blood calcium levels, and Fanconi syndrome. Cholecalciferol has the structure Cholecalciferol is produced in the skin after exposure to UV-B light (approximately 280-315 nm). In the liver, cholecalciferol is converted to calcifediol, or 25-hydroxyvitamin D, which is then converted in the kidneys to calcitriol, or 1,25-dihydroxyvitamin D. One of the actions of cholecalciferol is to increase calcium absorption in the intestines. Cholecalciferol is found in foods such as some fish, cheeses, and eggs. Cholecalciferol is inactive on its own. It is converted to its active form through two hydroxylations: the first in the liver, by CYP2R1 or CYP27A1, to form 25-hydroxycholecalciferol (calcifediol, 25-OH vitamin D3). The second hydroxylation occurs primarily in the kidney through the action of CYP27B1 to convert 25-OH vitamin D3 into 1,25-dihydroxycholecalciferol (calcitriol, 1,25-(OH)2 vitamin D3). All of these metabolites bind in the blood to vitamin D-binding protein. The action of calcitriol is mediated by the vitamin D receptor, a nuclear receptor that regulates the synthesis of hundreds of proteins and is present in virtually every cell of the body. Vitamin D4 is 22-dihydroergocalciferol, with the structure i racnn / zznz / E / YiAi Vitamin D5 is sitocalciferol, with the following structure: Since vitamin D3 can be synthesized in adequate amounts by most mammals exposed to sufficient sunlight, it is not an essential dietary factor and, therefore, technically not a vitamin. Instead, vitamin D could be considered a hormone, as activation of the vitamin D prohormone results in the active form, calcitriol, which then exerts its effects through a nuclear receptor at multiple locations. Cholecalciferol is converted in the liver to calcifediol (25,15-hydroxycholecalciferol); ergocalciferol is converted to 25-hydroxyergocalciferol. These two vitamin D metabolites (called 25-hydroxyvitamin D or 25(OH)D) are measured in serum to determine a person's vitamin D status. The kidneys further hydroxylate calcifediol to form calcitriol (also known as 1,25-dihydroxycholecalciferol), the biologically active form of vitamin D.Calcitriol circulates as a hormone in the blood and plays an important role in regulating calcium and phosphate levels, promoting healthy bone growth and remodeling. Calcitriol also has other effects, including those on cell growth, neuromuscular and immune function, and inflammation reduction. It is known that incipient periodontal inflammation, gingivitis, results from the inflammatory reaction to endotoxins released by the presence of bacterial biofilms in the general area of ​​the tooth anatomy. If left untreated, this condition frequently progresses to the more virulent pathological condition known as periodontitis. Frequent use of the supplemental topical vitamin D compositions of the invention provides protection by forming mucoadhesive gels that continuously release the vitamin D composition at the inflamed site. This induces the passive diffusion of vitamin D into the mucosa, which, in turn, increases the production of antimicrobial peptides and elicits a putative therapeutic immunomodulatory response. Periodontal diseases are initiated by a consortium of oral bacteria that trigger local inflammatory responses, leading to bleeding on probing, loss of periodontal attachment, and subsequent bone and tooth loss. They have been linked to systemic conditions, including heart disease, diabetes, obesity, and metabolic syndrome. The association between periodontal diseases and these systemic conditions appears to stem from a low-grade inflammatory burden that links them through a common pathophysiological mechanism. It is possible that locally secreted cytokines and periodontal pathogens can enter the bloodstream and contribute to damage in other parts of the body, and there appears to be some evidence of such a burden. Tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) are key cytokines in the initiation and maintenance of systemic inflammation that have been implicated in the progression and severity of periodontitis. Furthermore, higher serum levels of these cytokines have been observed in patients with periodontitis than in individuals with healthy periodontitis. Vitamin D plays an important role in bone growth and maintenance, which could be beneficial for maintaining periodontal health. Recently, it has been suggested that it has positive effects on periodontal disease, tooth loss, and gingival inflammation, not through its effects on bone metabolism, but through anti-inflammatory mechanisms. Therefore, maintaining adequate serum vitamin D levels through topical vitamin D supplementation could be important in the prevention and treatment of periodontal disease. Vitamin D plays an important role in calcium homeostasis, bone growth, and maintenance. It has been shown to inhibit antigen-induced T-cell proliferation and cytokine production, acting as an immunomodulatory agent. In one embodiment, the present invention provides an oral care composition that can be used to prevent a pathological condition by reinforcing the antimicrobial peptides (AMPs) of the host tissue in the oral cavity. Antimicrobial peptides, also called host defense peptides, play an important role in the innate immune response found in all forms of life. Fundamental differences exist between prokaryotic and eukaryotic cells, which may represent targets for antimicrobial peptides. Such peptides can be potent, broad-spectrum antibiotics that show potential as novel therapeutic agents. Antimicrobial peptides can destroy Gram-negative bacteria, Gram-positive bacteria, enveloped viruses, and fungi. Antimicrobial peptides can have both antimicrobial and mediating functions, providing the initial host defense mechanism.Unlike most conventional antibiotics, antimicrobial peptides can destabilize biological membranes, form transmembrane channels, and may also enhance immunity by acting as immunomodulators. Furthermore, in addition to antimicrobial defense, antimicrobial peptides play an important role in wound healing, reducing inflammation and strengthening the oral mucosal barrier by improving tissue integrity and promoting tissue regeneration. Furthermore, an antimicrobial peptide is a peptide that exhibits antimicrobial activity or a compound that affects microbial activity, meaning a compound that slows or stops the growth and / or proliferation rate, or paralyzes, inactivates, or destroys a microbe. Examples of antimicrobial peptides include antibiotics, antibacterials (e.g., bactericidal or bacteriostatic agents), antivirals (e.g., virucidal agents), antifungals (e.g., fungicidal or fungistatic agents), mold inhibitors, anthelmintics (e.g., vermifuge or vermicide agents), antiparasitics, and the like. Antimicrobial activity can be determined using methods described herein, as well as methods known in the art. In one embodiment, the present invention is directed to a method for strengthening the host tissue antimicrobial peptide in the oral cavity by applying i racnn / zznz / E / YiAi toothpaste to a portion of the oral cavity, wherein the toothpaste comprises the oral care composition comprising: sorbitol solution, silica, and vitamin D. Data show that topical application of the active form of vitamin D (1,25(OH)2D3) to gingival epithelial cells (GECs) induces enhanced expression of antimicrobial peptide proteins (LL-37) and thus helps maintain innate defense in oral gingival cells. However, this active form of vitamin D3 (1,25(OH)2D3) is unstable and expensive. Conventional biology argues that inactive vitamin D (cholecalciferol) is converted to 25(OH)D3 by 25-hydroxylase enzymes found in the liver, and that the circulating form is further activated by the enzyme 1-alpha-hydroxylase to the active form, 1,25(OH)2D3, in the kidney. The data show that GECs are also capable of converting inactive forms to the active form. Therefore, it is hypothesized that topical application of vitamin D, both inactive and active, directly to the GECs may have a general therapeutic effect on the etiology and development of periodontal disease. The data show an enhancement of LL-37 expression in gingival cells by both the inactive and active forms of vitamin D3. HPLC stability analysis data demonstrate a 100% stable recovery of vitamin D3 from the toothpaste formulation, both in fresh samples and in 2-month samples. In one embodiment, the present invention relates to an oral care composition comprising: sorbitol solution, silica, and vitamin D, wherein the oral care composition comprises from approximately 0.001% by weight to approximately 0.100% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.003% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.005% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.01% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.03% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.05% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.001% by weight to approximately 0.1% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.003% to approximately 0.005% by weight of vitamin D. 0.003% by weight to approximately 0.01% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.003% by weight to approximately 0.03% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.003% by weight to approximately 0.05% by weight of vitamin D. In one embodiment, the oral care composition comprises approximately 0.003% by weight to approximately 0.1% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.005% by weight to approximately 0.01% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.005% by weight to approximately 0.03% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.005% by weight to approximately 0.05% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.005% by weight to approximately 0.1% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.01% to approximately 0.03% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.01% to approximately 0.05% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.01% to approximately 0.1% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.03% to approximately 0.05% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.03% to approximately 0.1% by weight of vitamin D. In one formulation, the oral care composition comprises approximately 0.05% to approximately 0.1% by weight of vitamin D. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof. In one embodiment, the present invention relates to an oral care composition comprising: sorbitol solution, silica, and vitamin D, wherein the oral care composition further comprises a blue coloring agent. i racnn / zznz / E / YiAi The orally acceptable blue coloring agent comprises a blue dye that is safe for use in oral care applications, and includes blue dyes from natural sources as well as synthetic dyes approved for use in food or oral care products, e.g., FD&C Blue No. 1 and FD&C Blue No. 2. The dyes for use in the present invention to prepare the water-insoluble bleaching complex may be water-soluble. The term “water-soluble” in this particular context generally means that the dye has an aqueous solubility of at least 10 g / L at 25°C, with the maximum preference being at least 100 g / L at 25°C (where solubility is determined in distilled water without buffer). In specific formulations, the oral care dyes described herein have a maximum absorbance value in the visible spectrum (Amax) at wavelengths ranging from 550 nm to 650 nm, most preferably from 600 nm to 650 nm. The dyes described herein may be blue to blue-green in color with a hue angle in the CIELAB system ranging from 180 to 270 degrees, more particularly from 180 to 200 degrees. The dyes described herein include anionic triphenylmethane dyes and especially diaminotriphenylmethane dyes containing two to four sulfonate groups. An example of a dye useful in this description is FD&C Blue No. 1, also known as Brilliant Blue FCF (Blue 1) and by other trade names. FD&C Blue No. 1 is a colorant used in food and other substances to induce a color change. It is designated by the E number E133 and has a color index of 42090. It appears as a reddish-blue powder. It is soluble in water, and the solution has maximum absorption at approximately 628 nanometers. It is a synthetic dye produced using aromatic petroleum hydrocarbons. It is usually a disodium salt. The diammonium salt has the CAS number [2650-18-2]. Calcium and potassium salts are also known. Additional dyes can be used in conjunction with the blue dye, in order to adjust the precise color absorption as desired. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the coloring agent is a blue coloring agent having a blue to blue-violet color with a hue angle in the CIELAB system ranging from 200 degrees to 320 degrees.

[11109] i racnn / zznz / E / YiAi The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the blue coloring agent is a blue dye present in an amount of approximately 0.02% by weight to approximately 2% by weight, based on the total amount of the oral care composition. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the blue coloring agent comprises at least one of FD&C Blue #1, FD&C Blue #2, D&C Blue #4, Cl Food Blue 5, and Acid Blue 1. As used in this description, the term blue coloring agent refers to a substance in the form of a dry powder or liquid that imparts color to another substance. Coloring agents generally include pigments, dyes, lakes, or combinations thereof. In one respect, the blue coloring agent has a blue to blue-violet color with a hue angle in the CIELAB system ranging from 200 degrees to 320 degrees. In some embodiments, the whitening tooth compositions described herein may include a pigment. As used herein, a pigment is a natural or synthetic water-insoluble substance that imparts color to another substance. In some embodiments, pigments further enhance the whiteness of the teeth. As is known in the art, the visual perception of a white substance can be altered by the deposition of an optical brightener, a blue pigment, or a blue dye. This effect is commonly used in laundry detergents to make white clothing appear "whiter" to the human eye. The same concept has been applied to tooth whitening. See PCT Publication No. 2015 / 099642 to Colgate-Palmolive Company, which is incorporated herein in full by reference. In some forms, the pigment included in the whitening tooth compositions of the present description may have a shade angle, h, in the CIELAB system, ranging from 220 degrees to 320 degrees, typically between 250 degrees and 290 degrees. i racnn / zznz / E / YiAi The pigment used in whitening toothpaste compositions is capable of reflecting light sufficiently so that the treated tooth is noticeably whiter than its initial color. In some formulations, the pigment may be colored so that its natural color falls within the violet-red to green-blue range. More specifically, the pigment may be violet or blue, for example, one of those listed in the International Color Index. These pigments are listed as violet pigment ns1 through violet pigment na56 and blue pigment na1 through na83. In some forms, the violet pigment may be violet pigment ns1, 1:1, 1:2, 2, 3, 5:1, 13, 19, 23, 25, 27, 31, 32, 37, 39, 42, 44 and / or 50. In some forms, the blue pigments may be blue pigment na1, 2, 9, 10, 14, 15, 15:1, 15:2, 15:3, 15:4, 15:6, 16, 18, 19, 24:1, 25, 56, 60, 61, 62 and / or 66. Other suitable pigments are ultramarine blue and ultramarine violet.Typically, the pigment is na15 blue pigment, more typically na15:1, 15:2, 15:3, 15:4, 15:5 or 15:6 blue pigment, most typically 15:1. While single violet or blue pigments can be used in toothpaste compositions, the same effect can be achieved by blending pigments outside the 220- to 320-degree shade angle range. The desired shade angle can instead be obtained by blending a red and a blue-green pigment to produce a blue or violet shaded pigment. The amount of pigment in the whitening toothpaste composition can range from 0.01 to 0.075% by weight, such as 0.05%. In other formulations, the amount of pigment in the whitening toothpaste composition can range from 0.01 to 0.05% by weight or from 0.03 to 0.05% by weight, depending on the total amount of the whitening toothpaste composition. The pigment can be evenly distributed throughout the whitening toothpaste composition or it can be dispersed in a second phase, such as a strip or another coextruded second phase. Such "two-phase" compositions have the advantage that the phases can be of different colors, presenting a more visually appealing product to the consumer. As used herein, the term dye refers to an organic species that is essentially water-soluble in an aqueous medium in which the dye remains chemically stable. The dyes used with the whitening toothpaste composition described herein are generally food color additives currently certified under the Food, Drug, and Cosmetic Act for use in ingested foods and drugs, including dyes such as FD&C Red No. 3 (tetraiodofluorescein sodium salt), FD&C Yellow No. 5 (4-p-sulfophenylazo-1-p-sulfophenyl-5-hydroxypyrazol-3-carboxylic acid sodium salt), FD&C Yellow No. 6 (p-sulfophenylazo-β-naphthol-6-monosulfonate sodium salt), FD&C Green No. 3 (4-{[4-(N-ethyl-psulfobenzylamino)-phenyl]-(4-hydroxyl-2-sulfonyl-phenyl)-methylene}-[1-N-ethyl-Np-sulfobenzyl]-(4-hydroxyl-2-sulfonyl-phenyl)-methylene}-[1-N-ethyl-Np-sulfobenzyl] disodium salt.DELTA.-3,5-cyclohexadienim-ina], FD&C blue no.1 (disodium salt of dibenzyldiethyl-diaminotriphenylcarbinol trisulfonic acid anhydride), FD&C Blue No. 2 (sodium salt of indigotine disulfonic acid), D&C Green No. 5, D&C Orange No. 5, D&C Red No. 21, D&C Red No. 22, D&C Red No. 27, D&C Red No. 28, D&C Red No. 30, D&C Red No. 40, D&C Yellow No. 10 and mixtures thereof in various proportions. In one respect, the blue coloring agent is a blue color dye selected from FD&C Blue n.s1, FD&C Blue n.s2, D&C Blue η.θ4, Patent Blue 5, Acid Blue 1, or a mixture thereof. The amount of one or more of the dyes in the oral care composition may vary widely. For example, the amount of one or more of the dyes in the whitening toothpaste composition described herein may be from 0.02 to 2% by weight, or from 0.02 to 1.5% by weight, or from 0.02 to 1% by weight, or from 0.02 to 0.5% by weight, from 0.02 to 0.15% by weight, or from 0.02 to 0.1% by weight, depending on the total amount of the whitening toothpaste composition. In at least one embodiment, one or more of the dyes may be uniformly distributed throughout the whitening toothpaste composition. In another embodiment, one or more dyes may be distributed in different phases of the whitening toothpaste composition.For example, one or more of the dyes may be arranged or dispersed in a first phase (e.g., a hydrophobic phase) of the whitening tooth composition, and one or more of the remaining dyes, or no dye, may be arranged or dispersed in a second phase (e.g., a hydrophilic phase) of the whitening tooth composition. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the surfactant is selected from the group consisting of water-soluble salts of Cs-20 alkyl sulfates, sulfonated monoglycerides of Cs-20 fatty acids, sarcosinates, taurates, sodium lauryl sulfate, sodium cocoyl monoglyceride sulfonate, and lauryl sarcosinate. sodium, sodium lauryl isoethionate,sodium laureth carboxylate and sodium dodecylbenzenesulfonate, cocoamidopropyl betaine, and mixtures thereof. Additional examples of suitable surfactants include water-soluble salts of higher fatty acid monoglyceride monosulfates, such as sodium salt of monosulfated fatty acid monoglyceride of hydrogenated coconut oil; higher alkyl sulfates such as sodium lauryl sulfate; alkyl aryl sulfonates such as sodium dodecylbenzene sultanate; higher alkyl sulfoacetates such as sodium lauryl sulfoacetate; higher fatty acid esters of 1,2-dihydroxypropane sultanate; and substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic compounds, such as those having 12-16 carbons in the fatty acid, alkyl or acyl radicals; and the like. Examples of amides mentioned above include N-lauroyl sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine.Others include, for example, nonionic polyoxyethylene surfactants, such as Polyoxamer 407, Steareth 30, Polysorbate 20, and castor oil; and amphoteric surfactants, such as cocamidopropyl betaine (tegobaine) and cocamidopropyl betaine lauryl glucoside; condensation products of ethylene oxide with various hydrogen-containing compounds that are reactive with them and have long hydrocarbon chains (e.g., aliphatic chains of 12 to 20 carbon atoms); these condensation products (ethoxamers) contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, and other fatty moieties, and with propylene oxide and polypropylene oxides. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the viscosity modifier is selected from the group consisting of methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl propylcellulose, hydroxybutyl methylcellulose, carboxymethylcellulose, salts thereof, and mixtures thereof. In some embodiments, the compositions of the invention may optionally comprise an additional thickening agent acceptable for the oral route, selected from one or more, but not limited to, carbomers, also known as carboxyvinyl polymers, carrageenans, also known as Irish moss and more particularly carrageenan (carrageenan iota), high molecular weight polyethylene glycols (such as CARBOWAX®, available from The Dow Chemical Company), cellulosic polymers such as hydroxyethylcellulose, carboxymethylcellulose (CMC) and salts thereof, e.g., sodium CMC, natural gums such as karaya, xanthan, gum arabic and tragacanth, colloidal aluminum magnesium silicate, and mixtures thereof. Optionally, such additional thickening agents are present in a total amount of approximately 0.1% by weight to approximately 50% by weight, e.g., from approximately 0.1% by weight ai racnn / zznz / E / YiAi approximately 35% by weight, or from approximately 1% by weight to approximately 15% by weight, depending on the total weight of the composition. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the sweetener is selected from the group consisting of: saccharin, salts thereof, and mixtures thereof. In one embodiment, the composition of the invention comprises at least one sweetener, useful, for example, for improving the flavor of the composition. Any orally acceptable natural or artificial sweetener may be used, including, but not limited to, dextrose, sucrose, maltose, dextrin, dried invert sugar, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup (including high fructose corn syrup and corn syrup solids), partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, intense sweeteners based on dipeptides, cyclamates, and the like. One or more of the sweeteners are optionally present in a total amount that depends largely on the particular sweetener(s) selected, but is typically from 0.005% by weight to 5% by weight, in the total weight of the composition. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the hydrophilic polymer is selected from the group consisting of polyethylene glycol. The present invention also relates to an oral care composition comprising a solution of sorbitol, silica, and vitamin D, wherein the oral care composition further comprises a toothpaste ingredient selected from: a surfactant, a desensitizing agent, a hydrophilic polymer, a tartar control agent, a binder, a thickening agent, a detergent, an adhesion agent, a foam modulator, a pH modifier, a mouthfeel agent, a sweetener, a flavoring agent, a coloring agent, a humectant, a fluoride source, a viscosity modifier, and a mixture thereof, wherein the fluoride source is selected from the group consisting of sodium fluoride, stannous fluoride, sodium fluoride, amine fluoride, sodium monofluorophosphate, and mixtures thereof. In some embodiments, the composition includes a source of fluoride ions. Sources of fluoride ions include, but are not limited to: stannous fluoride, sodium fluoride, potassium fluoride, potassium monofluorophosphate, sodium monofluorophosphate, ammonium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride such as olaflur (N'-octadecyltrimethylethyleneamine-N,N,N'-t(2-ethanol)-dihydrofluoride), ammonium fluoride, and combinations thereof. In certain embodiments, the source of fluoride ions includes stannous fluoride, sodium fluoride, amine fluorides, sodium monofluorophosphate, and mixtures thereof. In certain embodiments, the oral care composition of the invention may also comprise a source of fluoride ions or an ingredient that provides fluoride in sufficient quantities to deliver from about 50 to about 5000 ppm of fluoride ions, e.g.From about 100 to about 1000, from about 200 to about 500, or about 250 ppm of fluoride ions. Sources of fluoride ions may be added to the compositions of the invention at a level of about 0.001 wt% to about 10 wt%, e.g., from about 0.003 wt% to about 5 wt%, from 0.01 wt% to about 1 wt%, or about 0.05 wt%. However, it should be understood that the weights of fluoride salts required to provide the appropriate level of fluoride ion will obviously vary depending on the weight of the counterion in the salt, and a person skilled in the art can readily determine these amounts. A preferred fluoride salt may be sodium fluoride. The present invention also relates to an oral care composition comprising: sorbitol solution, silica, and vitamin D, wherein the oral care composition is a toothpaste. In one modality, the oral care composition is a toothpaste, a liquid, a gel, a whitening strip, or a composition applied to the teeth with a dental tray. In certain modalities, the composition is a toothpaste. In some modalities, the toothpaste is adapted for application to the teeth by brushing. EXAMPLES Example 1 OKF6 cells (gingival epithelial cells) were cultured in 6-well tissue culture plates. The cell monolayer was treated with indicated doses (Figure 1) of vitamin D3 or phenylbutyrate alone or in combinations of the two, and the cells were further incubated in a tissue culture incubator for overnight incubation. After overnight incubation, the cells were collected in RNA lysis buffer. The samples were processed for RNA isolation using the Qiagen RNA isolation kit. The RNA was processed to prepare cDNA and further amplified (qPCR) using TaqMan gene-specific probes LL-37 (Hs 01011708_m1), Cyp24A1 (Hs00989018_m1), and GAPDH (Hs 99999905_m1). The qPCR data were analyzed for the induction of LL-37 expression times, and the relative differences in expression were plotted. These results are described in Figures 1 and 2.As illustrated by the data described in Figures 1 and 2, the inventive combinations of the present invention provide a synergistic increase in LL-37 and CYP24A1, respectively. Example 2 Gingival tissues (GIN 100) were purchased from Mattek Corporation. The tissues were treated in triplicate with vitamin D3, sodium butyrate, or phenyl butyrate, individually or in combination, at the indicated doses, and incubated overnight in a tissue culture incubator. The tissues were harvested, transferred to RNA buffer, and frozen at -70°C. When ready for processing, the tissues were homogenized and processed for RNA isolation and cDNA preparation and amplification by qPCR as previously described using TaqMan probes specific for LL-37 and GAPDH. These results are described in Figures 3A and 3B. As illustrated by the data described in Figures 3A and 3B, the inventive combinations of the present invention provide a synergistic increase in LL-37. Although the present invention has been described with reference to several embodiments, which are set forth in considerable detail for the purpose of providing a complete description of the invention, these embodiments are merely illustrative and are not intended to be a comprehensive enumeration of all aspects of the invention. The scope of the invention will be determined from the appended claims. Furthermore, it will be evident to those skilled in the art that numerous changes may be made to these details without departing from the spirit and principles of the invention.

Claims

1. An oral care composition comprising: vitamin D, or a derivative thereof; an alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a Ci to C13 hydrocarbyl group; and an orally acceptable carrier.

2. The oral care composition according to claim 1, wherein R is R'-(CH2)n-, wherein n = 1 to 3, and R' is H or a C1 to C12 hydrocarbyl group.

3. The oral care composition according to claim 1 or claim 2, wherein the alkanoic acid, or the alkali metal salt thereof, is present in the amount of approximately 300 μM to approximately 10 mM.

4. The oral care composition according to any of the preceding claims, wherein the alkanoic acid, or the alkali metal salt thereof, is present in the amount of approximately 10 pM to approximately 10 mM.

5. The oral care composition according to any of the preceding claims, wherein vitamin D, or a derivative thereof, is selected from: vitamin D1, ergocalciferol, lumisterol, vitamin D2, vitamin D3, cholecalciferol, vitamin D4, 22-dihydroergocalciferol, vitamin D5, sitocalciferol, calcitriol, vitamin D compounds having hydroxyl groups at carbon positions 1, 3 and 25, esters of 1α,25-dihydroxyvitamin D3, esters of 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, 1,25(OH)2D3 analogues, 25(OH)D3, 25(OH)D3 analogues and mixtures thereof.

6. The oral care composition according to any of the preceding claims, wherein vitamin D, or a derivative thereof, is selected from: vitamin D1, ergocalciferol, lumisterol, vitamin D2, vitamin D3, cholecalciferol, vitamin D4, 22-dlhydroergocalciferol, vitamin D5, sitocalciferol, calcitriol, and mixtures thereof.

7. The oral care composition according to any of the preceding claims, wherein the vitamin D, or a derivative thereof, is cholecalciferol.

8. The oral care composition according to the preceding claim, wherein vitamin D, or a derivative thereof, is present in an amount of approximately 0.001% by weight to approximately 0.100% by weight, based on the total weight of the oral care composition.

9. The oral care composition according to any of the preceding claims, wherein vitamin D, or a derivative thereof, is present in an amount of approximately 0.005% by weight to approximately 0.050% by weight, based on the total weight of the oral care composition.

10. The oral care composition according to any of the preceding claims, wherein an alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a Ci to C13 hydrocarbyl group selected from: sodium butyrate, phenylbutyrate, phenylbutyric acid; pyrenbutyric acid; and a combination of two or more of these.

11. The oral care composition according to any of the preceding claims, wherein the alkanoic acid of formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, is selected from: sodium butyrate, phenylbutyrate, phenylbutyric acid; and a combination of two or more of these.

12. The oral care composition according to any of the preceding claims, wherein the alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, comprises sodium butyrate.

13. The oral care composition according to any of the preceding claims, wherein the alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, comprises phenylbutyrate.

14. The oral care composition according to any of the preceding claims, wherein the alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, comprises phenylbutyric acid.

15. The oral care composition according to any of the preceding claims, wherein vitamin D, or a derivative thereof, and alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, are present in an amount effective to provide an anti-inflammatory benefit.

16. The oral care composition according to any of the preceding claims, wherein vitamin D, or a derivative thereof, and alkanoic acid of the formula R-COOH or an alkali metal salt thereof, wherein R is a C1 to C13 hydrocarbyl group, are present in an amount effective to provide a synergistic anti-inflammatory benefit.

17. The oral care composition according to any of the preceding claims, further comprising a source of metal ions.

18. The oral care composition according to claim 17, wherein the metal ion source is selected from: a zinc ion source; a tin ion source; a fluoride ion source; and a combination of two or more of these. 1 racnn / zznz / E / YiAi 19. The oral care composition according to claim 17 or claim 18, wherein the metal ion source comprises a soluble or sparingly soluble compound of tin, zinc or copper with organic or inorganic counterions.

20. The oral care composition according to claim 19, wherein the counterion is selected from: fluoride, chloride, chlorofluoride, acetate, hexafluorozirconate, sulfate, tartrate, gluconate, citrate, malate, glycinate, pyrophosphate, metaphosphate, oxalate, phosphate, carbonate salts, and oxides.

21. The oral care composition according to any one of claims 17 to 20, wherein the metal ion source is selected from: zinc oxide; zinc citrate; zinc phosphate; zinc pyrophosphate; zinc sulfate; stannous fluoride; stannous chloride; stannous gluconate; and a combination of two or more of these.

22. The oral care composition according to any one of claims 17 to 21, wherein the metal ion source comprises zinc oxide and zinc citrate.

23. The oral care composition according to any one of claims 17 to 22, wherein the metal ion source comprises zinc oxide, zinc citrate and a stannous ion source.

24. The oral care composition according to any one of claims 17 to 23, wherein the metal ion source comprises a zinc ion source and stannous fluoride.

25. The oral care composition according to any one of claims 17 to 24, wherein the metal ion source comprises zinc oxide, zinc citrate, and stannous fluoride.

26. The oral care composition according to any one of claims 17 to 21, wherein the metal ion source comprises zinc phosphate and stannous fluoride.

27. The oral care composition according to any of the preceding claims, further comprising an abrasive selected from: a silica abrasive (e.g., fused silica or precipitated silica); a calcium abrasive (e.g., calcium pyrophosphate, calcium carbonate or dibasic calcium phosphate dihydrate); mica; an aluminum abrasive (e.g., aluminum oxide or aluminum hydroxide); sodium bicarbonate; and a combination of two or more of these.

28. The oral care composition according to any of the preceding claims, comprising an abrasive system comprising a silica abrasive, a calcium abrasive, or a combination thereof.

29. The oral care composition according to any of the preceding claims, further comprising arginine. i racnn / zznz / E / YiAi 30. The oral care composition according to any of the preceding claims, wherein the oral care composition is in a form selected from: a paste; a gel; a tablet; a pellet; a mouthwash; a film strip; and a dental floss.

31. A method for treating, preventing or inhibiting an inflammatory disease, disorder or condition of the oral cavity comprising: administering an oral care composition according to any of the preceding claims to a subject in need.

32. A method for improving a symptom associated with an inflammatory disease, disorder, or condition of the oral cavity comprising: administering an oral care composition according to any one of claims 1 to 30, to a subject in need.

33. The method according to claim 31 or claim 32, wherein the inflammatory disease, disorder, or condition of the oral cavity is selected from gingivitis; periodontitis; ulcerative stomatitis; herpetic stomatitis; and oral herpes zoster.

34. A method for treating a bacterial infection of the oral cavity comprising administering an oral care composition according to any one of claims 1 to 30, to a subject in need.

35. The method according to any one of claims 31 to 34, wherein the oral care composition is administered to a surface of the oral cavity of a subject in need.