WO2023141140A1

WO2023141140A1 - Oral compositions for anticavity and remineralization use

Info

Publication number: WO2023141140A1
Application number: PCT/US2023/011025
Authority: WO
Inventors: Elham BABAIE
Original assignee: Dentia Inc
Current assignee: Dentia Inc
Priority date: 2022-01-21
Filing date: 2023-01-18
Publication date: 2023-07-27
Anticipated expiration: 2024-07-21

Abstract

Oral care commercial products, such as mouthwash, are regularly used by consumers as part of their hygienic oral care routine. Oral care products that are capable of providing users with both therapeutic and cosmetic benefits are advantageous. Such therapeutic benefits promote the prevention of cavities or gingivitis. Improved oral compositions are disclosed for anticavity and remineralization use, with such oral compositions being capable of both assisting with cavity prevention and providing remineralization to a user's teeth.

Description

ORAL COMPOSITIONS FOR ANTICAVITY AND REMINERALIZATION USE

RELATED APPLICATIONS

[0001 ] This application claims priority and is entitled to the filing date of U.S. provisional application serial number 63/301 ,874, filed on January 21 , 2022. The contents of the aforementioned application(s) are incorporated herein by reference.

BACKGROUND

[0002] The subject of this patent application relates generally to oral care, and more particularly to oral compositions for anticavity and remineralization use.

[0003] Applicant hereby incorporates herein by reference any and all patents and published patent applications cited or referred to in this application.

[0004] By way of background, oral care commercial products, such as mouthwash, are regularly used by consumers as part of their hygienic oral care routine. Oral care products that are capable of providing users with both therapeutic and cosmetic benefits are advantageous. Such therapeutic benefits promote the prevention of cavities or gingivitis. The former can typically be achieved using various fluoride salts and the latter by means of a microbicidal agent such as triclosan, stannous fluoride or essential oils. Current cosmetic advantages offered by oral care compositions focus on control of plaque formation and dental calculus, breath freshening and general enhancements in sensory impression in the mouth which may be largely defined as aesthetics of sensory impression in the mouth. A daily oral rinse at home should be able to offer a full range of therapeutic and cosmetic benefits such as anti-biofilm formation and subsequently prevent cavity and plaque formation.

[0005] A dental cavity is a disease caused by microbiome dysbiosis with the contribution of multiple cariogenic species, such as mutants streptococci (“MS”), and several other species that have the cariogenic behaviors of excessive acid production and acid tolerance. Conventional mouthwash does not change the cariogenic bacteria loading (microbiome dysbiosis) or acid production in the rest of the mouth and is often associated with the continuing development of cavities in high-caries-risk populations. Moreover, dynamic mineral loss (demineralization) is started by acid produced by oral bacteria. The demineralized or re-mineralizable portion of the remainder tooth structure can be repaired by remineralization only when acid production is reduced or neutralized by intrinsic or extrinsic buffering agents in dental plaque.

[0006] Conventional mouthwash products may contain antibacterial agents and/or fluoride but they generally do not prevent or repair the acid channels or enhance the delivery and retention of active agents or control the multi-specious bacteria populations of bacteria inside the oral cavity. Effective protection against such acid degradation to the tooth’s surface and structure should create a physical barrier against the acid attack in addition to improving the delivery and retention of an active agent that can neutralize the acid and/or strengthen the tooth enamel while preventing plaque and biofilm formation.

[0007] Thus, there remains a need for oral compositions that are capable of both assisting with cavity prevention and providing remineralization to a user’s teeth. Aspects of the present invention fulfill these needs and provide further related advantages as described in the following summary.

[0008] It should be noted that the above background description includes information that may be useful in understanding aspects of the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

SUMMARY

[0009] Aspects of the present invention teach certain benefits in construction and use which give rise to the exemplary advantages described below.

[0010] The present invention solves the problems described above by providing oral compositions for anticavity and remineralization use. In at least one embodiment, the oral composition comprises about 0.01 % to about 10% of an anticavity component, based on a total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition.

[0011 ] In at least one further embodiment, the oral composition is configured as a mouthwash and comprises about 0.01% to about 10% of an anticavity component, based on a total weight of the oral composition; about 0.01% to about 0.5% of a citric buffer, based on the total weight of the oral composition; about 0.01% to about 2% of a plurality of refrigerants, based on the total weight of the oral composition; about 1% to about 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition; about 5% to about 25% of a humectant, based on the total weight of the oral composition; about 0% to about 30% of alcohol, based on the total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition.

[0012] In at least one still further embodiment, the oral composition is configured as a mineralizing cement and comprises about 0.01% to about 20% of an anticavity component, based on a total weight of the oral composition; about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition; about 10% to about 80% of one or more of calcium phosphates and bioglass, based on the total weight of the oral composition; and a concentration of about 0.01% to about 30% of a setting solution, based on the total weight of the oral composition; whereby the mineralizing cement is formed using a biomimetic mineralization process.

[0013] Other features and advantages of aspects of the present invention will become apparent from the following more detailed description which illustrates, by way of example, the principles of aspects of the invention.

DETAILED DESCRIPTION

[0014] The present specification discloses oral compositions for anticavity and remineralization use. In at least one embodiment, the oral composition comprises an anticavity component. In at least one embodiment, the anticavity component contains arginine, a prebiotic amino acid, which maintains ecological homeostasis by inhibiting S. mutans growth and enriching the growth of S. sanguis and S. gordonii. In at least one such embodiment, the oral composition is configured as a mouthwash or throat gargle (hereinafter collectively referred to as “mouthwash” for simplicity purposes), which is an easy-to-use delivery approach that promotes ecological homeostasis and maximizes remineralization efficacy. The incorporation of arginine in such a mouthwash composition provides a new paradigm in cavity management as compared to traditional antibacterial mouthwash formulations, which are only capable of killing a single type of active bacteria. Thus, the oral composition’s ability to prevent the growth of multi-specious harmful bacteria, in at least one embodiment, allows for more effective therapies. Furthermore, while the use of traditional antibacterial or antiseptic mouthwash formulations can have adverse effects on arterial blood pressure and increase the risk of developing cardiovascular and other diseases, the vascular and antihypertensive effects of the L-arginine (also referred to herein as “arginine” for simplicity purposes) in the oral composition eliminates those potential issues by enriching alkali- producing bacteria and providing enhanced counter mechanisms against cariogenic pathogen and/or acid-producing bacteria. The ecological shift suppresses the oral commensals that exist in the microflora in healthy conditions. The commensals comprise S. sanguis and S. gordonii (alkali- producing bacteria) that neutralize pH by utilizing salivary/plaque arginine through the arginine deiminase system (“ADS”). The mechanism of the action of arginine in the oral biofilm’s ecology primarily involves S. gordonii and S. sanguis metabolizing arginine into ornithine, citrulline, ammonia, carbon dioxide, and a metabolic byproduct (“ATP”) through ADS. These oral bacteria associated with a biofilm compatible with health consume the ATP for their survival; thus, promoting ecological homeostasis. The presence of these bacteria and their metabolites also inhibits the growth of cariogenic bacteria due to a non-conducive alkalogenic environment. There is a significant association between saliva/plaque ADS activity and dental caries indicating an increase in ADS activity leads to a decrease in dental caries. In addition, external supplementation of arginine will increase ADS activity. Hence, caries preventive measures directed towards the enrichment of alkali-producing bacteria with concurrent suppression of cariogenic bacteria (e.g. S. mutants) are potentially beneficial. The effect of arginine in the oral composition has also been found to increase the formation of nitric oxide (“NO”) and enhanced nitrite, nitrate, and nitrosylated species concentrations, thus stimulating the enterosalivary cycle of nitrate. Additionally, it has been found that such embodiments of the oral composition have effects on other species of bacteria. For example, in at least one embodiment, at the phylum level, firmicutes have been found to increase and bacteroidetes decrease in proportion in the arginine group. As another example, in at least one embodiment, at the genus level, streptococcus and neisseria have been found to increase in proportion, whereas atopobium and catonella have been found to decrease significantly in proportion. Species of streptococcus and neisseria are typically abundant in early biofilms, whereas species of fusobacterium, porphyromonas, and prevotella are typically abundant in mature biofilms approximately 48 hours after formation, and increase after approximately 48 hours. Arginine tends to have a higher proportion of streptococcus and neisseria, similar to the observation in the bacterial flora of early biofilms. As such, arginine activity is believed to prevent the transition from early biofilms to mature biofilms and prevent dysbiosis by inhibiting the growth of opportunistic pathogens, such as atopobium and catonella.

[0015] In at least one such embodiment, the oral composition is comprised of about 0.05% to about 10% of arginine, based on a total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 0.05% or more than 10% of arginine. In at least one embodiment, where the oral composition is comprised of about 8% of arginine, the oral composition has been found to increase the concentration of NH4⁺ (raising pH) in the oral cavity and alter the diversity of the oral flora. [0016] In at least one further embodiment, the anticavity component contains a combination of arginine and fluoride. Fluoride is a known anti-caries agent. An antimicrobial effect of sodium fluoride (NaF) at >1200 ppm on S. mutans biofilms has been proven. The effects of fluoride on bacterial metabolism are described through cytoplasmic acidification induction and glycolytic enzymes inhibition. However the presence of biofilms negatively impacts the treatment outcome of the anti-caries agent such as NaF anti-caries. Moreover, long-term consumption of fluoride results in the evolution of fluoride-resistance S. mutants. Thus, augmenting the antibacterial impacts of fluorides with arginine biofilm modifiers may address these concerns without reducing the remineralization ability of fluoride. In at least one such embodiment, the oral composition is comprised of about 0.025% to about 0.055% of fluoride, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 0.025% or more than 0.055% of fluoride. In at least one alternate embodiment, theobromine is used as a complete or partial substitute for fluoride in the oral composition. In at least one such embodiment, the oral composition is comprised of about 0.02% to about 20% of theobromine, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 0.02% or more than 20% of theobromine.

[0017] In at least one such embodiment, possible effects of the oral composition may include one or more of a decrease in the intensity or a suppression of the development of dental caries; a decrease in the intensity or a suppression of demineralization, better ensuring remineralization of the teeth; a decrease in tooth sensitivity; a decrease in the intensity or a suppression of gingivitis; a decrease in levels of acid-forming bacteria; an increase in relative levels of arginolytic bacteria; an inhibiting or reduction of the formation of microbial biofilms in the oral cavity; a decrease in plaque buildup; enhancing the stability (or protection) of teeth against bacteria and their effect that causes caries; and increasing and/or maintaining the pH of plaque formation to at least pH 5.5 after using sugar-containing products.

[0018] In at least one alternate embodiment, the anticavity component contains polyvinylpyrrolidone iodine (“PVP-I"), long used as a skin antisepsis. In at least one such embodiment, the PVP-i is of the type commonly used as an over-the-counter antiseptic or antiviral mouthwash/gargling solution for intra-nasal or mouth. Accordingly, in at least one such embodiment, the oral composition is configured as a mouthwash, which can be used for the treatment of patients with a broad array of bacteria and viruses including Influenza A, the coronaviruses SARS-CoV and MERS-CoV, respiratory syncytial virus (“RSV”), streptococcus mutants, non-envelope human rotavirus strain, and other tooth decay bacteria. Not only is PVP-I capable of treating and reducing such bacteria and viruses, but it can also prevent the transmission of such bacteria and viruses due to its rapid inactivation capabilities. For example, influenza surface glycoproteins, hemagglutinin (“HA”) and neuraminidase (“NA”), act cooperatively to support efficient Influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. PVP-I involves the blockade of viral attachment to cellular receptors and the inhibition of viral release and spread from infected cells. As such, PVP-I is useful to prevent infection and limit the spread of human and avian influenza viruses. It is also currently believed that PVP-I functions with the same inhibitory mechanism in other viruses. Accordingly, with the oral composition configured as a mouthwash, the oral composition is capable of assisting in the treatment of bacteria, fungi, and virus infections of the mouth and throat, and can be used by high- risk patients, covid patients, or to complement any dental restoratives of choice with periodontal and gum sensitivity disease. PVP-I has shown superior salivary and mucosal antibacterial properties compared to its counterpart, “chlorhexidine gluconate” mouthwash. Because of its immediate capability to reduce the mucosal flora, the bacteremia after dental extraction or gingival surgery may be reduced immediately upon use. There has also been some recent interest regarding the use of some commercial mouthwashes in the treatment of the covid virus. In at least one such embodiment, the oral composition is comprised of about 0.01% to about 2.5% of PVP-I, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 0.01% or more than 2.5% of PVP-I.

[0019] In at least one such embodiment, possible effects of the oral composition may include one or more of a reduction in the number of microorganisms in the oral cavity causing the formation of plaque and the development of caries; cleaning the oral cavity and destroying microbes; decreasing the virus related to respiratory diseases such as SARS-CoV and MERS-CoV; controlling the number of tooth decay bacteria; and immediate antisepsis of mucosal or gingival surfaces prior to operative procedures.

[0020] In at least one embodiment, the oral composition further provides a citric buffer to prevent caries formation and reduce, destabilize, and potentially remove mature oral biofilms, which is due to the modulation capability of arginine and the chelating characteristic of citrate ions to bacteria. Coaggregation of S. mutans and lactobacillus are seen to be calcium dependent, and tight linkages within S. mutans bacteria in Streptococcus biofilms mediated by glucan-binding lectins are also dependent on divalent cations. In at least one such embodiment, the oral composition contains a concentration of about 0.01% to about 1% of the citric buffer, based on the total weight of the oral composition. However, in further embodiments, the oral composition may contain a concentration of less than 0.01% or more than 1% of the citric buffer. [0021 ] In at least one embodiment, the oral composition further comprises a plurality of refrigerants (e.g., menthol and an at least one secondary refrigerant such peppermint oil, for example) in an amount of about 0.01% to about 2%, based on the total weight of the oral composition. However, in further embodiments, the oral composition may comprise less than 0.04% or more than 1 .5% of the refrigerants. In at least one embodiment, the content of menthol in the oral composition is in the range of about 0.015% to about 2% (based on the total weight of the oral composition), and the content of the at least one secondary refrigerant is in the range from about 0.01% to about 0.5% (based on the total weight of the oral composition). Preferably, the total content of refrigerants is in the range of from about 0.03% to about 0.6%, based on the total weight of the oral composition.

[0022] In at least one embodiment, the oral composition further comprises an at least one polyol or polyhydric alcohol suitable for use in the oral composition, including but not limited to polyhydric alkanes (such as propylene glycol, glycerin, butylene glycol, hexylene glycol, 1 ,3-propanediol); esters of polyhydric alkanes (dipropylene glycol, ethoxydiglycol); polyalkylene glycols (such as polyethylene glycol, polypropylene glycol), as well as mixtures thereof. In at least one such embodiment, the oral composition comprises about 1 % to about 30% of the at least one polyol or polyhydric alcohol, based on the total weight of the oral composition.

[0023] In at least one embodiment, the oral composition further comprises a humectant (such as glycerin or glycerol, for example) in an amount of about 5% to about 25%, based on the total weight of the oral composition. However, in further embodiments, the humectant may be present in an amount less than 5% or more than 25%. In at least one alternate embodiment, where the humectant is glycerin, the humectant is present in an amount of about 7.5% to about 15%, based on the total weight of the oral composition. In at least one further alternate embodiment, where the humectant is propylene glycol, the humectant is present in an amount of about 5% to about 20%, based on the total weight of the oral composition. In at least one embodiment, the oral composition further comprises sodium hydroxide (“NaOH”).

[0024] In at least one embodiment, the oral composition further comprises an at least one sweetener. Sweeteners are useful and include orally acceptable natural or artificial, nutritional or non-nutritive sweeteners. Such sweeteners include dextrose, polydextrose, sucrose, maltose, dextrin, dry reversed sugar, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup (including high fructose syrup and corn syrup solids), partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomaltose, aspartame, neotame, stevia, saccharin and its salts, and gram sugar (sucralose). A powerful sweetener based on a peptide, serrami, dihydro-chalcone, and mixtures thereof may also be utilized in at least one embodiment. In general, in at least one such embodiment, the effective amount of sweetener is utilized to provide the level of sweetness desired for the oral composition will vary with the sweetener selected. None, one or more sweeteners are optionally present in the oral composition, the total amount being

5 strictly dependent on the sweetener selected but is usually from about 0.005% to about 5%, based on the total weight of the oral composition, and optionally from about 0.01% to about 5%, based on the total weight of the oral composition. However, in further embodiments, the sweetener may be present in an amount less than 0.005% or more than 5%. In at least one embodiment, where the taste of the oral composition is not favorable to the taste of customers, then sweeteners such

10 as sodium saccharin or stevia will be present at the above mentioned percentages of the total composition.

[0025] In at least one embodiment, the oral composition further comprises alcohol, which acts as a preservative during storage and use of the oral composition. A decrease in the alcohol

15 concentration in the formulation of the oral composition causes loss of the solubility of the active substances and another ingredient in the oral composition. Alcohol also increases the ability of the oral composition to destroy microorganisms that cause unpleasant odors, plaque formation, and the development of gum disease. In at least one such embodiment, alcohol is present in an amount of about 0% to about 30%, based on the total weight of the oral composition. However, in further

20 embodiments, alcohol may be present in an amount greater than 30%.

[0026] In at least one embodiment, the oral composition further comprises an antibiofilm component configured for preventing biofilm formation. In at least one such embodiment, the antibiofilm component may comprise one or more compounds including but not limited to nitrate,

25 succinic acid, beta-methyl-D-galactoside, and N-acetyl-D-mannosamine as prebiotic candidates or targeted antimicrobial peptides that can achieve targeted killing of selected pathogens. In at least one such embodiment, the oral composition comprises the antibiofilm component in an amount of about 1% to about 20%, based on the total weight of the oral composition. However, in further embodiments, the oral composition may comprise the antibiofilm component in an amount of less

30 than 1 % or more than 20%. Alternate active ingredients may also include a combination of zinc oxide or zinc citrate in an amount of about 0.5% to about 1% of the total weight of the oral composition in combination with arginine.

[0027] In at least one alternate embodiment, the oral composition is configured as a dental liner

35 mineralizing cement. In at least one such embodiment, the oral composition is based on a mixture of arginine and calcium phosphates, with the mineralizing cement formed using a biomimetic

8 mineralization process, such as a template-guided mineralization process or a process-directing agent. In at least one such embodiment, the oral composition is comprised of about 10% to about 80% of calcium phosphates, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 10% or more than 80% of calcium phosphates. In at least one alternate embodiment, nano bioactive bioglass is used as a complete or partial substitute for calcium phosphates in the oral composition. Additionally, in at least one embodiment, the oral composition is comprised of about 1% to about 20% of the anticavity component, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 1% or more than 20% of the anticavity component. In at least one embodiment, prior to being formed as a cement, the oral composition may be configured as a solution, a concentrated mouthwash, or a gel as a prebonding remineralization agent of dentin.

[0028] In at least one embodiment, where the biomimetic mineralization process involves a process-directing agent, the process-directing agent is at least one of polyallylamine hydrochloride ("PAH”), polyaspartic acid (“pAsp), phosvitin, osteopontin, amelogenin peptides (“P26”), mineralization-promoting peptides ("MPP3”) such as PGEKADRAEKADRA, biomimetic peptides, non-collagenous proteins such as dentin sialophosphoprotein (“DSPP”) and dentin matrix protein 1 (“DMP1”) based peptides, RGDS peptides, dentin phosphoprotein (“8DSS”), charged polymers such as polyacrylic acid and polyvinyl phosphonic acid, or combinations of thereof. However, in further embodiments, any other process-directing agent (now known or later developed) may be substituted. In at least one such embodiment, the oral composition is comprised of about 5% to about 40% of the process-directing agent, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 5% or more than 40% of the process-directing agent.

[0029] In at least one embodiment, where the biomimetic mineralization process involves a template-guided mineralization process, the template guide is at least one of L-glutamic acid, aspartic acid, glutaraldehyde, citrate, chondroitin sulfate, and polydopamine and polyamidoamine dendrimers. However, in further embodiments, any other molecules (now known or later developed) capable of being used as a template guide may be substituted. In at least one such embodiment, the oral composition is comprised of about 5% to about 40%% of the template guide, based on the total weight of the oral composition. However, in further embodiments, the oral composition may be comprised of less than 5% or more than 40% of the template guide. [0030] In at least one embodiment, the cement formation of the oral composition follows a chelating mechanism using optimized setting solutions. In at least one such embodiment, the setting solution is added to the oral composition at a concentration of about 0.01% to about 30%, based on the total weight of the oral composition. However, in further embodiments, the setting solution may added to the oral composition at a concentration of less than 0.01% or more than 30%. In at least one further embodiment, in situations where the cement is not sufficiently formed by chelating, an electrostatic interaction or acid-base reaction may be used.

[0031 ] In at least one embodiment, where the oral composition is configured as a cement, possible effects of the oral composition may include one or more of providing short-term moderation of acid challenges within the biofilm, favoring the mineralization reactions; exploiting the oral microbiome ecology to prevent cavities recurrence; providing a first translation of biomimetic mineralization (e.g., PILP) based approaches in conjunction with long-term rebalancing capabilities of dysbiosis using microbiome modifier; helping to control the occurrence of root canal and secondary cavities formation; and allowing for use in minimal invasive restoration practices to provide maximum conservation of dentin structure. In at least one embodiment, the PILP-based mineralization are able to form hydroxyapatite (i.e., dentin mineral portion) inside and outside of the collagen fibrils to reinforce natural dentin tissue conservation when the dental professional follows minimally invasive practices. In addition, in at least one embodiment, the oral composition may be combined with state-of-the art real-time, in situ techniques and methods to fabricate microporous restoratives by introducing a new degradable porogen based on magnesium granules (“Mg”). At least one such method uses biodegradable particles (e.g., Mg) as the porogen and due to the fast corrosion and dissolution kinetics can create macropores in real time during the setting of the cement and leave behind micropore. This additional technology can improve the release kinetics of PILP mineralization constituents and oral microbiome / anti-biofilm modifiers to facilitate natural repair while being translated in dental restoratives for the first time.

[0032] Aspects of the present specification may also be described as the following embodiments:

[0033] 1. An oral composition comprising: about 0.01% to about 10% of an anticavity component, based on a total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition.

[0034] 2. The oral composition according to embodiment 1 , wherein the anticavity component comprises about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition. [0035] 3. The oral composition according to embodiments 1-2, wherein the anticavity component comprises less than 0.05% of L-arginine, based on a total weight of the oral composition.

[0036] 4. The oral composition according to embodiments 1-3, wherein the anticavity component comprises more than 10% of L-arginine, based on a total weight of the oral composition.

[0037] 5. The oral composition according to embodiments 1-4, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.025% to about 0.055% of fluoride, based on the total weight of the oral composition.

[0038] 6. The oral composition according to embodiments 1-5, wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and about 0.025% to about 0.055% of fluoride, based on the total weight of the oral composition.

[0039] 7. The oral composition according to embodiments 1-6, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and less than 0.025% or more than 0.055% of fluoride, based on the total weight of the oral composition.

[0040] 8. The oral composition according to embodiments 1-7, wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and less than 0.025% or more than 0.055% of fluoride, based on the total weight of the oral composition.

[0041 ] 9. The oral composition according to embodiments 1-8, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.02% to about 20% of theobromine, based on the total weight of the oral composition.

[0042] 10. The oral composition according to embodiments 1 -9, wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and about 0.02% to about 20% of theobromine, based on the total weight of the oral composition.

[0043] 11. The oral composition according to embodiments 1 -10, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and less than 0.02% or more than 20% of theobromine, based on the total weight of the oral composition.

[0044] 12. The oral composition according to embodiments 1 -1 1 , wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and less than 0.02% or more than 20% of theobromine, based on the total weight of the oral composition.

[0045] 13. The oral composition according to embodiments 1 -12, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.5% to about 1% of zinc oxide or zinc citrate, based on the total weight of the oral composition.

[0046] 14. The oral composition according to embodiments 1 -13, wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and about 0.5% to about 1% of zinc oxide or zinc citrate, based on the total weight of the oral composition.

[0047] 15. The oral composition according to embodiments 1 -14, wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and less than 0.5% or more than 1% of zinc oxide or zinc citrate, based on the total weight of the oral composition.

[0048] 16. The oral composition according to embodiments 1 -15, wherein the anticavity component comprises: less than 0.05% or more than 10% of L-arginine, based on a total weight of the oral composition; and less than 0.5% or more than 1% of zinc oxide or zinc citrate, based on the total weight of the oral composition.

[0049] 17. The oral composition according to embodiments 1 -16, wherein the anticavity component comprises about 0.01 % to about 2.5% of PVP-I, based on the total weight of the oral composition.

[0050] 18. The oral composition according to embodiments 1 -17, wherein the anticavity component comprises less than 0.01% of PVP-I, based on the total weight of the oral composition.

[0051 ] 19. The oral composition according to embodiments 1 -18, wherein the anticavity component comprises more than 2.5% of PVP-I, based on the total weight of the oral composition. [0052] 20. The oral composition according to embodiments 1 -19, further comprising a concentration of about 0.01% to about 0.5% of a citric buffer, based on the total weight of the oral composition.

[0053] 21. The oral composition according to embodiments 1 -20, further comprising a concentration of less than 0.01% of the citric buffer, based on the total weight of the oral composition.

[0054] 22. The oral composition according to embodiments 1 -21 , further comprising a concentration of more than 0.5% of the citric buffer, based on the total weight of the oral composition.

[0055] 23. The oral composition according to embodiments 1 -22, further comprising a plurality of refrigerants in an amount of about 0.01% to about 2%, based on the total weight of the oral composition.

[0056] 24. The oral composition according to embodiments 1 -23, further comprising a plurality of refrigerants in an amount of less than 0.01%, based on the total weight of the oral composition.

[0057] 25. The oral composition according to embodiments 1 -24, further comprising a plurality of refrigerants in an amount of more than 2%, based on the total weight of the oral composition.

[0058] 26. The oral composition according to embodiments 1-25, wherein the refrigerants comprise: menthol in an amount of about 0.015% to about 2%, based on the total weight of the oral composition; and an at least one secondary refrigerant in an amount of about 0.01 % to about 0.5%, based on the total weight of the oral composition.

[0059] 27. The oral composition according to embodiments 1-26, wherein the refrigerants comprise: menthol in an amount of less than 0.015% or more than 2%, based on the total weight of the oral composition; and an at least one secondary refrigerant in an amount of about 0.01% to about 0.5%, based on the total weight of the oral composition.

[0060] 28. The oral composition according to embodiments 1-27, wherein the refrigerants comprise: menthol in an amount of about 0.015% to about 2%, based on the total weight of the oral composition; and an at least one secondary refrigerant in an amount of less than 0.01% or more than 0.5%, based on the total weight of the oral composition.

[0061 ] 29. The oral composition according to embodiments 1-28, wherein the refrigerants comprise: menthol in an amount of less than 0.015% or more than 2%, based on the total weight of the oral composition; and an at least one secondary refrigerant in an amount of less than 0.01% or more than 0.5%, based on the total weight of the oral composition.

[0062] 30. The oral composition according to embodiments 1-29, wherein the at least one secondary refrigerant is peppermint oil.

[0063] 31. The oral composition according to embodiments 1 -30, further comprising about 1% to about 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition.

[0064] 32. The oral composition according to embodiments 1 -31 , further comprising less than 1% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition.

[0065] 33. The oral composition according to embodiments 1 -32, further comprising more than 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition.

[0066] 34. The oral composition according to embodiments 1 -33, further comprising about 5% to about 25% of a humectant, based on the total weight of the oral composition.

[0067] 35. The oral composition according to embodiments 1 -34, further comprising less than 5% of a humectant, based on the total weight of the oral composition.

[0068] 36. The oral composition according to embodiments 1 -35, further comprising more than 25% of a humectant, based on the total weight of the oral composition.

[0069] 37. The oral composition according to embodiments 1 -36, wherein the humectant is selected from glycerin, glycerol and propylene glycol.

[0070] 38. The oral composition according to embodiments 1 -37, further comprising about 0.005% to about 5% of an at least one sweetener, based on the total weight of the oral composition.

[0071 ] 39. The oral composition according to embodiments 1 -38, further comprising less than 0.005% of an at least one sweetener, based on the total weight of the oral composition.

[0072] 40. The oral composition according to embodiments 1 -39, further comprising more than 5% of an at least one sweetener, based on the total weight of the oral composition. [0073] 41. The oral composition according to embodiments 1 -40, further comprising about 0% to about 30% of alcohol, based on the total weight of the oral composition.

[0074] 42. The oral composition according to embodiments 1 -41 , further comprising more than 30% of alcohol, based on the total weight of the oral composition.

[0075] 43. The oral composition according to embodiments 1 -42, wherein the antibiofilm component comprises at least one of nitrate, succinic acid, beta-methyl-D-galactoside, and N- acetyl-D-mannosamine.

[0076] 44. The oral composition according to embodiments 1 -43, wherein the oral composition is configured as a mouthwash.

[0077] 45. The oral composition according to embodiments 1 -44, wherein the oral composition is configured as a mineralizing cement and further comprises about 10% to about 80% of calcium phosphates, based on the total weight of the oral composition.

[0078] 46. The oral composition according to embodiments 1 -45, wherein the oral composition is configured as a mineralizing cement and further comprises less than 10% of calcium phosphates, based on the total weight of the oral composition.

[0079] 47. The oral composition according to embodiments 1 -46, wherein the oral composition is configured as a mineralizing cement and further comprises more than 80% of calcium phosphates, based on the total weight of the oral composition.

[0080] 48. The oral composition according to embodiments 1 -47, wherein the oral composition is configured as a mineralizing cement and further comprises about 10% to about 80% of bioglass, based on the total weight of the oral composition.

[0081 ] 49. The oral composition according to embodiments 1 -48, wherein the oral composition is configured as a mineralizing cement and further comprises less than 10% of bioglass, based on the total weight of the oral composition.

[0082] 50. The oral composition according to embodiments 1 -49, wherein the oral composition is configured as a mineralizing cement and further comprises more than 80% of bioglass, based on the total weight of the oral composition.

[0083] 51. The oral composition according to embodiments 1 -50, wherein the mineralizing cement is formed using a biomimetic mineralization process. [0084] 52. The oral composition according to embodiments 1 -51 , further comprising about 5% to about 40% of a process-directing agent, based on the total weight of the oral composition.

[0085] 53. The oral composition according to embodiments 1 -52, further comprising less than 5% of a process-directing agent, based on the total weight of the oral composition.

[0086] 54. The oral composition according to embodiments 1 -53, further comprising more than 40% of a process-directing agent, based on the total weight of the oral composition.

[0087] 55. The oral composition according to embodiments 1 -54, wherein the process-directing agent is at least one of polyallylamine hydrochloride (“PAH”), polyaspartic acid (“pAsp), phosvitin, osteopontin, amelogenin peptides (“P26”), mineralization-promoting peptides (“MPP3"), biomimetic peptides, non-collagenous proteins, RGDS peptides, dentin phosphoprotein (“8DSS”), and charged polymers.

[0088] 56. The oral composition according to embodiments 1 -55, wherein the mineralizing cement is formed using a template-guided mineralization process.

[0089] 57. The oral composition according to embodiments 1 -56, further comprising about 5% to about 40% of a template guide, based on the total weight of the oral composition.

[0090] 58. The oral composition according to embodiments 1 -57, further comprising less than 5% of a template guide, based on the total weight of the oral composition.

[0091 ] 59. The oral composition according to embodiments 1 -58, further comprising more than 40% of a template guide, based on the total weight of the oral composition.

[0092] 60. The oral composition according to embodiments 1 -59, wherein the template guide is at least one of L-glutamic acid, aspartic acid, glutaraldehyde, citrate, chondroitin sulfate, and polydopamine and polyamidoamine dendrimers.

[0093] 61. The oral composition according to embodiments 1 -60, further comprising a concentration of about 0.01% to about 30% of a setting solution, based on the total weight of the oral composition.

[0094] 62. The oral composition according to embodiments 1 -61 , further comprising a concentration of less than 0.01% of a setting solution, based on the total weight of the oral composition. [0095] 63. The oral composition according to embodiments 1 -62, further comprising a concentration of more than 30% of a setting solution, based on the total weight of the oral composition.

[0096] 64. An oral composition configured as a mouthwash comprising: about 0.01% to about 10% of an anticavity component, based on a total weight of the oral composition; about 0.01% to about 0.5% of a citric buffer, based on the total weight of the oral composition; about 0.01% to about 2% of a plurality of refrigerants, based on the total weight of the oral composition; about 1% to about 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition; about 5% to about 25% of a humectant, based on the total weight of the oral composition; about 0% to about 30% of alcohol, based on the total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition.

[0097] 65. An oral composition configured as a mineralizing cement comprising: about 0.01% to about 20% of an anticavity component, based on a total weight of the oral composition; about 1 % to about 20% of an antibiofilm component, based on the total weight of the oral composition; about 10% to about 80% of one or more of calcium phosphates and bioglass, based on the total weight of the oral composition; and a concentration of about 0.01% to about 30% of a setting solution, based on the total weight of the oral composition; whereby the mineralizing cement is formed using a biomimetic mineralization process.

[0098] In closing, regarding the exemplary embodiments of the present invention as shown and described herein, it will be appreciated that oral compositions are disclosed and configured for anticavity and remineralization use. Because the principles of the invention may be practiced in a number of configurations beyond those shown and described, it is to be understood that the invention is not in any way limited by the exemplary embodiments, but is generally directed to oral compositions for anticavity and remineralization use and is able to take numerous forms to do so without departing from the spirit and scope of the invention. It will also be appreciated by those skilled in the art that the present invention is not limited to the particular geometries and materials of construction disclosed, but may instead entail other functionally comparable structures or materials, now known or later developed, without departing from the spirit and scope of the invention.

[0099] Certain embodiments of the present invention are described herein, including the best mode known to the inventor(s) for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor(s) expect skilled artisans to employ such variations as appropriate, and the inventor(s) intend for the present invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described embodiments in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

[00100] Groupings of alternative embodiments, elements, or steps of the present invention are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other group members disclosed herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[00101] Unless otherwise indicated, all numbers expressing a characteristic, item, quantity, parameter, property, term, and so forth used in the present specification and claims are to be understood as being modified in all instances by the term “about” or “approximately.” As used herein, the terms “about” and “approximately” mean that the characteristic, item, quantity, parameter, property, or term so qualified encompasses a range of plus or minus ten percent above and below the value of the stated characteristic, item, quantity, parameter, property, or term. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical indication should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and values setting forth the broad scope of the invention are approximations, the numerical ranges and values set forth in the specific examples are reported as precisely as possible. Any numerical range or value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Recitation of numerical ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate numerical value falling within the range. Unless otherwise indicated herein, each individual value of a numerical range is incorporated into the present specification as if it were individually recited herein. Similarly, as used herein, unless indicated to the contrary, the term “substantially” is a term of degree intended to indicate an approximation of the characteristic, item, quantity, parameter, property, or term so qualified, encompassing a range that can be understood and construed by those of ordinary skill in the art.

[00102] Use of the terms “may” or “can” in reference to an embodiment or aspect of an embodiment also carries with it the alternative meaning of “may not" or “cannot.” As such, if the present specification discloses that an embodiment or an aspect of an embodiment may be or can be included as part of the inventive subject matter, then the negative limitation or exclusionary proviso is also explicitly meant, meaning that an embodiment or an aspect of an embodiment may not be or cannot be included as part of the inventive subject matter. In a similar manner, use of the term “optionally” in reference to an embodiment or aspect of an embodiment means that such embodiment or aspect of the embodiment may be included as part of the inventive subject matter or may not be included as part of the inventive subject matter. Whether such a negative limitation or exclusionary proviso applies will be based on whether the negative limitation or exclusionary proviso is recited in the claimed subject matter.

[00103] The terms “a,” “an,” “the” and similar references used in the context of describing the present invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Further, ordinal indicators - such as “first,” “second,” “third,” etc. - for identified elements are used to distinguish between the elements, and do not indicate or imply a required or limited number of such elements, and do not indicate a particular position or order of such elements unless otherwise specifically stated. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the present invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the present specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[00104] When used in the claims, whether as filed or added per amendment, the open-ended transitional term “comprising” (along with equivalent open-ended transitional phrases thereof such as “including,” “containing” and “having”) encompasses all the expressly recited elements, limitations, steps and/or features alone or in combination with un-recited subject matter; the named elements, limitations and/or features are essential, but other unnamed elements, limitations and/or features may be added and still form a construct within the scope of the claim. Specific embodiments disclosed herein may be further limited in the claims using the closed-ended transitional phrases “consisting of” or “consisting essentially of” in lieu of or as an amendment for “comprising.” When used in the claims, whether as filed or added per amendment, the closed- ended transitional phrase “consisting of” excludes any element, limitation, step, or feature not expressly recited in the claims. The closed-ended transitional phrase “consisting essentially of” limits the scope of a claim to the expressly recited elements, limitations, steps and/or features and any other elements, limitations, steps and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Thus, the meaning of the open-ended transitional phrase “comprising” is being defined as encompassing all the specifically recited elements, limitations, steps and/or features as well as any optional, additional unspecified ones. The meaning of the closed-ended transitional phrase “consisting of” is being defined as only including those elements, limitations, steps and/or features specifically recited in the claim, whereas the meaning of the closed-ended transitional phrase “consisting essentially of” is being defined as only including those elements, limitations, steps and/or features specifically recited in the claim and those elements, limitations, steps and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Therefore, the open-ended transitional phrase “comprising” (along with equivalent open-ended transitional phrases thereof) includes within its meaning, as a limiting case, claimed subject matter specified by the closed- ended transitional phrases “consisting of” or “consisting essentially of.” As such, embodiments described herein or so claimed with the phrase “comprising” are expressly or inherently unambiguously described, enabled and supported herein for the phrases “consisting essentially of” and “consisting of.”

[00105] Any claims intended to be treated under 35 U.S.C. §112(f) will begin with the words “means for,” but use of the term “for” in any other context is not intended to invoke treatment under 35 U.S.C. §1 12(f). Accordingly, Applicant reserves the right to pursue additional claims after filing this application, in either this application or in a continuing application.

[00106] It should be understood that the methods and the order in which the respective elements of each method are performed are purely exemplary. Depending on the implementation, they may be performed in any order or in parallel, unless indicated otherwise in the present disclosure.

[00107] All patents, patent publications, and other publications referenced and identified in the present specification are individually and expressly incorporated herein by reference in their entirety for the purpose of describing and disclosing, for example, the compositions and methodologies described in such publications that might be used in connection with the present invention. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.

[00108] While aspects of the invention have been described with reference to at least one exemplary embodiment, it is to be clearly understood by those skilled in the art that the invention is not limited thereto. Rather, the scope of the invention is to be interpreted only in conjunction with the appended claims and it is made clear, here, that the inventor(s) believe that the claimed subject matter is the invention.

Claims

CLAIMS What is claimed is:

1 . An oral composition comprising: about 0.01% to about 10% of an anticavity component, based on a total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition.

2. The oral composition of claim 1 , wherein the anticavity component comprises about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition.

3. The oral composition of claim 1 , wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.025% to about 0.055% of fluoride, based on the total weight of the oral composition.

4. The oral composition of claim 1 , wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.02% to about 20% of theobromine, based on the total weight of the oral composition.

5. The oral composition of claim 1 , wherein the anticavity component comprises: about 0.05% to about 10% of L-arginine, based on a total weight of the oral composition; and about 0.5% to about 1% of zinc oxide or zinc citrate, based on the total weight of the oral composition.

6. The oral composition of claim 1 , wherein the anticavity component comprises about 0.01% to about 2.5% of PVP-I, based on the total weight of the oral composition.

7. The oral composition of claim 1 , further comprising a concentration of about 0.01% to about 0.5% of a citric buffer, based on the total weight of the oral composition.

8. The oral composition of claim 1 , further comprising a plurality of refrigerants in an amount of about 0.01 % to about 2%, based on the total weight of the oral composition.

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9. The oral composition of claim 8, wherein the refrigerants comprise: menthol in an amount of about 0.015% to about 2%, based on the total weight of the oral composition; and an at least one secondary refrigerant in an amount of about 0.01% to about 0.5%, based on the total weight of the oral composition.

10. The oral composition of claim 1 , further comprising about 1% to about 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition.

11 . The oral composition of claim 1 , further comprising about 5% to about 25% of a humectant, based on the total weight of the oral composition.

12. The oral composition of claim 1 , further comprising about 0% to about 30% of alcohol, based on the total weight of the oral composition.

13. The oral composition of claim 1 , wherein the antibiofilm component comprises at least one of nitrate, succinic acid, beta-methyl-D-galactoside, and N-acetyl-D-mannosamine.

14. The oral composition of claim 1 , wherein the oral composition is configured as a mouthwash.

15. The oral composition of claim 1 , wherein the oral composition is configured as a mineralizing cement and further comprises about 10% to about 80% of one or more of calcium phosphates and bioglass, based on the total weight of the oral composition.

16. The oral composition of claim 15, further comprising about 5% to about 40% of a processdirecting agent, based on the total weight of the oral composition.

17. The oral composition of claim 15, further comprising about 5% to about 40% of a template guide, based on the total weight of the oral composition.

18. The oral composition of claim 15, further comprising a concentration of about 0.01% to about 30% of a setting solution, based on the total weight of the oral composition.

19. An oral composition configured as a mouthwash comprising: about 0.01% to about 10% of an anticavity component, based on a total weight of the oral composition; about 0.01 % to about 0.5% of a citric buffer, based on the total weight of the oral composition; about 0.01% to about 2% of a plurality of refrigerants, based on the total weight of the oral composition; about 1% to about 30% of an at least one polyol or polyhydric alcohol, based on the total weight of the oral composition; about 5% to about 25% of a humectant, based on the total weight of the oral composition; about 0% to about 30% of alcohol, based on the total weight of the oral composition; and about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition. An oral composition configured as a mineralizing cement comprising: about 0.01% to about 20% of an anticavity component, based on a total weight of the oral composition; about 1% to about 20% of an antibiofilm component, based on the total weight of the oral composition; about 10% to about 80% of one or more of calcium phosphates and bioglass, based on the total weight of the oral composition; and a concentration of about 0.01% to about 30% of a setting solution, based on the total weight of the oral composition; whereby the mineralizing cement is formed using a biomimetic mineralization process.