阅读说明：本技术 口腔护理组合物和使用方法 (Oral care compositions and methods of use ) 是由 沙米姆·安萨里 哈什·特里维迪 詹姆斯·G·马斯特斯 于 2017-05-17 设计创作，主要内容包括：本文公开了包含大麻籽油和辛乙二醇的口腔护理组合物。在某些实施例中,所述口腔护理组合物任选地还包含选自透明质酸和真芦荟的一种或多种成分。还提供了制备和使用所述组合物的方法。(Disclosed herein are oral care compositions comprising hemp seed oil and caprylyl glycol. In certain embodiments, the oral care composition optionally further comprises one or more ingredients selected from hyaluronic acid and aloe vera. Methods of making and using the compositions are also provided.)

1. An oral care composition comprising hemp seed oil and caprylyl glycol.

2. The oral care composition of claim 1, wherein the composition has a moisture retention capacity of at least 4.8 as measured in an in vitro moisture retention capacity assay.

3. The oral care composition of claim 2, wherein the hemp seed oil is present at a concentration of 0.8% to 1.2% by weight of the composition.

4. The oral care composition of claim 3, wherein the hemp seed oil is present at a concentration of 1.0% by weight of the composition.

5. The oral care composition of claim 3, wherein the caprylyl glycol is present at a concentration of from 0.15% to 0.35%, by weight of the composition.

6. The oral care composition of claim 5, wherein caprylyl glycol is present at a concentration of 0.25%, by weight of the composition.

7. The oral care composition according to any one of claims 1 to 6, further comprising aloe vera.

8. The oral care composition of claim 7, wherein the aloe vera is present at a concentration of 0.15% to 0.35% by weight of the composition.

9. The oral care composition of claim 8, wherein the aloe vera is present at a concentration of 0.25% by weight of the composition.

10. The oral care composition of any one of claims 1 to 6, further comprising hyaluronic acid.

11. The oral care composition of claim 10, wherein the hyaluronic acid is present at a concentration of 0.01% to 0.1% by weight of the composition.

12. The oral care composition of claim 11, wherein the hyaluronic acid is present at a concentration of 0.05% by weight of the composition.

13. A mouthwash composition comprising:

a) hemp seed oil at a concentration of 0.8% to 1.2% by weight of the composition;

b) caprylyl glycol at a concentration of 0.15% to 0.35% by weight of the composition;

c) optionally aloe vera at a concentration of 0.15% to 0.35% by weight of the composition; and

d) optionally hyaluronic acid at a concentration of 0.01% to 0.1% by weight of the composition.

14. The mouthwash composition of claim 13, wherein the composition has a moisture retention capacity of at least 4.8 as measured in an in vitro moisture retention capacity assay.

15. A method of improving oral health comprising applying an effective amount of the oral composition as set forth in any preceding claim set forth above to the oral cavity of an individual in need thereof.

16. The method of claim 15, wherein improving oral health may be selected from one or more of:

a. reducing or inhibiting caries formation;

b. reducing, repairing, or inhibiting early enamel damage;

c. reduce or inhibit demineralization and promote remineralization of teeth;

d. reducing the allergic reaction of the teeth;

e. reducing or inhibiting gingivitis;

f. promoting healing of ulcers or cuts in the mouth;

g. the content of acid-producing bacteria is reduced;

h. increasing the relative content of arginine-decomposing bacteria;

i. inhibiting microbial biofilm formation in the oral cavity;

j. raising and/or maintaining the pH of the plaque at a level of at least pH 5.5 after sugar challenge;

k. reducing plaque accumulation;

treating, alleviating or reducing dry mouth;

m. whitening teeth;

enhancing general health, including cardiovascular health;

reducing erosion of said teeth;

immunizing the teeth against cariogenic bacteria and their effects;

q. cleaning the teeth and oral cavity;

reducing inflammation;

s. increasing antioxidant levels;

t, reducing oral discomfort;

increasing lubrication;

reducing tissue friction due to desiccation; and

increase tissue hydration.

Technical Field

The present invention relates to oral care compositions comprising hemp seed oil and caprylyl glycol. In certain embodiments, the oral care composition optionally further comprises one or more ingredients selected from hyaluronic acid and aloe vera (aloe vera). Methods of making and using these compositions are also described.

Background

Dry mouth or xerostomia is a subjective complaint of dry mouth feel in humans. It is usually caused by a decrease in salivary flow or a change in the biochemical composition of saliva. Xerostomia is a major cause of oral stress and discomfort experienced by many individuals. Epidemiologically, xerostomia is one of the most common oral discomfort experienced by millions of people in the united states and the world. It is estimated that 4400 million people in the united states alone are affected by xerostomia. While dry mouth symptoms may affect people of any age group, dry mouth is more likely to occur in the elderly age group. Furthermore, the increased prevalence of dry mouth in the elderly age group may not be due to aging, but may be due to an underlying disease condition, such as sjogren's syndrome (b: (b))Syndrome), diabetes, cancer, and stroke. Typically, many instances of dry mouth are associated with the use of prescription or over-the-counter medications. There are over 1800 drugs that can induce xerostomia, and therefore those drugs are called "dry mouth".

Dry mouth can lead to a dry throat, sticky and soft mouth, which can make eating, drinking, and even speaking challenging. Dry mouth can also cause a sore and itchy throat due to lack of adequate lubricant from the saliva. Persistent xerostomia may damage taste receptors, increase the risk of developing tooth cavities, or increase the incidence of bacterial and fungal infections.

International patent application publication No. WO2014/049562 discloses an oral cosmetic having a combination of active agents comprising at least one polyunsaturated fatty acid and at least one carotenoid to improve the quality of nails. In certain embodiments, the at least one polyunsaturated fatty acid may be hemp oil.

U.S. patent application publication No. US2014/0349375 discloses the use of methylsulfonylmethane (MSM) to modulate microbial activity. In certain embodiments, MSM may be combined with hemp seed oil. In certain embodiments, MSM may be added to an oral care product such as a toothpaste, mouthwash or mouth wash (mouth-irrigant).

Korean patent application No. KR2011-0112498 discloses a toothpaste composition containing 0.1-4.0 wt% hemp (canabis sativa L.) seed oil.

International patent application publication No. WO2016/197015 discloses a composition and method for whitening and restoring natural tooth color, and a composition for application to skin cells or a portion of an area of skin. In certain embodiments, the composition comprises cannabis oil. In certain embodiments, the inventors contemplate that the composition is administered as a mouthwash.

The existing oral care market products cannot fully solve the problems of dryness and discomfort of the oral cavity. Accordingly, there is a need for oral compositions to provide effective relief by ameliorating and/or preventing dry mouth discomfort.

Disclosure of Invention

It has been surprisingly found that oral care compositions comprising cannabis seed oil and caprylyl glycol exhibit unexpected benefits in oral models. In certain embodiments, such compositions may optionally contain one or more molecules selected from hyaluronic acid and aloe vera.

In one embodiment, the present invention is an oral care composition comprising hemp seed oil and caprylyl glycol. In certain embodiments, the hemp seed oil is present at a concentration of 0.8% to 1.2% by weight of the composition. In certain embodiments, the hemp seed oil is present at a concentration of 1.0% by weight of the composition. In certain embodiments, the hemp seed oil is present at a concentration of 0.8% to 1.2% by weight of the composition and the caprylyl glycol is present at a concentration of 0.15% to 0.35% by weight of the composition. In certain embodiments, the hemp seed oil is present at a concentration of 0.8% to 1.2% by weight of the composition and the caprylyl glycol is present at a concentration of 0.25% by weight of the composition.

In other embodiments, the present invention is an oral care composition comprising cannabis seed oil and caprylyl glycol, further comprising aloe vera. In some embodiments, aloe vera is present at a concentration of 0.15% to 0.35% by weight of the composition. In some embodiments, aloe vera is present at a concentration of 0.25% by weight of the composition.

In other embodiments, the present invention is an oral care composition comprising hemp seed oil and caprylyl glycol, further comprising hyaluronic acid. In some embodiments, hyaluronic acid is present at a concentration of 0.01% to 0.1% by weight of the composition. In some embodiments, hyaluronic acid is present at a concentration of about 0.05%, by weight of the composition.

In further embodiments, the present invention is a method of improving oral health comprising applying an effective amount of any of the oral compositions described above to the oral cavity of an individual in need thereof. In certain embodiments, improving oral health may be selected from one or more of the following: a. reducing or inhibiting caries formation; b. reducing, repairing, or inhibiting early enamel damage; c. reduce or inhibit demineralization and promote remineralization of teeth; d. reducing the allergic reaction of the teeth; e. reducing or inhibiting gingivitis; f. promoting healing of ulcers or cuts in the mouth; g. the content of acid-producing bacteria is reduced; h. increasing the relative content of arginine-decomposing bacteria; i. inhibiting microbial biofilm formation in the oral cavity; j. raising and/or maintaining the pH of the plaque at a level of at least pH 5.5 after sugar challenge; k. reducing plaque accumulation; 1. treating, alleviating or alleviating dry mouth; m. whitening teeth; enhancing general health, including cardiovascular health; reducing erosion of said teeth; immunizing the teeth against cariogenic bacteria and their effects; q. cleaning the teeth and oral cavity; reducing inflammation; s. increasing antioxidant levels; t, reducing oral discomfort; increasing lubrication; reducing tissue friction due to desiccation; increasing tissue hydration.

In certain embodiments, the present invention is a composition obtained or obtainable by combining ingredients as set forth in any of the aforementioned compositions and methods.

Detailed Description

The following description of the embodiments of the invention is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

As used herein, the words "preferred" and "preferably" refer to embodiments of the invention that provide certain benefits under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.

Ranges are used throughout as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.

Unless otherwise indicated, all weight percentages of composition components given in this specification are based on 100% of the total composition or formulation weight. The recitation herein of specific values, whether referring to corresponding amounts of components or other features of the embodiments, is intended to mean that the values are plus or minus a degree of variability to account for measurement errors. For example, the 10% amount may include 9.5% or 10.5%, taking into account the degree of measurement error that will be understood and appreciated by those skilled in the art.

All references cited herein are incorporated by reference in their entirety. In the event of a conflict in a definition in the present disclosure and a definition in a cited reference, the present disclosure controls.

As used herein, the term "oral composition" refers to the entire composition delivered to the oral surface. The composition is also defined as a product that: during the course of normal use, the product is not intended for systemic administration of a particular therapeutic agent, is not intended to be swallowed, but is rather maintained in the oral cavity for a time sufficient to contact substantially all of the dental surfaces and/or oral tissues for purposes of oral activity. Examples of such compositions include, but are not limited to, toothpastes or dentifrices, mouthwashes or rinses, topical mouth gels, denture cleansers, dental strips, beads, lozenges, paints, paint-on compositions (paint-on compositions), dentifrices, chewing gums, and the like.

As used herein, unless otherwise specified, the term "dentifrice" refers to paste, gel, or liquid formulations. The dentifrice composition may be in any desired form, such as a deep stripe form, a surface stripe form, a multi-layer form, a form having a gel surrounding the paste, or any combination thereof. Alternatively, the oral composition may be in two phases dispensed from a separate chamber dispenser.

The term "mouthwash" in the present invention refers to oral compositions that are substantially liquid in character, such as mouthwashes, sprays, rinses, and the like. In such formulations, the orally acceptable carrier typically has an aqueous phase comprising water or a mixture of water and an alcohol. Further, in various embodiments, the oral vehicle includes a humectant and a surfactant. Generally, if an alcohol is present, the weight ratio of water to alcohol is in the range of 1: 1 to 20: 1, preferably 3: 1 to 10: 1, and more preferably 4: 1 to 6: 1. The total amount of water-alcohol mixture in this type of formulation is typically in an amount of 70 to 99.9% of the formulation. In various embodiments, the alcohol is typically ethanol or isopropanol.

The compositions of the present invention may be applied to the oral cavity of a subject (particularly the oral cavity of a human or animal subject) by any means. The means of application may vary depending on the formulation of the oral care composition. For example, in certain embodiments, the oral care composition is a dentifrice and can be topically applied to the oral cavity using an implement (e.g., a brush, toothbrush, stick, sponge, or cotton swab). In certain embodiments, the oral care composition is in the form of a mouthwash or mouthrinse, and is applied to the oral cavity by a lavage ("gargle"). In certain embodiments, the mouthwash or rinse is in a single phase. In certain embodiments, the mouthwash or rinse is in a dual phase. In certain embodiments, the oral care composition is applied to a surface in the oral cavity using a dental tray. In certain embodiments, the oral care composition is applied to a surface in the oral cavity using a dental strip (dental strip), for example by adhering the strip comprising the oral care composition to the surface of the teeth or gums. In certain embodiments, the oral care composition is applied to the oral cavity using an oral care pen. In certain embodiments, the oral care composition is applied to the oral cavity at least once or at least twice daily.

As used herein, the term "effective amount" means an amount of a composition of the present invention in an amount sufficient to achieve the intended purpose, e.g., to ameliorate and/or prevent dry mouth discomfort in an individual.

As used herein, the term "hemp seed oil" means an oil composition derived from hemp seed. In contrast, "hemp oil" is made from one or more materials selected from the leaves, flowers and fibers of the hemp plant.

The ingredients used in the compositions and formulations of the present invention are preferably cosmetically acceptable ingredients, unless explicitly stated otherwise. By "cosmetically acceptable" is meant suitable for use in formulations for topical application to human skin. For example, cosmetically acceptable excipients are excipients suitable for external application in the amounts and concentrations contemplated in the formulations of the present invention, and include, for example, excipients that are Recognized as Safe by the United States Food and Drug Administration (GRAS).

Compositions and formulations as provided herein are described and claimed with reference to their ingredients, as is common in the art. As will be apparent to those skilled in the art, the ingredients may sometimes react with each other such that the actual composition of the final formulation may not exactly correspond to the listed ingredients. Thus, it is to be understood that the invention extends to the products of the combinations of ingredients listed.

The present invention provides an oral care composition comprising hemp seed oil. In certain embodiments, the oral care composition may optionally further comprise one or more ingredients selected from caprylyl glycol, hyaluronic acid, and aloe vera. In some embodiments, the oral care composition contains 0.6% to 1.4% by weight hemp seed oil. In certain embodiments, the cannabis seed oil is 0.8% to 1.2% by weight of the oral care composition. In other embodiments, the hemp seed oil is 1.0% by weight of the oral care composition.

In other embodiments, the present invention provides oral care compositions comprising hemp seed oil and caprylyl glycol. In certain embodiments, the oral care composition may optionally further comprise one or more ingredients selected from hyaluronic acid and aloe vera. Such compositions provide unique characteristics, such as oral comfort benefits. In some embodiments, the hemp seed oil is present at 0.6% to 1.4% by weight of the composition. In certain embodiments, the hemp seed oil is present at 0.8% to 1.2% by weight of the oral care composition. In other embodiments, the hemp seed oil is present at 1.0% by weight of the oral care composition. In some embodiments, the caprylyl glycol is present at a concentration of 0.15% to 0.35%, by weight of the composition. In other embodiments, the caprylyl glycol is present at a concentration of 0.25%, by weight of the composition. In some embodiments, the hemp seed oil is present at 0.6% to 1.4% and caprylyl glycol is present at 0.15% to 0.35% by weight of the composition. In certain embodiments, the hemp seed oil is present at 0.8% to 1.2% and caprylyl glycol is present at 0.2% to 0.3% by weight of the oral care composition. In other embodiments, the hemp seed oil is present at 1.0% and the caprylyl glycol is present at 0.2% to 0.3% by weight of the oral care composition. In other embodiments, the hemp seed oil is present at 1.0% and the caprylyl glycol is present at a concentration of 0.25% by weight of the composition.

In some embodiments, the oral care composition contains cannabis seed oil, caprylyl glycol, and aloe vera. In some embodiments, the hemp seed oil is present at 0.6% to 1.4%, caprylyl glycol is present at 0.15% to 0.35%, and aloe vera is present at 0.15% to 0.35%, by weight of the composition. In certain embodiments, cannabis seed oil is present at 0.8% to 1.2%, caprylyl glycol is present at 0.2% to 0.3%, and aloe vera is present at 0.2% to 0.3%, by weight of the oral care composition. In other embodiments, cannabis seed oil is present at 1.0%, caprylyl glycol is present at 0.2% to 0.3%, and aloe vera is present at 0.2% to 0.3%, by weight of the oral care composition. In certain embodiments, cannabis seed oil is present at 1.0%, caprylyl glycol is present at a concentration of 0.25%, and aloe vera is present at 0.2% to 0.3% by weight of the composition. In other embodiments, cannabis oil is present at 1.0%, caprylyl glycol is present at a concentration of 0.25%, and aloe vera is present at 0.25%, by weight of the composition.

In some embodiments, the oral care composition comprises hemp seed oil, caprylyl glycol, and hyaluronic acid. In some embodiments, the hemp seed oil is present at 0.6% to 1.4%, the caprylyl glycol is present at 0.15% to 0.35%, and the hyaluronic acid is present at 0.01% to 0.1%, by weight of the composition. In certain embodiments, cannabis oil is present at 0.8% to 1.2%, caprylyl glycol is present at 0.2% to 0.3%, and hyaluronic acid is present at 0.01% to 0.1%, by weight of the oral care composition. In other embodiments, the hemp seed oil is present at 1%, the caprylyl glycol is present at 0.2% to 0.3%, and the hyaluronic acid is present at 0.01% to 0.1%, by weight of the composition. In other embodiments, cannabis oil is present at 1.0%, caprylyl glycol is present at a concentration of 0.25%, and hyaluronic acid is present at 0.05%, by weight of the composition.

The present invention further provides a method of improving oral health comprising administering to an individual in need thereof an effective amount of an oral care composition described herein. In certain embodiments, oral health can reduce or inhibit caries formation; reducing, repairing, or inhibiting early enamel damage; reduce or inhibit demineralization and promote remineralization of teeth; reducing the allergic reaction of the teeth; reducing or inhibiting gingivitis; promoting healing of ulcers or cuts in the mouth; the content of acid-producing bacteria is reduced; increasing the relative content of arginine-decomposing bacteria; inhibiting microbial biofilm formation in the oral cavity; raising and/or maintaining the pH of the plaque at a level of at least pH 5.5 after sugar challenge; reducing plaque accumulation; treating, alleviating or alleviating dry mouth; whitening teeth; enhancing general health, including cardiovascular health; reducing erosion of the teeth; immunizing the teeth against cariogenic bacteria and their effects; cleaning the teeth and oral cavity; reducing inflammation; increasing the level of antioxidants; reducing oral discomfort; increasing lubrication; reducing tissue friction due to desiccation; and increased tissue hydration.

In certain embodiments, cannabis seed oil, caprylyl glycol, and optionally one or more ingredients selected from hyaluronic acid and aloe vera are included in the oral care composition. In some embodiments, the oral care composition may be selected from the group selected from: toothpastes or dentifrices, mouthwashes, topical oral gels, denture cleansers, dental strips, beads, lozenges, paints, and paint-on compositions. In some embodiments, the oral care composition may be a toothpaste or dentifrice. In some embodiments, the oral care composition can be a mouthwash. In some embodiments, the oral care composition can be a topical oral gel and denture cleanser.

In further embodiments, the present invention is a method of improving oral health comprising applying an effective amount of an oral composition described herein to the oral cavity of an individual in need thereof. In certain embodiments, the method comprises the use of cannabis seed oil, caprylyl glycol, and optionally one or more ingredients selected from hyaluronic acid and aloe vera. In certain embodiments, the method comprises an oral care composition selected from the group consisting of: toothpastes or dentifrices, mouthwashes or rinses, topical oral gels, denture cleansers, dental strips, beads, buccal lozenges, paints, paint-on compositions, dentifrices, and the like.

The present invention also provides methods of ameliorating and/or preventing dry mouth discomfort, reducing oral discomfort, increasing lubrication, reducing tissue friction due to dryness, and increasing tissue hydration comprising administering to the oral cavity an effective amount of a composition of the present invention, e.g., any of the compositions described herein.

For example, the present invention provides methods of ameliorating and/or preventing dry mouth discomfort, reducing and inhibiting acid erosion of enamel, reducing or inhibiting gingival atrophy, controlling microbial growth, cleaning teeth, reducing bacterially-generated biofilm and plaque, reducing gingivitis, inhibiting the formation of cavities and cavities, and reducing dentinal hypersensitivity comprising applying to the oral cavity an effective amount of a composition of the invention, such as any of the compositions described herein, and subsequently rinsing with sufficient water or an aqueous solution.

Some embodiments provide mouthwashes for improving and/or preventing dry mouth discomfort, reducing and/or inhibiting acid erosion of enamel, reducing or inhibiting gingival atrophy, controlling microbial growth, cleaning teeth, reducing bacterially-produced biofilm and plaque, reducing gingivitis, inhibiting tooth decay and cavity formation, and/or reducing dentinal hypersensitivity reactions.

Some embodiments provide the use of cannabis seed oil, caprylyl glycol and optionally one or more ingredients selected from hyaluronic acid and aloe vera included in an oral care composition for the manufacture of a mouthwash. Other embodiments provide a method of treating or reducing dental enamel erosion, cleaning teeth, reducing or inhibiting gingival atrophy, reducing bacterially-produced biofilm and plaque, reducing gingivitis, inhibiting the formation of cavities and cavities, and/or reducing dentinal hypersensitivity comprising applying a mouthwash as described herein. Other embodiments provide methods further comprising the step of rinsing with sufficient water or aqueous solution.

The present invention further provides a method of preparing an oral care composition comprising combining cannabis seed oil, caprylyl glycol and optionally one or more ingredients selected from hyaluronic acid and aloe vera in an aqueous medium solution with other oral care ingredients known to those skilled in the art. In certain embodiments, the oral care composition is a toothpaste. In certain embodiments, the oral care base is a mouthwash base.

By "active" is meant a compound that provides a benefit or improvement to a target tissue when applied to the target tissue. The active may be delivered in the form of any oral care formulation, such as a toothpaste, a transparent paste, a gel, a mouthwash, a powder, a cream, a strip, a spray, a gel, or any other formulation known in the art.

If the ingredients are delivered in the form of a mouthwash, the person desiring the benefit rinses with a solution containing the ingredients of the invention. In certain embodiments, dual chambers may be implemented. In such aspects, the first chamber contains one or more components of the present invention. The dual chamber will also contain a second chamber containing dissolved one or more other ingredients of the invention. Upon application, the contents of the first and second chambers are mixed together, resulting in a complete solution containing each of the ingredients of the present invention.

In another embodiment, the mixture is prepared and immediately transferred to a holding tray, such as those used to contain the whitening gel, and the tray may be worn by the individual for an effective period of time. The teeth that come into contact with the mixture will be treated. For use with a holding tray, the mixture may be in the form of a low viscosity liquid or gel. In certain embodiments, the complex is formulated to comprisePolymer, glycerol and water.

In another embodiment, the stock solution or a mixture of the stock solution and water is applied to the teeth in the form of a gel formulation, for example, wherein the gel can remain on the teeth for an extended period of time to achieve effective treatment.

In another embodiment, the composition of the invention is a viscous liquid, preferably a gel, which will maintain its consistency during storage, enabling the product to be applied to the tooth surface with a soft paint applicator pen or brush. Some embodiments provide a method of delivering a composition with an applicator, wherein the applicator is a pen and the pen is stored within an oral care implement. In some embodiments, the pen is removed from the oral care implement prior to applying the composition to the teeth. In some embodiments, the composition is applied to the teeth after brushing. In some embodiments, the composition is applied to the teeth after brushing the teeth with the oral care implement.

In certain embodiments, the composition is anhydrous. Anhydrous is less than 5 wt% water, optionally less than 4 wt%, less than 3 wt%, less than 2 wt%, less than 1 wt%, less than 0.5 wt%, less than 0.1 wt% down to 0 wt% water.

A dentifrice or paste for topical application to a sensitive tooth site (e.g., cementum on an exposed tooth root surface of the mouth) may be one that is simpler in composition and applied with a soft applicator. Such dentifrices or pastes may or may not contain conventional abrasives, foaming agents and flavoring agents. The prepared local site of the tooth for tooth restoration, such as dentin, also involves a simpler composition and includes fillers, cavity lining agents and cements for endodontic covering and any other ingredients that one skilled in the art needs to use in the composition (Craig et al, 1989, restorative dental Materials Mosby, st. louis, page 189-. For example, levels of zinc oxide and eugenol of 20% and 25%, respectively, are suitable for dental cement compositions.

In certain embodiments, the oral care composition with ingredients of the present invention further comprises one or more agents selected from the group consisting of: diluents, bicarbonate salts, pH modifying agents, surfactants, foam modulators, additional thickeners, humectants, sweeteners, flavoring agents, pigments, antibacterial agents, anticaries agents, fluoride ion sources, antioxidants, antiallergic agents, anticalculus or tartar control agents, and mixtures thereof.

The oral composition according to the present invention may optionally include other materials such as cleaning agents, flavoring agents, sweeteners, adhesion agents, surfactants, foam modulators, abrasives, pH modifying agents, humectants, mouth feel agents, colorants, abrasives, preservatives, fluoride ion sources, saliva stimulating agents, emollients, viscosity modifiers, diluents, emulsifiers, nutrients and combinations thereof. Various components that may be added to the oral composition include, for example, sweetening agents such as saccharin or saccharin sodium; alcohols, such as ethanol; fluorineIon sources (such as sodium fluoride) and glycerol, sorbitol, polyethylene glycol. Poloxamer (Poloxamer) polymers, e.g.407、F108 (all available from BASF Corporation), Alkyl Polyglycoside (APG), polysorbate, PEG40, castor oil, menthol, and the like. It will be appreciated that while the general attributes of each of the above categories of materials may differ, there may be some common attributes and any given material may serve multiple purposes within two or more of these categories of materials. Preferably, such carrier materials are selected to be compatible with the active ingredient as well as the other ingredients of the composition.

Some embodiments further comprise an effective amount of a fluoride ion source within the composition.

In other embodiments, the invention comprises an orally acceptable base comprising an ingredient selected from one or more of the following: buffers, humectants, surfactants, thickeners, breath freshening agents, flavoring agents, fragrances, coloring agents, antibacterial agents, whitening agents, agents that interfere with or prevent bacterial attachment, sources of calcium, sources of phosphate, orally acceptable potassium salts, and anionic polymers.

The compositions of the present invention optionally contain other ingredients such as enzymes, vitamins and detackifiers. Enzymes such as proteases may be added for combating stains and other effects. Non-limiting examples of vitamins include vitamin C, vitamin E, vitamin B5, and folic acid. In various embodiments, the vitamin has antioxidant properties. Detackifiers include Ethyl Lauroyl Arginine (ELAH), solbrol, ficin (ficin), silicone polymers and derivatives, and quorum sensing inhibitors (quorum sensing inhibitor).

Flavoring agents useful in between those herein include any material or mixture of materials operable to enhance the taste of the composition. Any orally acceptable natural or synthetic flavoring agent can be used, such as essential oils, various flavoring aldehydes, flavoring oils, esters, alcohols, similar substances, and sweetening agents, such as saccharin sodium and combinations thereof. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Chemicals such as menthol, carvacrol and anethole are also suitable. Certain embodiments employ oils of peppermint and spearmint. Flavoring agents include vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils and essences including those derived from lemon, orange, lime, grapefruit, apricot, banana, grape, apple, strawberry, cherry, pineapple, and the like, bean and nut derived flavors (e.g., coffee, cocoa, cola, peanut, almond, and the like), adsorbed and encapsulated flavors and mixtures thereof. Also encompassed within the flavoring agents herein are ingredients that provide a fragrant and/or other sensory effect in the mouth, including a cooling or warming effect. Such ingredients include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, anethol, eugenol, cinnamon, raspberry ketone (oxanone), [ alpha ] -ionone, propenyl guaethol (propenyl guaethol), thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl-p-menthane-3-carboxamide, N, 2, 3-trimethyl-2-isopropyl butanamide, 3-1-menthoxypropane-1, 2-diol, Cinnamaldehyde Glycerol Acetal (CGA), Methane Glycerol Acetal (MGA), and mixtures thereof. One or more flavoring agents are optionally present in a total amount of 0.01% to about 5%, optionally 0.05% to about 2%, 0.1% to 2.5%, and 0.1% to 1.0% in various embodiments.

Sweeteners useful between those herein include dextrose, polydextrose, sucrose, maltose, dextrin, dried invert sugar, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, sucralose, dipeptide based intense sweeteners, cyclamate (cyclamate), dihydrochalcones, and mixtures thereof.

Mouthfeel agents include materials that impart a desired texture or other sensation during use of the compositions of the present invention.

The composition may also comprise an antioxidant. Any orally acceptable antioxidant may be used, including Butylated Hydroxyanisole (BHA), Butylated Hydroxytoluene (BHT), vitamin a, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid, herbal antioxidants, chlorophyll, melatonin, and mixtures thereof.

Colorants useful in between those herein include pigments, dyes, lakes, and agents that impart a particular gloss or reflectivity, such as pearlescent agents. In various embodiments, the colorant is operable to provide a white or light-colored coating on the tooth surface, serve as an indication of a location on the tooth surface that has been effectively contacted by the composition, and/or modify the appearance, particularly the color and/or opacity, of the composition to enhance appeal to the consumer. Any orally acceptable colorant can be used, including FD & C dyes and pigments, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, red, yellow, brown and black iron oxides, ferric ammonium ferrocyanide, manganese violet, ultramarine, titaniated mica, bismuth oxychloride, and mixtures thereof. One or more colorants are optionally present in a total amount of 0.001% to 20%, for example 0.01% to 10% or 0.1% to 5%.

Active agent(s):

the compositions of the present invention may comprise, in addition to or in addition to the zinc-amino acid-halide complex, various active agents which are effective in protecting and enhancing the strength and integrity of tooth enamel and tooth structure and/or reducing bacterial and related dental caries and/or gum disease. The effective concentration of the active ingredient used herein will depend on the particular agent and delivery system used. It will be appreciated that for example toothpastes will generally be diluted with water at the time of use, whereas mouthwashes will generally not be diluted with water. Thus, the effective concentration of active in a toothpaste will generally be 5-15 times the concentration required for a mouthwash. The concentration will also depend on the exact salt or polymer selected. For example, where the active agent is provided in the form of a salt, the counter ion will affect the weight of the salt, such that if the counter ion is heavier, more salt by weight will be required to provide the same concentration of active ion in the final product. When present, arginine may be present at a level of, for example, from about 0.1 to about 20 wt.% (expressed as weight of free base), for example, from about 1 to about 10 wt.% for a consumer toothpaste, or from about 7 to about 20 wt.% for a professional or prescription treatment product. When present, fluoride may be present at levels of, for example, from about 25 to about 25,000ppm, such as from about 750 to about 2,000ppm for consumer toothpaste, or from about 2,000 to about 25,000ppm for professional or prescription treatment products.

The compositions of the preferred embodiments may also optionally contain one or more antibacterial agents. The antimicrobial agent may be selected from halogenated diphenyl ethers (e.g. triclosan), herbal extracts and essential oils (e.g. rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitiol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak (miswak) extract, sea buckthorn extract), biguanide preservatives (e.g. chlorhexidine, alexidine or tinidine), quaternary ammonium compounds (e.g. cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic preservatives, hexetidine (hexetidine), tinidine, sanguinarine, povidone iodine, Delmopinol (delmopinol), 5-n-octanoyl-3' -trifluoromethylphenylsalicylamide (salifluor), metal ions (e.g., zinc salts (e.g., zinc citrate, zinc oxide), stannous salts, copper salts, iron salts), sanguinarine, propolis (propolis), and oxidizing agents (e.g., hydrogen peroxide, buffered sodium perborate or sodium peroxycarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, ascorbyl stearate, linoleate, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen bromide (domiphen bromide), delmopinol (delmopinol), octopamol and other piperidinyl derivatives, nicotinic acid (niacin) preparations, chlorite salts; and mixtures of any of the foregoing. In some embodiments, the antimicrobial agent is preferably not triclosan and may be selected from CPC, chlorhexidine, zinc citrate, zinc oxide, and mixtures thereof. If used, the antimicrobial agent is preferably present in an amount of from 0.01% to 10%, for example from 0.025% to 5%, more preferably from 0.05% to 1%, or from 0.075% to 0.5% by weight, based on the total weight of the composition. The level of antibacterial agent may vary depending on the oral composition, and levels used in toothpastes are, for example, about 5 to about 15 times higher than those used in mouthwashes. For example, a triclosan toothpaste may contain about 0.3% by weight triclosan.

The oral care composition may further comprise one or more fluoride ion sources, such as soluble fluoride salts. A wide variety of fluoride ion-generating materials can be used as a source of soluble fluoride in the compositions of the present invention. Examples of suitable fluoride ion-producing materials are found in U.S. Pat. No. 3,535,421 to Briner et al, U.S. Pat. No. 4,885,155 to Parran, Jr. et al, and U.S. Pat. No. 3,678,154 to Widder et al. Representative fluoride ion sources include, but are not limited to: stannous fluoride, sodium fluoride, potassium monofluorophosphate, sodium monofluorophosphate, ammonium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluorides such as, but not limited to olaflur (olaflur, N '-octadecyltrimethylendiamine-N, N' -tris (2-ethanol) -dihydrofluoride), ammonium fluoride, and combinations thereof. In certain embodiments, the fluoride ion source comprises stannous fluoride, sodium monofluorophosphate, and mixtures thereof. In certain embodiments, the oral care compositions of the present invention may also contain a source of fluoride ions or a fluorine-providing ingredient in an amount sufficient to provide from about 25ppm to about 25,000ppm fluoride ion, typically at least about 100ppm, such as from about 500 to about 2000ppm, such as from about 1000 to about 1600ppm, such as about 1450 ppm. The appropriate amount of fluoride will depend on the particular application. Toothpastes for general consumer use will typically have from about 1000 to about 1500ppm, with children's toothpastes being somewhat lower. Dentifrices or coating agents for professional use may have as much as 5,000ppm or even about 25,000ppm fluoride. A fluoride ion source may be added to the compositions of the present invention in an amount in one embodiment from about 0.01% to about 10%, or from about 0.03% to about 5%, and in another embodiment from about 0.1% to about 1%, by weight of the composition, in another embodiment. The weight of fluoride salt used to provide the appropriate fluoride ion content will obviously vary depending on the weight of counter ion in the salt.

The oral care compositions of the present invention may also include an agent that increases the amount of foam generated when brushing the oral cavity. Illustrative examples of agents that increase the amount of foam include, but are not limited to, polyoxyethylene and certain polymers, including, but not limited to, alginate polymers. The polyoxyethylene may increase the amount of foam and the thickening of the foam produced by the oral care carrier component of the present invention. Polyoxyethylene is also commonly referred to as polyethylene glycol ("PEG") or polyethylene oxide. The polyoxyethylene suitable for the present invention will have a molecular weight of from about 200,000 to about 7,000,000. In one embodiment, the molecular weight will be from about 600,000 to about 2,000,000, and in another embodiment from about 800,000 to about 1,000,000.Is the trade name for high molecular weight polyoxyethylene produced by Union Carbide. The polyoxyethylene may be present in an amount of from about 1% to about 90%, in one embodiment from about 5% to about 50%, and in another embodiment from about 10% to about 20%, by weight of the oral care carrier component of the oral care compositions of the present invention. When present, the amount of foaming agent in the oral care composition (i.e., a single dose) is from about 0.01 to about 0.9 weight%, from about 0.05 to about 0.5 weight%, and in another embodiment from about 0.1 to about 0.2 weight%.

In various embodiments of the present invention, the composition comprises an anticalculus (tartar control) agent. Suitable anticalculus agents include, but are not limited to, phosphates and polyphosphates (e.g., pyrophosphates), polyaminopropanesulfonic Acid (AMPS), hexametaphosphate, zinc citrate trihydrate, polypeptides, polyolefin sulfonates, polyolefin phosphatesSalts, bisphosphonates. The present invention may therefore comprise phosphate. In particular embodiments, these salts are alkali metal phosphates, i.e., salts of alkali metal hydroxides or alkaline earth metal hydroxides, such as sodium, potassium or calcium salts. As used herein, "phosphate" encompasses orally acceptable mono-and polyphosphates, for example P1-6 phosphate, for example monomeric phosphates, such as mono-, di-or tri-phosphates; dimeric phosphates such as pyrophosphate; and polyphosphates, such as sodium hexametaphosphate. In particular examples, the selected phosphate is selected from alkali metal diphosphates and alkali metal pyrophosphates, for example from disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any two or more of these. In a particular embodiment, for example, the composition comprises tetrasodium pyrophosphate (Na)₄P₂O₇) Calcium pyrophosphate (Ca)₂P₂O₇) And disodium hydrogen phosphate (Na)₂HPO₄) E.g., in amounts of about 3-4% disodium hydrogen phosphate and about 0.2-1% of each pyrophosphate. In another embodiment, the composition comprises tetrasodium pyrophosphate (TSPP) and Sodium Tripolyphosphate (STPP) (Na)₅P₃O₁₀) For example in the proportion of about 1-2% TSPP and about 7% to about 10% STPP. Such phosphates are provided in an amount effective to reduce erosion of the enamel, to aid in cleaning the teeth, and/or to reduce the accumulation of tartar on the teeth, for example in an amount of from 2 to 20%, for example from about 5 to 15% by weight of the composition.

The compositions of the invention optionally incorporate one or more anti-sensitizers, for example potassium salts such as potassium nitrate, potassium bicarbonate, potassium chloride, potassium citrate and potassium oxalate; capsaicin; eugenol; a strontium salt; and combinations thereof. Depending on the agent selected, such agent may be added in an effective amount, for example, from about 1% to about 20% by weight, based on the total weight of the composition.

The oral care compositions of the present invention may also include additional polymers to adjust the viscosity of the formulation or enhance the solubility of other ingredients. Such additional polymers include polyethylene glycol, polyvinylmethylether maleic acid copolymers, polysaccharides (e.g., cellulose derivatives such as carboxymethylcellulose; or polysaccharide gums such as xanthan gum or carrageenan). The acidic polymer (e.g., polyacrylate gel) may be provided in the form of its free acid or partially or fully neutralized water soluble alkali metal (e.g., potassium and sodium) or ammonium salt. Certain embodiments include 1: 4 to 4: 1 copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer, such as methyl vinyl ether (methoxyethylene), having a molecular weight (M.W.) of about 30,000 to about 1,000,000. These copolymers are available, for example, as Gantrez AN 139(m.w.500,000), AN 119(m.w.250,000) and S-97 pharmaceutical grades (m.w.70,000) from GAF chemicals.

Other functional polymers include those such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA No. 1103, M.W.10,000, and EMA grade 61; and 1: 1 copolymers of acrylic acid with methyl methacrylate or hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Generally, suitable are polymerized ethylenically or ethylenically unsaturated carboxylic acids containing an activated carbon-carbon olefinic double bond and at least one carboxyl group, i.e., acids containing an olefinic double bond that readily functions in polymerization because it is present in the monomer molecule in the alpha-beta position relative to the carboxyl group or as part of the terminal methylene group. Examples of such acids are acrylic acid, methacrylic acid, ethacrylic acid, alpha-chloroacrylic acid, crotonic acid, beta-acryloxypropionic acid, sorbic acid, alpha-chlorosorbic acid, cinnamic acid, beta-styrylacrylic acid, myxofuroic acid, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, alpha-phenylacrylic acid, 2-phenylmethylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymer contains sufficient carboxylate groups for water solubility.

Another class of polymerization agents includes compositions containing homopolymers of substituted acrylamides and/or homopolymers of unsaturated sulfonic acids and salts thereof, particularly where the polymer is an unsaturated sulfonic acid based on a group selected from acrylamidoalkylsulfonic acids (such as 2-acrylamido 2-methylpropane sulfonic acid) having a molecular weight of from about 1,000 to about 2,000,000, as described in U.S. patent No. 4,842,847 to Zahid, 6.27.1989, which is incorporated herein by reference.

Another class of suitable polymerization agents includes polyamino acids, especially those containing a proportional proportion of anionic surface active amino acids such as aspartic acid, glutamic acid, and phosphoserine, as disclosed in U.S. patent No. 4,866,161 to Sikes et al, incorporated herein by reference.

Silica thickeners which form a polymer structure or gel in an aqueous medium may be present. It should be noted that these silica thickeners are physically and functionally distinct from the particulate silica abrasives also present in the composition, as the silica thickeners are very finely dispersed and provide little or no abrasive action. Other thickeners are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic and gum tragacanth can also be incorporated. Colloidal magnesium aluminium silicate may also be used as a component of the thickening composition in order to further improve the texture of the composition. In certain embodiments, the thickening agent is used in an amount of about 0.5% to about 5.0% by weight of the total composition.

The compositions of the present invention may include an anionic polymer, for example, in an amount of from about 0.05% to about 5%. Such agents are generally known for use in dentifrices, although not for this particular application, such agents useful in the present invention are disclosed in U.S. Pat. Nos. 5,188,821 and 5,192,531; and include synthetic anionically polymerized polycarboxylates such as 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight (M.W.) of about 30,000 to about 1,000,000, most preferably about 300,000 to about 800,000. These copolymers are available, for example, as Gantrez, such as AN 139(m.w.500,000), AN 119(m.w.250,000), and preferably S-97 pharmaceutical grade (m.w.700,000), available from ISP technologies, inc., Bound Brook, n.j. The enhancer (when present) is present in an amount in the range of about 0.05 to about 3 weight percent. Other functional polymers include those such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA No. 1103, M.W.10,000, and EMA grade 61; and 1: 1 copolymers of acrylic acid with methyl methacrylate or hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Generally, suitable are polymerized ethylenically or ethylenically unsaturated carboxylic acids containing an activated carbon-carbon olefinic double bond and at least one carboxyl group, i.e., acids containing an olefinic double bond that readily functions in polymerization because it is present in the monomer molecule in the alpha-beta position relative to the carboxyl group or as part of a terminal methylene group. Examples of such acids are acrylic acid, methacrylic acid, ethacrylic acid, alpha-chloroacrylic acid, crotonic acid, beta-acryloxypropionic acid, sorbic acid, alpha-chlorosorbic acid, cinnamic acid, beta-styrylacrylic acid, myxofuroic acid, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, alpha-phenylacrylic acid, 2-phenylmethylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymer contains sufficient carboxylate groups for water solubility. Another class of polymerization agents includes compositions containing homopolymers of substituted acrylamides and/or homopolymers of unsaturated sulfonic acids and salts thereof, particularly where the polymer is an unsaturated sulfonic acid based on a group selected from acrylamidoalkylsulfonic acids (such as 2-acrylamido 2-methylpropane sulfonic acid) having a molecular weight of from about 1,000 to about 2,000,000, as described in U.S. Pat. No. 4,842,847 to Zahid, 6.27.1989. Another class of suitable polymerization agents includes polyamino acids containing a proportion of anionic surface active amino acids such as aspartic acid, glutamic acid, and phosphoserine, for example, as disclosed in U.S. patent No. 4,866,161 issued to Sikes et al.

The oral composition may comprise a significant level of water. The water used in the preparation of commercial oral compositions should be deionized and free of organic impurities. The amount of water in the composition includes the free water added plus the amount of water introduced with the other materials.

In certain embodiments of the oral composition, it is also desirable to incorporate a humectant to reduce evaporation and also to aid in preservation by reducing the activity of water. Certain humectants can also impart desirable sweetness or flavor to the composition. The humectant may be present in the composition in an amount of from 10 wt% to 40 wt% in one embodiment, and from 15 wt% to 30 wt% in another embodiment, based on the total weight of the composition. Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol, as well as other polyols and mixtures of these humectants. Typically, the compositions of the present invention comprise a combination of glycerin and sorbitol.

In addition to the above components, embodiments of the present invention may contain a variety of optional dentifrice ingredients, some of which are described below. Optional ingredients include, for example, but are not limited to, binders, foaming agents, flavoring agents, sweetening agents, additional antiplaque agents, abrasives, and coloring agents. These and other optional components are further described in U.S. Pat. No. 5,004,597 to Majeti, U.S. Pat. No. 3,959,458 to Agricola et al, and U.S. Pat. No. 3,937,807 to Haefele, all of which are incorporated herein by reference.

Basic amino acids useful in the compositions and methods of the invention include not only naturally occurring basic amino acids such as arginine, lysine and histidine, but also any basic amino acid having a carboxyl group and an amino group in the molecule that is water soluble and provides an aqueous solution having a pH of 7 or greater.

Thus, basic amino acids include, but are not limited to, arginine, lysine, serine, citrulline, ornithine, sarcosine, histidine, diaminobutyric acid, diaminopropionic acid, salts thereof, and/or combinations thereof. In a particular embodiment, the basic amino acid is selected from arginine, citrulline, and ornithine. In certain embodiments, the basic amino acid is arginine, e.g., L-arginine, or a salt thereof.

In certain embodiments, the basic amino acid is present in an amount corresponding to 0.1% to 15%, such as 0.1% to 10%, such as 0.1 to 5%, such as 0.5% to 3%, by weight, about, e.g., 1%, 1.5%, 2%, 3%, 4%, 5%, or 8% by weight of the total composition, wherein the weight of the basic amino acid is calculated as free form.

In certain embodiments, a salt is used within the formulation. Suitable salts include those known in the art as pharmaceutically acceptable salts, which are generally considered physiologically acceptable in the amounts and concentrations provided. Physiologically acceptable salts include salts derived from pharmaceutically acceptable inorganic or organic acids or bases, for example acid addition salts formed with acids that form physiologically acceptable anions, for example hydrochloride or bromide salts, and base addition salts formed with bases that form physiologically acceptable cations, for example base addition salts derived from alkali metals (such as potassium and sodium) or alkaline earth metals (such as calcium and magnesium). Physiologically acceptable salts can be obtained using standard procedures known in the art, for example by reacting a compound having sufficient basicity (such as an amine) with a suitable acid to provide a physiologically acceptable anion.

The present invention may in some embodiments contain anionic surfactants, for example, water soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, such as sodium N-methyl N-cocoyl taurate, sodium coco glyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl ether sulfates, e.g. of the formula CH₃(CH₂)_mCH₂(OCH₂CH₂)_nOSO₃X, wherein m is 6 to 16, e.g. 10, n is 1 to 6, e.g. 2, 3 or 4, andx is Na or, for example, sodium laureth-2 sulphate (CH)₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na); higher alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate (sodium dodecylbenzene sulfonate); higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1, 2-dihydroxypropanesulfonic acid, sulfolaurate (sulfolaurate) (potassium N-2-ethyllaurate sulfoacetamide), and sodium lauryl sarcosinate. "higher alkyl" means, for example, C_6-3o alkyl group. In particular embodiments, the anionic surfactant (when present) is selected from sodium lauryl sulfate and sodium lauryl ether sulfate. When present, the anionic surfactant is present in an amount that is effective (e.g., greater than 0.001% by weight of the formulation), but not at a concentration (e.g., 1%) that will stimulate oral tissue, and the optimal concentration depends on the particular formulation and the particular surfactant. In one embodiment, the anionic surfactant is present at 0.03 wt% to 5 wt% (e.g., 1.5 wt%).

In another embodiment, the cationic surfactants suitable for use in the present invention may be broadly defined as derivatives of aliphatic quaternary ammonium compounds having one long alkyl chain containing from 8 to 18 carbon atoms, such as lauryl trimethyl ammonium chloride, cetyl pyridinium chloride, cetyl trimethyl ammonium bromide, diisobutyl phenoxyethyl dimethyl benzyl ammonium chloride, coco alkyl trimethyl ammonium nitrite, cetyl pyridinium fluoride and mixtures thereof. Illustrative cationic surfactants are the quaternary ammonium fluorides described in U.S. Pat. No. 3,535,421 to Briner et al, which is incorporated by reference. Certain cationic surfactants may also act as bactericides in the composition.

Illustrative nonionic surfactants useful in the compositions of the present invention can be broadly defined as compounds produced by condensing alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkyl aromatic in nature. Examples of suitable nonionic surfactants include, but are not limited to, Pluronics, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and mixtures of such materials. In a particular embodiment, the composition of the invention comprises a nonionic surfactant selected from poloxamers (e.g., poloxamer 407), polysorbates (e.g., polysorbate 20), pegylated hydrogenated castor oil (e.g., pegylated 40 hydrogenated castor oil), and mixtures thereof.

Illustrative amphoteric surfactants that may be used in the compositions of the present invention include: betaines (such as cocamidopropyl betaine); derivatives of aliphatic secondary and tertiary amines in which the aliphatic groups can be straight or branched chain and in which one of the aliphatic substituents contains from about 8 to 18 carbon atoms and one contains an anionic water-solubilizing group (e.g., carboxylate, sulfonate, sulfate, phosphate, or phosphonate); and mixtures of such materials.

The surfactant or mixture of compatible surfactants may be present in the compositions of the present invention at 0.1% to 10%, in another embodiment 0.3% to 7% and in another embodiment 0.5% to 2% by weight of the total composition.

The oral care compositions of the present invention may also include flavoring agents. Flavoring agents useful in the practice of the present invention include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols, and the like, as well as sweetening agents, such as saccharin sodium. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Chemicals such as menthol, carvacrol and anethole are also suitable. Certain embodiments employ oils of peppermint and spearmint. The flavoring agent is incorporated into the oral composition at a concentration of 0.01% to 1.5% by weight of the composition.

The oral care compositions of the present invention may also include one or more chelating agents capable of complexing calcium present in the bacterial cell wall. This calcium binding weakens the bacterial cell wall and enhances bacterial lysis.

Another group of agents suitable for use as chelating agents and anticalculus agents in the present invention are soluble pyrophosphates. The pyrophosphate salt used in the composition of the present invention may be any of the alkali metal pyrophosphate salts. In certain embodiments, the salts include tetra alkali metal pyrophosphate, di alkali metal dihydrogen pyrophosphate, tri alkali metal monohydrogen pyrophosphate, and mixtures thereof, wherein the alkali metal is sodium or potassium. Salts in both hydrated and unhydrated forms are suitable. An effective amount of pyrophosphate salt useful in the compositions of the present invention is generally sufficient to provide at least 0.1 wt.% pyrophosphate ion, e.g., 0.1 to 3 wt.% 5, e.g., 0.1 to 2 wt.%, e.g., 0.1 to 1 wt.%, e.g., 0.2 to 0.5 wt.%. Pyrophosphate salts also help preserve the composition by reducing the activity of water.

In preparing oral care compositions, it is sometimes necessary to add some thickening material to provide a desirable consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agent is a carboxyvinyl polymer, carrageenan, xanthan gum, hydroxyethyl cellulose, and water soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic and gum tragacanth can also be incorporated. Silica may also be used as a thickener, for example, synthetic amorphous silica. Colloidal magnesium aluminium silicate or finely divided silica may be used as a component of the thickening composition in order to further improve the texture of the composition. In certain embodiments, the thickening agent is used in an amount of about 0.5% to about 5.0% by weight of the total composition. The thickener may be present in an amount of 1 to 15 wt%, 3 to 10 wt%, 4 to 9 wt%, 5 to 8 wt%, for example 5, 6, 7 or 8 wt%.

Natural calcium carbonate is present in rocks such as chalk, limestone, marble and travertine. It is also a major component of eggshells and mollusk shells. The natural calcium carbonate abrasive of the present invention is typically ground limestone, which may optionally be refined or partially refined to remove impurities. For use in the present invention, the material has an average particle size of less than 10 microns, for example 3 to 7 microns, for example about 55 microns. For example, the small particle silica may have an average particle size (D50) of 2.5-4.5 microns. Preferably no more than 0.01 wt%, preferably no more than 0.004 wt% of the particles will not pass through a 325 mesh screen simply because natural calcium carbonate may contain a high proportion of relatively large particles which are not carefully controlled, which would unacceptably increase abrasiveness. The material has a strong crystalline structure and is therefore much harder and more abrasive than precipitated calcium carbonate. The natural calcium carbonate has a tap density of, for example, between 1 and 1.5g/cc, such as about 1.2, for example about 1.19 g/cc. Natural calcium carbonate exists in different polymorphs, such as calcite, aragonite and vaterite, calcite being preferred for the purposes of the present invention. Examples of commercially available products suitable for use in the present invention include those from GMZ25-11 FG。

Precipitated calcium carbonate is typically prepared by: limestone is calcined to produce calcium oxide (lime) which can then be converted back to calcium carbonate by reaction with carbon dioxide in water. Precipitated calcium carbonate has a different crystal structure than natural calcium carbonate. It is generally more brittle and more porous and therefore has lower abrasiveness and higher water absorption. For use in the present invention, the particles are small, e.g. having an average particle size of 1-5 microns, and for example no more than 0.1 wt%, preferably no more than 0.05 wt% of the particles will not pass through a 325 mesh screen. The particles may, for example, have a D50 of 3-6 microns, e.g., 3.8 ═ 4.9, e.g., about 4.3; d50 of 1 to 4 microns, such as 2.2 to 2.6 microns, for example about 2.4 microns; and D10 of 1 to 2 microns, such as 1.2 to 1.4, for example about 1.3 microns. The particles have a relatively high water absorption, for example at least 25g/100g, for example 30 to 70g/100 g. Examples of commercially available products suitable for use in the present invention include, for example, those from Lagos Industria Quimica15 Plus。

In certain embodiments, the invention may comprise additional calcium-containing abrasives, such as calcium phosphate abrasives, e.g., tricalcium phosphate (Ca)₃(PO₄)₂) Hydroxyapatite (Ca)₁₀(PO₄)₆(OH)₂) Or dicalcium phosphate dihydrate (CaHPO)₄·2H₂O, sometimes also referred to herein as DiCal) or calcium pyrophosphate; and/or abrasive silica, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other siliceous material, or combinations thereof.

In certain embodiments, any silica suitable for use in oral care compositions can be used, such as precipitated silicas or silica gels. For example, the silica may also be a small particle silica (e.g., Sorbosil AC43 from PQ, Warrington, United Kingdom). The composition preferably contains 5 to 20 wt% of small particle silica, or for example 10-15 wt%, or for example 5 wt%, 10 wt%, 15 wt% or 20 wt% of small particle silica.

In another embodiment, the abrasive can be a high cleaning force precipitated silica having a film cleaning ratio (PCR) of greater than 85 when tested at a 20% loading, which is known in the art as high cleaning force silica. In general, the high-cleaning silicas also have an average particle size d of from 5 to 15 μm₅₀And 40 to 120cm³Oil absorption per 100g of silica. The cleaning efficacy of precipitated silica is expressed using a thin film cleaning ratio (PCR). This is typically measured at 20% silica loading. The high cleaning power silica preferably has a PCR value of greater than 85. The efficacy of precipitated silicas may also be expressed in terms of their abrasive characteristics using Radioactive Dentin Abrasion (RDA). Ideally, the RDA value of the oral composition should be below about 250 to protect the enamel/dentin. Methods for performing PCR and RDA are described, for example, in U.S. Pat. Nos. 5,939,051 and 6,290,933, as well as in vitro Stain Removal With Dentifrice (Invitro Removal of Stain With Dentification), G.K. Stookey et al, dental research (DentalResearch), Vol.61, pp.1236-9, 11 months 1982. In general, the precipitated silicas have an average particle size d of from 5 to 15 μm₅₀And 40 to 120cm³Oil absorption per 100g of silica. Average particle size d₅₀Is 5 to 15 μm andand an oil absorption of 40 to 120cm³Examples of precipitated silicas per 100g of silica include commercially available silicas such as103 and105(Huber Silica Americas)。

the composition preferably contains 3 to 20 wt% high cleaning force precipitated silica, or for example 10-15 wt%, or for example 5 wt%, 10 wt%, 15 wt% or 20 wt% high cleaning force precipitated silica.

The composition may also include an abrasive silica, which has an acidic pH in the composition. For example, Sylodent can be used^TMProphy silica obtained from Grace. The acidic silica abrasive is included in the dentifrice component at a concentration of about 2 to about 35 wt%, about 3 to about 20 wt%, about 3 to about 15 wt%, about 10 to about 15 wt%. In certain embodiments, the acidic silica abrasive may be present in an amount between 2-7%. In other embodiments, it may be present in an amount between 7-15 wt%. In still other embodiments, it may be present in an amount between 15-30 wt.%. For example, the acidic silica abrasive may be present in an amount selected from: 2, 3, 4,5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 wt%.

A commercially available acidic silica abrasive is Sylodent783 available from graves corporation (w.r. grace & Company) (Baltimore, Md). Sylodent783 had a pH of 3.4-4.2 when measured as a 5 wt% water slurry. For use in the present invention, the silica material has an average particle size of less than 10 microns, for example 3 to 7 microns, for example about 5.5 microns.

In some embodiments, the compositions of the present disclosure contain a buffering agent. Examples of buffering agents include anhydrous carbonates such as sodium carbonate, sesquicarbonates, bicarbonates such as sodium bicarbonate, silicates, bisulfates, phosphates (e.g., monopotassium phosphate, dipotassium phosphate, trisodium phosphate, sodium tripolyphosphate, phosphoric acid), citrates (e.g., citric acid, trisodium citrate dehydrate), pyrophosphates (sodium and potassium salts), and combinations thereof. The amount of buffering agent is sufficient to provide a pH of about 5 to about 9, preferably about 6 to about 8, and more preferably about 7, when the composition is dissolved in water, mouthwash base, or toothpaste base. Typical amounts of buffering agents are about 5% to about 35%, in one embodiment about 10% to about 30%, and in another embodiment about 15% to about 25%, by total weight of the composition.

Various other materials may be incorporated into the oral formulations of the present invention, such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated materials, such as urea, ammonium dihydrogen phosphate and mixtures thereof. These adjuvants, when present, are incorporated into the formulation in amounts that do not substantially adversely affect the desired properties and characteristics.

The present invention, in its method aspects, relates to applying a safe and effective amount of a composition described herein to the oral cavity.

The following examples further describe and demonstrate illustrative embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from its spirit and scope. Various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art and are intended to fall within the scope of the appended claims.

EXAMPLE 1 measurement of coefficient of friction

The apparatus used in these studies used a Butterfly haptens Magnetically Levitated Haptic Device (MLHD) manufactured by Butterfly headsets (Pittsburgh, Pa.) and a custom-made haptic (see Yardley et al, Skin Research and Technology, 2016; 22: 115-. MLHD is a six degree of freedom (6-DOF) device that uses six Lorentz actuator coils (Lorentz actuator coils) to generate rotational and linear forces on a central component called 'float'. In operation, the buoyancy of the MLHD is not in physical contact with the rest of the device and therefore does not create friction or backlash. MLHD is capable of moving the levitator with a spherical diameter of 24mm, with a positional resolution < 2.0 microns and a positional bandwidth of 140 Hz. MLHD is also capable of producing a maximum force of 40N at a resolution of 20mN at bandwidths > 2000 Hz.

Since MLHD is not equipped with a force/torque sensor, the buoyancy of MLHD has been modified to accept an ATI Nano-176 axial force/torque sensor (ATI Industrial Automation, Apex, NC), north carolina. The sensor is fixed at two areas of 968mm²Wherein the contacts are fixed on the two aluminum plates by bolts, and the brass coupler is fixed on the bottom plate.

To test the pig tongue in vitro with MLHD, a platform was constructed to hold the tongue sample and to bring the trigger into contact with it. The platform was custom made from a 762mm by 203mm by 3.2mm aluminium plate with a 38.1mm by 19mm slot milled in the centre of the plate to expose a portion of the tongue sample to be tested. The dimensions of the slot are determined experimentally. The platform is secured to a pair of laboratory jacks by installing two screws in each jack. Screws are placed through a pair of corresponding holes at each end of the platform and the position of the jack is maintained by marking two square areas on the table housing the MLHD using masking tape. A platform height of 114mm was used.

Once the tongue sample is fixed to the platform, the control algorithm is activated and the touch implement is moved over the surface of the tongue sample. The feeler moves ten times over a length of 22mm while maintaining a constant normal force of 0.1N and a speed of 1 mm/s. Since the MLHD workspace is 24mm in length in the x-axis, a travel distance of 22mm can maximize data collection while maintaining a safe distance from the edges of the workspace.

The pig tongue is very close to the human tongue. Each tongue has an anterior portion covered by fungiform papillae interspersed between filamentary papillae. The fungiform papillae is mushroom-shaped and contains taste buds. The filamentary papillae is the largest number of papillae and increases the friction between the tongue and the food. The filamentous papilla of the human tongue and the pig tongue have the same shape and a similar keratinization process, and the interpupillary epithelium is parakeratotic.

The pig tongue was stored in a freezer at about-20 ℃. To prepare the tongues for testing, each tongue was thawed, rinsed with cold tap water, patted dry with paper towels, and cut into two pieces approximately 2.5 "from the front of the tongue for use. Each tongue constitutes a tongue sample. Each tongue sample was placed on an aluminum platform and a plastic plate was bolted to the top to hold the sample. The back of the platform has an exposed surface of the tongue. The aluminum platform was then placed to center the exposed area over the contactor. MLHD was set to ten strokes, 22mm in length, and a normal force of 0.1N. Each tongue sample was tested at ambient temperature and humidity.

The five mouthwash solutions listed in table 1a were tested on 10 tongue samples (n ═ 10) each time. The final concentrations were as follows: hemp seed oil: 1%, caprylyl glycol 0.25%, aloe vera oil: 0.25%, and hyaluronic acid: 0.05 percent. Tongue samples were dried at ambient conditions for 45 minutes, after which the coefficient of friction was measured. Those tongue samples that were not treated with artificial saliva or mouthwash are referred to as untreated. After drying the tongue samples, a coating of 0.5mL of artificial saliva was applied evenly to each tongue sample in order to simulate natural conditions. This was done to simulate the general oral condition where oral tissue is always coated with a certain level of saliva. A coating of 0.5mL of the selected aqueous mouthwash solution was then applied.

Tables 1a and 1 b: mouthwash formulations

Table 1 b: mouthwash formulations

Table 2: the coefficient of friction on the tongue surface of pigs treated with the mouthwash product is reduced.

These mouthwash solutions cause statistically significant differences in the coefficient of friction relative to each other. Certain mouthwash formulations, for example, mouthwashes containing cannabis oil and caprylyl glycol, produced lower coefficients of friction than the control formulation of mouthwash a and the untreated sample. We hypothesize that the lower coefficient of friction here correlates with a pronounced slippery feel (oral comfort) while maintaining a sensation of hydration (high moisture content) for the individual.