RU2395271C2 - Compositions for oral cavity care, containing zinc and phytate - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to compositions for oral cavity care. Described are compositions, which include: (a) from approximately 0.01 to approximately 10 wt % of in fact water-insoluble zinc compound, (b) from approximately 0.01% to approximately 10 wt % of water-soluble polyphosphorilated inosite compound, selected from phytic acid, myoinosite pentakis(dihydrophosphate); myoinosite tetrakis(dihydrophosphate); myoinosite trikis(dihydrophosphate) and their salts of alkali metals, alkali earth metals or ammonium and their mixtures; and orally acceptable carrier.

EFFECT: compositions are efficient for prevention and control of oral cavity states, including dental deposit, dental tartar, caries, periodontal disease, unpleasant smell from mouth and dental erosion, and have acceptable esthetic characteristics without unpleasant astringent and metallic taste associated with zinc application.

12 cl, 2 tbl, 3 ex

Description

Technical field

The present invention relates to an oral composition comprising an essentially water-insoluble zinc compound and a phytate compound.

Prior art

The use of zinc compounds in oral care products such as mouthwashes, mouthwashes and toothpastes is a common practice. Zinc is used due to its ability to neutralize bad breath and to provide antimicrobial, anti-plaque and anticalculus activities. The activity of zinc compounds is generally attributed to zinc ions, especially divalent zinc ions (Zn ^{+ 2} ). Thus, water-soluble and easily ionizable zinc compounds, such as zinc chloride, which readily form active zinc ions, find use in oral care compositions that typically have an aqueous base. However, soluble zinc compounds have disadvantages in that they leave an unpleasant astringent and metallic taste in the mouth, and also have short-term effectiveness against plaque, tartar and as an odor inhibitor. Therefore, moderately water-soluble salts such as zinc citrate and zinc lactate were used to control the release of zinc ions, thereby reducing the astringent properties and providing a slow dissolution of the zinc compound by saliva to increase the duration of its activity in the oral cavity. The moderately soluble nature of these zinc compounds contributes to an increase in duration of action due to initial or immediate effectiveness. The use of zinc compounds with different solubilities has been disclosed, for example, in US patent No. 4082841; 4,100,269; 40,22880; 4,138,477; 4,144,323; 4,154,815; 4,289,755; 4,325,939; 4,339,432; 4,425,325; 4,416,867; 4,469,674; 4,522,806; 4,568,540; 4,647,452; 4,664,906; 4,814,163; 4,814,164; 4,992,259; 5,000,944; 5,085,850; 5,188,820; 5455024; 5,456,902; 5,587,147; 5,855,873; 6015547; 6,592,849; 6,723,305.

The use of phytic acid and phytate salts in oral care products has also been a subject of the prior art, with an emphasis on anticariotic, anticalculus, chelating and stain activity of these compounds, such as those described in US Patent Nos. 4,225,316; 4,335,102; 4,305,928; 4,394,371; 4,528,181; 4,826,675; 5,282,410; 5,286,479; 5,300,289; 5,762,911; and 5891448; in WO 02/02060; WO 04/024112; WO 04/045594; JP 04036229 A2; JP 10087458 A2; JP 10182383 A2; JP 11021216 A2; JP 11171749 A2; JP 11349460 A2; JP 56018911 A2; JP 56018912 A2; JP 56018913 A2; JP 56022721 A2; JP 56039008 A2; JP 56045408 A2; JP 56075422 A2; JP 2001233750 A2; and JP 2003335646 A2.

Although both zinc compounds and phytate compounds have been recommended for various purposes in oral care compositions, none of the known documents suggest that a combination of an insoluble zinc compound and a phytate compound in an oral care composition will be especially effective for the prevention and control of oral conditions, including tartar, plaque, caries, periodontal disease and halitosis. The compositions of the present invention take advantage of such combinations and, importantly, provide a lasting effect, while avoiding the unwanted astringent and metallic taste associated with the use of zinc.

SUMMARY OF THE INVENTION

The present invention relates to compositions for caring for the oral cavity and their use, containing in an acceptable oral carrier:

(a) from about 0.01 to about 10 wt.% essentially water-insoluble zinc compounds, and

(b) from about 0.01 to about 10% by weight of a compound containing a C — O — P bond selected from polyphosphorylated inositol compounds such as phytic acid, myoinositol pentakis (dihydrogen phosphate); myoinositide tetrakis (dihydrogen phosphate), myoinositrite (dihydrogen phosphate) and their salts of an alkali metal, alkaline earth metal or ammonium.

The compositions are effective for the prevention and control of oral conditions, including plaque, tartar, caries, periodontal disease and halitosis, and have acceptable aesthetic characteristics without the unpleasant astringent and metallic taste associated with the use of zinc.

These and other features, aspects and advantages of the invention will be apparent to those skilled in the art upon reading the description of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Although the description ends with a claims specifically indicating and clearly formulating features of the invention, it is believed that the present invention will be better understood from the following description.

All percentages and ratios used here are calculated based on the total weight of the composition, unless otherwise indicated. All percentages, ratios, and levels of ingredients indicated herein are based on the actual amount of the ingredient and do not include solvents, excipients, or other materials with which the ingredient may be combined in a commercially available product, unless otherwise indicated.

All measurements described here were performed at 25 ° C, unless indicated

otherwise.

As used herein, “including” means that other steps and other components that do not affect the end result can be added. This term covers the terms “consisting of” and “essentially consisting of”.

As used herein, the word “include” and its variants are considered non-limiting, so that listing elements of the list does not exclude other similar elements that may also be suitable for use in the materials, compositions, devices and methods of the present invention.

As used herein, the words "preferred," "preferably," and variants refer to embodiments of the invention that provide certain beneficial effects under certain conditions. However, other embodiments may also be preferred under the same or other conditions. In addition, listing one or more preferred embodiments does not imply that other embodiments will not be useful, nor does it exclude other embodiments from the scope of the invention.

"Oral care composition" or "oral composition" means a product that, when used normally, is not specifically swallowed for systemic administration of specific therapeutic agents, but is retained in the oral cavity for a time sufficient to substantially contact with the entire tooth surface and / or oral tissues in order to exhibit activity in the oral cavity. In addition to brushing your teeth to remove plaque, the function of the oral compositions is to prevent the formation of tartar and disorders such as caries, periodontitis and gingivitis, as well as the elimination and prevention of bad breath or bad breath and stains. Examples of forms of oral care products include toothpaste, dentifrice, tooth gel, subgingival gel, mouthwash, mouth spray, mousse, foam, denture care products, lozenges, chewable tablets, or chewable gum and strips or films for direct application or attachment to oral surfaces.

The term “dentifrice” as used herein means a paste, gel, or liquid formulation of the compositions, unless otherwise indicated. The dentifrice composition may be a single phase composition or may be a combination of two or more separate dentifrice compositions. The dentifrice composition may be of any desired shape, such as with internal veins, with superficial veins, multilayer, with gel surrounding the paste, or any combination thereof. Each dentifrice composition in a dentifrice comprising two or more separate dentifrice compositions may be contained in a physically separate dispenser compartment and dosed in parallel.

The term “dispenser” as used herein means any pump, tube or container suitable for dispensing compositions such as dentifrices.

The term "tooth" as used here refers to natural teeth, as well as to artificial teeth or dentures.

In this description, the terms "tartar" and "dental plaque" are used interchangeably and refer to mineralized plaque biofilms.

The term “orally acceptable carrier” as used herein includes any safe and effective materials for use in the compositions of the present invention. Such materials include conventional additives to oral care compositions, including, but not limited to, a fluoride ion source, anticalculus or anti-tartar agents, desensitizing agents, tooth whitening agents such as peroxide sources, abrasives such as silicon dioxide , herbal agents, chelating agents, buffers, anti-staining agents, alkali metal bicarbonate salts, thickening materials, wetting agents, water, surfactants, titanium dioxide, flavors system, sweetening agents, xylitol, coloring agents, and mixtures thereof.

Active and other suitable ingredients for use may be classified or described herein by their cosmetic and / or therapeutic effect or by their intended mechanism of action or function. However, it should be understood that the active and other ingredients suitable for use may in some cases provide more than one cosmetic and / or therapeutic effect or function or have more than one mechanism of action. Therefore, the classification is done here for convenience and does not limit the ingredient to the specified use or list of uses.

Oral care compositions of the present invention include, as main ingredients, a substantially water-insoluble zinc compound and a complexing agent selected from polyphosphorylated inositol compounds such as phytic acid, myoinositol pentakis (dihydrogen phosphate), myoinositol tetracycid (dihydrogen phosphate) myo din and their alkali metal or ammonium salts. Phytic acid, also known as myoinositol-1,2,3,4,5,6-hexakis (dihydrophosphate), or inositol hexaphosphoric acid and its alkali metal, alkaline earth metal or ammonium salts are preferred compounds containing C — O — P bonds, functioning as a complexing agent, promoting the solubilization of the essentially water-insoluble zinc compound to ensure the release of divalent zinc ions (Zn ^{+ 2} ), which function as an antimicrobial, anticalculus agent, anti-plaque agent and n bad smell. As used herein, the term “phytate” includes phytic acid and its salts, as well as other polyphosphorylated inositol compounds. Phytates also act as an anticariotic agent and an inhibitor of the formation of hydroxyapatite or tartar.

The term “substantially water insoluble” as used herein with respect to zinc compounds means that the zinc-containing compound has a solubility in water of less than about 0.1 grams per 100 milliliters of water at 25 ° C. Examples of substantially water-insoluble zinc compounds suitable for use include zinc carbonate, zinc oxide, zinc silicate, zinc phosphate, zinc pyrophosphate and zinc-containing minerals such as smitsonite, hydrozincite (zinc carbonate-hydroxide), aurichalcite and rosazite. A preferred zinc compound is zinc carbonate, and the term as used herein includes various forms, including a crystalline form, also called basic zinc carbonate, commercially available as basic zinc carbonate (Cater Chemicals: Bensenville, IL, USA), zinc carbonate (Shepherd Chemicals : Norwood, OH, USA), zinc carbonate (CPS Union Corp .: New York, NY, USA), zinc carbonate (Elementis Pigments: Durham, UK) and zinc carbonate AC (Bruggemann Chemicals: Newtown Square, PA, USA).

Basic zinc carbonate is a synthetic version consisting of materials close to naturally occurring hydrozincite. Idealized stoichiometry is represented as Zn ₅ (OH) ₆ (CO ₃ ) ₂ , but the actual stoichiometric ratio may vary slightly and other impurities may be included in the crystal lattice.

In accordance with certain aspects of the present invention, there are provided oral care compositions comprising, from an orally acceptable carrier, from about 0.01 to about 10% by weight of the phytate compound and from about 0.01 to about 10% by weight of one or a mixture thereof insoluble zinc compounds. In some embodiments, the substantially insoluble zinc compound is zinc carbonate, zinc oxide or zinc pyrophosphate, and the phytate compound is phytic acid or an alkali metal or ammonium salt thereof. The level of insoluble zinc compound in these embodiments is up to about 10%, typically from about 0.01% to about 5%. The level of phytate compound is up to about 10%, typically from about 0.01% to about 5%.

Although it is believed that divalent zinc ions generally have activities useful for treating the oral cavity, an important consideration in this regard is that the finished product should not be excessively astringent or have an unpleasant taste, which makes it unacceptable to the user. It is known that many soluble or moderately soluble zinc compounds, including zinc chloride, zinc acetate, zinc sulfate and zinc citrate, which readily form active zinc ions, have highly astringent properties when incorporated into aqueous oral care compositions. Therefore, the present invention uses essentially insoluble zinc compounds, which tend to be significantly less astringent than soluble or moderately soluble zinc compounds. Phytate compounds are present in the compositions to provide a solubilizing function by complexing with zinc and providing a source of active divalent zinc ions. It is also believed that the zinc / phytate complex and some insoluble zinc compounds are deposited on the teeth and other oral surfaces, thereby providing a reservoir of zinc ions released over an extended period of time. Soluble zinc salts will normally simply be washed off with water when rinsing or with saliva and, therefore, cannot provide prolonged activity.

The oral composition of the present invention may take various forms, including toothpaste, dentifrice, tooth gel, subgingival gel, mouthwash, mouth spray, mousse, foam, denture care product, candy, chewable tablets or chewing gum. The oral composition may also be included in strips or films for direct application or attachment to oral surfaces.

The compositions of the present invention will optimally have a pH in the range of from about 4.0 to about 10.0. In some embodiments, the pH of the compositions is from about 6.0 to about 9.0. The pH of the dentifrice compositions is measured in a 3: 1 aqueous suspension of dentifrice, for example, 3 parts water per 1 part toothpaste.

In addition to the components described above, the compositions of the present invention may include additional optional components collectively referred to as orally acceptable carrier materials, which are described in the following paragraphs.

Orally acceptable carrier materials

An orally acceptable carrier includes one or more compatible solid or liquid excipients or diluents suitable for topical administration to the oral cavity. "Compatible" as used here means that the components of the composition can be mixed without interaction, which would significantly reduce the stability and / or effectiveness of the composition.

Carriers or excipients of the present invention may include standard and conventional dentifrice components, non-abrasive gels, subgingival gels, mouthwashes or mouthwashes, mouth sprays, chewing gums, lollipops, and mint candies to freshen breath, as more described below.

The choice of carrier for use is primarily determined by the way the composition is to be introduced into the oral cavity. Carrier materials for toothpaste, tooth gel, etc. include abrasives, blowing agents, binders, wetting agents, flavors and sweeteners, etc., as disclosed, for example, in US Pat. No. 3,988,433 to Benedict. Carrier materials for two-phase dentifrice compositions are disclosed in US Pat. Nos. 5,213,790, issued May 23, 1993; 5,145,666, issued September 8, 1992; and 5281410, issued January 25, 1994, all in the name of Lukacovic et al. and U.S. Patent Nos. 4,849,213 and 4,528,180 to Schaeffer. Carrier materials for mouthwashes, rinses or mouthwashes typically include water, a flavor and sweeteners, etc., as disclosed, for example, in US Pat. No. 3,988,433 to Benedict. Candy carrier materials typically include a candy base; chewing gum carrier materials include a gum base, a flavoring agent, and sweeteners, such as, for example, US Pat. No. 4083955 to Grabenstetter et al. Sachets carrier materials typically include sachets, flavors, and sweeteners. For subgingival gels used to deliver active substances into or around periodontal pockets, a “subgingival gel carrier” is selected as disclosed, for example, in US Pat. Nos. 5,198,220 and 5,242,910, issued March 30, 1993 and September 7, 1993. , respectively, both in the name of Damani. Carriers suitable for the manufacture of the compositions of the present invention are well known in the art. Their choice will depend on secondary considerations, such as taste, cost and storage stability, etc.

The compositions of the present invention may take the form of non-abrasive gels and subgingival gels, which may be aqueous or non-aqueous. Aqueous gels typically include a thickening agent (from about 0.1% to about 20%), a wetting agent (from about 10% to about 55%), a flavoring agent (from about 0.04% to about 2%), a sweetener (from about 0.1% to about 3%), a coloring agent (from about 0.01% to about 0.5%) and the rest is water. Compositions may include an anticariotic agent (from about 0.05% to about 0.3% in terms of fluoride ion) and an anticalculus agent (from about 0.1% to about 13%).

In one embodiment, the compositions of the present invention are in the form of dentifrices, such as toothpastes, tooth gels, and tooth powders. The components of such toothpastes and tooth gels typically include one or more dental abrasives (from about 6% to about 50%), a surfactant (from about 0.5% to about 10%), a thickener (from about 0.1% up to about 5%), wetting agent (from about 10% to about 55%), flavoring agent (from about 0.04% to about 2%), sweetener (from about 0.1% to about 3%), coloring agent (from about 0.01% to about 0.5%) and water (from about 2% to about 45%). Such toothpastes or tooth gels may also include one or more anticariotic agent (from about 0.05% to about 0.3% in terms of fluoride ion) and anticalculus agent (from about 0.1% to about 13%). Tooth powders, of course, contain essentially all non-liquid components.

Other embodiments of the subject of the invention are mouthwashes or mouthwashes and mouth sprays. The components of such mouthwashes and mouth sprays typically include one or more of water (from about 45% to about 95%), ethanol (from about 0% to about 25%), a wetting agent (from about 0% to about 50 %), a surfactant (from about 0.01% to about 7%), a flavoring agent (from about 0.04% to about 2%), a sweetener (from about 0.1% to about 3%) and a coloring agent (from about 0.001% to about 0.5%). Such mouthwashes and mouth sprays may also include one or more anticariotic agent (from about 0.05% to about 0.3% in terms of fluoride ion) and anticalculus agent (from about 0.1% to about 3 %).

The compositions of the present invention may also be in the form of tooth solutions and rinsing fluids. The components of such dental solutions typically include one or more of water (from about 90% to about 99%), a preservative (from about 0.01% to about 0.5%), a thickener (from 0% to about 5%), a flavoring agent (from about 0.04% to about 2%), a sweetener (from about 0.1% to about 3%) and a surfactant (from 0% to about 5%).

Chewing gum compositions typically include one or more of a gum base (from about 50% to about 99%), a flavoring agent (from about 0.4% to about 2%), and a sweetener (from about 0.01% to about 20%).

The term “lollipops” as used here includes: mint candies for breath freshening, lozenges, lozenges, microcapsules and instant solid forms, including lyophilized forms (lozenges, capsules, thin films, tablets) and compressed tablets. The term “instant solid” as used herein means that the solid dosage form dissolves in less than about 60 seconds, preferably less than about 15 seconds, more preferably less than about 5 seconds, after the solid dosage form is placed in the oral cavity. Instant solid forms are disclosed in publicly available WO 95/33446 and WO 95/11671; US 4,642,903; US 4,946,684; US 4,305,502; US 4,371,516; US 5,188,825; US 5,215,756; US 5,298,261; and US 4,687,662.

Lollipops include solid disk-shaped products containing a flavored therapeutic agent. The base may be hard candy caramel, glycerinated gelatin, or a combination of sugar with enough sticky substances to shape it. These dosage forms are generally described in Remington: The Science and Practice of Pharmacy, 19th Ed., Vol. II, Chapter 92, 1995. Lollipop compositions (such as compressed tablets) typically include one or more excipients (compression sugar), flavoring agents, and lubricants. Microcapsules of the type provided herein are disclosed in US Pat. No. 5,370,864 to Peterson et al., Issued December 6, 1994.

In yet another aspect, the invention provides a dentifrice impregnated with the composition of the present invention. The dentifrice includes a device for contacting teeth and other tissues of the oral cavity, said device being impregnated with the composition of the present invention. The dentifrice may be impregnated fibers, including a thread or ribbon for cleaning interdental spaces, toothpicks, strips, films, and polymer fibers.

The types of orally acceptable carriers or excipients that may be included in the compositions of the present invention, together with specific non-limiting examples, are described in the following sections.

Fluoride source

It is common practice to use a water-soluble fluoride compound in dentifrices and other oral care compositions in an amount sufficient to provide a concentration of fluoride ion in the composition, and / or when used, from about 0.0025 to about 5.0 wt. %, preferably from about 0.005 to about 2.0 wt.%, to provide an anti-carious effect. Various fluoride ion generating materials can be used as sources of soluble fluoride in the compositions of the present invention. Examples of suitable fluoride ion release materials are shown in US Pat. No. 3,535,421, October 20, 1970, to Briner et al., And US Patent No. 3,368,154, July 18, 1972, to Widder et al. Typical sources of fluoride ions include tin (II) fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, indium fluoride, amine fluoride and many others. Tin (II) fluoride and sodium fluoride, as well as mixtures thereof, are preferred.

Abrasives

Dental abrasives suitable for use in topical oral carriers of the compositions of the present invention include many different materials. The selected material should be compatible with the compositions of interest and not excessively peel the dentin. Suitable abrasives include, for example, silicas, including gels and precipitates, insoluble sodium polymetaphosphate, hydrated alumina, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and tar abrasive materials such as dispersed formides.

Another class of abrasives for use in the compositions of the present invention are dispersed thermosetting polymerized resins, as described in US Pat. No. 3,070,510, issued to Cooley & Grabenstetter on December 25, 1962. Suitable resins include, for example, melamines, phenolic resins, urea, melamine- urea, melamine formaldehyde, urea formaldehyde, melamine urea formaldehyde, crosslinked epoxides and crosslinked polyesters.

Silica-based dental abrasives of various types are preferred due to their unique effect of exceptional toothbrushing and polishing without unnecessarily peeling tooth enamel or dentin. In this specification, silica abrasive polishing materials as well as other abrasives typically have an average particle size in the range of from about 0.1 to about 30 microns, preferably from about 5 to about 15 microns. The abrasive may be precipitated silica or silica gels such as silica xerogels described in Pader et al., US Pat. No. 3,538,230 issued March 2, 1970 and DiGiulio, US Pat. No. 3,862,307 issued January 21, 1975 Examples include silica xerogels sold under the Syloid trademark by WRGrace & Company, Davison Chemical Division, and precipitated silica materials, such as those sold by JMHuber Corporation under the Zeodent ^® trademark, in particular silica, designated Zeodent ^® 119, Zeodent ^® 118, Zeodent® 109 and Zeodent ^® 129. Types of dental abrasives based on d silica suitable for use in the toothpastes of the present invention are described more fully in Wason, US Pat. No. 4,340,583, issued July 29, 1982; and U.S. Patent Nos. 5,603,920, issued February 18, 1997; 5,589,160 issued December 31, 1996; 5,658,553 issued August 19, 1997; 5651958, issued July 29, 1997, and 6740311, issued May 25, 2004.

There may be used mixtures of abrasives, such as mixtures of the various grades of abrasives based on silica Zeodent ^®, above. The total amount of abrasive in the dentifrice composition of the present invention typically ranges from about 6 to about 70% by weight; toothpastes preferably contain from about 10 to about 50% abrasives by weight of the composition. The compositions of the dentifrice, mouthwash, mouthwash and non-abrasive gel of the present invention typically contain a small amount of abrasive or not.

Anticalculus agent

The compositions of the present invention may optionally include an additional anticalculus agent, such as a pyrophosphate salt, as a source of pyrophosphate ion. Pyrophosphate salts suitable for use in the compositions of the present invention include disubstituted pyrophosphate salts of alkali metals, tetrasubstituted pyrophosphate salts of alkali metals, and mixtures thereof. Disodium dihydropyrophosphate (Na ₂ H ₂ P ₂ O ₇ ), tetrasodium pyrophosphate (Na ₄ P ₂ O ₇ ) and tetracal pyrophosphate (K ₄ P ₂ O ₇ ) in their unhydrated as well as hydrated forms are preferred materials. In the compositions of the present invention, the pyrophosphate salt can be present in one of three ways: predominantly dissolved, predominantly undissolved, or as a mixture of dissolved and undissolved pyrophosphate.

Compositions comprising predominantly dissolved pyrophosphate include compositions in which at least one source of pyrophosphate ion is present in an amount sufficient to provide at least about 1.0% free pyrophosphate ions. The amount of free pyrophosphate ions can be from about 1 to about 15%, from about 1.5 to about 10% in one embodiment, and from about 2 to about 6% in another embodiment. Free pyrophosphate ions may be present in various protonated states depending on the pH of the composition.

Compositions comprising predominantly undissolved pyrophosphate include compositions containing not more than about 20% of the total amount of pyrophosphate salt dissolved in the composition, preferably less than about 10% of the total amount of pyrophosphate dissolved in the composition. The tetrasodium pyrophosphate salt is the preferred pyrophosphate salt in these compositions. Tetrasodium pyrophosphate can be an anhydrous salt form or a decahydrate form, or any other form, stable in solid form in dentifrice compositions. The salt is in the form of solid particles, which may be in a crystalline and / or amorphous state, and the particle size of the salt is preferably small enough to provide aesthetic acceptability and good solubility in use. The amount of pyrophosphate salt used to prepare such compositions is any amount effective for controlling tartar, typically from about 1.5 to about 15%, preferably from about 2 to about 10%, and most preferably from about 3 up to about 8% by weight of the dentifrice composition.

Compositions may also include a mixture of dissolved and undissolved pyrophosphate salts. Any of the aforementioned pyrophosphate salts may be used.

Pyrophosphate salts are described in more detail in Kirk-Othmer Encyclopedia of Chemical Technology, 3rd Ed., Vol.17, Wiley-lnterscience (1982).

Optional agents for use in place of or in combination with the pyrophosphate salt include such well-known materials as synthetic anionic polymers, including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), as described, for example, in US Pat. No. 4,627,977, to Gaffar et al., As well as, for example, polyaminopropanesulfonic acid (AMPS), polyphosphates (e.g. tripolyphosphate and hexametaphosphate), diphosphonates (e.g. EHDP; ANP), polypeptides (such as polyaspartic and polyglutamic acids ) and mixtures thereof.

Examples of phosphonate copolymers include diphosphonate-derivatized polymers in US Pat. No. 5,011,913 to Benedict et al., Such as diphosphonate-modified polyacrylic acid. Other suitable phosphonate-containing polymers are described in US Pat. No. 5,980,776 to Zakikhani, et al. And US Pat. No. 6,071,434 to Davis et al.

Polyphosphates can also be included in the compositions of the present invention. Polyphosphate is generally considered to be composed of two or more phosphate groups located predominantly in a linear configuration, although some cyclic derivatives may be present. In addition to pyrophosphates and tripolyphosphate, which are formally polyphosphates, polyphosphates having an average of about four or more phosphate groups, i.e. tetrapolyphosphate and hexametaphosphate, will also be desirable, among others. Polyphosphates larger than tetrapolyphosphate are usually amorphous glassy materials, with linear "glassy" polyphosphates having the formula:

XO (XPO ₃ ) _n X,

where X is sodium or potassium and n is from about 6 to about 125. Preferred polyphosphates are manufactured by FMC Corporation and are commercially known as Sodaphos (n≈6), Hexaphos (n≈13) and Glass H (n≈21). These polyphosphates can be used alone or in combination.

Chelating agents

Other optional agents are chelating agents, also called sequestrants, such as gluconic acid, tartaric acid, citric acid and their pharmaceutically acceptable salts. Chelating agents are capable of complexing with calcium present in bacterial cell walls. Chelating agents can also destroy plaque by removing calcium from calcium bridges to help keep this biomass intact. However, it is undesirable to use a chelating agent that has too high an affinity for calcium, as this can lead to demineralization of the teeth, which contradicts the purpose and essence of the present invention. Suitable chelating agents will typically have a calcium binding constant of about 10 ¹ to 10 ⁵ to provide improved cleaning with less plaque and tartar formation. Chelating agents also have the ability to complex with metal ions and are thus useful in preventing their negative effects on the stability or appearance of the products. Complexation of ions, such as iron or copper, helps to slow the oxidative degradation of finished products.

Examples of suitable chelating agents are gluconate and sodium or potassium citrate; citric acid / alkali metal citrate combination; disodium tartrate; dipotassium tartrate; sodium potassium tartrate; acidic sodium tartrate; potassium tartrate acid; polyphosphates of sodium, potassium or ammonium and mixtures thereof. Amounts of a chelating agent suitable for use in the present invention are from about 0.1 to about 2.5%, preferably from about 0.5 to about 2.5%, and more preferably from about 1.0 to about 2 ,5%.

Still other chelating agents suitable for use in the present invention are anionic polymeric polycarboxylates. Such materials are well known to those skilled in the art and are used in the form of free acids or partially or preferably completely neutralized, water-soluble alkali metal salts (e.g. potassium, preferably sodium) or ammonium salts. Examples are copolymers from 1: 4 to 4: 1 of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether (methoxyethylene) having a molecular weight (MW) of from about 30,000 to about 1,000,000. These copolymers are available, for example, as Gantrez AN 139 (MW 500,000), AN 119 (MW 250,000) and S-97 Pharmaceuticals (MW 70,000), from GAF Chemical Corporation.

Other functional polymer polycarboxylates include 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. 10000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional functional polymer polycarboxylates are disclosed in US Pat. No. 4,138,477, February 6, 1979, in the name of Gaffar, and US Pat. No. 4,183,914, January 15, 1980, in the name of Gaffar et al., And include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether. ; polyacrylic, polyitaconic and polymaleic acid; and sulfoacrylic oligomers with M.W. only 1000 available as Uniroyal ND-2.

Active teeth whitening agents

Active teeth whitening agents may be included in the oral compositions of the present invention. Active ingredients suitable for whitening include peroxides, metal chlorites, perborates, percarbonates, peroxyacids, persulfates, and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, urea peroxide, calcium peroxide, and mixtures thereof. Suitable metal chlorites include calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite and potassium chlorite. A preferred chlorite is sodium chlorite. Additional bleaching agents may be hypochlorite and chlorine dioxide. A preferred percarbonate is sodium percarbonate. Other suitable whitening agents include mono- and tetrahydrates of persulphates and potassium, ammonium, sodium and lithium perborate and sodium pyrophosphate peroxyhydrate.

Other active agents

The present invention may optionally include other agents, such as antimicrobial agents. Such agents include water-insoluble non-cationic antimicrobial agents, such as halogenated diphenyl ethers, phenolic compounds, including phenol and its homologs, mono- and polyalkyl and aromatic halogen phenols, resorcinol and its derivatives, bisphenol compounds and halogenated salicylanilides, benzoic esters and ganilides. Water-soluble antimicrobial agents include, but are not limited to, quaternary ammonium salts and bis-biguanide salts. Triclosan monophosphate is an additional water-soluble antimicrobial agent. Quaternary ammonium agents include those in which one or two quaternary nitrogen substituents have a carbon chain (typically alkyl groups) from about 8 to about 20, typically from about 10 to about 18 carbon atoms, and the rest of the substituents (typically alkyl or benzyl groups) contain fewer carbon atoms, for example, from about 1 to about 7 carbon atoms, typically methyl or ethyl groups. Dodecyltrimethylammonium bromide, tetradecylpyridinium chloride, domiphene bromide, N-tetradecyl-4-ethylpyridinium chloride, dodecyldimethyl- (2-phenoxyethyl) ammonium bromide, benzyl dimethylstearylammonium chloride, cetylpyridinium-2-chloro-2-benzylindinium chloride 5-methylhexahydropyrimidine, benzalkonium chloride, benzetonium chloride and methylbenzetonium chloride are examples of typical quaternary ammonium antibacterial agents. Other compounds are bis [4- (R-amino) -1-pyridinium] alkanes disclosed in US Pat. No. 4,206,215 issued June 3, 1980 to Bailey. Other antimicrobial agents may also be included, such as copper salts, zinc salts and tin (II) salts. Also suitable are enzymes, including endoglycosidase, papain, dextranase, mutanase, and mixtures thereof. Such agents are disclosed in US Pat. No. 2,946,725, July 26, 1960, in the name of Norn's et al., And US Pat. No. 4,051,234, September 27, 1977, in the name of Gieske et al. Specific examples of antimicrobial agents include chlorhexidine, triclosan, triclosan monophosphate, and flavoring oils such as thymol. Triclosan and other agents of this type are disclosed in Parran, Jr. et al., US Pat. No. 5,015,466, issued May 14, 1991, and US Pat. No. 4,894,220. January 16, 1990, addressed to Nabi et al. These anti-plaque agents may be present at a level of from about 0.01 to about 5.0% by weight of the dentifrice composition.

Surfactants

The compositions of the present invention may also include surfactants, also commonly referred to as blowing agents. Suitable surfactants are those which have sufficient stability and foaming ability over a wide pH range. The surfactant may be anionic, nonionic, amphoteric, zwitterionic, cationic, or mixtures thereof.

Suitable anionic surfactants include water-soluble salts of alkyl sulfates containing from 8 to 20 carbon atoms in an alkyl radical (e.g. sodium alkyl sulfate) and water-soluble salts of sulfonated fatty acid monoglycerides containing from 8 to 20 carbon atoms. Sodium lauryl sulfate (SLS) and coconut oil monoglyceride sulfonate sodium salts are examples of this type of anionic surfactants. Other suitable anionic surfactants are sarcosinates, such as sodium lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate and sodium dodecylbenzenesulfonate. Mixtures of anionic surfactants can also be used. Many suitable anionic surfactants are disclosed by Agricola et al., US Pat. No. 3,959,458, issued May 25, 1976. The composition of the present invention typically comprises an anionic surfactant at a level of from about 0.025 to about 9%, from about 0.05 to about 5% in some embodiments, and from about 0.1 to about 1% in other embodiments.

Another suitable surfactant is a compound selected from the group consisting of sarcosinate surfactants, isethionate surfactants and taurate surfactants. Preferred for use in this invention are the alkali metal or ammonium salts of these surfactants, such as the following sodium and potassium salts: lauroyl sarcosinate, myristoyl sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate and oleoyl sarcosinate. The sarcosinate surfactant of the present invention may approximately be present in the present compositions 0.1 to about 2.5%, preferably from about 0.5 to about 2.0 wt.% Of the total composition.

Cationic surfactants suitable for use in the present invention include derivatives of aliphatic quaternary ammonium compounds having one long alkyl chain containing from about 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride; cetyl pyridinium chloride; cetyltrimethylammonium bromide; diisobutylphenoxyethyl dimethylbenzylammonium chloride; (coconut oil fats) alkyltrimethylammonium nitrite; cetylpyridinium fluoride; etc. Preferred compounds are quaternary ammonium fluorides, described in US Pat. No. 3,535,421, October 20, 1970, to Briner et al., Wherein said quaternary ammonium fluorides have detergent properties. Certain cationic surfactants may also act as germicides in the compositions disclosed herein. Cationic surfactants such as chlorhexidine, although suitable for use in the present invention, are not preferred because of their ability to stain hard tissues of the oral cavity. Those skilled in the art are aware of this possibility and should include cationic surfactants in view of this limitation.

Non-ionic surfactants that can be used in the compositions of the present invention include compounds obtained by condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound, which may be aliphatic or alkyl aromatic in nature. Examples of suitable non-ionic surfactants include Pluronics, condensation products of polyethylene oxide with alkyl phenols, products obtained by condensation of ethylene oxide with a reaction product of propylene oxide and ethylene diamine, condensation products of ethylene oxide with aliphatic alcohols, long chain tertiary amine oxides, long chain oxides of tertiary oxides and long chain oxides mixtures of such materials.

Zwitterionic synthetic surfactants suitable for use in the present invention include derivatives of aliphatic quaternary ammonium, phosphonium and sulfonium compounds in which aliphatic radicals can be linear or branched and in which one of the aliphatic substituents contains from about 8 to 18 carbon atoms, and one contains an anionic water solubilizing group, for example, carboxy, sulfonate, sulfate, phosphate or phosphonate.

Suitable betaine surfactants are disclosed in US Pat. No. 5,180,577 to Polefka et al., Issued January 19, 1993. Typical alkydimethyl betaines include decyl betaine or 2- (N-decyl-N, N-dimethylammonio) acetate, cocobetaine or 2- ( N-coc-N, N-dimethylammonio) acetate, myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine, cetyl betaine, stearyl betaine, etc. Amidobetaines are represented by cocoamidoethyl betaine, cocoamidopropyl betaine, lauramidopropyl betaine, and the like. The best betaines are preferably cocoamidopropyl betaine and more preferably lauramidopropyl betaine.

Thickeners

When preparing toothpastes or gels, thickeners are added to provide the desired consistency of the composition, to provide the desired release characteristics of the active substances in use, to ensure storage stability and to ensure the stability of the composition, etc. Suitable thickeners include one or a combination of carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose (HEC), natural and synthetic clays (e.g. Veegum and laponite), and water soluble cellulose ether salts such as carboxymethyl cellulose sodium salt (CMC) and carboxymethyl sodium hydroxymethyl salt. Natural gums such as karaya gum, xanthan gum, gum arabic and tragacanth gum can also be used. Colloidal magnesium aluminum silicate or finely divided silica can be used as a thickener component to further improve texture.

Suitable carboxyvinyl polymers that can be used as thickeners or gelling agents include carbomers, which are homopolymers of acrylic acid, crosslinked with pentaerythritol alkyl ether or sucrose alkyl ether. Carbomers are commercially available from BFGoodrich as a series of Carbopol ^® products, including Carbopol 934, 940, 941, 956 and mixtures thereof.

Copolymers of lactide and glycolide monomers having a number average molecular weight in the range of from about 1000 to about 120,000 are suitable for delivering active substances to or around periodontal pockets as “subgingival gel carriers”. These polymers are described in US Patent Nos. 5198220 and 5242910, issued March 30, 1993 and September 7, 1993, respectively, both in the name Damani, and 4443430, issued April 17, 1984, in the name Mattei.

Thickeners are typically present in an amount of from about 0.1 to about 15%, preferably from about 2 to about 10%, more preferably, from about 4 to about 8% of the total weight of the toothpaste or gel composition can be used. Higher concentrations can be used for chewing gums, candies and mint sweets to freshen breath, sachets, non-abrasive gels and subgingival gels.

Wetting agents

Another optional carrier material for the compositions of the present invention is a wetting agent. The wetting agent serves to prevent hardening of the toothpaste compositions by air, to give the compositions a moist sensation in the mouth, and, in the case of specific wetting agents, to give the desired sweet taste to the toothpaste compositions. The wetting agent, in terms of pure wetting agent, usually comprises from about 0 to about 70%, preferably from about 5 to about 25% by weight of the compositions of the present invention. Suitable wetting agents for use in the compositions of the present invention include edible polybasic alcohols such as glycerol, sorbitol, xylitol, butylene glycol, polyethylene glycol, propylene glycol and trimethyl glycine.

Flavors and Sweeteners

Flavoring agents may also be added to the composition. Suitable flavoring agents include wintergreen oil, peppermint oil, spearmint oil, flower bud cloves, menthol, anethole, methyl salicylate, eucalyptol, cassia, 1-methyl acetate, sage, eugenol, parsley oil, oxanone, alpha-irisone, alpha-irisone, lemon, orange, propenylguaethol, cinnamon, vanillin, thymol, linalool, cinnamaldehyde-glycerol acetal, known as CGA and mixtures thereof. Flavoring agents are typically used in compositions at a level of from about 0.001 to about 5% by weight of the composition.

Sweeteners that can be used include sucrose, glucose, saccharin, sucralose, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones, acesulfame and especially sodium cyclamate, sucralose and saccharin sodium, and mixtures thereof. The composition preferably contains from about 0.1 to about 10% of these agents, preferably from about 0.1 to about 1%, by weight of the composition.

In addition to flavors and sweeteners, cold sensing agents, salivating agents, warming agents, and numbing agents may be used as optional ingredients in the compositions of the present invention. These agents are present in the compositions at a level of from about 0.001 to about 10%, preferably from about 0.1 to about 1%, by weight of the composition.

Cold sensing agents can be any of a wide variety of materials. Such materials include carboxamides, menthol, ketals, diols and mixtures thereof. Preferred cold sensing agents in the compositions of the present invention are paramentanocarboxyamide agents, such as N-ethyl-p-menthane-3-carboxamide, commercially known as "WS-3", N, 2,3-trimethyl-2-isopropylbutanamide known as "WS-23", and mixtures thereof. Additional preferred cold-sensing agents are selected from the group consisting of menthol, 3-1-menthoxypropane-1,2-diol, known as TK-10, manufactured by Takasago, a menthol glycerol acetal known as MGA, manufactured by Haarmann and Reimer, and menthyl lactate known as Frescolat ^®, manufactured by Haarmann and Reimer. The terms menthol and menthil as used here include the right- and levorotatory isomers of these compounds and their racemic mixtures. TK-10 is described in US patent No. 4459425, Amano et al., Issued 7/10/84. WS-3 and other agents are described in US patent 4136163, Watson, etal.

Suitable agents, salivating the present invention include Jambu ^®, manufactured by Takasago. Examples of heat sensing agents are capsicum and nicotinic acid esters such as benzyl nicotinate. Suitable numbing agents include benzocaine, lidocaine, flower bud clove oil, and ethanol.

Various media materials

The water used to prepare commercially suitable oral care compositions should preferably have a low ion content and no organic impurities. Water typically comprises from about 5 to about 70%, preferably from about 20 to about 50%, by weight of the aqueous composition of the present invention. These amounts of water include added free water plus water introduced with other materials such as sorbitol.

The present invention may also include an alkali metal bicarbonate salt, which can perform a number of functions, including abrasive, deodorizing, buffering and pH adjustment. Bicarbonate salts of an alkali metal are soluble in water and in an unstabilized form tend to release carbon dioxide in the aqueous system. Sodium bicarbonate, also known as baking soda, is a commonly used alkali metal bicarbonate salt. The composition of the present invention may contain from about 0.5 to about 30%, preferably from about 0.5 to about 15%, and most preferably from about 0.5 to about 5%, of an alkali metal bicarbonate salt.

The pH of the compositions of the present invention can be adjusted using buffering agents. Buffer agents, as used herein, refer to agents that can be used to adjust the pH of the compositions in the range of from about pH 4.0 to about pH 10.0. Buffering agents include sodium bicarbonate, monosodium phosphate, trisodium phosphate, sodium hydroxide, sodium carbonate, acidic sodium pyrophosphate, citric acid and sodium citrate. Buffer agents typically comprise from about 0.5 to about 10% by weight of the compositions of the present invention.

Poloxamers can be used in the compositions of the present invention. Poloxamer is classified as a non-ionic surfactant and can also function as an emulsifier, a binder, a stabilizer and to perform other similar functions. Poloxamers are difunctional block polymers with terminal primary hydroxyl groups having molecular weights ranging from 1000 to over 15,000. Poloxamers are sold under the trademark Pluronics and Pluraflo by BASF. Suitable poloxamers for this invention are Poloxamer 407 and Pluraflo L4370,

Other emulsifying agents that may be used in the present compositions include polymeric emulsifiers such as series products Pemulen ^®, available from BF Goodrich, and which are predominantly high molecular weight polymers are polyacrylic acids suitable for use as emulsifiers for hydrophobic substances.

Titanium dioxide may also be added to the composition of the present invention. Titanium dioxide is a white powder that gives the compositions opacity. Titanium dioxide is typically included in an amount of from about 0.25 to about 5% by weight of the dentifrice composition.

Other optional agents that may be used in the compositions of the present invention include dimethicone copolyols selected from alkyl and alkoxy dimethicone copolyols, such as C ₁₂ -C ₂₀ alkyl dimethicone copolyols and mixtures thereof. Most preferred is cetyl dimethicone copolyol sold under the trademark Abil EM90. Dimethicone copolyol is usually present at a level of from about 0.01 to about 25%, preferably from about 0.1 to about 5%, more preferably from about 0.5 to about 1.5 wt.%. Dimethicone copolyols contribute to the effect of a pleasant feeling on the teeth.

Another optional component of the compositions of the present invention is a dentin desensitizing agent for treating hypersensitivity such as potassium, calcium, strontium and tin salts, including nitrate, chloride, fluoride, phosphates, pyrophosphate, polyphosphate, citrate, oxalate and sulfate.

METHOD OF USE

The present invention also relates to methods for cleaning teeth and preventing undesirable oral conditions, including caries, microbial infection, plaque, tartar, stains and halitosis and dental erosion.

The use of the present invention includes contacting the surface of the tooth enamel of the subject and the oral mucosa with the oral care compositions of the present invention. The method of application may be brushing using a dentifrice, rinsing with a suspension of dentifrice or mouthwash, or chewing a chewing product. Other methods include contacting a topical gel in the oral cavity, a mouth spray or other forms with the subject's teeth and oral mucosa. It should be understood that the present invention relates not only to methods of delivering the composition of the present invention to the oral cavity of a person, but also to methods of delivering these compositions to the oral cavity of other animals, for example pets or other domestic animals or animals held in captivity.

For example, a use method may include brushing a dog’s teeth using one of the dentifrice compositions. Another example would include rinsing a cat's mouth with an oral composition for a time sufficient to exhibit a beneficial effect. Pet care products, such as chewing products and toys, may be formulated to contain the oral care compositions of the present invention. The composition is included in a relatively flexible, but strong and durable material, such as untreated leather, ropes made from natural or synthetic fibers, and polymer products made from nylon, polyester or thermoplastic polyurethane. When an animal chews, licks or gnaws a product, the active elements included are released into the animal's oral cavity in saliva, which is comparable to the effect of brushing or rinsing.

EXAMPLES

The following examples further describe and demonstrate embodiments within the scope of the present invention. These examples are for illustrative purposes only and should not be construed as limitations of the present invention, since many of their options are possible without violating the essence and scope of the invention.

Example I - Dentifrice Compositions

The dentifrice compositions of the present invention (IA-IF) and comparative examples (IG and IH) are given below, with amounts of components indicated in wt.%. These compositions are prepared in the usual way.

Ingredient IA IB 1C ID IE IF IG Ih Phytic acid (20% solution) 4,000 2,000 0,100 10,000 Sodium phytate (20% solution) 10,000 0,500 Zinc carbonate ¹ 2,000 1,000 2,000 Zinc oxide 5,000 Aurichalcite 2,000 Zinc Pyrophosphate 8,000 Zinc Lactate 2,500 Polyphosphate Na 13,000 Tin (II) Fluoride 0.454 0.454 0.454 0.454 0.454 Sodium fluoride 0.243 0.243 0.243 Sodium Gluconate 0.672 0,600 0.672 0,600 0.672 0.652 2,100 Tin (II) Chloride 1,500 1,500 Sorbitol solution 34,275 35,785 34,275 34,275 35,785 34,275 37,496 Glycerol 38,519 14,425 Hydroxyethyl cellulose 0,300 0,300 0,300 0,300 0,300 0300 Na-CMC 1,200 1,300 1,200 1,200 1,300 1,200 0,600 Carrageenan 0,500 0,500 0,500 0,500 0,500 0,500 0,600 Xanthan gum 0.350 0.700 Polyethylene glycol 7,000 Propylene glycol 7,000 Abrasive silicon dioxide 20,000 16,000 20,000 20,000 16,000 20,000 25,000 20,000 TiO ₂ (anatase) 0.525 0.525 0.525 0.525 0.525 0.525 0.525 SLS (28% solution) 4,000 7,500 4,000 4,000 7,500 4,000 2,500 5,000 Na-Saccharin 0.250 0.250 0.250 0.250 0.250 0.250 0,500 0,300 Flavoring 0.950 0.950 0.950 0.950 0.950 0.950 0,800 1,000 NaOH 0.006 0.122 0.006 0.006 0.122 0.006 0,600 Na phosphate tribasic 1,100 Water and minor additives, such as dye solution QS QS QS QS QS QS QS QS ¹ Zinc carbonate AC supplied by Bruggemann Chemical: Newtown Square, PA, USA

Example II - The effectiveness of the compositions

The antimicrobial efficacy of the compositions of the present invention is measured using an in vitro glycolysis and plaque regrowth (i-PGRM) model. The effectiveness of the control of supragingival tartar is determined by the activity of preventing calcification of plaque using a modified analysis of the growth and mineralization of plaque. The effectiveness of stain prevention by formulations of compositions containing staining-associated ingredients such as tin (II) and copper ions is measured using an in vitro tea stain film model (i-PTSM). The aesthetic acceptability of a composition, such as a decrease in astringency, palatability, and application characteristics, is measured by controlled consumer testing.

Antimicrobial activity

The concentration of zinc ions and the bioavailability required to provide a therapeutic effect may vary for different types of clinical effect, for example, anti-plaque activity compared to the anti-gingivitis effect. However, it is critically important to establish a minimum level of antimicrobial activity, since below this level the therapeutic activity of zinc may be lost. To maintain antimicrobial efficacy, it is important to provide a sufficient concentration of zinc ions from the insoluble zinc compound used in the compositions of the present invention. In this description, the minimum efficiency provided by the source of zinc ion is determined by the effect of creating metabolic inhibition of bacterial plaque biofilms responsible for numerous undesirable conditions in the oral cavity. Antimicrobial efficacy is thus determined in situ by a marked and significant decrease in plaque metabolism, as measured using the in vitro model of glycolysis and plaque re-growth (i-PGRM) developed by Procter & Gamble Laboratories.

i-PGRM is a technique in which plaque is grown from human saliva and treated with agents designed to provide different levels of antimicrobial activity. The purpose of this technique is to provide a simple and quick way to determine whether compounds have a direct effect on the metabolic pathways that plaque microorganisms use to produce toxins that adversely affect gum health. In particular, the model focuses on the production of organic acids, including lactic, acetic, propionic and butyric. This method uses plaque grown on polished glass rods, which are dipped in saliva during the night, in soy broth and sucrose for 6 hours and again in saliva during the night. The mass of plaque grown on glass rods is then treated for 1 minute with a 3: 1 suspension of water and dentifrices. The mass is then placed in soy broth / sucrose solution for 6 hours and the pH of the incubated solution is measured after 6 hours. Thus, measured pH values are obtained before incubation and pH after incubation for both the tested formulation formulations and the controls. Such testing is typically carried out with several parallel measurements to reduce experimental error and the average pH is calculated from the results of parallel measurements. Due to their high ability to affect saccharolytic organisms, compositions containing high levels of bioavailable zinc ions cause significant inhibition of acid generation in plaque in i-PGRM analysis. This makes it relatively easy to compare the compositional variations in bioavailability of zinc ions.

The results of i-PGRM are calculated by the formula:

Average pH values refer to the pH of the incubated medium obtained after processing and control application of sucrose. Negative or zinc-free dental plaque control samples produce large amounts of acid and therefore their pH is lower than that of dental plaque treated with a positive control. The pH difference between the positive and negative controls will typically be at least about 0.6 pH units, ideally at least about 1.0 pH units. The negative or zinc-free control used is a sodium fluoride-containing toothpaste sold under the name Crest ^® Cavity Protection, and the positive control is a composition containing relatively high levels of tin (II), described as comparative example IH above and described in US 5004597, in the name of Majeti et al. It was shown that such compositions with a high content of tin (II) provide significant inhibition of acid formation in plaque when analyzed by i-PGRM. The composition described in comparative example IG above containing zinc lactate (a soluble zinc compound) was also tested for comparison with compositions of the present invention containing an insoluble zinc compound.

The efficacy of a composition made from a combination of an insoluble zinc and phytate compound should ideally be comparable to the positive control, and therefore the ideal i-PGRM score should be close to 100%. As shown in the i-PGRM analysis in Table 1 below, the formulations of the compositions of the present invention are more effective for inhibiting plaque acid formation than a composition containing high levels of tin (II) or a composition containing a soluble zinc salt.

Table 1
The results of the analysis of formulation formulations using i-PGRM Composition i-PGRM Score. Zinc-free control (Crest ^® Cavity Protection) 0 High Tin (I) Positive Control (Example IH) one hundred Composition with soluble zinc lactate (Example IG) 84.85 Example IA (2% zinc carbonate + phytate) 131.75 Example IB (1% zinc carbonate + phytate) 127.96

Example III - Anti-erosion Efficiency

In addition to the aforementioned therapeutic and cosmetic effects, the compositions of the present invention, including insoluble zinc salts and phytate, also provide protection against the initiation and development of dental erosion, as studies using an in vitro cyclic erosion model have demonstrated. Here, by erosion is meant permanent loss of dental substance from the surface under the influence of chemicals such as rough abrasives and acids, in contrast to subsurface demineralization or caries caused by exposure to bacteria. Dental erosion is a condition that is not associated with plaque bacteria and therefore differs from dental caries, which is a disease caused by acids generated by plaque bacteria. It is believed that the compositions of the present invention form a barrier film or coating on the surface of the tooth, thereby protecting the tooth from the action of erosion agents in contact with them.

Human enamel samples were subjected to a 5-day cyclic erosion regimen. After the initial film formation, the samples were subjected to seven (7) treatment sequences per day, at intervals of one (1) hour. The treatment sequences consisted of suspension treatment of dentifrices (1 part of dentifrice: 3 parts of freshly collected combined human saliva [weight: weight]), remineralization with saliva and erosive acid treatment. At the end of the cyclic processing phase, the samples were analyzed using a computer program for transverse microradiography (TMR). The average surface loss was determined for each treatment group in microns of the lost enamel.

Enamel samples were prepared by cutting 3 mm cores from pulled out people's teeth using a diamond hollow drill. Teeth harvested by local surgeons were stored in 5% thymol at room temperature. Enamel cores were installed in 1/4 inch diameter Lucite rods using acrylic tooth glue (Dura Base, Reliance Mfg. Co.) covering all but the surface. A 600 grit caliber silicon carbide slurry polish is used to remove approximately 50 microns of external enamel. After that, the samples are polished for 90 minutes with gamma alumina (Linde No. 3, AB Gamma Polishing Alumina). Enamel samples with visible surface defects were rejected. After such preparation, nail polish was applied on approximately 2/3 of the surface, 1/3 on both sides, leaving the central part open as a window for processing. Samples were randomly assigned to treatment groups (5 samples / group).

In the evening before the treatment phase, each group of samples was placed in 20 ml of fresh combined human saliva to initiate film formation on the enamel surface. To begin the treatment phase, suspensions of dentifrices were prepared by mixing 5 grams of dentifrice with 15 grams of fresh combined human saliva for at least 4 and not more than 5 minutes before use. A fresh suspension is prepared for each treatment. Each treatment cycle includes: a suspension of dentifrices (1 min) → rinsing with deionized distilled water (ddiH ₂ O) → saliva (5 min) → erosion treatment (15 min) → rinsing with ddiH ₂ O. 7 treatments were performed per day for a total of five days of processing. The treatment with the dentifrice consisted of immersing the samples in a suspension of dentifrice for one minute while rotating at a speed of 75 rpm. Erosion treatment consisted in filling each treatment group with 20 ml of cola (at room temperature). Fresh cola volume was used for each treatment cycle. Saliva was renewed 3x / day at the 1st, 4th and 7th treatment cycles. All the time until the samples were processed, they were in 20 ml of combined human saliva (with stirring). At night, each group of samples remained immersed in saliva (with stirring, at room temperature).

After 5 days of treatment, the samples were washed thoroughly with ddiH ₂ O and stored in a refrigerator in a humid environment until analysis. To begin the analysis phase, a layer of nail polish was applied to the entire surface of each sample in order to close the surface and protect fragile eroded areas. Samples are cut plane-parallel using a microtome saw for hard tissues. Each slice is cut to analyze the control and the treated area. A thin section (-100 μm) is taken from each sample and placed flat on a specially designed holder compatible with the camera mounted on the x-ray source. These sections were then exposed to CuKa radiation. Radiographic images were obtained using a holographic film Kodak S0253. The film was processed by standard methods of developing a black and white film. Radiographic images were then analyzed using TMR, a computer image analysis system (Inspektor Research). By comparing the initial surface for the control (untreated) area with the surface after treatment, it is possible to measure the depth of eroded areas (μm of lost mineral matter).

The research results are shown in Table 2 below, including (1) erosion depth (μm); (2) the average value for the treatment group; and (3) `standard error of the mean (SEM). The data demonstrate the ability of the compositions of the present invention to protect human enamel from the initiation and development of dental erosion compared with the control treatment group (Crest ^® Cavity Protection). The dentifrice of the present invention, comprising 0.4% phytic acid and 1% basic zinc carbonate, provides statistically greater erosion protection than Crest ^® Cavity Protection.

table 2
Erosion depth Treatment Sample No. Erosion Depth (μm) Average Sem Crest ^® CP one 15.4 2 9.7 3 20.6 four 18.7 5 8.8 14.64 2,36 Example IB one 9.7 2 * - 3 12.0 four 6.9 5 4.0 8.15 1.55 * The sample was damaged and measurement results were not obtained.

The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact indicated numerical values. Instead, unless otherwise indicated, each such size shall denote both the indicated value and the functionally equivalent interval surrounding this value. For example, a dimension disclosed as “40 mm” should mean “about 40 mm”.

All documents cited in the detailed description of the invention, in relevant part, are incorporated herein by reference; reference to any document should not be construed as an assumption that it represents the prior art in relation to the present invention. To the extent that any meaning or definition of a term in this written document is contrary to any meaning or definition of a term in a document incorporated by reference, the meaning or definition ascribed to the term in this written document shall prevail.

Although specific embodiments of the present invention have been illustrated and described, those skilled in the art will understand that various other changes and modifications can be made without violating the spirit and scope of the invention. Therefore, it is intended that the appended claims cover all such changes and modifications that fall within the scope of the present invention.

Claims (12)

1. An oral care composition having an antimicrobial, anticalculus, anticariotic effect, a plaque elimination effect and an oral malodor control effect, comprising:
(a) from about 0.01 to about 10 wt.%, essentially water-insoluble zinc compounds,
(b) from about 0.01 to about 10 wt.% a water-soluble polyphosphorylated inositol compound selected from phytic acid, myoinositol pentakis (dihydrogen phosphate); myoinositide tetrakis (dihydrogen phosphate), myoinositrite (dihydrogen phosphate) of their alkali metal salts, alkaline earth metals or ammonium and mixtures thereof; and
orally acceptable carrier. 2. The oral composition according to claim 1, characterized in that the essentially water-insoluble zinc compound is selected from zinc carbonate, zinc oxide, zinc silicate, zinc phosphate, zinc pyrophosphate, smitsonite, hydrozincite, aurichalcite and rosazite and mixtures thereof. 3. The oral composition according to claim 1, characterized in that the polyphosphorylated inositol compound is selected from phytic acid and its salts of alkali metals, alkaline earth metals or ammonium. 4. The oral composition according to claim 1, characterized in that it further comprises one or more orally acceptable components selected from a source of fluoride ions, anticalculus agents, antimicrobial agents, tooth whitening agents, desensitizing agents, abrasives, chelating agents agents, thickeners, buffering agents, alkali metal bicarbonate salts, surfactants, coloring agents, flavoring systems, sweeteners, stain removing agents and mixtures thereof. 5. The oral composition according to claim 1, characterized in that it further comprises a source of fluoride ion selected from tin (II) fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, indium fluoride, amine fluoride and mixtures thereof. 6. The oral composition according to claim 1, characterized in that it further comprises an anticalculus agent selected from linear polyphosphates having an average chain length of from 2 to 125. 7. The oral composition according to claim 6, characterized in that the polyphosphate anticalculus agent has an average chain length of from 2 to 21. 8. The oral composition according to claim 1, characterized in that it further comprises a chelating agent. 9. The oral composition of claim 8, wherein the chelating agent is selected from gluconic acid, citric acid, tartaric acid, their alkali metal or ammonium salts and mixtures thereof. 10. The oral composition according to claim 1, characterized in that it further comprises an antimicrobial agent selected from an agent that releases tin (II) ion, triclosan, triclosan monophosphate, chlorhexidine, domifenbromide; cetylpyridinium chloride, an agent releasing copper ion, essential oils and mixtures thereof. 11. A method for the prevention and control of plaque, tartar, caries, periodontal disease and halitosis in subjects - people and animals, in which a composition is introduced into the oral cavity of a subject, comprising:
(a) from about 0.01 to about 10 wt.%, essentially water-insoluble zinc compounds,
(b) from about 0.01 to about 10 wt.% a water-soluble polyphosphorylated inositol compound selected from phytic acid, myoinositol pentakis (dihydrogen phosphate); myoinositide tetrakis (dihydrogen phosphate), myoinositrite (dihydrogen phosphate), their salts of alkali metals, alkaline earth metals or ammonium and mixtures thereof; and orally acceptable carrier. 12. A method of protecting subjects - humans and animals from the initiation and development of dental erosion, in which a composition is introduced into the oral cavity of a subject, comprising:
(a) from about 0.01 to about 10 wt.% essentially water-insoluble zinc compounds and
(b) from about 0.01 to about 10 wt.% a water-soluble polyphosphorylated inositol compound selected from phytic acid, myoinositol pentakis (dihydrogen phosphate); myoinositide tetrakis (dihydrogen phosphate), myoinositrite (dihydrogen phosphate), their salts of alkali metals, alkaline earth metals or ammonium and mixtures thereof; and orally acceptable carrier.