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WO1995017159A1 - Concentrated mouthrinse for efficient delivery of antimicrobials - Google Patents

Concentrated mouthrinse for efficient delivery of antimicrobials

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Publication number
WO1995017159A1
WO1995017159A1 PCT/US1994/014757 US9414757W WO1995017159A1 WO 1995017159 A1 WO1995017159 A1 WO 1995017159A1 US 9414757 W US9414757 W US 9414757W WO 1995017159 A1 WO1995017159 A1 WO 1995017159A1
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WO
Grant status
Application
Patent type
Prior art keywords
water
invention
present
chlorophenol
antimicrobial
Prior art date
Application number
PCT/US1994/014757
Other languages
French (fr)
Inventor
William Gerald Hall
Original Assignee
The Procter & Gamble Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILET PREPARATIONS
    • A61Q11/00Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/347Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41Amines
    • A61K8/416Quaternary ammonium compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/43Guanidines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings

Abstract

Concentrated mouthrinse, methods of use and methods of manufacturing the mouthrinse for efficient delivery of cationic and water-insoluble noncationic antimicrobials wherein the composition is concentrated and substantially free of non-cationic surfactants.

Description

CONCENTRATED MOUTH RINSE FOR EFFICIENT DELIVERY OF ANTIMICROBIALS

TECHNICAL FIELD The present invention relates to a concentrated mouthrinse and methods of use and methods of making the same, wherein there is an efficient delivery of an¬ timicrobials to the oral cavity thereby reducing oral bacteria, mouth malodor and further promoting oral health.

BACKGROUND OF THE INVENTION Plaque is an organic rrtixture of living bacteria found in the mouth. The bacteria found in plaque can secrete acids, enzymes and microtoxins which can cause caries, oral malodor and periodontal diseases such as gingivitis. It has been discovered that the compositions of the present invention possess a unique ability to form a concentrated and aesthetically pleasing mouthrinse. This invention provides a system by which, upon dilution, relatively low concentrations of germ-killing antimicrobials can be efficiently delivered to the oral cavity. In combination with the delivery of the antimicrobial, it has also been discovered this mechanism efficiently delivers a flavoring agent. This discovery therefore provides, without non-cationic surfactants, excellent taste and breath refreshment, and also efficient delivery of antimicrobial agents providing effective germ -tilling activity, thereby promoting oral health.

The use of mouthrinses to reduce or eliminate the bacterial flora of the oral cavity has been recognized for some time. Examples of previous references include: U.S. Patent 4.994.262. February 19, 1991 to tharbonneau et al.; U.S. Patent 4.923.685. May 8, 1990 to Wuelknitz et al.; U.S. Patent 4.839.158. June 13, 1989 to Michaels; U.S. Patent 4.824.661. April 25, 1989 to Wagner, U.S. Patent 4 719- 100 January 12, 1988 to Frosch; U.S. Patent 4.716.035. December 29, 1987 to Sampathkumar; U.S. Patent 4.606.911. August 19, 1986 to Hayashi et al.; U.S. Patent 4.525.343. June 25, 1985 to Raaf; U.S. Patent 4.323.551. April 6, 1982 to Pa-rran, Jr.; U.S. Patent 4.312.889. January 26, 1982 to Melsheimer, U.S. Patent 4.152.418. May 1, 1979 to Pader, U.S. Patent 4.082.841. April 4, 1978 to Pader; U.S. Patent 3.988.433. October 26, 1976 to Benedict; U.S. Patent 3.954.962. May 4, 1976 to Prussin and U.S. Patent 3.560.608. February 2, 1971 to Griebstein et al.

In addition to the compositions set forth in the above-mentioned U.S. Pa- tents, several additional references disclose mouthrinses for use in the oral cavity. See for example: Belgian Patent 776.425. published June 8, 1972 to Imperial Chemic-al Industries Limited; Canadian Patent 1081-127. published July 8, 1980; Japanese Kokai 54008-713. published January 23, 1979; Japanese Kokai 49007-440. published January 23, 1974; Soviet Union Patent 874-061. published October 25, 1981 to Krasd Perfume Works, Soviet Union Patent Application 740-248. published June 6, 1980 to Mosc Svoboda Cosmetics (similar to U.S. Patent 3.591 675 July 6, 1971 to Brilliant).

While antimicrobials have long been used in oral mouthrinses, there is still a need for additional formulations which provide improved performance in combating oral disease along with increased user acceptance.

The present invention relates to compositions comprising certain solvents, cationic antimicrobials and noncationic antimicrobials solubilized into a concentrated solution which is aesthetically pleasing. This mouthrinse is diluted with water to provide a safe and effective means for reducing bacteria found in the oral cavity and further provides a signal of efficacy to users. Compared to the ready-to-use conventional mouthwashes and rinses, the antimicrobials and flavoring agents of the present invention are delivered more efficiently while employing similar concentrations.

It is therefore an object of the present invention to provide a concentrated and aesthetically pleasing mouthrinse which upon dilution delivers more effectively the antimicrobials and flavoring agents while employing concentrations of these ingredients similar to ready-to-use mouthwashes and rinses.

A further object of the present invention is to provide mouthrinse compo¬ sitions which deliver improved antiplaque benefit.

Still a further object of the present invention is to provide a safe and effective means of preparing a mouthrinse from the concentrated solution. These objects and other objects will become more apparent from the detailed description that follows.

SUMMARY OF THE INVENΗON The present invention relates to compositions of non-carbonated, concen¬ trated, oil-in-water emulsions suitable for use as oral mouthrinses, comprising: (a) a safe and effective amount of a cationic antimicrobial agent;

(b) a safe and effective amount of a water-insoluble, noncationic antimicrobial agent;

(c) a safe and effective amount of a solvent suitable for use in the oral cavity,

(d) a safe and effective amount of a flavoring agent; and (e) water wherein the pH of the composition is from about 5 to about 8 and wherein the composition is substantially free of anionic and non-ionic surfactants and wherein the said oil-in-water emulsion breaks upon dilution with greater than about 5% v/v o an aqueous solution. Methods of use are also disclosed.

All concentrations and ratios herein are by weight and all measurements ar made at 25°C, unless otherwise specified. DETAILED DESCRIPTION OF THE INVENΗON

By "safe and effective amount" as used herein, means an amount sufficient t reduce oral bacteria and or enhance such reduction while providing no advers effects to the hard and soft tissues of the oral cavity.

By "substantially free of anionic surfactant" as used herein, means less tha 0.05%, preferably less than 0.01% and most preferably less than 0.001% of an anionic surfactant. By "substantially free of non-ionic surfactant" as used herein, means an amount which will not substantially impair the activity of the cationic surfactant. Generally, this means the composition must contain less then about 0.5%, preferably less than 0.3% and most preferably less than 0.2% of the nonionic surfactant.

The compositions of this invention employ a cationic antimicrobial agent, a water-insoluble noncationic antimicrobial, a solvent or a mixture of solvents, a flavoring agent or mixture of flavoring agents and water. The concentrated mouthrinse is preferably clear. By "clear" as used herein does not mean colorless, but means substantially lacking the presence of particles of sufficient size to scatter visible light as detected visually.

At the time of usage, the concentrated mouthrinse is mixed with a desired amount of water. This mixing allows for phase separation immediately prior to use.

Without being limited by theory, it is believed that this phase separation provides an efficient delivery of a sufficient level of antimicrobial agents, while allowing for optimal taste and aesthetics.

The amount of water added to the concentrated mouthrinse mixture must be high enough to result in the necessary phase change as described below. This phase change is conveniently observed by the user during dilution and provides a visual signal alerting the consumer the composition is ready for use.

Without being limited by theory, it is believed during dilution, as the oil phase and aqueous phase mix, the flavoring oils which are highly water-insoluble become uniformly dispersed within the water phase of the ready-to-use mouthrinse. The water-insoluble, noncationic antimicrobial of the present invention, combining with the flavor oils, is likewise dispersed throughout this phase. The cationic antimicrobials of the present invention, due to the inherent properties of both a hydrophobic and hydrophylic moiety, reside primarily at the oil-water interface. Specifically, the hydrophobic moities of the cationic antimicrobial reside within the dispersed oily phase of the bi-phasic mixture whereas the charged, hydrophilic moities of the cationic antimicrobial position themselves around the surface (or oil- water interface) of the oily droplets, forming countless micellar particles. It is the formation of this biphasic mixture and, in particular, the positioning of the cationic antimicrobial at the oil-in-water interface which contributes to the efficient antimicrobial delivery of the present invention. In addition to its antimicrobial activity, the cationic antimicrobial also acts as a magnetic towing device, delivering its micellar contents, which include the water insoluble, noncationic antimicrobial(s), to the oppositely charged surfaces of the oral mucosa. This results in a more efficient delivery of the water insoluble, noncationic antimicrobial as well. Thus, while the water-insoluble, noncationic antimicrobial is not structured so as to ensure primary residence at the oil-water interface, h still enjoys the benefit.

This phase separation, where the oily phase is dispersed within the water phase of the diluted mouthrinse, remains for several hours. However, eventually the oily phase will coalesce and form a separate layer. Therefore, it is undesirable to dilute more concentrate than will be immediately used.

The pH of the present concentrated compositions range from about 5.0 to about 8.0 with the preferred pH being from about 6.5 to about 7.0 with the most preferred pH being about 6.9. The essential, as well as optional components of the compositions of the present invention are described below.

ESSENTIAL INGREDIENTS Cationic antimicrobial agents The cationic antimicrobials used in the compositions of the present invention may be selected from the group consisting of quaternary ammonium compounds and substituted guanidines such as chlorhexidine and the corresponding compound alexidine. Mixtures of these cationic antimicrobials may also be used in the present invention.

Antimicrobial quaternary ammonium compounds include those in which one or two of the substitutes on the quaternary nitrogen has a carbon chain length (typically alkyl group) from about 8 to about 20, typically from about 10 to about 18 carbon atoms while the remaining substitutes (typically alkyl or benzyl group) have a lower number of carbon atoms, such as from about 1 to about 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethyl ammonium bromide, tetrade- cylpyridinium chloride, domiphen bromide, N-tetradecyl-4-ethyl pyridinium chloride, dodecyl dimethyl (2-phenoxyethy.) ammonium bromide, benzyl dimethylstearyl ammonium chloride, cetyl pyridinium chloride, quaternized 5-amino-l,3-bis(2-ethyl-hexyl)-5-methyl hexa hydropyrimidine, benzalkoniu chloride, benzethonium chloride and methyl benzethonium chloride are exemplary o typical quaternary ammonium antimicrobial agents. Other compounds ar bis[4-(R-amino)-l -pyridinium] alkanes as disclosed in U.S. Pat. No. 4.206.215, Jun 3, 1980 to Bailey which is incorporated herein by reference. The pyridiniu compounds are the preferred quaternary ammonium compounds, the most preferre being cetylpyridinium chloride or tetradecyipyridinium chloride. Quaternar ammonium antimicrobial agents are included in the present invention at levels o about 0.05% to about 10.0-%, preferably from about 0.2% to 3.0%, more preferabl from about 0.5% to about 3.0% and most preferably from about 0.5% to abou 2.0%.

The substituted guanidines are also suitable for use in this invention. Bis biguanide compounds, which are preferred for use in the present invention, are thos having the generic formula:

R NH NH NH NH R

I I I I I I

A- X)z-N-C-NH- -NH(CH2)n--NH-C-NH-C-N- X')n-A, wherein A and A* can be either (1) a phenyl radical which optionally is substituted b an alkyl or alkoxy group containing from 1 to about 4 carbon atoms, a nitro group, or a halogen atom; (2) an alkyl group containing from about 1 to about 12 carbo atoms; or (3) alicyclic groups containing from about 4 to about 12 carbon atoms wherein X and X each represent an alkylene radical containing from about 1 to abou 3 carbon atoms; wherein Z and Z' each can be either 0 or 1; wherein R and R' eac represent either hydrogen, an alkyl radical containing from about 1 to about 1 carbon atoms, or an aralkyi radical containing from about 7 to about 12 carbo atoms; wherein n is an integer from 2 to 12 inclusive; wherein the polymethylen chain (CH2) may optionally be interrupted for example by oxygen, sulfur atoms o aromatic nuclei. The water soluble salts of the above compounds are especially preferred for use herein. Suitable water soluble salts include the chloride, the fluoride, and especially the acetate salt. The preferred substituted guanidine is chlorhexidine-[l,6-di(-N<5>-pchlorophenyl-N-digu^do)-hexane]. The substituted guanidine antimicrobials are generally used in the present compositions at a level o from about 0.05% to about 3.0%, preferably from about 0.5% to about 3.0% and most preferably from about 0.5% to about 2.0%. Water-insoluble, Noncationic Antimicrobials The second essential component is a water-insoluble, noncatio antimicrobial. Given below are examples of water insoluble, noncatio antimicrobial agents useful to the present invention.

Halogenated Diphenyl Ethers 2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan) 2,2,-dihydroxy-5,5,-dibromo-diphenyl ether.

Phenolic Compounds (including phenol and its homologs, mono- and pol alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic compoun and halogenated salicylanilides). Phenol and its Homologs Phenol 5-Methyl-2-(l-methy1ethyl) - phenol (Thymol)

2 Methyl - Phenol

3 Methyl - Phenol

4 Methyl - Phenol

4 Ethyl - Phenol

2,4-Dimethyl - Phenol

2,5-Dimethyl - Phenol

3,4-Dimethyl - Phenol

2,6-Dimethyl - Phenol

4-n-Propyl - Phenol

4-n-Butyl - Phenol

4-n-Amyi - Phenol

4-tert--\myl - Phenol

4-n-Hexyl - Phenol

4-n-Heptyl - Phenol

Mono- and Polv-Alkvi and Aromatic HaloDhenols p-Chlorophenol

Methyl - p-Chlorophenol

Ethyl - p-Chlorophenol n-Propyl - p-Chlorophenol n-Butyl - p-Chlorophenol n-Amyl - p-Chlorophenol sec-- myl - p-Chlorophenol n-Hexyi - p-Chlorophenol Cyclohexyl p-Chlorophenol n-Heptyl p-Chlorophenol n-Octyl p-Chlorophenol o-Chlorophenol

Methyl o-Chlorophenol

Ethyl - o-Chlorophenol n-Propyl o-Chlorophenol n-Butyl o-Chlorophenol n-Amyi o-Chlorophenol

10 tert-Amyl o-Chlorophenol n-Hexyl o-Chlorophenol n-Heptyl o-Chlorophenol o-Benzyl - p-Chlorophenol o-Benxyl-m-methyl - p-Chlorophenol

15 o-Benzyl-m, m-dimethyl - p-Chlorophenol o-Phenylethyl - p-Chlorophenol o-Phenylethyl-m-methyl - p-Chlorophenol

3-Methyl - p-Chlorophenol

3,5-Dimethyl - p-Chlorophenol

20 6-Ethyl-3-methyi - p-Chlorophenol

6-n-Propyl-3-methyl - p-Chlorophenol

6-iso-Propyl-3-methyi - p-Chlorophenol

2-Ethyl-3,5-dimethyl - p-Chlorophenol

6-sec-Butyl-3-methyl - p-Chlorophenol

25 2-iso-Propyl-3,5-<i-methyl - p-Chlorophenol

6-Diethylmethyl-3-methyl - p-Chlorophenol

6-iso-Propyl-2-ethyl-3-methyl - p-Chlorophenol

2-sec- Amyl-3 , 5-dimethyl - p-Chlorophenol

2-Diethylmethyl-3,5-dimethyl - p-Chlorophenol

30 6-sec-Octyl-3-methyl - p-Chlorophenol p-Bromophenol

Methyl p-Bromophenol

Ethyl p-Bromophenol n-Propyl p-Bromophenol

35 n-Butyl p-Bromophenol n-Amyl p-Bromophenol sec-Amyl p-Bromophenol n-Hexyl p-Bromophenol cyclohexyl p-Bromophenol o-Bromophenol tert-Amyl - o-Bromophenol n-Hexyl - o-Bromophenol n-Propyl-m,mDimethyl - o-Bromophenol

2-Phenyl Phenol

4-Chloro-2-methyi phenol

4-Chloro-3-methyi phenol

4-Chloro-3,5-diπ_ethyi phenol

2,4-dichloro-3,5-dimethylphenol

3,4,5,6-terabromo-2-methylphenol

5-methyl-2-pentvlphenol

4-isopropyl-3-methylphenol

5 -Chloro-2-hydroxydiphenylmethane

Resorcinol and its Derivatives

Resorcinol

Methyl - Resorcinol

Ethyl - Resorcinol n-Propyl - Resorcinol n-Butyl - Resorcinol n-Amyl - Resorcinol n-Hexyl - Resorcinol (n = 4, Hexylresorcinol) n-Heptyl - Resorcinol n-Octyl - Resorcinol n-Nonyl - Resorcinol

Phenyl - Resorcinol

Benzyl - Resorcinol

Phenylethyi - Resorcinol

Phenylpropyl - Resorcinol p-Chlorobenzyl - Resorcinol

5-Chloro -2,4-Dihydroxydiphenyl Methane

4'-Chloro -2,4-Dihydroxydiphenyl Methane

5-Bromo -2,4-Dihydroxydiphenyl Methane

4'-Bromo -2,4-Dihydroxydiphenyl Methane Bisphenolic Compounds

2,2'-methylene bis (4-chlorophenol) 2,2'-methylene bis (3,4,6-trichlorophenol) 2,2'-methylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulphide bis (2-hydroxy-5-chlorobenzyl) sulphide

Halogenated Salicylanilides

4',5-dibromosalicyianilide

3 ,4', 5 -tribromosalicylanilide

2,3,3',5-tetrachlorosalicylanilide

3,3',5-trichlorosalicylanilide

3,5-dibromo-3'-trifluoromethyl salicylanilide 5-n-octanoyl-3'-tri--luoromethyl salicylanilide

3,5-dibromo-4'-trifluoromethyI salicylanilide

3,5-dibromo-3'-tri--luoromethyl salicylanilide (Fluorophene)

Benzoic Esters p-Hydroxybenzoic Acid

Methyl - p-Hydroxybenzoic Acid

Ethyl - p-Hydroxybenzoic Acid

Propyl - p-Hydroxybenzoic Acid Butyl - p-Hydroxybenzoic Acid

Halogenated Carbanilides

3,4,4'-tricUorc«arbani_ide 3 -trifluoromethyl-4,4'-dichlorocarbanilide 3,3',4-trichlorocarbanilide

Without being limited by theory, it is believed that the unique combination of both the cationic and water-insoluble, noncationic antimicrobials delivered in the oil- in-water emulsion of the present invention provides improved antiplaque benefits. Specifically, it is believed that the water-insoluble noncationic compounds provide an access to bacterial colonies located within plaque matrices not readily available to cationic antimicrobials. The novel combination of these two classes of antimicrobials, thus, results in a potent antiplaque composition delivering effectiv antiplaque activity regardless of the degree of existing plaque build-up.

The water-insoluble, noncationic antimicrobial is present in the ora composition prepared using the claimed method in an effective antiplaque amount, typically about 0.01-5% by weight, preferably about 0.03-1%. The antimicrobial agent is substantially water-insoluble, meaning that its solubility is less than about 1% by weight in water at 25°C and may be even less than about 0.1%. If an ionizable group is present solubility is determined at a pH at which ionization does not occur. Solvents or Solvent System

Another essential ingredient of the composition of the present invention is solvent or solvent system such as those described in U.S. Patent 5.141.961. August 25, 1992 to Coapman, herein incorporated by reference. The solvent(s), which constitute the bulk of the present composition act as a carrier for the flavoring oils. The solvent or solvent system solubilizes the flavoring oils in the concentrate and aids in dispersing, upon dilution with added water, all oil soluble components of the concentrated formulation thereby forming a uniformly dispersed mixture. The solvents most preferred for use in the present invention are: polyethylene glycols, propylene glycol, butylene glycol and hexylene glycol or mixtures thereof. Propylene glycol being the most preferred.

Propylene glycol is well known in the art and available from any of a number of suppliers. Propylene glycol is miscibie in all proportions with water and also has the ability to dissolve the flavoring agent(s) of the present invention. Propylene glycol suitable for use in the present invention is obtainable from any number of sources such as Dow Chemical. Polyethylene glycols are also well known in the art and lower molecular weight species possess characteristics similar to propylene glycol. Polyethylene glycols suitable for use in the present invention are the polyethylene glycols having an average molecular weight of less than or equal to 600, such as PEG 300 "Carbowax" supplied by Union Carbide. Solvents comprise from about 30% to about 90%, preferably from about 35% to about 80% and most preferably from about 45% to about 80% of the concentrated form of the mouthrinse.

Water Water is present in the concentrated composition of the present invention. Water comprises from about 10% to about 40%, preferably from about 10% to about 30% and most preferably from about 10% to about 25% of the oral compositions described herein. These amounts of water include the free water which is added, plus that amount which is introduced with other materials such as with sorbitol. Th water, used in the present invention should preferably be deionized, distilled, free o organic impurities and bacteria and substantially free of metal ions.

Flavoring Agents Another essential ingredient of the present invention is a flavoring agent or mixture of compatible flavoring agents. Such flavoring agents are well known in th art. Suitable flavoring agents include: anise, cassia, clove, dihydroanethole estragole, menthol, peppermint, oxanone, phenyl ethyl alcohol, sweet birch, thymol eugenol, eucalyptol, wintergreen, spearmint, cinnamic aldehyde, menthone, alpha-ionone, ethyl vanillin, limonene, isoamylacetate, benzaldehyde, ethylbutyrat and many others. In the herein described compositions the flavoring agents compris from about 0.2% to about 9.0%, preferably from about 0.6% to about 4.0% and most preferably from about 2.0% to about 4.0% of the herein described composition.

OPTIONAL COMPONENTS An optional ingredient useful in the present invention is a humectant or mixture of compatible humectants. Humectants are well known in the art. In th present invention suitable humectants include the poryhydric alcohols such as xylitol- glycerin and sorbitol as well as other polyhydroxy alcohols and mixtures of these humectants. Although, it is feasible to use a single humectant, it is preferred to incorporate a combination of humectants. Humectants provide from 0% to about

55%, and most preferably from about 15% to about 30% of the herein described invention. The preferred combination of humectants includes glycerin and sorbitol in a ratio of about 10: 1 to about 1 :4, and most preferably from about 3: 1 to about 1 :2.

Other optional components include, but are not limited to: coloring agents; sweeteners, including saccharin, dextrose, levulose, cyclamate and aspartate, along with many others; buffering systems such as benzoic acid and sodium benzoate, citric acid and sodium citrate and any other buffering system compatible with the invention's herein described essential components. Another optional component of the present invention is ethyl alcohol. Ethyl alcohol provides several functions when combined in the compositions of the present invention. Its inclusion can be, but is not limited to use as an additional antimicrobial or as an astringent. Ethyl alcohol can be incorporated in the present invention at a level of less than about 40%, preferably less than about 10% and most preferably in concentrations of less than 2%.

Still another optional component of the present invention is a cooling agent such as those described in U.S. Patent 4.136.163. January 23, 1979, to Watson et al, U.S. Patent 4.230.668. October 28, 1980 to Rowsell et al. and U.S. Patent 4.032.661. to Rowsell et al. all herein incorporated by reference. One particularly preferred cooling agent is N-ethyl-p-menthane-3-carboxamide (WS-3 supplied by Sterling Organics), taught by the above incorporated U.S. Patent 4.136.163.

PROCESS OF PREPARING The present invention to be effectively used as an antimicrobial mouthrinse should be prepared by the user just prior to use by adding an aqueous solution, preferably water to the concentrated oil-in-water emulsion or by adding the con¬ centrated oil-in-water emulsion to water. Upon dilution, the oil-in-water emulsion breaks, leaving the diluted composition cloudy (or opaque). This generally occurs with the addition to the emulsion of greater than 5% v/V, preferably from about 10% and most preferably from about 20% of an aqueous solution. Therefore, after dilution, the resulting composition is not completely transparent. This transformation can be visually observed, or can be readily measured using a spectrophotometer. Any appreciable difference in the absorbance of light as between the undiluted concentrate and the diluted concentrate signifies the interaction and diffusion of light necessary to the invention, establishing the range of "cloudiness." No additional agitation or mixing energy is required to cause rapid dispersion, forming a uniformly dispersed mixture of the compositions antimicrobials), flavoring oil(s) and other ingredients. The dilution of the mouthrinse concentrate requires mixing the concentrate with water in a range of ratios from about 1:1 to about 1:100, preferably from about 1:2 to about 1:50, more preferably from about 1:5 to about 1:50 and most preferably from about 1:20 to about 1:50.

COMPOSITION USE The present invention in its method aspect involves rinsing the oral cavity with a safe and effective amount of a mouthrinse prepared by the user by diluting the herein described concentrate with a suitable amount of water. Generally, an amount of at least about 0.01 grams of the antimicrobial becomes available by diluting the concentrate as described above and is effective in eliminating or reducing the bacterial flora residing within the oral cavity.

METHOD OF MANUFACTURING The method of manufacturing the disclosed compositions of the present invention are common in the oral products area.

The following examples further describe and demonstrate preferred embodi¬ ments within the scope of the present invention. The examples are given solely for illustration, and are not to be construed as limiting this invention as many variations thereof are possible without departing from its spirit and scope. EXAMPLE I A concentrated mouthrinse of the present invention is prepared by combini the following ingredients as described below. Also given is the dilution factor diluting the concentrated composition.

Dilution Ratio (concentrate:water') = 1 :39

Cetylpyridinium Chloride 2.000%

Triclosan 3.0000%

Propylene Glycol 77.0000%

Water 11.0000%

Flavor 3.0000%

WS-3* 1.0000%

Sodium Saccharin 3.0000%

*N-ethyl-p-methane-3-carboxamide, offered by WiJJtinson-Sword, Inc. In a stainless steel or glass mixing tank containing the quantity of solvent, s quentially add the following ingredients dissolving each with agitation: flavo cooling agent, benzoic acid, antimicrobial, humectant(s), purified water, sodiu benzoate, sweetening agent and dye.

To the above concentrate a user adds 39 parts water.

The diluted composition will become cloudy signaling the user the mouthrin is ready for use. The user then rinses the oral cavity with approximately 20 ml of th diluted composition and expels the mouthrinse. This use reduces or eliminates t bacteria found in the oral cavity, preventing gingivitis and oral calamity. Substantiall similar results are achieved when the above exemplified antimicrobial agent replaced in whole or in part with Dodecyl trimethyl ammonium bromid tetradecylpyridinium chloride, domiphen bromide, N-tetradecyl-4-ethyl pyridiniu chloride, dodecyl dimethyl (2-phenoxyethyl) ammonium bromide, benzyl dimet ylstearyl ammonium chloride, cetyl pyridinium chloride, quaternized 5-amin

-l,3-bis(2-ethyl-hexyl)-5-methyl hexa hydropyrimidine, benzalkonium chlorid benzethonium chloride and methyl benzethonium chloride or any of the other herei described antimicrobial agents.

EXAMPLE π Dilution Ratio (concentrate:water) = 1 :39 Cetylpyridinium Chloride 2.000% Thymol 2.0000% Propylene Glycol 75.0000%

Water 14.5000%

Flavor 3.0000% WS-3 0.5000%

Sodium Saccharin 3.0000%

EXAMPLE m Dilution Ratio (concentrate:water) = 1 :9 Cetylpyridinium Chloride 0.5000%

Thymol 0.5000%

Propylene Glycol 70.0000%

Water 27.3000%

Flavor 1.0000% Sodium Saccharin 0.7000%

Examples H & DI are combinations are manufactured in a manne substantially similar to Example I.

Claims

What is Claimed is:
1. A non-carbonated, concentrated, oral composition in the form of an oil-in- water emulsion comprising:
(a) from 0.05% to 10.0% of a cationic antimicrobial agent;
(b) from 0.05 to 10.0 of a water-insoluble, noncationic antimicrobial agent;
(c) from 30% to 90% of a solvent safe for use in the oral cavity;
(d) from 0.2% to 9.0% of a flavoring agent; and
(e) from 10% to 40% water wherein the pH of the composition is from 5 to 8 and wherein the composition is substantially free of anionic and nonionic surfactants and characterized in that said oil-in-water emulsion breaks upon dilution with greater than 5% v/v of an aqueous solution.
2. An oral composition according to Claim 1 wherein the antimicrobial compound is selected from the quaternary ammonium antimicrobial group consisting of cetylpyridinium chloride and tetradecylpyridinium chloride and mixtures thereof.
3. An oral composition according to any one of the preceding Claims wherein the quaternary ammonium antimicrobial compound is present at a level of from 0.5% to 3.0%.
4. An oral composition according to any one of the preceding Claims wherein the water-insoluble, noncationic antimicrobial is selected from the group consisting of thymol, phenol, hexylresorcinol, and triclosan and mixtures thereof.
5. An oral composition according to any one of the preceding Claims wherein the water-insoluble, noncationic antimicrobial is triclosan.
6. An oral composition according to any one of the preceding Claims wherein the solvent is present at a level of from 40% to 80%.
7. An oral composition according to any one of the preceding Claims wherein the solvent is selected from the group consisting of propylene glycol and polyethylene glycol, butylene glycol, hexylene glycol and mixtures thereof.
8. An oral composition according to any one of the preceding Claims wherein the flavoring agent is from 0.6% to 4.0%.
9. An oral composition according to any one of the preceding Claims which additionally comprises from 5.0% to 55.0% of a humectant selected from the group consisting of glycerin and sorbitol and mixtures thereof.
10. An oral composition according to any one of the preceding Claims which additionally comprises from 0% to 20% ethyl alcohol.
PCT/US1994/014757 1993-12-22 1994-12-21 Concentrated mouthrinse for efficient delivery of antimicrobials WO1995017159A1 (en)

Priority Applications (2)

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US08/171,576 1993-12-22

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EP19950906064 EP0735856A1 (en) 1993-12-22 1994-12-21 Concentrated mouthrinse for efficient delivery of antimicrobials
JP51758694A JPH09510186A (en) 1993-12-22 1994-12-21 Concentrated mouthrinse for the efficient delivery of antimicrobial agents

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WO1995034276A1 (en) * 1994-06-10 1995-12-21 The Procter & Gamble Company Mouthrinse compositions
WO1995034277A1 (en) * 1994-06-10 1995-12-21 The Procter & Gamble Company Mouthrinse compositions
US5891422A (en) * 1996-10-10 1999-04-06 Warner-Lambert Company Antimicrobial composition containing a C3 -C6 alcohol
US5961970A (en) * 1993-10-29 1999-10-05 Pharmos Corporation Submicron emulsions as vaccine adjuvants
WO2001054502A2 (en) * 2000-01-31 2001-08-02 University Of Arkansas Concentrated solution of quaternary ammonium compounds and methods of use
EP1148870A1 (en) * 1999-02-03 2001-10-31 Wm. Wrigley Jr. Company Anti-plaque emulsions and products containing same
US6440395B1 (en) 1992-06-22 2002-08-27 Barry M. Libin Antiplaque mouth rinse
WO2005072693A1 (en) * 2004-01-29 2005-08-11 The Procter & Gamble Company Oral care compositions comprising increased bioavailable levels of quaternary ammonium antimicrobials
WO2012015420A1 (en) * 2010-07-30 2012-02-02 Colgate-Palmolive Company Mouthwash formulations for use with toothbrush delivery device
EP2415473A1 (en) * 2006-11-10 2012-02-08 The Procter and Gamble Company Oral Care Compositions Containing Combinations of Anti-Bacterial and Host-Response Modulating Agents
WO2013070198A1 (en) * 2011-11-09 2013-05-16 Colgate-Palmolive Company Alcohol-free mouthwash
US8920168B2 (en) 2007-01-24 2014-12-30 Colgate-Palmolive Company Oral care implement having fluid delivery system
US9402700B2 (en) 2011-03-09 2016-08-02 Colgate-Palmolive Company Interdental cleaning device
US9554641B2 (en) 2012-10-26 2017-01-31 Colgate-Palmolive Company Oral care implement
US9717667B2 (en) 2012-12-20 2017-08-01 Colgate-Palmolive Company Oral care composition containing ionic liquids
RU2648461C2 (en) * 2012-06-21 2018-03-26 Дзе Проктер Энд Гэмбл Компани Mouth rinse emulsions

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Cited By (31)

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US6440395B1 (en) 1992-06-22 2002-08-27 Barry M. Libin Antiplaque mouth rinse
US5961970A (en) * 1993-10-29 1999-10-05 Pharmos Corporation Submicron emulsions as vaccine adjuvants
WO1995034277A1 (en) * 1994-06-10 1995-12-21 The Procter & Gamble Company Mouthrinse compositions
US5681549A (en) * 1994-06-10 1997-10-28 The Procter & Gamble Company Mouthrinse compositions
US5686063A (en) * 1994-06-10 1997-11-11 The Procter & Gamble Company Mouthrinse compositions
WO1995034276A1 (en) * 1994-06-10 1995-12-21 The Procter & Gamble Company Mouthrinse compositions
US8323673B2 (en) 1996-04-12 2012-12-04 University Of Arkansas Concentrated, non-foaming solution of quaternary ammonium compounds and methods of use
US6864269B2 (en) 1996-04-12 2005-03-08 University Of Arkansas Concentrated, non-foaming solution of quarternary ammonium compounds and methods of use
US7541045B2 (en) 1996-04-12 2009-06-02 University Of Arkansas Concentrated, non-foaming solution of quaternary ammonium compounds and methods of use
US5891422A (en) * 1996-10-10 1999-04-06 Warner-Lambert Company Antimicrobial composition containing a C3 -C6 alcohol
US6436369B2 (en) * 1998-12-17 2002-08-20 Wm. Wrigley Jr. Company Anti-plaque emulsions and products containing same
US7022314B2 (en) * 1998-12-17 2006-04-04 Wm. Wrigley Jr. Company Anti-plaque emulsions and products containing same
EP1148870A1 (en) * 1999-02-03 2001-10-31 Wm. Wrigley Jr. Company Anti-plaque emulsions and products containing same
EP1148870A4 (en) * 1999-02-03 2005-12-14 Wrigley W M Jun Co Anti-plaque emulsions and products containing same
WO2001054502A2 (en) * 2000-01-31 2001-08-02 University Of Arkansas Concentrated solution of quaternary ammonium compounds and methods of use
WO2001054502A3 (en) * 2000-01-31 2002-03-07 Univ Arkansas Concentrated solution of quaternary ammonium compounds and methods of use
WO2005072693A1 (en) * 2004-01-29 2005-08-11 The Procter & Gamble Company Oral care compositions comprising increased bioavailable levels of quaternary ammonium antimicrobials
US9241885B2 (en) 2004-01-29 2016-01-26 The Procter & Gamble Company Oral care compositions comprising increased bioavailable levels of quaternary ammonium antimicrobials
CN1909875B (en) 2004-01-29 2012-09-05 宝洁公司 Oral care compositions comprising increased bioavailable levels of quaternary ammonium antimicrobials
EP2415473A1 (en) * 2006-11-10 2012-02-08 The Procter and Gamble Company Oral Care Compositions Containing Combinations of Anti-Bacterial and Host-Response Modulating Agents
US8920168B2 (en) 2007-01-24 2014-12-30 Colgate-Palmolive Company Oral care implement having fluid delivery system
US9167886B2 (en) 2007-01-24 2015-10-27 Colgate-Palmolive Company Oral care implement having fluid delivery system
WO2012015420A1 (en) * 2010-07-30 2012-02-02 Colgate-Palmolive Company Mouthwash formulations for use with toothbrush delivery device
US9271565B2 (en) 2010-07-30 2016-03-01 Colgate-Palmolive Company Mouthwash formulations for use with toothbrush delivery device
US9402700B2 (en) 2011-03-09 2016-08-02 Colgate-Palmolive Company Interdental cleaning device
WO2013070198A1 (en) * 2011-11-09 2013-05-16 Colgate-Palmolive Company Alcohol-free mouthwash
US9192565B2 (en) 2011-11-09 2015-11-24 Colgate-Palmolive Company Alcohol-free mouthwash
US20140286880A1 (en) * 2011-11-09 2014-09-25 Colgate-Palmolive Company Alcohol-free mouthwash
RU2648461C2 (en) * 2012-06-21 2018-03-26 Дзе Проктер Энд Гэмбл Компани Mouth rinse emulsions
US9554641B2 (en) 2012-10-26 2017-01-31 Colgate-Palmolive Company Oral care implement
US9717667B2 (en) 2012-12-20 2017-08-01 Colgate-Palmolive Company Oral care composition containing ionic liquids

Also Published As

Publication number Publication date Type
EP0735856A1 (en) 1996-10-09 application
CN1137750A (en) 1996-12-11 application
JPH09510186A (en) 1997-10-14 application

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