MOUTHRINSE COMPOSITIONS

Abstract: The present invention relates to a mouthrinse and methods of use providing improved antimicrobial activity and thereby reducing oral bacteria, mouth malodor and further promoting oral health.

Description: MOUTHPJNSE COMPOSITIONS TECHNICAL FIELD The present invention relates to a mouthrinse and methods of use providing improved activity and thereby reducing oral bacteria, mouth malodor and further promoting oral health. BACKGROUND OF THE INVENTION Dental plaque is a mixed matrix of bacteria, epithelial cells, leukocytes, macro- phages and other oral exudate. Bacteria comprise approximately three-quarters of the plaque matrix. Any given sample of dental plaque could contain as many as 400 different varieties of microorganisms. This mix includes both aerobic and anaerobic bacteria, fungi and protozoa. Viruses have also been found in samples of dental plaque. This matrix of organisms and oral exudate continues expanding and coalesces with other plaque growths situated nearby. The bacteria synthesize levans and glucans from sucrose found in the oral cavity providing energy for the microorgan- isms. These glucans, levans and microorganisms form an adhesive skeleton for the continued proliferation of plaque. The bacteria found in plaque can secrete acids, enzymes and microtoxins which can cause caries, oral malodor and periodontal diseases such as gingivitis 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 Charbonneau et al.; U.S. Patent 4.992.276. February 12, 1991, to Dills et al.; U.S. Patent 4.945.087. July 31, 1990, to Talwar 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; IIS, 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 Parran, 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 Chemi¬ cal 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 and 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 Brillant). While antimicrobials have long been used in oral mouthrinses, there is still a need for improved formulations which provide, for example, improved antimicrobial activity along with increased user acceptance. The present invention relates to improved mouthrinse compositions com¬ bining thymol and a polyhydric alcohol. Talwar et al. discloses compositions comprising thymol together with an anethole and sugar alcohol combination to mask thymol's bitter taste. In cases where the oral composition is a toothpaste, dental cream or gel, the disclosure also suggests the use of a suitable humectant (e.g. propylene glycol). Dills et al. discloses compositions comprising a combination of thymol with hexetidine together with a suitable humectant (e.g. propylene glycol). The present invention is directed at a good tasting mouthrinse composition providing improved activity using thymol without the need for additional antimicrobials and/or taste masking agents such as anethole. It is therefore an object of the present invention to provide improved mouthrinse compositions. A still further object of the present invention is to provide an effective method of treating or preventing plaque and related periodontal diseases such as gingivitis. These objects and other objects will become more apparent from the detailed description that follows. SUMMARY OF THE INVENTION The present invention relates to a clear mouthrinse composition comprising: a.) from about 0.01% to about 0.4% of thymol; b.) from about 5% to about 30% of a polyhydric alcohol selected from among the group consisting of propylene glycol, butylene glycol, hexylene glycol and mixtures thereof; and c.) an orally acceptable carrier wherein the viscosity of said composition is below about 5 centipoise and further wherein the levels of hexetidine and anethole in said composition are less than about 0.01%. All levels and ratios are by weight of the total composition, unless otherwise indicated. Additionally, all measurements are made at 25°C unless otherwise speci¬ fied. DETAILED DESCRIPTION OF THE INVENTION The mouthrinse compositions of the present invention are 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. By the term "orally acceptable carrier," as used herein, means a suitable vehicle which can be used to apply the present compositions to the oral cavity in a safe and effective manner. The pH of those compositions herein described range from about 4.0 to about 9.5, with the preferred pH being from about 4.0 to about 9.0 and the most preferred pH being 4.5 to about 8.5. The essential as well as optional components of the compositions of the present invention are described in the following paragraphs. ESSENTIAL INGREDIENTS Thymol Thymol, also known as 5-methyl-2-(l-methylethyl)-phenol, is obtained from the essential oil of Thym s vulgari Linne 1 and Monarch punctata Linne 1 , Labiataer or from other botanical sources by fractional distillation. Alternatively, thymol may be synthesized from ?-cymene, and by interaction of w-cresol and isopropyl chloride. Essential oils are generally plant derived volatile oils and usually carry the odor or flavor of the plant. Thymol is a white crystalline powder with an aromatic odor and taste and is soluble in organic solvents and only slightly soluble in water. Thymol is incorporated in the present invention at levels of about 0.01% to about 0.4%, prefer¬ ably from about 0.05% to below about 0.1%, more preferably from about 0.06% to about 0.08%. Polyhydric Alcohols Another essential ingredient of the present invention is the polyhydric alcohol. Polyhydric alcohols are best known for their solvent and humectant properties. These alcohols are soluble in water, alcohols, ethers and lower aliphatic hydrocar- bons and also act to solubilize the flavoring agents of the present invention. The polyhydric alcohols useful in the present invention include those selected from among the group consisting of propylene glycol, butylene glycol, hexylene glycol and rriixtures thereof. The polyhydric alcohols comprise from about 5% to about 30% of the inven¬ tive compositions, preferably from about 10% to about 20%. Water Water is also present in the mouthrinse compositions of the present invention. Water comprises from about 50% to about 90%, preferably from about 70% to about 85% of the mouthrinse 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. The water, used in the present invention should preferably be deionized, distilled, free of organic impurities and bacteria and substan¬ tially free of metal ions. OPTIONAL COMPONENTS The present invention may optionally include antitartar (anticalculus or chelat- ing) agents. Antitartar agents are able to complex calcium found in the mixed matrix layers of plaque. This facilitates the loosening of plaque. Suitable antitartar agents include: di- and/or tri- carboxylic acids such as tartaric acid, citric acid, pharmaceuti¬ cally acceptable salts thereof and mixtures thereof; polymeric polycarboxylates such as methyl vinyl ether; and the various soluble pyrophosphate salts, including tetra- alkali metal pyrophosphate, di-alkali metal diacid pyrophosphate, tri-alkali metal monoacid pyrophosphate and mixtures thereof. Polymeric polycarboxylates are further described in U.S. Patent 5.096.699. herein incorporated by reference. Similarly, a further description of the various pyrophosphates is found in Kirk & Othmer, Encyclopedia of Chemical Technology. 2 n ^ ed., vol. 15, Interscience Publishers (1968) and in U.S. Patent 5.180.576. both of which are, additionally, herein incorporated by reference. Mixtures of the above described antitartar agents may also be used. Additionally, the present invention may optionally include a water-soluble fluoride compound present in the composition in an amount sufficient to give a fluoride ion concentration in the composition at 25°C of from about 0.0025% to about 5.0% by weight, preferably from about 0.005% to about 2.0% by weight when it is used to provide additional anticaries effectiveness. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-yielding materials are found in U.S. Patent No. 3.535.421. October 20, 1970 to Briner et al. and U.S. Patent No. 3.678.154. July 18, 1972 to Widder et al., both being incorporated herein by refer¬ ence. Representative fluoride ion sources include: stannous fluoride, sodium fluo- ride, potassium fluoride, sodium monofluorophosphate and many others. Stannous fluoride and sodium fluoride are particularly preferred, as well as mixtures thereof. Abrasives useful in abrading grinding and polishing teeth may also be option¬ ally incorporated into compositions of the present invention. Typical dentally ac- ceptable abrasives include insoluble calcium salts, alumina, silica, synthetic resins and mixtures thereof. Suitable silica abrasives are described in U.S. Patent 5.176.900. herein incorporated by reference. Similarly, U.S. Patent 4.623.536 discloses sodium bicarbonate, baking soda, as a mild abrasive and is herein incorporated by reference. Other compounds useful as abrasives are described in U.S. Patent 5.176.901 which is also herein incorporated by reference. Mixtures of the above described abrasives may also be used. Also desirable for inclusion in the compositions of the present invention are other stannous salts such as stannous pyrophosphate and stannous gluconate and other antimicrobials such as bis-biquanide salts, copper bisglycinate and nonionic antimicrobial salts. Also useful are enzymes, including endoglycosidase, papain, dextranase, mutanase and mixtures thereof. Such agents are disclosed in U.S. Patent No. 2.946.725. July 26, 1960, to Norris et al. and U.S. Patent No. 4.051.234. Sep¬ tember 27, 1977 to Gieske et al., both of which are herein incorporated by reference. Surfactants useful as optional components of the present invention include nonionic surfactants, betaines, zwitterionic surfactants or mixtures thereof. Suitable nonionic surfactants are described in U.S. Patent 4.992.276. February 12, 1991, Dills et al., incorporated herein by reference. Most preferred from among the nonionic surfactants are the poloxamer surfactants. A particularly preferred poloxamer is Poloxamer 407, which is sold under the tradename Pluronic F-127 by BASF-Wyan- dotte, Parsippany, N.J. Betaine surfactants are also useful in the compositions of the present invention. Preferred betaine surfactants are disclosed in U.S. Patent 5.180.577. January 19, 1993, to Polefka et al., incorporated herein by reference. Typical alkyl dimethyl betaines include decyl betaine or 2-(N-decyl-N,N-dimethylammonio) acetate, coco betaine or 2-(N-coc-N, N-dimethyl ammonio) acetate, myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine, cetyl betaine, stearyl betaine, etc. The amido- betaines are exemplified by cocoamidoethyl betaine, cocoamidopropyl betaine, lauramidopropyl betaine and the like. The betaines of choice are preferably the cocoamidopropyl betaine and, more preferably, the lauramido propyl betaine. Zwitterionic surfactants, like betaines, carry both a charged acidic and a charged basic moiety on the same molecule. Preferred zwitterionic synthetic surfac¬ tants can be broadly described as derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, in which the aliphatic radicals can be straight chain or branched, and wherein one of the aliphatic substituents contains from about 8 to 18 carbon atoms and one contains an anionic water-solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate or phosphonate. Zwitterionic surfactants suitable for use in the present invention are further described in U.S. Patent 4.198.392. April 15, 1980, to Juneja, incorporated herein by reference. Another optional ingredient is a humectant. Humectants are well known in the art. The humectant may be a single agent or a mixture of compatible humectants In the present invention, suitable humectants include xylitol, glycerin and sorbitol as well as other polyhydroxy alcohols other than the required alcohols of the present in¬ vention. While it is feasible to use a combination of humectants, the preferred embodiment incorporates the use of a single humectant. Humectants provide from about 0% to about 55%, and most preferably from about 5% to about 20% of the herein described invention. The preferred humectants include glycerin and/or sorbi- tol. The compositions of the present invention can also incorporate a flavoring agent or a mixture of compatible flavoring agents other than thymol. Such flavoring agents are well known in the art. Preferable flavoring agents are selected from among the group of essential aromatic flavor oils consisting of eucalyptol, methyl salicylate, menthol and mixtures thereof. These essential aromatic flavoring agents are included at levels of from about 0.01 to about 0.5%, preferably from about 0.04% to about 0.3%. Additional, or further optional, flavoring agents also suitable for use in the present invention include: anise, cassia, clove, dihydroanethole, es- tragole, peppermint, oxanone, phenyl ethyl alcohol, sweet birch, eugenol, spearmint, cinnamic aldehyde, menthone, alpha-ionone, ethyl vanillin, limonene, isoamylacetate, benzaldehyde, ethylbutyrate and many others. These additional, or further optional, flavoring agents comprise from about 0.01% to about 5.0%, preferably from about 0.05% to about 2.0% and most preferably from about 0.1% to about 1.0% of the herein described composition. Another preferred nonessential component of the present invention is a cool¬ ing agent or a combination of cooling agents. Suitable cooling agents are those des¬ cribed in U.S. Patent 4.136.163. January 23, 1979, to Watson et al., U.S. Patent 4.230.688. October 28, 1980, to Rowsell et al. and U.S. Patent 4.032.661. to Rowsell et al., all of which are herein incorporated by reference. Particularly pre- ferred cooling agents are N-ethyl-p-menthane-3-carboxamide (WS-3 supplied by Sterling Organics), taught by the above incorporated U.S. Patent 4.136.163 and N,2,3-trimethyl-2-isopropylbutanamide which is commercially available as WS-23 from Wilkinson Sword Limited and taught by the above incorporated U.S. Patent 4.230.688. Another particularly preferred cooling agent is 3-1-menthoxypropane 1,2-diol (TK-10 supplied by Takasago Perfumery Co., Ltd., Tokyo, Japan). This material is described in detail in U.S. Patent 4.459.425. July 10, 1984 to Amano et al. and incorporated herein by reference. 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, bicarbonates, peroxides, nitrate salts such as sodium and potassium nitrate and any other buffering system compatible with the invention's herein described essential components. These agents, if present, are included at levels of from about 0.01% to about 30%. 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 antibacterial 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 about 2%. EXAMPLES The following examples further describe and demonstrate preferred em- bodiments within the scope of the present invention. The examples are given solely for illustration, and are not to be construed as limitation of this invention as many variations thereof are possible without departing from its spirit and scope. EXAMPLE I A mouthrinse of the present invention is prepared by sequentially dissolving each of the following ingredients with agitation in a stainless steel or glass mixing tank containing the butylene glycol: Ingredients % WAV Butylene Glycol 20.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500 Examples II -VI are combinations made by incorporating the components using conventional mixing technology similar to that described in Example I. EXAMPLE II Ingredients % W/W Propylene Glycol 20.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500 EXAMPLE in Ingredients % W/W Hexylene Glycol 20.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500 EXAMPLE IV Ingredients % W/W Propylene Glycol 10.0000 Hexylene Glycol 10.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500 EXAMPLE V Ingredients % W/W Butylene Glycol 10.0000 Hexylene Glycol 10.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500 EXAMPLE VI Ingredients % W/W Butylene Glycol 10.0000 Propylene Glycol 10.0000 Poloxamer-407 0.5000 Eucalyptol 0.0900 Thymol 0.0600 Methyl Salicylate 0.0600 Menthol 0.0400 Sodium Saccharin 0.1000 Sodium Benzoate 0.0550 Benzoic Acid 0.0050 Glycerin 10.0000 Flavor 0.1000 Water, USP Purified 68.4500

Claims: What is claimed is: 1. A clear mouthrinse composition comprising: a.) from 0.01% to 0.4%, preferably from 0.06% to below 0.08%, of thymol; b.) from 5% to 30% of a polyhydric alcohol selected from among the group consisting of propylene glycol, butylene glycol, hexylene glycol and mixtures thereof; and c.) an orally acceptable carrier wherein the viscosity of said composition is below 5 centipoise and further wherein the levels of hexetidine and anethole in said composition are less than 0.01%. 2. A mouthrinse composition according to Claim 1 wherein said composition further comprises an essential aromatic flavor oil, preferably selected from the group consisting of menthol, eucalyptol, methyl salicylate and mixtures thereof. 3. A mouthrinse composition according to any one of the preceding Claims which further comprises from 5.0% to 55% of a humectant, preferably selected from the group consisting of glycerin, sorbitol and mixtures thereof. 4. A mouthrinse composition according to any one of the preceding Claims which further comprises from 0% to 20% of ethyl alcohol. 5. A mouthrinse composition according to any one of the preceding Claims which further comprises an active ingredient providing antitartar activity, preferably selected from the group consisting of citric acid, alkali metal citrate, polycarboxylates, alkali metal pyrophosphates, diphosphonates and mixtures thereof. 6. A mouthrinse composition according to any one of the preceding Claims which further comprises a dentally acceptable abrasive, preferably selected from the group consisting of sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, calcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate calcium carbonate, zirconium silicate, hydrated alumina, hydrated silica, silica gel, alkali-metal alumina silica, bentonite and mixtures thereof. 7. A pharmaceutical composition according to any one of the preceding Claims, further comprising a cooling agent, preferably selected from the group consisting of : 3-1-methoxypropane 1,2-diol, N-ethyl-p-methane-3- carboxamide, N,2,3-trimethyl-2-isopropylbutanamide and mixtures thereof.

Inventors: HALL WILLIAM GERALD, HUNTER-RINDERLE STEPHEN JOSEPH, MCLAUGHLIN KEVIN THOMAS, HALL, WILLIAM, GERALD, HUNTER-RINDERLE, STEPHEN, JOSEPH, MCLAUGHLIN, KEVIN, THOMAS
Applicants: PROCTER & GAMBLE, THE PROCTER & GAMBLE COMPANY
Application year: 1995
Main classification: A61K7
IPC codes: A61K8, A61Q11