GB2210265A - Dentifrice compositions - Google Patents

Abstract

Dentifrice compositions comprise a pharmaceutically-acceptable carrier incorporating (a) from about 0.001% to about 20% by weight of a cationic antimicrobial agent; (b) from about 1% to about 20% of sodium or potassium chloride; and (c) from about 6% to about 90% of a calcium pyrophosphate dentifrice abrasive. The compositions display enhanced antiplaque and antigingivitis activity.

Description

ORAL COMPOSITIONS Technical Field The present invention relates to oral compositions.

In particular, the invention relates to dentifrice compositions having improved antigingival/antiplaque activity.

Backaround In normal healthy subjects, the oral gingivae are pink and firmly attached to the underlying alveolar bone.

Gingivitis, which is a condition in which the gingivae become inflamed, swell, and extrude fluid in the crevicular area between the enamel and the teeth, is believed to be related to accumulation of plaque at the enamel/gingival junction as a result of interaction between bacteria in the mouth with nutriants in saliva. It has been suggested that if the accumulation of plaque at the enamel/gingival junction can be prevented or retarded, the severity of gingivitis and periodontitis can be reduced.

The use of antimicrobial agents to reduce plaque has been recognised for many years. It has also been recognised that such agents can promote teeth staining problems, probably by inducing mineralization of plaque. Included among references disclosing oral compositions containing antimicrobials are; US Pat. No 3,937,805, Feb 10, 1976 to Harrison; US Pat. No.

3,937,807, Feb 10, 1976 to Haefele; US Pat. No.

4,080,441, Mar 21, 1978 to Gaffar et al; US Pat. No.

4,118,474, Oct 3, 1978 to Gaffar et al; US Pat. No.

4,370,314, Jan 25, 1983 to Gaffar; US Pat. No.

4,241,049, Dec 23, 1980 to Colodney et al; US Pat. No.

3,925,543, Dec 9, 1975 to Donohue; and US. Pat. No.

4,256,731, Mar 17, 1981 to Curtis et al.

The use of salt in dentifrices for oral hygiene purposes is also generally known in the art and dentifrice formulations containing salt have been marketed in Europe for a number of years. Salt, in higher concentrations, is believed to have a stimulating effect on the gum tissues, allegedly in its ability to draw body fluids out of the gums by osmotic pressure.

It now has been found that oral compositions combining certain cationic antimicrobial agents, salt and certain dentifrice abrasive materials are especially valuable from the viewpoint of providing enhanced antiplaque and antigingivitis activity and are also effective in controlling stain. While the antimicrobial compounds, abrasives, and salt are individually known for use in dentifrice compositions it would appear that the value of the combined system for improving antiplaque and antigingivitis efficacy has not been previously disclosed or appreciated in the art.

Summary of Invention Accordingly, the present invention provides a dentifrice composition comprising a pharmaceutically acceptable carrier incorporating: (a) from about 0.001% to about 20% by weight of a cationic antimicrobial agent; (b) from about 1% to about 20% of sodium or potassium chloride; and (c) from about 6% to about 90% of a calcium pyrophosphate dentifrice abrasive.

All percentages and ratios herein are by weight unless otherwise specified.

The antimicrobials used in the compositions of the present invention can be any of a wide variety of cationic antimicrobial agents such as quaternary ammonium compounds and substituted guanidines such as chlorhexidine and the corresponding compound alexidine. Mixtures of cationic antimicrobials may also be used in the present invention.

Antimicrobial quaternary ammonium compounds include those in which one or two of the substituents on the quaternary nitrogen has a carbon chain length (typically alkyl group) of some 8 to 20, typically 10 to 18 carbon atoms while the remaining substituents (typically alkyl or benzyl group) have a lower number of carbon atoms, such as 1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethyl ammonium bromide, tetradecyl pyridinium chloride, tetradecyl ethyl pyridinium chloride, dodecyl dimethyl (2-phenoxyethyl)ammonium bromide, benzyl dimethylstearyl ammonium chloride, cetyl pyridinium chloride, quaternized 5-amino-l,3-bis(2-ethyl-hexyl) -5-methyl hexahydropyrimidine and benzethonium chloride are exemplary of typical quaternary ammonium antibacterial agents.Other compounds are the bist4-(R-amino)-l-pyridinium] alkanes as disclosed in US Pat. No. 4,206,215, June 3, 1980 to Bailey. The pyridinium compounds are the preferred quaternary ammonium compounds.

The substituted guanidines of this invention include bisbiguanide compounds having generic formula.

wherein A and A' each represent either (1) a phenyl radical which optionally is substituted by 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 carbon atoms; or (3) alicyclic groups containing from 4 to about 12 carbon atoms; wherein X and X' each represent an alkylene radical containing from 1 to 3 carbon atoms; wherein Z and Z' each can either by 0 or 1; wherein R and R' each represent either hydrogen, an alkyl radical containing from 1 to about 12 carbon atoms, or an aralkyl radical containing from 7 to about 12 carbon atoms; wherein n is an integer from 2 to 12 inclusive; wherein the polymethylene chain (CH2)n may optionally be interupted by oxygen or sulfur atoms, aromatic nuclei, etc.The water soluble salts of the above compounds are preferred for use herein. Suitable water soluble salts include the chloride, the fluoride, and especially the acetate salt. The preferred substituted guanidine is chlorhexidine -(1, 6-di(-N5-pchlorophenyl -N-diguanido)hexane).

Of all the above, the preferred antimicrobial component of the oral compositions herein is an optionally substituted N-tetradecyl pyridinium compound and is preferably selected from the N-tetradecylpyridinium salts, N-tetradecyl4-ethylpyridinium salts and mixtures thereof.

The N-tetradecylpyridinium salt can be represented as follows:

wherein X- is an acid ion constituent such as fluoride chloride, bromide, iodide, nitrate, acetate, phenylsulfonate among many others. The preferred ions are the fluoride, chloride, bromide and iodide with chloride being the most preferred.

The tetradecylethylpyridinium salt has the ethyl group at the "4" position on the ring and can be represented similarly.

wherein X is as defined above.

The amount of antimicrobial agent used in the present compositions can be any amount that is safe to use in the mouth and capable of providing reduced plaque/gingivitis and breath odor. This amount will vary depending on the pharmaceutically acceptable carrier selected but generally is in the range of from 0.001% to about 20%, preferably from about 0.01% to about 7% more preferably from about 0.05% to about 1% by weight.

Another critical component of the invention is sodium or potassium chloride which is incorporated at a level of from about 1% to about 20%, preferably from about 4% to about 12% by weight of the composition.

The abrasive polishing component of the dentifrice compositions of the present invention is calcium pyrophosphate. In particular, it is a feature of the invention that the customary abrasives such as the silica dental abrasives are apparently unsuitable for compatability reasons in salt/cationic antimicrobial systems as defined.

The abrasive polishing materials useful herein generally have an average particle size ranging from about 0.1 to about 30 microns, preferably from about 5 to about 15 microns. The abrasive is generally present at a level of from about 6% to about 70%, preferably from about 15% to about 25% when the dentifrice is a toothpaste. Higher levels, as high as 90%, may be used if the composition is a toothpowder.

Flavoring agents can also be added to dentifrice compositions. Suitable flavoring agents include essential oils such as oil of wintergreen, oil of peppermint, oil of spearmint, oil of sassafras, and oil of clove. Sweetening agents which can be used include aspartame, acesulfame, saccharin, dextrose, levulose and sodium cyclamate. Flavoring and sweetening agents are generally used in dentifrices at levels of from about 0.005% to about 2% by weight.

Dentifrice compositions can also contain emulsifying agents. Suitable emulsifying agents are those which are reasonably stable and foam throughout a wide pH range, including non-soap anionic, nonionic, cat ionic, zwitterionic and amphoteric organic synthetic detergents. Many of these suitable surfactants are disclosed by Gieske et al., US Pat. No. 4,051,234, September 27, 1977.

It is common to have a water-soluble fluoride compound present in dentifrices in an amount sufficient to give a fluoride concentration of from about 0.0025% to about 5.0% by weight, preferably from about 0.005% to about 2.0% by weight, to provide additional anticaries effectiveness. Preferred fluorides are sodium fluoride, stannous fluoride, indium fluoride, and sodium monofluorophosphate. Norris et al., US Pat.

No. 2,946,735, issued July 26, 1960 and Widder et al., US Pat. No. 3,678,154, issued July 18, 1972 disclose such salts as well as others.

Another material useful in the present toothpastes is an anionic anticalculus agent. The anionic calculus inhibitors useful in the compositions of the present invention can be any of the agents which are known to provide calculus reduction. Many of such agents are disclosed in the references listed in the background section. Preferred agents include soluble pyrophosphate salts, soluble polycarboxylic salts (e.g., polyacrylic acid), and polyphosphates among many others. The anionic agent can be present at a level of from about 0.01% to about 10%, preferably from about 1% to about 5%.

Water is also present in the toothpastes of this invention. Water employed in the preparation of commercially suitable toothpastes should preferably be deionized and free of organic impurities. Water generally comprises from about 10% to 50, preferably from about 20% to 40%, by weight of the toothpaste composition herein. These amounts of water include free water which is added plus that which is introduced with other materials such as with sorbitol.

In preparing toothpastes, it is necessary to add some thickening material to provide a desirable consistency. Suitable thickening agents include carboxyvinyl polymers such as the Carbopols (RTM), carrageenan (lambda, kappa and iota forms and mixtures thereof), hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, starch, starch glycolate, polyvinyl alcohol, sodium alginate and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as gum karaya, xanthan gum, gum arabic, and gum tragacanth can also be used.

Thickening agents in an amount from 0.2% to 5.0% preferably from about 0.5% to about 2.0% by weight of the total composition can be used. Colloidal magnesium aluminum silicate or finely divided silica such as Silodent 15, Cab-O-Sil M-5, Syloid 244, Syloid 266 and Aerosil D200 can also be added in amounts of from about 0.5% to about 20% to further improve texture.

It is also desirable to include some humectant material in a toothpaste to keep it from hardening.

Suitable humectants include glycerin, sorbitol, and other edible polyhydric alcohols such as polyethylene glycols, mannitols, sugar alcohols and polyoxyethylene alcohols. The humectant is normally present at a level of from about 15% to about 70%, preferably from about 20% to about 50% by weight of composition.

The pH of the present composition and/or its pH in the mouth can be any pH which is safe for the mouth's hard and soft tissues. Such pH's are generally from about 3 to about 10, preferably from about 4 to about 8.

EXAMPLES I - IV The following are representative compositions of the present invention. The compositions are prepared by mixing the sorbitol, glycerine, fluoride, sweetener and water in a mix tank at a temperature of from about 60"C. to about 80"C., adding the remaining components with the antimicrobial last, mixing under vacuum for about 30 minutes and packing.

Components Weight % I II III IV Sodium fluoride 0.3 - 0.3 0.3 Sodium chloride 7.5 5 9 10 Natrosol 250M1 1 1.5 1 1.5 Glycerine 7 6 8 5 Sorbitol (70%) solution 14 15 13 16 Calcium pyrophosphate 40 40 40 40 Titanium dioxide 0.4 0.4 0.4 0.4 PEG40-SD1S2 0.6 0.6 0.6 0.6 Acesulfam - K3 0.4 0.4 0.4 0.4 Flavour 2 2 2 2 Colour 0.05 0.05 0.05 0.05 HC1 (1M) 0.5 0.5 0.5 0.5 TDEPC4 0.7 1.1 - 0.9 Chlorhexidine - - 0.8 Azulene 0.05 - - 0.05 Double reverse osmosis water ~~~~~~~~~~~to to 100 100 1. Natrosol 250M Hydroxyethylcellulose supplied by Hercules Inc.

2. PEG40-SD1S PEG40-sorbitan diisostearate 3. Acesulfam-K Potassium salt of 3,4-dihydro-6-methyl-1,2,3, -oxathiazin-4-on-2,2-dioxide 4. TDEPC Tetradecylethylpyridinium chloride.

The compositions display excellent antiplaque and antigingivitis efficacy and improved stain control.

Claims (7)

1. A dentifrice composition comprising a pharmaceutically-acceptable carrier incorporating (a) from about 0.001% to about 20% by weight of a cationic antimicrobial agent; (b) from about 1% to about 20% of sodium or potassium chloride; and (c) from about 6% to about 90% of a calcium pyrophosphate dentifrice abrasive.

2. A composition according to Claim 1 wherein the cationic antimicrobial agent is selected from quaternary ammonium and substituted guanidine compounds and mixtures thereof.

3. A composition according to Claim 2, wherein the cationic antimicrobial agent is an optionally substituted C10-C18 alkyl pyridinium compound.

4. A composition according to Claim 3 wherein the cationic anti-microbial agent is an optionally substituted N-tetradecyl pyridinium compound.

5. A composition according to Claim 4 wherein the cationic microbial agent is selected from N-tetradecyl pyridinium salts and N-tetradecyl-4-ethyl-pyridinium salts and mixtures thereof.

6. A composition according to any of Claims 1 to 5 comprising from about 0.01% to about 7%, preferably from about 0.05% to about 1% of the antimicrobial.

7. A composition according to any of Claims 1 to 6 comprising from about 4% to about 12% of sodium chloride or potassium chloride.