# Patent

## Title
Antiplaque antibacterial oral composition

## Abstract

The polyethylene glycol helps to maintain an effective level of orally available Triclosan.

## Background
The present invention relates to an oral hygiene composition containing an anti-microbial material, in particular material selected from the bis-phenol group of anti-microbials.

U.S. Pat. No 4022880 discloses the use of a particular member of the bis-phenol group of antimicrobials, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, in oral hygiene formulations.

A problem associated with the use of such antimicrobials is that, due to their lipophilic nature, they tend to partition into a hydrophobic oil phase and a surfactant micellar phase and are thereby rendered unavailable for adsorption onto the oral surfaces. Since the oil/micellar phases in an oral hygiene compositions are conventionally provided by flavouring oils (such as peppermint or spearmint) and anionic detergents (such as sodium lauryl sulphate), and oils and surfactants cannot generally be removed without resulting in a product of poor consumer appeal, it would be advantageous to devise a method of making the antimicrobial available for absorption on the oral surfaces without reducing the amount of flavour or surfactant to an unacceptable level.

It has now surprisingly been found that by incorporating specified amounts of certain polyethylene glycols into oral hygiene compositions, the oral availability of antimicrobial compounds can be maintained at an effective level without severe restrictions on the quantity of oil or other hydrophobic ingredients which may be used in the composition.

According to the present invention there is provided an oral hygiene composition comprising (a) from 0.01 to 2% by weight of the composition of an antimicrobial compound of formula (I) ##STR1##

in which R.sup.1 is oxygen;

each of R.sup.2 to R.sup.6 is hydrogen, hydroxyl alkyl and, or halogen, and each of R.sup.2 to R.sup.6 is hydrogen, hydroxyl alkyl and/or halogen;

(b) from 2% to 10% by weight of the composition of one or more polyethylene glycols of molecular weight from 200 to 1000, and

(c) from 0.1% to 2% of oil-based flavour material, together with an orally acceptable excipient.

Preferably, the composition of the invention contains from 4 to 8%, more preferably from 5 to 7%, by weight of polyethylene glycol.

The preferred molecular weight range of polyethylene glycol is from 200 to 600, more preferably 200 to 400 and particularly about 300.

Examples of compounds of formula (I) are:

Triclosan is a particularly preferred compound of formula (I)

The preferred weight range of compound of formula (I) is from 0.01 to 1.0%, particularly 0.1% to 0.5%.

The quantity of oil-based flavour material is not critical within the given range, but a range of about 0.5 to 1% is generally preferred. The orally acceptable excipient in the composition of the invention can include any of the well known ingredients commonly present in oral hygiene preparations, provided they are compatible with the essential ingredients of the invention. Thus, the excipient will normally include a detergent, preferably an anionic detergent such as sodium lauryl sulphate, in an amount of from 0.05 to 5%, preferably 0.5 to 3%, and particularly 0.5 to 2%, by weight of the composition.

The excipient may also contain an abrasive or polishing agent, which may include calcium carbonate, calcium phosphate, water-insoluble sodium or potassium metaphosphates, calcium pyrophosphate, aluminium trihydrate or calcium silicate.

The various forms of silica may also be used as abrasive or polishing agents, especially silica xerogels as defined in U.S. Pat. No. 3538230

Abrasives or polishing agents may be employed in a total amount of from about 10 to 90% by weight of the composition preferably from 20 to 75% by weight.

Fluoride sources may also be present in the composition of the invention, and these may include ionic fluorides, such as alkali-metal fluorides, preferably sodium fluoride, and/or ionic monofluorophosphates. A preferred ionic monofluorophosphate is an alkali-metal monofluorophosphate especially sodium monofluorophosphate.

The composition of the invention may also contain other ingredients such as humectants (for example glycerine, sorbitol and/or further glycols) gelling agents (for example natural or synthetic gums, gum tragacanth, sodium carboxymethylcellulose, polyvinyl pyrolledone or starch), sweetening agents, for example soluble sacharin, chloroform, colouring or whitening agents (for example titanium dioxide), preservatives, emulsifying agents, silicones, alcohol, menthol, chlorophyll compounds (for example sodium copper chlorophyllin), anti-plaque agents, anticalculus agents, agents for sensitive dentine (for example strontium salts, formaldehyde), and agents which enhance the anti-caries activity of fluorides (for example calcium glycerophosphate).

The compositions of the invention are preferably in the form of dentifrices, but may also take the form of compositions which will be chewed by the user, for example chewing gum, tablets, pastil les and lozenges. Such compositions will contain conventional base materials together with suitable flavours and sweetening agents and may be formulated in known manner.

The invention is now illustrated by means of the following Examples: Toothpaste Formulation % w/w ______________________________________ Sorbitol solution (70%) 24.00 Saccharin              0.42 Triclosan              0.20 Carboxymethyl Cellulose 0.85 Natrosol 250H          0.10 Calcium silicate       0.20 Sodium monofluorophosphate (28.6%) 2.80 Calcium glycerophosphate 0.13 Chalk                  45.77 Empicol                1.00 Peppermint Oil         0.50 PEG 300                6.00 Water                  18.03 TOTAL                  100.00 ______________________________________ Gel Toothpaste (opacified) % w/w ______________________________________ Zeodent 113            18.00 Sorbitol               50.00 Syloblanc 34           3.50 PEG 400                6.00 Carboxymethyl cellulose CMC 7MF 1.00 Peppermint Oil         0.50 15% Saccharin solution 1.20 Sodium monofluorophosphate (28.6%) 2.80 Nipagin sodium         0.15 Empicol (30%)          3.00 Calcium glycerophosphate 0.07 Natrosol 250H          1.50 Triclosan              0.20 Water                  11.93 TOTAL                  100.00 ______________________________________ Zeodent is a trade mark of the Huber Corporation Syloblanc is a trade mark of W. R. Grace & Co. Empicol is sodium lauryl sulphate Natrosol is a trade mark of Hercules Ltd.

The following test mixture A was made up by normal admixture of the ingredients: Mixture A ______________________________________ .sup.1 Irgasan DP 300 0.20 Sodium Lauryl sulphate 1.00 Peppermint Oil     0.50 Sodium hydroxide   0.25 Sorbitol (70%)     30.00 Water              25.00 ______________________________________ A 1:6 dilution of the above with sterile deionised water was considered t be representative of the slurry formed in the oral cavity during brushing with a typical toothpaste formulation. .sup.1 Trade mark of Ciby Geigy for Triclosan

Mixture A was modified by incorporating therein PEG 300 (polyethylene glycol of M.W. ca 300) in amounts of from 4% to 8% by weight, in 0.5% increments.

Hydroxyapatitic discs, prepared by the method of Forward (Forward G. C. Caries Res. 11, 9-15, 1976) were incubated in sterile human saliva overnight at 37.degree. C. After 1 minute rinsing in sterile deionised water, triplicate discs were treated for 1 minute with 1.6 dilutions of the various mixtures. Discs exposed for 1 minute to a series of standard solutions containing 50-300 ppm Irgasan DP300 were similarly treated.

Three one minute rinses with sterile deionised water were employed to eliminate the effects of any carried-over, unadsorbed anti microbial.

Irgasan adsorption was assessed by agar diffusion, the rinsed discs being placed, treated surface downwards, onto the surface of assay plates containing Brain Heart Infusion agar seeded with approximately 10.sup.6 cfu/ml Staphylococcus aureus ATCC 6548. Plates were incubated aerobically for 24 hours at 37.degree. C., and the resulting zone diameter measured.

The Irgasan availability of each solution was determined by interpolation from the standard curve.

The effect of PEG 300 on the availability of Irgasan in the various mixtures is summarized in the following Table: EFFECT of PEG 300 on the availability of Irgasan Available Irgasan (ppm) % PEG 300    1        2      3      4    Mean ______________________________________ 4.0          148       96     94     92  108 4.5          159      109    108    105  123 5.0          170      127    124    120  135 5.5          187      149    140    162  160 6.0          208      191    181    194  194 6.5          187      161    199    182  182 7.0          167      146    167    160  160 7.5          156      128    154    146  146 8.0          152      120    147    136  139 0.2% Irgasan/ 112       88     90     82   93 0.5% Peppermint Oil 1.00% SLS system minus PEG (control) ______________________________________

The available Irgasan from a control formulation without PEG 300 was also measured (control contained 0.2% Irgasan, 0.5% Peppermint oil and 1% SLS).

The results show that from 4% to 8% of PEG provided enhanced Irgasan availability, with a peak valve occurring around 6%. The level of available Irgasan was shown to be significantly greater than that in the control formulation, which did not contain PEG 300.

## Claims

1. An oral hygiene composition comprising (a) from 0.01 to 2% by weight of a composition of an antimicrobial compound of formula (I) as the active therapeutic agent ##STR2## in which R.sup.1 is oxygen; each of R.sup.2 and R.sup.6 is a substituent selected from the group consisting of hydrogen, hydroxyl, alkyl and halogen, and each of R.sup.2, to R.sup.6, is a substituent selected from the group consisting of hydrogen, hydroxyl, alkyl and halogen; 200 to 1000 sufficient to increase the oral availability of the antimicrobial compound, said amount being from 2% to 10% by weight of the composition; and orally acceptable excipient.

2. A composition according to claim 1, which contains from 4 to 8% by weight of polyethylene glycol.

3. A composition according to claim 1 in which the polyethylene glycol has a molecular weight range of from 200 to 600.

4. A composition according to claim 1, in which the compound of formula (I) is selected from the group consisting of

5. A composition according to claims 1, which includes from 0.05 to 5% by weight of detergent.