Claims:1. An anti-staining mouthwash composition comprising chlorhexidine gluconate, an effective amount of an anti-staining agent and one or more orally acceptable excipients.

2. The anti-staining mouthwash composition as claimed in claim 1, wherein the anti-staining agent is a combination of polyvinylpyrrolidone and sodium citrate.

3. The anti-staining mouthwash composition as claimed in claim 2, wherein the polyvinylpyrrolidone is present in an amount of 1 to 5% w/w.

4. The anti-staining mouthwash composition as claimed in claim 2, wherein the sodium citrate is present in an amount of 0.1 to 10% w/w.

5. An anti-staining mouthwash composition comprising 1% w/w chlorhexidine gluconate, 1% w/w polyvinylpyrrolidone, 1% w/w sodium citrate and one or more orally acceptable excipients.

6. The anti-staining mouthwash composition as claimed in any of the preceding claim for anti-plaque, anti-caries, anticalculus and/or periodontal therapy.
, Description:The following specification particularly describes the invention and the manners in which it is to be performed
ANTI-STAINING CHLORHEXIDINE MOUTHWASH COMPOSITIONS

FIELD OF THE INVENTION
The present invention relates to an anti-staining mouthwash composition of cationic antibacterial agents such as chlorhexidine.

BACKGROUND OF THE INVENTION
Chorhexidine based mouthwashes for oral hygiene is already well known since this compound is a strong antibacterial agent due to its ability to penetrate the outer membrane of bacteria and to coagulate their internal proteins. Chlorhexidine additionally has intense antiplaque activity. It prevents the formation of bacterial plaque by competing with calcium ions and thus preventing the formation of the cuticle, the agglutination of bacteria, their adhesion to cuticle and the bond between glycoproteins.

However, the use of chlorhexidine based mouthwash in oral hygiene has the known drawback of forming a brownish pigmentation on teeth. This is believed to arise from an interaction between the chlorhexidine and certain dietary components, particularly those rich in tannins such as tea, coffee and red wine. Whilst this problem may to some extent be alleviated by brushing of the teeth with toothpaste prior to use of the product containing the cationic antibacterial agent. In many instances, it is found necessary to resort to professionally administered scaling and polishing to remove the stain.

In consequence there have been many suggestions in the patent literature for chemical anti staining agents which may be incorporated along with the cationic antibacterial agent or which may, in some instances, be used instead separately, after the cationic antibacterial agent. Examples include carboxylic acids (US4256731), aminocarboxylate compounds (US4080441), phosphonoacetic acid (US4118474), peroxydiphosphate salts (US4273759) and a polymer having certain pendant polyalkylene oxide chains (GB 2213721-A).

The present inventors have now surprisingly found that the development of stain may be at least substantially mitigated if not eliminated by the use of a combination of polyvinylpyrrolidone (PVP) and sodium citrate in chlorhexidine based mouthwash composition. There is no prior art which discloses the use of this specific combination as an anti-staining agent in a single mouthwash composition of chlorhexidine.

An object of the present invention is therefore to provide an anti-staining mouthwash composition for oral hygiene comprising chlorhexidine, polyvinylpyrrolidone (PVP) and sodium citrate.

SUMMARY OF THE INVENTION
The present specification relates to an anti-staining mouthwash composition of cationic antibacterial agents such as chlorhexidine.

In one aspect, the present specification relates to a mouthwash composition comprising chlorhexidine or its orally acceptable salts and an effective amount of an anti-staining agent.

In another aspect, the present specification relates to a mouthwash composition comprising chlorhexidine gluconate, an effective amount of an anti-staining agent and one or more orally acceptable excipients, characterized in that the anti-staining agent is a combination of polyvinylpyrrolidone (PVP) and sodium citrate.

In another aspect, the present specification relates to a mouthwash composition which may be used for anti-plaque, anti-caries, anticalculus and/or periodontal (including anti-gingivitis) therapy.

BRIEF DESCRIPTION OF FIGURES
Figure 1: Comparative stain color development (?E) on the HAP discs for examples 1 to 3.

DESCRIPTION OF THE INVENTION
The present specification relates to an anti-staining mouthwash composition of cationic antibacterial agents such as chlorhexidine.

In one aspect, the present specification relates to a mouthwash composition comprising chlorhexidine or its orally acceptable salts and an effective amount of an anti-staining agent.

In another aspect, the present specification relates to a mouthwash composition comprising chlorhexidine gluconate and an effective amount of an anti-staining agent.

In another aspect, the present specification relates to a mouthwash composition comprising chlorhexidine gluconate, an effective amount of an anti-staining agent and one or more orally acceptable excipients.

In another aspect, the present specification relates to a mouthwash composition comprising chlorhexidine gluconate, an effective amount of an anti-staining agent and one or more orally acceptable excipients, characterized in that the anti-staining agent is a combination of polyvinylpyrrolidone (PVP) and sodium citrate.

In another aspect, the present specification relates to an anti-staining mouthwash composition which may be used for anti-plaque, anti-caries, anticalculus and/or periodontal (including anti-gingivitis) therapy.

Suitable salts of chlorhexidine include gluconate, digluconate, diformate, diacetate, dipropionate, dihydroiodide, dihydrochloride, dilactate, dinitrate, sulphate, and tartrate. Suitably, chlorhexidine or an orally acceptable acid addition salt thereof is present in a range from 0.005 to 10% w/w, 0.01 to 5% w/w, eg. 0.01 to 2% w/w by weight of the composition.

An effective amount of polyvinylpyrrolidone (PVP) is suitably present in a range from 1 to 5% w/w, eg. 1% or 2% w/w by weight of the composition.

An effective amount of sodium citrate is suitably present in a range from 0.1 to 10% w/w, eg. 1% to 2% w/w, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% w/w by weight of the composition.

It will be appreciated by those skilled in the art that in order to ensure that the antibacterial efficacy of the cationic antibacterial agent is not substantially diminished, compatible components will be selected for inclusion in the orally acceptable excipients. Accordingly, the skilled man will readily appreciate that where necessary anionic species should be preferably avoided as such species may cause inactivation of the cationic antibacterial agent by the formation of an insoluble precipitate therewith. Thus, anionic surfactants should preferably be rejected in favour of non-anionic counterparts such as nonionic, cationic or amphoteric surfactants.

Suitable nonionic surfactants may be selected from polyethoxylated sorbitol esters, polyethoxylated sorbitol monoesters, PEG(40) sorbitan di-isostearate, polyoxyethylene Sorbitan Fatty Acid Esters, polycondensates of ethylene oxide and propylene oxide (poloxamers, condensates of propylene glycol, polyethoxylated 40 hydrogenated castor oil, cremophors, sorbitan fatty esters or combination thereof. The surfactant as described above may be employed in the present specification in the range from 0.005 to 20% w/w, 0.1 to 10% w/w, eg. 0.1 to 5% w/w by weight of the composition.

Suitable humectants may be selected from glycerine, sorbitol, propylene glycol, polyethylene glycol or combination thereof. The humectant as described above may be employed in the present specification in the range from 5 to 70% w/w, 5 to 30% w/w, eg. 10 to 30% w/w by weight of the composition.

Examples of orally acceptable buffers and pH modifiers include a base such as sodium hydroxide, or an acid such as acetic, gluconic, tartaric, citric, lactic, or phosphoric acid or a soluble salt thereof. These can be used individually or as combination. The buffer or pH modifier should be present in sufficient quantity to provide the desired buffering effect, suitably from 0.01 to 10% w/w, eg. 0.1 to 2% w/w by weight of the composition.

The compositions of the present specification may also contain an ionic fluorine-containing compound. Suitable ionic fluorine containing compounds include, fluoride salts such as amine fluorides and alkali metal fluoride salts, eg. sodium fluoride, and monofluorophosphate salts such as alkali metal monofluorophosphate salts, eg. sodium monofluorophosphate. The ionic fluorine containing compounds as described above may be employed in the present specification in the range from 0.001 to 5% w/w.

Other materials may be added to the compositions if required, for instance sweetening agents, flavouring agents, colouring and whitening agents, preservatives, chelating agent and emulsifiers.

The pH of a composition according to the specification is orally acceptable and typically is in the range of pH 4 to 9.

A carrier for the mouthwash according to the present specification is preferably an aqueous or an aqueous/ethanol solution. The carrier may be present in the range from 40 to 90% w/w, eg. 50 to 70% w/w by weight of the composition.

Mouthwash compositions according to the present specification may be prepared by mixing the ingredients thereof in the required proportions and in any order that is convenient and thereafter and if necessary adjusting the pH to the required value.

Accordingly, in a further aspect, the present specification provides an oral hygiene composition for use in therapy, in particular anti-plaque, anti-caries, anticalculus and/or periodontal (including anti-gingivitis) therapy.

EXAMPLES

Composition Example 1 Example 2 Example 3
Chlorhexidine Gluconate 1.0 1.0 1.0
Polyoxyl 40 Hydrogenated Castor Oil 2 2 2
Poloxamer 188 1 0.5 0.5
Sorbitol Solution (70%) 15 15 15
Menthol 0.05 0.05 0.03
Fresh Mint SC499668 0.2 0.2 0.1
Glycerin 30 30 30
Sodium Fluoride 0.05 0.05 0.05
Sodium Citrate 1.2 0.7 0.2
Zinc Chloride 0.09 0.09 0.09
Citric Acid Monohydrate 0.2 0.2 0.2
Sodium Benzoate 0.2 0.2 0.2
Disodium EDTA 0.05 0.05 0.05
Povidone 1 2 -
Fast Green FCF 0.0005 0.0005 0.0005
Purified water q.s. to 100 q.s. to 100 q.s. to 100

Manufacturing Process:
The compositions were prepared by dissolving all the material one after another in a mixture of glycerin, sorbitol and part quantity of water in a mixing vessel and made up to final volume with remaining quantity of water.

In-vitro study:
An in-vitro study was performed using “artificial teeth” – hydroxyapatite (HAP) discs to evaluate the anti-staining effect of these three compositions. In this experiment, the pellicle coated HAP discs were treated with mouthwash and then challenged with a tea solution, prior to taking the color measurement. The experimental protocol is described in the below table.

Cycle 1 1% Mucin supernatant solution 20 hours
Base-Line Color Measurement ----------
5 ml Mouthwash Treatment 5 min.
Tea Stain 15 min.
Read HAP Disc Color (front/back) ----------
Cycle 2 1% Mucin supernatant solution 45 min.
5 ml Mouthwash Treatment 5 min.
Tea Stain 15 min.
Read HAP Disc Color (front/back) ----------
Cycle 3 1% Mucin supernatant solution 45 min.
5 ml Mouthwash Treatment 5 min.
Tea Stain 15 min.
Read HAP Disc Color (front/back) ----------
Cycle 4 1% Mucin supernatant solution 45 min.
5 ml Mouthwash Treatment 5 min.
Tea Stain 15 min.
Read HAP Disc Color (front/back) ----------

Result:
Figure 1 shows the color development (?E) on the HAP discs. In this case, a smaller ?E value refers to less staining. Examples 1 and 2 were found to be better in preventing stain in comparison to example 3.