WO2006012977A1

WO2006012977A1 - Composition

Info

Publication number: WO2006012977A1
Application number: PCT/EP2005/007529
Authority: WO
Inventors: Phlip Christopher Waterfield
Original assignee: Unilever N.V.; Unilever Plc; Hindustan Lever Limited
Priority date: 2004-08-03
Filing date: 2005-07-04
Publication date: 2006-02-09

Abstract

Toothpaste composition and method for making such, the toothpaste comprising water, a zinc salt, a chelating agent for the zinc, the chelating agent having a log Ks1 as herein defined of from 3.0 to 7.0, and calcium carbonate as abrasive.

Description

COMPOSITION

The present invention relates to a toothpaste composition comprising bioactive zinc salts in a chalk formulation. The invention also relates to a method for making said composition.

EP-Al-O 740 932 (Unilever) discloses a visually-clear gel type dentifrice comprising a zinc salt which is more water soluble than zinc citrate, an amino acid which can bind zinc and a low refractive index type abrasive silica.

US 5 470 561 (Klugkist) discloses an anti-plaque mouthwash comprising a zinc salt and triclosan. The composition may also comprise glycine and has a pH of between 4 and 8, preferably between 5 and 7, the preferred pH being 6.

GBA-2 052 978 (Unilever) discloses a toothpaste comprising zinc salts with glycine and a pH of from 4.5 to 8.0.

US 5 632 972 (Williams) discloses a method for minimising damage to gingival and periodontal tissue by delivering a first component comprising zinc and a second component comprising a bicarbonate.

The invention provides a toothpaste composition comprising a first phase and a second phase stored in contact with one another, the first phase comprising water and a zinc salt, the second phase comprising calcium carbonate as abrasive and a chelating agent for the zinc salt, the chelating agent having a log K₃I as herein defined of from 3.0 to 7.0. The zinc salt is present at from 0.01 to 5% by weight of the toothpaste composition, preferably from 0.5 to 3.0% by weight of the composition. Where the zinc salt is sparingly soluble, for example zinc citrate, the log K_sl of the chelating ligand with the zinc ion is equal to or greater than the log K_Ξ1 of the acid anion and the zinc ion of the sparingly soluble zinc salt. However, water soluble zinc salts are preferred. Suitable zinc salts include zinc chloride, zinc sulphate and zinc fluoride. The preferred zinc salt is zinc sulphate which, in this type of formulation, provides an optimal balance between making enough zinc ions bioavailable, and capable of interacting with bacteria, without forming a deleterious amount of water-insoluble zinc hydroxide.

It is preferred that the chelating agent for the zinc salt has a log K₃I of from 4.0 to 6.0. The log K₃I is the logarithm of the primary Stability Constant which is the binding affinity for a particular ligand with a particular metal ion, in the present invention zinc. For example, when the chelating agent is glycine, the primary Stability Constant is the binding affinity for one glycine ligand with the free zinc ion and is defined by the following: K₃I = [ML] / [M] . [L] , where [ML] is the concentration of the metal- ligand complex, [M] is the concentration of the free metal ion and [L] is the concentration of the free ligand. Since [L] is a function of the solution pH, due to the required initial deprotonation of the ligand, as a reference point, the log K₃I values described were recorded at pH 7.4. The chelating agent is present at from 0.001 to 6% by weight of the composition, preferably at from 0.5 to 4.0% by weight of the composition. Preferred chelating agents include alkali metal salts of citric acid, alanine, glycine and serine. The most preferred is glycine, which provides an optimal balance between being able to protect the zinc salt from hydrolysis (leading to formation of insoluble zinc hydroxide) in the chalk system and keeping it soluble and bioavailable.

The abrasive system employed in the present invention is calcium carbonate based. This does not prevent the use of non-calcium carbonate abrasives in addition, such as silicas, tungsten carbide and silicon carbide.

The abrasive system is present at from 10 to 70% by weight of the second phase of the composition. In a preferred embodiment this comprises calcium carbonate at from 10 to 70% by weight of the second phase, more preferably from 20% and most preferably from 45 to 60% by weight of the second phase calcium carbonate.

Preferred calcium carbonates include fine ground natural chalk since it has a surprising stability with regard to its interactivity with zinc salts. The term fine ground natural chalk (FGNC) is a known term in the art and suitable examples of such are disclosed in US 2003/0072721 Al (Riley) the contents of which with regards to the definition, types and grades of FGNC are incorporated herein by reference. Nevertheless, by FGNC is meant chalk which is obtained by milling limestone or marble deposits. Preferably, the FGNC comprises particulate matter of weight-based median particle size ranging from 1 to 15 μm and BET surface area ranging from 0.5 to 3 m²/g.

The composition according to the invention also preferably comprises a fluoride ion source such as an alkali metal salt of monofluorophosphate, preferably sodium monofluorophosphate. Such fluoride ion source will be present at such an amount to provide free fluoride ion at from 100 to 2000 ppm, preferably from 900 to 1500 ppm.

The oral composition according to the invention comprise further ingredients which are common in the art, such as:

antimicrobial agents, e.g. chlorhexidine, sanguinarine extract, metronidazole, quaternary ammonium compounds, such as cetylpyridinium chloride; bis-guanides, such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenolic compounds, such as 2,2' methylenebis- (4-chloro-6-bromophenol) ;

anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin, indomethacin etc.;

anti-caries agents such as sodium- and stannous fluoride, aminefluorides, sodium monofluorophosphate, sodium trimeta phosphate and casein;

plague buffers such as urea, calcium lactate, calcium glycerophosphate and strontium polyacrylates; vitamins such as Vitamins A, C and E;

plant extracts;

desensitising agents, e.g. potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and strontium salts;

anti-calculus agents, e.g. alkali-metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates and phosphocitrates etc. ;

biomolecules, e.g. bacteriocins, antibodies, enzymes, etc.;

flavours, e.g. peppermint and spearmint oils;

proteinaceous materials such as collagen;

preservatives;

opacifying agents;

colouring agents;

pH-adjusting agents;

sweetening agents;

pharmaceutically acceptable carriers, e.g. starch, sucrose, water or water/alcohol systems etc.; surfactants, such as anionic, nonionic, cationic and zwitterionic or amphoteric surfactants;

particulate abrasive materials such as silicas, aluminas, calcium carbonates, dicalciumphosphates, calcium pyrophosphates, hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates and so on, including agglomerated particulate abrasive materials, usually in amounts between 3 and 60% by weight of the oral care composition. Preferred abrasives are chalk and silica, more preferably fine ground natural chalk.

Humectants such as glycerol, sorbitol, propyleneglycol, xylitol, lactitol etc.;

binders and thickeners such as sodium carboxymethyl- cellulose, hydroxyethyl cellulose (Natrosol^®) , xanthan gum, gum arabic etc. as well as synthetic polymers such as polyacrylates and carboxyvinyl polymers such as Carbopol^®;

polymeric compounds which can enhance the delivery of active ingredients such as antimicrobial agents can also be included;

buffers and salts to buffer the pH and ionic strength of the oral care composition; and

other optional ingredients that may be included are e.g. bleaching agents such as peroxy compounds e.g. potassium peroxydiphosphate, effervescing systems such as sodium bicarbonate/citric acid systems, colour change systems, and so on.

Liposomes may also be used to improve delivery or stability of active ingredients.

In a second aspect of the invention there is provided a method of making an oral composition according to the first aspect the method comprising the steps of forming a zinc- chelate solution and buffering to a pH which is equal to or higher than that of the calcium carbonate in an aqueous suspension before mixing with the suspended calcium carbonate. Further materials such as flavours may be added to the final mix.

Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material ought to be understood as modified by the word ^λabout' .

The term Comprising' is meant not to be limiting to any subsequently stated elements but rather to encompass non- specified elements of major or minor functional importance. In other words the listed steps, elements or options need not be exhaustive. Whenever the words 'including' or

'having' are used, these terms are meant to be equivalent to 'comprising' as defined above.

Embodiments according to the invention shall now be discussed with reference to the following non-limiting examples. EXAMPLE 1

The following example formulation is an embodiment according to the invention.

Claims

1. Toothpaste composition comprising a first phase and a second phase stored in contact with one another, the first phase comprising water and a zinc salt, the second phase comprising calcium carbonate as abrasive and a chelating agent for the zinc salt, the chelating agent having a log K_sl as herein defined of from 3.0 to 7.0.

2. Toothpaste composition according to claim 1, wherein the second phase has a pH of from 8.0 to 10.0

3. Toothpaste composition according to any preceding claim, wherein the calcium carbonate is fine ground natural chalk.

4. Toothpaste composition according to any preceding claim, wherein the composition comprises a fluoride ion source.

5. Toothpaste composition according to any preceding claim, wherein the zinc salt is a water soluble zinc salt.

6. Toothpaste composition according to any preceding claim, wherein the zinc salt is zinc sulphate.

7. Toothpaste composition according to any preceding claim, wherein the chelating agent is glycine.

8. Toothpaste composition according to any preceding claim, wherein the chelating agent is serine.

9. Toothpaste composition according to any preceding claim, wherein the chelating agent is alanine.

10. Toothpaste composition according to any preceding claim, wherein the chelating agent is an alkali metal salt of citric acid.

11. Toothpaste according to any preceding claim comprising an agent selected from the group consisting of anti- caries agents, anti-tartar agents, anti-malodour agents, whitening teeth agents, anti-gingivitis agents and mixtures thereof.

12. Toothpaste according to any preceding claim, wherein the first and second phases are coaxially arranged in and dispensed from a toothpaste tube, the first phase substantially surrounding the second phase.