WO2008006725A1

WO2008006725A1 - Toothpaste composition

Info

Publication number: WO2008006725A1
Application number: PCT/EP2007/056627
Authority: WO
Inventors: Victoria Cromwell; Philip Christopher Waterfield
Original assignee: Unilever Plc; Unilever N.V.; Hindustan Unilever Limited
Priority date: 2006-07-13
Filing date: 2007-07-02
Publication date: 2008-01-17
Also published as: CN101489628A; BRPI0711979A2; EP2046454A1

Abstract

An opaque toothpaste composition comprising: water; a zinc salt; a chelating agent for the zinc salt, the chelating agent having a log Ks1 as herein defined of from 3.0 to 7.0; calcium carbonate at from 10% to 70% by weight of the toothpaste composition; a monofluorophosphate salt; and trisodium phosphate.

Description

TOOTHPASTE COMPOSITION

The present invention relates to an opaque 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.

US 4 425 325 (Sapone et al) discloses an oral composition containing biologically active zinc ions with glycine and having an adjusted pH of about 4.5 to 9.4.

GB 1 319 247 (Beecham INC) discloses a non-liquid anticalculus dental composition comprising a dental vehicle, and a zinc, cupric or zirconium complex of a fluorinated β- diketone .

US 4 325 939 (Shah) discloses an alkali metal or ammonium zinc citrate prepared for use in dental compositions and especially in mouthwash compositions.

US 5 188 820 (Cummins et al) discloses oral compositions such as dentifrices comprising a mixture of a stannous salt such as stannous fluoride or stannous pyrophosphate and a zinc salt such as zinc citrate.

In a first aspect of the present invention there is provided an opaque toothpaste composition according to claim 1.

The monofluorophosphate salt provides flurode ion to the toothpaste composition, the fluoride ion is an effective anti-caries agent. However, monofluorophosphate salts are not stable in chalk-containing toothpastes and so a stabilising agent is required. While trisodium phosphate

(TSP) is a suitable stabilising agent before now it has not been possible to put TSP into a zinc-containing toothpaste since the free zinc ions react with the TSP to form zinc phosphate. Zinc phosphate is not a good source of bioavailable zinc. Therefore, by incorporating a chelating agent for the zinc the levels of monofluorophosphate, and also zinc can be maintained after prolonged storage.

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 K₃I of the chelating ligand with the zinc ion is equal to or greater than the log K₃I 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 the optimum balance as described above .

The alkali metal is preferably potassium or sodium, most preferably sodium.

The alkali metal phosphate is preferably a mono, di- or tri- phosphate salt, most preferably a triphosphate.

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. - A -

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 are the alkali metal salts of citric acid, especially potassium citrate and most preferably tri-potassium citrate, which provides an optimal balance between being able to protect the zinc salt from hydrolysis (leading to the formation of carbon dioxide) in the chalk system and keeping it soluble and bioavailable .

The abrasive system is present at from 10 to 70% by weight of the toothpaste composition, preferably at from 20 to 60% and most preferably at from 35 to 45% by weight of the toothpaste composition.

The alkali metal phosphate is present at from 0.01 to 2% by weight, preferably from 0.15 to 1% and especially preferably from 0.2 to 0.5% by weight of the composition.

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.

In a preferred embodiment the abrasive system comprises at least 50% by weight calcium carbonate, more preferably at least 75% by weight calcium carbonate and most preferably at least 95% by weight calcium carbonate. In the most preferred embodiment of the present invention the abrasive system comprises 100% by weight calcium carbonate although mixtures of calcium carbonate and additional abrasives are possible.

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 toothpaste 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;

plaque 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 toothpaste 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 toothpaste 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 opaque toothpaste 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 ^Λcomprising' 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 ^Λincluding' or

^Λhaving' 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. It is made by mixing first the zinc sulphate heptahydrate with glycine (and other minors) and buffering to a pH of from 8.5 to 9.5 with sodium hydroxide. The calcium carbonate, surfactant and structurants are then added to the zinc-chelate mix. The flavours are added last.

Claims

1. An opaque toothpaste composition comprising:

water;

a zinc salt;

a chelating agent for the zinc salt, the chelating agent having a log K₃I as herein defined of from 3.0 to 7.0;

calcium carbonate at from 10% to 70% by weight of the toothpaste composition;

a monofluorophosphate salt; and

alkali metal phosphate.

2. An opaque toothpaste composition according to claim 1, wherein the composition has a pH of from 8.0 to 10.0.

3. An opaque toothpaste composition according to claim 1 or 2 wherein the alkali metal phosphate is trisodium phosphate.

4. An opaque toothpaste composition according to any preceding claim, wherein the calcium carbonate is fine ground natural chalk.

5. An opaque toothpaste composition according to any preceding claim, wherein the composition comprises a fluoride ion source.

6. An opaque toothpaste composition according to any preceding claim, wherein the zinc salt is a water soluble zinc salt.

7. An opaque toothpaste composition according to any preceding claim, wherein the zinc salt is zinc sulphate .

8. An opaque toothpaste composition according to any preceding claim, wherein the chelating agent is glycine.

9. An opaque toothpaste composition according to any preceding claim, wherein the chelating agent is serine.

10. An opaque toothpaste composition according to any preceding claim, wherein the chelating agent is alanine .

11. An opaque toothpaste composition according to any preceding claim, wherein the chelating agent is an alkali metal salt of citric acid.

12. An opaque 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.

13. An opaque toothpaste according to any preceding claim wherein the trisodium phosphate is present at from 0.1 to 1% by weight of the composition.

14. Method of making an opaque toothpaste composition, the toothpaste comprising water, a zinc salt, a chelating agent for the zinc salt, the chelating agent having a log K₃I as herein defined of from 3.0 to 7.0, and an abrasive present at from 10% to 70% by weight of the toothpaste composition, said abrasive comprising calcium carbonate, the method comprising:

-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 calcium carbonate and optionally adding any further materials at any stage.