Field of the Invention

The present invention relates to a process of manufacturing a non-aqueous compositions.

Background of the Invention

Paste compositions that are non-aqueous can prove difficult to manufacture in that the rheology of the paste is difficult to control. The stability of non-aqueous paste can also be problematic.

A problem with non-aqueous formulations such as those disclosed in W096/03108 is that they do not behave rheologically like a typical aqueous dentifrice. This problem is observed both during manufacture and during use by the consumer. It has led to manufacturing difficulties and reduced acceptance amongst consumers. Viscosity profile and flow characteristics are key factors governing ease of processing, product performance and consumer perception of a dentifrice.

EP 2 089040 describes oral care compositions which remineralises eroded teeth and/or whitens the teeth. The composition can be a dual phase composition comprising a source of calcium ions, a source of phosphate ions. With such systems it is preferable if the level of water within the composition is low.

There remains a need for non-aqueous pastes, in particular oral care toothpastes that have excellent rheology such as viscosity, are stable and preferably comprises a high level of materials that can remineralise tooth enamel.

Description of the Invention

The present invention provides a process for the manufacture of a non-aqueous composition comprising the following sequential steps: i) heating an organic polyol and structurant in a mix to a temperature of 69 °C or above, ii) addition of an abrasive and other non-flavour ingredients to the mix, iii) rapid cooling the resulting mix at a cooling rate of 5°C/min or above to form a paste or gel.

Detailed Description of the Invention

Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use may optionally be understood as modified by the word “about’. All amounts are by weight of the composition, unless otherwise specified.

It should be noted that in specifying any ranges of values, any upper value can be associated with any particular lower value.

Where a feature is disclosed with respect to a particular aspect of the invention (for example a composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

Any ingredients mentioned in this application that are natural or naturally derived have been sourced from Europe.

The composition of the invention is used to preferably used to clean the surfaces of the oral cavity and is known as an oral care composition. Accordingly, preferred product forms for compositions of the invention are those which are suitable for brushing and/or rinsing the surfaces of the oral cavity.

The composition of the invention is most preferably in the form of a dentifrice. The term "dentifrice" denotes an oral composition which is used to clean the surfaces of the oral cavity. Such a composition is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is applied to the oral cavity, used to treat the oral cavity and then expectorated. Typically such a composition is used in conjunction with a cleaning implement such as a toothbrush, usually by applying it to the bristles of the toothbrush and then brushing the accessible surfaces of the oral cavity.

Preferably the dentifrice/toothpaste is in the form of an extrudable semi-solid such as a cream, paste or gel (or mixture thereof).

A composition according to the invention (such as a dentifrice/toothpaste) will generally contain further ingredients to enhance performance and/or consumer acceptability, in addition to the ingredients specified above.

The rheological behaviour compositions prepared by this process can be well controlled to achieve the desired sensory effects. A further particular advantage of the composition of the invention is its storage stability. The composition of the invention is non-aqueous. By “non-aqueous” it is generally meant that water is not deliberately added to the composition in any significant quantity. However, the term “nonaqueous” does not mean that small amounts of water cannot be present, for example as a consequence of its association with hygroscopic raw materials. Accordingly, for the purposes of this invention, the term “non-aqueous” generally means that water is present in an amount no greater than about 5%, more preferably no greater than about 3% by weight based on the total weight of the composition.

Polyol

The composition of the invention comprises an organic polyol. Polyols for use in the invention comprise glycerol and /or Other polyols may be present such as , xylitol, mannitol, lactitol, maltitol, erythritol, and hydrogenated partially hydrolyzed polysaccharides. I. Mixtures of any of the above described materials may also be used.

The level of organic polyol will depend on the particular type chosen, but generally ranges from about 20 to 90% by weight based on the total weight of the composition. The amount of organic polyol suitably ranges from 35 to 75%, more preferably from 45 to 70% by total weight organic polyol based on the total weight of the composition. In the context of the present invention, the term “organic polyol” means that the composition is not oil-based or water-based, but instead, organic polyols (as defined above) are a principal component in the composition. By “principal component’ is meant that the organic polyols (as defined above) when taken together, make up a higher portion of the composition's weight than any other compound. Ideally the composition of the invention is glycerol-based (i.e glycerol makes up a higher portion of the composition's weight than any other compound) and contains from 45 to 70% by weight glycerol based on the total weight of the composition.

Structurant

The invention of the composition comprises a structurant. A preferred structurant is crystals of one or more solid polyethylene glycols having a melting point of 25°C or above. Preferably the melting point ranges from 35 to 65°C, more preferably from 55 to 60°C.

Polyethylene glycols have the general formula H(OCH2CH2) _n OH where n is the number of repeating oxyethylene units. Commercially available polyethylene glycols are usually not uniform chemical compounds, but instead consist of a distribution of similar polymer members of the homologous polyethylene glycol series, defined by average values of n and molecular weight. The melting point generally increases with increasing average values of n and molecular weight. Suitable solid polyethylene glycols have an average value of n in the above general formula ranging from about 20 to 220, preferably from about 40 to 150, more preferably from about 32 to 90, most preferably from about 60 to 75. The average molecular weight suitably ranges from about 950 to 11 ,250, preferably from about 1800 to 6600, more preferably from about 1400 to 4400, most preferably from about 2700 to 3700 g/mol. Suitable commercially available materials include for example Polyglykol® 3000 (ex Clariant). Mixtures of any of the above described materials may also be used.

The amount of solid polyethylene glycol (as defined above) in compositions of the invention suitably ranges from 0.1 to 5%, preferably from 0.5 to 3%, more preferably from 1 to 2.5% by total weight solid polyethylene glycol (as defined above) based on the total weight of the composition.

An alternative structurant comprises xanthan gum. Xanthan gum is a fermentation product prepared by action of the bacteria of the genus Xanthomonas upon carbohydrates. Four species of Xanthomonas, namely X.campestris, Xphaseoli, Xmalvoceamm and Xcarotae are reported in the literature to be the most efficient gum producers.

Xanthan gum may be generally characterised as an anionic heteropolysaccharide, with a primary structure consisting of repeating pentasaccharide units formed by two glucose units, two mannose units, and a glucuronic acid unit. These repeating pentasaccharide units give xanthan gum its characteristic backbone, which consists of (1 — >4) p-D-glucopyranosyl units substituted at C-3 on every other glucose residue with a charged trisaccharide sidechain. The trisaccharide sidechain consists of a D-glucuronic acid unit between 2 D-mannose units. Slightly less than half (about 40%) of the terminal D-mannose residues contain a pyruvic acid residue linked via keto groups to the four and six positions, and the D-mannose linked to the main chain mostly contains an acetyl group at position O-6. Some side chains may be missing. The acetate and pyruvate contents are variable on the side chain, and depend on the bacterial strains and on the fermentation conditions used to produce the gum.

Xanthan gum generally has a molecular weight of from 1 million to 50 million. Its viscosity generally ranges from 850 to 1 ,700 mPa.s (when measured at 25°C using a 1 % solution of the gum in 1 % KCI, on a viscometer of the Brookfield LV type, at 60 rpm using Spindle No. 3).

Xanthan gum is available from several commercial suppliers such a RT Vanderbilt Company and CP Kelco. Examples of suitable xanthan gums are Keltrol®, Keltrol® F, Keltrol® T, Keltrol® TF, Xantural® 180 and Vanzan® NF. The amount of xanthan gum in the composition of the invention preferably ranges from 0.05 to 1 ,5wt%, more preferably from 0.1 to 0.9wt% (by weight based on the total weight of the oral care composition).

A further embodiment of the invention comprises Carrageenan as a structurant. preferably the carrageenan is present at weight ratios of 1 :2 to 2: 1 of iota to kappa carrageenan.

The carrageenan present in the composition of the invention preferably consists from 33wt% to 66wt% of the total level of iota carrageenan and 33 wt% to 66 wt% of kappa carrageenan.

The total level of carrageenan is from 0.05 to 1 wt% of the total composition, more preferably 0.08 to 0.5 wt% most preferably 0.05 to 0.25 wt%.

Mixtures of structurants may be used.

Re-mineralising agents

In one embodiment a preferred class of oral care active for inclusion in the compositions of the invention includes agents for the remineralisation of teeth. The term “remineralisation” in the context of the present invention means the in situ generation of hydroxyapatite on teeth.

A specific example of a suitable agent for the remineralisation of teeth is a mixture of a calcium source and a phosphate source which, when delivered to the teeth results in the in situ generation of hydroxyapatite on teeth.

Illustrative examples of the types of calcium source that may be used in this context (hereinafter termed “remineralising calcium sources”) include, for example, calcium phosphate, calcium gluconate, calcium oxide, calcium lactate, calcium glycerophosphate, calcium carbonate, calcium hydroxide, calcium sulphate, calcium carboxymethyl cellulose, calcium alginate, calcium salts of citric acid, calcium silicate and mixtures thereof. Preferably the remineralising calcium source is calcium silicate.

The amount of remineralising calcium source(s) (e.g. calcium silicate) in the composition of the invention typically ranges from 1 to 30%, preferably from 5 to 20% by total weight remineralising calcium source based on the total weight of the oral care composition. lllustrative examples of the types of phosphate source that may be used in this context (hereinafter termed “remineralising phosphate sources”) include, for example, monosodium dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, potassium dihydrogenphosphate, trisodium phosphate, tripotassium phosphate and mixtures thereof. Preferably the remineralising phosphate source is a mixture of trisodium phosphate and sodium dihydrogen phosphate.

The amount of remineralising phosphate source(s) (e.g. trisodium phosphate and sodium dihydrogen phosphate) in the composition of this invention typically ranges from 2 to 15%, preferably from 4 to 10% by total weight remineralising phosphate source based on the total weight of the oral care composition.

Mixtures of any of the above described materials may also be used.

Further Ingredients

Compositions according to the invention, particularly toothpastes, preferably comprise 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.

Preferably the composition, particularly a toothpaste, comprises a silica based abrasive. The preferred abrasive silicas used in the present invention is a silica with a low refractive index. It may be used as the sole abrasive silica, or in conjunction with a low level of other abrasive silicas, e.g. those according to EP 236070. The low refractive index silicas, used as abrasives in the present invention are preferably silicas with an apparent refractive index (R.l.) in the range of 1.41 - 1 .47, preferably 1 .435 - 1.445, preferably having a weight mean particle size of between 5 and 15 mm, a BET (nitrogen) surface area of between 10 and 100 m ² /g and an oil absorption of about 70 - 150 cm ³ /100 g, but abrasive silicas with a lower apparent refractive index may also be used. Typical examples of suitable low refractive index abrasive silicas (e.g. having an R.l. of between 1.435 and 1.445) are Tixosil 63 and 73 ex Rhone Poulenc; Sident 10 ex Degussa; Zeodent 113 ex Zeofinn; Zeodent 124 ex Evonik, Sorbosil AC 77 ex PQ Corporation (having an R.l. of approximately 1.440). The amount of these silicas in the composition generally ranges from 5-60% by weight, usually 5-20% by weight. The composition, particularly if a toothpaste preferably comprises an inorganic or a natural or synthetic thickener or gelling agent in proportions of about 0.10 to about 15% by weight depending on the material chosen. These proportions of thickeners in the dentifrice compositions of the present invention form an extrudable, shape-retaining product which can be squeezed from a tube onto a toothbrush and will not fall between the bristles of the brush but rather, will substantially maintain its shape thereon. Suitable thickeners or gelling agents useful in the practice of the present invention include inorganic thickening silicas such as amorphous silicas available from Huber Corporation under the trade designation Zeodent 165, Irish moss, iota-carrageenan, gum tragacanth, and polyvinylpyrrolidone.

Compositions according to the invention preferably comprise a polymeric deposition aid. Preferably the composition comprises acid anhydride polymers, particularly preferred are co-polymers of maleic anhydride with methyl vinylether, in which the anhydride moiety may be in a partially or fully hydrolysed or alcoholysed form. Preferred copolymers include Gantrez(R) polymers such as: Gantrez S-95: molecular weight 216,000; free acid;

Gantrez S-96: molecular weight 700,000; free acid;

Gantrez S-97: molecular weight 1 ,500,000; free acid; and

Gantrez MS-955: molecular weight 1,060,000; calcium/sodium salt.

Particularly preferred co-polymers of maleic acid and methyl vinylether have a molecular weight of 1 ,000,000 or greater and an especially preferred material is Gantrez S-97.

Compositions according to the invention may comprise a tooth whitening agent. The whitening agent preferably comprises a green and/or a blue pigment. In the context of the present invention a pigment is generally understood to be a shade/material which is insoluble in the relevant medium, at the relevant temperature. This is in contrast to dyes which are soluble. In the context of this invention, the "relevant medium" is human saliva, the liquid medium in which the composition is used, at the temperature of the oral cavity during brushing of the teeth, i.e. up to 37 Degrees C. As a reasonable approximation, the relevant medium may be considered to be water and the relevant temperature to be 25 Degrees C.

Preferably the blue pigment is Pigment Blue 15, more preferably Pigment Blue 15:1 , 15:2, 15:3, 15:4, 15:5 or 15:6, most preferably 15:1. A preferred pigment is blue pigment is Phthalocyanine Blue Pigment, Cl No. 74160, blue covarine.

The preferred Green pigment is Phthalocyanine Green, preferably Phthalocyanine Green CI-74260. Preferably the total level of pigment in the composition is from 0.01 wt% to 3 wt, more preferably from 0.02 to 2 wt%.

If the composition is a toothpaste it may be a dual phase paste, with the whitening pigments present in one phase.

Compositions according to the invention may comprise water-soluble or sparingly water-soluble sources of metal salts Preferred are zinc ions such as zinc chloride, zinc acetate, zinc gluconate, zinc sulphate, zinc fluoride, zinc citrate, zinc lactate, zinc oxide, zinc monoglycerolate, zinc tartrate, zinc pyrophosphate and zinc maleate; also preferred are stannous ions such as stannous fluoride and stannous chloride.

Compositions according to the invention may comprise oral care enzyme systems such as hydrogen peroxide producing enzyme systems (e.g. the oxidoreductase enzyme glucose oxidase), amyloglucosidase, dextranase and/or mutanase, (optionally in the presence of zinc ion providing compounds and/or 8- hydroxyquinoline derivatives), lactoperoxidase, lactoferrin, lysozyme and mixtures thereof.

Compositions of the invention may comprises fluoride sources such as sodium fluoride, stannous fluoride, sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, calcium fluoride, cobalt ammonium fluoride and mixtures thereof;

The composition according the invention will 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; cetylpyridium chloride clay complex 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; plant-derivable antioxidants such as flavonoid, catechin, polyphenol, and tannin compounds and mixtures thereof; 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; hyaluronic acid; amino acids such as arginine; 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; 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.

Process

The process for the manufacture of a non-aqueous composition comprising the following sequential steps: i) heating a mix of structurant and organic polyol comprising sorbitol and/or glycerol to a temperature of 69 °C or above, ii) addition of an abrasive and other non-flavour ingredients to the mix, iii) rapid cooling the resulting mix at a cooling rate of 5°C/min or above to form a paste or gel. It is preferred if the process is carried out under vacuum. The vacuum can be achieved by any suitable means, preferably by a standard a rotary vacuum pump capable of maintaining a vacuum of at least - 800 mbar(g), preferably - 950 mbar(g). An example of a suitable.

The rapid cooling rate can be achieved by any suitable means preferably by liquid nitrogen or carbon dioxide preferably the rapid cooling is achieved by the use of cardice (solid carbon dioxide. At pressures below 5.13 atm and temperatures above -56.4°C solid CO2 undergoes sublimation, changing state from a solid to a gas with no intermediate liquid formation. At atmospheric pressure, sublimation occurs at a temperature of -78.5°C, with an associated enthalpy of sublimation of AHsub = +25.2 kJ mol ^-1 (+571 kJ kg ^-1 ). The highly endothermic nature of this phase change dictates that it must be accompanied by the absorption of large quantities of heat from the material’s surroundings, enabling solid CO2 to act as an effective coolant.

The rate of sublimation is dependent on operating conditions of temperature, pressure, and thermal properties of the fluid it is being contacted with, as well as the surface area of the solid CO2 material. When intimately mixed with product at elevated temperatures of 70°C within the mixer, sublimation occurs rapidly; sublimation rates of up to 32 kg h' ¹ have been measured during pilot-plant operation. Sublimation rates can be significantly slowed with appropriate storage of material within insulated containers, yielding sublimation rates as low as 0.19 kg h' ¹ .

CO2 is a preferred method of rapid cooling as it boasts several other properties which make it favourable for use as a directly added coolant. Gaseous CO2 is non-flammable, colourless, odourless and readily recoverable from the mixing vessel via vacuum.

In an alternative embodiment, the coolant could be liquid nitrogen. Nitrogen exists under atmospheric pressure as a colourless, low viscosity liquid at temperatures between 63.1 K and 77.3K (or -221 ,8°C and -195.9°C). It can be readily obtained from air, either via cryogenic distillation or pressure swing adsorption. The associated enthalpy change of vaporisation is +5.59 kJ mol' ¹ (+199.6 kJ kg ^-1 ). It must be stored and transported in thermally insulated vacuum flasks to minimise evaporative losses and maintain cryogenic storage conditions.

Less preferably, the coolant could also be liquid carbon dioxide. Carbon dioxide only exists as a liquid at pressures above 5.13 atm, and temperatures between -56.6°C (the triple point temperature of CO2) and 31.1°C (the critical temperature of CO2), so requires pressurised storage. The associated enthalpy change of vaporisation is +16.7 kJ mol' ¹ (+379.6 kJ kg' ¹ ). Preferably the process has an initial cooling rate of the liquid ii) of less than 2 °C/min (this is achieved by conventional cooling using a jacketed vessel, where the coolant temperature ranges from 20°C to -18°C) followed by rapid cooling at a rate of 5°C/min or above (this is achieved by direct addition into the mixing vessel of liquid carbon dioxide or nitrogen, or most preferably cardice).

Preferably the mix is cooled at an initial cooling rate of less than 2 °C/min to 50 °C to 40 °C, preferably followed by addition of temperature sensitive ingredients such as perfume and flavour. After the initial slow cooling the mix is rapid cooled at a rate of 5°C/min or above to a temperature of 30 °C or below.

It is preferred if the rapid cooling rate is 10°C/min, preferably 15°C/min, more preferably 20°C/min. Particularly preferred is a rapid cooling rate between 20°C/min and 30°C/min.

Preferably the perfume or flavour is added at a temperature of 45 °C or below.

The invention will now be illustrated by the following non-limiting examples: Processes according to the invention were illustrated by a number, comparative Examples by a letter

Example

The following Examples were prepared using the following process:

The structuring components, such as various forms of carrageenans, various grades of PEG, xanthan gum or a combination thereof, are either pre-mixed, or alternatively dissolved or dispersed in a portion of the bulk liquid, before they are added overhead into the mixing vessel along with the remainder of the bulk liquid phase. The entire in-vessel manufacturing process takes place under vacuum of at least -800 mbar(g) to minimise air entrainment. The liquid mixture in the vessel is first heated to an elevated temperature between 60 and 80°C and held for between 30 and 60 minutes to activate and/or sufficiently swell the structuring components. Next, the temperature may be maintained, or reduced as low as 50°C before several sequential overhead additions of the other solid active components and powdered abrasives. These are dispersed and suspended by providing appropriate levels of mixing and shear from the overhead agitators. Following the completion of all solid additions and mixing steps, the product is cooled from an elevated temperature.

For examples 1 and 2 pertaining to the proposed invention, rapid cooling is achieved via the direct addition of a mass of cardice equal to between 14% and 17% of the total mass of product. For both examples, flavourings and perfumes are added to the vessel immediately prior to the cardice, as part of the same overhead addition process. Adding solid cardice pellets to the viscous, elevated temperature product causes their immediate and rapid sublimation, resulting in the formation of carbon dioxide gas and causing the temperature of the product to decrease rapidly, at a rapid cooling rate of between 10°C/min and 40°C/min. After cooling to the desired product filling temperature, the product underwenta further mixing stage to encourage deaeration.

For comparative examples A and B, cooling is achieved via the circulation of chilled silicon oil through the jacket surrounding the vessel. Product is first cooled to an intermediate temperature, preferably 45°C, with a cooling rate of between 1.1 and 1 ,3°C/min. Flavouring and perfumes are then added via a final overhead addition, before the product is further cooled to the required product filling temperature, (30°C) with a conventional cooling rate of between 0.6 and 0.8°C/min. After each batch is made, a viscosity measurement was taken using a Brookfield

Viscometer Model DV-I with a T bar type spindle of size E for 60 s at 5 RPM at 25°C.