Chewable composition comprising porous silica particles

Abstract

There is provided herein a chewable composition comprising porous silica particles having pores in the mesoporous range, wherein the average pore size of the pores in the mesoporous range is from about 7 to about 25 nm.

Description

[0001] CHEWABLE COMPOSITION COMPRISING POROUS SILICA PARTICLES

[0002] Field of the Invention

[0003] The present invention is concerned with chewable compositions containing silica particles. In particular, the present invention relates to chewable oral care compositions comprising porous silica particles, which compositions are useful in the prevention of tooth decay, formation of dental caries, and gum disease (e.g. gingivitis).

[0004] Background to the Invention

[0005] The listing or discussion of any prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

[0006] Tooth (dental) decay, or the development of dental caries, occurs when the enamel of the tooth is damaged, causing lesions within the tooth which can develop into cavities. Infection of the resulting cavities may lead to complications including inflammation of the tissue around the tooth, tooth loss, infection and abscess formation.

[0007] Dental caries may develop for a number of reasons. In particular, they may develop when bacteria in the mouth metabolise sugars to produce acids which demineralize the hard tissues of the tooth (enamel and dentine). Such sugars may be present in the mouth as a direct result of food consumption or may be produced in situ, such as through the action of the salivary amylase enzyme in breaking down starches into sugars (e.g. maltose). Bacteria then engage in the fermentation of such sugars to produce acids (e.g. lactic acid), which in turn cause damage to the tooth enamel.

[0008] The reduction of the formation of dental caries is typically achieved through improved oral hygiene, the aim of which is to remove food material from the mouth, and thereby remove sources of starches and sugars, and to reduce the population of cariogenic bacteria, thereby reducing the production of acids through fermentation. Brushing of the teeth with toothpaste products is typically directed at food removal, although some antibacterial effects may also arise. Reduction in bacterial populations may also be achieved through the use of mouthwash products, such as those containing antibacterial agents and / or denaturing agents (e.g. alcohols). In between brushing of the teeth or when brushing of the teeth is not possible, chewable compositions (such as chewing gums and gummies) may be used instead for removal of food material and reduction of the cariogenic bacterial population in the oral cavity. Chewable compositions may stimulate the production of saliva, which helps to provide a number of dental benefits including the more rapid oral clearance of sugars due to the increased rate of saliva production, the high pH and buffering capacity of the stimulated saliva may help neutralise plaque pH, and lastly, enhanced remineralisation of early carieslike lesions.

[0009] Other agents may be included in chewable compositions such as chewing gums to strengthen the enamel of the tooth (e.g. fluoride), to improve flavour, to modify the appearance of the product (e.g. colourants) and to combat halitosis.

[0010] Porous silica particles have been used in a number of healthcare applications, such as in providing a medium for drug loading and delivery of therapeutic agents. They are thermally and chemically stable, and are exclusively composed of pure silicon dioxide.

[0011] These silica particles may possess controllable pore sizes, which gives them a high surface area and large total pore volume. These properties, amongst others such as stability and biocompatibility, make them particularly suited for biomedical applications (see, for example, Wang, Y. et al., Nanomedicine Nanotechnology, Biol. Med. 11, 313-327 (2015)). Moreover, similar materials have previously been approved as food additives (European Center for Ecotoxicology and Toxicology of Chemicals Synthetic Amorphous Silica (CAS No. 7631-86-9), JACC No. 51, page 14 (ECETOC, 2006)).

[0012] WO 2014 / 072363 discusses the use of highly structured, porous silica materials having a specific average pore size of pores in the mesoporous range in the treatment of conditions such as obesity and dyslipidemia. It does not provide any teaching relating to oral hygiene, or the prevention or reduction of dental caries.

[0013] Detailed Description of the Invention

[0014] We have found that certain porous silica materials having a specific average pore size in the mesoporous range are able to effectively act as molecular sieves for certain biological molecules that are normally found in the oral cavity, and thus have properties rendering them useful in chewable compositions (e.g., for oral care purposes), such as in the prevention of or reduction in the formation of dental caries. Specifically, porous silica particles according to the present invention are designed to possess certain physiochemical properties, as herein described, allowing for a significant biological effect of relevance to the above-mentioned applications. Control of certain particle properties, such as average pore size, has been unexpectedly found to provide these biological effects, such as by allowing for the adsorption of salivary amylase enzyme in the mouth, which in turn may lead to reduced production of acids by cariogenic bacteria which are detrimental to oral (e.g. dental) health.

[0015] Surprisingly, the silica particles are able to exert this effect (i.e. adsorption of salivary amylase enzyme in the mouth) even when incorporated in chewable products, such as chewing gums and gummies.

[0016] Chewable compositions

[0017] In a first aspect of the invention, there is provided a chewable composition comprising porous silica particles having pores in the mesoporous range, wherein the average pore size of the pores in the mesoporous range is from about 7 to about 25 nm.

[0018] For the avoidance of doubt, the silica particles as defined in the first aspect of the invention (including all embodiments and features thereof) may also be referred to as "the silica (or silica material or silica particles) of the invention (or of the first aspect of the invention)," or the like. Similarly, compositions as defined in the first aspect of the invention (including all embodiments and features thereof) may also be referred to as "the composition(s) of the invention (or of the first aspect of the invention)," or the like.

[0019] Unless indicated otherwise, all technical and scientific terms used herein will have their common meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0020] When used herein in relation to a specific value (such as an amount), the term "about" (or similar terms, such as "approximately") will be understood as indicating that such values may vary by up to 10% (particularly, up to 5%, such as up to 4%, 3%, 2% or 1%) of the value defined. It is contemplated that, at each instance, such terms may be replaced with the notation "±10%", or the like (or by indicating a variance of a specific amount calculated based on the relevant value). It is also contemplated that, at each instance, such terms may be deleted. For the avoidance of doubt, the skilled person will understand that where percentages of a certain feature are defined as belonging to different (i.e. non-overlapping) groups, the sum of these percentages cannot exceed 100%. Similarly, where it is possible for such features to belong to other, non-specified groups, there is no requirement for the sum of the specified features to equal 100%.

[0021] As described herein, the chewable compositions of the first aspect of the invention have properties rendering them useful for oral care purposes, such as in the prevention of or reduction in the formation of dental caries. As such, chewable compositions of the first aspect of the invention may be referred to as oral care compositions, oral hygiene compositions, dental care compositions, dental hygiene compositions, or the like.

[0022] For example, in a particular embodiment, the chewable compositions of the first aspect of the invention may be referred to as chewable oral care compositions.

[0023] The skilled person will understand that the porous silica particles as provided in the compositions of the first aspect of the invention may be referred to as a plurality thereof, which plurality may be referred to as a porous silica material.

[0024] The skilled person will understand that chewable compositions of the first aspect of the invention include compositions of a general type that can be chewed by an animal (e.g. human), such as chewing gum or a jelly-like composition (such as a gummy) or other preparation in a form suitable for chewing.

[0025] The skilled person will understand that the chewable compositions of the present invention are not in the form of liquid, paste, powder, or gel (e.g. are not dentifrice, toothpaste or mouthwash). A dentifrice includes references to compositions in an extrudable semi-solid form, such as pastes (i.e. a toothpaste) and gels, and to powders (i.e. a toothpowder), including loose and compressed (e.g. loose) powders, which compositions are suitable for use in the brushing and / or polishing (e.g. brushing) of the teeth (e.g. using a suitable tooth cleaning implement, such as a toothbrush). As such the term dentifrice may denote an oral composition which is used to clean (the surfaces of) the oral cavity. The skilled person will also understand that references to gels may refer to substances having the physical properties of a liquid but with substantially zero flow.

[0026] In particular embodiments, the chewable composition is in the form of a chewable solid and / or (e.g. or) a chewable semi-solid (e.g. hydrogel). The skilled person will understand that a composition of the invention is referred to as solid and / or semi-solid even if it comprises a liquid or semi-liquid component (such a core).

[0027] In certain embodiments, the chewable composition does not comprise a liquid or semiliquid component.

[0028] In more particular embodiments, the chewable composition is in the form of a chewable solid.

[0029] In particular embodiments, the chewable composition is a confectionery composition (which, for the avoidance of doubt, will also act as an oral care composition).

[0030] The skilled person will understand that the chewable compositions of the first aspect of the invention may be swallowable or non-swallowable (i.e. in typical use by a human or animal subject, e.g. a human, the composition may, particularly after being chewed by said subject, be swallowed or be ejected from the mouth).

[0031] In a particular embodiment, the composition is non-swallowable (i.e. is in a form typically not swallowed after use).

[0032] In particular embodiments, the chewable solid is in the form of a chewing gum.

[0033] The term chewing gum will be well known to those skilled in the art, such as by referring to a soft, cohesive substance designed to be chewed without being swallowed.

[0034] In such embodiments, the chewable composition may comprise, in addition to the porous silica particles as described herein, one or more additional components as typically provided in order to form such compositions, which will include those as described herein.

[0035] For example, in addition to the silica particles as described herein, such compositions may also comprise a gum base, glycerin, softeners, plasticisers, colourants, fragrances, sweeteners (e.g. xylitol and / or erythritol) and / or flavourings, suitable relative proportions of which may be determined by the those skilled in the art.

[0036] In particular embodiments, the chewable composition comprises a sweetener, such as an artificial sweetener or a natural sweetener (e.g. a sugar alcohol or steviol glycoside). In particular, the artificial and natural sweetener may be a sugar-free sweetener. In more particular embodiments, the chewable composition comprises substantially no sugar (such as the composition comprises less than 0.5 wt% sugar, such as less than 0.1 wt% sugar). In such embodiments, the chewable composition may be referred to as a sugar-free composition.

[0037] Thus, in particular embodiments, references to a chewable composition may be replaced with references to a chewing gum, which term the skilled person will understand as referring to a cohesive substance designed to be chewed without being swallowed. In particular, a chewing gum may be a composition suitable for chewing (i.e. being chewed) by a human for a period of time, such as for a period of about thirty seconds to thirty minutes, and then ejecting the composition or part thereof (e.g. ejecting essentially the gum base that did not degrade during chewing) from the mouth.

[0038] Thus, it will be understood by those skilled in the art that such certain compositions (particularly chewing gums) are typically not intentionally swallowed for purposes of systemic administration of therapeutic agents, but are instead temporarily chewed and then ejected from the body via the mouth. As such, certain compositions (particularly chewing gums) as described herein may be referred to as being non-systemic, topical (as it pertains to the oral cavity, e.g. orally topical), not for swallowing, not for consumption, and the like.

[0039] In further embodiments, the composition may be swallowable.

[0040] In particular embodiments, the chewable semi-solid is in the form of a chewable hydrogel, such as a chewable jelly-like composition.

[0041] The skilled person will understand that in embodiments where the chewable composition is in the form of a chewable hydrogel, the composition does not flow even when pressure is applied (e.g. when the composition is squeezed), but instead it disintegrates (i.e. it breaks rather than flows).

[0042] In more particular embodiments, the chewable semi-solid is in the form of a chewable and swallowable jelly-like composition.

[0043] As used herein, the term "jelly-like composition" refers to compositions having the consistency of jelly i.e. soft and elastic solids, such as gelatinous solids (which may also be referred to as a gummy). In such embodiments, the composition may comprise, in addition to the porous silica particles as described herein, one or more additional components as typically provided in order to form such compositions, including those as described herein.

[0044] Thus, in particular embodiments, references to a chewable composition may be replaced with references to a jelly-like composition (or a gummy, or the like), which term the skilled person will understand as referring to a composition suitable for chewing (i.e. being chewed) by an animal (e.g., human) for a period of time (e.g. from thirty seconds to ten minutes), during which time the composition is being broken down (i.e. degraded) by the action of chewing until the composition is swallowed in its entirety.

[0045] In particular embodiments, the jelly-like composition is in the form of a gummy (which is also known as a gummy candy or a jelly sweet).

[0046] As used herein, "gummy" (or similarly "gummy candy", "jelly sweets", or "wine gums") refers to a composition typically made from a gelatine, pectin, agar, or a gum base (which is similar to the base found in soft caramels, marshmallows, wine gums, pastilles, and other sweets) and a blend of other ingredients such as cornstarch, sweeteners, colorant, acidity modifiers, preservatives, and / or flavourings. The gelatine (or similar) gives the gummy its elasticity, the desired chewy consistency and a longer shelf-life.

[0047] The skilled person will understand that such gummies may be in any shape, such as in the shape of an animal or household object. In particular embodiments, the gummy may be the form of a bear, frog, shark, worm, bottle, ring, or worm, such as a bear.

[0048] For the avoidance of doubt, the skilled person will understand that compositions as described herein will be of a size suitable to be placed in the mouth of a subject (e.g. a human) and chewed.

[0049] As discussed herein, the chewable composition may comprise additional components as typically present in the relevant type of composition, which components will be known to those skilled in the art (Hartel, R.W., von Elbe, J.H., Hofberger, R. (2018). 12. Jellies, Gummies and Licorices and 14. Chewing and Bubble Gum;. In : Confectionery Science and Technology. Springer, Cham.).

[0050] For example, where the chewable composition is provided in the form of a chewing gum, the chewing composition may further comprise components including: gum base, which may be present in an amount of from about 10 wt% to 90 wt% by weight based on the total weight of the composition. Suitable gum bases typically comprise a resin, a wax, and an elastomer. The resin is typically the main chewable portion. The wax softens the gum. The elastomer adds flexibility. Suitable gum bases that may be mentioned include natural ingredients (such as Chicle, Chiquibul, Crown gum, Gutta hang kang, Massaranduba balata, Massaranduba chocolate, Nispero, Rosidinha, Venezuelan chicle, Jelutong, Leche caspi (sorva), Pendare, Perillo, Leche de vaca derived from Moraceae, Niger gutta, Tunu (tuno), Chilte, Natural rubber) and synthetic ingredients (Butadiene-styrene rubber, Isobutylene-isoprene copolymer (butyl rubber), Paraffin, Petroleum wax, Polyethylene, Polyisobutylene, Polyvinyl acetate); binders and / or thickening agents, which may be present in an amount of from about 1 wt% to 30 wt% by weight based on the total weight of the composition. Suitable binders or thickening agents that may be mentioned include carboxyvinyl polymers (such as polyacrylic acids cross-linked with polyallyl sucrose or polyallyl pentaerythritol), hydroxyethyl cellulose, hydroxypropyl cellulose, natural gums (such as carrageenan, gum karaya, guar gum, xanthan gum, gum arabic, and gum tragacanth). Natural gum-based thickeners, in particular carrageenan, may also be mentioned. Particular thickeners that may be mentioned include gums such as Irish moss, iota-carrageenan, gum tragacanth, and polyvinylpyrrolidone. For the avoidance of doubt, the skilled person will understand that the essential silica component of the first aspect of the invention may also function as a thickener. fluoride sources. Particular fluoride sources that may be mentioned include sodium fluoride, stannous fluoride, sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, calcium fluoride, cobalt ammonium fluoride and mixtures thereof; further optional ingredients customary in the art, such as antimicrobial agents such as chlorhexidine, sanguinarine extract, metronidazole, quaternary ammonium compounds (e.g. cetylpyridinium chloride), bis-guanides (e.g. chlorhexidine digluconate, hexetidine, octenidine and alexidine) and halogenated bisphenolic compounds (e.g. 2,2' methylenebis- (4-chloro-6-bromophenol)), anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin and indomethacin, 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 such as potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and strontium salts, anti-calculus agents such as alkali-metal pyrophosphates, hypophosphite- containing polymers, organic phosphonates and phosphocitrates, biomolecules such as bacteriocins, antibodies and enzymes, flavours such as peppermint and spearmint oils, proteinaceous materials such as collagen, preservatives, opacifying agents, amino acids such as arginine, colouring agents, sweetening agents, pharmaceutically acceptable carriers such as starch, sucrose, pH-adjusting agents including buffers and salts to buffer the pH and ionic strength of the chewable composition, bleaching agents such as peroxy compounds (e.g. potassium peroxydiphosphate), effervescing systems such as sodium bicarbonate / citric acid systems, and colour change systems; other agents, such as sweeteners (e.g. sugar or, particulalry, artificial sweeteners such as xylitol and / or erythritol), flavourings (e.g. mint or fruit flavourings), colourants, fragrances (e.g. mint or fruit fragrances) and / or preservatives (e.g. sodium benzoate or potassium sorbate).

[0051] Similarly, where the chewable composition is provided in the form of a jelly-like composition (e.g. a gummy), the chewable composition may further comprise components including: water, which may be present in an amount from about 5 to about 90 wt% of the total composition; a gelling agent (inorganic, natural or synthetic), which agent may be present in amounts from about 0.1 to about 15.0 wt% of the total composition. The skilled person will understand that the amount (and proportions) of the gelling agent will be selected in order to form a chewable (i.e. elastic product), which can be chewed for a suitably long period of time (before it breaks down and it is swallowed), to provide the beneficial effect in terms of oral health as described herein. Suitable gelling agents include gelatine, pectine, starch, agar, carrageenan, xantham gum, Arabic gum, calcium salts. a buffer, such as sodium bisulfate, sodium citrate, or citric acid; other agents, such as sweeteners (e.g. sugar or, particularly, artificial sweeteners such as xylitol and / or erythritol), flavourings (e.g. mint or fruit flavourings), colourants, fragrances (e.g. mint or fruit fragrances) and / or preservatives (e.g. sodium benzoate or potassium sorbate). In some embodiments, the gelling agent may be one or a mixture of two or more of gelatine (i.e. gelatin), pectin, starch, agar (i.e. agar-agar), carrageenan, xanthan gum, and gum arabic.

[0052] In particular embodiments, the gelling agent is pectin and / or (e.g. or) agar.

[0053] In particular embodiments, where the gelling agent comprises pectin, the chewable composition may further comprise calcium salts. Such calcium salts help thicken the composition, in particular a sugar-free pectin-based composition.

[0054] The skilled person will also understand that such chewing gum and / or (e.g. and) jelly-like compositions may comprise further ingredients as may be desirable in the circumstances, such as anti-bacterial agents (e.g. an alcohol), colourants and / or flavourings (such as menthol).

[0055] Without wishing to be bound by theory, it is thought that the presence of surfactants, such as those commonly used in some oral care compositions (although not typically used in chewing gums or jelly-like compositions), may inhibit or reduce the effects of the silica particles and thus reduce the beneficial effects of the composition.

[0056] Thus, in particular embodiments, the chewable composition (e.g. the chewing gum and / or jelly-like composition) is substantially free of surfactant.

[0057] Particular surfactants that may be mentioned include: anionic surfactants, such as sodium lauryl sulfate; zwitterionic (zero net charge) surfactants, such as cocamidopropyl betaine; and nonionic surfactants, such as polyethoxylated fatty acid sorbitan esters (e.g. polysorbate 80), ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid, monoglycerides and diglycerides, and ethylene oxide / propylene oxide block polymers, and polyethylene glycol ethers of fatty alcohols, in particular polyethylene glycol ethers having from 2 to 200 (e.g. 20 to 40) ethylene oxide groups per unit, such as polyoxyethylene (2- 100, e.g. 4) lauryl ether, and 'steareth' surfactants, such as Steareth 30.

[0058] As used herein, the skilled person will understand that the reference to being substantially free of surfactant may refer to presence of components classified as surfactants (such as those referred to herein) at concentrations at or below about 0.5 wt% of the total composition, such as at or below about 0.4, 0.3, 0.02 or, particularly, 0.1 wt% of the total composition (e.g. at or below about 0.09, 0.08, 0.07, 0;06 or 0.05 wt% of the total composition, particularly below about 0.04, 0.03, 0.02 or 0.01 wt% of the total composition).

[0059] In particular embodiments, the skilled person will understand that the reference to being substantially free of surfactant may refer to the absence of (i.e. the absence of detectable levels of) components classified as surfactants, which may indicate that the preparation of such compositions does not involve addition of any such components.

[0060] As used herein, being substantially free of a component may be indicated by stating that the composition "does not contain a substantial concentration of" or "does not contain" that component, respectively.

[0061] The skilled person will also understand that the maximum about of surfactant that may be present may vary depending on the nature of the surfactant component, with such levels being determined using routine techniques.

[0062] For example: in respect of anionic surfactants, such as sodium lauryl sulfate, the surfactant may be present at levels at or below about 0.05 wt% (e.g. below about 0.04, 0.03, 0.02 or, particularly, 0.01 wt%), or may be referred to in terms of the absence thereof; in respect of zwitterionic (zero net charge) surfactants, such as cocamidopropyl betaine, the surfactant may be present at levels at or below about 0.05 wt%; nonionic surfactants, such as polyethoxylated fatty acid sorbitan esters (e.g. polysorbate 80), the surfactant may be present at levels at or below about 0.1 (or, particularly, 0.05) wt%, or may be referred to in terms of the absence thereof.

[0063] In particular embodiments, where amounts of specific surfactants are referred to, compositions will be substantially free of other surfactants.

[0064] For the avoidance of doubt, the skilled person will understand that references herein to particles forming part of a composition may include only particles of a suitable size to be considered as forming part of the composition (i.e. particles that may be able to function as a component of the composition). The skilled person will be able to determine the amount of the silica of the invention required in compositions of the invention in order to provide the effects as described herein, which amounts may depend on the type of composition used.

[0065] In particular embodiments, the silica of the invention may be present in compositions of the invention in amounts from about 0.1 to about 20.0 wt%.

[0066] For example, the silica of the invention may be present in compositions of the invention in amounts of about 0.5 wt% (e.g. about 0.44 wt%).

[0067] As used herein, the term "consists essentially of" may indicate that the relevant composition consists of at least 90% by weight (e.g. at least 95% by weight, such as at least 99% by weight or, particularly, at least 99.9%) of the relevant substance.

[0068] In alternative embodiments of the first aspect of the invention, the porous silica particle content (or, alternatively, the silica particle content) of the composition consists of (or consists essentially of) the silica particles as defined herein (i.e. such that components other than porous silica material may be present).

[0069] The skilled person will understand that the properties of the silica of the invention may be such that the use of other enzyme inhibiting / denaturing and / or adsorbing materials / substances is not required (i.e. the composition of the invention may produce the effects as described herein without the need for the presence of such agents).

[0070] In particular embodiments of first aspect of the invention, the composition comprises the porous silica material (as defined in the first aspect of the invention) as the only (i.e. sole) ingredient capable of adsorbing enzymes.

[0071] Thus, in further embodiments of first aspects of the invention, the composition is substantially free of other enzyme adsorbing ingredients.

[0072] As used in relation to other enzyme adsorbing ingredients, the term substantially free will refer to the essential material (e.g. the composition referred to) comprising no significant (i.e. clinically significant) amount of the other material referred to (e.g. the other therapeutically active ingredient(s)), which may indicate the presence of less than 10% (e.g. less than 5%, such as less than 2%, less than 1%, less than 0.5% or, particularly, less than 0.1%, less than 0.01% or less than 0.001%) by weight of the other material, or more particularly the presence of no detectable amount of the other material. Porous silica particles

[0073] The skilled person will understand that references herein to pores being of a certain size will refer to the average diameter of the relevant pores (i.e. the average diameter of each individual pore, considering the dimensions thereof). For the avoidance of doubt, the skilled person will understand that references to average pore size may refer in particular to the average size of the opening of each pore (or, in the case of a pore the channel of which internally traverses the body of the particle, the average size of all openings to the pore(s)), which may be referred to as the pore window(s) (or the window(s) of the pore).

[0074] For the avoidance of doubt, unless otherwise stated, averages referred to herein will be calculated as the mean average.

[0075] Unless otherwise stated, pore sizes as described herein is measured by nitrogen sorption and calculated using the Density Functional Theory (DFT) method (see, for example, the methods as described in Landers, J. et al., Colloids and Surfaces A: Physicochem. Engineering Aspects, 437, 3-32 (2013)). As such, unless otherwise stated, references herein to an average pore size will refer to pore size as measured by nitrogen sorption and calculated using the Density Functional Theory (DFT).

[0076] The skilled person will understand that references to the percentage of pores present being in a particular range may be understood to be references to the pore size distribution (PSD) of such particles. As such, references to the percentage of pores present being in a particular range will refer to the combined volume of pores present in each range as a percentage of the total pore volume of the relevant group(s) of pores (e.g. pores in the mesoporous range).

[0077] For the avoidance of doubt, references to particles having a particular average pore size may in certain instances include references to pores that are functionally equivalent (e.g. when utilised in the manner described herein) with particles having such average pore sizes.

[0078] The skilled person will understand that pore size distribution of the silica material may be measured using DFT pore size distribution curves, which is a technique well-understood by those skilled in the art (see, for example, Olivier, J. P., Conklin, W. B. and Szombathely, M. V., Studies in Surface Science and Catalysis, 87, 81-89 (1994)). The percentage of the pores are calculated from the DFT cumulative pore size distribution curves. The skilled person will understand that references to porous silica particles having pores in the mesoporous range will take its normal meaning in the art, i.e. as referring to porous silica particles having (or containing / comprising) pores with a diameter in the range 2 to 50 nm, which materials may be referred to as mesoporous and which pores may be referred to as mesopores.

[0079] For the avoidance of doubt, the skilled person will understand that the porous silica material referred to in the first aspect of the invention may also have (i.e. further containing / comprising) pores with a diameter outside of the mesoporous range, such as by having micropores (i.e. pores with a diameter of less than 2 nm) and / or macropores (i.e. pores with a diameter of greater than 50 nm).

[0080] For the avoidance of doubt, unless otherwise stated, references for percentages of pores as used herein will refer to the percentage by volume.

[0081] In a particular embodiment, at least about 40% (i.e., 40% by volume) of the pores present in the silica material of the invention are in the mesoporous range.

[0082] In a more particular embodiment, at least about 50%, such as at least about 60%, particularly at least about 70%, of the pores present in the silica material of the invention are in the mesoporous range.

[0083] The skilled person will understand that, in relation to the pores in a given range, there may also be calculated an average (i.e. mean average) pore size. As described herein, such average pore size may be measured by the nitrogen sorption technique and calculated using the Density Functional Theory (DFT), which will be well-known to those skilled in the art (see: Olivier, J. P., Conklin, W. B. and Szombathely, M. V., Studies in Surface Science and Catalysis, 87, 81-89 (1994); Landers, J., et al., Colloids and Surfaces A: Physicochem. Eng. Aspects, 437, 3-32 (2013)). As such, unless otherwise stated, references herein to average pore size will refer to average pore size as measured by nitrogen sorption and calculated using DFT.

[0084] As described herein, the average pore size of the pores in the mesoporous range is from about 7 to about 25 nm.

[0085] In particular, the average pore size of the pores in the mesoporous range may be described as being from about 7.0 to about 25.0 nm. In particular embodiments, the average pore size of the pores in the mesoporous range is from about 7.0 to about 22.0 nm.

[0086] In more particular embodiments, the average pore size of the pores in the mesoporous range is from about 7.0 to about 21.0 nm.

[0087] In yet more particular embodiments, the average pore size of the pores in the mesoporous range is from about 7.0 to about 20.0 nm.

[0088] For example, in certain embodiments the average pore size of the pores in the mesoporous range is: from about 7.0 to about 19.0 nm; from about 7.0 to about 18.0 nm; from about 7.0 to about 17.0 nm; from about 7.0 to about 16.0 nm; from about 7.0 to about 15.0 nm; from about 7.0 to about 14.0 nm; from about 7.0 to about 13.0 nm; or from about 7.0 to about 12.0 nm.

[0089] In certain embodiments, the average pore size of the pores in the mesoporous range is from about 8.0 to about 13.0 nm.

[0090] In more particular embodiments, the average pore size of the pores in the mesoporous range is from about 8.0 to about 12.0 nm.

[0091] In more particular embodiments, the average pore size of the pores in the mesoporous range is from about 8.0 to about 11.0 nm.

[0092] In alternative embodiments, the average pore size of the pores in the mesoporous range is at least from about 9.0 nm, such as from about 9.0 to about 11.0 nm.

[0093] In yet more particular embodiments, the average pore size of the pores in the mesoporous range is at least about 10.0 nm, such as from about 10.0 to about 18.0 nm.

[0094] In yet more particular embodiments, the average pore size of the pores in the mesoporous range is at least about 10.1 nm, such as from about 10.1 to about 18.0 nm. In yet more particular embodiments, the average pore size of the pores in the mesoporous range is at least about 10.2 nm, such as from about 10.2 to about 18.0 nm.

[0095] In yet more particular embodiments, the average pore size of the pores in the mesoporous range is at least about 10.5 nm, such as from about 10.5 to about 18.0 nm.

[0096] In yet more particular embodiments, the average pore size of the pores in the mesoporous range is at least about 10.8 nm, such as from about 10.8 to about 16.0 nm.

[0097] The skilled person will understand that, in addition to referring to the (mean) average pore size, as described herein, the silica material of the invention may also be defined by reference to the distribution of pore sizes, such as the distribution of pore sizes of the pores in the mesoporous range.

[0098] In particular embodiments of the first aspect of the invention, at least 21% (such as at least at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27% at least 28% or at least 29%) of the pores in the mesoporous range (by volume) have a diameter in within the range of the specified for the average pore size (i.e. the range as specified for the average pore size).

[0099] In more particular embodiments of the first aspect of the invention, at least about 30% of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0100] In yet more particular embodiments of the first aspect of the invention, at least about 35% (such as at least 40% or at least 45%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0101] In still more particular embodiments of the first aspect of the invention, at least about 50% (such as at least 55%, at least 60%, at least about 65%, at least about 70% or, particularly, at least about 72%) of the pores in the mesoporous range have a diameter in within the range of the average pore size (i.e. the range given for the average pore size of the pores in the mesoporous range, as defined herein).

[0102] For example, in certain embodiments at least about 50% (such as at least 55%, at least 60%, at least about 65%, at least about 70% or, particularly, at least about 72%) of the pores in the mesoporous range have a diameter in within the range about 7.0 to about 25.0 nm.

[0103] In certain embodiments, up to about 100% (or up to about 99%, about 95%, or about 90%) of the pores in the mesoporous range have a diameter in within the range of the average pore size (i.e. the average pore size range as specified herein).

[0104] In certain embodiments, from about 21% to about 100% (or, particularly, about 25% to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0105] In yet more particular embodiments of the first aspect of the invention, at least about 30% (e.g. about 30% to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0106] In yet more particular embodiments of the first aspect of the invention, at least about 35% (e.g. about 35% to about 99%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0107] In yet more particular embodiments of the first aspect of the invention, about 40% to about 90% (or to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0108] In certain embodiments of the first aspect of the invention, about 50% to about 90% (or to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0109] In certain embodiments of the first aspect of the invention, about 55% to about 90% (or to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0110] In certain embodiments of the first aspect of the invention, about 60% to about 90% (or to about 99% or 100%) of the pores in the mesoporous range have a diameter in within the range of the average pore size.

[0111] For example, in a particular embodiment (i.e. a particular embodiment of the first aspect of the invention), at least about 25% (e.g. about 25% to about 99%, such as about 50% to about 99% or 100%) of the pores of the silica particle are mesopores of a size in the range of from about 7.0 to about 25.0 nm (such as about 7.0 to about 18.0 nm, or about 7.0 to about 16.0 nm).

[0112] Similarly, in a particular embodiment, at least about 50% (e.g. about 50% to about 99%, such as about 50% to about 90%) of the pores of the silica particle are mesopores of a size in the range of from about 7.0 to about 25.0 nm (such as about 7.0 to about 18.0 nm, or about 7.0 to about 16.0 nm).

[0113] In a particular embodiment (i.e. a particular embodiment of the first aspect of the invention), at least about 50% (e.g. about 50% to about 99%) of the pores of the silica particle are mesopores of a size in the range of from about 9.0 to about 18.0 nm, or about 9.0 to about 16.0 nm.

[0114] In a further embodiment, at least about 25% (e.g. at least about 50%, about 60% or about 70%) of the pores of the silica particle are mesopores of a size in the range of from about 9.0 to about 18 nm.

[0115] In a further embodiment, at least about 25% (e.g. at least about 50%, about 55%, about 60%, about 65% or about 70%) of the pores of the silica particle are mesopores of a size in the range of from about 9.0 to about 16 nm.

[0116] In a more particular embodiment, at least about 25% (e.g. about 25% to about 99%) of the pores of the silica particle are mesopores of a size in the range of from about 10.1 to about 16 nm.

[0117] In a yet more particular embodiment, at least about 25% (e.g. about 25% to about 99%) of the pores of the silica particle are mesopores of a size in the range of from about 10.1 to about 15 nm.

[0118] The skilled person will understand that references to porous silica particles having pores in the mesoporous range will necessarily require that such particles are porous, which will include particles behaving in a porous manner. As such, porous silica particles will refer to particles having a significant degree of porosity, which may in certain embodiments be defined by reference to features such as the pore volume and / or surface area of the particles, such as by reference to those parameters as defined herein (which features as described herein may, as with other features described herein, be taken both alone and in combination). The skilled person will understand that the surface area of a particle (or a sample of particles) may be calculated using the Brunauer Emmett Teller (BET) theory, a technique well-known to those skilled in the art (see, for example, Brunauer, S., Emmett, P. H., and Teller, E., J. Am. Chem. Soc., 60(2), 309-319 (1938)).

[0119] In a particular embodiment, the silica particles have a BET surface area of at least about 150 m2 / g.

[0120] In a more particular embodiment, the silica particles have a BET surface area of at least about 200 m2 / g.

[0121] In a yet more particular embodiment, the silica particles have a BET surface area of at least about 225 m2 / g (such as at least about 250 m2 / g).

[0122] In a still more particular embodiment, the silica particles have a BET surface area of at least about 400 m2 / g (such as at least about 450 m2 / g).

[0123] In a particular embodiment, the silica particles have a BET surface area of at least about 500 m2 / g.

[0124] In particular embodiments, the BET surface area is up to about 1500 m2 / g (such as up to about 1200 m2 / g or 1000 m2 / g).

[0125] For example, in a particular embodiment, the silica particles have a BET surface area of from about 200 to about 1500 m2 / g.

[0126] In a further embodiment, the silica particles have a BET surface area of from about 200 to about 1200 m2 / g.

[0127] In a yet more particular embodiment, the silica particles have a BET surface area of from about 200 to about 1000 m2 / g.

[0128] In an alternative embodiment, the silica particles have a BET surface area of from about 200 to about 800 m2 / g.

[0129] In a further alternative embodiment, the silica particles have a BET surface area of from about 200 to about 400 m2 / g, such as from about 200 to about 300 m2 / g. In a yet further alternative embodiment, the silica particles have a BET surface area of from about 225 to about 275 m2 / g.

[0130] The skilled person will understand that the porous silica particles may be provided in a variety of shapes.

[0131] In a particular embodiment, the silica particles have a substantially non-spherical morphology (i.e. an aspect ratio of greater than 1 : 1, such as greater than 1.1: 1).

[0132] In a more particular embodiment, the silica particles have an aspect ratio of greater than 1.5: 1, such as greater than 1.8: 1.

[0133] In a yet more particular embodiment, the silica particles have an aspect ratio equal to or greater than 2: 1.

[0134] As used herein, the term "aspect ratio" will be understood to refer to the ratio between the largest cross-section diameter of the silica particle and the smallest cross-section diameter.

[0135] Alternatively, such particles (i.e. particles having a substantially non-spherical morphology) may be described as having at least one plane (i.e. an equally dividing plane bisecting the particle) of asymmetry (i.e. such that the morphology of the particle differs about the plane).

[0136] In a more particular embodiment, the silica particles have an essentially rod-shaped morphology. Thus, in particular embodiments, the porous silica particle may be characterized by having an essentially rod-shaped morphology, as seen by electron microscopy (such as by Scanning Electron Microscopy (SEM) or Transmission Electron Microscopy (TEM), using techniques known to those skilled in the art), such as with a rodlength of from about 0.5 to about 5.0 pm.

[0137] As used herein, the term essentially rod-shaped will be understood as referring to a particle of an elongate form resembling a rod, in which the rod may be straight or curved (e.g. such rod shaped particles may be substantially straight).

[0138] In an alternative embodiment, the silica particles of the invention may be substantially spherical (or referred to as spherical). Thus, in a particular embodiment, the silica particles of the invention may have an aspect ratio (or an average aspect ratio) of about 1: 1. In further embodiments, the silica particles of the invention may be of amorphous shape.

[0139] The skilled person will understand that the term mean particle size, as used herein, will refer to the mean diameter of the particles at the greatest point thereof (e.g. in the case of rod-shaped particles, the length thereof; or in the case spherical particles, the diameter thereof.), which may be measured using techniques well-known to those skilled in the art, for example using electron microscopy techniques (such as by Scanning Electron Microscopy (SEM) or Transmission Electron Microscopy (TEM) technique known to those skilled in the art). In a particular embodiment, particle size is determined using electron microscopy (e.g. using SEM).

[0140] In particular embodiments, such as those in which the particles are spherical, the size of particles may be defined by reference to the diameter thereof.

[0141] In a particular such embodiment, the silica particles have a mean particle size of from about 0.1 to about 20.0 pm.

[0142] In a more particular embodiment, the silica particles have a mean particle size of from about 0.1 to about 15.0 pm.

[0143] In a yet more particular embodiment, the silica particles have a mean particle size of from about 0.1 to about 10.0 pm.

[0144] In a yet more particular embodiment, the silica particles have a mean particle size of from about 0.5 to about 10.0 pm.

[0145] In a still more particular embodiment, the silica particles have a mean particle size of from about 0.5 to about 5.0 pm.

[0146] In certain embodiments, the silica particles have a mean particle size of from about 0.5 to about 4.5 pm.

[0147] In particular embodiments, the silica particles have a mean particle size of from about 1.0 to about 10.0 pm.

[0148] In particular embodiments, the silica particles have a mean particle size of from about 1.0 to about 5.0 pm. In more particular embodiments, the silica particles have a mean particle size of from about 1.0 to about 4.0 pm.

[0149] In more particular embodiments, the silica particles have a mean particle size of from about 1.0 to about 4.0 pm.

[0150] In yet more particular embodiments, the silica particles have a mean particle size of from about 1.0 to about 2.0 pm.

[0151] In still more particular embodiments, the silica particles have a mean particle size of at least 500 nm.

[0152] In further embodiments, such as those in which the particles are rod-shaped, the size of particles may be defined (or also defined) by reference to the width thereof (which will refer to the diameter at the narrowest point).

[0153] In a particular such embodiment, the silica particles have a mean width of from about 0.05 to about 0.6 pm.

[0154] In a more particular embodiment, the silica particles have a mean width of from about 0.1 to about 0.6 pm.

[0155] In a yet more particular embodiment, the silica particles have a mean width of from about 0.1 to about 0.4 pm.

[0156] In a yet more particular embodiment, the silica particles have a mean width of from about 0.2 to about 0.4 pm.

[0157] The skilled person will understand that porous silica materials of the type described in the present invention are typically non-crystalline. Thus, in certain embodiments, the porous silica particle may be described as a substantially non-crystalline porous silica particle (and materials formed from a plurality of such particles may be described in the same manner). As such, the porous silica particle may be described as a non-crystalline porous silica particle.

[0158] In alternative embodiments, the silica material present in particles as described in the first aspect of the invention may be described as being amorphous. In such embodiments, it will be understood that the term amorphous will indicate that the structure of the silica material (excluding the pores present therein) has no substantial order, such as the order which may be present in a crystalline substance (i.e. the porous silica particles, or silica material, may be referred to as non-crystalline).

[0159] As described herein, the skilled person will understand that the silica materials of the invention are porous. As such, silica particles of the invention may be referred to as having a certain minimum total pore volume, as measured using nitrogen sorption (e.g. taken as the volume adsorbed at the highest value of P / Po, for example, P / Po = 0.995), or a range of such volumes.

[0160] In particular embodiments, the total pore volume is at least about 0.2 cm3 / g (such as at least about 0.3, 0.4, 0.5, 0.6 or 0.7 cm3 / g).

[0161] In particular embodiments, the total pore volume is from about 0.2 to about 2.5 cm3 / g.

[0162] In more particular embodiments, the total pore volume is from about 0.2 to about 2.0 cm3 / g.

[0163] In yet more particular embodiments, the total pore volume is from about 0.5 to about 1.5 cm3 / g.

[0164] In still more particular embodiments, the total pore volume is from about 0.6 to about 1.4 cm3 / g.

[0165] For example, in certain embodiments, the total pore volume is from about 0.7 to about 1.3 cm3 / g.

[0166] In further embodiments, the total pore volume is from about 0.6 to about 1.3 cm3 / g.

[0167] In further embodiments, the total pore volume is from about 0.6 to about 1.2 cm3 / g.

[0168] In further embodiments, the total pore volume is from about 0.6 to about 1.0 cm3 / g.

[0169] In particular embodiments, the chewable composition of the invention comprises at least about 1 wt% of the porous silica particles, such as: from about 1 to about 15 wt%; from about 1 to about 14 wt%; from about 1 to about 13 wt%; from about 1 to about 12 wt%; from about 1 to about 11 wt%; from about 1 to about 10 wt%; from about 1 to about 9 wt%; from about 1 to about 8 wt%; or from about 1 to about 7 wt%.

[0170] In certain embodiments, the chewable composition of the invention comprises at least 2 wt% of the porous silica particles, such as from about 2 wt% to about 15 wt%.

[0171] In more particular embodiments, the chewable composition of the invention comprises from about 2 to about 13 wt% of the porous silica particles.

[0172] In more particular embodiments, the chewable composition of the invention comprises from about 2 to about 12 wt% of the porous silica particles.

[0173] In more particular embodiments, the chewable composition of the invention comprises from about 2 to about 11 wt% of the porous silica particles.

[0174] In more particular embodiments, the chewable composition of the invention comprises from about 2 to about 10 wt% of the porous silica particles.

[0175] In certain embodiments, the chewable composition of the invention comprises at least 3 wt% of the porous silica particles, such as from about 3 wt% to about 15 wt%.

[0176] In more particular embodiments, the chewable composition of the invention comprises from about 3 to about 13 wt% of the porous silica particles.

[0177] In more particular embodiments, the chewable composition of the invention comprises from about 3 to about 12 wt% of the porous silica particles.

[0178] In more particular embodiments, the chewable composition of the invention comprises from about 3 to about 11 wt% of the porous silica particles.

[0179] In more particular embodiments, the chewable composition of the invention comprises from about 3 to about 10 wt% of the porous silica particles. In certain embodiments, the chewable composition of the invention comprises from about 1 to about 5 wt% of the porous silica particles.

[0180] Uses and processes

[0181] As described herein, the chewable compositions of the first aspect of the invention may be useful in oral care, such as in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss in a subject in need thereof.

[0182] In some embodiments, the chewable composition of the first aspect of the invention may be useful in oral care, such as in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease, and / or tooth loss in a subject in need thereof.

[0183] In a second aspect of the invention, there is provided the use of a chewable composition as defined in the first aspect of the invention in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss.

[0184] In some embodiments, the use of the chewable composition is in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease, and / or tooth loss.

[0185] In an alternative second aspect of the invention, there is provided a chewable composition as defined in the first aspect of the invention for use in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease (e.g. gingivitis), periodontitis, and / or tooth loss.

[0186] In some embodiments, the chewable composition is for use in the prevention (or prophylaxis) of dental caries, the accumulation of dental plaque, gum disease, and / or tooth loss.

[0187] In a further alternative second aspect of the invention, there is provided a method of preventing (or prophylaxis of) the formation of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss, in a subject in need thereof, comprising the step of using (or administering / applying, such as to oral cavity, i.e. the mouth, e.g. the surfaces of the teeth and gums) an effective amount of a chewable composition as defined in the first aspect of the invention. In some embodiments, there is provided a method of preventing (or prophylaxis of) the formation of dental caries, the accumulation of dental plaque, gum disease, and / or tooth loss, in a subject in need thereof, comprising the step of using (or administering / applying, such as to oral cavity, i.e. the mouth, e.g. the surfaces of the teeth and gums) an effective amount of a chewable composition as defined in the first aspect of the invention.

[0188] As used herein, the term prevention (and, similarly, preventing) will include references to the prophylaxis of a condition (and vice-versa). In particular, such terms term may refer to achieving a reduction (for example, at least a 2% reduction, such as at least a 5%, 10%, 20%, 30% or 40% reduction, e.g. at least a 50% reduction) in the likelihood of a subject developing the condition.

[0189] For the avoidance of doubt, the skilled person will understand that such uses and methods will be performed in a subject in need thereof. The need of a subject for such uses and methods may be assessed by those skilled the art using routine techniques.

[0190] As used herein, references to a subject will refer to a living subject being treated, including mammalian (e.g. human) patients. In particular, references to a subject will refer to human, such as a human of adult age (i.e. a human aged 18 years or over).

[0191] The skilled person will understand that uses and methods relating to the chewable composition of the first aspect of the invention may further comprises such steps as may be appropriate for its use in the form provided.

[0192] For example, where the chewable composition is provided in the form of a chewing gum, such uses and methods may comprise the step(s) taking a suitable amount of the composition into the mouth, chewing the composition for a period of time (e.g., about 2 min to 20 min, such as 2 min to 10 min), then ejecting the composition from the mouth.

[0193] As described herein, where the chewable composition is provided in the form of a gummy, such uses and methods may comprise the step(s) taking a suitable amount of the composition into the mouth (e.g., one piece of the gummy), chewing the composition for a period of time (e.g., about 10 seconds to 2 minutes, such as 10 to 60 seconds).

[0194] In a third aspect of the invention, there is provided the use of a composition as described in the first aspect of the invention as an oral care product. The skilled person will understand that references to oral care products will include references to oral health products (i.e. products for promoting oral health), such as products for the prevention or prophylaxis of the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss, and for the treatment or prevention (or prophylaxis) of infections of the mouth.

[0195] The skilled person will understand that the chewable composition as described in the first aspect of the invention may be prepared using standard techniques as known in the art, such as through mixing of the components thereof.

[0196] Thus, in a further aspect of the invention there is provided a process for preparing a chewable composition comprising the bringing the components of the composition in the form of a mixture (such as a substantially homogenous mixture) thereof.

[0197] In a still further aspect of the invention, there is provided the use of a silica material as defined in relation to the first aspect of the invention in the manufacture of a chewable composition as defined herein (e.g. in the first and second aspects of the invention).

[0198] Without wishing to be bound by theory, it is believed that the use of certain porous silica materials having a specific average pore size of pores in the mesoporous range that are able to effectively act as molecular sieves for biological molecules in vivo allows for the preparation of chewable compositions for oral care purposes, having improved properties in the reduction of the formation of dental caries and in other aspects of improved oral hygiene.

[0199] In particular, it is believed that the use of mesoporous silica particles having a specific average pore size of pores in the mesoporous range, as described herein, allows for the effective absorption of salivary amylase enzyme in the mouth, which is not observed for silica particles lacking such pores and so provides advantages over chewable compositions (e.g., chewing gums and gummies) as known in the art. Further, the use of such mesoporous silica particles is believed to reduce cariogenic bacterial biofilm formation, which has further benefits in improving oral health.

[0200] Brief Description of the Figures

[0201] Figure 1.1 (A)-(D): Nitrogen sorption analysis. Adsorption-desorption isotherms (Figure 1.1 (A) and 1.1 (B)) and pore size distributions derived from the adsorption curve using the DFT model (Figure 1.1 (C) and 1.1 (D)) of the different types of silicas described in Example 1.

[0202] Figure 1.2: SEM micrographs of silicas from Example 1

[0203] Figure 2: Silica with a similar average pore size as silica of the invention but with broad pore size distribution (silica 8) was not able to reduce carbohydrate digestion. The 'No silica' sample represents the basal level of digestion, and the level of digestion for silica 8 does not differ from the basal level. Data are presented as mean ± SE (n = 2).

[0204] Figure 3: Silica reduces carbohydrate digestion by salivary amylase in human saliva. Two different types of silica were incubated with human saliva to determine their efficacies in reducing carbohydrate digestion. Data are presented as mean ± Standard Deviation (SD) (n=4).

[0205] Figure 4.1 (A)-(E): Effect of different silicas on cariogenic bacterial growth. Silica 3 and 4 were pre-incubated with human salivary amylase and subsequently subjected to carbohydrate digestion assay. After enzyme de-activation, digested products of starch were fed to S. mutans cultures. Several measurements were taken: bacterial growth for the first 8 hr (A, B), amount of undigested starch in the digestion mix after salivary amylase de-activation at various time points (C), bacterial mass 24 hr after the exposure to the digested products (D), and amount of undigested starch in the culture medium 24 hr after the exposure to the digested products (E). Data are presented as mean ± SE (n = 28).

[0206] Figure 4.2 (A)-(E): Effect of different silicas on cariogenic bacterial growth in 1% starch medium. Silica 3 and 4 were pre-incubated with human salivary amylase. The preincubation mix was added to S. mutans culture containing 1% starch. Several measurements were taken: bacterial growth (A, B), amount of undigested starch in the culture medium after the exposure to the pre-incubation mix at various time points (C), bacterial mass 24 hr after the exposure to the pre-incubation mix (D) amount of undigested starch in the culture medium 24 hr after the exposure to the pre-incubation mix (E). Data are presented as mean ± SE (n = 28).

[0207] Figure 4.3 (A)-(E): Effect of different silicas on cariogenic bacterial growth in the culture medium containing 1% starch. Silica 3, 5, and 7 were pre-incubated with human salivary amylase. The pre-incubation mix was added to S. mutans culture containing 1% starch. Several measurements were taken: bacterial growth for the first 8 hr (A-C), bacterial mass 24 hr after the addition of the pre-incubation mix (D), amount of undigested starch in the culture medium 24 hr after the addition of the pre-incubation mix (E). Data are presented as mean ± SE (n = ll).

[0208] Figure 5: Effect of different silicas on cariogenic bacterial biofilm formation. Silica 3, 5, and 7 were pre-incubated with human salivary amylase. Amylase in the pre-incubation mix was added to S. mutans culture containing 1% starch. Several measurements were taken: bacterial growth 24 hr after the addition of the pre-incubation mix (A), amount of undigested starch in the culture medium 24 hr after the addition of the pre-incubation mix (B), and amount of biofilm formed 24 hr after the addition of the pre-incubation mix (C). Data are presented as mean ± SE (n = 22).

[0209] Figure 6: Percent of human salivary a-amylase adsorbed by the silica particles in different gummy formulations.

[0210] Figure 7: Percent of human salivary a-amylase adsorbed by the silica particles in different chewing gum formulations.

[0211] Examples

[0212] The present invention will be further described by reference to the following examples, which are not intended to limit the scope of the invention.

[0213] Example 1 : Preparation / characterization of porous silica materials

[0214] Materials

[0215] Silica 1, Silica 2 and Silica 3 were manufactured according to a process previously described (see Waara, ER et al., Adv. Healthcare Mater. 9(11), e2000057 (2020) and Baek, J et al., Nanomedicine (2021), in particular the experimental procedures described therein).

[0216] In brief, a meso-structure templating agent (P123, a triblock copolymer with average molecular weight = 5800 g mol-1, PEO20PPO70PEO20) was dissolved in aqueous hydrochloric acid (HCI), with acid concentration equivalent to 1.6 M. Complete dissolution of P123 was followed by addition of tetraethyl orthosilicate (TEOS) under vigorous stirring at 40 °C. The final molar ratio of P123: TEOS in the solution was 0.02: 1.00 and the molar ratio of TEOS: HCI: H2O was 1:6:235 (Silica 1), 1 :7:250 (Silica 2) or 1 :7:230 (Silica 3). The synthesis was kept static at 40 °C for 20 h and further hydrothermally treated for 20 h at 100 °C (Silica 1), 1.3 h at 85 °C (Silica 2) or 10 h at 100 °C (Silica 3). Silica 4 was Kromasil 100-13-SIL purchased from Nouryon Pulp and Performance Chemicals AB.

[0217] Silica 5 (Sylodent) was Sylodent SM850C, a non-porous silica commonly used in toothpaste, obtained from W. R. Grace & Co.

[0218] Silica 7 was Sunsphere NP-30 obtained from AGC Si-Tech.

[0219] Silica 8 was LO-VEL 6200 obtained from PPG Industries, Inc.

[0220] Nitrogen sorption analysis

[0221] Brunauer-Emmett-Teller (BET) surface area was calculated from sorption isotherm at a relative pressure (p / p°) of <0.2 (plots in Figure 1.1A and Figure 1.1B). Total pore volume were recorded at a relative pressure (p / p°) = 0.995. Average pore size and pore size distributions were derived from the adsorption curves using the Density Functional Theory (DFT) method. The pore size distribution data for the silica particles derived from the adsorption curves using DFT and a cylindrical pores - oxide surface model is presented in Figure 1.1C and Figure 1.1D. The measurements were performed at liquid nitrogen temperature (-196 °C) using a TriStar II volumetric adsorption analyser and data analysis was performed using the software MicroActive for TriStar II version 2.03 (Micromeritics Instrument Corp., GA, USA).

[0222] Particle size

[0223] Scanning electron microscopy using a JSM-7401F (JEOL Ltd., Tokyo, Japan) was used to characterize the particle size and morphology from SEM micrographs (Figure 1.2). The mean particle size (length and width for rod-shaped particles Silica 1, Silica 2 and Silica 3 and diameter for spherical particles Silica 4, Silica 6 and Silica 7) were analyzed from >50 particles using Image! (Fiji; see Schindelin J, Arganda-Carreras I, Frise E et al., Fiji: an open-source platform for biological-image analysis., Nat. Methods, 9(7), 676-682 (2012)).

[0224] Table 1 : Material characteristics

[0225] Various properties of the studied silica materials were measured using above listed techniques with operational conditions. The features identified are described in Table 1 below.

[0226] 2Calculated on adsorption curves, using DFT model

[0227] 4Calculated from the DFT pore size distribution and total pore volume: [(Pore Volume at 50 nm - Pore Volume at 2 nm) / Total Pore Volume] x 1005Calculated from the DFT pore size distribution : [(Pore Volume at 25 nm - Pore Volume at 7 nm) / (Pore Volume at 50 nm - Pore Volume at 2 nm)] x 100

[0228] 6Calculated from the DFT pore size distribution : [(Pore Volume at 18 nm - Pore Volume at 7 nm) / (Pore Volume at 50 nm - Pore Volume at 2 nm)] x 100 Analysis of the properties of these silica materials is also provided in Figures 1.1 (A)-(D) and Figure 1.2 as described herein.

[0229] Example 2: Carbohydrate digestion assay (Silica 8) Preparation of working solutions and standard curve samples

[0230] Prior to the assay, several working solutions were prepared. Firstly, 60-80 mg of silica were weighed and dried overnight at 120 °C. On the next day, silica was weighed again to obtain precise post-dried weight and 20 mg / mL silica suspension was prepared using double distilled water (ddHzO). lx PBS was prepared by dissolving 1 PBS tablet (Medicago, 09-2052-100) in 200 mL ddHzO. Once dissolved, pH was adjusted to 5.4. Lyophilized human salivary amylase was rehydrated in ddHzO to make 40 mg / mL stock solution. A working solution (8 mg / mL) was freshly prepared on the day of the experiment by diluting the necessary amount of stock solution with lx PBS (pH 5.4). Starch stock solution (6 mg / mL) was prepared by mixing pure starch powder (Generation Ucan) in lx PBS (pH 5.4). Starch does not readily dissolve in PBS, therefore the starch solution was microwaved several times (10-20 sec each time) until it started to boil and there was no more starch powder settling down at the bottom. When all dissolved, the starch solution remained opaque. When performing the digestion part of the assay, the starch stock solution was equilibrated to room temperature before starting the digestion. The starch standard curve samples (300 pL each) were prepared by serial dilution using lx PBS (pH 5.4). The concentrations of the standard curve samples were: 1.5, 0.75, 0.375, 0.1875, 0.0938, 0.0465, and 0 mg / mL. Following serial dilution, 75 pL of IN HCI (Sigma Aldrich, 1090571000) was added to each standard curve sample.

[0231] For testing of Silica 8, 40 pl of silica suspension in water (20 mg / mL) was mixed with 140 pl of lx PBS solution to have a silica dispersion of 4 mg / mL. The incubation mix was prepared by mixing 20 pL of salivary amylase solution (8 mg / mL) and 180 pL of silica suspension (4 mg / mL) in 1.5 mL microcentrifuge tube. This incubation mix was then incubated for 15 min at 37 °C with vertical rotation using a rotator (Harvard Apparatus, 74-2302).

[0232] Following the incubation, the diluted incubation mix was prepared by mixing 150 pL of the incubation mix with 1.45 mL of ddHzO and 3.4 mL of lx PBS (pH 5.4). For each carbohydrate digestion assay, a blank sample (No silica sample) was always included to monitor basal digestion level. For this sample, ddHzO was added to the test formulation instead of silica suspension.

[0233] Starch digestion

[0234] The starch digestion was carried out for various durations: 0, 5 or 20 min. The reaction mix (800 pL) was prepared for each time point, which contained 1: 1 ratio of starch (6 mg / mL) and diluted incubation mix. For each time point, 400 pL of starch stock solution (6 mg / mL) was aliquoted in 1.5 mL microcentrifuge tube. Then, 400 pL of diluted incubation mix was added to each tube. For the 0 min time point, 200 pL of IN HCI was firstly added to starch solution, then 400 pL of diluted incubation mix was added. Each reaction mix was immediately mixed by inversion then incubated in a water bath at 37 °C with horizontal shaking (200 rpm) for each respective duration. When incubation was complete, 200 pL of IN HCI was immediately added to terminate digestion.

[0235] Colorimetric determination of digested starch

[0236] The amount of digested starch was quantified at different time points using 5 mM iodine (Merck, 1.09099.1003). Each reaction mix was briefly vortexed before aliquoting into the 96-well plate (Corning, CLS3370). 75 pL of each reaction mix (silica samples as well as standard curve samples) was aliquoted in duplicate. Into each well, 75 pL of 5 mM iodine solution was aliquoted using a multi-channel pipette, then the absorbance was read at 570 nm.

[0237] Calculation of the amount of digested starch

[0238] The amount of the digested starch illustrates the efficacy of a given silica to reduce the digestion. The concentration of the undigested starch in each sample was extrapolated from the slope and the intercept of the starch standard curve. The percentage of undigested starch was then calculated by taking the 0 min time point as the 100% undigested starch. The percentage of digested starch was calculated by subtracting the percentage of undigested starch from 100. The percentage of digested starch at 20 min (testing of Silica 8) time point was plotted as a bar graph. For every digestion assay, No silica sample was included which represented the basal digestion level.

[0239] Results of these experiments are also presented in Figure 2 as described herein.

[0240] Example 3: Carbohydrate digestion assay using human saliva

[0241] Preparation of 2x PBS

[0242] 2x PBS was prepared by dissolving 2 PBS tablets (Medicago, 09-2052-100) in 200 mL double distilled water (ddHzO). Once dissolved, pH was adjusted to 5.4.

[0243] Collection and preparation of human saliva

[0244] Human saliva (2-3 mL) was collected in a test tube. Immediately after collection, saliva samples were centrifuged at 5000 rpm for 5 min to remove any particles or sediments. The supernatant (250pL per sample) was collected and stored at -20 °C until the analysis. On the day of analysis, saliva sample was thawed and 1 :50 dilution was made using 2x PBS (pH 5.4). This was referred to as a saliva working solution.

[0245] Preparation of silica and its working solution Approximately 60-80 mg of mesoporous silica was weighed and dried overnight at 120 °C. On the next day, silica was weighed again to obtain precise post-dried weight and 20 mg / mL silica suspension was prepared using ddHzO. Sonication of silica suspension was needed for homogeneous dispersion of silica. A microtip (Vibra cell, 630-0423) was fitted into the sonicator (Vibra cell, VCX 130) and silica suspension was sonicated for 3 min at 40% amplitude without pulse. Generally, two rounds of sonication resulted a homogenous solution with no or minimal clumps remaining.

[0246] Preparation of starch solution and DNS reagent

[0247] Starch solution (3 mg / mL) was prepared by mixing pure starch powder (Sigma Aldrich, 33615) in lx PBS (pH 7.4). Starch does not readily dissolve in PBS, therefore the starch solution was microwaved several times (10-20 sec each time) until it started to boil and there was no more starch powder settling down at the bottom. When all dissolved, the starch solution remained opaque. When performing the digestion part of the assay, the starch solution was equilibrated to room temperature before starting the digestion. 3,5- d i n itrosa I icyl ic acid (DNS, Sigma Aldrich, D0550; 0.2 pM) was prepared by dissolving 1 g of DNS in 20 mL of 2 M NaOH. Into this solution, 30 g of sodium tartrate was added. The solution was topped up with ddHzO to a final volume of 100 mL. The solution was stirred constantly using a magnetic stirrer and heated at 50 °C for 2 hr. The final solution was filtered and stored at 4 °C.

[0248] Adsorption of salivary amylase by silica

[0249] Different silica concentrations (0.312 - 20 mg / mL, 60 pL each) was prepared by serial dilution in 96-well PCR plate (VWR, 732-2387) using ddHzO. Sixty pL of saliva working solution was aliquoted into each well. The plate was sealed (Bio-rad, MSB1001) and incubated at 37 °C for 30 min with rotation using a rotator (Harvard Apparatus, 74-2302). When incubation was completed, the plate was centrifuged at 2000 x g for 5 min at room temperature. The supernatant (30 pL) from each well was transferred to a new 96-well PCR plate.

[0250] Colorimetric determination of reducing sugars

[0251] Into each well containing the supernatant, 30 pL of starch solution (3 mg / mL) was added. The plate was sealed and incubated at 37 °C for 30 min with rotation using a rotator. Once incubation was finished, 60 pL of DNS solution (0.2 pM) was added into each well. The plate was sealed and incubated again at 95 °C for 7 min using a PCR machine. Following the final incubation, 100 pL of the solution was transferred to a 96-well plate (Corning, CLS3370) and the absorbance was read at 540 nm. Results of these experiments are also presented in Figure 3 as described herein.

[0252] Example 4: ic bacterial measurement

[0253] Preparation of working solutions lx PBS: lx PBS was prepared by dissolving 1 PBS tablet (Medicago, 09-2052-100) in 200 mL double distilled water (ddHzO). Once dissolved, pH was adjusted to 5.4. The solution was subsequently autoclaved (121 °C, 20 min).

[0254] Brain Heart Infusion (BHI) broth: 37 g of BHI powder (BD Diagnostic Systems, 237500) was dissolved in 1 L of ddHzO. To prepare BHI broth containing 1% starch, 10 g of starch powder (Generation Ucan) was added in the BHI broth solution. The broths were subsequently autoclaved (121 °C, 20 min).

[0255] Starch stock solution (6 mg / mL): To prepare a starch stock solution, starch powder was sterilized by heating at 120 °C for 6 hr. The sterilized starch powder was added in autoclaved lx PBS (pH 5.4) to make 6 mg / mL stock solution. Since starch does not readily dissolve in PBS, the solution was microwaved several times (10-20 sec each time) until it started to boil and there was no more starch powder settling down at the bottom. When all dissolved, the starch solution remained opaque.

[0256] Silica (20 mg / mL): 60-80 mg of mesoporous silica or control silica were weighed and dried overnight at 120 °C. On the next day, silica was weighed again to obtain precise post-dried weight and 20 mg / mL silica suspension was prepared using autoclaved ddHzO. For Silica 3, sonication was necessary for homogeneous suspension. Briefly, 2 mm microtip (Vibra cell) was fit into the sonicator (Vibra cell) and the silica suspension was sonicated for 3 min at 40% amplitude without pulse. After the sonication, silica suspension was mixed several times by inversion and inspected visually. If silica clumps were still present, sonication was repeated once more. Generally, two rounds of sonication resulted a dispersion with no or minimal clumps remaining.

[0257] Human salivary amylase: Lyophilized human salivary amylase (Sigma Aldrich, A1031) was rehydrated in ddHzO to make 40 mg / mL stock solution. A working solution (8 mg / mL) was freshly prepared on the day of the experiment by diluting the necessary amount of stock solution in autoclaved lx PBS (pH 5.4). Preparation of Streptococcus mutans culture

[0258] Streptococcus mutans (S. mutans) is one of the main cariogenic bacteria found in oral cavity that significantly contributes to dental caries. Lyophilized S. mutans (American Type Culture Collection (ATCC), 25175) was rehydrated in 5 mL of BHI broth. 0.5 mL of the suspension was aliquoted in four autoclaved test tubes and 4.5 mL of BHI broth was subsequently added in all test tubes. The inoculated tubes were incubated at 37 °C with constant agitation (shaker set at 120 rpm) for at least 30 hr. Following incubation, cultured samples were stored at -80 °C in 10 or 20% glycerol (Sigma Aldrich, G9012). S. mutans was cultured in BHI broth or in BHI broth containing 1% starch. S. mutans in 10% glycerol stock was used to inoculate 45 mL of the respective broth and cultured for 24-30 hr at 37 °C with constant agitation. The culture was kept at 4 °C until the day of the experiment, however not more than 48 hr. On the day of the experiment, 40 mL of the respective broth was added in the culture and incubated for 1 hr at 37 °C on a rotating platform. Following this incubation, the bacterial culture was diluted using the respective broth to adjust OD600 to approximately 0.1 (early logarithmic phase).

[0259] Adsorption of salivary amylase by silica

[0260] Prior to starch digestion step, each silica sample was firstly incubated with salivary amylase for enzyme adsorption. The incubation mix was prepared by mixing 140 pL of lx PBS (pH 5.4), 40 pL of silica (4 mg / mL) and 20 pL of salivary amylase working solution (8 mg / mL) in 1.5 mL microcentrifuge tube. As a control, a blank sample (No silica sample) was always included, in which ddHzO was added instead of silica. The incubation mix was incubated for 15 min at 37 °C with vertical rotation using a rotator (Harvard Apparatus, 74-2302). Following the incubation, 150 pL of the incubation mix was diluted in 1.48 mL ddHzO and 3.4 mL lx PBS (pH 5.4).

[0261] Starch digestion and feeding S. mutans with starch digestion products

[0262] 400 pL of diluted incubation mix was mixed with 400 pL of autoclaved starch stock solution (6 mg / mL) and incubated in the water bath at 37 °C with horizontal shaking (200 rpm) for 10 min. Subsequently, the samples were incubated at 95 °C for 45 min to deactivate salivary amylase. Following deactivation, the samples were centrifuged at 5000 rpm for 5 min at room temperature. The supernatant was then transferred to new 1.5 mL microcentrifuge tubes. Final concentrations in this reaction mix were: 60 pg / mL silica, 12 pg / mL salivary amylase, 3 mg / mL starch. The reaction mix (digestion mix) was kept at room temperature, the amount of undigested starch was quantified immediately after deactivation and after 4, 8 and 24 hr by colorimetric measurement using iodine. 150 pL of the bacterial culture was aliquoted in a 96-well plate (Corning, CLS3370) and 50 pL of the reaction mix was added into each well. As a control, 100 pL of lx PBS was added instead of the reaction mix. The culture was incubated at 37 °C for 24 hr with constant agitation. During the first 8 hr, bacterial growth was monitored by OD600 measurement every 30 min. After 24 hr, final OD600 was measured. The amount of undigested starch was also quantified after 24 hr by colorimetric measurement using iodine.

[0263] Growing S. mutans while starch digestion occurs in culture in real-time

[0264] In this set up, S. mutans was grown in BHI broth containing 1% starch. The digestion of starch in BHI broth occurred in real-time when the diluted salivary amylase- silica incubation mix was added to the bacterial culture. Adsorption of salivary amylase by silica was performed as described above. Following enzyme adsorption by silica, the incubation mix was centrifuged at 5000 rpm for 5 min at room temperature. Then 150 pL of the supernatant was diluted in 1.48 mL ddHzO and 3.4 mL lx PBS (pH 5.4) to prepare the diluted salivary amylase-silica incubation mix. In a 96-well plate, 150 pL of the bacterial culture (in BHI broth with 1% starch) was aliquoted in each well then 50 pL of the diluted salivary amylase-silica incubation mix was added. As a control, 50 pL of lx PBS (pH 5.4) was added instead of the incubation mix. The culture was incubated at 37 °C with constant agitation up to 24 hr. During the first 8 hr, bacterial growth was monitored by OD600 measurement every 30 min, and final OD600 measurement was read after 24 hr. To quantify the amount of undigested starch in culture broth throughout incubation period, a plate was prepared for each representative incubation time point (0, 4, 8, and 24 hr). The amount of undigested starch was quantified by colorimetric measurement using iodine.

[0265] Colorimetric determination of undigested starch

[0266] The amount of undigested starch in reaction mix or culture broth was quantified by using iodine (Merck, 1.09099.1003). Briefly, 60 pL of reaction mix or 30 pL of culture broth was transferred to a new 96-well plate, then 15 pL of ddHzO was aliquoted into each well containing the reaction mix and 45 pL of ddHzO was aliquoted into each well containing the culture broth. Then, 75 pL of 5 mM iodine was added to all wells and the absorbance was read at 570 nm.

[0267] Results of these experiments are also presented in Figure 4.1 (A)-(E), Figure 4.2 (A)-(E), and Figure 4.3 (A)-(E) as described herein. Example 5: Biofilm formation assay

[0268] Preparation of bacteria cultures for biofilm formation

[0269] Streptococcus mutans bacterial culture was prepared and plated in a 96-well plate (Corning, CLS3370). 50 pL of the pre-incubation reaction mix was added in each well as described in the bacterial growth assessment. The culture was incubated at 37 °C for 24 hr without agitation.

[0270] Colorimetric determination of biofilm mass

[0271] After the 24-hr incubation, S. mutans culture medium was removed by inversion of the plate and the wells were washed with 150 pL of 1 x PBS. The plate was inverted to discard the PBS and any remaining solution in each well was removed using a 200 pL pipette. 200 pL of methanol (Sigma Aldrich, 179957) was added in all wells to fix the biofilm and the plate was incubated statically at RT for 20 min. After removal of methanol by plate inversion, the plate was left open at RT for approximately 10 min to let any remaining methanol in each well to evaporate. After methanol had evaporated and the wells were dried, 200 pL of 0.002% crystal violet solution was added in each well to stain the biofilm. The 0.002% crystal violet solution was prepared by diluting 1% crystal violet stock solution (Sigma Aldrich, V5265) with ddH2O. Once the 0.002% crystal violet was added, the plate was covered with aluminium foil and incubated statically at RT for 40 min. After the incubation, the 0.002% crystal violet solution was discarded by plate inversion and any remaining solution was removed using a 200 pL pipette. Into each well, 200 pL of 98% ethanol (Sigma Aldrich, 1009831011) was added then the plate was covered in aluminium foil and was incubated at RT for 30 min on a shaking platform. The amount of biofilm formed was assessed by measuring the OD in the wells immediately after the de-staining step with ethanol at a wavelength of 590 nm.

[0272] Other measurements

[0273] After the 24-hr incubation, the growth of bacteria was assessed as described above (by measuring the OD at 600nm). After the measurement, 30 pL of culture medium was transferred to a new 96-well plate and 45 pL of ddHzO was aliquoted in each well. To quantify the remaining undigested starch levels in the media 75 pL of 5 mM iodine was added and colorimetric measurement was done as described above.

[0274] Results of these experiments are also presented in Figure 5 (A)-(C) as described herein. Example 6: Preparation of chewing gums with and without silica

[0275] Glycerin, mint flavour and xylitol were purchased from KitchenLab. Erythritol was purchased from Intenson. Gum base was part of a bubble gum kit from Thames&Kosmos. The gum base was added to a pre-weighed glass container that was placed in a hot water bath until the gum appeared very malleable. The glycerin, xylitol and flavour (if any) were added while stirring until the mixture appeared uniform. The hot gum mixture was transferred to a mound of powder (Silica 6 for GUMOl and GUM03, erythritol crushed to a fine powder using a mortar and pestle for GUM02) and the powder was kneaded into the gum mixture until the gum no longer felt sticky to the touch. The gum was then rolled and cut into small pieces. The unused powder was collected and weighed to calculate the actual amount of powder incorporated into the gum. The glass container with gum residue was also weighed to calculate the amount of gum base actually incorporated into the gum. Amount of ingredients incorporated in the chewing gums are presented in Table 2.

[0276] Table 2. Chewing gum formulations

[0277] Example 7: Preparation of pectin base qummies with and without silica

[0278] Citric acid, mint flavour, pectin, sorbitol and xylitol were purchased from KitchenLab. Water was obtained from a Milli-Q water purification system.

[0279] A premix of pectin (1.5 g), sorbitol (3.5 g) and xylitol (1.5 g) were added to 12 g of water while stirring. Another portion of sorbitol (20 g) and Xylitol (20 g) were added and the mixture was stirred until it appeared uniform. The mixture was placed on a hot plate and heated to 120°C and kept at that temperature for 2 minutes before allowing the mixture to cool down below 70°C. The flavour (0.3 g) and silica (3 g in GUM04, none in GUM05) were added with stirring until the mixture appeared uniform. A solution of citric acid (0.2 g in 2 g of water) was added with stirring and the mixture was then poured into molds. Table 3. Pectin qummies formulations

[0280] Example 8: Preparation of agar-agar base qummies with and without silica

[0281] Agar-agar, citric acid and mint flavour were purchased from KitchenLab. Erythritol was purchased from Intenson. Potassium sorbate (cat no 1.05119.1000) was purchased from Sigma-Aldrich. Steviol glycosides (Intesse Stevia 2.0) was obtained from Tate&Lyle. Xantham gum (Keltrol RD) was obtained from CP Kelco. Water was obtained from a Milli- Q water purification system. Formulations were homogenized using a Witeg HG-15A homogenizer equipped with the HT1018 dispersing tool.

[0282] Preparation of stock solutions

[0283] Xantham gum 0.5%: Xantham gum was added to water and homogenized at medium speed until the gel appeared uniform and no lumps were visible.

[0284] Steviol glycosides 0.5%: Steviol glycosides were dissolved in water with stirring for few minutes.

[0285] Preparation of gummies

[0286] Erythritol (4.0 g), agar-agar (1.0 g), citric acid (0.1 g) and potassium sorbate (0.05 g) were added to water (amount adjusted to have a total weight of 50 g) and homogenized at low speed for 1 minute before adding the flavour (0.15 g) and steviol glycosides solution (2 g). The mixture was heated to 85°C for 3 min in a water bath before allowing the solution to cool down below 70°C. The silica (5 g in GUM07, none in GUM06) and the xantham gum gel (4 g) were added while stirring with the homogenizer at medium speed for 30 seconds. The mixture was then poured into molds. Table 4. Agar-agar oummies formulations

[0287] Example 9: Assessment of salivary amylase absorption by the chewing gums of Example 6 and oummies of Examples 7 and 8

[0288] Materials

[0289] Preparation of stock and working solutions

[0290] Prior to the assay, several stock and working solutions were prepared. lx Running buffer 50 mL Bolt MES running buffer 20x was mixed with 950 mL double distilled water (ddHzO). lOx TBS, pH = 7.6

[0291] 80 g NaCI and 24.2 g Trizma base were dissolved in 700 mL ddHzO. pH was adjusted to 7.6 with IN HCI. ddHzO was added to a final volume of IL. lx TBS 100 mL lOx TBS was mixed with 900 mL ddHzO. TBST

[0292] 200 mL lOx TBS was mixed with 1780 mL ddHzO and subsequently, 20 mL 10% Tween was added.

[0293] 10% Tween

[0294] 10 mL Tween-20 was mixed with 90 mL ddHzO. lx LDS buffer

[0295] 1250 pL Bolt™ 4X LDS sample buffer was mixed with 500 pL Bolt™ Sample Reduction Agent (lOx) and 3250 pL deionized water.

[0296] 2x PBS stock solution, pH = 5.4

[0297] 10 PBS tablets were dissolved in 950 mL deionized water. Once dissolved, pH was adjusted to 5.4 with IN HCI and deionized water was added up to IL. lx PBS working solution, pH = 5.4

[0298] 50 mL 2x PBS stock solution was mixed with 50 mL deionized water to obtain a lx PBS working solution.

[0299] Salivary a-amylase stock and working solution a-amylase from human saliva, Type XI were provided in lyophilized form at 79.1 mg of solid powder. This contained 63.2 Units of enzyme per mg solid. 1.9775 mL of deionized water was added to the powder to obtain a stock solution of 40 mg / mL or 2528 U / mL. The stock solution was stored at +4°C. Working solution (252.8 U / mL) was made by 1: 10 dilution of the stock solution in deionized water.

[0300] Adsorption of a-amylase protein by silica in different formulations

[0301] 40 - 80 mg of chewing gum or gummy was weighed in a 1.5 mL microcentrifuge tube. The volume of deionized water to add to the weighed chewing gum or gummy was calculated based on the percentage of silica content in the chewing gum or gummy. Calculated amount of deionized water was added to obtain 20 mg / mL silica suspension for each test sample. After adding deionized water to the tube, chewing gum / gummy was warmed at 37 °C for 15 min, and then manually crushed using a pestle for microtubes. The incubation mix was then prepared by adding salivary a-amylase working solution and lx PBS (pH 5.4) to the gummy / silica solution and mixed by inversion. The final concentrations of this incubation mix were 4mg / mL of silica and 25.28 U / mL of a-amylase. The incubation mix was incubated for 30 min at 37 °C with vertical rotation using a rotator. Sample preparation for gel electrophoresis

[0302] Following a-amylase adsorption, the incubation mixes were centrifuged at 10,000 ref for 5 min at room temperature to separate the adsorbed and non-adsorbed a-amylase. Following the centrifugation, the solid gum pieces, the silica, and the adsorbed a-amylase were pulled down in the pellet fraction, while the non-adsorbed a-amylase remained in the supernatant fraction. 700 pL of the supernatant was transferred to a new 1.5 mL microcentrifuge tube and the pellet was discarded. 65 pL of the supernatant was transferred to a new 1.5 mL tube and mixed with 35 pL 2x LDS buffer.

[0303] To calculate the relative amount of adsorbed a-amylase, a standard curve of known protein concentrations was prepared (16.52 - 2.065 U / mL). More specifically, 140 pL lx PBS was mixed with 40 pL of deionized water and 20 pL of the a-amylase working solution (252.8 U / rnL) to obtain a protein solution of 25.28 U / mL. Subsequently, 130 pL of this solution was transferred to a new 1.5 mL tube and mixed with 70 pL 2xLDS buffer, which resulted in a 16.52 U / mL protein solution. This was labeled as Standard 1. Next, Standard 1 was serially diluted three times (1: 1 dilution; 100 pL Standard 1 + 100 pL lx LDS buffer, etc.). 25 pL of each standard sample was loaded onto the gel, which resulted a total protein content of 413, 206.5, 103.25 and 51.625 U of a-amylase in the standard samples, respectively. To denature the proteins, all standards and samples were heated at 65°C for 15 minutes in the heat block.

[0304] Gel electrophoresis

[0305] Gel electrophoresis was performed according to manufacturer's instruction (Thermo Fisher Scientific). Briefly, the gel was placed in the cassette clamp and in the chamber of the Mini Gel Tank. Once the gel is secured in the tank, supernatant and standard samples were loaded into the gel. The amounts loaded were: 25 pL of the supernatant and the standard samples, and 3 pL of each of the molecular weight ladders. The tank was then closed, and the electrodes were connected to the PowerPac 300. The samples were run at 80 V to go through the stacking gel, then at 120 V until the end of the gel.

[0306] Protein transfer to PVDF membrane

[0307] After the gel electrophoresis, the cassette containing the gel was removed from the tank and the two plates were separated. The gel was then placed in a tray containing ddHzO. To assemble the transfer cassette, the bottom stack of a Mini Trans-Blot Turbo transfer pack was placed in the bottom part of the cassette and pressed gently with the western blot roller to remove air bubbles. Subsequently, the gel was place on top of the bottom stack, pressed with the roller and then the top stack containing a PVDF membrane was placed over the gel. The whole stack was pressed with the roller again and the lid of the cassette was placed on top and locked. The proteins were transferred using the Turbo transfer program for 7 min. a-amylase detection

[0308] After the transfer of the proteins, the PVDF membrane was placed in a 50 mL tube with the transferred side facing inwards. 5 mL Intercept® blocking buffer was added and the membrane was incubated for 1 hr at room temperature with a low-speed rolling on the tube roller. Following the blocking stage, the blocking buffer was discarded and replaced with the primary antibody solution, which contained 2.5 mL Intercept® blocking buffer, 2.5 mL TBST and 5 pL anti-a-amylase antibody (1: 1000 dilution). The membrane was incubated overnight at 4°C on the tube roller.

[0309] The next day, the primary antibody solution was discarded, and the membrane was washed with 20 mL TBST 3 times, 10 min each at room temperature. After the last wash, the secondary antibody solution was added. The secondary antibody solution contained 3 mL Intercept® blocking buffer, 12 mL TBST and 1 pL fluorescently labeled anti-rabbit secondary antibody (1: 15,000 dilution). Once the secondary antibody solution was added the tube was covered with aluminum foil to avoid bleaching of the fluorescence signal. The membrane was incubated for 1 hr at room temperature on the tube roller. After the incubation, the membrane was washed 3 times, 10 min each with 20 mL TBST. The membrane was further washed 3 times, 10 min each with 20 mL lx TBS.

[0310] Image analysis

[0311] An image of the membrane was acquired at a 2 min exposure time using the Odyssey Fc instrument and analyzed with the Empiria Studio® software. With the Empiria Studio® software, the signal intensity of the band for each standard and sample is analyzed, and a standard curve is then generated using the signal intensity of each known standard concentration. The non-adsorbed a-amylase concentration in the supernatant of the chewing gum / gummies sample is then calculated from the standard curve. The % of amylase adsorbed by the silica in the chewing gum / gummies is then calculated relative to the starting amylase concentration, which is the highest point of the standard curve.

[0312] The percentage of adsorbed a-amylase in the gummies is shown in Figure 6.

[0313] The percentage of adsorbed a-amylase in the chewing gum is shown in Figure 7.

Claims

Claims1. A chewable composition comprising porous silica particles having pores in the mesoporous range, wherein the average pore size of the pores in the mesoporous range is from about 7 to about 25 nm.

2. A composition according to Claim 1, wherein the chewable composition is a chewing gum.

3. A composition as claimed in Claim 1, wherein the chewable composition is a jelly- like composition, such as a gummy.

4. A composition as claimed in any one of Claims 1 to 3, wherein the average pore size of the pores in the mesoporous range is from about 7.0 to about 22.0 nm.

5. A composition as claimed in any one of Claims 1 to 4, wherein the average pore size of the pores in the mesoporous range is from about 7.0 to about 20.0 nm.

6. A composition as claimed in any one of Claims 1 to 5, wherein the average pore size of the pores in the mesoporous range is from about 8.0 to about 13.0 nm.

7. A composition as claimed in any one of Claims 1 to 6, wherein at least about 40% by volume of the pores are in the mesoporous range.

8. A composition as claimed in any one of Claims 1 to 7, wherein the silica particles have a BET surface area of at least about 200 m2 / g.

9. A composition as claimed in any one of Claims 1 to 8, wherein the silica particles have a mean particle size of from about 0.1 to about 20.0 pm.

10. A composition as claimed in any one of Claims 1 to 9, wherein the silica particles have a mean particle size of from about 1.0 to about 5.0 pm.

11. A composition as claimed in any one of Claims 1 to 10, wherein the silica particles have a total pore volume from about 0.6 to about 1.3 cm3 / g.

12. The use of a chewable composition as defined in any one of Claims 1 to 11 in : the prevention of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss; or the treatment or prevention of infections of the mouth.

13. A chewable composition as defined in any one of Claims 1 to 11 for use in : the prevention of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss; or the treatment or prevention of infections of the mouth.

14. A method of: the prevention of dental caries, the accumulation of dental plaque, gum disease, periodontitis, and / or tooth loss; or the treatment or prevention of infections of the mouth, in a subject in need thereof comprising the step of using an effective amount of a chewable composition as defined in any one of Claims 1 to 11.

15. The use of a composition as defined in any one of Claims 1 to 11 as an oral care product.

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