Dietary supplement comprising silica particles

Abstract

Provided herein are: an oral dietary supplement comprising: (a) water, (b) silica particles, and (c) a thickener wherein the thickener is xanthan gum; and formulations thereof.

Description

Technical Field

[0001] The present invention relates to novel formulations and uses of such formulations, such as their use as food supplements.

[0002] In particular, the present invention relates to novel aqueous formulations for oral administration comprising silicon dioxide particles and a thickener, and to the use of such formulations as orally edible dietary supplements. Background Art

[0003] The listing or discussion of any previously published document in this specification should not necessarily be taken as an admission that the document is part of the state of the art or is common general knowledge.

[0004] The use of silica as a food supplement is associated with a number of health benefits. Depending on the type of silica administered, these benefits may include promoting hair, skin and nail health; improving joint, bone and cartilage health; promoting detoxification of the body; promoting collagen production; aiding digestion; and improving heart health (see, e.g., Martin, KR, J Nutr Health Aging, 11(2), 94-7 (2007)).

[0005] There is also evidence that silica particles with a specific porosity can reduce adipose tissue in animal model systems (see: WO 2014 / 072363 and Kupferschmidt, N. et al., Nanomedicine, 9(9), 1353-1362 (2014)) and can also reduce levels of HbA1c, a biomarker whose levels correspond to long-term plasma glucose levels (see Baek, J. et al., Nanomedicine, 17:1, 9-22 (2022)).

[0006] Ideally, silica is administered in the form of silica particles that can be taken orally with or without food. However, the use of silica particles as an oral food supplement faces significant challenges. In particular, the amount of silica material required to achieve a therapeutic effect is often relatively large, typically in the range of several grams, which makes it inconvenient to present such materials in the form of tablets or capsules because restrictions on the size and shape of individual tablets and capsules suitable for oral administration result in the need to consume multiple dosage units.

[0007] To address this problem, silica materials can be presented in the form of liquids that can be consumed orally. However, such liquid formulations are unstable because the silica material may separate from the formulation, causing the silica material to become unevenly distributed and have poor taste characteristics, such as having a gritty texture and causing a feeling of dry mouth after consumption.

[0008] Therefore, there is a need for oral formulations of silica materials that are stable and have a pleasant texture, making them easier to consume. DETAILED DESCRIPTION

[0009] It has been unexpectedly discovered that improved oral formulations of silica materials can be prepared by adding specific thickeners. Such formulations can be used as dietary supplements.

[0010] New formulations

[0011] In a first aspect of the present invention, there is provided an oral dietary supplement comprising:

[0012] (a) water;

[0013] (b) silica particles; and

[0014] (c) a thickener,

[0015] The thickener is xanthan gum.

[0016] Unless defined otherwise, all technical and scientific terms used herein have the same common meaning as understood by one of ordinary skill in the art to which this invention belongs.

[0017] For the avoidance of doubt, oral dietary supplements may also be referred to as oral preparations, and vice versa.

[0018] The dietary supplement formulation as defined in the first aspect of the present invention (including all embodiments and features thereof) may also be referred to as "the formulation of the present invention (or the first aspect of the present invention)" etc. Such formulations may also be referred to as compositions, and these terms may be used interchangeably. Similarly, the silica particles mentioned in the first aspect of the present invention (including all embodiments and features thereof) may also be referred to as "the silica (or silica material or silica particles) of the present invention (or the first aspect of the present invention)" etc.

[0019] When used herein with respect to a particular value (such as an amount), the term "about" (or similar terms, such as "approximately") will be understood to indicate that such value can vary by up to 10% (particularly, up to 5%, such as up to 4%, 3%, 2% or 1%) of the defined value. It is contemplated that, in each case, such terms may be replaced with the notation "±10%" or the like (or by indicating a variance of a particular amount calculated based on the relevant value). With respect to percentage amounts mentioned herein, the term "about" (or similar terms, such as "approximately") will be understood to indicate that such value can vary by up to 10% (particularly, up to 5%, such as up to 4%, 3%, 2% or 1%) of the defined percentage value. It is also contemplated that, in each case, the term "about" may be deleted.

[0020] For the avoidance of doubt, reference to a formulation comprising certain ingredients will include the possibility that such formulation may consist of (or consist essentially of) those ingredients.

[0021] For the avoidance of doubt, the skilled person will appreciate that where percentages of a component are defined as belonging to different (i.e., non-overlapping) groups, the sum of these percentages cannot exceed 100%. Thus, where the maximum value in one or more non-overlapping groups of components exceeds 100%, the skilled person will appreciate that one or more of those components must be present in an amount less than the maximum value. Similarly, where other components may be present in the formulation, it is not required that the sum of the specified components equal 100%.

[0022] The skilled artisan will understand that reference to an oral formulation will refer to a formulation intended for (e.g., suitable for) oral consumption, such as by a human or animal (e.g., a mammal, such as a household pet or recreational animal, such as a cat, dog, horse, rabbit, etc., or livestock, such as cattle, pigs, sheep, goats, chickens, turkeys, etc.). In some cases, reference to consumption by such a human or animal subject (also referred to as a patient in connection with a medical treatment method) will specifically refer to consumption by an adult (e.g., fully grown) subject.

[0023] For the avoidance of doubt, the skilled artisan will understand that references to oral formulations include orally ingestible (ie suitable for ingestion) products such as medical devices.

[0024] In particular, reference to an oral formulation will refer to a formulation intended for (eg suitable for) oral consumption by a human, such as an adult (eg a human who is at least 18 years of age).

[0025] The skilled person will understand that references herein to oral consumption will refer to swallowing the formulation by the subject in one action or in several actions. Thus, the skilled person will understand that the formulation of the present invention may be in the form of a liquid so that the formulation may be easily swallowed in the manner of drinking.

[0026] Thus, in certain embodiments, the formulation is a liquid (in which case it may be referred to as a liquid formulation).

[0027] The skilled person will understand that the term "liquid" will typically refer to a substance that is free-flowing but has a constant volume, typically having a consistency similar to that of water or liquid oil.

[0028] The skilled artisan will appreciate that the amount of each component present in the formulation can be adjusted in order to achieve the desired viscosity and flowability.

[0029] In certain embodiments, the formulation can be provided in a form having a viscosity classified as low to medium, such as having a viscosity and / or flowability similar to that of a milkshake or similar drink / food item.

[0030] As described herein, the formulations of the present invention include water. In particular, the formulation will typically include water as an important component, such as being the main (i.e., largest) component by weight. Therefore, the formulation can be described as an aqueous (or substantially aqueous) formulation.

[0031] The skilled artisan will appreciate that the amount of water included in the formulation may be selected so as to achieve desired properties of the formulation, such as a desired viscosity and / or flowability.

[0032] In certain embodiments, the formulation comprises:

[0033] At least about 70.0% (such as at least about 71.0%, 72.0%, 73.0%, 74.0%, 75.0%, 76.0%, 77.0%, 78.0%, 79.0%) water by weight (wt %); and / or (e.g., and)

[0034] At least about 80.0 wt % (such as at least about 81.0 wt %, 82.0 wt %, 83.0 wt %, 84.0 wt % or 85.0 wt %) water.

[0035] In particular embodiments, the formulation comprises up to about 95.0 wt % (such as up to about 94.0 wt %, 93.0 wt %, 92.0 wt %, or 91.0 wt %) water.

[0036] In more particular embodiments, the formulation comprises up to about 90.0 wt % (such as up to about 89.0 wt %, 88.0 wt %, 87.0 wt %, 86.0 wt % or 85.0 wt %) water.

[0037] For example, in certain embodiments, the formulation comprises from about 70.0 wt % to about 95.0 wt % water.

[0038] In more particular embodiments, the formulation comprises from about 75.0 wt % to about 95.0 wt % water.

[0039] In more particular embodiments, the formulation comprises about 80.0 wt % to about 95.0 wt % water.

[0040] In more particular embodiments, the formulation comprises from about 75.0 wt % to about 90.0 wt % water.

[0041] In more particular embodiments, the formulation comprises about 80.0 wt % to about 90.0 wt % water.

[0042] In more particular embodiments, the formulation comprises about 82.0 wt % to about 88.0 wt % water.

[0043] In more particular embodiments, the formulation comprises about 83.0 wt % to about 87.0 wt % water.

[0044] In more particular embodiments, the formulation comprises about 84.0 wt % to about 86.0 wt % water.

[0045] In certain embodiments, the formulation comprises about 84.0 wt % to about 91.0 wt % water.

[0046] In certain embodiments, the formulation comprises about 84.0 wt % to about 90.0 wt % water.

[0047] In particular embodiments, the formulation comprises about 85 wt % to about 86 wt % water, such as about 85.6 wt % water.

[0048] In particular embodiments, the formulation comprises from about 89 wt % to about 90 wt % water, such as from about 89.0 wt % to about 90.0 wt % water.

[0049] In certain embodiments, it is understood that where amounts of other ingredients are specified, the remainder of the composition (eg, by weight) is water.

[0050] As described herein, the formulations of the present invention include silica particles. The skilled artisan will appreciate that the amount of such silica particles in the formulation can be selected to provide an appropriate loading so that administration of an appropriate amount of the formulation can deliver a desired amount of silica material (e.g., the dose required to achieve a desired health benefit).

[0051] In certain embodiments, the formulation comprises:

[0052] At least about 5.0 wt % (such as at least about 6.0 wt %, 7.0 wt %, 8.0 wt % or 9.0 wt %) of silica particles; and / or (e.g., and)

[0053] Up to about 15.0 wt % (such as at least about 14.0 wt %, 13.0 wt %, 12.0 wt % or 11.0 wt %) silica particles.

[0054] In certain embodiments, the formulation comprises from about 5.0 wt % to about 15.0 wt % of the silica particles.

[0055] In more specific embodiments, the formulation comprises from about 6.0 wt % to about 14.0 wt % of the silica particles.

[0056] In more specific embodiments, the formulation comprises from about 7.0 wt % to about 13.0 wt % of the silica particles.

[0057] In more specific embodiments, the formulation comprises from about 8.0 wt % to about 12.0 wt % of the silica particles.

[0058] In more specific embodiments, the formulation comprises from about 9.0 wt % to about 11.0 wt % of the silica particles.

[0059] In more specific embodiments, the formulation comprises from about 9.0 wt % to about 10.5 wt % of the silica particles.

[0060] In particular embodiments, the formulation comprises from about 9.0 wt % to about 10.0 wt % of the silica particles, such as about 10.0 wt % or about 9.4 wt % of the silica particles.

[0061] As described herein, the formulations of the present invention comprise a thickener, wherein the thickener is xanthan gum.

[0062] As described herein, it has been found that the use of such thickeners allows for the preparation of formulations that provide improved properties in terms of stability, texture and palatability.

[0063] The skilled artisan will be able to select an appropriate amount of thickener in order to achieve the desired characteristics of the formulation, such as its viscosity and flowability.

[0064] As described herein, it has been discovered that certain amounts (wt %) of the thickener xanthan gum unexpectedly provide enhanced long term stability of the formulation.

[0065] Thus, in certain embodiments, the formulations comprise from about 0.4 wt % to about 2.0 wt % of a thickener.

[0066] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.9 wt % of a thickening agent.

[0067] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.8 wt % of a thickening agent.

[0068] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.7 wt % of a thickening agent.

[0069] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.6 wt % of a thickening agent.

[0070] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.5 wt % of a thickening agent.

[0071] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.4 wt % of a thickening agent.

[0072] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.3 wt % of a thickening agent.

[0073] In more specific embodiments, the formulation comprises from about 0.4 wt % to about 1.2 wt % of a thickening agent.

[0074] In more specific embodiments, the formulation comprises from about 0.5 wt % to about 1.2 wt % of a thickening agent.

[0075] In more specific embodiments, the formulation comprises from about 0.5 wt % to about 1.1 wt % of a thickening agent.

[0076] In more specific embodiments, the formulation comprises from about 0.6 wt % to about 1.1 wt % of a thickening agent.

[0077] In more specific embodiments, the formulation comprises from about 0.5 wt % to about 1.0 wt % of a thickening agent.

[0078] In more specific embodiments, the formulation comprises from about 0.6 wt % to about 1.0 wt % thickener (eg, about 0.6 wt % or about 1.0 wt % thickener).

[0079] In certain embodiments, the formulation comprises from about 0.4 wt % to about 0.8 wt % of a thickening agent.

[0080] In certain embodiments, the formulation comprises from about 0.5 wt % to about 0.7 wt % of a thickening agent.

[0081] For example, in certain embodiments, the formulation comprises about 0.6 wt % of a thickener.

[0082] Those skilled in the art will appreciate that the formulations of the present invention may include additional components in order to adjust and / or maintain properties such as freshness / food safety (i.e., freedom from contaminants such as bacterial and mold growth), taste, aroma and / or color of the formulation.

[0083] Thus, in certain embodiments, the formulation further comprises:

[0084] (d) optionally, one or more preservatives, sweeteners, flavoring agents, fragrances and / or coloring agents.

[0085] In particular embodiments, optional component (d) is present in the formulation in an amount up to about 10.0 wt % (such as up to about 9.0 wt %, 8.0 wt %, 7.0 wt % or 6.0 wt %) of the formulation.

[0086] In more particular embodiments, optional component (d) is present in the formulation in an amount up to about 5.0 wt % (such as up to about 4.9 wt %, 4.8 wt %, 4.7 wt %, 4.6 wt %, 4.5 wt % or 4.4 wt %) of the formulation.

[0087] For example, the formulation may further comprise one or more preservatives, such as those food preservatives known to those skilled in the art to be suitable for human consumption.

[0088] For example, suitable preservatives would include lactic acid, benzoic acid and its pharmaceutically acceptable salts (such as sodium benzoate), sorbic acid and its pharmaceutically acceptable salts (such as potassium sorbate) and citric acid, including mixtures thereof.

[0089] Specific preservatives that may be mentioned include citric acid and potassium sorbate, including mixtures thereof.

[0090] For the avoidance of doubt, preservatives, such as those described herein, may also be referred to as acidity modifiers.

[0091] In certain embodiments, the formulations further comprise one or more preservatives.

[0092] For example, in certain embodiments, the formulation includes the preservatives citric acid (e.g., in an amount of about 0.1 wt % to about 0.3 wt % of the formulation, such as about 0.2 wt % of the formulation, e.g., about 0.22 wt % of the formulation) and potassium sorbate (e.g., in an amount of about 0.05 wt % to about 0.15 wt % of the formulation, such as about 0.1 wt % of the formulation, e.g., about 0.09 wt % of the formulation).

[0093] The formulations may also contain one or more flavoring and / or sweetening agents, such as those known to those skilled in the art to be suitable for human consumption.

[0094] For example, suitable sweeteners may include sugars (such as sucrose, tagatose and psicose), sugar alcohols (such as erythritol, xylitol, sorbitol and mannitol), artificial sweeteners (such as sucralose, saccharin, acesulfame-K and aspartame) and plant extracts (such as steviol glycosides and monk fruit extracts). Specific sweeteners that may be mentioned include non-caloric sweeteners, particularly sugar alcohols (such as erythritol) and plant extracts (such as steviol glycosides).

[0095] In certain embodiments, the formulations include one or more sweeteners.

[0096] The skilled artisan will be able to select appropriate sweeteners and amounts thereof in order to achieve the desired taste characteristics of the formulation.

[0097] In particular embodiments, the sweetener is present in an amount from about 0.01 wt % to about 10.0 wt % of the formulation.

[0098] In more particular embodiments, the sweetener is present in an amount from about 0.05 wt % to about 10.0 wt % of the formulation.

[0099] In more specific embodiments, the sweetener is present in an amount from about 0.1 wt % to about 10.0 wt % of the formulation.

[0100] In more specific embodiments, the sweetener is present in an amount from about 0.5 wt % to about 10.0 wt % of the formulation.

[0101] In more specific embodiments, the sweetener is present in an amount from about 1.0 wt % to about 10.0 wt % of the formulation.

[0102] In more specific embodiments, the sweetener is present in an amount from about 2.0 wt % to about 9.0 wt % of the formulation.

[0103] In more specific embodiments, the sweetener is present in an amount from about 2.0 wt % to about 8.0 wt % of the formulation.

[0104] In more specific embodiments, the sweetener is present in an amount from about 2.0 wt % to about 7.0 wt % of the formulation.

[0105] In more specific embodiments, the sweetener is present in an amount from about 2.0 wt % to about 6.0 wt % of the formulation.

[0106] In more specific embodiments, the sweetener is present in an amount from about 3.0 wt % to about 5.0 wt % of the formulation.

[0107] In more specific embodiments, the sweetener is present in an amount from about 3.0 wt % to about 4.0 wt % of the formulation.

[0108] In more specific embodiments, the sweetener is present in an amount from about 3.5 wt % to about 3.9 wt % of the formulation.

[0109] In more specific embodiments, the sweetener is present in an amount from about 3.6 wt % to about 3.9 wt % of the formulation.

[0110] In particular embodiments, the sweetener is present in an amount of about 4 wt % of the formulation, such as about 3.8 wt % of the formulation.

[0111] In more specific embodiments, the sweetener is erythritol or a mixture of erythritol and steviol glycosides.

[0112] In particular such embodiments (i.e., where the sweeteners are erythritol and steviol glycosides), the sweeteners are present in an amount of about 4 wt % of the formulation, such as about 3.8 wt % of the formulation, for example wherein erythritol is present in an amount of about 3.7 wt % to about 3.8 wt % of the formulation, such as about 3.75 wt % of the formulation, and steviol glycosides are present in an amount of about 0.01 wt % of the formulation.

[0113] As described herein, the formulations may additionally include flavorings (eg, vanilla and / or fruit flavorings), which may be derived from extracts and / or artificial agents.

[0114] Such flavoring agents may be present in an amount of about 0.01 wt % to about 0.50 wt % of the formulation, for example about 0.01 wt % to about 0.30 wt % of the formulation, such as about 0.25 wt % of the formulation.

[0115] In certain embodiments, the formulation is free (or substantially free) of additional active agents (ie, active agents other than the silica materials of the present invention).

[0116] For the avoidance of doubt, the formulation may comprise further additional components which may be selected so as to enhance and / or supplement the properties of the formulation.

[0117] For example, the skilled artisan will appreciate that other such additional components, such as colorants and flavorings, may be selected in order to provide an attractive formulation to a subject. Where present, such components may be present in substantially negligible amounts when compared to the other components.

[0118] In certain embodiments, the amount of a component as specified herein (i.e., components (a) to (c) or (a) to (d) as appropriate) is equal to 100% (in these embodiments, the formulation can be said to consist of or consist essentially of the components as specified herein).

[0119] In other embodiments, other components may be added to the formulations of the invention in amounts that are additional to the components and their relative amounts as specified above without changing the properties of the formulation. In such embodiments, the formulation comprises the components as specified herein (i.e., components (a) to (c) or (a) to (d) as required) (wherein the relative amounts of these components are equal to 100%), optionally comprising additional components.

[0120] The skilled person will appreciate that the formulations of the present invention will contain each component as a mixture thereof. In particular, such mixtures will contain each component such that each component is evenly distributed throughout the formulation, which formulation can be described as homogeneous (or substantially homogeneous).

[0121] As described herein, the formulations of the invention will be stable, which can mean that the composition of the formulation and the distribution of such components in the formulation will not change over an extended period of time, such as a period of at least 42 days, such as at least 1 year (365 days).

[0122] In particular embodiments, the formulation will be stable for at least 42 days (such as at least 1 year (365 days)), such as where the formulation will remain homogeneous (or substantially homogeneous) after storage for a period of at least 42 days (such as at least 1 year (365 days); for example at room temperature and pressure, protected from moisture and light).

[0123] Silica particles

[0124] The skilled person will appreciate that the silica particles as provided in the formulation of the first aspect of the invention may be referred to as a plurality of silica particles, which may be referred to as a silica material.

[0125] For the avoidance of doubt, such silica particles may be porous, such as silica particles having pores in the mesoporous range (which may be referred to as mesoporous silica particles). Porous silica materials that may be used include those described in Baek, J. et al., Nanomedicine, 17: 1, 9-22 (2022), the contents of which are hereby incorporated by reference herein.

[0126] The skilled artisan will also appreciate that the silica particles may have a particular surface area, which may be affected by properties such as the porosity of the silica particles.

[0127] The skilled artisan will also appreciate that the silica particles can be provided in a variety of shapes, such as spheres or rods, and may vary in relation to particle size.

[0128] The skilled person will understand that the term "average particle size" as used herein will refer to the average diameter of the particles at their largest point (e.g., in the case of rod-shaped particles, their length; or in the case of spherical particles, their diameter.), which can 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) techniques known to those skilled in the art). In specific embodiments, the particle size is determined using electron microscopy (e.g., using SEM) or by laser diffraction.

[0129] Where the particle is spherical, the size of the particle (as measured by SEM) may be defined by reference to the diameter of the particle, such as having:

[0130] About 0.1 μm to about 20.0 μm;

[0131] About 0.1 μm to about 15.0 μm;

[0132] About 0.1 μm to about 10.0 μm;

[0133] About 0.5 μm to about 10.0 μm;

[0134] About 0.5 μm to about 5.0 μm;

[0135] About 0.5 μm to about 4.5 μm;

[0136] About 1.0 μm to about 10.0 μm;

[0137] About 1.0 μm to about 5.0 μm;

[0138] About 1.0 μm to about 4.0 μm;

[0139] About 1.0 μm to about 4.0 μm;

[0140] about 2.0 μm to about 4.0 μm; or

[0141] The average particle size is about 3.0 μm to about 4.0 μm.

[0142] Where the particles are rod-shaped, the size of the particles (as measured by SEM) may (or may also) be defined by reference to the width of the particles, such as having:

[0143] About 0.05 μm to about 0.6 μm;

[0144] About 0.1 μm to about 0.6 μm;

[0145] about 0.1 μm to about 0.4 μm; or

[0146] Average width of about 0.2 μm to about 0.4 μm.

[0147] Where the particles are spherical, the size of the particles (as measured by laser diffraction) may be defined by reference to the diameter of the particle, such as having:

[0148] About 1.5 μm to about 20.0 μm;

[0149] About 1.5 μm to about 15.0 μm;

[0150] About 1.5 μm to about 10.0 μm;

[0151] About 2.0 μm to about 10.0 μm;

[0152] About 2.0 μm to about 7.5 μm;

[0153] About 2.0 μm to about 5.0 μm;

[0154] About 2.0 μm to about 4.5 μm;

[0155] About 2.5 μm to about 4.5 μm;

[0156] About 3.0 μm to about 4.5 μm;

[0157] about 3.5 μm to about 4.5 μm; or

[0158] The average particle size is about 3.5 μm to about 4.5 μm.

[0159] Where the particle is rod-shaped, the size of the particle (as measured by laser diffraction) may (or may also) be defined by reference to its width, such as having:

[0160] About 1.5 μm to about 20.0 μm;

[0161] About 2.0 μm to about 10.0 μm;

[0162] about 2.0 μm to about 5.0 μm; or

[0163] Average width of about 3.5 μm to about 4.5 μm.

[0164] The skilled person will appreciate that silica materials of the type described in the present invention are typically non-crystalline. Thus, in certain embodiments, the silica particles may be described as substantially non-crystalline silica particles (and materials formed from a plurality of such particles can be described in the same manner). Thus, the silica particles may be described as non-crystalline silica particles.

[0165] In alternative embodiments, the silica material present in the 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 mean that the structure of the silica material (excluding the pores present therein) has no substantial order, such as may be present in a crystalline material (i.e., the silica particles or silica material may be referred to as non-crystalline).

[0166] Use as a dietary supplement

[0167] As described herein, the formulations of the present invention can be used as dietary supplements and can therefore be provided in a form suitable for such use. Thus, the formulations of the present invention can be described as dietary supplement formulations (eg, oral dietary supplement formulations).

[0168] In a second aspect of the present invention there is provided a formulation as defined in the first aspect of the present invention (including all embodiments and features thereof) for use as a dietary supplement.

[0169] For the avoidance of doubt, a formulation referred to as a dietary supplement formulation may also be suitable for use as a food supplement, and vice versa. Thus, the formulation of the present invention may be referred to as a food supplement or the like.

[0170] The skilled person will appreciate that the formulation of the present invention may be taken (ie administered) simultaneously with, or as part of, a food (eg a meal) or a drink.

[0171] The skilled person will understand that references herein to administration with food (or similarly, administration with a meal) or administration with a drink may refer to administration simultaneously with consumption of the food or drink, or administration shortly before or after consumption of the food or drink (e.g. up to 2 hours, such as up to 1 hour, or in particular up to 30 minutes before or after consumption of the food).

[0172] The skilled artisan will also appreciate that when used as a dietary supplement, the formulations of the present invention can induce the biological effects as described herein. Therefore, the dietary supplement formulations as described herein may also be referred to as active dietary supplement formulations.

[0173] The skilled artisan will understand that reference to a formulation for use as a dietary supplement refers to a formulation that is orally consumed (i.e., eaten by mouth) by a human or animal (e.g., a mammal such as a household pet or recreationally related animal such as a cat, dog, horse, rabbit, etc., or livestock such as cattle, pigs, sheep, goats, chickens, turkeys, etc.).

[0174] Packaging and manufacturing

[0175] The skilled artisan will appreciate that the formulations of the present invention can be packaged (eg, for distribution and sale) in any manner suitable for a dietary or food supplement, as long as it is suitable for the intended use.

[0176] For example, the formulations of the invention may be packaged in a single-serving container, such as a container from which the formulation may be consumed directly (eg, a single-serving bottle or pouch, or a stick pack).

[0177] The formulations of the invention can be prepared using techniques known to those skilled in the art, such as by mixing the components of the composition (either in one process or sequentially in subsets of such processes) to obtain a substantially homogeneous mixture of the components.

[0178] Therefore, in a further aspect of the invention, there is provided a method for preparing a formulation according to the first aspect of the invention (including all embodiments and features thereof), the method comprising the steps of bringing the components of the formulation together to form a mixture of these components and homogenizing the mixture.

[0179] Without wishing to be bound by theory, it is believed that the formulations of the present invention allow for the provision of silica particles in a form that is stable and easily consumed by a subject without the unpleasant mouthfeel (i.e., grittiness and dry aftertaste) associated with other formulations, thereby increasing the palatability of the formulation.

[0180] Examples

[0181] The present invention will be further described by reference to the following examples, which are not intended to limit the scope of the present invention.

[0182] Material

[0183] The silica particles were mesoporous spherical silica particles (MSP) and had an average particle size of 4 μm as measured by laser diffraction and an average particle size of 1.5 μm as measured by scanning electron microscopy (SEM).

[0184] Particle size measured by laser diffraction

[0185] The size of silica particles dispersed in water was measured using a Mastersizer 3000 (Malvern Panalytical, Malvern, UK) equipped with a Hydro LV dispersion unit. While stirring (3500 rpm), silica powder was added to the dispersion unit until a minimum laser obscuration of 5% was achieved. Stirring was continued for 2 minutes and then ultrasonicated for 3 minutes before measuring the particle size. The average particle size was reported as the median particle size calculated from the volume particle size distribution (n=3).

[0186] Particle size measured by SEM

[0187] A scanning electron microscope using JSM-7401F (JEOL Ltd., Tokyo, Japan) was used to characterize particle size and morphology from SEM micrographs. The average particle size (diameter of spherical particles) was analyzed from ≥100 particles using ImageJ (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)).

[0188] The following ingredients were purchased from Sigma-Aldrich: potassium sorbate (1.05119.1000), karaya gum (G0503), 2-hydroxyethylcellulose (434981), sodium carboxymethylcellulose (419303), and guar gum (G4129). Xanthan gum was obtained from CP Kelco ( RD). Tragacanth gum was purchased from Rainbow Dust Colours. Colloidal crystalline cellulose was obtained from JRS Pharma ( MCG 900XF). Flavoring agents were obtained from Einar Willumsen: vanilla extract (22219), blueberry flavor (35144), and peach flavor (12101). Erythritol was purchased from Amazon (ASIN B01MFCXDZA). Stevioside was obtained from Tate & Lyle (Intesse TM Stevia 2.0).

[0189] Example 1: Preparation of formulation

[0190] Preparation of stock solutions

[0191] Solution 1: Dissolve potassium sorbate in water. Then add citric acid to the same solution and stir until dissolved. The concentration of potassium sorbate is 0.125wt% and the concentration of citric acid is 0.250wt%

[0192] Solution 2: Stevioside (0.4 g) was dissolved in 20 g of water.

[0193] Solution 3: Blueberry flavor (0.6 g) was diluted in 20 g water.

[0194] Solution 4: Peach flavor (0.6 g) was diluted in 20 g water.

[0195] Recipe 1 to Recipe 15

[0196] While homogenizing, thickener (concentration according to Table 1; also referred to as thickener) was slowly added to 40.15 g of Solution 1 and water (the amount was adjusted to have a total weight of 50 g). As the formulation thickened, the homogenization speed was slowly increased from low to medium. After the thickener was added, the formulation was homogenized for another 3 minutes at medium speed. The thickener appeared to be fully dispersed (lumps were no longer visible). Finally, 5 g of MSP was added to the formulation and homogenized for 3 minutes at medium speed.

[0197] Recipe 16

[0198] Potassium sorbate (0.2g) is dissolved in water (163.28g).Add vanilla extract (0.32g), solution 2 (1.0g), solution 3 (4.0g), solution 4 (2.0g), citric acid (0.4g) and erythritol (7.6g) and stir until dissolved.While homogenizing, xanthan gum (1.2g) is lentamente added to the solution.Along with the preparation thickening, the homogenization speed is slowly increased to medium speed from low speed.After adding xanthan gum, the preparation is homogenized again for 3 minutes at medium speed.Xanthan gum looks to be fully dispersed (caking is no longer visible).Finally, 20g of MSP is added to the preparation and homogenized for 3 minutes at medium speed.

[0199] To prepare samples for consumer trials (Example 3), the manufacture of Formulations 4, 12, 13, 14 and 16 was repeated on a larger scale (200 grams).

[0200] Table 1: Preparation

[0201]

[0202] * Guar gum in recipes 1 to 2, tragacanth gum in recipes 3 to 4, karaya gum in recipes 5 to 6, 2-hydroxyethylcellulose in recipes 7 to 8, sodium carboxymethylcellulose in recipes 9 to 10, colloidal crystalline cellulose in recipes 11 to 12, and xanthan gum in recipes 13 to 16

[0203] # Erythritol (3.80 wt%) and steviol glycosides (0.01 wt%)

[0204] ¤ Vanilla (0.16 wt%), blueberry (0.06 wt%) and peach (0.03 wt%) flavoring

[0205] Example 2: Evaluation of Suspension Stability

[0206] On the second day after manufacturing, about 20mL of each formulation was transferred to a glass vial and stored in the dark at room temperature. After six weeks, visual observation samples were made. If separation was observed (clear liquid on top), the suspension was unstable. If separation was not observed after six weeks, the suspension was considered to be stable under the conditions of the experiment. The results are presented in Table 2.

[0207] Table 2. Results of suspension stability evaluation

[0208] formula Thickener Suspension stability Recipe 1 Guar gum 1.0wt% Unstable Recipe 2* Guar gum 2.0wt% Stablize Recipe 3 Tragacanth gum 1.0wt% Unstable Recipe 4 Tragacanth gum 2.0wt% Stablize Recipe 5 Karaya gum 1.0wt% Unstable Recipe 6 Karaya gum 2.0wt% Unstable Recipe 7 2-Hydroxyethyl cellulose 1.0wt% Unstable Recipe 8 2-Hydroxyethyl cellulose 1.0wt% Unstable Recipe 9 Sodium carboxymethyl cellulose 1.0wt% Unstable Recipe 10 Sodium carboxymethyl cellulose 2.0wt% Unstable Recipe 11 Colloidal microcrystalline cellulose 1.0wt% Unstable Recipe 12 Colloidal microcrystalline cellulose 2.0wt% Stablize Recipe 13 Xanthan gum 0.3% Stablize Recipe 14 Xanthan gum 0.6% Stablize Recipe 15 Xanthan gum 1.0% Stablize Recipe 16 Xanthan gum 0.6% Stablize

[0209] *This formula forms a very thick gel and is difficult to pack

[0210] Example 3: Evaluation of suspension stability after 1 year

[0211] Some samples (Example 2) that looked stable after six weeks of storage in the dark at room temperature were kept under the same conditions. After 1 year, the samples were visually observed again. If separation was observed (clear liquid on top), the suspension was unstable. If separation was not observed after 1 year, the suspension was considered to be stable under the conditions of this experiment. The results are presented in Table 3.

[0212] Table 3. Results of the suspension stability evaluation after 1 year of storage at room temperature

[0213]

[0214]

[0215] Example 4: Consumer Test

[0216] Volunteers were provided with test tubes containing approximately 10 mL of each formulation selected for the consumer trial. Volunteers were instructed to taste a small amount (one tablespoon) of each product, drinking water (at least one sip) between tastings of each product. For each product, volunteers were asked to rate their level of agreement with the statements listed in Table 4 using a 5-point rating scale. A score of 1 indicated the lowest level of agreement with the statement, and a score of 5 indicated the highest level of agreement with the statement.

[0217] Feedback from 13 volunteers was collected and the average score was calculated. An average score below 4.0 was considered a failure, and an average score of 4.0 or above was considered a pass. The results are summarized in Table 4.

[0218] Table 4. Consumer test results

[0219]

Claims

1. An oral dietary supplement, comprising: (a) water; (b) silica particles; and (c) a thickener, The thickener is xanthan gum.

2. The dietary supplement of claim 1, wherein the dietary supplement comprises about 70.0 wt% to about 95.0 wt% water.

3. The dietary supplement of claim 1 or claim 2, wherein the dietary supplement comprises from about 5.0 wt% to about 15.0 wt% of the silicon dioxide particles.

4. The dietary supplement of any one of claims 1 to 3, wherein the dietary supplement comprises from about 0.4 wt% to about 2.0 wt% of the thickener.

5. The dietary supplement of any one of claims 1 to 4, wherein the dietary supplement comprises from about 0.4 wt% to about 1.2 wt% of the thickener.

6. The formulation according to any one of claims 1 to 5, wherein the dietary supplement further comprises: (d) one or more preservatives, sweeteners, flavoring agents, fragrances and / or coloring agents.

7. The formulation of any one of claims 1 to 6, wherein the silica particles are porous.

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