Composition

Abstract

The present invention relates to compositions comprising gingeroids or ginger oleoresin; in particular, compositions comprising gingeroids or ginger oleoresin that are highly water soluble and have increased bioavailability. The present invention also relates to processes for providing such compositions and uses of such compositions.

Description

[Technical field]

[0001] FIELD OF THE PRESENT APPLICATION The present invention relates to compositions comprising ginger or, in particular, ginger oleoresin, which is highly water insoluble. Gingeroids are defined as the sum of gingerols, including but not limited to 6-gingerol, 8-gingerol and 10-gingerol, and shogaols, including but not limited to 6-shogaol, 8-shogaol and 10-shogaol. The present invention also relates to processes for providing such compositions and uses of such compositions. [Background technology]

[0002] 2. Background of the Invention The listing or discussion of an apparently 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.

[0003] Ginger, the rhizome of Zingiber officinale, is a member of the Zingberaceae family that has been used as a spice for many years. Ginger contains a wide variety of volatile and non-volatile compounds in varying concentrations depending on where the plant is grown and the methods used to harvest and process the plant. The main constituents of ginger include carbohydrates, lipids, terpenes and phenolic compounds. Phenolic compounds include gingerol, paradol and shogaol.

[0004] The rhizome has been used since ancient times in various traditional medicine systems to treat cold, fever, sore throat, infectious diseases, arthritis, rheumatism, sprains, muscle pain, pain, convulsions, high blood pressure, dementia, migraine, neurological diseases, gingivitis, toothache, asthma, stroke, and diabetes, and is also used as a home remedy in the treatment of various stomach diseases such as constipation, diarrhea, indigestion, belching, abdominal distension, gastritis, upper abdominal discomfort, gastric ulcer, digestive disorders, nausea, and vomiting (Giacosa, A., et al. (2015). Eur Rev Med Pharmacol Sci, 19 (7), 1291-6.; Haniadka, R., et al. (2013). Food & function, 4 (6), 845-855.; Lete, I., & Allue, J. (2016). The Effectiveness Of Ginger In The Prevention Of Nausea And Vomiting During Pregnancy And Chemotherapy(jurnal).Spain:Clinical Management Unit of Obstetrics and Gynecology,Hospital Universitario Araba,Vitoria,Spain.Plant Physiology Laboratory,Faculty of Biosciences,Universitat Autonoma de Barcelona,Bellatera,Spain).

[0005] This long and well-established history of medical use of ginger in humans, coupled with the growing interest in natural remedies, has stimulated clinical trials to scientifically evaluate the effectiveness of ginger as an adjunct therapy in several diseases, especially gastrointestinal diseases, or as a complementary and alternative medicine (Lete, I., & Allue, J. (2016). The Effectiveness of Ginger In The Prevention of Nausea And Vomiting During Pregnancy And Chemotherapy (jurnal). Spain: Clinical Management Unit of Obstetrics and Gynecology, Hospital Universitario Araba, Vitoria, Spain. Plant Physiology Laboratory, Faculty of Biosciences, Universitat Autonoma de Barcelona, ​​Bellatera, Spain. Lete & Allue, 2016).

[0006] However, although ginger has shown efficacy against a number of human disorders, it is also known to have limited bioavailability due to poor absorption, rapid metabolism, and rapid systemic excretion. Ginger extracts that are highly rich in gingeroids such as oleoresins have been found to be poorly water-soluble.

[0007] Rapid metabolism, poor water solubility, and low uptake by tissues dramatically limit the potential usefulness of ginger, including the potential use of gingeroids (used herein to refer to both gingerols and shogaols, particularly 6, 8, and 10 gingerols and 6, 8, and 10 shogaols) in the treatment of conditions such as gastrointestinal disorders.

[0008] The present invention seeks to address the above-mentioned problems associated with the poor water solubility of ginger and to provide a ginger / gingeroid-containing composition that is highly water soluble and stable at physiological pH. Summary of the Invention

[0009] Disclosure of the Invention The inventors have surprisingly found that a composition comprising ginger oleoresin or gingeroids, a gum (such as gum arabic) and at least one saponin (such as an extract obtained or obtainable from Quillaja quillaja) provides sustained release of the gingeroids, is highly water soluble and stable at physiological pH, and has increased bioaccessibility, bioavailability, bioefficacy and / or bioactivity of the gingeroids.

[0010] According to the present invention, (i) Gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin A composition comprising:

[0011] Further, according to the present invention, (i) Gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin A sustained release composition is provided comprising:

[0012] Such compositions may hereinafter be referred to as "compositions of the invention."

[0013] According to the present invention, the term "sustained release" refers to delayed and extended release, which means that the active ingredient (gingeroid) is released after at least 30 minutes and then over an extended period of at least 1 hour, 4 hours or at least 8 hours.

[0014] The inventors of the present invention have shown that in the compositions of the present invention, the active substances (gingeroids) are released much slower than in the control ginger extract. The sustained release effect is shown in Tables 11 and 13, where similar maximum gingeroid concentrations in the blood at similar Tmax are seen between the formulations, but the compositions of the present invention provide a slower decline in blood gingeroid concentrations compared to both ginger powder and ginger 5% at all time points: 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours. This results in a 2,84-fold increase in half-life of the compositions of the present invention over ginger powder and a 1,8-fold increase in half-life of the compositions of the present invention over ginger 5%.

[0015] The gingeroids used in the compositions of the present invention may be obtained from any source, however it is preferred that the gingeroids are obtained from natural sources, i.e., they are not synthetic but are plant-based.

[0016] Gingeroids are defined herein as the sum of gingerols, including but not limited to 6-gingerol, 8-gingerol and 10-gingerol, and shogaols, including but not limited to 6-shogaol, 8-shogaol and 10-shogaol. Other gingerols and shogaols, such as 12-gingerol, may be present in the compositions of the present invention.

[0017] The composition may comprise at least about 5% gingeroids by weight, such as at least about 7.5%, or at least about 10% or at least about 20% gingeroids by weight of the composition.

[0018] For example, the gingeroids may be present in an amount of about 5% to about 60% by weight, such as about 7.5% to about 50% by weight, or about 10% to about 40% by weight of the composition.

[0019] Gingeroids may be obtained or available from the root (rhizome) of ginger (Zingiber officinale). Gingeroids may be provided by extraction and optional purification from the root (rhizome) of ginger (Zingiber officinale). These ginger extracts in the present invention include, but are not limited to, ginger oleoresin, defatted ginger oleoresin, and mixtures thereof. Thus, the gingeroids may be in the form of an extract or purified extract (such as ginger oleoresin, defatted ginger oleoresin and mixtures thereof) of the root (rhizome) of ginger (Zingiber officinale), the extract comprising from about 10% to about 100% gingeroids by weight, such as from about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or 90% to about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50% or 45% gingeroids by weight of the extract.

[0020] When the gingeroids are provided as an extract of ginger (Zingiber officinale) root (rhizome), such as ginger oleoresin, defatted ginger oleoresin and mixtures thereof, the ginger (Zingiber officinale) root (rhizome), ginger oleoresin, defatted ginger oleoresin and mixtures thereof may be extracted using organic solvents or non-organic solvents or mixtures thereof.

[0021] For example, ginger (Zingiber officinale) root (rhizome) may be subjected to extraction with an organic solvent at one or more temperatures ranging from 0 to 150° C., depending on the solvent used. The organic solvent extract may be separated from the remaining ginger root (rhizome) powder by any method known in the art. The organic extract may optionally be concentrated using any suitable method known in the art.

[0022] Examples of suitable organic solvents include, but are not limited to, hydrocarbons such as pentane, petroleum ether, hexane, heptane or cyclohexane, including eutectic mixtures, optionally containing water; alcohols such as methanol, 2-methoxyethanol, ethanol, n-propanol, isopropanol, all isomers of butyl alcohol, benzyl alcohol, 1,2,6-trihydroxyhexane, ethylene glycol, 1,2-propanediol, dipropylene glycol, 1,3-butanediol, 2-butoxyethanol, 1,3-butylene glycol, glycerol; esters such as ethyl acetate, isopropyl acetate, 2-butoxyethyl acetate, glycerol esters such as glyceryl diacetate, glyceryl triacetate, glyceryl tributyrate; ethers such as diethyl ether, 2-ethoxyethanol; ketones such as acetone, 2-butanone; chlorinated or fluorinated hydrocarbons such as betaine, toluene, dichloromethane; and mixtures thereof. In a preferred embodiment, the organic solvent is ethyl acetate.

[0023] For example, ginger (Zingiber officinale) root (rhizome) may be subjected to extraction with an alcoholic or hydroalcoholic solvent at one or more temperatures ranging from 0 to 150°C, depending on the solvent used. For example, the alcohol-based extraction solvent may be water / methanol (i.e., a mixture of water and methanol) or water / ethanol (i.e., a mixture of water and ethanol) or methanol or ethanol. The organic solvent extract may be separated from the remaining ginger root (rhizome) powder by any method known in the art. The alcoholic or hydroalcoholic extract may optionally be concentrated using any suitable method known in the art.

[0024] When the extraction solvent comprises a water / alcohol mixture, the ratio of water to alcohol can be from about 25:75 to about 1:99, such as from about 20:80 to about 5:95 or about 10:90. For example, the extraction solvent can be water / ethanol in a ratio of from about 25:75 to about 1:99, such as from about 20:80 to about 5:95 or about 10:90.

[0025] Alternatively, the root (rhizome) of ginger (Zingiber officinale) can be extracted using CO2 extraction.

[0026] The extract (such as an organic extract or a CO2 extract) may then be further refined to provide a purified extract of gingeroids comprising from about 10% to about 100% gingeroids by weight, such as from about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or 90% to about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50% or 45% gingeroids by weight of the extract.

[0027] Purification of the extract may be carried out using such techniques known in the art. Typically, the extract is purified using an alcoholic solvent such as 100% methanol or 100% ethanol.

[0028] The extract may optionally be dried to remove excess solvent.

[0029] The gingeroids may be provided as a liquid or powder, such as a powder, for example a powdered ginger extract. In a preferred embodiment, the gingeroids are provided as an oleoresin.

[0030] As noted above, the term "gingeroid" as used herein includes, but is not limited to, the 6, 8 and 10 gingerols and the 6, 8 and 10 shogaols.

[0031] When the gingeroid is provided in the form of an extract from the root (rhizome) of ginger (Zingiber officinale) as defined above (such as ginger oleoresin, defatted ginger oleoresin and mixtures thereof), the composition may comprise the extract in an amount of at least 10% by weight of the composition, such as at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% by weight of the composition.

[0032] For example, the composition may comprise an extract from the root (rhizome) of ginger (Zingiber officinale) as defined above (such as ginger oleoresin, defatted ginger oleoresin and mixtures thereof) in an amount of about 10% to about 40% by weight of the composition, such as about 15% to about 30% by weight of the composition.

[0033] For example, the composition may comprise about 25% (i.e., 30%) to about 35% by weight of the composition of an extract from the root (rhizome) of ginger (Zingiber officinale) (such as ginger oleoresin, defatted ginger oleoresin, and mixtures thereof), which comprises about 5%, 10%, 20%, 30%, 40% to about 50%, 60%, 70%, 80% or 99% gingeroids by weight, such as about 10% to 20%, such as 11% by weight of the extract from the root (rhizome) of ginger (Zingiber officinale) (such as ginger oleoresin, defatted ginger oleoresin, and mixtures thereof), providing a composition comprising about 5% to 30% gingeroids by weight of the composition.

[0034] It may be preferred that the gingeroids are provided in the form of ginger oleoresin.

[0035] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin In a preferred embodiment, the gum is gum arabic.

[0036] Ginger oleoresin can be obtained via supercritical CO2 extraction of ginger root.

[0037] In certain embodiments where the composition comprises ginger oleoresin, the ginger oleoresin may be present in the composition in an amount of at least 10% by weight of the composition, such as at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% by weight of the composition. For example, the composition may comprise from about 10% to about 40% ginger oleoresin by weight of the composition, such as from about 15% to about 30% by weight of the composition.

[0038] In certain embodiments, the final composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition.

[0039] For example, the composition may comprise from about 25% (i.e., 30%) to about 35% ginger oleoresin by weight of the composition, the ginger oleoresin comprising from about 11% gingeroids by weight of the ginger oleoresin, providing a composition comprising from about 5% to about 30% gingeroids by weight of the composition.

[0040] The ginger oleoresin that is actually commercialized is a liquid product with a high content of lipids and fatty acids. During the extraction of gingeroids from ginger, and due to the chemical properties of gingeroids, the gingeroid-rich extract is also rich in lipids. Other natural constituents, such as the curcumin extract from turmeric, which is rich in curcuminoids, are in the form of powders with low or very low amounts of fat. These curcuminoids are usually present in the form of crystals.

[0041] In certain embodiments, the ginger oleoresin, defatted oleoresin and mixtures thereof have a lipid content of at least 40%, such as at least 50%, such as at least 70%.

[0042] In certain embodiments, the ginger oleoresin has a lipid content of at least 40%, such as at least 50%, such as at least 70%.

[0043] In certain embodiments, the gingeroids are provided in the form of an extract, such as an oleoresin, and do not form crystals.

[0044] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin wherein the ginger oleoresin comprises at least 50% lipids, such as at least 30% gingeroids and at least 70% lipids.

[0045] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin wherein the ginger oleoresin comprises at least 50% lipids, such as at least 30% gingeroids and at least 70% lipids, and optionally the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0046] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin wherein the final composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition, and optionally the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0047] Gums, such as gum arabic, guar gum, xanthan gum, locust bean gum, gum tragacanth or mixtures thereof, may be present in the compositions of the invention in an amount of about 20% to about 80% by weight of the composition, such as about 50% to about 70% by weight of the composition or about 68% by weight of the composition. In certain preferred embodiments, gums (such as gum arabic) may be present in the compositions of the invention in an amount of about 20% to about 80% by weight of the composition, such as about 50% to about 70% by weight of the composition or about 68% by weight of the composition.

[0048] Natural gums as defined above are usually commercially available and highly refined. In certain embodiments, the gums (such as gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof) are food grade.

[0049] In a preferred embodiment, the gum is gum arabic.

[0050] According to the present invention, (i) Gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin wherein the composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition; the gum (e.g., gum arabic) is present in an amount of about 20% to about 80% by weight of the composition, such as about 50% to about 70% by weight of the composition, or about 68% by weight of the composition; And optionally, the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0051] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin containing gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin A composition comprising: the composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition; the gum (e.g., gum arabic) is present in an amount of about 20% to about 80% by weight of the composition, such as about 50% to about 70% by weight of the composition, or about 68% by weight of the composition; And optionally, the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0052] Saponins are a group of naturally occurring glycosides found mainly in the plant kingdom. They contain a non-carbohydrate aglycone linked to a sugar unit. Saponins are divided into two groups: steroidal saponins and triterpene saponins. Over 100 steroidal saponins and an even larger number of triterpene saponins have been identified so far. (K. Hostettmann, & A. Marston, Saponins (Cambridge University Press 1995). The saponin of the present invention can be of natural or synthetic origin. It can be one or more saponins from the same or different sources.

[0053] For example, the saponin can be obtained or available from plants such as soybean, bean, pea, oat, Solanum species and Allium species, tomato, asparagus, tea, peanut, spinach, sugar beet, yam, blackberry, licorice root, primula root, senega root, tea, liquorice, ginseng, Quillaja (e.g., Quillaja saponaria), Yucca (e.g., Yucca shidigera), and / or gypsophila. In one embodiment, the saponin is Quillaja saponin. In one preferred embodiment, the saponin is not ginger saponin.

[0054] The saponin or saponins used in the present invention may be highly purified or may be a natural extract.

[0055] As used herein, the terms "Quillaja saponin," "yucca saponin," "oat saponin," and the like refer to one or more saponins that may be obtained or obtained from any member of the Quillaja family, or any saponin-containing plant, such as those described above. The Quillaja saponin or mixture of Quillaja saponins (or yucca saponin or mixture of yucca saponins) may be of synthetic or natural origin.

[0056] As will be appreciated by those of skill in the art, the term "available from" as used herein means that the saponin may be obtained from or isolated from the plant, or may be obtained from an alternative source, such as by chemical synthesis or enzymatic production, whereas the term "obtained" as used herein means that the saponin is derived directly from the plant. For example, in one embodiment, the saponin may be a "natural extract containing saponin."

[0057] The at least one saponin may be of natural or synthetic origin.

[0058] "Purified saponin" means one or more saponins of natural or synthetic origin having a concentration of at least about 80%, at least about 90%, at least about 95%, at least about 99%, at least about 99.9% of one or more of the above saponins (such as Quillaja saponin and / or Yucca saponin).

[0059] "Extract containing saponin" means any natural extract containing at least one of said saponins, which may be derived, for example, but not limited to, from soybean, bean, pea, oat, Solanum and Allium species, tomato, asparagus, tea, peanut, spinach, sugar beet, yam, blackberry, licorice root, primula root, senega root, quillaja (such as Quillaja saponaria), yucca (such as Yucca shidigera), and / or gypsophila.

[0060] According to the present invention, the at least one saponin may be derived from a single source or from multiple sources.

[0061] According to the present invention, an extract containing at least one saponin may be derived from a single source or from multiple sources.

[0062] Yucca aloifolia, Yucca angustissima, Yucca arkansana, Yucca baccata, Yucca baileyi, Yucca brevifolia, Yucca campestris, Yucca capensis, Yucca carnerosana, Yucca cernua, Yucca coahuilensis, Yucca constricta, Yucca decipiens, Yucca declinata, Yucca desmetiana, Yucca data, Yucca endlichiana, Yucca faxoniana, Yucca filamentosa, Yucca filifera、Yucca flaccida、Yucca gigantean、Yucca glauca、Yucca gloriosa、Yucca grandiflora、Yucca harrimaniae、Yucca intermedia、Yucca jaliscensis、Yucca lacandonica、Yucca linearifolia、Yucca luminosa、Yucca madrensis、Yucca mixtecana、Yucca necopina、Yucca neomexicana、Yucca pallida、Yucca periculosa、Yucca potosina、Yucca queretaroensis、Yucca reverchonii、Yucca rostrata、Yucca rupicola、Yucca schidigera、Yucca schottii、Yucca sterilis、Yucca tenuistyla、Yucca thompsoniana、Yucca treculeana、Yucca utahensis、またはYucca valid.

[0063] The most abundant Y. schidigera stem / bark saponins are steroidal saponins. They differ in the structure of their aglycone, according to which they are classified as spirostane-type or furostan-type derivatives. The major saponins are glycosides of three C-25 epimeric pairs of sapogenins: sarsapogenin and smilagenin, marcogenin and samogenin, gitogenin and neogotogenin. In both spirostane and furostan derivatives, the C-3 carbohydrate chain is typically a branched oligosaccharide with pentapyranosyl and / or hexopyranosyl units. As far as furostan bidesmosides are concerned, the C-26 linked carbohydrate usually corresponds to a hexopyranose. It should be noted that other derivatives of sapogenins are present as minor compounds in Y. schidigera stem / bark.

[0064] Examples of Quillaja include, but are not limited to, Quillaja brasiliensis, Quillaja lanceolata, Quillaja lancifolia, Quillaja molinae, Quillaja petiolaris, Quillaja poeppigii, Quillaja saponaria, Quillaja sellowiana, or Quillaja smegmadermos. In certain preferred embodiments, the Quillaja is Quillaja saponaria.

[0065] Classical methods currently used in the measurement of steroidal saponins include spectrophotometry, foam height measurement or gravimetry. HPLC / ELSD technique is an accurate and reliable method that gives results of suitable repeatability and reproducibility.

[0066] Those skilled in the art will recognize that the botanical name as used herein may refer to the plant as a whole or any part of the plant, such as the root, stem or trunk, bark, leaves, flowers, stalks or seeds, or combinations thereof. These plant parts may be used fresh or dried, and may be whole, pulverized, crushed, comminuted, or ground. Extracts from any one or more parts of the plant are also contemplated.

[0067] Saponin extracts can be obtained using extraction methods similar to those described previously for ginger extracts. In a preferred embodiment, the solvent is methanol / water (e.g., 70:30 v / v) and the incubation time is 24 hours at ambient temperature. Another extraction solvent can be water alone. In a particular embodiment, the Quillaja-containing material is incubated with water at a temperature of 50-100°C (such as 50-60°C or 100°C). Extraction can be performed using a Soxhlet extractor or by immersion and filtration. Incubation times can be from a few hours (such as 10 hours) to 24 hours or more.

[0068] Extracts containing saponins may include other compounds that are not saponins, such as naturally occurring glycocomponents, polyphenols, salts and sugars.

[0069] In certain embodiments, the purified saponin or "natural extract containing saponin" is from Yucca schidigera and / or Quillaja saponaria. Further, the at least one saponin or extract containing saponin can be selected from steroidal saponins and triterpene saponins, and mixtures thereof.

[0070] In a preferred embodiment, at least one saponin (such as a purified saponin or a saponin extract) is obtained or available from Quillaja (such as Q. saponaria).

[0071] In a preferred embodiment, at least one saponin (such as a purified saponin or a saponin extract) is obtained or available from Yucca (such as Yucca schidigera).

[0072] In another preferred embodiment, at least one saponin (such as a purified saponin or a saponin extract) is obtained or available from Quillaja (such as Q. saponaria) and Yucca (such as Yucca schidigera).

[0073] This application relates to Yucca or Quillaja extracts, juices, or any other products containing saponins, more precisely saponins corresponding to any Yucca or Quillaja saponin structure. Extracts or spray-dried extracts of Y. schidigera or Q. Saponaria in the presence of invert sugar or any other drying support known in the art may be used in this application.

[0074] In certain embodiments of the present invention, the at least one saponin is a natural extract such as Quillaja extract, tea extract, licorice extract, beet root extract, sugar beet extract, ginseng extract, oat extract, yucca extract or mixtures thereof, which comprises (or essentially consists of) at least 5% w / w, or at least 10% w / w, or at least 15% w / w, or at least 20% w / w, or at least 25% w / w, or at least 30% w / w, or at least 35% w / w, or at least 40% w / w, or at least 50% w / w, or at least 60% w / w, or at least 70% w / w, or at least 80% w / w, or at least 95% w / w of saponin. In one embodiment, the saponin component may be a Quillaja extract that comprises at least 60% saponin, such as at least 80% w / w of saponin as defined above (such as triterpene saponins and steroid saponins).

[0075] At least one saponin (such as Quillaja saponin) may be present in the compositions of the invention in an amount of from about 0.1% to about 5% by weight (w / w) of the composition, such as from about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition.

[0076] As will be appreciated by those skilled in the art, the term "obtainable from" as used herein means that the extract (e.g., Quillaja extract) can be obtained from a Quillaja plant (such as Quillaja Saponaria Molina), or can be isolated from a Quillaja plant, or can be obtained from an alternative source, for example, by chemical synthesis or enzymatic production. On the other hand, the term "obtained" as used herein means that the extract is directly derived from a plant, for example, a Quillaja plant.

[0077] In one embodiment, the saponin is an extract obtained or obtainable from Quillaja in the composition and may contain at least 50% saponin by weight, such as at least 60% saponin or at least 65% saponin by weight of the Quillaja extract. For example, the Quillaja used in the composition may contain about 50% to about 80% or about 60% to about 75% saponin by weight of the Quillaja extract.

[0078] The saponin (such as the extract obtained or obtainable from Quillaja japonica) used in the process of the present invention may be in any form, such as a liquid or solid. For example, the saponin (such as the Quillaja japonica extract) may be used in a solid form, such as a powder.

[0079] If present in the composition, other solvents such as water and / or alcohol may be added to the solid or liquid quillaja. For example, quillaja may be present in the composition as an aqueous solution.

[0080] According to the present invention, (i) Gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin wherein the final composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition; the saponin (such as Quillaja saponin) is present in the composition in an amount of about 0.1% to about 5% by weight (w / w) of the composition, such as about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition; And optionally, the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0081] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin containing gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin A composition comprising: the final composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition; the saponin (such as Quillaja saponin) is present in the composition in an amount of about 0.1% to about 5% by weight (w / w) of the composition, such as about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition; And optionally, the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0082] Thus, the present invention also provides a method for producing a method for the treatment of atopic dermatitis. (i) Ginger oleoresin containing gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof, preferably gum arabic; and (iii) at least one saponin A composition comprising: the final composition comprises at least 5% gingeroids by weight of the composition, such as at least 10%, at least 15%, at least 20%, at least 30%, or at least 40%, or at least 50% gingeroids by weight of the composition; the gum (e.g., gum arabic) is present in an amount of about 20% to about 80% by weight of the composition, such as about 50% to about 70% by weight of the composition, or about 68% by weight of the composition; The saponin (such as Quillaja saponin) is present in an amount of about 0.1% to about 5% by weight (w / w) of the composition, such as about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition, and optionally the composition is a dry composition comprising particles having an average diameter of 150-300 and a D90 of 280-500.

[0083] The composition may optionally include a food acceptable alkali metal carbonate or alkaline earth metal carbonate, such as calcium carbonate. The alkali metal carbonate or alkaline earth metal carbonate may be present in the composition in an amount of about % to about 20% by weight of the alkali metal carbonate or alkaline earth metal carbonate, such as about 2.5% to about 10% or about 5% by weight of the composition.

[0084] Unless otherwise stated herein, the weight percentages recited are based on the total weight (w / w) of the resulting (dry / liquid) composition.

[0085] The present invention also relates to a process or method for preparing a composition as defined above (or a process or method of preparation of the invention), the process comprising: (i) preparing an aqueous solution of a gum (such as gum arabic) and at least one saponin; (ii) mixing the aqueous solution from (i) with gingeroids and optionally calcium carbonate to obtain an emulsion. In a preferred embodiment, the gingeroids are provided as ginger oleoresin. In an even more preferred embodiment, the ginger oleoresin has a lipid content of at least 40%, such as at least 50%, such as at least 70%.

[0086] In certain embodiments, natural gums may be used as described above (gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof). Thus, in certain embodiments, the present invention relates to a process for preparing a composition as defined above, the process comprising: (i) preparing an aqueous solution of gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or a mixture thereof and at least one saponin; (ii) mixing the aqueous solution from (i) with gingeroids and optionally calcium carbonate to obtain an emulsion. The present invention provides a process including:

[0087] In a preferred embodiment, the gingeroids are provided as ginger oleoresin in liquid form. In an even more preferred embodiment, the ginger oleoresin has a lipid content of at least 40%, such as at least 50%, such as at least 70%.

[0088] In a preferred embodiment, the mixture is homogenized.

[0089] Emulsions obtained using the method of the present invention may have a particle size of 0.9-10, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.5, 0.2-0.8, 0.2-0.9, 0.3, such as 0.9-10 microns, 20-30, such as 0.5-30 microns, such as 20-50, such as 10-50, such as 10-70, such as 10-80, The droplets may have an average diameter of 0.05 to 100 microns, such as 0.05 to 10, such as 0.05 to 9, 0.05 to 8, 0.05 to 6, 0.05 to 5, 0.05 to 3, 0.05 to 2, such as 0.1 to 10, such as 0.1 to 90, such as 0.1 to 50, such as 0.1 to 100.

[0090] In certain embodiments, the droplets may have an average diameter of about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or 45 microns.

[0091] The droplet size of the emulsion formation step (ii) may also be expressed as D90, which describes the diameter at which 90 percent of the distribution has a smaller droplet size and 10 percent has a larger droplet size.

[0092] Emulsions obtained using the method of the present invention may have a particle size of 0.9-10 microns, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.8, 0.2-0.9, 0.3-0, such as 0.9-10 microns, 20-30, such as 0.5-30 microns, such as 20-50, such as 10-50, such as 10-70, such as 10-80, such as 0.9-10, 0.5-1, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.8, 0.2-0.9, 0.3-0 The droplets may have a particle size with a D90 of 0.05 to 500 microns, such as 0.1 to 10, such as 0.1 to 90, 0.1 to 50, such as 0.1 to 100, such as 0.9, 0.3 to 1, 0.1 to 10, 0.1 to 9, 0.1 to 8, 0.1 to 6, 0.1 to 5, 0.1 to 3, 0.1 to 2, 0.1 to 1, such as 0.05 to 10, 0.05 to 9, 0.05 to 8, 0.05 to 6, 0.05 to 5, 0.05 to 3, 0.05 to 2.

[0093] In certain embodiments, the D90 is about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 or 45 microns.

[0094] The process may optionally include a step of drying the product of (ii) to obtain a composition comprising particles having an average diameter of from about 5 microns to about 1000 microns, such as from 100 to 500 microns, such as from 200 to 450 microns.

[0095] Drying of the product may be carried out using standard techniques known to those skilled in the art, such as spray drying.

[0096] In certain embodiments, the dry product is free of nanoparticles or the dry product contains less than 10% (by number) of particles having at least one dimension less than 500 nm.

[0097] In certain embodiments, the particles of the dry product may be 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 400, 500, 600, 700, 80 ...500, 600, 800, 90, 100, 150, 200, 250, 300, 400, 500, 600, 90, 100, 150, 200, 250, 300, 400, 500, 600, 90, 100, 150, 250, 400, 500, 600, 90, 100, 150, 250, 300, 400, 500, 600, 90, 100, 150, 250, 400, 500, 700, 800, 900, 100, 150, 250, 400, 500, 100, 150, 250, 400, 500, 100, 150, 250, 400, 500, 100, 150, 250, 400, The particles may have an average diameter of from about 5 microns to about 1000 microns, such as from 50, 500, 600, 700, 800, 900 microns to about 800, 700, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 microns (this phraseology includes all combinations of each increasing number to any one of the decreasing numbers).

[0098] Particle size may also be expressed as D90. In certain embodiments, the particles of the dry product may be 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 450, 500, 600, 700, 800, 90, 100, 150, 200, 250, 300, 400, 450, 500, 800, 900, 100, 150, 200, 250, 300, 400, 450, 5 ... It may have a D90 of from about 5 microns to about 1000 microns, such as 600, 700, 800, 900 microns to about 800, 700, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 microns (this phraseology includes all combinations of each increasing number to any one of the decreasing numbers).

[0099] In a preferred embodiment of the process of the present invention, the gingeroids are provided as ginger oleoresin. In an even more preferred embodiment, the ginger oleoresin has a lipid content of at least 40%, such as at least 50%, such as at least 70%, and a gingeroid content of at least 10%, such as at least 17%, such as at least 30% w / w gingeroids.

[0100] For example, the present invention relates to a process for preparing a composition as defined above, the process comprising the steps of: (i) preparing an aqueous solution of gum arabic and at least one saponin; (ii) mixing the aqueous solution from (i) with gingeroids (such as ginger oleoresin), and optionally calcium carbonate, to obtain an emulsion; and (iii) drying the product of (ii) to obtain a composition comprising particles having an average diameter of 150-300 and a D90 of 280-500. A process may be provided, comprising:

[0101] After drying (such as spray drying), the particles may be blended, crushed, milled and / or compressed to provide a more uniform size.

[0102] Typically, in the process of the present invention, the gingeroids may have a purity of about 5% to about 100% by weight of the gingeroid source, i.e., the ginger extract may contain about 5% to about 100% gingeroids, such as about 5% w / w, 10% w / w, 20%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or 90% to about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50% or 45% w / w gingeroids, based on the percentage of the total weight of the extract. In a preferred embodiment, the gingeroids may have a purity of 20% to 40%, such as about 30% w / w. In certain embodiments, the ginger extract may have at least 5% w / w gingeroids, such as at least 20%, such as at least 10%, such as at least 30% w / w gingeroids.

[0103] Typically, in the process of the present invention, the weight concentration of gingeroids or ginger oleoresin in the aqueous solution may be from about 1% to about 95%, such as from about 5% to about 80% or from about 7% to about 40% w / w.

[0104] In the process of the present invention, an aqueous gum solution (such as a gum arabic solution) may be prepared by mixing a gum (such as gum arabic) with water.

[0105] The aqueous gum (eg, gum arabic) solution may have a weight concentration of gum (eg, gum arabic) of about 20% to about 80%, such as about 40% to about 60% w / w.

[0106] Typically, an aqueous solution of gingeroids or ginger oleoresin and an aqueous solution of gum arabic are mixed using stirring.

[0107] In the process of the present invention, the saponin (such as the extract obtained or obtainable from Quillaja saponaria) may be as defined above in relation to the composition.

[0108] The saponin (such as an extract obtained or obtainable from Quillaja japonica) used in the process of the present invention may be in any form, such as a liquid or solid. For example, the saponin (such as an extract obtained or obtainable from Quillaja japonica) may be used in a solid form, such as a powder.

[0109] Typically, in the process of the present invention, at least one saponin (such as Quillaja saponin) may be present in the final composition of the present invention in an amount of from about 0.1% to about 5% by weight of the composition, such as from about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition.

[0110] In the process of the present invention, the saponin (which may be provided as Quillaja extract) may be mixed using agitation.

[0111] The mixture of an aqueous solution containing gum arabic and a saponin (such as Quillaja) mixed with a gingeroid (such as ginger oleoresin) as defined above provides an emulsion.

[0112] The process of the invention may optionally include a step of removing additional solvent as necessary to provide a substantially dry product, i.e. a product from which at least 90%, such as at least 95% or 99% of the water present has been removed. Additionally, a pasteurization step may be performed.

[0113] As mentioned above, the compositions of the present invention may be in the form of an emulsion, or the compositions may be in the form of a solid, for example in the form of a powder.

[0114] As used herein, the term "emulsion" refers to a type of lipid dispersion formed by combining two liquids that do not normally mix. Typically, one of the liquids contains a dispersion of the other liquid.

[0115] The terms "colloid" and "emulsion" are sometimes used interchangeably, however, as used herein, the term emulsion applies when both phases of the mixture are liquid (ginger oleoresin as the first liquid and an aqueous solution of saponins and gums as the second liquid).

[0116] A colloidal solution, sometimes specified as a colloidal suspension, is a mixture in which solid particles are regularly suspended in a fluid. In a preferred embodiment, the product of step (ii) is an emulsion rather than a colloidal solution.

[0117] In certain embodiments of the compositions of the invention, where the composition is in the form of an emulsion, the droplets may be 0.9-10, such as 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.5, 0.2-0.8, such as 0.9-10 microns, 20-30, such as 0.5-30 microns, such as 20-50, such as 10-50, such as 10-70, such as 10-80. 0.05-100 microns, such as 0.2-0.9, 0.3-0.9, 0.3-1, 0.1-10, 0.1-9, 0.1-8, 0.1-6, 0.1-5, 0.1-3, 0.1-2, 0.1-1, 0.05-10, 0.05-9, 0.05-8, 0.05-6, 0.05-5, 0.05-3, 0.05-2, such as 0.1-10, 0.1-90, such as 0.1-50, 0.1-100.

[0118] In certain embodiments, the droplets may have an average diameter of about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or 45 microns.

[0119] Emulsions may be 0.9-10 microns, 0.5-1, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.8, 0.2-0.9, 0.3-0.9, 0.9-10 microns, 20-30, 0.5-30 microns, 20-50, 10-50, 10-70, 10-80, 0.9-10, 0.5-1, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, 0.1-0.7, 0.1-0.9, 0.2-0.6, 0.2-0.8, 0.2-0.9, 0.3-0.9, 0.9-10 microns ... The droplets may have a D90 of 0.05 to 500 microns, such as 0.1 to 10, 0.1 to 9, 0.1 to 8, 0.1 to 6, 0.1 to 5, 0.1 to 3, 0.1 to 2, 0.1 to 1, such as 0.05 to 10, 0.05 to 9, 0.05 to 8, 0.05 to 6, 0.05 to 5, 0.05 to 3, 0.05 to 2, such as 0.1 to 10, 0.1 to 90, 0.1 to 50, such as 0.1 to 100, such as 0.3 to 1.

[0120] In certain embodiments, the D90 is about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 or 45 microns.

[0121] As previously mentioned, the emulsion may then be dried to obtain a solid.

[0122] When the composition is in the form of a solid, such as a powder, the composition may be, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 400, 500, 600, 700, 800, 90, 100, 150, 200, 250, 300, 400, 500, 600, 800, 90, 100, 150, 200, 250, 300, 400, 500, 600, 90, 100, 150, 200, 250, 300, 400, 500, 600, 100, 150, 200, 250, 300, 400, 500, 600, 100, 150, 25 ...50, 400, 500, 600, 100, 150, 250, 400, 500, 600, 100, 150, 250, 400, 500, 600, 100, 150, 250, 400, 500, 600 It may include particles having an average diameter of from about 5 microns to about 1000 microns, such as from 50, 500, 600, 700, 800, 900 microns to about 800, 700, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 microns (this phraseology includes all combinations of each increasing number to any one of the decreasing numbers).

[0123] Particle size may also be expressed as D90. In certain embodiments, the particles of the dry product may be 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 450, 500, 600, 700, 800, 90, 100, 150, 200, 250, 300, 400, 450, 500, 800, 900, 100, 150, 200, 250, 300, 400, 450, 5 ... It may have a D90 of from about 5 microns to about 1000 microns, such as 600, 700, 800, 900 microns to about 800, 700, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 microns (this phraseology includes all combinations of each increasing number to any one of the decreasing numbers).

[0124] The particles in the composition may be in the form of micelles.

[0125] After formation of the particles (eg, after drying, such as by spray drying), the particles may be crushed and / or milled (such as by ball milling) to provide a more uniform size.

[0126] The size of the particles can be measured by method CQ-MO-304 (using a Mastersizer Malvern instrument). The droplet size can be measured using a Mastersizer.

[0127] The composition may be provided in solid or liquid form, preferably a solid form such as a powder. Solid form encompasses that the compound may be provided as an amorphous solid, or as a crystalline or partially crystalline solid.

[0128] The compositions are typically highly water soluble and / or stable at a pH of 4 or greater, such as a pH of about 4 to about 7.

[0129] The term water-soluble means that at least about 50%, such as at least about 60%, 70%, 80%, 90% or 95% of the composition is soluble in water at room temperature, i.e., a temperature of about 25°C.

[0130] For the avoidance of doubt, preferences, options, particular features, etc., indicated for a given aspect, feature or parameter of the invention should be considered as disclosed in combination with any and all other preferences, options, particular features, etc., indicated for the same or other aspects, features and parameters of the invention, unless the context dictates otherwise.

[0131] As used herein, the term "about," for example when referring to a measurable value (such as the amount or weight of a particular component in a reaction mixture), refers to a variation of ±20%, ±10%, ±5%, ±1%, ±0.5%, or especially ±0.1% from the specified amount. For example, a ±0.5% variation with respect to the percentage of a component in a composition means a 0.5% variation from the given percentage, i.e., ±0.5% of 10% means a variation of 9.5% to 10.5%.

[0132] According to the invention, the composition may be provided in the form of, or may form part of, a nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a herbicide, a dietary supplement, a fragrance or flavoring, a pharmaceutical or veterinary preparation, an oenological or cosmetic formulation.

[0133] The present invention therefore also refers to a nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, an aroma or flavoring agent, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation comprising the composition of the present invention as defined above.

[0134] For example, the invention provides a nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a nutritional supplement, a fragrance or flavoring, a pharmaceutical or veterinary preparation, an oenological or cosmetic formulation that comprises, consists of or consists essentially of the composition of the invention (i.e. at least 90% w / w of the nutraceutical formulation, human or animal feed or food product, nutritional supplement, fragrance or flavoring, pharmaceutical or veterinary preparation, oenological or cosmetic formulation is the composition, such as at least 95%, or 99% or 99.5% being the composition of the invention).

[0135] The present invention also provides the use of the compositions of the present invention in a nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavoring, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation.

[0136] The composition is in the form of a nutraceutical formulation, a human or animal feed or food product (functional food formulation, i.e. food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavouring, a pharmaceutical or veterinary preparation, an oenological or cosmetic formulation or is in the form of a nutraceutical formulation, a human or animal feed or food product (functional food formulation, i.e. food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, If they may form part of a fragrance or flavouring agent, pharmaceutical or veterinary preparation, oenological or cosmetic formulation, a nutraceutical formulation, a feed or food product for humans or animals (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavouring agent, pharmaceutical or veterinary preparation, oenological or cosmetic formulation, may optionally further comprise, as appropriate, a pharmaceutical / veterinary ingredient such as an excipient or carrier or a (functional) food-acceptable ingredient and mixtures thereof.

[0137] As used herein, references to pharma- ceutically acceptable excipients may refer to pharma- ceutically acceptable adjuvants, diluents and / or carriers known to those skilled in the art.

[0138] Food-acceptable ingredients include those known in the art (including those referred to herein as pharma- ceutically acceptable excipients) and can be natural or non-natural, i.e., their structures may or may not occur in nature. In certain instances, food-acceptable ingredients originate from natural compounds and can be subsequently modified (e.g., maltodextrin).

[0139] "Pharmaceutically / nutraceutically acceptable" means that the additional components of the composition are sterile and pyrogen-free. Such components must also be "acceptable" in the sense of being compatible with the composition and not harmful to its recipient. Thus, "pharmaceutically acceptable" includes any compound used to form part of a formulation that is intended to act merely as an excipient, i.e., not to have biological activity of its own. Thus, pharmaceutically acceptable excipients are generally safe, non-toxic, and not biologically or otherwise undesirable.

[0140] Where the composition forms part of a nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavouring, a pharmaceutical or veterinary preparation, an enological formulation or a cosmetic formulation, the composition may be present in an amount of about 0.01%, 0.1%, 1%, 5%, 10%, 20% by weight of the nutraceutical formulation, the human or animal feed or food product, the dietary supplement, the fragrance or flavouring, the pharmaceutical or veterinary preparation, the enological formulation or the cosmetic formulation. The nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavoring, pharmaceutical or veterinary formulation, oenological formulation or cosmetic formulation may be present in the nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavoring, pharmaceutical or veterinary formulation, oenological formulation or cosmetic formulation in an amount of from about 1 to about 99% by weight of the nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavoring, pharmaceutical or veterinary formulation, oenological formulation or cosmetic formulation, such as from about 1% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 80% by weight, 70% by weight, 60% by weight, 50% by weight, 40% by weight, 3 ...

[0141] The skilled artisan will understand that the composition is in the form of a nutraceutical formulation, a human or animal feed or food product (functional food formulation, i.e. food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavoring, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation or a nutraceutical formulation, a human or animal feed or food product (functional food formulation, i.e. food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, a fragrance or flavoring, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation. It will be understood that, in either case, the nutraceutical formulation, human or animal feed or food product (such as a functional food formulation, i.e., a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), dietary supplement, fragrance or flavoring, pharmaceutical or veterinary preparation, oenological formulation or cosmetic formulation comprises the composition, may be administered to a patient or subject (e.g., a human or animal patient or subject) by any suitable route, such as oral, rectal, nasal, pulmonary, buccal, sublingual, transdermal, intracisternal, intraperitoneal, and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) routes.

[0142] In particular, the compositions of the invention, as well as nutraceutical formulations, human or animal feed or food products (such as functional food formulations, i.e. foods, beverages, feeds or pet foods or food, beverage, feed or pet food supplements), dietary supplements, fragrances or flavorings, pharmaceutical or veterinary preparations, oenological or cosmetic formulations, may be administered orally. In such cases, the pharmaceutical compositions according to the invention may be specifically formulated for administration by the oral route.

[0143] Pharmaceutical or nutraceutical formulations for oral administration include solid dosage forms such as hard or soft capsules, tablets, troches, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings, or they can be formulated to provide controlled release of the active ingredient, such as sustained or extended release, according to methods well known in the art.

[0144] Liquid dosage forms for oral administration include solutions, emulsions, aqueous or oily / oil suspensions, syrups and elixirs.

[0145] Nutritional pharmaceutical formulations, human or animal feed or food products (functional food formulations, i.e. foods, beverages, feeds or pet foods or food, beverage, feed or pet food supplements, dietary supplements, fragrances or flavorings, pharmaceutical or veterinary preparations, oenological or cosmetic formulations described herein, such as those intended for oral administration, may be prepared according to methods known to those skilled in the art, such as by blending the components of the composition.

[0146] Such nutraceutical formulations, human or animal feed or food products (functional food formulations, i.e., food, beverage, feed or pet food or food, beverage, feed or pet food supplements, dietary supplements, fragrances or flavorings, pharmaceutical or veterinary preparations, oenological formulations or cosmetic formulations described herein may contain one or more additional components selected from the group consisting of food ingredients such as sweeteners, flavorings, colorants and preservatives. Tablets may contain one or more active ingredients mixed with non-toxic pharmaceutically acceptable excipients (or ingredients) suitable for the manufacture of tablets. These excipients (or ingredients) may be, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, such as corn starch, maltodextrin or alginic acid; binding agents, such as starch, gelatin or acacia; and lubricants, such as magnesium stearate, stearic acid or talc. The tablets can be uncoated or they can be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period, for example, a time delay material such as glyceryl monostearate or glyceryl distearate can be employed.

[0147] Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solutions and various organic solvents.The examples of solid carriers are lactose, terra alba, sucrose, cyclodextrin, maltodextrin, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid, gum arabic, modified starch and lower alkyl ether of cellulose.The examples of liquid carriers are syrup, peanut oil, olive oil, phospholipids, fatty acids, fatty acid amines, polyoxyethylene and water.In addition, carriers or diluents can include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with wax.

[0148] Depending on the disorder and the patient to be treated, and the route of administration, the compositions of the present invention can be administered in various doses (i.e., therapeutically effective doses administered to patients in need thereof). In this regard, those skilled in the art will recognize that the dose administered to a mammal, particularly a human, in the context of the present invention should be sufficient to produce a therapeutic response in the mammal over a reasonable time frame. Those skilled in the art will recognize that the selection of the exact dose and formulation, as well as the most appropriate delivery regimen, will also be influenced by, among other things, the pharmacological properties of the formulation, the nature and severity of the condition to be treated, and the physical condition and mental acuity of the recipient, as well as the potency of the specific compound, the age, condition, weight, sex and response of the patient to be treated, and the stage / severity of the disease.

[0149] Typically, the composition or nutraceutical formulation, human or animal feed or food product (functional food formulation, i.e. food, beverage, feed or pet food or food, beverage, feed or pet food supplement, dietary supplement, fragrance or flavoring agent, pharmaceutical or veterinary preparation, oenological or cosmetic formulation as defined above is administered to provide gingeroids in an amount of about 10 mg gingeroids, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 70 mg, about 100 mg, about 200 mg, about 300 mg gingeroids. In one embodiment, the composition or nutraceutical formulation, human or animal feed or food product (such as a functional food formulation, i.e., a food, drink, feed or pet food or a supplement to a food, drink, feed or pet food), dietary supplement, fragrance or flavoring agent, pharmaceutical or veterinary formulation, oenological or cosmetic formulation as defined above is administered to provide gingeroid in an amount of about 5 mg / day of gingeroid to about 400 mg / day of gingeroid, such as about 5 mg / day of gingeroid, about 10 mg / day of gingeroid, about 15 mg / day, about 20 mg / day, about 30 mg / day, about 40 mg / day, about 50 mg / day, about 70 mg / day, about 100 mg / day, about 200 mg / day or about 300 mg / day of gingeroid.

[0150] For example, a composition or nutraceutical formulation, human or animal feed or food product (such as a functional food formulation, i.e., a food, drink, feed or pet food or a food, drink, feed or pet food supplement), dietary supplement, fragrance or flavoring, pharmaceutical or veterinary preparation, enological formulation or cosmetic formulation may provide gingeroid in an amount of about 0.08 mg gingeroid per kg body weight to about 6.5 mg gingeroid per kg body weight, such as 1.5 mg gingeroid per kg body weight, 0.2 mg gingeroid per kg body weight, 0.5 mg gingeroid per kg body weight, 1 mg gingeroid per kg body weight, 2 mg gingeroid per kg body weight, 3 mg gingeroid per kg body weight, or 5 mg gingeroid per kg body weight. In certain embodiments, the composition may provide gingeroid in an amount of 1.6 mg gingeroid per kg body weight to 3.4 mg gingeroid per kg body weight.

[0151] In certain embodiments, the gingeroids are on a daily basis per kg of body weight.

[0152] In any event, a physician or other skilled artisan may routinely determine the actual dosage which will be most suitable for an individual patient. The dosages set forth above are exemplary of the average case; there can, of course, be individual instances in which higher or lower dosage ranges are merited, and such are within the scope of this invention.

[0153] The high water solubility and stability of the composition means that the composition can be used to improve the bioaccessibility, bioavailability, bioefficacy and / or bioactivity of gingeroids or ginger oleoresin in mammals.

[0154] The improved bioaccessibility, bioavailability, bioefficacy and / or bioactivity of gingeroids or ginger oleoresins allows the compositions to be used to prevent and / or treat diseases where in the past poor water solubility and stability of gingeroids or ginger oleoresins was an issue.

[0155] Thus, the present invention provides a method for improving the bioaccessibility, bioavailability, bioefficacy and / or bioactivity of a gingeroid or ginger oleoresin in a mammal, comprising administration of said gingeroid or ginger oleoresin in the form of a composition as defined above.

[0156] The method may hereinafter be referred to as the "method of the invention".

[0157] The present invention also provides the use of a composition as defined above for improving the bioaccessibility, bioavailability, bioefficacy and / or bioactivity of a gingeroid or ginger oleoresin in a mammal.

[0158] The use may hereinafter be referred to as "use of the invention".

[0159] In the methods or uses described herein, the improved bioaccessibility, bioavailability, bioefficacy and / or bioactivity of the gingeroid or ginger oleoresin in a mammal may be due to a composition providing improved gastrointestinal tolerance of the gingeroid or ginger oleoresin and / or improved absorption of the gingeroid or ginger oleoresin by intestinal cells and / or improved blood circulation.

[0160] In the methods or uses described herein, the improved bioaccessibility, bioavailability, bioefficacy and / or bioactivity of the gingeroids or ginger oleoresin in a mammal may be due to the composition providing improved water solubility and / or improved stability at a pH of about 4 to about 7.

[0161] Thus, the present invention provides a method for improving the water solubility and / or pH stability of a gingeroid or ginger oleoresin, the method comprising administration of said gingeroid or ginger oleoresin in the form of a composition as defined above.

[0162] The present invention also provides the use of a composition as defined above for improving the water solubility and / or pH stability of a gingeroid or ginger oleoresin.

[0163] The present invention also provides a method for providing sustained release of gingeroids in the intestine of a mammal comprising administration of said gingeroids or ginger oleoresin in the form of a composition of the present invention or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical formulation or veterinary formulation comprising the composition of the present invention.

[0164] The present invention also provides the use of a composition of the present invention or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical formulation or veterinary formulation according to the present invention for providing a sustained release of gingeroids in the intestine of a mammal.

[0165] In the methods or uses described herein, the gingeroid may be selected from the group consisting of 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol or a mixture thereof.

[0166] As described above, the sustained release and improved bioaccessibility, bioavailability, bioefficacy and / or bioactivity of gingeroids or ginger oleoresin allows the composition to be used to prevent and / or treat diseases where poor water solubility and stability of gingeroids or ginger oleoresin was a problem in the past.

[0167] All the different diseases and conditions that can be prevented or treated using ginger extracts and oleoresins (Nguyen Hoang Anh et al. Nutrients 2020, 12, 157) can be treated or prevented using the compositions of the present invention. Some examples of diseases and conditions are listed herein without any kind of limitation.

[0168] The present invention therefore provides a composition as defined above or a nutraceutical formulation, a human or animal feed or food product, a dietary supplement, an aroma or flavouring, a pharmaceutical or veterinary preparation, an oenological or cosmetic formulation as defined above for use in preventing or treating a gastrointestinal disorder, a metabolic disorder primary dysmenorrhea, heavy menstrual bleeding, a metabolic disorder, a sleep disorder (such as insomnia), a neuropsychiatric disorder (such as depression and anxiety), a neurodegenerative disease (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood.

[0169] The present invention also provides a method for preventing or treating gastrointestinal disorders, primary dysmenorrhea, heavy menstrual bleeding, metabolic disorders, sleep disorders (such as insomnia), neuropsychiatric disorders (such as depression and anxiety), neurodegenerative diseases (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood, the method comprising the administration of a composition as defined above or a nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavouring agent, pharmaceutical or veterinary formulation, oenological formulation or cosmetic formulation as defined above to a patient in need thereof.

[0170] The present invention also provides the use of a composition as defined above in the manufacture of a medicament for the treatment or prevention of gastrointestinal disorders, primary dysmenorrhea, heavy menstrual bleeding, metabolic disorders, sleep disorders (such as insomnia), neuropsychiatric disorders (such as depression and anxiety), neurodegenerative diseases (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood.

[0171] The present invention also provides a method for supporting gastrointestinal health in a human or animal in need thereof, the method comprising administering to the human or animal an effective amount of a composition as defined above or a nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavouring agent, pharmaceutical or veterinary formulation, oenological or cosmetic formulation as defined above.

[0172] The present invention provides a composition as defined above, a nutraceutical formulation as defined above, a human or animal feed or food product, a dietary supplement, a fragrance or flavouring agent, a pharmaceutical or veterinary formulation, an oenological formulation or a cosmetic formulation for use in supporting gastrointestinal health.

[0173] Gastrointestinal disorders include, but are not limited to, dyspepsia and other problems related to gastric emptying and dysrhythmia, irritable bowel syndrome (IBS), constipation, hemorrhoids, anal fissures, perianal abscesses, fistulas, perianal infections, diverticular disease, colitis, colon polyps, diarrhea, colorectal cancer, CINV in cancer patients, nausea or vomiting (such as chemotherapy induced nausea and vomiting, pregnancy nausea and vomiting, postoperative nausea and vomiting, hyperemesis gravidarum or motion sickness).

[0174] In preferred embodiments of the uses and methods described therein, the gastrointestinal disorder is selected from dyspepsia, irritable bowel syndrome (IBS), colorectal cancer, nausea or vomiting (such as chemotherapy induced nausea and vomiting, pregnancy nausea and vomiting, postoperative nausea and vomiting, hyperemesis gravidarum or motion sickness).

[0175] Other diseases and ailments can be treated using ginger.

[0176] The present invention therefore provides a composition as defined above, a nutraceutical formulation, a human or animal feed or food product, a dietary supplement, a fragrance or flavouring agent, a pharmaceutical or veterinary formulation, an oenological formulation or a cosmetic formulation as defined above for use in supporting muscle health (such as reducing muscle pain, inflammation and dysfunction induced by exercise or muscle injury, delayed onset muscle soreness, etc.).

[0177] The present invention therefore provides a composition as defined above or a nutraceutical formulation, a human or animal feed or food product, a dietary supplement, a fragrance or flavouring agent, a pharmaceutical or veterinary formulation, an oenological or cosmetic formulation as defined above for use in preventing or treating muscle pain, inflammation and dysfunction induced by exercise or muscle injury, delayed onset muscle soreness.

[0178] The present invention also provides a method for preventing or treating muscle pain, inflammation and dysfunction induced by exercise or muscle injury, delayed onset muscle soreness, comprising the administration of a composition as defined above or a nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavouring agent, pharmaceutical or veterinary formulation, oenological or cosmetic formulation as defined above to a patient in need thereof.

[0179] The present invention also provides the use of a composition as defined above in the manufacture of a medicament for preventing or treating muscle pain, inflammation and dysfunction induced by exercise or muscle injury, delayed onset muscle soreness.

[0180] The present invention also provides a method of supporting muscle health in a human or animal in need thereof, the method comprising administering to the human or animal an effective amount of a composition as defined above or a nutraceutical formulation, human or animal feed or food product, dietary supplement, fragrance or flavouring agent, pharmaceutical or veterinary formulation, oenological or cosmetic formulation as defined above.

[0181] In the methods and uses described herein, the mammal may be a human.

[0182] As used herein, the term "bioavailability" can be defined as the percentage of an ingested component that is available at the site of action for utilization in normal physiological function, as determined through in vivo assays (Guerra A, Etienne-Mesmin L, Livrelli V et al (2012) Relevance and challenges in modeling human gastric and small intestinal digestion. Trends Biotechnol 30:591-600). Bioavailability is the result of three main steps: digestibility and solubility of the element in the gastrointestinal tract; absorption of the element by enterocytes and transport into the circulation; and uptake from the circulation into functional entities or targets (Wienk KJH, Marx JJM, Beynen AC(1999)The concept of iron bioavailability and its assessment.Eur J Nutr 38:51-75;Etcheverry P,Grusak MA,Fleige LE(2012)Application of in vitro bioaccessibility and bioavailability methods for calcium,carotenoids,folate,iron,magnesium,polyphenols,zinc,and vitamins B6,B12,D,and E.Front Physiol 3:1-21).

[0183] As used herein, the term "bioaccessibility" can be defined as the fraction of a compound that is released from its food matrix in the gastrointestinal tract and thus becomes available for intestinal absorption (typically established from in vitro procedures). This encompasses the series of events that occur during food digestion for conversion into potentially bioaccessible materials, but excludes absorption / assimilation through epithelial tissues and presystemic metabolism (both intestine and liver) (Alegria A., Garcia-Llatas G., Cilla A. (2015) Static Digestion Models: General Introduction. In: Verhoeckx K. et al. (eds) The Impact of Food Bioactives on Health. Springer, Cham).

[0184] As used herein, the term "bioactivity" can be defined as how a nutrient or bioactive compound is transported to reach target tissues, how it interacts with biomolecules, the metabolism or biotransformation it may undergo, and the production of biomarkers and physiological responses induced (Alegria A., Garcia-Llatas G., Cilla A. (2015) Static Digestion Models: General Introduction. In: Verhoeckx K. et al. (eds) The Impact of Food Bioactives on Health. Springer, Cham).

[0185] Gastrointestinal disorders include, but are not limited to, dyspepsia and other problems related to gastric emptying and dysrhythmia, irritable bowel syndrome (IBS), colorectal cancer, CINV in cancer patients, nausea or vomiting (such as chemotherapy induced nausea and vomiting, pregnancy nausea and vomiting, postoperative nausea and vomiting, hyperemesis gravidarum or motion sickness).

[0186] Metabolic disorders that can be treated with the compositions of the present invention include, but are not limited to, glucose control, insulin sensitivity, type 2 diabetes, insulin resistance, reduction of obesity-related metabolic disorders (such as diabetes), and the like.

[0187] For the avoidance of doubt, in this specification, when the term "comprising" or "comprises" is used, it means that the extract or composition described must contain the listed components, but may optionally contain additional components. When the term "consisting essentially of" or "consists essentially of" is used, it means that the extract or composition described must contain the listed components, and may also contain small amounts (e.g., up to 5% by weight, or up to 1% by weight or 0.1% by weight) of other components, so long as any additional components do not affect the essential properties of the extract or composition. When the term "consisting of" or "consists of" is used, it means that the extract or composition described must only contain the listed components.

[0188] It is also intended that the terms "comprise" or "comprises" or "comprising" may be replaced with "consist" or "consisting" or "consisting essentially of" where appropriate throughout this application.

[0189] The terms "a" and "an" are defined as one or more, unless otherwise stated or constrained by other language herein. An element or feature following "a" or "an" may be interpreted as one recited element or feature, or as two or more elements or features. For example, gum may be interpreted as one type of gum, or as multiple types of gum (e.g., gum arabic and guar gum).

[0190] The terms "about," "approximately," "essentially," "substantially," and any other versions thereof, or any other similar relative or similar approximation terms, are defined as close to what would be understood by one of ordinary skill in the art. As non-limiting exemplary embodiments, these terms are defined to be within 20% of the recited value, or within 10% of the recited value, or within 5% of the recited value, or within 4% of the recited value, or within 3% of the recited value, or within 2% of the recited value, or within 1% of the recited value, or within 0.5% of the recited value, or within 0.25% of the recited value, or within 0.1% of the recited value.

[0191] It should be understood that when amounts in weight percent are set forth in this disclosure, any and all amounts within the range, including the endpoints, should be considered expressly disclosed. For example, a disclosure of "a range of about 1 to about 10" should be read as indicating any and all possible numbers along a continuum between about 1 and about 10. It should be understood that the inventors recognize and understand that any and all data points within the range should be considered specified, and that the inventors own the entire range and all points within the range.

[0192] For the avoidance of doubt, preferences, options, particular features, etc., indicated for a given aspect, feature or parameter of the invention should be considered as disclosed in combination with any and all other preferences, options, particular features, etc., indicated for the same or other aspects, features and parameters of the invention, unless the context dictates otherwise.

[0193] The following text provides an extensive description of many different embodiments of the present disclosure. The description should be construed as merely illustrative and does not describe all possible embodiments, as describing all possible embodiments would be impractical, if not impossible. It will be understood that any feature, characteristic, component, composition, ingredient, product, step, or methodology described herein can be deleted, combined, or substituted, in whole or in part, with any other feature, characteristic, component, composition, ingredient, product, step, or methodology described herein. Numerous alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and would still fall within the scope of the claims.

[0194] Preferred and / or optional features of the invention will now be presented. Any aspect of the invention may be combined with any other aspect of the invention unless the context requires otherwise. Any preferred or optional feature of any aspect may be combined, alone or in combination, with any aspect of the invention, as well as with any other preferred or optional feature, unless the context requires otherwise. [Brief description of the drawings]

[0195] [Figure 1] Figure 1 shows the results of visual inspection of the samples. [Diagram 2] Figure 2 shows the Lab* development. [Diagram 3]Figure 3 shows a general scheme of the adapted SHIME system used to test the survival of probiotics in the gastrointestinal tract. The system consists of one reactor used to simulate first the gastric and then the small intestinal environment, both under fasting or fed conditions. In this experiment, the system is coupled with a Caco-2 transport assay. [Figure 4] Figure 4: Bioaccessibility of total gingeroids after passage through the upper gastrointestinal tract (GIT). The % bioaccessibility was calculated based on a theoretical final concentration of 20 or 10 μg gingeroids / mL in the apical compartment at the start (i.e., ([AP 0 hours] / 20 or 10)*100). Bars represent the mean ± SEM (n=3). [Diagram 5] Figure 5 shows gingeroid bioavailability calculated as % transport × % bioaccessibility, where % transport is defined as ([BL 4 hr] / 20 or 10)*100, where 20 or 10 μg / mL is the theoretically added concentration of total gingeroids to the apical compartment at 0 hr. [Figure 6] Figure 6 shows gingeroid bioavailability calculated as % absorption x % bioaccessibility, where % absorption is defined as ([BL 4 hr] + [cells 4 hr] / 20 or 10) * 100, where 20 or 10 μg / mL is the theoretically added concentration of total gingeroids to the apical compartment at 0 hr. [Figure 7] FIG. 7 is a microscopic view of dry composition A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0196] Working Example The invention is further illustrated by reference to the following non-limiting examples.

[0197] Example 1 - Preparation of a composition of the present invention Composition A is prepared as follows: First, aqueous solutions of gum arabic and quillaja extract (having more than 65% saponin) were prepared.

[0198] The aqueous solutions of gum arabic and quillaja were then mixed with ginger oleoresin (total gingeroids >30% and lipid content >70% w / w). The % w / w of each component is presented in Table 1.

[0199] The ingredients are mixed to create an emulsion, which is then dried using a spray drying apparatus (Composition A).

[0200] Example 2. Characterization of the compositions of the present invention [Table 1] [Table 2]

[0201] Dried product particles were measured using a Keyence VHX-700 digital microscope. The Mastersizer instrument measures particle size and particle size distribution by laser diffraction (laser light scattering) (CQ-MO-304 method).

[0202] In FIG. 7, it can be seen that Composition A particles exhibit small spherical structures resulting from the dried emulsion.

[0203] 2.1. Materials and Methods [Table 3] Suggested dosage: 10 and 20 mg of gingeroids in a 60 mL beverage. Process Steps: Weigh all ingredients into a glass bucket, fill with water and stir until completely homogenized. [Table 4] [Table 5] Characterization: Photography (visual overview, sedimentation observation), pH control (effect of extracts in formulation), ΔLab* (to evaluate color + sedimentation correction), turbidity measurement (to evaluate cloudiness)

[0204] After one week, a yellow ring was observed on the top of the reference sample bottle (ginger 5%). Many particles (powder) can be seen in the suspension in the reference bottle (Figure 1). Over a two-week period, we do not visually observe any significant color change for any sample, including the Composition A formulation, except for the reference (ginger 5%). This phenomenon does not appear in the Composition A formulation with the equivalent gingeroid dose (see Figure 1).

[0205] After 2 weeks, the reference sample (5% ginger) has a ΔE of more than 10, while Composition A has a ΔE of less than 3. The inventors have not observed any lab changes in the formulation of the present invention (Composition A) over a period of 1-2 weeks. * There has been no development either (Figure 2).

[0206] Example 3 - Simulator of the human intestinal microbial ecosystem (SHIME®) The objective of this study was to evaluate the absorption of gingeroids from the four test formulations at the same levels of gingeroids, 20 mg and 10 mg, for Composition A after passage through the human upper GIT under fasting conditions. For this purpose, a simulator of the human intestinal microbial ecosystem (SHIME®) was used in conjunction with a Caco-2 transport assay (Figure 3).

[0207] 3.1 Materials and Methods The reactor setup was adapted from SHIME, which represents the adult gastrointestinal tract (GIT), as described by Molly et al. (1993). SHIME consists of a series of five reactors simulating different parts of the human gastrointestinal tract. The first two reactors are of the fill-and-draw principle to simulate the different steps of food intake and digestion, with peristaltic pumps adding defined amounts of SHIME feeding fluid as well as pancreatic and bile juices to the stomach and small intestine compartments, respectively, and emptying each reactor after a specified interval. The last three compartments (continuously stirred reactors with constant volume and pH control) simulate the ascending, transverse and descending colons. Retention times and pH of the different vessels are chosen to resemble in vivo conditions in the different parts of the gastrointestinal tract.

[0208] 3.2 Upper GIT experiment A typical experiment performed by ProDigest to evaluate the bioaccessibility of active substances makes use of an adapted SHIME® system that represents physiological conditions of the stomach and small intestine in the same reactor over time (Figure 3). A specific gastric suspension is added to the reactor to mimic fed or fasted conditions. After this, standardized enzymes and bile solutions are added to simulate small intestinal conditions. Incubation conditions (pH profile, incubation time) are optimized to resemble the in vivo conditions in different regions of the gastrointestinal tract for fasted or fed conditions.

[0209] To ensure that simulations of the adult upper GIT under fasted and fed conditions are performed under the most representative conditions, ProDigest recently updated its in-house developed protocols based on the InfoGest consensus method together with recent in vivo data.

[0210] Within the COST Action InfoGest, a consensus digestion method (which virtually simulates feeding conditions) was recently (2015) developed with the aim of enhancing the comparison of digestion experiments between research teams2.

[0211] However, the updated ProDigest protocol contains such a dynamic pH profile, as it more closely mimics in vivo conditions. The conditions applied are summarized below: Gastric phase (fasting state) Incubate for 45 minutes at 37°C, pH=2.0, with mixing via agitation. ·Addition of 4x lower pepsin and phosphatidylcholine levels4. -Only salts and mucin are provided as background medium.

[0212] 3.3. Small intestinal phase (fasting state) Recent publications on the differences in human duodenal fluid in fasted and fed conditions further necessitated an update of the in-house developed protocol to simulate human upper GIT conditions. Based on Riethorst et al. (2015), the following parameters were adapted in comparison to the fed protocol: While mixing via stirring, the pH is first automatically increased from 2.0 to 5.5 within 5 min, then the pH is gradually increased from 5.5 to 7.0 during a 3 h incubation at 37 °C, the pH is automatically controlled by the software (standard protocol). For pancreatic enzymes, a live animal pancreatic extract (pancreatin) is used which contains all the relevant enzymes in specific proportions. · For bile salts, 3 mM bovine bile extract is commonly supplemented (bovine bile is closer to human than porcine with respect to taurocholate and glycocholate). · Sampling at t = 3 h ( SI end ) for coupling with Caco-2 transport assay.

[0213] 3.4. Transport assay in Caco-2 cells Caco-2 cells (HTB-37; American Type Culture Collection) were seeded on 12-well semipermeable membranes (0.4 μm pore size) coated with collagen (type I) from rat tail and grown in complete medium (Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% heat-inactivated fetal bovine serum, 10 mM HEPES and 1× antibiotic-antimycotic) for 21 days with 3 medium changes / week. After 21 days, transepithelial electrical resistance (TEER) was measured (=0 h time point) to assess barrier integrity. The monolayer was then washed and pre-equilibrated in transport medium (HBSS+10 mM HEPES). The cells were treated apically with upper GIT medium at a concentration of 20% in transport medium. After 4 h, TEER was measured again (=4 h time point) and apical and basal fractions were collected to determine gingeroid bioavailability. Additionally, cells were lysed in PBS containing 20% ​​EtOH and 0.1% Tween-20. The apical fraction at time 0 was also included to determine bioavailability. Finally, 100 μL of apical medium at 4 h of incubation was collected for use in the LDH assay.

[0214] 3.5. Test Products The test formulations and their test doses investigated in this phase of the project are shown in Table 1. Formulations were added at the beginning of the gastric phase. All experiments were performed in biological triplicates to account for biological variability. [Table 6] [Table 7]

[0215] 3.6. Statistics All statistical tests were performed using Graphpad Prism software version 8.3.0 (San Diego, USA). Statistically significant differences between treatments are shown within fasting conditions.

[0216] Statistically significant differences between gingeroid concentrations of Composition A (20 mg), Composition A (20 mg), and Composition B (20 mg) were shown in fasting conditions using a conventional one-way ANOVA with Dunnett's multiple comparison test. * ) or Composition A (10 mg) ($). * ) or ($) = p < 0.05;( ** ) or ($$) = p < 0.01;( *** ) or ($$$)=p<0.001 and ( **** ) or ($$$$)=p<0.0001.

[0217] 3.7.Result summary. The bioaccessibility, defined as the gingeroids available after intestinal degradation, was highest from ginger 5% and composition A compared to ginger powder and ginger oleoresin (Figure 4). The bioavailability, defined as the bioaccessibility taking into account the transport and absorption of total gingeroids, was highest from composition A compared to all other formulations (Figures 5 and 6).

[0218] 3.7.1 Outcome 1: Bioaccessibility The bioaccessibility of the products after passage through the upper GIT was calculated based on the measured concentration in the apical compartment at time 0 h and the theoretically added concentration of total gingeroids (i.e., ([AP 0 h] / 20 or 10) * 100) (Figure 4).

[0219] From this, it could be concluded that the bioaccessibility of total gingeroids from composition A was the highest compared to the other formulations (Figure 4). Furthermore, the bioaccessibility of total gingeroids from composition A at a dose of 20 mg was significantly higher compared to all formulations. In contrast, the bioaccessibility from the lower dose of composition A at 10 mg was not significantly different from the oleoresin and ginger powder formulations at 20 mg. Composition A 10 mg was significantly lower compared to Ginger 5% 20 mg, but less significantly compared to Composition A 20 mg.

[0220] Figure 4 shows the bioaccessibility of total gingeroids after passage through the upper gastrointestinal tract (GIT). The total gingeroids concentration present in the apical sample at time 0 hours was measured. Products were incubated under fasted upper gastrointestinal tract (GIT) conditions at concentrations corresponding to an effective dose of either 20 mg or 10 mg of gingeroids. Based on the theoretical final concentration of 20 or 10 μg gingeroids / mL in the apical compartment at the start, the % bioaccessibility was calculated (i.e., ([AP 0 hours] / 20 or 10) * 100). Bars represent the mean ± SEM (n = 3). * ) represents a statistically significant difference between 20 mg of Composition A and other treatments. ($) represents a statistically significant difference between 10 mg of Composition A and other treatments. ($)=p<0.05; ( ** ) or ($$) = p < 0.01;( *** )=p<0.001.

[0221] 3.7.2. Results 2a and b: Bioavailability The bioavailability of total gingeroids in Caco-2 transport assay was then calculated taking into account the bioaccessibility in two different ways: Results 2a: First, gingeroid bioavailability was calculated as % transport × % bioaccessibility. % transport was calculated as ([BL 4 h] / 20 or 10) * Defined as 100, 20 or 10 μg / mL being the theoretically added concentration of total gingeroids to the apical compartment at time 0, the bioavailability of total gingeroids from the 20 mg dose of Composition A was significantly higher than other formulations including Composition A 10 mg of gingeroids (FIG. 5). Meanwhile, the lower dose of Composition A at 10 mg was not statistically significant against any of the formulations showing similar percentage bioavailability against the other three formulations with a 2-fold lower starting gingeroid concentration.

[0222] Figure 5 shows the bioavailability of total gingeroids in the GIT-coupled Caco-2 transport assay. Bioavailability is expressed as % transport of total gingeroids to the basolateral compartment upon 4 h of incubation x % bioaccessibility (i.e., % transport = ([BL 4 h] / [20 or 10]). * 100 and bioavailability % ([AP 0 hours] / 20 or 10) * 100). Products were incubated under fasted upper gastrointestinal (GIT) conditions at concentrations corresponding to effective doses of either 20 mg or 10 mg of gingeroids. Bars represent the mean ± SEM (n=3). * ) represents a statistically significant difference between 20 mg of Composition A and other treatments. ($) represents a statistically significant difference between 10 mg of Composition A and other treatments. ( * ) or ($) = p < 0.05;( ** )=p<0.01.

[0223] Results 2b. Second, gingeroid bioavailability was calculated as % absorption × % bioaccessibility. % absorption was calculated as ([BL 4 hr] + [cells 4 hr] / 20 or 10). * 100, 20 or 10 μg / mL is the theoretically added concentration of total gingeroids to the apical compartment at time 0. The bioavailability of total gingeroids from the 20 mg dose of Composition A was significantly higher than other formulations including Composition A 10 mg of gingeroids (FIG. 6). Meanwhile, the low dose of Composition A at 10 mg was not statistically significant against any of the formulations showing similar percentage bioavailability against the other three formulations with 2-fold lower starting gingeroid concentrations.

[0224] Figure 6 shows the bioavailability of total gingeroids in the GIT-coupled Caco-2 transport assay. Bioavailability is expressed as % absorption x % bioaccessibility of total gingeroids into the basal compartment and cells upon 4 h of incubation (i.e., % absorption = ([BL 4 h] + [cells 4 h] / [20 or 10]). * 100 and bioavailability % ([AP 0 hours] / 20 or 10) * 100). Products were incubated under fasted upper gastrointestinal (GIT) conditions at concentrations corresponding to effective doses of either 20 mg or 10 mg of gingeroids. Bars represent the mean ± SEM (n=3). * ) represents a statistically significant difference between 20 mg of Composition A and other treatments. ($) represents a statistically significant difference between 10 mg of Composition A and other treatments. ( * ) or ($) = p < 0.05;( ** )=p<0.01.

[0225] In conclusion, at similar levels of gingeroid concentration, the bioaccessibility and bioavailability of total gingeroids was highest for the Composition A formulation compared to ginger 5%, ginger powder, and ginger oleoresin. Furthermore, Composition A used at a lower dosage of 10 mg had no difference in bioaccessibility or bioavailability compared to the other formulations at 20 mg. This result demonstrates that by lowering the dosage of Composition A by two-fold, the bioavailability and bioaccessibility are equivalent to a two-fold higher concentration of gingeroids in ginger 5%, ginger powder, and ginger oleoresin.

[0226] Example 4. In vivo testing. The objective of this study was to evaluate the absorption of gingeroid metabolites, including free 6,8,10 gingerol and free glucuronide and sulfate metabolites of 6,8,10 shogaol, from three formulations: dry ginger powder, ginger 5% and composition A (formulation in the table below). [Table 8]

[0227] Materials and Methods Ginger samples were subjected to pharmacokinetic studies using an in vivo model involving oral administration to mice. All animals were provided by the Cell for Cell Laboratory Animal Center under animal care protocol number E-005-20. Pharmacokinetic studies were performed in male BALB / c mice (7-9 weeks old, weighing 20-25 g) randomly divided into three groups (n=5) maintained under a controlled environment at 22°C with a 12-h light-dark cycle. Food and water were provided ad libitum and all mice were acclimated for 1 week before the study. Before the study, mice were fasted for 1.5 h and marked on the tail. Ginger powder was suspended in water to obtain a concentration of 2.5 mg / mL in the gavage solution. Mice were administered 6.3 mg / kg body weight in a single dose by intragastric administration using a rigid administration cannula, and tramadol (0.5 mg / mL of tramadol hydrochloride - Drug Pharma) was injected subcutaneously to avoid pain during administration. Blood samples were collected at different fixed times (0.25, 0.5, 1, 2, 4, 8 hours) after gavage. Each time, ketamine / xylazine anesthesia was used as the euthanasia procedure, and then blood samples were taken from the celiac artery. Whole blood was collected in tubes containing EDTA, and plasma was obtained by centrifugation at 7500 rpm for 15 minutes at 4°C. Samples were then stored in aliquots and frozen at -80°C until analysis.

[0228] 4.2. Sample preparation: To control the retention time stability and to correct for system deviations, calibration curves were constructed in the range 2-2500 ng / mL for each of the six gingeroids (Phytolab, Vestenbergsgreuth, Germany) by adding 25 ng / mL PAV (pelargonic acid vanillylamide, Merck, Darmstadt, Germany) as an internal standard. Methanol was used as diluent for each stock standard solution. For the determination of free gingeroids, exactly 200 μL of the internal standard solution (31.25 ng / mL in methanol) was loaded onto 50 μL of plasma sample in a Captiva ND 96-well plate (Agilent number A5969002). After mixing (30 s) and filtering (under vacuum), the eluent is ready to be injected into the LC / MS system. For the determination of total conjugated gingeroid metabolites (glucuronide and sulfate metabolites), 40 μL of plasma sample was mixed with 40 μL of enzyme solution (glucuronidase 1000 units / mL, Sigma no. G7017; or sulfatase, Sigma no. S9626, 100 units / mL, both in acetate buffer pH 5.0) for 1 h at 37 °C. After this hydrolysis step, 50 μL of solution is mixed as well with 200 μL of methanol (containing internal standard) in a Captiva ND 96-well plate. After mixing (30 s) and filtration (under vacuum), the eluent is ready to be injected into the LC / MS system.

[0229] 4.3.LC / MS conditions: The liquid chromatography system used was an Agilent Infinity 1290 system coupled to an Agilent 6420 triple quadrupole mass spectrometer in electrospray ionization mode. The autosampler was kept at 15 °C. Metabolites were eluted from a Poroshell 120 EC-C 8 column (50 × 3 mm, 1.9 μm; Agilent) at 25 °C with a mobile phase consisting of 0.1% formic acid LC-MS grade in water (solvent A) and 0.1% formic acid LC-MS grade in acetonitrile (solvent B) at a flow rate of 0.8 mL / min. Elution was as follows: 0–1 min, 45–45% B; 1–2 min, 50% B; 2–4 min, 55% B; 4–8 min, 90% B. Injection volumes were 5 μL for standards and samples. For each compound, the relevant transitions of precursor versus product ions were determined. MRM transitions were optimized using direct injection and the Optimizer B.08.00 workstation software solution (Agilent technologies, Santa Clara, CA, USA). Two modifiers were selected to verify the specificity of the detected peaks (see Table 1). Mass spectrometer parameters were set as follows: ESI source in positive mode; drying gas (N2) flow rate, 10 L / min; gas temperature, 300 °C; nebulizer, 40 psi; and capillary, 4.0 kV. The MS system was fully calibrated before the run according to the manufacturer's guidelines. Data analysis was post-processed with Agilent MassHunter Quantitative / Qualitative analysis B.07.00 (Agilent technologies, Santa Clara, CA, USA). [Table 9]

[0230] 4.5. Captiva ND Protocol for Plasma Treatment Prior to Injection. a) Captiva ND with 50 μl of plasma * Add b) Add 200 μl of methanol containing the internal standard c) Mixing d) Apply vacuum until all volume has passed through the cartridge for complete elution.

[0231] Appendix Standards and Reagents 6-gingerol assay (HPLC) ≥ 95% (Phytolab, reference 89201); 8-gingerol assay (HPLC) ≥ 95% (Phytolab, reference 89202); 10-gingerol assay (HPLC) ≥ 95% (Phytolab, reference 89203); 6-Shogaol assay (HPLC) ≥ 90% (Phytolab, reference 89792); 8-Shogaol assay (HPLC) ≥ 90% (Phytolab, reference 83910); 10-Shogaol assay (HPLC) ≥ 90% (Phytolab, reference 83911); Pelargonic acid vanillylamide PAV (internal standard) (Sigma, reference V 9130) β-glucuronidase type HP-2 from Helix pomatia (Sigma, ref. G7017) Sulfatase type H-1 from Helix pomatia (Sigma, ref. S9626) material: Captiva ND 96-well filter plate, 0.2 μm pore size, polypropylene filters (Agilent A5969002)

[0232] 4.7.Results As reported in Tables 10 and 12, the data demonstrated that Composition A had a significantly higher area under the curve (AUC) compared to ginger powder or ginger 5%. The increased AUC was +53.08% and +26.26%, respectively.

[0233] The higher bioavailability combined with sustained release is confirmed by the relative bioavailability data in Table 14, where the single gingeroid in Composition A is 1.96 more bioavailable than the single gingeroid in ginger powder and 1.38 more bioavailable than the single gingeroid in ginger 5%.

[0234] Furthermore, Cmax (Tables 10 and 12) was not statistically different between groups (Tables 11 and 12, data at 30 minutes, p>0.05). This result indicates that there was no statistically significant difference in maximum gingeroid blood levels for any of the groups.

[0235] On the other hand, composition A induces a statistically significant shift in the half-life (t 1 / 2 (hours) reported in Tables 9 and 11), increasing 2.84-fold compared to ginger powder and 1.80-fold compared to ginger 5%. This shift is due to statistically significantly higher gingeroid plasma levels at 30 min, 1 h, 4 h and 8 h after ingestion of composition A compared to ingestion of ginger powder and at 30 min and 1 h compared to ingestion of ginger 5% (Tables 10 and 11 report values ​​of p<0.05 in bold).

[0236] These results highlight the sustained release effect of Composition A demonstrated by higher gingeroid blood levels from 30 minutes sustained for up to 8 hours, indicating a longer gingeroid release over time, in other words, Composition A provides a gingeroid sustained release effect characterized by a longer half-life and extended release up to 8 hours after ingestion. [Table 10] [Table 11] [Table 12] [Table 13] [Table 14]

[0237] 5. Example of human pharmacokinetic study Example 5: Examination of the Efficacy of Composition A to Enhance the Bioavailability of Gingeroids in Healthy Volunteers Through a Comparative Pharmacokinetic Study The purpose of this study is to compare the efficacy of Composition A to a standard ginger root powder and a standard ginger extract 5% in humans. The hypothesis of this study is that Composition A will be superior in terms of plasma bioavailability as measured by dose-normalized area under the curve (AUC) compared to ginger root powder providing the same amount of active substance (gingeroids).

[0238] The primary objective of this study is to evaluate the plasma concentration profile of total gingeroids (6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol and their glucuronide and sulfate metabolites) over an 8 hour period following consumption of a single dose of Composition A of 100 mg (16.7 mg / kg body weight assuming a 60 kg human) compared to a single dose of ginger root powder delivering the same amount of gingeroids.

[0239] A secondary objective of this study is to evaluate the plasma concentration profile of the following parameters following consumption of a single dose of each test product: -Total gingeroids; - Parent compounds: 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol; -Metabolites: 6-, 8-, or 10-gingerol glucuronide, 6-, 8-, or 10-gingerol sulfate, 6-, 8-, or 10-shogaol glucuronide, 6-, 8-, or 10-shogaol sulfate.

[0240] Secondary objectives of this study included evaluation of Composition A in comparison to a standard ginger extract.

[0241] The pharmacokinetic study is a single-center, randomized, crossover, pilot and open clinical trial. There is a screening / enrollment visit (V0), followed by three experimental sessions (V1-V3), during which the test product is consumed by the subject (one different product in each session for each randomized subject). The V1 visit takes place a maximum of three weeks after V0 and can also constitute the randomization visit. Each experimental session (V1-V3) is separated by a minimum of one week and a maximum of two weeks. During each experimental session, subjects undergo blood sample kinetics over an 8-hour period. The final kinetic blood sample is realized after each experimental session, 8 hours after the start of the kinetics. Urine collections are also performed during these visits for biobanking. Subjects must collect their first void (this entire first void) in the morning of each experimental visit, and urine from 0 to 8 hours during the kinetics on-site. The end of the study can be the day after the last experimental session, V3.

[0242] For this study, healthy men and women (e.g., 18-35 years old) will be recruited to participate in this study. Participants will be enrolled in the study if they meet all inclusion criteria and do not present any of the exclusion criteria. Ethical approval will be obtained from the ethical committee.

[0243] Participants are included in the study if: - Healthy males and females, -Age is between 18 and 45 years (inclusive), -BMI between 19 and 25 kg / m 2 Between (including the limits) - Weight has been stable within ±3kg for the past 3 months, - Have routine blood chemistry values ​​within normal ranges, - For women: non-menopausal and using the same reliable contraception for at least 3 cycles prior to study initiation and agreeing to maintain it for the entire duration of the study (condoms containing spermicidal gel and combined estrogen / progestin contraception are permitted) or menopausal without or with hormone replacement therapy (estrogen replacement therapy started for less than 3 months is excluded); - Non-smoker or consuming 5 cigarettes / day or less and agreeing not to smoke during all experimental sessions (V1-V3), - Agree to refrain from consuming foods, beverages, and condiments containing ginger, ginger powder, or ginger extracts for one week prior to and throughout the study.

[0244] The study is conducted in a crossover fashion, with each subject consuming the three test products in a randomized order during each experimental session (V1-V3). After randomization, the subjects (30 participants) consume each test product once with a glass of water (240 ml to be exact) during each experimental session (V1-V3). The test products are consumed at the T0 time point of the study. The test products are administered directly to the subjects during the experimental sessions (V1-V3) according to a randomized list of product attribute sequences.

[0245] Three products, which are dietary supplements in capsule form, will be tested as part of this trial. - Composition A 100 mg (1 capsule; 100 mg per capsule), with a minimum of 10% gingeroids consumed as a capsule; -Standard ginger root powder, 700-800 mg (2 capsules; 350-400 mg per capsule), delivered as a capsule, delivers the same amount of gingeroids, -200mg of standardized ginger root extract with a minimum of 5% gingeroids consumed as a capsule (1 capsule; 200mg per capsule). - To guarantee the health status of the subject and check the eligibility criteria, a blood sample is realized during the V0 visit for control record analysis and pregnancy test (βhCG administration) for non-menopausal women. The subject must come to the clinical investigation center in a 12-hour fasting state. After the realization of the physical examination and the verification of the eligibility criteria, blood sampling is realized. Only one puncture is required and a maximum of 10 mL will be collected. Parameters are analyzed in serum and plasma, therefore EDTA, fluorescent and dry tubes are used. Blood pressure measurements are performed at each visit. This is performed during the physical examination using an electronic blood pressure monitor. Heart rate (HR, bpm), systolic blood pressure (SBP, mmHg) and diastolic blood pressure (DBP, mmHg) are evaluated. The subject is asked to come to the clinical investigation center in a 12-hour fasting state. - The session may last eight (8) hours on-site. Subjects will remain at the Clinical Research Center for the entire session. Ten (10) blood draws will be performed according to the following schedule: -T-5 (baseline), -T15>T30>T45>T60>T75>T90>T105>T120>T150>T180>T240>T300>T360>T480, -A margin of ±30 seconds is permitted for T15, ±1 minute for T30 and T45, ±2 minutes for T60, T75, T90, T105, and ±5 minutes for T120 to T480.

[0246] The T0 time point corresponds to consumption of the test product. Volunteers are allowed to consume their standard lunch approximately 4 hours after test product consumption (immediately after the T240 time point) and a standard snack approximately 8 hours after test product consumption. Lunch will have to be consumed in a maximum of 30 minutes. Water is not allowed 1 hour before and 1 hour after product administration.

[0247] Since the biological parameters evaluated in these samples are analyzed in plasma, only EDTA tubes are used (5 mL per sample).

[0248] 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol and their metabolites are analyzed using the LC / MS method as described in Example 4.

[0249] The dose-normalized area under the curve (AUC) (AUC 0-8h / dose) of total gingeroids (6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol as well as the sum of their metabolites) plasma concentrations from 0 to 8 hours after consumption of the ginger product (expressed in ng.h / mL / mg) is calculated. The dose-normalized AUC is the AUC normalized according to the gingeroid intake by dividing the observed AUC by the corresponding gingeroid dose of each administration. The following time points are considered: T15, T30, T45, T60, T75, T90, T105, T120, T150, T180, T240, T300, T360 and T480. T-5 can be considered as the baseline value (T0) for the AUC calculation. The main comparison is 100mg of Composition A versus 700-800mg of standard ginger root powder.

[0250] Secondary endpoints following consumption of the different formulations in this study will be evaluated: -AUC of total gingeroids plasma concentration from 0 to 8 hours (AUC 0-8h) (expressed in ng.h / mL); -AUC of individual gingeroids (6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol) and their metabolites plasma concentrations from 0 to 8 h (AUC 0–8 h) (expressed in ng.h / mL); -AUC of total gingeroids plasma concentration from 0 to infinity normalized according to gingeroid intake (AUC 0 to ∞ / dose) (expressed in ng.time / mL / mg); -AUC of total gingeroids plasma concentration from 0 to infinity (AUC 0~∞) (expressed in ng.h / mL); -AUC of individual gingeroids and their metabolites plasma concentrations from 0 to infinity (AUC 0 to ∞) (expressed in ng.h / mL); - Peak total gingeroids plasma concentration (Cmax / dose) normalized according to gingeroid intake (expressed in ng / mL / mg); - peak total gingeroids plasma concentration (Cmax) (expressed in ng / mL); - Peak plasma concentrations (Cmax) of individual gingeroids and their metabolites (expressed in ng / mL); - half-life of total gingeroids plasma concentration (t1 / 2, expressed in minutes); - half-lives (t1 / 2, expressed in minutes) of individual gingeroids and their metabolites; -elimination rate constant of total gingeroids in plasma (λz); -elimination rate constants of individual gingeroids and their metabolites in plasma (λz); - time to peak total gingeroids plasma concentration (Tmax, expressed in minutes); - time to peak of individual gingeroids and their metabolites (Tmax, expressed in minutes); - Relative bioavailability, defined as the ratio of the dose-normalized AUC 0-8h of total gingeroids for the different test formulations to the dose-normalized AUC 0-8h obtained for the reference product (standard ginger root powder).

[0251] For AUC, the following time points are considered: T0, T15, T30, T45, T60, T90, T120, T240, T360, T480 and T24 hours. T-5 can be considered as the baseline value (T0) for AUC calculation.

[0252] Gingeroids are defined as 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol, and metabolites are defined as 6-gingerol glucuronide, 6-gingerol sulfate, 8-gingerol glucuronide, 8-gingerol sulfate, 10-gingerol glucuronide, 10-gingerol sulfate, 6-shogaol glucuronide, 6-shogaol sulfate, 8-shogaol glucuronide, 8-shogaol sulfate, 10-shogaol glucuronide, 10-shogaol sulfate. Total gingeroids can correspond to the sum of 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol in plasma and their metabolites.

[0253] Statistical analyses will be performed on both the intention-to-treat (ITT) and per-protocol (PP) populations.

[0254] The primary analysis of bioavailability is the dose-normalized AUC between 0 and 8 hours. This is analyzed using a mixed model for repeated measures (SAS® PROC MIXED, statistical model number 1): Y = Product + Visit + Baseline + Subject 無作為 (In the formula, -Y: Dose-normalized AUC of analyte plasma concentration from 0 to 8 hours -Product: Standardized ginger root powder or Standardized ginger root extract 5% or Composition A 100 mg, -Visit: Visits V1 to V3 - Baseline: value of parameter at time point T-5 (T0 for AUC calculation); -subject 無作為 : Random factor).

[0255] The same statistical model will be used to evaluate all secondary endpoints of the bioavailability assessment.

[0256] The results show increased bioavailability of gingeroids when consumed in the form of Composition A compared to standard ginger root powder.

[0257] The results show increased bioavailability of gingeroids when consumed in the form of Composition A compared to a standardized ginger root extract of 5%.

Claims

1. (i) gingeroids; (ii) gum arabic, guar gum, xanthan gum, locust bean gum, tragacanth gum or mixtures thereof; and (iii) at least one saponin A composition comprising:

2. (i) gingeroids; (ii) gum arabic; and (iii) at least one saponin The composition of claim 1 , comprising:

3. (i) gingeroids; (ii) gum arabic; and (iii) at least one saponin The composition of claim 1, which is a sustained release composition comprising:

4. 2. The composition of claim 1, wherein the gingeroid comprises 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, or a mixture thereof.

5. 2. The composition of claim 1, wherein component (i) is ginger oleoresin, optionally obtained via CO2 extraction.

6. 6. The composition of claim 5, wherein the ginger oleoresin contains at least about 10% gingerol.

7. 2. The composition of claim 1, wherein the gingeroid is obtained from Zingiber officinale.

8. 2. The composition of claim 1, wherein the composition comprises at least about 5% by weight of gingeroids, such as at least about 7.5% by weight of the composition, or at least about 10% by weight or at least about 20% by weight of the composition.

9. 2. The composition of claim 1, wherein the saponin is selected from Quillaja saponin, Yucca saponin, Tea saponin, Licorice saponin, Ginseng saponin or mixtures thereof, optionally in solid form.

10. 2. The composition of claim 1, wherein the saponin is an extract obtained or obtainable from Quillaja japonica, optionally containing more than 50% w / w saponin.

11. 2. The composition of claim 1, wherein the gum (such as gum arabic) is present in the composition of the present invention in an amount from about 20% to about 80% by weight of the composition, such as from about 50% to about 70% by weight of the composition or about 68% by weight of the composition.

12. 2. The composition of claim 1, wherein the at least one saponin is present in an amount of from about 0.1% to about 5% by weight (w / w) of the composition, such as from about 0.5% to about 3% by weight or about 2% by weight of the composition, such as 1.3 to about 1.5% by weight of the composition.

13. When the composition is in a dry form, the particles may be 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 20, such as 150-250 microns, such as 140-250 microns, such as 100-250 microns, such as 100-300 microns, such as 200-500 microns, 900-800 microns, 500-600 microns, 100-500 microns, 10. The composition of claim 1 having an average diameter of from about 5 microns to about 1000 microns, such as from 0, 250, 300, 400, 450, 500, 600, 700, 800, 900 microns to about 800, 700, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10 microns.

14. Use of a composition according to any one of claims 1 to 13 in the preparation of a nutraceutical formulation, a feed or food product for humans or animals (such as a functional food formulation, i.e. a food, drink, feed or pet food or a food, drink, feed or pet food supplement), a dietary supplement, an aroma or flavouring, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation.

15. 15. Use according to claim 14, wherein the nutraceutical formulation, human or animal feed or food product (functional food formulation, i.e. food, drink, feed or pet food or a food, drink, feed or pet food supplement, etc.), dietary supplement, fragrance or flavouring, pharmaceutical or veterinary preparation, oenological formulation or cosmetic formulation further comprises, if necessary, pharmaceutical / veterinary ingredients such as excipients or carriers or (functional) food-acceptable ingredients and mixtures thereof.

16. A nutraceutical formulation, a human or animal feed or food product (such as a functional food formulation, i.e. a food, beverage, feed or pet food or a food, beverage, feed or pet food supplement), a dietary supplement, an aroma or flavouring, a pharmaceutical or veterinary preparation, an oenological formulation or a cosmetic formulation, consisting of, consisting essentially of or comprising a composition as defined in any one of claims 1 to 13.

17. A process for preparing a composition as defined in any one of claims 1 to 13, the process comprising the steps of: (i) preparing an aqueous solution of gingeroid (such as ginger oleoresin); (ii) mixing the aqueous solution from (i) with an aqueous gum (such as gum arabic) solution and at least one saponin (such as an extract obtained or obtainable from Quillaja japonica) and optionally a plant and / or vegetable oil to obtain an emulsion; and optionally (iii) drying the product of (ii) to obtain the composition. The process includes:

18. 14. A method for improving the bioaccessibility, bioavailability, bioefficacy and / or bioactivity of a gingeroid in a mammal comprising administration of a gingeroid in the form of a composition as defined in any one of claims 1 to 13, or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation consisting of, consisting essentially of or comprising said composition.

19. 14. Use in the manufacture of a nutraceutical formulation, a human or animal feed or food product, a dietary supplement, a pharmaceutical or veterinary formulation comprising, consisting essentially of, or consisting of a composition as defined in any one of claims 1 to 13, for improving the bioaccessibility, bioavailability, bioefficacy and / or bioactivity of gingeroids in a mammal.

20. 14. A composition as defined in any one of claims 1 to 13, or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation comprising said composition, for use in a method for providing a sustained release of said gingeroid in the intestine of a mammal comprising administration of said gingeroid in the form of a composition as defined in any one of claims 1 to 13, or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation comprising said composition.

21. 14. Use in the manufacture of a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation comprising, consisting essentially of, or comprising a composition as defined in any one of claims 1 to 13, for providing sustained release of gingeroids in the intestine of a mammal.

22. 14. A nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation consisting of, consisting essentially of, or comprising the composition according to any one of claims 1 to 13 or said composition for use in preventing or treating gastrointestinal disorders, primary dysmenorrhea, heavy menstrual bleeding, metabolic disorders, sleep disorders (such as insomnia), neuropsychiatric disorders (such as depression and anxiety), neurodegenerative diseases (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood.

23. 14. A method for preventing or treating gastrointestinal disorders, primary dysmenorrhea, heavy menstrual bleeding, metabolic disorders, sleep disorders (such as insomnia), neuropsychiatric disorders (such as depression and anxiety), neurodegenerative diseases (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood, the method comprising administration of the composition or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical or veterinary formulation comprising, consisting essentially of, or comprising the composition according to any one of claims 1 to 13 to a patient in need thereof.

24. 14. Use of a composition according to any one of claims 1 to 13 in the manufacture of a medicament for treating gastrointestinal disorders, primary dysmenorrhea, heavy menstrual bleeding, metabolic disorders, sleep disorders (such as insomnia), neuropsychiatric disorders (such as depression and anxiety), neurodegenerative diseases (such as schizophrenia, Alzheimer's disease, Parkinson's disease), and / or age-related cognitive decline attention, wakefulness and / or mood.

25. 20. A composition or a nutraceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical formulation or veterinary formulation consisting of, consisting essentially of, or comprising said composition, for use in the method of claim 18, wherein the mammal is a human.

26. 20. A composition or a nutritional pharmaceutical formulation, human or animal feed or food product, dietary supplement, pharmaceutical formulation or veterinary formulation comprising said composition, for use in the method of claim 18, wherein the gingeroid is provided in an amount of about 0.08 mg gingeroid per kg body weight to about 6.5 mg gingeroid per kg body weight, such as 1.5 mg gingeroid per kg body weight, 1.6 mg gingeroid per kg body weight, 0.2 mg gingeroid per kg body weight, 0.5 mg gingeroid per kg body weight, 1 mg gingeroid per kg body weight, 2 mg gingeroid per kg body weight, 3 mg gingeroid per kg body weight, 3.4 mg gingeroid per kg body weight or 5 mg gingeroid per kg body weight.

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