Use of the composition for the manufacture of a medicament for preventing or treating hyperuricemia caused by xanthine oxidase

Abstract

A composition for administration to a subject is disclosed. The composition comprises at least one plant-active component. The plant-active component is present in the composition in an amount that effectively inhibits xanthine oxidase (XO) in the subject. The plant-active component comprises at least one extract selected from the group consisting of: i) an extract of *Potentilla fruticosa*; ii) an extract of *Hedyotis diffusa*; and iii) a combination of i) and ii). The composition may also comprise one or more supplementary extracts. The composition may be in the form of an oral composition, for example, for ingestion. The composition may also be in the form of a topical composition, for example, for topical application. A method for inhibiting xanthine oxidase (XO) in a subject is also provided. The method comprises administering an effective amount of the composition to the subject.

Description

Invention Field

[0001] This invention generally relates to compositions and methods for inhibiting xanthine oxidase, and more specifically, to compositions containing plant extracts for inhibiting xanthine oxidase in a subject. Related methods are also provided. Background of the Invention

[0002] Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and subsequently xanthine to uric acid, producing hydrogen peroxide (H₂O₂) as a byproduct, and sometimes superoxide ions (O₂•₂). – The production of uric acid and / or xanthine oxidation byproducts can contribute to pathological disorders such as hyperuricemia, gout, ulcers, cancer, local ischemia, hypertension, cardiovascular disease, and oxidative stress.

[0003] Given the above, there remains an opportunity to provide new and useful xanthine oxidase inhibitors. Such xanthine oxidase inhibitors could offer potential preventative and therapeutic approaches for reducing the risk of hyperuricemia, gout, ulcers, cancer, local ischemia, hypertension, cardiovascular disease, oxidative stress, oxidative damage, or other pathogenic complications caused by xanthine oxidation. Therefore, there also remains an opportunity to provide new and useful compositions and methods for inhibiting xanthine oxidase. Invention Overview

[0004] A composition is provided for administration to a subject. The composition comprises at least one plant-active component. The plant-active component is typically present in the composition in an amount that effectively inhibits xanthine oxidase (XO) in the subject. The plant-active component comprises at least one extract selected from the group consisting of: i) an extract of *Potentilla fruticosa*; ii) an extract of *Hedyotis diffusa*; and iii) a combination of i) and ii).

[0005] In various embodiments, the composition is an oral composition formulated for oral administration to a subject. In other embodiments, the composition is a topical composition formulated for topical administration to a subject.

[0006] The composition can be used to inhibit XO in a subject. A method for inhibiting XO in a subject includes administering an effective amount of the composition to the subject. Brief description of the attached diagram

[0007] Figure 1 It is a graph showing the inhibition rate of xanthine oxidase (XO) using the aqueous extract of *Potentilla chinensis*.

[0008] Figure 2 It is a graph showing the XO inhibition rate using the 70% ethanol extract of Paulownia tomentosa;

[0009] Figure 3 This is a graph showing the XO inhibition rate using the aqueous extract of *Houttuynia cordata*; and

[0010] Figure 4 This is a graph showing the XO inhibition rate using the 70% ethanol extract of *Houttuynia cordata*.

[0011] Detailed description of the current implementation plan

[0012] A composition for administration to a subject is disclosed. The composition comprises at least one plant-based active ingredient. The composition is described below, followed by related uses and methods.

[0013] As will be understood from this disclosure, there are no particular limitations on the composition except for the plant active ingredients, particularly their extracts, and the associated components and methods. Therefore, the composition can be formulated as, for example, a topical composition (e.g., a cosmetic composition), or as an oral composition, health product, pharmaceutical product, or supplement, and can be used as a sole and independent therapeutic agent or in combination with other compatible therapeutic agents.

[0014] This composition can be used to treat, prevent, and / or improve various conditions, such as those related to xanthine oxidation. Specifically, as will be appreciated from the following description and examples, it is believed that the composition of this embodiment can inhibit xanthine oxidation, and more specifically, inhibit xanthine oxidase in a subject.

[0015] Therefore, this composition can be used to treat (i.e., alleviate, prevent, reverse, etc.) conditions that are usually associated with xanthine oxidation, such as hyperuricemia, gout, and complications associated with other health disorders, such as ulcers, cancer, local ischemia, hypertension, cardiovascular disease, oxidative stress, and oxidative damage.

[0016] As described above, the composition contains a plant-based active ingredient. More specifically, the plant-based active ingredient contains at least one extract, optionally consisting essentially of at least one extract, or optionally consisting of at least one extract selected from: i) an extract of *Potentilla fruticosa*; ii) an extract of *Eupatorium fortunei*; and iii) a combination of i) and ii).

[0017] In some embodiments, only one of the two extracts i) and ii) is present in the composition. In other embodiments, both extracts i) and ii) are present in the composition. The individual extracts i) and ii) may be simply referred to as "botanical extract" or collectively as "botanical extracts," and are described below in sequence.

[0018] The term "extract" is used herein in its conventional sense to refer to a composition obtained by fluid extraction from a source material. Therefore, the term "plant extract" should be understood as a composition obtained from a plant source (i.e., plant material) by fluid extraction (e.g., solvent extraction, gas extraction, CO2 extraction, etc.). Plant extracts suitable for this composition can be obtained by any extraction method or combination of these methods known in the art, including water extraction, steam extraction, solvent extraction, etc. Exemplary extraction techniques are described below. However, plant extracts are generally not limited to specific extraction methods or additional / auxiliary techniques used to obtain plant extracts, but can vary according to the parameters described herein. Furthermore, the extraction step is not necessary for the preparation of the plant active ingredient and / or the composition, as suitable extracts (e.g., standardized extracts) are readily available from many commercial suppliers.

[0019] Plant extracts suitable for use or as active components of plants include those obtained by solvent extraction, such as using polar solvents like alcohols (e.g., methanol, ethanol, butanediol, etc.), ethers (e.g., diethyl ether, methyl tert-butyl ether, etc.), ketones (e.g., acetone), esters (e.g., ethyl acetate), phenols, water, etc., and non-polar solvents like benzene, xylene, toluene, etc., and their derivatives, modifications, and combinations (e.g., solvent-water blends, including alcohol-water, acetone-water, etc.). Additional and alternative extraction techniques include sequential fractionations, total hydro-ethanol extractions, lump-sum extractions, supercritical fluid extraction (e.g., with CO2), and those utilizing sequential or secondary extractions from a first extract (e.g., non-polar solvent extracts of plant extracts obtained from polar solvent extractions) or other processing techniques such as filtration, purification, distillation, dehydration, evaporation, concentration, drying, etc. Specific examples of suitable extraction methods are described in U.S. Patent No. 7,897,184, which is incorporated herein by reference.

[0020] As understood in the art, various segments or parts of plants can be used to obtain essential oils and extracts, such as bark, berries, flowers, fruits, leaves, skin, resins, rhizomes, roots, seeds, and / or wood. Essential oils can be obtained by many methods, such as distillation (e.g., using steam), pressing, solvent extraction, absolute oil extraction, resin tapping, and / or cold pressing.

[0021] In various embodiments, the solvent used to obtain the plant extract suitable for use in this disclosure is a solvent in which the resulting plant extract and / or its subsequent forms (e.g., plant extract powder) are suitable for ingestion. For example, the solvent is water or ethanol.

[0022] In one instance, plant extracts can be obtained using organic solvent extraction techniques. In another instance, plant extracts can be obtained using solvent sequential fractionation. Total hydro-ethanolic extraction can also be used to obtain plant extracts. This is often referred to as lump-sum extraction. The plant extracts produced in this method contain a wide variety of phytochemicals present in the extraction material, including both fat-soluble and water-soluble phytochemicals. After collecting the plant extract solution, the solvent is evaporated to obtain the plant extract.

[0023] Total ethanol extraction can also be used. This technique uses ethanol as a solvent. This extraction technique produces plant extracts that may include fat-soluble and / or lipophilic compounds in addition to water-soluble compounds. Total methanol extraction can also be used in a similar manner, with similar results.

[0024] Another example of an extraction technique that can be used to obtain plant extracts is supercritical fluid carbon dioxide extraction (SFE). In this extraction procedure, the material to be extracted is not exposed to any organic solvent. Instead, the extraction solvent is carbon dioxide (CO2) under supercritical conditions (e.g., >31.3 °C and >73.8 bar), with or without a modifier. Those skilled in the art will recognize that temperature and pressure conditions can be varied to obtain optimal yields of plant extracts. Similar to the total hexane and ethyl acetate extraction techniques that can also be used, this technique yields plant extracts containing lipophilic and / or fat-soluble compounds.

[0025] The extraction methods described above may also include one or more additional processing steps as understood in the art and / or used in combination with them. For example, the plant material may be crushed, broken up, ground, etc. One or more filtration steps may also be present to remove, for example, cellulose / fibrous materials or other solid materials. One or more purification steps may also be present to remove, for example, certain components and / or contaminants. Such purification may be achieved, for example, by distillation, evaporation, centrifugation, etc. One or more concentration and / or drying steps may also be present to remove water and / or other volatiles, such as alcohols, lighter compounds, VOCs, etc. Furthermore, acids and / or bases may be added to adjust the pH or neutralize it. Depending on the desired form of the final / terminal plant extract, various additional steps as understood in the art may also be used, such as screening, pressing, milling, grinding, mixing, dispersing, etc. It should be recognized that combinations of these additional processing steps, repeated and / or in different orders, are also considered.

[0026] Silver Dewberry

[0027] In some embodiments, the plant-active component and therefore the composition comprises an extract of *Potentilla fruticosa*, i.e., an extract comprising, optionally substantially composed of material from the flowering plant species *Potentilla fruticosa*, such as flowers or leaves. The *Potentilla fruticosa* extract is not particularly limited and may comprise or be derived from any flower extract, leaf extract, or combination of flower and / or leaf extracts from the *Potentilla fruticosa* plant suitable for the embodiments described herein. More specifically, exemplary *Potentilla fruticosa* flower and / or leaf extracts include those capable of inhibiting XO or initiating / exhibiting any other such activities described herein as part of the plant-active component.

[0028] Silver cinnamon has been reported to contain various bioactive components, such as phenolic acids, flavonoids, terpenoids, triterpenes, tannins, polyphenols, saponins, polysaccharides, and other compounds. Silver cinnamon ( Potentilla glabra It can be abbreviated as P. glabra or various other names such as Potentilla glabra Lodd.、 Potentilla glabra G. Lodd., Dasiphora glabra (G. Lodd.) Soják, Silver Dew Plum, Yinlumei, or Silver Dew Plum. Potentilla glabra The leaves and flowers of *Lodd.* may be called Yaowang tea. In various implementations, *Potentilla anserina* may belong to the cultivar group. Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.–Mazz, which may be called BaimaoYinlumei, White-haired Silver Lumei, or White-haired Silver Lumei (variant).

[0029] Specific examples of *Potentilla fruticosa* extracts are known in the art. Therefore, *Potentilla fruticosa* extracts can be purchased or otherwise commercially obtained from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof. In some embodiments, the extract of *Potentilla fruticosa* is obtained by aqueous extraction (or water-based extraction) of the plant material of *Potentilla fruticosa*, including but not limited to flowers and / or leaves. In further or other embodiments, the extract of *Potentilla fruticosa* is obtained by alcoholic extraction (e.g., ethanol extraction) of the plant material of *Potentilla fruticosa*, including but not limited to flowers and / or leaves.

[0030] In some embodiments, extracts of *Potentilla fruticosa* flowers and / or leaves are obtained by aqueous extraction (or water-based extraction) of the flowers, floral substrates, leaves, or leaf-based substrates of *Potentilla fruticosa*. In further or other embodiments, extracts of *Potentilla fruticosa* flowers and / or leaves are obtained by alcoholic extraction (e.g., ethanol extraction) of the flowers, floral substrates, leaves, or leaf-based substrates of *Potentilla fruticosa*. The flowers and / or leaves can be fresh or dried, typically dried to prevent decay. The dried flowers and / or leaves can then be formed into a powder, which can be used as an extract on its own, or more typically, the powdered flowers and / or leaves can be further processed to form an extract as described below.

[0031] As those skilled in the art will understand, the cultivation of *Potentilla fruticosa* is primarily for its flowers and / or leaves. Therefore, in various embodiments, extracts of *Potentilla fruticosa* are extracts of its flowers and / or leaves. Suitable extractions include those noted above, such as water and ethanol extracts of the flowers and / or leaves. The flowers and / or leaves may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0032] For example, certain extracts can be obtained by grinding *Potentilla fruticosa* (e.g., flowers and / or leaves) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0033] In various embodiments, the plant-active component comprises extracts of *Potentilla fruticosa* flowers and / or leaves. In further or other embodiments, the composition is substantially to completely free of components derived from non-floral and / or non-folial plant materials of *Potentilla fruticosa*. In these embodiments, the non-floral and non-folial plant materials of *Potentilla fruticosa* can be, for example, the roots, branches, bark, rhizomes, or branches of the *Potentilla fruticosa* plant. Without being bound by any particular theory, it is believed that the flowers and leaves of *Potentilla fruticosa* are most effective at inhibiting xanthine oxidase; while other parts of *Potentilla fruticosa* are not (as described in the Examples section below).

[0034] In other embodiments, the *Potentilla fruticosa* extract may comprise material from any part or combination of parts of the plant, and is not limited to flower and / or leaf extracts. For example, the *Potentilla fruticosa* extract may comprise material extracted from one or more parts of the *Potentilla fruticosa* plant, including its roots, branches, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the *Potentilla fruticosa* extract. Similarly, the *Potentilla fruticosa* plant may be extracted in its original form or processed prior to the extraction of the *Potentilla fruticosa* extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant active component comprises a *Potentilla fruticosa* extract containing material obtained from (i.e. extracted from) the flowers and / or leaves of *Potentilla fruticosa*.

[0035] The amount of *Potentilla fruticosa* extract used in the plant active ingredient is variable and selected based on the quantity and type of components used in the plant active ingredient. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of *Potentilla fruticosa* extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of *Potentilla fruticosa* extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of *Potentilla fruticosa* extract. In various embodiments, the plant-active component may include an amount of *Potentilla vulgaris* extract optionally greater than 1, 5, 10, 25, 50, 75, 80, or 95% by weight based on the total weight of the plant-active component. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-active component, respectively.

[0036] In some embodiments, the plant active ingredient comprises more than one *Potentilla discolor* extract, such as two, three, four, or more *Potentilla discolor* extracts. In such embodiments, each *Potentilla discolor* extract is selected independently, may be the same as or different from any other *Potentilla discolor* extract, and is used in the amounts described above.

[0037] The *Potentilla fruticosa* extract can be used in any form, such as pure (i.e., without solvents, carrier media, diluents, etc.) or in a carrier media, such as a solvent or dispersant. If present, the carrier media may contain aqueous solvents (e.g., water), organic solvents, fluids, or oils, or combinations thereof. When used, the carrier media should be selected based on the plant active ingredient and / or the specific components of the composition, such as the specific *Potentilla fruticosa* extract used. It should be recognized that if a carrier media is used, the *Potentilla fruticosa* extract may be incorporated with the carrier media before, during, or after incorporation with the plant active ingredient and / or any other components of the composition.

[0038] Fragrant Grass

[0039] In some embodiments, the plant-active component and therefore the composition comprises an extract of *Hedyotis diffusa*, i.e., an extract comprising, optionally substantially composed of materials from the plant species *Hedyotis diffusa*, such as branches and / or roots. The *Hedyotis diffusa* extract is not particularly limited and may comprise or be a combination of any branch extract, root extract, or branch and / or root extract from the *Hedyotis diffusa* plant suitable for the embodiments described herein. More specifically, exemplary *Hedyotis diffusa* branch and / or root extracts include those capable of inhibiting XO or initiating / exhibiting any other such activities described herein as part of the plant-active component.

[0040] Fragrant grass has been reported to contain various bioactive components, such as phenolic acids, flavonoids, flavanols, flavonoids, organic acids, fatty acids, triterpenoids, and other compounds. Fragrant grass ( Anisochilus carnosus It can be abbreviated as A. carnosus or various other names such as Anisochilus carnosus (L.) Wall., “Xiang Pai Cao” or Xiang Pai Cao.

[0041] Specific examples of extracts of *Hedyotis diffusa* are known in the art. Therefore, extracts of *Hedyotis diffusa* can be purchased or otherwise commercially obtained from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof. In some embodiments, extracts of *Hedyotis diffusa* are obtained by aqueous extraction (or water-based extraction) of the plant material of *Hedyotis diffusa*. In further or other embodiments, extracts of *Hedyotis diffusa* are obtained by alcoholic extraction (e.g., ethanol extraction) of the plant material of *Hedyotis diffusa*.

[0042] As those skilled in the art will understand, the cultivation of *Cymbidium faberi* is primarily for its plant material, including but not limited to its stems and roots. Therefore, in various embodiments, extracts of *Cymbidium faberi* are extracts of its stems and roots. Suitable extractions include those noted above, such as water and ethanol extractions of stems and roots. Stems and roots may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0043] For example, certain extracts can be obtained by grinding *Gynostemma pentaphyllum* (e.g., branches and roots) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0044] In various embodiments, the plant-active component comprises extracts from the branches and roots of *Hedyotis diffusa*. In further or other embodiments, the composition is substantially to completely free of components derived from non-branch-based and / or non-root-based plant materials of *Hedyotis diffusa*. In these embodiments, the non-branch-based and non-root-based plant materials of *Hedyotis diffusa* can be, for example, flowers, leaves, buds, seeds, and / or fruits of the *Hedyotis diffusa* plant. Without being bound by any particular theory, it is believed that the branches and / or roots of *Hedyotis diffusa* are most effective at inhibiting xanthine oxidase; while other parts of *Hedyotis diffusa* are not (as described in the Examples section below).

[0045] In other embodiments, the *Cymbidium goeringii* extract may comprise material from any part or combination of parts of the plant, and is not limited to stem and / or root extracts. For example, the *Cymbidium goeringii* extract may comprise material extracted from one or more parts of the *Cymbidium goeringii* plant, including its flowers, leaves, buds, seeds, and / or fruits. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the *Cymbidium goeringii* extract. Similarly, the *Cymbidium goeringii* plant may be extracted in its original form or processed prior to the extraction of the *Cymbidium goeringii* extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant active component comprises a *Cymbidium goeringii* extract containing material obtained from (i.e. extracted from) the whole *Cymbidium goeringii* plant.

[0046] The amount of *Houttuynia cordata* extract used in the plant active ingredient is variable and selected based on the quantity and type of components used in the plant active ingredient. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of *Houttuynia cordata* extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of *Houttuynia cordata* extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of *Houttuynia cordata* extract. In various embodiments, the plant-based active ingredient may include an amount of *Houttuynia cordata* extract optionally greater than 1, 5, 10, 25, 50, 75, 80, or 95% by weight based on the total weight of the plant-based active ingredient. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-based active ingredient, respectively.

[0047] In some embodiments, the plant-active ingredient comprises more than one herb extract, such as two, three, four, or more herb extracts. In such embodiments, each herb extract is selected independently, may be the same as or different from any other herb extract, and is used in the amounts described above.

[0048] Herba Sedum extract can be used in any form, such as pure (i.e., without solvents, carriers, diluents, etc.) or in a carrier medium, such as a solvent or dispersant. If present, the carrier medium may contain aqueous solvents (e.g., water), organic solvents, fluids, or oils, or combinations thereof. When used, the carrier medium should be selected based on the plant active ingredient and / or specific components of the composition, such as the specific Herba Sedum extract used. It should be recognized that if a carrier medium is used, the Herba Sedum extract may be incorporated with the carrier medium before, during, or after incorporation with the plant active ingredient and / or any other components of the composition.

[0049] supplement extract

[0050] In various embodiments, the composition further comprises one or more supplementary extracts. More specifically, in addition to extracts of *Potentilla fruticosa* flowers / leaves and / or *Hedyotis diffusa* branches / roots (each as described above), the plant-active component (and therefore the composition) further comprises at least one supplementary extract, optionally consisting substantially of at least one supplementary extract, or optionally consisting of at least one supplementary extract selected from: i) chicory extract; ii) sour cherry extract; iii) celery extract; iv) lotus extract; and v) combinations of i) to iv). In some embodiments, the compositions disclosed herein do not contain other active ingredients. “Other active ingredients” generally refers to the absence of other types of traditional Chinese medicines (“TCM”; or “Chinese medicines”) that are different from the extracts described above and those exemplified below. Other types of TCM are understood in the art.

[0051] In some embodiments, only one of the four supplementary extracts i) to iv) is present in the composition. In other embodiments, only two of the four supplementary extracts i) to iv) are present in the composition. In still other embodiments, only three of the four supplementary extracts i) to iv) are present in the composition. In yet other embodiments, all four supplementary extracts i) to iv) are present in the composition. Each supplementary extract i) to iv) may be simply referred to as a "botanical extract" or collectively as "botanical extracts," and is described below in sequence.

[0052] endive

[0053] In some embodiments, the plant-active component and therefore the composition comprises an extract of chicory, i.e., an extract comprising, optionally substantially composed of material from the flowering plant species chicory. The chicory extract is not particularly limited and may comprise or be derived from any extract or combination of extracts from the chicory plant suitable for the embodiments described herein.

[0054] Chicory has been reported to contain a variety of bioactive components, such as inulin-type polysaccharides, sesquiterpene lactones, lactucin, guaianolid glycosides, hydroxycinnamic acids (e.g., chicoric acid, chlorogenic acid, and caffeic acid derivatives), flavonoids (e.g., quercetin and kaempferol derivatives), anthocyanins, and coumarins. Chicory ( Cichorium intybus It can be abbreviated as C. intybus or various other names such as Cichorium intybusL., Chicory, Common Chicory, Witloof Chicory, Blue Daisy, Bluedandelion, Blue Sailors, Blueweed, Bunk, Coffeeweed, Hendibeh, Horseweed, Ragged Sailors, Succory, Wildbachelor's Buttons, Wild Endive, Ju Qu, Juju, Cichorii herba Cichorii radix, or Chicory.

[0055] Specific examples of chicory extracts are known in the art. Therefore, chicory extracts can be purchased or otherwise commercially obtained from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof. In some embodiments, chicory extracts are obtained by aqueous extraction (or water-based extraction) of the chicory plant material. In further or other embodiments, chicory extracts are obtained by alcoholic extraction (e.g., ethanol extraction) of the chicory plant material.

[0056] As those skilled in the art will understand, chicory is cultivated primarily for the whole plant. Therefore, in various embodiments, chicory extracts are extracts of the aerial parts of the chicory plant (e.g., stems, leaves, buds, and / or flowers). Suitable extractions include those noted above, such as water and ethanol extractions of the aerial parts of the plant. The aerial parts may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0057] For example, certain extracts can be obtained by grinding chicory (e.g., the aerial parts) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0058] In various embodiments, the plant-active component comprises an extract of the aerial parts of chicory. In further or other embodiments, the composition is substantially to completely free of components derived from non-aerial plant material of chicory. In these embodiments, the non-aerial plant material of chicory may be, for example, the root of the chicory plant. Without being bound by any particular theory, it is believed that the aerial parts of chicory are most helpful in promoting uric acid excretion in this formulation; while other parts of chicory are not.

[0059] In other embodiments, the chicory extract may comprise material from any part or combination of parts of the plant, and is not limited to extracts from the aerial parts. For example, the chicory extract may comprise material extracted from one or more parts of the chicory plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the chicory extract. Similarly, the chicory plant may be extracted in its original form or processed prior to the extraction of the chicory extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant active component comprises a chicory extract containing material obtained from (i.e. extracted from) the aerial parts of chicory.

[0060] The amount of chicory extract used in the plant active ingredient is variable and selected based on the quantity and type of components used in the plant active ingredient. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of chicory extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of chicory extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of chicory extract. In various embodiments, the plant-active component may include chicory extract in an amount optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95% by weight based on the total weight of the plant-active component. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-active component, respectively.

[0061] In some embodiments, the plant-active component comprises more than one chicory extract, such as two, three, four, or more chicory extracts. In such embodiments, each chicory extract is selected independently, may be the same as or different from any other chicory extract, and is used in the amounts described above.

[0062] Chicory extract can be used in any form, such as pure (i.e., without solvents, carrier media, diluents, etc.) or in a carrier media, such as a solvent or dispersant. If present, the carrier media may contain aqueous solvents (e.g., water), organic solvents, fluids, or oils, or combinations thereof. When used, the carrier media should be selected based on the plant active ingredient and / or specific components of the composition, such as the specific chicory extract used. It should be recognized that if a carrier media is used, the chicory extract may be incorporated with the carrier media before, during, or after incorporation with the plant active ingredient and / or any other components of the composition.

[0063] Sour Cherries

[0064] In some embodiments, the plant-active component and therefore the composition comprises an extract of sour cherry, i.e., an extract comprising, optionally substantially composed of material from the fruiting plant species sour cherry. The sour cherry extract is not particularly limited and may comprise or be derived from any extract or combination of extracts from the sour cherry plant suitable for the embodiments described herein.

[0065] Sour cherries have been reported to contain various bioactive components, such as fatty acids, tocochromanols, tocopherols, tocotrienols, carotenoids, squalene, sterols, polyphenols, flavonoids, cyanidin, 3-rutinoside, paeoniflorin, 3-glucoside, isorhamnetin, quercetin, ferulic acid, chlorogenic acid, p-coumaric acid, and other compounds. Sour cherries ( Prunus cerasus It can be abbreviated as P. cerasus or various other names such as Prunus cerasus L., sour cherry, tartcherry, dwarf cherry, or sour cherry.

[0066] Specific examples of sour cherry extracts are known in the art. Therefore, sour cherry extracts can be purchased or otherwise commercially obtained from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof. In some embodiments, the extract of sour cherry is obtained by aqueous extraction (or water-based extraction) of the sour cherry plant material. In further or other embodiments, the extract of sour cherry is obtained by alcoholic extraction (e.g., ethanol extraction) of the sour cherry plant material.

[0067] As those skilled in the art will understand, sour cherry cultivation is primarily for its plant material, including but not limited to its fruit. Therefore, in various embodiments, the extract of sour cherry is an extract of the fruit of the sour cherry. Suitable extractions include those noted above, such as aqueous and ethanolic extractions of the fruit. The fruit may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0068] For example, some extracts can be obtained by grinding sour cherries (e.g., the fruit) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0069] In various embodiments, the plant-based active ingredient consists of an extract of sour cherry fruit. In further or other embodiments, the composition is substantially to completely free of components derived from non-fruit-based plant material of sour cherry. In these embodiments, the non-fruit-based plant material of sour cherry can be, for example, the flowers, leaves, buds, seeds, and / or branches of the sour cherry plant. Without being bound by any particular theory, it is believed that the fruit of the sour cherry is most effective in anti-inflammatory activity in this formulation; while other parts of the sour cherry are not.

[0070] In other embodiments, the sour cherry extract may comprise material from any part or combination of parts of the plant, and is not limited to fruit extracts. For example, the sour cherry extract may comprise material extracted from one or more parts of the sour cherry plant, including its roots, branches, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the sour cherry extract. Similarly, the sour cherry plant may be extracted in its original form or processed prior to the extraction of the sour cherry extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant active component comprises a sour cherry extract containing material obtained from (i.e. extracted from) the sour cherry fruit.

[0071] The amount of tart cherry extract used in the plant active ingredient is variable and selected based on the quantity and type of the components used. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of tart cherry extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of tart cherry extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of tart cherry extract. In various embodiments, the plant-based active ingredient may include an amount of tart cherry extract optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95% by weight based on the total weight of the plant-based active ingredient. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-based active ingredient, respectively.

[0072] In some embodiments, the plant-based active ingredient comprises more than one tart cherry extract, such as two, three, four, or more tart cherry extracts. In such embodiments, each tart cherry extract is selected independently, may be the same as or different from any other tart cherry extract, and is used in the amounts described above.

[0073] Tart cherry extract can be used in any form, such as pure (i.e., without solvents, carriers, diluents, etc.) or in a carrier medium, such as a solvent or dispersant. If present, the carrier medium may contain aqueous solvents (e.g., water), organic solvents, fluids, or oils, or combinations thereof. When used, the carrier medium should be selected based on the plant active ingredient and / or the specific components of the composition, such as the specific tart cherry extract used. It should be recognized that if a carrier medium is used, the tart cherry extract may be incorporated with the carrier medium before, during, or after incorporation with the plant active ingredient and / or any other components of the composition.

[0074] dry celery

[0075] In some embodiments, the plant-active component and therefore the composition comprises an extract of celery, i.e., an extract comprising, optionally substantially composed of material from the flowering plant species celery. The celery extract is not particularly limited and may comprise or be derived from any extract or combination of extracts from the celery plant suitable for the embodiments described herein.

[0076] Celery has been reported to contain various bioactive components, such as flavonoids, chlorogenic acid, carotenoids, terpenes, coumarins, unsaturated fatty acids, methoxybenzene, sedanolides, senkyunolides, indole, tryptophan, and other compounds. Apium graveolens It can be abbreviated as A. graveolens or various other names such as Apium graveolens L., celery, wild celery, Han Qin, dry celery or celery seeds.

[0077] Specific examples of celery extracts are known in the art. Therefore, celery extracts can be commercially obtained, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof, from a variety of sources. In some embodiments, celery extracts are obtained by aqueous extraction (or water-based extraction) of the celery plant material. In further or other embodiments, celery extracts are obtained by alcoholic extraction (e.g., ethanol extraction) of the celery plant material.

[0078] As those skilled in the art will understand, celery is cultivated primarily for its plant material, including but not limited to its stems, leaves, and seeds. Therefore, in various embodiments, the extract of celery is an extract of celery seeds. Suitable extractions include those noted above, such as aqueous and ethanolic extractions of the seeds. The seeds may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0079] For example, some extracts can be obtained by grinding celery (e.g., seeds) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0080] In various embodiments, the plant-active component comprises an extract of celery seeds. In further or other embodiments, the composition is substantially to completely free of components derived from non-seed-based plant material of celery. In these embodiments, the non-seed-based plant material of celery may be, for example, the flowers, leaves, branches, and / or stems of the celery plant. Without being bound by any particular theory, it is believed that celery seeds are most effective at inhibiting xanthine oxidase in this formulation; while other parts of celery are not.

[0081] In other embodiments, the celery extract may comprise material from any part or combination of parts of the plant, and is not limited to seed extracts. For example, the celery extract may comprise material extracted from one or more parts of the celery plant, including its roots, branches, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the celery extract. Similarly, the celery plant may be extracted in its original form or processed prior to the extraction of the celery extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant-active component comprises a celery extract containing material obtained from (i.e. extracted from) the seeds of celery.

[0082] The amount of celery extract used in the plant active ingredient is variable and selected based on the quantity and type of components used in the plant active ingredient. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of celery extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of celery extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of celery extract. In various embodiments, the plant-active component may include an amount of celery extract optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95% by weight based on the total weight of the plant-active component. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-active component, respectively.

[0083] In some embodiments, the plant-active component comprises more than one celery extract, such as two, three, four, or more celery extracts. In such embodiments, each celery extract is selected independently, may be the same as or different from any other celery extract, and is used in the amounts described above.

[0084] Celery extract can be used in any form, such as pure (i.e., without solvents, carriers, diluents, etc.) or in a carrier, such as a solvent or dispersant. If present, the carrier may contain aqueous solvents (e.g., water), organic solvents, fluids, or oils, or combinations thereof. When used, the carrier should be selected based on the plant active ingredient and / or specific components of the composition, such as the specific celery extract used. It should be recognized that if a carrier is used, the celery extract may be incorporated with the carrier before, during, or after incorporation with the plant active ingredient and / or any other components of the composition.

[0085] lotus

[0086] In some embodiments, the plant-active component and therefore the composition comprises lotus extract, i.e., an extract comprising, optionally substantially composed of material from the flowering plant species lotus. The lotus extract is not particularly limited and may comprise or be derived from any extract or combination of extracts from the lotus plant suitable for the embodiments described herein.

[0087] Lotus has been reported to contain various bioactive components, such as alkaloids, steroids, flavonoids, glycosides, triterpenoids, polyphenols, and other compounds. (Lotus) Nelumbo nucifera It can be abbreviated as N. nucifera or various other names such as Nelumbo nucifera Gaertn., East Indian lotus, Hindu lotus, Chinese waterlily, sacred lotus, He Ye, Nelumbinis folium, or lotus leaf.

[0088] Specific examples of lotus extracts are known in the art. Therefore, lotus extracts can be purchased or otherwise commercially obtained from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein), or combinations thereof. In some embodiments, lotus extracts are obtained by aqueous extraction (or water-based extraction) of the lotus plant material. In further or other embodiments, lotus extracts are obtained by alcoholic extraction (e.g., ethanol extraction) of the lotus plant material.

[0089] As those skilled in the art will understand, lotus is cultivated primarily for its botanical material, including but not limited to its leaves and flowers. Therefore, in various embodiments, lotus extracts are extracts of lotus leaves. Suitable extractions include those noted above, such as aqueous and ethanolic extracts of the leaves. The leaves may be derived from one or more plants and may be fresh, dried, or otherwise aged.

[0090] For example, certain extracts can be obtained by grinding lotus (e.g., leaves) into uniform size in a mill. The resulting powder is then extracted with a water or ethanol solution. The solution is then filtered, and the filtrate can be concentrated under reduced pressure to obtain a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0091] In various embodiments, the plant-active component consists of an extract from lotus leaves. In further or other embodiments, the composition is substantially to completely free of components derived from non-leaf-based plant material of the lotus. In these embodiments, the non-leaf-based plant material of the lotus can be, for example, the flowers, seeds, and / or rhizomes of the lotus plant. Without being bound by any particular theory, it is believed that the lotus leaves are most helpful in promoting uric acid excretion in this formulation; while other parts of the lotus are not.

[0092] In other embodiments, the lotus extract may comprise material from any part or combination of parts of the plant, and is not limited to leaf extracts. For example, the lotus extract may comprise material extracted from one or more parts of the lotus plant, including its roots, branches, rhizomes, leaves, buds, flowers, and / or seeds. Furthermore, such extracts may be further processed (e.g., defatting, partial defatting, grinding, drying, precipitation, washing, filtering, screening, extraction, distillation, concentration, etc.) to obtain the lotus extract. Similarly, the lotus plant may be extracted in its original form or processed prior to the extraction of the lotus extract (e.g., used in its original form, suspension form, dehydrated form, concentrated form, etc.). In some embodiments, the plant active component comprises a lotus extract containing material obtained from (i.e. extracted from) the leaves of the lotus.

[0093] The amount of lotus extract used in the plant active ingredient is variable and selected based on the quantity and type of the components used. In some embodiments, the plant active ingredient comprises 1 to 2000 mg of lotus extract, such as 1 to 1000, optionally 2 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside these ranges may also be used. For example, in some embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of lotus extract. In these or other embodiments, upper limits may be selected so that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, or ≤5000 mg of lotus extract. In various embodiments, the plant-active component may include lotus extract in an amount optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95% by weight based on the total weight of the plant-active component. In such embodiments, the upper limits may be typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99% by weight based on the total weight of the plant-active component, respectively.

[0094] In some embodiments, the plant-active component comprises more than one lotus extract, such as two, three, four, or more lotus extracts. In such embodiments, each lotus extract is selected independently, may be the same as or different from any other lotus extract, and is used in the amounts described above.

[0095] Lotus extract can be used in any form, such as pure (i.e., without solvents, carriers, diluents, etc.) or in a carrier, such as a solvent or dispersant. If present, the carrier may contain an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or a combination thereof. When used, the carrier should be selected based on the plant active ingredient and / or a specific component of the composition, such as the specific lotus extract used. It should be recognized that if a carrier is used, the lotus extract may be incorporated with the carrier before, during, or after incorporation with the plant active ingredient and / or any other component of the composition.

[0096] definition

[0097] To provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0098] The terms "composition" or "formulation" refer to a product that treats, improves, promotes, increases, manages, controls, maintains, optimizes, modifies, reduces, inhibits, or prevents a particular condition associated with a natural state, biological process, or disease or disorder. For example, a composition or formulation may improve, minimize, inhibit, or prevent at least one of hyperuricemia, gout, ulcers, cancer, local ischemia, and hypertension. The terms composition and formulation include, but are not limited to, pharmaceutical (i.e., drug), over-the-counter (OTC) drugs, cosmetics, food, food ingredients, or dietary supplement compositions comprising an effective amount of an extract, at least one of its components, or a mixture thereof. Exemplary compositions and / or formulations include creams, cosmetic lotions, packs, or powders, or as emulsions, lotions, liniment foams, tablets, plasters, granules, or ointments. Preferred compositions are formulated for topical administration / application and for oral administration / ingestion.

[0099] As used herein, the terms "effective amount" or "therapeutic effective amount," referring to pure compounds, compositions, extracts, mixtures of extracts, components of extracts, and / or active agents or ingredients, or combinations thereof, mean an amount effective for a dose and time period sufficient to achieve the desired result. For example, an "effective amount" or "therapeutic effective amount" refers to the amount of a pure compound, composition, extract, plant extract, mixture of extracts, mixture of plant extracts, components of extracts, and / or combinations thereof of the present invention sufficient to achieve a treatment, such as improvement, minimization, inhibition, or prevention, of at least one of hyperuricemia, gout, ulcers, cancer, ischemia, and hypertension, when administered to a subject (e.g., a mammal, such as a human). The amounts of compositions, extracts, plant extracts, mixtures of extracts, mixtures of plant extracts, components of extracts, and / or active agents or ingredients of the present disclosure constituting an "effective amount" or "therapeutically effective treatment" will vary depending on the active agent or compound, the condition being treated and its severity, the manner of administration, the duration of treatment, or the age of the subject being treated, but can be determined by those skilled in the art in their own knowledge and in a conventional manner according to the present disclosure.

[0100] The term "pharmaceutical acceptable" refers to drugs, pharmaceutical preparations, extracts, or inert ingredients that are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, etc., and that are commensurate with a reasonable benefit / risk ratio.

[0101] The terms "administration" and "application" are defined as providing a subject with the composition via routes known in the art, including but not limited to local, intravenous, intra-arterial, oral, parenteral, buccal, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal administration. In a preferred embodiment, local and / or oral administration of the composition is suitable.

[0102] The terms “minimize,” “reduce,” “prevent,” “lower,” and / or “inhibit” refer to the reduction or decrease of xanthine oxidation and / or its downstream effects by inhibiting xanthine oxidase in the presence of a botanical (or plant) ingredient or plant extract as described herein, compared to xanthine oxidase activity in a control sample in the absence of such botanical ingredients or plant extracts. The extent to which xanthine oxidation and / or its downstream effects are reduced by inhibiting xanthine oxidase will vary with the nature and amount of the botanical ingredient or plant extract present, but will be clearly visible, for example, as a detectable reduction in xanthine oxidase activity; ideally, the reduction will be greater than about 5%, about 10%, about 15%, about 20%, about 25%, about 50%, about 75%, about 90%, about 95%, or about 99% (or any reduction in the range of about 5% to about 99%) compared to xanthine oxidase activity in the absence of the botanical ingredient or plant extract. For example, compositions containing plant components or plant extracts of silver pothos and / or senna can minimize or reduce xanthine oxidase activity.

[0103] As used herein, the terms "subject" or "individual" include mammals to which the composition may be administered. Non-limiting examples of mammals include humans, non-human primates, rodents (including transgenic and non-transgenic mice), etc. In some embodiments, the subject is a mammal, and in some embodiments, the subject is a human.

[0104] Composition (or formulation)

[0105] The composition may include any amount of plant-active components, selected based on the quantity and type of components used throughout the composition. Generally, the plant-active components are present in the composition in an amount that effectively inhibits xanthine oxidase (XO) in the subject.

[0106] In some embodiments, the composition comprises an amount of plant active ingredient of 1 to 5000, optionally 2 to 2000 mg, optionally 5 to 1750, optionally 10 to 1500, optionally 15 to 1250, optionally 20 to 1000, optionally 25 to 750, optionally 30 to 500, optionally 35 to 500, optionally 40 to 500, optionally 45 to 450, optionally 50 to 450, or optionally 50 to 400 mg. However, amounts outside and / or overlapping with these ranges may also be used. For example, it should be recognized that the ranges described above regarding the amounts of each plant extract in the plant active ingredient are equally applicable to the amounts of each plant extract in the whole composition, such as when the plant active ingredient consists of only one component of a plant extract.

[0107] In some embodiments of the composition, the formulation comprises: Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz extract and / or Anisochilus carnosus (L.) Wall. extract. In some embodiments, Anisochilus carnosus The addition of (L.) Wall. extract is optional and may not be included in the formulation. In a specific embodiment, the formulation for treating gout contains... Cichorium intybus L. (chicory) Prunus cerasus L. (sour cherry), Apium graveolens L. (celery seed) Nelumbo nucifera Gaertn. (lotus leaf) Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz (White-haired Silver Lucky) and Anisochiluscarnosus (L.) Wall. (fragrant grass).

[0108] More specific implementation methods are shown in Table 1 below. While not bound by any particular theory, it is believed that the following preparations are particularly effective in inhibiting xanthine oxidase and are therefore more suitable for the treatment, relief, and / or prevention of gout.

[0109] Table 1:

[0110]

[0111] * Not bound or limited by any particular theory.

[0112] In the table above, flavorings and artificial sweeteners can be any type of conventional component understood in the art, such as flavoring agents. Plant (or botanical) extracts can each be as described above. Examples of suitable flavoring agents are further described below. In some other embodiments, the amounts in the table above can be individually varied to ±0–100, ±0–50, ±0–25, or ±0–10% of the values ​​shown in the table above.

[0113] Generally, apart from containing plant-based active ingredients and their extracts, the composition is not limited in terms of formulation, peripheral components, form, or number of functions. Instead, the composition can be varied and formulated in any manner consistent with this disclosure.

[0114] Typically, the composition is formulated or otherwise adapted for use in mammalian subjects (e.g., humans). For example, in various embodiments, the composition is adapted for topical or consumed and / or oral administration to human subjects.

[0115] In some embodiments, the composition is further defined as a topical composition formulated for topical application to a subject. In such embodiments, the composition may also be referred to as a cosmetic composition and typically includes at least one cosmetically acceptable carrier in addition to a bioactive agent composition. In specific embodiments, the cosmetically acceptable carrier is not naturally occurring. In other words, the carrier is not a natural product in these specific embodiments. In other embodiments, the carrier is selected from conventional carriers understood in the art and can be used in conventional amounts.

[0116] In other embodiments, the composition is further defined as an oral composition formulated for oral administration to a subject. In such embodiments, the composition may also be referred to as an ingestible composition and typically contains at least one pharmaceutically acceptable additive in addition to a bioactive agent composition. In specific embodiments, the pharmaceutically acceptable additive is not naturally occurring. In other words, the pharmaceutically acceptable additive in these specific embodiments is not a natural product. In other embodiments, the pharmaceutically acceptable additive is selected from conventional additives understood in the art and can be used in conventional amounts.

[0117] Therefore, it should be recognized that the specific additives, carriers, excipients, fillers, etc., present in or combined with the composition are variable. Furthermore, the physical form of the composition is not limited and will be selected based on the specific components of the composition, the intended use of the composition, etc. Thus, as will be understood from the description herein, the composition can be formulated as a liquid, dry powder, suspension, emulsion, gel, paste, etc., and combinations thereof. In some embodiments, the composition is formulated as a sterile, pyrogen-free liquid solution or suspension, coated capsule, suppository, lyophilized powder, transdermal patch, soft capsule, or other known forms. Other examples of suitable forms include solids, gels, liquids, creams, lotions, pomades, mousses, powders, foams, sprays, ointments, or other such formulations, wherein the plant-based active ingredient is placed in a suitable carrier excipient, such as those described herein.

[0118] This composition can be prepared using various methods. For example, the active ingredient (such as a plant extract) and optionally one or more inactive ingredients (such as one or more conventional components, additives, excipients, etc.) of the composition can be mixed or blended and compressed or compounded using various techniques understood in the art. The compositions disclosed herein are not limited to a specific sequence of manufacturing steps or manufacturing method.

[0119] In various embodiments, the composition is administered orally by ingestion by a subject. Subjects are typically human and may include men and women of various ages. The methods / compositions disclosed herein are not limited to a specific subject.

[0120] The composition can be in various forms. Examples of suitable forms include solids, gels, and liquids. For example, the composition can be formulated as a gel, cream, lotion, pomades, mousses, powder, or foam to be applied to the skin of a subject. In another example, the composition can be formulated as a spray to be applied to the skin of a subject. The composition can be formulated as an aerosol spray or a pump spray. In yet another example, the composition can be formulated for application using a pre-wetted wipe. In another example, the composition can be formulated as a solid and rubbed onto the skin of a subject. In yet another example, the composition can be formulated for delivery by means of a patch that adheres to the skin of a subject.

[0121] In addition to the plant-based active ingredient (i.e., the “active substance” or “active component”), the composition may also include pharmaceutically acceptable additives as inactive substances (or “inactive components”), including but not limited to excipients such as diluents and binders; granulating agents; flow aids (or flow promoters); fillers; lubricants; preservatives; stabilizers; coating agents; disintegrants; fragrances; and pigments. The active ingredient and pharmaceutically acceptable additives may be combined or blended as needed to form a single dose (individual dose) that provides the required amount of the active ingredient to a human subject upon topical application.

[0122] Optionally, the composition may include one or more additional components, such as additives. Suitable additives include those understood in the art, including but not limited to moisturizers, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, preservatives, pharmaceuticals and active pharmaceutical ingredients, analgesic compounds, analgesic compounds, antioxidants, blood circulation promoters, antidepressant compounds, anti-anxiety compounds, anti-stress compounds, sunscreens, insect repellents, preservatives, exfoliating agents, fragrances, colorants, fillers, solvents, mediators, carriers, other types of additives known to those skilled in the art, and combinations thereof. These additives may be used alone or in combination. Generally, optional additives can be of any type used in personal care and cosmetic products.

[0123] Excipients can be further classified into other components. Specifically, excipients used in oral solid dosage forms have been classified based on their function into the following groups: such as diluents, disintegrants, binders, compression aids, granulators, flow aids, lubricants, controlled-release polymers, stabilizers (such as antioxidants, chelating agents, and pH adjusters), film-coating polymers, coating agents, mediators, plasticizers, surfactants, colorants, sweeteners, and flavors.

[0124] In various embodiments, the composition comprises at least one component selected from adhesives, lubricants, flow aids, and combinations thereof. In some embodiments, the composition comprises one or more compounds, including but not limited to methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, cellulose acetate phthalate, gum arabic, gums, waxes, glyceryl monostearate, acrylic polymers and copolymers, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, lactose, calcium sulfate, dicalcium phosphate, sugars, microcrystalline cellulose (MCC), starch, sodium glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. Combinations of these components may be used, and these components, along with other components used in conventional tablets, are understood in the art.

[0125] As used herein, “diluent” can refer to an inert substance added to increase the volume of a composition so that tablets reach a practical size for compression. Therefore, they may also be referred to as fillers. Commonly used diluents include, but are not limited to, microcrystalline cellulose (MCC), wood cellulose, corn starch, modified corn starch, tricalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch, (powdered) sugar, dextrose, mannitol, sorbitol, etc. Diluents / fillers may be used alone or in various mixtures, and in any amount known in the art for use in oral compositions.

[0126] As used herein, “flavoring agent” refers to a compound intended to impart a more palatable taste to a composition. Flavoring agents vary widely in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex volatile oils. Almost any desired type of synthetic flavoring agent is now available and is well known in the art. If astringency, sourness, or bitterness originating from the raw material can be suppressed by flavoring or flavoring, the composition may include acidifiers (e.g., citric acid, tartaric acid, malic acid, ascorbic acid, etc.), sweeteners (e.g., sodium saccharin, dipotassium glycyrrhizate, aspartame, stevia, thaumatin, etc.), or flavorings (e.g., various fruit flavorings containing lemon oil, orange oil, or strawberry, as well as yogurt, mint, menthol, etc.). Flavoring agents may be used alone or in various mixtures, and in any amount known in the art for oral composition.

[0127] As used herein, "lubricant" refers to a material that performs many functions related to the composition. In some embodiments, such as tablet manufacturing, lubricants perform one or more functions, such as improving the flow rate of tablet granulation, preventing tablet material from adhering to the surfaces of the die and punch, reducing interparticle friction, and facilitating tablet ejection from the die cavity. Examples of suitable lubricants include, but are not limited to, zinc stearate, gum arabic powder, cocoa butter, carbamate wax, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, caropeptide, aqueous silica, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicate, light liquid paraffin, crystalline cellulose, hardened oil, synthetic aluminum silicate, sesame oil, flour starch, beeswax, magnesium oxide, dimethyl polysiloxane, potassium sodium tartrate, sucrose fatty acid esters, glyceryl fatty acid esters, silicone resins, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyethylene stearate. Stearate, magnesium stearate, cetyl alcohol, gelatin, talc, magnesium carbonate, precipitated calcium carbonate, corn starch, lactose, stearic acid, sucrose, potato starch, hydroxypropyl cellulose, fumaric acid, sodium stearyl fumarate, polyethylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, beeswax, magnesium aluminum metasilicate, methylcellulose, Japanese wax, glyceryl monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, phosphoric acid, palmitic acid, and hydrogenated vegetable oils and fats. The lubricant can be used alone or in various mixtures, and in any amount known in the art for oral compositions.

[0128] As used herein, "binder" is an agent used to impart cohesiveness to powdered materials. Binders, or sometimes called "granulators," impart cohesiveness to tablet formulations to ensure that tablets remain intact after compression and to improve free-flowing properties by formulating particles of the desired hardness and size. Materials commonly used as binders include starches, such as corn starch and pregelatinized starch; gelatin; sugars, such as sucrose, glucose, dextrose, molasses, and lactose; and natural and synthetic gums, such as gum arabic, sodium alginate, Irish moss extract, panwar gum, Indian gum, mucilage of isapol husks, carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone (PVP), veegum, microcrystalline cellulose, microcrystalline dextrose, amylose, larch arabinogalactan, ethyl cellulose, cellulose acetate, etc. Binders can be used alone or in various mixtures and in any amount known in the art for use in oral compositions.

[0129] As used herein, "coloring agent" is an agent that imparts a more pleasing appearance to a composition, and also helps manufacturers control the product during its preparation and helps users identify it. Any approved, certified water-soluble FD&C dye, mixtures thereof, or their corresponding lakes can be used to color tablets. A lake is a combination obtained by adsorbing a water-soluble dye onto a hydrated oxide of a heavy metal, thus yielding an insoluble form of the dye. Coloring agents can be used alone or in various mixtures, and in any amount known in the art for use in oral compositions.

[0130] Other conventional ingredients that may be present in the composition include preservatives, stabilizers, anti-adhesion agents, or silica flow modifiers or flow aids, such as silica. These ingredients may be used alone or in various mixtures, and in any amount known in the art for use in oral compositions.

[0131] It should be recognized that certain components or additives may be classified under different technical terms, and the fact that a component or additive is classified under a term does not mean that it is limited to that function. If used, additives may be present in the composition in various amounts. For example, when used for topical or oral application, optional additional ingredients for the composition are described in U.S. Patent Nos. 5,747,006; 5,980,904; 6,994,874; 7,060,304; 7,247,321; 7,348,034; 7,364,759; 7,700,110; 7,722,904; 8,202,556; 8,916,212; 9,445,975; 9,801,809; 10,307,366; 10,532,024; and 10,537,516; and U.S. Publication No. The publications of No. 2006 / 0257509; No. 2007 / 0224154; No. 2008 / 0081082; No. 2008 / 0124409; No. 2013 / 0302265; No. 2017 / 0252293; No. 2017 / 0281666; No. 2018 / 0200285; No. 2019 / 0083566; No. 2019 / 0160117; No. 2020 / 0171117; No. 2020 / 0383898; No. 2021 / 0017240; and No. 2021 / 0212926 are hereby cited in their entirety and incorporated herein by reference.

[0132] Application method

[0133] This composition may be administered or given as needed, daily, several times daily, or in any suitable regimen to achieve the desired results. In the methods disclosed herein, the frequency of administration (e.g., oral ingestion) may depend on several factors, including the desired level of xanthine oxidase (XO) inhibition. Typically, the regimen involves ingesting the composition once or twice daily, including administration in the morning and / or at night. The dosage and / or frequency of administration of the composition may depend on several factors, including the level of desired results and the specific composition.

[0134] Improved XO inhibition can be achieved by applying the formulations of the present invention externally, internally, or in some combination thereof. Preferably, the formulations of the present invention are applied together with an acceptable carrier. For example, the formulations of the present invention can be applied externally together with an acceptable carrier in the form of gels, lotions, creams, tonics, emulsions, etc. As a further example, the formulations of the present invention can be applied internally together with an acceptable carrier in the form of pills, tablets, powders, bars, beverages, etc. Therefore, the formulations described herein can be used in a wide variety of finished products, including pharmaceutical, food, and beverage compositions. Preferably, the product can be used to provide XO inhibition for mammals.

[0135] When the formulations of the present invention are administered orally in liquid form, the liquid may be water-based, milk-based, tea-based, fruit juice-based, or some combination thereof. Solid and liquid formulations for internal use according to the present invention may further comprise thickeners, including xanthan gum, carboxymethyl cellulose, carboxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, microcrystalline cellulose, starch, dextrin, fermented whey, tofu, maltodextrin, polyols including sugar alcohols (e.g., sorbitol and mannitol), carbohydrates (e.g., lactose), propylene glycol alginate, gellan gum, guar gum, pectin, tragacanth gum, acacia gum, locust bean gum, gum arabic, gelatin, and mixtures of these thickeners. These thickeners are typically included in the formulations of the present invention at a maximum of about 0.1%, depending on the specific thickener involved and the desired viscosity effect.

[0136] The solid and liquid (food and beverage) formulations of the present invention may contain, and typically contain, effective amounts of one or more sweeteners, including carbohydrate sweeteners and natural and / or artificial zero / low-calorie sweeteners. The amount of sweetener used in the formulations of the present invention varies, but generally depends on the type of sweetener used and the desired sweetness intensity.

[0137] In another example, the formulations of the present invention are applied topically in the form of solutions, gels, lotions, creams, ointments, oil-in-water emulsions, water-in-oil emulsions, sticks, sprays, pastes, mousses, tonics, foundations or other cosmetics and other suitable topical forms.

[0138] Preferably, the formulation of the present invention suitable for topical application is mixed with an acceptable carrier. The acceptable carrier can act in various ways as a solvent, carrier, diluent, or dispersant for the components of the composition, allowing the components to be uniformly applied to the skin surface with appropriate dilution. The acceptable carrier can also promote the penetration of the composition into the skin.

[0139] In one example of a formulation for topical application, an acceptable carrier constitutes from about 70% to about 99.99% by weight of the total composition. In other examples, an acceptable carrier constitutes from about 85% to 99.99% by weight of the total composition. An acceptable carrier may also constitute from about 90% to about 99.99% by weight of the total composition; or from about 99.95% to about 99.999% by weight of the total composition. An acceptable carrier may constitute the remainder of the composition in the absence of other cosmetic adjuvants or additives.

[0140] The various components used in carrying out this invention may be soluble or insoluble in an acceptable carrier. If all components of the formulation are soluble in an acceptable carrier, the carrier acts as a solvent. However, if all or some components of the formulation are insoluble in an acceptable carrier, these components are dispersed in the carrier by means of, for example, a suspension, emulsion, gel, cream, or paste.

[0141] Therefore, it will be apparent to those skilled in the art that the range of possible acceptable carriers is very broad. For example, an acceptable carrier may be an emulsion, lotion, cream, or tonic. An acceptable carrier may contain water, ethanol, butylene glycol, or various other solvents that facilitate skin penetration. Examples of suitable media are described in U.S. Patent Nos. 6,184,247 and 6,579,516, the entire contents of which are incorporated herein by reference.

[0142] Preferably, the acceptable carrier for carrying out the invention comprises water and ethanol. Optionally, the acceptable carrier also contains butanediol. For example, the acceptable carrier may contain 2-5% butanediol by weight of the composition. In practice, it is preferred to mix such an acceptable carrier with 2% by weight of the formulation of the invention constituting the total composition. In other examples, the acceptable carrier is mixed with 0.001% to 30% by weight of the total composition; 1% to 5% by weight of the total composition; 0.01% to 15% by weight of the total composition; or 0.5% to 1.0% by weight of the formulation of the invention constituting the total composition.

[0143] However, generally speaking, acceptable carriers according to the invention may comprise, but are not limited to, any of the following examples: water; castor oil; ethylene glycol monobutyl ether; diethylene glycol monoethyl ether; corn oil; dimethyl sulfoxide; ethylene glycol; isopropanol; soybean oil; glycerin; soluble collagen; safflower seed oil; meadowfoam seed oil; mineral oil; squalene; shea butter; borage oil; or rice bran oil; polyquaternium-10; methylparaben; PEG-8; disodium lauroamphoacetate; sodium tridecyl ether sulfate; hexanediol; sodium methyl cocoyl taurate; lauryl sulfate TEA salt; lauryl betaine; sodium myristoyl sarcosinate; PEG-150 distearate; anhydrous citric acid; sodium citrate dihydrate; diazonyl alkyl Urea; Disodium EDTA; Propylparaben; Polysorbate 60; Isopropyl palmitate; Octyl palmitate; C12-15 alkyl benzoate; Dipropylene glycol dibenzoate; PPG-15 stearyl ether benzoate; Isododecane; Isoeicosane; Squalane; Jojoba oil; Polydimethylsiloxane; Glyceryl stearate; PEG-100 stearate; Cetyl alcohol; Butylene glycol; Chlorphenesin; Fragrance; Polyacrylamide; C13-14 isoparaffin; Lauryl ether-7; Aloe vera powder; Aloe vera gel; Hydroxyethyl acrylate; Sodium acryloyl dimethyl taurate copolymer; Behenyl alcohol; Tocopheryl acetate; Isodecyl neopentanoate; Glyceryl tricaprylate; Cetearyl alcohol; Cetearyl glucoside; Chamomile flower extract; Biosaccharide gum-1 Pentadecyl lactone; Dipropylene glycol; Cyclomethicone; PEG / PPG-18 / 18 polydimethylsiloxane; Cyclopentasiloxane; Distearate dimethylammonium lithium montmorillonite; SD alcohol 40; Phenoxyethanol; Ethyl p-hydroxybenzoate; Trimethylsiloxysilicate; Triethoxyoctylsilane; Micronized titanium dioxide; Titanium dioxide; Zinc oxide; Iron oxide (yellow; red; black; etc.); Octylsilane; Sodium chloride; Diisopropyl dimer dilinoleate; Aluminum hydroxide; Stearic acid; Polyethylene beads; C12-15 alkyl benzoate; Acrylates / C10-30 alkyl acrylates; Xanthan gum; Sorbitol laurate; Panthenol; Petrolatum; Isopropyl isostearate; Polydimethylsiloxane; Arginine; Phenoxyethanol; Acryloyl dimethylsiloxane Methyl taurate copolymer; isohexadecane; polysorbate 80; hydroxyethyl acrylate; sodium acryloyl dimethyl taurate copolymer; octinoxate; oxybenzone; dioctyl ether; isodecanyl valerate; cetearyl alcohol; cetearyl glucoside; benzyl alcohol; HDI / trimethylolcaprolactone crosspolymer; silica; isodecanyl valerate; cocoyl glucoside; C20-22 alkyl phosphate; C20-22 alcohol; palmitoyl proline; magnesium palmitoyl glutamate; sodium palmitoyl sarcosinate; C30-45 alkyl cetearyl crosspolymer; polyacrylate 13; polyisobutylene; polysorbate 20; iodopropynyl butylcarbamate; sodium magnesium silicate.Methyl glucitol polyether-20; dimethyl isosorbide; silica; SD alcohol 40-B; salicylic acid; cetyl alcohol polyether-20; fragrance; or witch hazel.

[0144] Additionally, acceptable carriers for use in this invention may optionally comprise one or more wetting agents, including but not limited to: dibutyl phthalate; soluble collagen; sorbitol; or sodium 2-pyrrolidone-5-carboxylate. Other examples of wetting agents that can be used to carry out this invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0145] Additionally, the acceptable carrier in this invention may optionally comprise one or more emollients, including but not limited to: butyl-1,3-diol; cetyl palmitate; dimethylpolysiloxane; glyceryl monoricinoleate; glyceryl monostearate; isobutyl palmitate; isocetyl stearate; isopropyl palmitate; isopropyl stearate; butyl stearate; isopropyl lauryl oleate; hexyl lauryl oleate; isopropyl myristate; lauryl lactate; octadecane- 2-Alcohol; Caprylic / Capric Triglyceride; Caprylic / Capric Triglyceride; Polyethylene Glycol; Propylene-1,2-Diol; Triethylene Glycol; Sesame Oil; Coconut Oil; Safflower Oil; Isoamyl Laurate; Nonoxynol-9; Panthenol; Hydrogenated Vegetable Oil; Tocopheryl Acetate; Tocopheryl Linoleate; Allantoin; Propylene Glycol; Peanut Oil; Castor Oil; Isostearic Acid; Palmitic Acid; Isopropyl Linoleate; Lauryl Lactate; Myristyl Lactate; Decyl Oleate; or Myristyl Myristate. Other examples of emollients that can be used to practice the present invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0146] Additionally, the acceptable carriers used in this invention may optionally contain one or more penetration enhancers, including but not limited to: pyrrolidone, such as 2-pyrrolidone; alcohols, such as ethanol; alkanols, such as decanol; diols, such as propylene glycol, dipropylene glycol, and butanediol; surfactants; or terpenes.

[0147] Other acceptable carriers that can be used to implement the present invention are obvious to those skilled in the art and are included within the scope of the present invention.

[0148] For example, an acceptable carrier may be a topical lotion. The lotion may contain carbomer 981, water, glycerin, isopropyl myristate, mineral oil, shea butter, stearic acid, ethylene glycol stearate, cetyl alcohol, polydimethylsiloxane, preservatives, TEA, and various components of the formulations of this invention.

[0149] The formulations of the present invention may also contain a variety of known and conventional cosmetic adjuvants, provided they do not adversely affect the desired improvement provided by the formulation. For example, the formulations of the present invention may further include one or more additives or other optional ingredients well known in the art, which may include, but are not limited to, fillers (e.g., solid, semi-solid, liquid, etc.); carriers; diluents; thickeners; gelling agents; vitamins, vitamin A-like substances, and retinols (e.g., vitamin B3, vitamin A, etc.); pigments; fragrances; chemical sunscreens and physical sunblocks; antioxidants and free radical scavengers; organic hydroxy acids; exfoliating agents; skin conditioning agents; moisturizers; ceramides, pseudoceramides, phospholipids, sphingolipids, cholesterol, glucosamine, pharmaceutically acceptable penetrants (e.g., n-decylmethyl sulfoxide, lecithin organic gel, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids such as proline, pyrrolidone carboxylic acid, their derivatives and salts, and saccharide isomers. isomerates, panthenol, buffers with bases such as triethanolamine or sodium hydroxide; waxes such as beeswax, ceresin, and paraffin; plant extracts such as aloe vera, cornflower, witch hazel, elderflower, or cucumber, and combinations thereof. Other suitable additives and / or adjuvants are described in U.S. Patent No. 6,184,247, the entire contents of which are incorporated herein by reference.

[0150] The formulation may include additional inactive ingredients, including but not limited to surfactants, solubilizers, and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, may be included in the formulation. Specific surfactants may be used based on the overall composition of the formulation and its intended delivery. Available surfactants include polyethoxylated (PEG) fatty acids, PEG-fatty acid diesters, mixtures of PEG-fatty acid monoesters and diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerolized fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters and glycerol esters, glycerol monoesters and diesters, sterols and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, polysaccharide esters, polyethylene glycol alkylphenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants, and mixtures thereof.

[0151] The formulation may also include cosolvents such as alcohols and polyols, polyethylene glycol ethers, amides, esters, other suitable cosolvents, and mixtures thereof. The formulation may also include excipients or additives such as sweeteners, flavoring agents, coloring agents, antioxidants, preservatives, chelating agents, viscosity modifiers, tonicifiers, odorants, emulsifiers, suspending agents, binders, and mixtures thereof.

[0152] Typically, the formulations of the present invention are applied topically or orally for at least a period of time each day sufficient to achieve the desired level of improvement in xanthine oxidase inhibition. Topical or oral administration of the formulations of the present invention can continue for any suitable period of time. More specifically, within hours to days of initial administration or ingestion, the user may notice an improvement in symptoms of hyperuricemia, gout, ulcers, cancer, local ischemia, or hypertension. It should be understood that the frequency of administration or ingestion of the formulations of the present invention varies depending on the desired level of improvement. In particular, the degree of symptom relief will vary directly with the total amount of the composition used.

[0153] Useful dosage forms can be prepared by methods and techniques fully understood by those skilled in the art and may include the use of additional ingredients in the production of tablets, capsules or liquid dosage forms.

[0154] Industrial applicability

[0155] This disclosure provides novel and useful inhibitors of advanced xanthine oxidase (XO) comprising the plant extracts described herein. Such XO inhibitors provide potential preventative and therapeutic methods for reducing the risk of hyperuricemia, gout, ulcers, cancer, local ischemia, hypertension, oxidative stress, oxidative damage, or other pathogenic complications caused by XO activity. Therefore, the compositions and methods described herein can be used to inhibit XO.

[0156] The general compositions and product families disclosed herein relate to personal care, nutritional, skin care, and nutritional beauty products utilizing such XO inhibitors, and specific examples include pills and liquids utilizing such XO inhibitors.

[0157] XO is a metabolic pathway involved in uric acid formation. Elevated blood uric acid levels can lead to gout when high levels of uric acid crystallize and deposit in joints, tendons, and surrounding tissues. Elevated blood uric acid can also affect cardiovascular health. Additionally, byproducts of XO activity, such as hydrogen peroxide, can cause oxidative stress. The compositions and methods disclosed herein provide potential preventative and therapeutic methods for reducing the risk of hyperuricemia, gout, ulcers, cancer, local ischemia, hypertension, oxidative stress, oxidative damage, or other pathogenic complications caused by XO.

[0158] The following examples illustrating the compositions and methods of this disclosure are intended to be illustrative and not limiting of this disclosure. Example

[0159] The inhibitory effects of water and ethanol extracts of two plants on xanthine oxidase (XO) were evaluated. Specifically, the inhibitory potential of two *Potentilla fruticosa* extracts and two *Eupatorium fortunei* extracts on XO was evaluated. As shown in the table and figures below, all four extracts exhibited inhibition. The extracts were prepared in the laboratory but are also commercially available.

[0160] XO inhibition

[0161] The inhibitory activity of the extract was determined by spectrophotometry using a 96-well plate. The reaction mixture consisted of 50 μL of sample and 50 μL of 0.02 U / mL xanthine oxidase solution, shaken gently for 30 seconds, and incubated at 25°C for 5 minutes. Then, 150 μL of 0.48 mM xanthine solution was added, the mixture was again carefully shaken for 30 seconds, and incubated at 37°C for 30 minutes. The incubated solution was then used for the following measurements.

[0162] Determination of inhibition rate

[0163] Measure the absorbance of the incubated solution. Calculate the inhibition rate of XO using the following equation:

[0164] Inhibition rate (%) =

[0165] Where A1 is the absorbance of the mixture of sample and XO, A2 is the absorbance of the mixture of sample and buffer, A3 is the absorbance of the mixture of buffer and XO, and A4 is the absorbance of the buffer.

[0166] The results are shown in the table below. The average inhibition rate can also be understood by referring to the attached figures.

[0167] Table 2:

[0168]

[0169] * See also Figure 1 (Where the X-axis represents concentration and the Y-axis represents % inhibition).

[0170] Table 3:

[0171]

[0172] * See also Figure 2 (Where the X-axis represents concentration and the Y-axis represents % inhibition).

[0173] Table 4:

[0174]

[0175] * See also Figure 3 (Where the X-axis represents concentration and the Y-axis represents % inhibition).

[0176] Table 5:

[0177]

[0178] * See also Figure 4(Where the X-axis represents concentration and the Y-axis represents % inhibition).

[0179] As shown in the table above, for both Potentilla chinensis and Clematis armandii, the 70% ethanol extract generally exhibits higher XO inhibition compared to the aqueous extract.

[0180] The term “comprising” is used herein in its broadest sense to indicate and encompass the concepts of “including,” “essentially consisting of,” and “composed of.” The use of “for example,” “such as,” and “including” to list illustrative examples is not limited to those listed. Therefore, “for example” or “such as” means “for example but not limited to” or “such but not limited to” and covers other similar or equivalent examples. The term “about” as used herein is used to reasonably cover or describe slight variations in values ​​measured by instrumental analysis or caused by sample processing. Such slight variations may be about ±0–10, ±0–5, or ±0–2.5% of the value. Furthermore, the term “about” applies to both values ​​when relating to a range of values. Additionally, the term “about” may apply to values ​​even if not explicitly stated otherwise.

[0181] Generally, as used herein, the hyphen “-” or the superscript “–” in a numerical range means “to” or “to”; ">” means “higher than” or “greater than”; “≥” means “at least” or “greater than or equal to”; “<” means “lower than” or “less than”; and “≤” means “at most” or “less than or equal to”. On an individual basis, each of the foregoing patent applications, patents and / or patent application disclosures is expressly and entirely incorporated herein by reference in one or more non-limiting embodiments.

[0182] It should be understood that the appended claims are not limited to the specific compounds, compositions, or methods described in the detailed description, and they may vary among specific embodiments falling within the scope of the appended claims. Regarding any Markush group on which the various embodiments are described herein, it should be recognized that different, specific, and / or unexpected results can be obtained by each member of each Markush group independently of all other Markush members. The members of the Markush groups can be relied upon individually and / or in combination to provide sufficient support for the specific embodiments within the scope of the appended claims.

[0183] It should also be understood that any scope and subscopes upon which the various embodiments of the invention are described fall independently and collectively within the scope of the appended claims, and are to be understood as describing and considering all ranges of integer and / or fractional values ​​included therein, even if such values ​​are not expressly stated herein. Those skilled in the art will readily recognize that the enumerated scopes and subscopes are sufficient to describe and implement the various embodiments of the invention, and that such scopes and subscopes may be further described as related 1 / 2, 1 / 3, 1 / 4, 1 / 5, and so on. For example, the range “0.1 to 0.9” may be further described as the lower 1 / 3, i.e., 0.1 to 0.3, the middle 1 / 3, i.e., 0.4 to 0.6, and the upper 1 / 3, i.e., 0.7 to 0.9, which fall independently and collectively within the scope of the appended claims and may independently and / or collectively provide sufficient support for the specific embodiments within the scope of the appended claims. Furthermore, regarding terms defining or modifying scope, such as “at least,” “greater than,” “less than,” “not greater than,” etc., it should be understood that such terms include subscopes and / or upper or lower limits. As another example, the scope of "at least 10" inherently includes sub-scopes of at least 10 to 35, at least 10 to 25, 25 to 35, and so on, and each sub-scope can be relied upon independently and / or collectively to provide sufficient support for specific embodiments within the scope of the appended claims. Finally, independent numerical values ​​within the disclosed scope can be relied upon to provide sufficient support for specific embodiments within the scope of the appended claims. For example, the scope of "1 to 9" includes various independent integers, such as 3, and independent numerical values ​​(or fractions) with decimal points, such as 4.1, which can be relied upon to provide sufficient support for specific embodiments within the scope of the appended claims.

[0184] The invention has been described herein by way of example, and it is to be understood that the terminology used is descriptive rather than restrictive. Many modifications and variations of the invention are possible in accordance with the foregoing teachings. The invention may be practiced in ways different from the specific description within the scope of the appended claims. The subject matter of all combinations of independent and dependent claims (including single and multiple dependent claims) is expressly contemplated herein.

Claims

1. Use of a composition for the manufacture of a medicament for the prevention or treatment of hyperuricemia caused by xanthine oxidase (XO), wherein the composition is made from i) an extract of Anisochilus carnosus, or from i) an extract of Anisochilus carnosus and ii) an extract of Potentilla glabra, wherein the extracts are present in the composition in an amount effective to inhibit xanthine oxidase (XO) in a subject, wherein the extract of Anisochilus carnosus is an ethanol and / or aqueous extract, and the extract of Potentilla glabra is an ethanol and / or aqueous extract.

2. Use according to claim 1, wherein the extract of Potentilla glabra consists of one or both of an extract of Potentilla glabra flowers and an extract of Potentilla glabra leaves.

3. Use according to claim 2, wherein the extract of Potentilla glabra is obtained by aqueous extraction of one or more of Potentilla glabra flowers, flower-based plant material, leaves, and leaf-based plant material.

4. Use according to claim 2, wherein the extract of Potentilla glabra is obtained by water extraction of one or more of Potentilla glabra flowers, flower-based plant material, leaves, and leaf-based plant material.

5. Use according to claim 2, wherein the extract of Potentilla glabra is obtained by ethanol extraction of one or more of Potentilla glabra flowers, flower-based plant material, leaves, and leaf-based plant material.

6. Use according to claim 1, wherein the composition is substantially to completely free of components derived from non-flower-based plant material and non-leaf-based plant material of Potentilla glabra.

7. Use according to claim 1, wherein the Duchesnea indica is the variety Duchesnea indica var. mandshurica (Maxim.) Hand.-Mazz. Potentilla glabra Lodd. var.mandshurica (Maxim.) Hand.-Mazz.

8. Use according to claim 1, wherein the extract of Anisochilus carnosus consists of one or both of an extract of Anisochilus carnosus roots and an extract of Anisochilus carnosus stems.

9. Use according to claim 8, wherein the extract of Anisochilus carnosus is obtained by aqueous extraction of one or more of Anisochilus carnosus stems, stem-based plant material, roots, and root-based plant material.

10. Use according to claim 8, wherein the extract of Anisochilus carnosus is obtained by water extraction of one or more of Anisochilus carnosus stems, stem-based plant material, roots, and root-based plant material.

11. Use according to claim 8, wherein the extract of Anisochilus carnosus is obtained by ethanol extraction of one or more of Anisochilus carnosus stems, stem-based plant material, roots, and root-based plant material.

12. Use according to claim 1, wherein the composition is substantially to completely free of components derived from non-stem-based plant material and non-root-based plant material of Anisochilus carnosus.

13. Use according to claim 1, wherein Anisochilus carnosus is the species Anisochilus carnosus (L.) Wall.

14. Use according to any one of claims 1 to 13, wherein the composition is further defined as an oral composition formulated for oral administration to a subject.

15. The use according to claim 14, wherein the composition further comprises a pharmaceutically acceptable additive.

16. The use according to claim 15, wherein the pharmaceutically acceptable additive is not naturally occurring.

17. The use according to any one of claims 1 to 13, wherein the composition is further defined as a topical composition formulated for topical application to a subject.

18. The use according to claim 17, wherein the composition further comprises a cosmetically acceptable carrier.

19. The use according to claim 18, wherein the cosmetically acceptable carrier is not naturally occurring.

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