Compositions and methods for inhibiting alpha-glucosidase, lipase and xanthine oxidase

Abstract

The present invention relates to compositions and methods for inhibiting alpha-glucosidase, lipase and xanthine oxidase. The compositions comprise at least one plant active component present in an amount effective to inhibit one or more of alpha-glucosidase, lipase, and xanthine oxidase in a subject. The plant active component comprises Mongolidine F, and is basically composed of Mongolidine F, or the plant active component is Mongolidine F. The composition may be in the form of an oral composition, for example for ingestion, or in the form of a topical composition, for example for topical application. Also provided are uses of the composition for inhibiting at least one of alpha-glucosidase, lipase and xanthine oxidase in a subject, and uses of the composition for preparing a medicament for treating at least one of hyperglycemia, hyperlipidemia and hyperuricemia. Also provided are methods of inhibiting at least one of an alpha-glucosidase, a lipase, and a xanthine oxidase in a subject. The method comprises administering to the subject an effective amount of the composition.

Description

Technical Field

[0001] The present invention generally relates to compositions and methods for inhibiting α-glucosidase, lipase, and / or xanthine oxidase, and more particularly, to compositions containing plant extracts for inhibiting α-glucosidase, lipase, and / or xanthine oxidase in a subject. Background Art

[0002] α-Glucosidase is an enzyme that catalyzes the cleavage of glycosidic bonds in oligosaccharides or glycoconjugates to break down starch and disaccharides into glucose. α-Glucosidase is localized in the brush border of the small intestine and is responsible for metabolizing oligosaccharides and disaccharides into monosaccharides. High levels of glucose in the blood are referred to as hyperglycemia. Postprandial hyperglycemia remains a problem in the management of type 2 diabetes. Postprandial hyperglycemia significantly contributes to the development of chronic diabetic complications, particularly the cardiovascular and microvascular complications of diabetes. Among all available antidiabetic drugs, α-glucosidase inhibitors appear to be the most effective in reducing postprandial hyperglycemia.

[0003] Pancreatic lipase (PL) is a key enzyme in the human gastrointestinal system responsible for hydrolyzing 50%-70% of dietary fat and has been recognized as one of the key enzymes for fat digestion and absorption. PL inhibitors can reduce the hydrolysis activity of this key enzyme to lower the breakdown (metabolism) and absorption of dietary fat in the human digestive organs, thereby alleviating and preventing the symptoms of metabolic diseases such as hyperlipidemia.

[0004] Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and the subsequent oxidation of xanthine to uric acid, thereby also generating hydrogen peroxide (H2O2) as a byproduct and sometimes also producing superoxide ions (O2· - )). The production of uric acid and / or xanthine oxidation byproducts can be a contributor to pathological conditions such as hyperuricemia, gout, ulcers, cancer, ischemia, hypertension, cardiovascular disease, and oxidative stress.

[0005] In view of the foregoing, there is an opportunity to provide new and useful α-glucosidase inhibitors. Such α-glucosidase inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperglycemia, diabetes, or other pathogenic complications caused by α-glucosidase. There is also an opportunity to provide new and useful pancreatic lipase inhibitors. Such pancreatic lipase inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperlipidemia or other pathogenic complications caused by pancreatic lipase activity. Additionally, there is an opportunity to provide new and useful xanthine oxidase inhibitors. Such xanthine oxidase inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperuricemia, gout, ulcers, cancer, ischemia, hypertension, cardiovascular diseases, oxidative stress, oxidative damage, or other pathogenic complications caused by xanthine oxidation. Accordingly, there is also an opportunity to provide new and useful compositions and methods for inhibiting one or more of α-glucosidase, pancreatic lipase, and xanthine oxidase. Summary of the Invention

[0006] Compositions for administration to a subject are provided. The compositions comprise at least one phytologically active component. The phytologically active component is generally present in the composition in an amount effective to inhibit at least one of α-glucosidase, pancreatic lipase, and xanthine oxidase (XO) in the subject. The phytologically active component comprises Mongolidine F, consists essentially of Mongolidine F, or is Mongolidine F.

[0007] 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.

[0008] The composition can be used to inhibit one or more of α-glucosidase, pancreatic lipase, and xanthine oxidase in a subject. A method of inhibiting one or more of α-glucosidase, pancreatic lipase, and xanthine oxidase in a subject comprises administering to the subject an effective amount of the composition. The composition can also be used to prepare a medicament for treating one or more of hyperglycemia, hyperlipidemia, and hyperuricemia. Brief Description of the Drawings

[0009] Figure 1 is a graph showing the inhibition rate of α-glucosidase using Mongolidine F.

[0010] Figure 2 is a graph showing the inhibition rate of pancreatic lipase (PL) using Mongolidine F; and

[0011] Figure 3It is a graph showing the inhibition rate of xanthine oxidase (XO) using Mongolidine F. Detailed implementation mode

[0012] Compositions for administration to a subject are disclosed. The composition comprises at least one phytologically active component, which comprises Mongolidine F, consists essentially of Mongolidine F, or is Mongolidine F. The composition is described below, followed by a description of related uses and methods.

[0013] As will be understood in view of the present disclosure, apart from the phytologically active component and in particular Mongolidine F, the composition and related components and methods are not particularly limited. Thus, the composition can be formulated, for example, as a topical composition (e.g., a cosmetic composition), or an oral composition or a nutritional product, a drug or a supplement, and can be utilized as a unique and independent therapeutic agent or in combination with other therapeutic agents with which it is compatible.

[0014] The composition can be used to treat, prevent and / or improve various conditions, such as those related to α-glucosidase activity. Specifically, as will be appreciated in view of the description and examples below, the compositions of the embodiments herein are considered to be capable of inhibiting α-glucosidase, and more specifically, inhibiting α-glucosidase in a subject.

[0015] The composition can also be used to treat, prevent and / or improve various conditions, such as those related to pancreatic lipase activity. Specifically, as will be appreciated in view of the description and examples below, the compositions of the embodiments herein are considered to be capable of inhibiting pancreatic lipase, and more specifically, inhibiting pancreatic lipase in a subject.

[0016] The composition can also be used to treat, prevent and / or improve various conditions, such as those related to xanthine oxidation. Specifically, as will be appreciated in view of the description and examples below, the compositions of the embodiments herein are considered to be capable of inhibiting xanthine oxidation, and more specifically, inhibiting xanthine oxidase in a subject.

[0017] Accordingly, the composition can be used to treat (i.e., slow down, prevent, reverse, etc.) conditions generally associated with α-glucosidase activity, such as complications associated with hyperglycemia, diabetes, and other health disorders. The composition can also be used to treat (i.e., slow down, prevent, reverse, etc.) conditions generally associated with pancreatic lipase activity, such as complications associated with hyperlipidemia and other health disorders. The composition can also be used to treat (i.e., slow down, prevent, reverse, etc.) conditions generally associated with xanthine oxidation, such as complications associated with hyperuricemia, gout, and other health disorders, such as ulcers, cancer, ischemia, hypertension, cardiovascular diseases, oxidative stress, and oxidative damage.

[0018] As described above, the composition comprises a plant active component. More specifically, the plant active component comprises Mongolidine F, optionally consisting essentially of Mongolidine F, optionally consisting of Mongolidine F, or optionally being Mongolidine F. Mongolidine F is a polyamine-based compound and is assigned the CAS registration number 2252197-27-4. Mongolidine F can be obtained as a single isolated extract of the plant species Potentilla glabra. Alternatively, Mongolidine F can be an isolated extract obtained from Quercus mongolica pollen. The extract may be abbreviated as "plant extract".

[0019] The term "extract" is used herein in its conventional meaning to refer to a composition that has been obtained from source material by fluid extraction. Thus, the term "plant extract" should be understood to mean a composition obtained from a plant source (i.e., plant material) via fluid extraction (e.g., solvent extraction, gas extraction, CO2 extraction, etc.). Suitable plant extracts for the composition can be obtained via any extraction method known in the art or a combination of such methods, including water extraction, steam extraction, solvent extraction, etc. Exemplary extraction techniques are described below. However, plant extracts are generally not limited to a specific extraction method or additional / auxiliary techniques used to obtain the plant extract, but can vary according to the parameters described herein. Additionally, an extraction step is not required to prepare the plant active component and / or the composition, as suitable extracts (e.g., standardized extracts) are readily available from many commercial suppliers.

[0020] Plant extracts suitable for or as the plant active component include those obtained by solvent extraction, such as by using polar solvents such as alcohols (e.g., methanol, ethanol, butylene glycol, etc.), ethers (e.g., diethyl ether, methyl tert-butyl ether, etc.), ketones (e.g., acetone), esters (e.g., ethyl acetate), phenols, water, etc., non-polar solvents such as benzene, xylene, toluene, etc., and their derivatives, modifications and combinations (e.g., solvent-water blends, including ethanol-water, acetone-water, etc.). Additionally and alternatively, extraction techniques include continuous fractionation, total hydro-ethanolic extraction, lump-sum extraction, supercritical fluid extraction (e.g., with CO2), etc., and those techniques utilizing a sequential or second extraction from a first extract (e.g., a non-polar solvent extract of a plant extract obtained from a polar solvent extraction), 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.

[0021] 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, peels, resins, rhizomes, roots, seeds, and / or wood. Essential oils can be obtained by a variety of methods, such as by distillation (e.g., using steam), pressing, solvent extraction, absolute oil extraction, resin tapping, and / or cold pressing.

[0022] In various embodiments, the solvent used to obtain a suitable plant extract for the present disclosure is a solvent in which the resulting plant extract and / or its subsequent form (e.g., plant extract powder) is suitable for ingestion. For example, the solvent is water or ethanol.

[0023] In one example, a plant extract can be obtained using an organic solvent extraction technique. In another example, solvent continuous fractionation can be used to obtain a plant extract. Total hydro-ethanolic extraction techniques can also be used to obtain a plant extract. Generally, this is referred to as lump-sum extraction. The plant extract generated in this process will contain a wide variety of phytochemicals present in the extraction material, including lipophilic and hydrophilic phytochemicals. After collecting the plant extract solution, the solvent is evaporated to produce the plant extract.

[0024] Absolute ethanol extraction can also be used. This technique uses ethanol as a solvent. This extraction technique yields a plant extract that can include lipophilic and / or fat-soluble compounds in addition to water-soluble compounds. Absolute methanol extraction can also be used in a similar manner with similar results.

[0025] Another example of an extraction technique that can be used to obtain a plant extract is supercritical fluid carbon dioxide extraction (SFE). In this extraction procedure, the material to be extracted is not exposed to any organic solvents. Instead, the extraction solvent is carbon dioxide (CO2) at supercritical conditions (e.g., >31.3 °C and >73.8 bar), with or without a modifier. Those skilled in the art will understand that the temperature and pressure conditions can be varied to obtain an optimal yield of the plant extract. This technique yields a plant extract of lipophilic and / or fat-soluble compounds, similar to the absolute hexane and ethyl acetate extraction techniques that can also be used.

[0026] Each of the above extraction methods can also include one or more additional processing steps understood in the art and / or be used in combination therewith. For example, the plant material can be crushed, ground, milled, etc. There can also be one or more filtration steps to remove, for example, cellulose / fiber or other solid materials. There can also be one or more purification steps to remove, for example, certain constituents and / or contaminants. Such purification can be accomplished, for example, by distillation, evaporation, centrifugation, etc. There can also be one or more concentration and / or drying steps to remove water and / or other volatiles, such as alcohols, lighter compounds, VOCs, etc. Additionally, acids and / or bases can be added to adjust the pH or neutralize. Depending on the desired form of the final / terminal plant extract, various other steps understood in the art can also be utilized, such as sieving, pressing, grinding, milling, mixing, dispersing, etc. It should be understood that combinations of these additional processing steps in repeated and / or different orders are also contemplated.

[0027] Potentilla acaulis L

[0028] In some embodiments, the plant active ingredient and thus the composition comprises an extract of Potentilla acaulis L., i.e., an extract comprising, optionally consisting essentially of, material from the flowering plant species Potentilla acaulis L., such as flowers or leaves. More specifically, exemplary Potentilla acaulis L. flower and / or leaf extracts include those extracts that are part of the plant active ingredient and are capable of inhibiting one or more of α-glucosidase, lipase, and xanthine oxidase, or eliciting / displaying any other such activity described herein. In particular, the Potentilla acaulis L. extract is Mongolidine F.

[0029] Potentilla glabra has been reported to contain various bioactive components, such as phenolic acids, flavonoids, terpenes, triterpenes, tannins, polyphenols, saponins, polysaccharides, and other compounds. Potentilla glabra can be abbreviated as P. glabra, or referred to by various other names such as Potentilla glabra Lodd., Potentilla glabra G. Lodd., Dasiphora glabra (G. Lodd.) Soják, Silver Dew Plum, Yinlumei, or Potentilla glabra. The leaves and flowers of Potentilla glabra can be called Yaowang tea. In various embodiments, Potentilla glabra can be the variety Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz, which can be called BaimaoYinlumei, Baimao Yinlumei, or Baimao Yinlumei (variety).

[0030] Specific examples of Potentilla glabra extracts are known in the art. Thus, Potentilla glabra extracts can be purchased from various sources or otherwise obtained commercially, prepared (e.g., using any conventional extraction techniques known in the art, such as any of the techniques described herein), or a combination thereof. In certain embodiments, an extract of Potentilla glabra is obtained by water extraction (or aqueous extraction) of the plant material of Potentilla glabra, including but not limited to flowers and / or leaves. In further or other embodiments, an extract of Potentilla glabra is obtained by alcohol extraction (e.g., ethanol extraction) of the plant material of Potentilla glabra, including but not limited to flowers and / or leaves.

[0031] In certain embodiments, an extract of Potentilla glabra flowers and / or leaves is obtained by water extraction (or aqueous extraction) of the flowers, flower-based plant material, leaves, or leaf-based plant material of Potentilla glabra. In further or other embodiments, an extract of Potentilla glabra flowers and / or leaves is obtained by alcohol extraction (e.g., ethanol extraction) of the flowers, flower-based plant material, leaves, or leaf-based plant material of Potentilla glabra. The flowers and / or leaves can be fresh or dried, typically dried to prevent spoilage. The dried flowers and / or leaves can then be formed into a powder, which can be used as the extract itself, or more typically, the powdered flowers and / or leaves are further processed as described below to form the extract.

[0032] As will be understood by those skilled in the art, Potentilla glabra Lodd. is mainly cultivated for its flowers and / or leaves. Thus, in various embodiments, the extract of Potentilla glabra Lodd. is an extract of the flowers and / or leaves of Potentilla glabra Lodd.. Suitable extractions include those pointed out above, such as water and ethanol extractions of the flowers and / or leaves. The flowers and / or leaves can be from one or more plants and can be fresh, dried or otherwise aged.

[0033] For example, certain extracts can be obtained in which Potentilla glabra Lodd. (e.g., the flowers and / or leaves) are ground in a mill to a uniform size. Next, the resulting powder is extracted using a water or ethanol solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to produce a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0034] In various embodiments, the plant active component consists of an extract of the flowers and / or leaves of Potentilla glabra Lodd.. In further or other embodiments, the composition is substantially to completely free of components obtained from non-flower-based plant materials and / or non-leaf-based plant materials of Potentilla glabra Lodd.. In these embodiments, the non-flower-based plant materials and non-leaf-based plant materials of Potentilla glabra Lodd. can be, for example, the roots, stems, barks or rhizomes of the Potentilla glabra Lodd. plant. Without being bound by any particular theory, it is believed that the inhibitory effect of the Potentilla glabra Lodd. extract Mongolidine F on α-glucosidase, lipase and xanthine oxidase is the most useful; while other extracts of Potentilla glabra Lodd. are not (as shown in the Examples section below).

[0035] In other embodiments, the Potentilla glabra Lodd. extract can contain materials from any part or combination of parts of the plant and is not limited to flower and / or leaf extracts. For example, the Potentilla glabra Lodd. extract can contain materials extracted from one or more parts of the Potentilla glabra Lodd. plant, including its roots, stems, barks, rhizomes, leaves, buds, flowers, seeds and / or fruits. In addition, such extracts can be further processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, mesh-sorted, extracted, distilled, concentrated, etc.) to obtain the Potentilla glabra Lodd. extract. Similarly, the Potentilla glabra Lodd. plant can be extracted in its original form or processed (e.g., used in its original form, suspended form, dehydrated form, concentrated form, etc.) before extracting the Potentilla glabra Lodd. extract. In certain embodiments, the plant active component comprises a Potentilla glabra Lodd. extract that contains materials obtained (i.e., extracted) from the flowers and / or leaves of Potentilla glabra Lodd..

[0036] The amount of Potentilla acaulis extract utilized in the botanical active ingredient, particularly Mongolidine F, can vary and will be selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises from 0.1 to 2000 mg of Mongolidine F, such as from 0.1 to 1000, optionally from 1 to 900, optionally from 5 to 800, optionally from 20 to 750, or optionally from 50 to 500 mg. However, amounts outside of these ranges can also be utilized. For example, in certain embodiments, the botanical active ingredient comprises Mongolidine F in an amount of: at least 0.1, optionally at least 1, optionally at least 5, optionally at least 10, 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. In these or other embodiments, the upper boundary can be selected such that the botanical active ingredient comprises Mongolidine F in an amount of: ≤ 100, ≤ 250, ≤ 500, ≤ 750, ≤ 1000, ≤ 2000, ≤ 5000 mg. In various embodiments, the botanical active ingredient can comprise optionally Mongolidine F in an amount of: 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 weight % based on the total weight of the botanical active ingredient. In such embodiments, the upper boundary can be selected to generally be ≤ 10, ≤ 20, ≤ 30, ≤ 40, ≤ 50, ≤ 60, ≤ 70, ≤ 80, ≤ 90 and ≤ 99 weight % respectively based on the total weight of the botanical active ingredient.

[0037] The Potentilla acaulis extract can be utilized in any form, such as pure (i.e., free of solvents, carrier vehicles, diluents, etc.), or placed in a carrier vehicle such as a solvent or dispersant. If present, the carrier vehicle can comprise an aqueous solvent (such as water), an organic solvent, a fluid or an oil, etc., or a combination thereof. When utilized, the carrier vehicle will be selected based on the botanical active ingredient and / or the specific ingredients of the composition, such as the specific Potentilla acaulis extract utilized. It should be understood that if utilized, the Potentilla acaulis extract can be combined with the carrier vehicle before, during, or after combination with any other ingredients of the botanical active ingredient and / or the composition.

[0038] Quercus mongolica Fisch

[0039] In some embodiments, the phytoactive component, and therefore the composition, comprises an extract of Quercus mongolica, i.e., an extract comprising, optionally consisting essentially of, material from the plant species Quercus mongolica, such as pollen of Quercus mongolica. More specifically, exemplary extracts of Quercus mongolica (Potentilla glabra) pollen include those extracts that, as part of the phytoactive component, are capable of inhibiting one or more of α-glucosidase, lipase, and xanthine oxidase, or inducing / exhibiting any other such activity described herein. In particular, the Quercus mongolica extract is Mongolidine F.

[0040] Mongolica has been reported to contain various bioactive components, such as polyamines, flavono-ellagitannins, and other compounds. Quercus mongolica may be referred to simply as Q. mongolica, or by various other names such as Mongolian Oak, Meng GuLi, or Mongolian Oak, or other common names such as Eurasian oak, oak tree, Liaodong oak, large-fruited Mongolian oak, rough-toothed Mongolian oak, small-leaved oak, or sharp-toothed Mongolian oak.

[0041] The specific example of Mongolian oak extract is known in the art. Therefore, Mongolian oak extract can be purchased from various sources or otherwise commercially obtained, prepared (for example using any conventional extraction technology known in the art, for example any technology described herein) or its combination. In certain embodiments, the extract of Mongolian oak is obtained by water extraction (or aqueous extraction) of the plant material of Mongolian oak, including but not limited to pollen. In further or other embodiments, the extract of Mongolian oak is obtained by alcohol extraction (for example, ethanol extraction) of the plant material of Mongolian oak, including but not limited to pollen.

[0042] In certain embodiments, the extract of Quercus mongolica pollen is obtained by the pollen of water extraction (or aqueous extraction) Quercus mongolica or the plant material based on pollen. Further or in other embodiments, the extract of Quercus mongolica pollen is obtained by the pollen of alcohol extraction (for example, ethanol extraction) Quercus mongolica or the plant material based on pollen. Pollen can be fresh or dry, normally dry to prevent rotting. Dry pollen can be formed into powder then, it can be used as extract itself, or more generally, further process powdered pollen as described below to form extract.

[0043] For example, certain extracts of Quercus mongolica (e.g., pollen) can be obtained by grinding the extracts into uniform sizes in a mill. Next, the resulting powder is extracted with water or an ethanol solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to produce a syrup. The syrup can then be freeze-dried to dryness to obtain the extract.

[0044] In various embodiments, the plant active ingredient consists of an extract of Mongolian oak pollen. In further or other embodiments, the composition is substantially to completely free of components obtained from non-pollen-based plant materials of Mongolian oak. In these embodiments, the non-pollen-based plant materials of Mongolian oak can be, for example, the roots, stems, bark, rhizomes or leaves of the Mongolian oak plant. Without being bound by any particular theory, it is believed that the inhibitory effect of Mongolidine F from Mongolian oak extract on α-glucosidase, lipase and xanthine oxidase is the most useful; while other extracts of Mongolian oak are not (as shown in the Examples section below).

[0045] In other embodiments, the Mongolian oak extract can contain materials from any part or combination of parts of the plant and is not limited to pollen extracts. For example, the Mongolian oak extract can contain materials extracted from one or more parts of the Mongolian oak plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds and / or fruits. In addition, such extracts can be further processed (such as defatting, partial defatting, grinding, drying, precipitation, washing, filtering, sieving, extraction, distillation, concentration, etc.) to obtain the Mongolian oak extract. Similarly, the Mongolian oak plant can be extracted in its original form or processed before extracting the Mongolian oak extract (such as used in its original form, suspension form, dehydrated form, concentrated form, etc.). In certain embodiments, the plant active ingredient comprises a Mongolian oak extract that contains materials obtained (i.e., extracted) from the pollen of Mongolian oak.

[0046] The amount of Mongolian oak extract utilized in the plant active ingredient, particularly Mongolidine F, can vary and will be selected based on the number and type of ingredients utilized in the plant active ingredient. In certain embodiments, the plant active ingredient comprises 0.1 to 2000 mg of Mongolidine F, such as 0.1 to 1000, optionally 1 to 900, optionally 5 to 800, optionally 20 to 750, or optionally 50 to 500 mg. However, amounts outside of these ranges can also be utilized. For example, in certain embodiments, the plant active ingredient comprises Mongolidine F in an amount of: at least 0.1, optionally at least 1, optionally at least 5, optionally at least 10, 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. In these or other embodiments, the upper boundary can be selected such that the plant active ingredient comprises Mongolidine F in an amount of: ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, ≤5000 mg. In various embodiments, the plant active ingredient can optionally comprise Mongolidine F in an amount of: 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 weight % based on the total weight of the plant active ingredient. In such embodiments, the upper boundary can be selected to generally be ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99 weight % respectively based on the total weight of the plant active ingredient.

[0047] The Mongolian oak extract can be utilized in any form, such as pure (i.e., free of solvents, carrier vehicles, diluents, etc.), or placed in a carrier vehicle such as a solvent or dispersant. If present, the carrier vehicle can comprise an aqueous solvent (such as water), an organic solvent, a fluid, an oil, etc., or a combination thereof. When utilized, the carrier vehicle will be selected based on the plant active ingredient and / or the specific components of the composition, such as the specific Mongolian oak extract utilized. It should be understood that if utilized, the Mongolian oak extract can be combined with the carrier vehicle before, during, or after combination with any other components of the plant active ingredient and / or the composition.

[0048] Definition

[0049] For the purpose of providing a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0050] The term "composition" or "preparation" refers to a product that treats, improves, promotes, increases, manages, controls, maintains, optimizes, modifies, reduces, inhibits, or prevents a specific condition related to the natural state, biological processes, or a disease or disorder. For example, the composition or preparation improves, minimizes, inhibits, or prevents at least one of hyperglycemia, diabetes, hyperlipidemia, hyperuricemia, gout, ulcers, cancer, ischemia, and hypertension. The terms composition and preparation include, but are not limited to, pharmaceuticals (i.e., drugs), over-the-counter (OTC) medications, cosmetics, foods, food ingredients, or dietary supplement compositions that contain an effective amount of a plant active component, and in particular Mongolidine F. Exemplary compositions and / or preparations include creams, cosmetic lotions, packages, or powders, or as emulsions, lotions, liniments, foams, tablets, plasters, granules, or ointments. Preferred compositions are formulated for topical application / administration and oral administration / ingestion.

[0051] As used herein, the "effective amount" or "therapeutically effective amount" of a pure compound, composition, extract, extract mixture, component of an extract, and / or active agent or ingredient or combination thereof refers to an amount that is effective at a dosage and for a period of time sufficient to achieve the desired result. For example, the "effective amount" or "therapeutically effective amount" refers to the amount of a pure compound, composition, extract, plant extract, extract mixture, plant extract mixture, component of an extract, and / or active agent or ingredient or combination thereof of the present invention that, when administered to a subject (e.g., a mammal, such as a human), is sufficient to effect a treatment, such as improving, minimizing, inhibiting, or preventing at least one of hyperglycemia, diabetes, hyperlipidemia, hyperuricemia, gout, ulcers, cancer, ischemia, and hypertension. The amount of the composition, extract, plant extract, extract mixture, plant extract mixture, component of an extract, plant active component, and / or active agent or ingredient that constitutes an "effective amount" or "therapeutically effective treatment" of the present disclosure will vary depending on the active agent or compound, the condition being treated and its severity, the mode of administration, the duration of the treatment, or the age of the subject being treated, but can be determined routinely by one of ordinary skill in the art in view of his own knowledge and the present disclosure.

[0052] The term "pharmaceutically acceptable" means a drug, agent, extract, or inert ingredient that is suitable for contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, etc., commensurate with a reasonable benefit / risk ratio.

[0053] The terms "administer" and "administration" are defined as providing a composition to a subject via a route known in the art, including but not limited to topical, intravenous, intra-arterial, oral, parenteral, buccal, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal or intraperitoneal administration routes. In a preferred embodiment, the topical and / or oral route of administering the composition is suitable.

[0054] The terms "minimize", "reduce", "suppress", "decrease" and / or "inhibit" refer to a decrease or reduction in hyperglycaemia via inhibition of α-glucosidase, a decrease or reduction in fat metabolism and absorption via inhibition of pancreatic lipase, and / or a decrease or reduction in xanthine oxidation via inhibition of xanthine oxidase and / or its downstream effects, when compared to α-glucosidase activity, pancreatic lipase activity and / or xanthine oxidase activity in the absence of a botanical (or plant) ingredient or plant extract as described herein, e.g. in a control sample. The degree of decrease in hyperglycaemia via inhibition of α-glucosidase, the degree of decrease in fat metabolism and absorption via inhibition of pancreatic lipase, and / or the degree of decrease in xanthine oxidation via inhibition of xanthine oxidase and / or its downstream effects will vary with the nature and amount of the botanical ingredient or plant extract present, but will be evident as a detectable decrease in, for example, α-glucosidase activity, pancreatic lipase activity and / or xanthine oxidase activity; desirably, a degree of decrease of 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 degree of decrease in the range of about 5% to about 99%) compared to α-glucosidase, pancreatic lipase activity and / or xanthine oxidase activity in the absence of the botanical ingredient or plant extract. For example, a composition comprising a botanical ingredient or plant extract of Dasiphora davurica, particularly Mongolidine F, can minimize or reduce α-glucosidase activity, pancreatic lipase activity and / or xanthine oxidase activity.

[0055] As used herein, the terms "subject" or "individual" include mammals to which the composition can be administered. Non-limiting examples of mammals include humans, non-human primates, rodents (including transgenic and non-transgenic mice), and the like. In some embodiments, the subject is a mammal, and in some embodiments, the subject is a human.

[0056] Composition (or preparation)

[0057] The composition can contain any amount of the plant active ingredient, which will be selected based on the number and type of ingredients utilized in the composition as a whole. Generally, the plant active ingredient is present in the composition in an amount effective to inhibit one or more of α-glucosidase, pancreatic lipase, and xanthine oxidase (XO) in a subject.

[0058] In certain embodiments, the composition contains the plant active ingredient in an amount of: 0.1 to 5000, optionally 1 to 3000, optionally 2 to 2000, 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 these ranges can also be utilized. For example, it should be understood that the ranges described above regarding the amount of each plant extract in the plant active ingredient can equally apply to the amount of each plant extract in the composition as a whole, such as when the plant active ingredient component consists only of one of the plant extracts.

[0059] In some embodiments of the composition, the formulation contains Mongolidine F, which can be obtained as an extract of Potentilla acaulis L. var. glabra or Quercus mongolica Fisch. However, Mongolidine F can be obtained from other suitable sources. Without being bound by any particular theory, it is believed that the formulation is particularly useful for one or more of the α-glucosidase inhibitory effect, lipase inhibitory effect, and xanthine oxidase inhibitory effect, and even more useful for treating, reducing, and / or preventing gout.

[0060] A flavoring essence and / or a sugar substitute can be included in the composition and can be any type of conventional component understood in the art, such as a flavoring agent. The plant (or botanical) extracts can each be as described above. Examples of suitable flavoring agents are further described below.

[0061] Generally, in addition to containing the plant active ingredient and its plant extracts, the composition is not limited in terms of formulation, minor ingredients, form, number of functions, etc. On the contrary, the composition can vary and can be formulated in any manner consistent with the present disclosure.

[0062] Typically, the composition is formulated or otherwise suitable for administration to a mammalian subject (such as a human). For example, in various embodiments, the composition is suitable for topical administration or consumption and / or oral administration to a human subject.

[0063] In certain embodiments, the composition is further defined as a topical composition formulated for topical administration to a subject. In such embodiments, the composition may also be referred to as a cosmetic composition and, in addition to the bioactive agent composition, typically further comprises at least one cosmetically acceptable carrier. In specific embodiments, the cosmetically acceptable carrier is not naturally occurring. In other words, in these specific embodiments, the carrier is not a natural product. In other embodiments, the carrier is selected from conventional carriers understood in the art and may be used in conventional amounts.

[0064] In certain 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, in addition to the bioactive agent composition, typically further comprises at least one pharmaceutically acceptable additive. In specific embodiments, the pharmaceutically acceptable additive is not naturally occurring. In other words, in these specific embodiments, the pharmaceutically acceptable additive is not a natural product. In other embodiments, the pharmaceutically acceptable additive is selected from conventional additives understood in the art and may be used in conventional amounts.

[0065] Thus, it should be understood that the specific additives, carriers, adjuvants, fillers, etc. present in or combined with the composition can vary. Additionally, the physical form of the composition is not limited and will be selected based on the specific components of the composition, the desired use of the composition, etc. Thus, as will be understood in view of the present specification, the composition can be formulated as a liquid, dry powder, suspension, emulsion, gel, paste, etc. and combinations thereof. In certain 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 in which the plant active ingredient is placed in a suitable carrier vehicle, such as any of those described herein.

[0066] The composition can be prepared using various methods. For example, the active ingredient of the composition (such as a plant extract) and optionally one or more inactive ingredients (such as one or more conventional components, additives, excipients, etc.) can be mixed or blended and compressed or compounded using various techniques understood in the art. The compositions of the present disclosure are not limited to a particular order of manufacturing steps or manufacturing methods.

[0067] In various embodiments, the composition is orally administered by ingestion via the subject. The subject is typically a human and can include males and females of different ages. The methods / compositions of the present disclosure are not limited to a particular subject.

[0068] The composition can be in various forms. Examples of suitable forms include solids, gels, and liquids. For example, the composition can be formulated for application to the skin of a subject as a gel, cream, lotion, pomade, mousse, powder, or foam. In another example, the composition can be formulated for spraying onto the skin of a subject. The composition can be formulated as an aerosol spray or a pump spray for spraying. In yet another example, the composition can be formulated for application using a pre-moistened towel. In another example, the composition can be formulated as a solid for rubbing onto the skin of a subject. In another example, the composition is formulated for delivery via a patch that adheres to the skin of a subject.

[0069] In addition to the plant active ingredient (i.e., “active” or “active ingredient”), the composition can also contain pharmaceutically acceptable additives that are inactive (or “inactive ingredients”), including but not limited to excipients such as diluents and binders; granulating agents; glidants (or flow aids); fillers; lubricants; preservatives; stabilizers; coatings; disintegrants; fragrances; and pigments. The active ingredient and the pharmaceutically acceptable additives can be combined or compounded as needed to form individual dosages that provide the desired amount of the active ingredient upon topical application to a human subject.

[0070] Optionally, the composition can contain one or more additional components, such as additives. Suitable additives include those understood in the art, including but not limited to humectants, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, antibacterial agents, pharmaceuticals and drug substances, analgesic compounds, antineuralgic compounds, antioxidants, blood circulation promoters, antidepressant compounds, anxiolytic compounds, antistress compounds, sunscreens, insect repellents, preservatives, exfoliants, fragrances, pigments, fillers, solvents, vehicles, carriers, other types of additives known to those skilled in the art, and combinations thereof. Such additives can be utilized individually or in combination. Generally, the optional additives can be of any type used in personal care products and cosmetics.

[0071] Excipients can be further classified into other components. Specifically, excipients used in oral solid dosage forms have been grouped based on their functionality, such as diluents, disintegrants, binders, compression aids, granulating agents, glidants, lubricants, controlled release polymers, stabilizers (such as antioxidants, chelating agents, and pH regulators), film coating polymers, coating agents, vehicles, plasticizers, surfactants, colorants, sweeteners, and fragrances.

[0072] In various embodiments, the composition comprises at least one component selected from binders, lubricants, glidants, and combinations thereof. In certain embodiments, the composition includes one or more compounds including, but not limited to, methylcellulose, hydroxypropylmethylcellulose, 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, calcium hydrogen phosphate, sugars, microcrystalline cellulose (MCC), starch, sodium starch glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. Combinations of such components can be utilized, and such components and other components used in conventional tablets are understood in the art.

[0073] As used herein, "diluents" can be inert substances added to increase the bulk of the composition to give the tablet a practical size for compression. Thus, they can 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, and the like. Diluents / fillers can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0074] As used herein, "flavorants" are compounds designed to impart a more palatable taste to the composition. Flavorants vary quite widely in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex volatile oils. Virtually any desired type of synthetic flavor is currently available and well known in the art. If the hard taste, sour taste, or bitter taste derived from the raw materials can be suppressed by flavorings or seasonings, then acidulants (such as citric acid, tartaric acid, malic acid, ascorbic acid, etc.), sweeteners (such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevioside, thaumatin, etc.), or flavor essences (such as various fruit essences containing lemon oil, orange oil, or strawberry, as well as yogurt, mint, menthol, etc.) can be included in the composition. Flavorants can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0075] As used herein, "lubricant" is a material that performs a variety of functions related to the composition. In certain embodiments, such as tablet manufacturing, the lubricant performs one or more functions, such as improving the flow rate of tablet granulation, preventing the tablet material from adhering to the surfaces of the die and punch, reducing interparticle friction, and facilitating the ejection of the tablet from the die cavity. Examples of suitable lubricants include, but are not limited to, zinc stearate, gum arabic powder, cocoa butter, carnauba wax, calcium carboxymethylcellulose, sodium carboxymethylcellulose, caropeptide, hydrated silica, dried aluminum hydroxide gel, glycerol, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, sesame oil, flour starch, white beeswax, magnesium oxide, dimethylpolysiloxane, sodium potassium tartrate, sucrose fatty acid ester, glycerol fatty acid ester, silicone resin, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl stearate, magnesium stearate, cetyl alcohol, gelatin, talc, magnesium carbonate, precipitated calcium carbonate, corn starch, lactose, stearin, sucrose, potato starch, hydroxypropyl cellulose, fumaric acid, sodium stearyl fumarate, polyethylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, beeswax, magnesium aluminum metasilicate, methyl cellulose, Japan wax, glycerol monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, phosphoric acid, palmitic acid, and hydrogenated vegetable oils and fats. The lubricants can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0076] As used herein, "binder" is a reagent used to impart cohesive properties to powder materials. Binders, or as they are sometimes known, "granulators", impart cohesiveness to tablet formulations, which ensures that the tablets remain intact after compression and improves the free-flow properties by formulating granules 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; natural and synthetic gums, such as gum arabic, sodium alginate, Irish moss extract, panwar gum, ghatti gum, isapol husk mucilage, carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone (PVP), Veegum, microcrystalline cellulose, microcrystalline dextrin, amylose, larch arabinogalactan, ethyl cellulose, cellulose acetate, and the like. The binders can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0077] As used herein, "colorant" is a reagent that gives the composition a more pleasing appearance and additionally helps the manufacturer control the product during its preparation and helps the user identify the product. Any approved and qualified water-soluble FD&C dye, its mixture, or its corresponding lake can be used to color the tablets. Lakes are combinations of adsorbed water-soluble dyes with hydrated oxides of heavy metals, resulting in insoluble forms of the dyes. Colorants can be used alone or in various mixtures and are used in oral compositions in any amount known in the art.

[0078] Other conventional ingredients that may optionally be present in the composition include preservatives, stabilizers, anti-adhesives, or silica flow regulators or glidants such as silica. Such ingredients can be used alone or in various mixtures and are used in oral compositions in any amount known in the art.

[0079] It should be understood that certain components or additives may be classified under different specialized terms and just because a component or additive is classified under such a term does not mean that it is limited to that function. If utilized, one or more additives may be present in the composition in different amounts. For example, when suitable for topical or oral administration, additional ingredients optionally used in 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 Nos. 2006 / 0257509; 2007 / 0224154; 2008 / 0081082; 2008 / 0124409; 2013 / 0302265; 2017 / 0252293; 2017 / 0281666; 2018 / 0200285; 2019 / 0083566; 2019 / 0160117; 2020 / 0171117; 2020 / 0383898; 2021 / 0017240; and 2021 / 0212926; the disclosures of which are hereby incorporated by reference in their entirety.

[0080] Application method

[0081] The composition can be administered or applied once a day, several times a day, or according to any suitable regimen as needed, such that the desired result is achieved. In the methods of the present disclosure, the frequency of administration (e.g., oral ingestion) can depend on several factors, including the desired levels of alpha-glucosidase inhibition, pancreatic lipase inhibition, and / or xanthine oxidase (XO) inhibition. Generally, the regimen includes ingesting the composition once or twice a day, to include an administration in the morning and / or an administration in the evening. The amount and / or frequency of administration of the composition can depend on several factors, including the level of the desired result and the specific composition.

[0082] Improved alpha-glucosidase, lipase, and / or xanthine oxidase inhibition can be achieved by administering the formulations of the present invention externally, internally, or some combination thereof. Preferably, the formulations of the present invention are administered with an acceptable carrier. For example, the formulations of the present invention can be administered externally in the form of gels, lotions, creams, tonics, emulsions, etc., with an acceptable carrier. As a further example, the formulations of the present invention can be administered internally in the form of pills, tablets, powders, bars, beverages, etc., with an acceptable carrier. Thus, the formulations described herein are useful in a wide variety of end products, including pharmaceutical products, food products, and beverage compositions. Preferably, the products are useful for providing alpha-glucosidase, lipase, and / or xanthine oxidase inhibition to a mammal.

[0083] When the formulations of the present invention are administered orally in liquid form, the liquid can be water-based, milk-based, tea-based, juice-based, or some combination thereof. The solid and liquid formulations for internal administration according to the present invention can further contain thickening agents, 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, gum acacia, locust bean gum, gum arabic, gelatin, and mixtures of these thickening agents. These thickening agents are typically included in the formulations of the present invention at levels up to about 0.1%, depending on the specific thickening agent involved and the desired viscosity effect.

[0084] The solid and liquid (food and beverage) formulations of the present invention can and typically will contain an effective amount of one or more sweeteners, including carbohydrate sweeteners and natural and / or artificial non / low-calorie sweeteners. The amount of sweetener used in the formulations of the present invention will vary, but generally depends on the type of sweetener used and the desired intensity of sweetness.

[0085] In another instance, the formulations of the present invention are topically applied in the following forms: solutions, gels, lotions, creams, ointments, oil-in-water emulsions, water-in-oil emulsions, sticks, sprays, pastes, mousses, tonics, foundations, or other cosmetically and topically suitable forms.

[0086] Preferably, the formulations of the present invention suitable for topical application are mixed with an acceptable carrier. The acceptable carrier can variously serve as a solvent, vehicle, diluent, or dispersant for the components of the composition and allows the components to be uniformly applied to the surface of the skin at an appropriate dilution. The acceptable carrier can also facilitate the penetration of the composition into the skin.

[0087] In one instance of the formulation for topical application, the acceptable carrier constitutes from about 70% to about 99.99% by weight of the total composition. In other instances, the acceptable carrier constitutes from about 85% to 99.99% by weight of the total composition. The acceptable carrier can 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. In the absence of other cosmetic excipients or additives, the acceptable carrier can constitute the balance of the composition.

[0088] The various ingredients for practicing the present invention can be soluble or insoluble in the acceptable carrier. If all the ingredients of the formulation are soluble in the acceptable carrier, the vehicle serves as a solvent. However, if all or some of the ingredients of the formulation are insoluble in the acceptable carrier, these ingredients are dispersed in the vehicle by means of, for example, suspensions, emulsions, gels, creams, or pastes, etc.

[0089] Thus, it will be apparent to those skilled in the art that the range of possible acceptable carriers is very wide. For example, the acceptable carrier can be an emulsion, lotion, cream, or tonic. The acceptable carrier can contain water, ethanol, butylene glycol, or various other solvents that aid in skin penetration. Some examples of suitable vehicles are described in U.S. Patent Nos. 6,184,247 and 6,579,516, the entire contents of which are incorporated herein by reference.

[0090] Preferably, acceptable carriers for practicing the present invention comprise water and ethanol. Optionally, the acceptable carrier further contains butylene glycol. For example, the acceptable carrier may comprise 2-5% by weight of the composition of butylene glycol. When practicing the present invention, preferably, such an acceptable carrier is mixed with a preparation of the present invention accounting for 2% by weight of the total composition. In other examples, the acceptable carrier is mixed with such a preparation of the present invention, which accounts for 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 total composition.

[0091] However, in general, acceptable carriers according to the present invention may include 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; isopropyl alcohol; soybean oil; glycerol; soluble collagen; safflower oil; meadowfoam seed oil; mineral oil; squalene; shea butter; borage oil; or rice bran oil; polyquaternium-10; methylparaben; PEG-8; disodium lauroamphodacetate; sodium laureth sulfate; hexylene glycol; sodium methyl cocoyl taurate; TEA-lauryl sulfate; lauryl betaine; sodium myristoyl sarcosinate; PEG-150 distearate; anhydrous citric acid; sodium citrate dihydrate; diazolidinyl 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; dimethicone; glyceryl stearate; PEG-100 stearate; cetyl alcohol; butylene glycol; chlorphenesin; fragrance; polyacrylamide; C13-14 isoparaffin; laureth-7; aloe powder; aloe gel, hydroxyethyl acrylate; acryloyldimethyltaurate copolymer; behenyl alcohol; tocopheryl acetate; isodecyl neopentanoate; glyceryl trioctanoate; cetearyl alcohol; cetearyl glucoside; chamomile flower extract; biosaccharide gum-1; pentadecanolide; dipropylene glycol; cyclomethicone; PEG / PPG-18 / 18 dimethicone; cyclopentasiloxane; dimethyldistearylammonium hectorite; SD alcohol 40; phenoxyethanol; ethylparaben; trimethylsilyloxy silicate; triethoxysilane octyl; micronized titanium dioxide; titanium dioxide; zinc oxide; iron oxide (yellow; red; black, etc.); octyl silane; sodium chloride; diisopropyl dimer dilinoleate; aluminum hydroxide; stearic acid; polyethylene beads; C12-15 alkyl benzoate; acrylate / C10-30 alkyl acrylate; xanthan gum; sorbitan laurate; panthenol; petrolatum; isopropyl isostearate; dimethicone; arginine; phenoxyethanol; acryloyldimethyltaurate copolymer; isocetane; polysorbate 80; hydroxyethyl acrylate; acryloyldimethyltaurate copolymer; octinoxate (octyl methoxycinnamate); oxybenzone; dioctyl ether; isodecyl neopentanoate; cetearyl alcohol; cetearyl glucoside; benzyl alcohol; HDI / trimetylol hexylactone crosslinked polymer; silica; isodecyl neopentanoate; cocoyl glucoside; C20-22 alkyl phosphate; C20-22 alcohol; palmitoyl proline; magnesium palmitoyl glutamate; sodium palmitoyl sarcosinate; C30-45 alkyl cetearyl crosslinked polymer; polyacrylate 13; polyisobutene; polysorbate 20; iodopropynyl butylcarbamate; magnesium sodium silicate; methyl gluceth-20; isosorbide dimethyl ether;Silica; SD Alcohol 40-B; Salicylic Acid; Ceteth-20; Fragrance; or Witch Hazel.

[0092] In addition, the acceptable carriers used in the present invention may optionally contain one or more humectants, including but not limited to: dibutyl phthalate; soluble collagen; sorbitol; or sodium 2-pyrrolidone-5-carboxylate. Other examples of humectants 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.

[0093] In addition, the acceptable carriers in the present invention may optionally contain one or more emollients, including but not limited to: 1,3-butylene glycol; cetyl palmitate; dimethicone; glyceryl monocaprylate; glyceryl monostearate; isobutyl palmitate; isocetyl stearate; isopropyl palmitate; isopropyl stearate; butyl stearate; isopropyl laurate; hexyl laurate; decyl oleate; isopropyl myristate; lauryl lactate; 2-octadecanol; triglyceride caprylic acid; triglyceride capric acid; polyethylene glycol; 1,2-propylene glycol; triethylene glycol; sesame oil; coconut oil; safflower oil; isopentyl 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 alcohol lactate; myristyl alcohol 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.

[0094] In addition, the acceptable carriers used in the present invention may optionally contain one or more penetration enhancers, including but not limited to: pyrrolidones, such as 2-pyrrolidone; alcohols, such as ethanol; alkanols, such as decanol; diols, such as propylene glycol, dipropylene glycol, butylene glycol; surfactants; or terpenes.

[0095] Other acceptable carriers that can be used to practice the present invention will be apparent to those skilled in the art and are included within the scope of the present invention.

[0096] For example, an acceptable carrier can be a topically applied lotion. The lotion can contain cabomer 981, water, glycerol, isopropyl myristate, mineral oil, shea butter, stearic acid, ethylene glycol stearate, cetyl alcohol, dimethicone, preservatives, tea, and various components of the formulation of the present invention.

[0097] The formulations of the present invention may also contain various known and conventional cosmetic adjuvants, provided that they do not adversely affect the desired improvements provided by the formulations. For example, the formulations of the present invention may further comprise one or more additives or other optional ingredients well known in the art, which may include but are not limited to fillers (e.g., solids, semi-solids, liquids, etc.); carriers; diluents; thickeners; gelling agents; vitamins, retinoids and retinol (e.g., vitamin B3, vitamin A, etc.); pigments; fragrances; sunscreens and sunblocks; antioxidants and free radical scavengers; organic hydroxy acids; exfoliants; skin conditioners; humectants; ceramides, pseudoceramides, phospholipids, sphingolipids, cholesterol, glucosamine, pharmaceutically acceptable penetrants (e.g., n-decylmethyl sulfoxide, lecithin organogel, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids such as proline, pyrrolidone carboxylic acid, its derivatives and salts, saccharide isomerate, panthenol, buffers together with bases such as triethanolamine or sodium hydroxide; waxes, such as beeswax, ozokerite, paraffin wax; plant extracts, such as aloe vera, cornflower, witch hazel, elderflower or cucumber and combinations thereof. Other suitable additives and / or excipients are described in U.S. Patent No. 6,184,247, the entire content of which is incorporated herein by reference.

[0098] The formulations may contain additional inactive ingredients, which include but are not limited to surfactants, co-solvents and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, may be included in the formulations. Specific surfactants may be used based on the overall composition of the formulation and the intended delivery of the formulation. Useful surfactants include polyethoxylated (PEG) fatty acids, PEG-fatty acid diesters, PEG-fatty acid monoester and diester mixtures, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerolated fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters-glycerol esters, glycerol monoesters and glycerol diesters, sterols and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, polysaccharide esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants and mixtures thereof.

[0099] The formulations may also contain co-solvents, such as alcohols and polyols, polyethylene glycol ethers, amides, esters, other suitable co-solvents and mixtures thereof. The formulations may also contain excipients or additives, such as sweeteners, flavoring agents, coloring agents, antioxidants, preservatives, chelating agents, viscosity modifiers, tonicifiers, odorants, opacifiers, suspending agents, binders and mixtures thereof.

[0100] Generally, the formulations of the present invention are administered topically or orally at least once a day for a period of time sufficient to effect the desired level of improvement in α-glucosidase, lipase, and / or xanthine oxidase inhibition. The 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 the initial administration or ingestion, the user may notice that the symptoms of hyperglycemia, diabetes, hyperlipidemia, hyperuricemia, gout, ulcers, cancer, ischemia, and / or hypertension have improved. It should be understood that the frequency at which the formulations of the present invention should be administered or ingested will vary depending on the desired level of improvement. In particular, the degree of symptom alleviation will vary directly with the total amount of the composition used.

[0101] Useful dosage forms can be prepared by methods and techniques well understood by those skilled in the art and can include the use of additional ingredients in the production of tablets, capsules, or liquid dosage forms.

[0102] Industrial Applicability

[0103] The present disclosure provides new and useful advanced α-glucosidase inhibitors, pancreatic lipase (PL) inhibitors, and / or xanthine oxidase (XO) inhibitors that comprise the plant active components described herein. Such α-glucosidase inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperglycemia, diabetes, or other pathogenic complications caused by α-glucosidase activity. Such PL inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperlipidemia or other pathogenic complications caused by PL activity. Such XO inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hyperuricemia, gout, ulcers, cancer, ischemia, hypertension, oxidative stress, oxidative damage, or other pathogenic complications caused by XO activity. Thus, the compositions and methods described herein can be used to inhibit α-glucosidase, PL, and / or XO.

[0104] The general compositions and product lines provided by the present disclosure relate to personal care, nutrition, skin care, and nutricosmetic products that utilize such α-glucosidase, PL, and / or XO inhibitors, and specific examples include pills and liquids that utilize such α-glucosidase, PL, and / or XO inhibitors.

[0105] α-Glucosidase is a metabolic pathway that breaks down carbohydrates (oligosaccharides and disaccharides) into monosaccharides and thus absorbs glucose. Elevated blood glucose levels (hyperglycemia) are a complication in individuals with type Ⅱ diabetes and can lead to or exacerbate other medical conditions such as cardiovascular disease. Hyperglycemia can also lead to ketoacidosis. The compositions and methods of the present disclosure provide potential prophylactic and therapeutic methods for reducing the risk of hyperglycemia, diabetes, or other pathogenic complications caused by α-glucosidase.

[0106] PL is a metabolic pathway for the breakdown and absorption of dietary fats. Elevated lipid levels in the body can lead to serious diseases, which may ultimately result in death. For example, elevated lipid levels can cause the development of atherosclerosis and may thus affect cardiovascular health. The compositions and methods of the present disclosure provide potential prophylactic and therapeutic methods for reducing the risk of hyperlipidemia or other pathogenic complications caused by PL.

[0107] XO is a metabolic pathway for uric acid formation. Elevated blood uric acid levels can lead to gout when high levels of uric acid crystallize and become deposited in joints, tendons, and surrounding tissues. Elevated blood uric acid can also affect cardiovascular health. Additionally, by-products of XO activity such as hydrogen peroxide can cause oxidative stress. The compositions and methods of the present disclosure provide potential prophylactic and therapeutic methods for reducing the risk of hyperuricemia, gout, ulcers, cancer, ischemia, hypertension, oxidative stress, oxidative damage, or other pathogenic complications caused by XO.

[0108] The following examples illustrating the compositions and methods of the present disclosure are intended to illustrate and not limit the present disclosure.

[0109] Examples

[0110] The inhibitory effects of Mongolidine F on α-glucosidase, pancreatic lipase (PL), and xanthine oxidase (XO) were evaluated. Mongolidine F showed inhibition of α-glucosidase, pancreatic lipase (PL), and xanthine oxidase (XO), as shown in the following table and figures.

[0111] Inhibition of α-glucosidase

[0112] 40 μL of the test subject (Mongolidine F) was added to 40 μL of α-glucosidase solution (0.1 U / mL in PBS), and then mixed for 5 minutes. Next, 20 μL of PNPG (2.5 mmol / L) as the α-glucosidase substrate was added to the mixture, and incubated at 37 °C for 15 minutes. Then, 100 μL of sodium carbonate solution (0.1 mol / L) was used to terminate the reaction. The absorbance at 405 nm was measured, and the inhibition rate of α-glucosidase was calculated by the following formula:

[0113]

[0114] Where A1 is the absorbance of the mixture of the sample and α-glucosidase, A2 is the absorbance of the mixture of the sample and the buffer solution, A3 is the absorbance of the mixture of the buffer solution and α-glucosidase, and A4 is the absorbance of the buffer solution.

[0115] The results are shown in Table 1 below. The average inhibition rate can also be referred to Figure 1 for understanding.

[0116] Table 1:

[0117]

[0118] * Also see Figure 1 (where the X-axis is concentration and the Y-axis is % inhibition)

[0119] Inhibition of pancreatic lipase (PL)

[0120] Add 25 μL of the test object (Mongolidine F) to 25 μL of the lipase solution (1 mg / mL), and then mix well. Next, add 50 μL of 4-methylumbelliferyl oleate (0.1 mmol / L) as the lipase substrate to the mixture, and incubate at 23 °C for 20 minutes. Then, use 100 μL of sodium citrate (0.1 mol / L, pH 4.2) to terminate the reaction. To measure the absorbance, the excitation wavelength and the emission wavelength are set to 320 nm and 450 nm, respectively. Tris buffer (pH 8.0) with the sample (without enzyme) represents the background group, Tris buffer with the enzyme (without sample) represents the control group, and Tris buffer alone represents the blank group. All experiments are repeated three times. Measure the absorbance of the solution. Calculate the inhibition rate of PL by the following formula:

[0121]

[0122] where A1 is the absorbance of the mixture of the sample and PL, A2 is the absorbance of the mixture of the sample and the buffer solution, A3 is the absorbance of the mixture of the buffer solution and PL, and A4 is the absorbance of the buffer solution.

[0123] The results are shown in Table 2 below. The average inhibition rate can also be referred to Figure 2 for understanding.

[0124] Table 2:

[0125]

[0126] * Also see Figure 2 (where the X-axis is concentration and the Y-axis is % inhibition)

[0127] Inhibition of xanthine oxidase (XO) <>

[0128] The activity of xanthine oxidase was measured by 96-well plate spectrophotometry to determine the inhibitory ability of Mongolidine F. The reaction mixture contained 50 μL of sample and 50 μL of 0.02 U / mL xanthine oxidase solution, which was shaken appropriately for 30 seconds and incubated at 25 °C for 5 minutes. Then 150 μL of 0.48 mM xanthine solution was added, and the mixture was carefully shaken again for 30 seconds and incubated at 37 °C for 30 minutes. The absorbance of the incubated solution was measured. The inhibition rate of XO was calculated by the following formula:

[0129]

[0130] where A1 is the absorbance of the mixture of the sample and XO, A2 is the absorbance of the mixture of the sample and the buffer solution, A3 is the absorbance of the mixture of the buffer solution and XO, and A4 is the absorbance of the buffer solution.

[0131] The results are shown in Table 3 below. The average inhibition rate can also be referred to Figure 3 for understanding.

[0132] Table 3:

[0133]

[0134]

[0135] * Also see Figure 3 (where the X-axis is concentration and the Y-axis is % inhibition)

[0136] The term "comprising" or "comprise" is used herein in its broadest sense to mean and encompass the concepts of "including", "include", "consist(ing) essentially of", and "consist(ing) of". The use of "for example", "e.g.", "such as", and "including" to list illustrative examples is not limited to the examples listed. Thus, "for example" or "such as" means "for example, but not limited to" or "such as, but not limited to", and encompasses other similar or equivalent examples. As used herein, the term "about" functions to reasonably encompass or describe minor variations in a numerical value measured as a result of instrumental analysis or as part of sample processing. Such minor variations can be about ±0 - 10, ±0 - 5, or ±0 - 2.5% of the numerical value. Further, when related to a range of values, the term "about" applies to both numerical values. Additionally, even if not explicitly stated, the term "about" can apply to a numerical value.

[0137] Generally, as used herein, the hyphen "-" or dash "-" within a range of values is "to" or "until"; ">" is "higher than" or "greater than"; "≥" is "at least" or "greater than or equal to"; "<" is "lower than" or "less than"; and "≤" is "at most" or "less than or equal to". On an individual basis, each of the foregoing patent applications, patents, and / or patent application publications is hereby expressly incorporated by reference in its entirety into one or more non-limiting embodiments herein.

[0138] It should be understood that the appended claims are not limited to the specific and explicit compounds, compositions, or methods described in the detailed description, which may vary between specific embodiments falling within the scope of the appended claims. With respect to any Markush group that depends on specific features or aspects described in the individual embodiments herein, it should be understood that different, special, and / or unexpected results can be obtained from each member of the Markush group independently of all other Markush members. Each member of the Markush group can be relied upon individually and / or in combination and provides sufficient support for specific embodiments within the scope of the appended claims.

[0139] It should also be understood that any ranges and sub-ranges relied upon in describing various embodiments of the present invention independently and collectively fall within the scope of the appended claims, and it should be understood to describe and contemplate all ranges including integral values and / or fractional values therein, even if such values are not explicitly written herein. It will be readily recognized by those skilled in the art that the recited ranges and sub-ranges fully describe and enable the various embodiments of the present invention, and such ranges and sub-ranges can be further divided into related halves, thirds, quarters, fifths, and so on. Merely by way of example, the range "from 0.1 to 0.9" can be further divided into a lower third, i.e., from 0.1 to 0.3, a middle third, i.e., from 0.4 to 0.6, and an upper third, i.e., from 0.7 to 0.9, which individually and collectively fall within the scope of the appended claims and can be individually and / or collectively relied upon and provide adequate support for specific embodiments within the scope of the appended claims. Additionally, with respect to language that defines or modifies a range, such as "at least", "greater than", "less than", "not more than", etc., it should be understood that such language includes sub-ranges and / or upper or lower limits. As another example, the range "at least 10" inherently includes sub-ranges of at least 10 to 35, at least 10 to 25, 25 to 35, and so on, and each sub-range can be individually and / or collectively relied upon and provide adequate support for specific embodiments within the scope of the appended claims. Finally, each individual number within the disclosed ranges can be relied upon and provide adequate support for specific embodiments within the scope of the appended claims. For example, the range "from 1 to 9" includes various individual integers such as 3, and individual numbers (or fractions) including a decimal point such as 4.1, which can be relied upon and provide adequate support for specific embodiments within the scope of the appended claims.

[0140] The present invention has been described herein in an illustrative manner, and it should be understood that the terms used are intended to be of a descriptive rather than a restrictive nature. Many modifications and variations of the present invention are possible in light of the above teachings. The present invention may be practiced in a manner different from that specifically described within the scope of the appended claims. All combinations of the subject matter of the independent and dependent claims (both single dependent and multiple dependent) are explicitly contemplated herein.

Claims

1. A composition for administration to a subject, the composition comprising: At least one phytologically active component, wherein the phytologically active component comprises Mongolidine F, consists essentially of Mongolidine F, or is Mongolidine F; Wherein the phytologically active component is present in the composition in an amount effective to inhibit one or more of α-glucosidase, lipase, and xanthine oxidase (XO) in the subject.

2. The composition according to claim 1, wherein the composition is further defined as an oral composition formulated for oral administration to a subject.

3. The composition according to claim 2, which further comprises a pharmaceutically acceptable additive, optionally wherein the pharmaceutically acceptable additive is not naturally occurring.

4. The composition according to claim 1, wherein the composition is further defined as a topical composition formulated for topical administration to a subject.

5. The composition according to claim 4, which further comprises a cosmetically acceptable carrier, optionally wherein the cosmetically acceptable carrier is not naturally occurring.

6. Use of the composition according to any one of claims 1 to 5 for inhibiting α-glucosidase in a subject.

7. Use of the composition according to any one of claims 1 to 5 for inhibiting lipase in a subject.

8. Use of the composition according to any one of claims 1 to 5 for inhibiting xanthine oxidase (XO) in a subject.

9. Use of the composition according to any one of claims 1 to 5 in the preparation of a medicament for the treatment of hyperglycemia.

10. Use of the composition according to any one of claims 1 to 5 in the preparation of a medicament for the treatment of hyperlipidemia.

11. Use of the composition according to any one of claims 1 to 5 in the preparation of a medicament for the treatment of hyperuricemia.

12. A method for inhibiting α-glucosidase in a subject, the method comprising administering to the subject an effective amount of a composition, wherein the composition is the composition according to any one of claims 1 to 5.

13. The method of claim 12, wherein the composition is orally administered to the subject.

14. The method of claim 12, wherein the composition is topically administered to the subject.

15. A method for inhibiting lipase in a subject, the method comprising administering to the subject an effective amount of a composition, wherein the composition is the composition according to any one of claims 1 to 5.

16. The method of claim 15, wherein the composition is orally administered to the subject.

17. The method of claim 15, wherein the composition is topically administered to the subject.

18. A method for inhibiting xanthine oxidase (XO) in a subject, the method comprising administering to the subject an effective amount of a composition, wherein the composition is the composition according to any one of claims 1 to 5.

19. The method of claim 18, wherein the composition is orally administered to the subject.

20. The method of claim 18, wherein the composition is topically administered to the subject.

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