Compositions and methods for inhibiting elastase activity

Abstract

Disclosed is a composition for administration to a subject. The composition comprises at least one botanical active ingredient. The botanical active ingredient is present in the composition in an amount effective to inhibit elastase activity in the subject's skin. The botanical active ingredient comprises at least one extract selected from the group consisting of: i) Potentilla gracilis leaf extract; ii) Panya flower extract; iii) Amomum villosum seed extract; iv) Amomum clavan fruit extract; v) Cornus officinalis fruit extract; and vi) a combination of i)-v). The composition may be in the form of a topical composition, e.g., for topical application. The composition may also be in the form of an oral composition, e.g., for ingestion. Also provided is a method for inhibiting elastase activity in a subject's skin. The method comprises administering an effective amount of the composition to the subject.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and all benefits of Chinese Application No. 202211078986.5, filed on September 5, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] FIELD OF THE INVENTION The present invention relates generally to compositions and methods for inhibiting elastase activity, and more particularly to compositions containing botanical extracts for inhibiting elastase activity in the skin of a subject. Related methods are also provided. [Background technology]

[0003] Background of the Invention Due to its inherent elasticity, elastin is essential for providing elasticity to organs, connective tissues, and skin. Various elastases are involved in the damage of elastin, i.e., elastic fibers, in various types of tissues during inflammation or disease, as well as aging. Accumulative exposure to the sun or UV radiation causes the formation of wrinkles, which are associated with a significant decrease in skin elasticity. In the skin, elastase is primarily involved in the degradation of elastin, which is associated with the formation of wrinkles.

[0004] In recent years, bioactive molecules derived from plants have been widely used as cosmeceutical ingredients due to their key properties of slowing down the intrinsic and different extrinsic skin aging processes. Several natural products and extracts have been reported for the development of anti-aging skin care products. For example, polyphenols from green tea, such as epigallocatechin gallate (EGCG), have been formulated into anti-aging skin care products that exhibit reduced elastase inhibition.

[0005] In view of the above, there remains an opportunity to provide new and useful elastase inhibitors, which would offer potential preventative and therapeutic approaches to alleviate elastase-induced skin aging, such as wrinkle formation. Thus, there also remains an opportunity to provide new and useful compositions and methods for inhibiting elastase activity. Summary of the Invention

[0006] BRIEF SUMMARY OF THE INVENTION Compositions for administration to a subject are provided. The compositions include at least one botanical active ingredient. The botanical active ingredient is generally provided in the composition in an amount effective to inhibit elastase in the subject's skin. The botanical active ingredient includes at least one extract selected from the group consisting of: i) Potentilla glabra leaf extract; ii) Bombax malabaricum flower extract; iii) Amomum villosum seed extract; iv) Amomum kravanh seed extract; v) Cornus officinalis fruit extract; and vi) a combination of i) through v).

[0007] In various embodiments, the composition is a topical composition formulated for topical administration to a subject, hi other embodiments, the composition is an oral composition formulated for oral administration to a subject.

[0008] The composition can be used to inhibit elastase in the skin of a subject. A method of inhibiting elastase in the skin of a subject comprises administering to the subject an effective amount of the composition. [Brief explanation of the drawings]

[0009] [Figure 1] Figure 1 is a plot showing the mean percent elastase inhibition using EGCG as a control;

[0010] [Figure 2] FIG. 2 is a plot showing the average elastase inhibition rate using Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz (leaf)-ethanol extract;

[0011] [Figure 3] Figure 3 is a plot showing the average elastase inhibition percentage using Panya DC. (flower)-ethanol extract;

[0012] [Figure 4] FIG. 4 is a plot showing the average elastase inhibition rate using Amomum villosum Lour (seed)-ethanol extract;

[0013] [Figure 5] FIG. 5 is a plot showing the average elastase inhibition percentage using the ethanol extract of Amomum kravanh Pierre ex Gagnep (fruit);

[0014] [Figure 6] FIG. 6 is a plot showing the average elastase inhibition rate using Cornus officinalis Sieb. et Zucc. (fruit) aqueous extract; and

[0015] [Figure 7] FIG. 7 is a plot showing the mean percent elastase inhibition using Cornus cherry (fruit) ethanol extract. DETAILED DESCRIPTION OF THE INVENTION

[0016] Detailed Description of the Embodiment Disclosed are compositions for administration to a subject. The compositions include at least one botanical active ingredient. The compositions are described below, followed by a description of related uses and methods.

[0017] In view of this disclosure, it will be understood that the compositions are not particularly limited apart from the botanical active ingredient(s), and particularly the extract(s) thereof, and related ingredients, and methods, and thus may be formulated, for example, as a topical composition (e.g., a cosmetic composition), or as an oral composition, or as a nutraceutical, pharmaceutical, or supplement, and may be utilized alone as a therapeutic agent or in combination with other therapeutic agents with which they may be mixed.

[0018] The compositions are useful for treating, preventing, and / or ameliorating various conditions, such as those associated with aging. Specifically, as will be understood in light of the following description and examples, it is believed that the compositions of the embodiments are capable of inhibiting elastase activity, and more specifically, inhibiting elastin degradation caused by elastase in the skin of a subject.

[0019] As such, the compositions may be utilized to treat (i.e., slow, prevent, reverse, etc.) age-related conditions such as wrinkle formation or other conditions commonly associated with elastase activity.

[0020] As previously mentioned, the composition contains a botanical active ingredient. More specifically, the botanical active ingredient comprises, optionally consisting essentially of, or optionally consisting of at least one extract selected from the group consisting of: i) Potentilla gracilis leaf extract; ii) Panax ginseng flower extract; iii) Amomum virosum seed extract; iv) Amomum clavan seed extract; v) Cornus officinalis fruit extract; and vi) a combination of i)-v). In certain embodiments, the composition of this disclosure does not contain other active ingredients. By "other active ingredients," it is generally meant that the composition does not contain other types of traditional Chinese medicines ("TCM" or "herbal medicines") other than the above extracts or those exemplified below. Other types of TCM are understood in the art.

[0021] In certain embodiments, only one of the five extracts i)-v) is present in the composition. In other embodiments, only two of the five extracts i)-v) are present in the composition. In yet other embodiments, only three of the five extracts i)-v) are present in the composition. In yet other embodiments, only four of the five extracts i)-v) are present in the composition. In yet other embodiments, all five of the five extracts i)-v) are present in the composition. Each of the extracts i)-iv) individually may be referred to simply as a "botanical extract" or collectively as the "botanical extracts," and are described in turn below.

[0022] The term "extract" is used herein in its conventional sense to refer to a composition obtained by liquid extraction from a raw material. Thus, the term "botanical extract" is understood to refer to a composition obtained by liquid extraction (e.g., solvent extraction, gas extraction, CO2 extraction, etc.) from a botanical source (i.e., plant material). Botanical extracts suitable for use in the compositions can be obtained by any extraction method or combination of such methods known in the art, including aqueous extraction, steam extraction, solvent extraction, etc. Exemplary extraction techniques are described below. However, botanical extracts are generally not limited to a particular extraction method or additional / auxiliary techniques used to obtain the botanical extract, but rather may be modified according to the parameters described herein. Furthermore, when suitable extracts (e.g., standardized extracts) are readily available from many commercial suppliers, an extraction step is not necessary to prepare the botanical active ingredients and / or compositions.

[0023] Botanical extracts suitable for use in or as botanical active ingredients include those obtained by solvent extraction 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), phenol, water, and non-polar solvents such as benzene, xylene, toluene, and the like, as well as derivatives, modifications, and combinations thereof (e.g., solvent-water mixtures including alcohol-water, acetone-water, etc.). Additional and alternative extraction techniques include continuous fractional distillation, total hydro-ethanolic extractions, lump-sum extractions, supercritical fluid extraction (e.g., using CO2), and the like; sequential or secondary extractions from a primary extraction (e.g., non-polar solvent extraction of a botanical extract obtained from a polar solvent extraction), or other processing techniques such as filtration, purification, distillation, dehydration, evaporation, concentration, drying, and the like. An example of a suitable extraction method is described in US Pat. No. 7,897,184, which is incorporated herein by reference.

[0024] As is understood in the art, various parts or portions of plants can be used to obtain essential oils and extracts, such as bark, berries, flowers, fruits, leaves, peel, resin, rhizomes, roots, seeds, and / or wood. Essential oils can be obtained by a number of processes, such as distillation (e.g., using steam), expression, solvent extraction, pure oil extraction, resin tapping, and / or cold pressing.

[0025] In various embodiments, the solvent used to obtain a suitable botanical extract for this disclosure is one in which the resulting botanical extract and / or its subsequent form (e.g., botanical extract powder) is suitable for ingestion. For example, the solvent is water or ethanol.

[0026] In one example, the botanical extract can be obtained using organic solvent extraction techniques. In another example, continuous solvent fractional distillation can be used to obtain the botanical extract. Total hydroethanol extraction techniques can also be used to obtain the botanical extract. This is commonly referred to as lump-sum extraction. The botanical extract produced by this process contains a wide range of botanical compounds present in the extract, including fats and water-soluble plant compounds. Following collection of the botanical extract solution, the solvent is evaporated to yield the botanical extract.

[0027] Alternatively, a total ethanol extract may be used. This technique uses ethanol as a solvent. This extraction technique produces a plant extract that may contain fat-soluble and / or lipophilic compounds in addition to water-soluble compounds. A total methanol extract may also be used in a similar manner with similar results.

[0028] Another example of an extraction technique that can be used to obtain botanical extracts is supercritical fluid carbon dioxide extraction (SFE). In this extraction technique, the material to be extracted is not exposed to any organic solvent. Rather, the extraction solvent is carbon dioxide (CO2) in a supercritical state (e.g., >31.3°C and >73.8 bar), with or without modifiers. Those skilled in the art will understand that temperature and pressure conditions can be modified to obtain the best yield of botanical extract. This technique produces a botanical extract of fat-soluble and / or lipophilic compounds similar to total hexane and ethyl acetate extraction techniques (and this extraction technique can also be used).

[0029] Each of the above extraction methods may include and / or be used in combination with one or more additional processing steps known in the art. For example, the plant material may be subjected to crushing, grinding, grinding, etc. One or more filtration steps may also be used, for example, to remove cellulosic / fibrous materials or other solid materials. One or more purification steps may also be used, for example, to remove certain components and / or contaminants. Such purification may be achieved, for example, by distillation, evaporation, centrifugation, etc. One or more drying and / or concentration steps may also be used to remove water and / or other volatiles, such as alcohol, lighter compounds, VOCs, etc. Furthermore, acids and / or bases may be added to adjust or neutralize the pH. Depending on the desired form of the final botanical extract, various additional steps known in the art, such as screening, pressing, milling, grinding, mixing, dispersing, etc., may also be used. It is understood that overlapping and / or differently ordered combinations of these additional processing steps are contemplated. Potentilla

[0030] In some embodiments, the botanical active ingredient, and compositions therefrom, include an extract of Potentilla gracilis, i.e., an extract comprising, and optionally consisting essentially of, material from the flowering plant species Potentilla gracilis, such as leaves. Potentilla gracilis extracts are not particularly limited and may include any leaf extract or combination of extracts from the Potentilla gracilis plant suitable for use in embodiments herein. More specifically, exemplary Potentilla gracilis leaf extracts include those capable of inhibiting elastase activity or eliciting / exhibiting other such activities described herein as part of the botanical active ingredient.

[0031] Potentilla glabra has been reported to contain various bioactive components, such as phenolic acids, flavonoids, terpenoids, triterpenes, tannins, polyphenols, saponins, polysaccharides, and other compounds. Potentilla glabra is often referred to simply as P. glabra, or by various other names, such as Potentilla glabra Lodd., Potentilla glabra G. Lodd., Dasiphora glabra (G. Lodd.) Sojak, Silver Dew Plum, Yinlumei, or other names. [ka] The leaves and flowers of Potentilla glabra Lodd. are sometimes called Yaowang tea. In various embodiments, the potentilla may be a variety of Potentilla glabra, which is also known as Baimao Yinlumei, [ka] or [ka] It is also sometimes called.

[0032] Specific examples of Potentilla extracts are known in the art. As such, Potentilla extracts may be purchased or otherwise obtained commercially from various suppliers, prepared (e.g., using any conventional extraction technique(s) known in the art, such as any of those described herein), or combinations thereof. In certain embodiments, an extract of Potentilla is obtained by alcohol extraction (e.g., ethanol extraction) of Potentilla plant material, including, but not limited to, the leaves. In other embodiments, an extract of Potentilla may be obtained by water extraction (or aqueous extraction) of Potentilla plant material.

[0033] In certain embodiments, an extract of Potentilla gracilis leaves is obtained by alcohol extraction (e.g., ethanol extraction) of Potentilla gracilis leaves or leaf-based plant material. The leaves may be fresh or dried, typically dried to prevent spoilage. The dried leaves may then be formed into a powder, which can be used as the extract itself, or more typically, the powdered leaves are further processed as described below to form the extract.

[0034] As will be appreciated by those skilled in the art, Potentilla gracilis is primarily cultivated for its leaves. Thus, in various embodiments, the Potentilla gracilis extract is an extract of Potentilla gracilis leaves. Suitable extracts include those previously mentioned, such as ethanol and aqueous extracts of leaves. The leaves may be from one or more plants and may be fresh, dried, or otherwise aged.

[0035] For example, a specific extract can be obtained when Potentilla gracilis (e.g., leaves) is powdered to a uniform size using a mill. The resulting powder is then extracted using an ethanol solution. The solution is then filtered, and the filtrate is concentrated under reduced pressure to obtain a syrup. The syrup is then freeze-dried to a dry state to obtain the extract.

[0036] In various embodiments, the botanical active ingredient consists of an extract of Potentilla radiata leaves. In further or alternative embodiments, the composition is substantially free of ingredients derived from plant material other than Potentilla radiata leaves. In these embodiments, the plant material other than Potentilla radiata leaves may be, for example, the roots, stems, bark, rhizomes, seeds, or flowers of the Potentilla radiata plant. Without being bound by any particular theory, it is believed that Potentilla radiata leaves are most useful for elastase inhibitory effects; whereas, other parts of Potentilla radiata (as illustrated in the Examples section below) are not.

[0037] Suitable leaf extracts may be processed (e.g., defatted, partially defatted, milled, dried, precipitated, washed, filtered, mesh-screened, extracted, distilled, concentrated, etc.) to obtain a Potentilla gracilis leaf extract. Similarly, Potentilla gracilis leaves may be extracted in raw form or may be processed prior to extraction of the Potentilla gracilis leaf extract (e.g., used in raw, suspended, dried, concentrated, etc.). In other embodiments, Potentilla gracilis extracts are not limited to leaf extracts, as they may include material from any part or combination of parts of the plant. For example, Potentilla gracilis extracts may include material extracted from one or more parts of the Potentilla gracilis plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruit.

[0038] The amount of Potentilla gracilis extract utilized in the botanical active ingredient may vary and is selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1 to 2000 mg of Potentilla gracilis extract, e.g., 1 to 1000 mg, optionally 2 to 800 mg, optionally 20 to 750 mg, or optionally 50 to 500 mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active ingredient includes Potentilla gracilis extract in an amount of at least 1 mg, optionally at least about 20 mg, optionally at least about 50 mg, optionally at least 100 mg, optionally at least 250 mg, optionally at least 500 mg, optionally at least 1000 mg, or optionally at least 1500 mg. In these or other embodiments, the upper boundary may be selected such that the botanical active ingredient comprises Potentilla radiata extract in an amount of ≦100, ≦250, ≦500, ≦750, ≦1000, ≦2000, ≦5000 mg. In various embodiments, the botanical active ingredient can include an amount of Potentilla radiata extract of optionally greater than 1 wt.%, optionally greater than 5 wt.%, optionally greater than 10 wt.%, optionally greater than 25 wt.%, optionally greater than 50 wt.%, optionally greater than 75 wt.%, optionally greater than 80 wt.%, or optionally greater than 95 wt.% based on the total weight of the botanical active ingredient. In such embodiments, the upper boundaries may be selected to be generally ≦10 wt.%, ≦20 wt.%, ≦30 wt.%, ≦40 wt.%, ≦50 wt.%, ≦60 wt.%, ≦70 wt.%, ≦80 wt.%, ≦90 wt.%, and ≦99 wt.%, respectively, based on the total weight of the botanical active ingredients.

[0039] In certain embodiments, the botanical active ingredient comprises two or more Potentilla spp. extracts, e.g., two, three, four, etc., or more Potentilla spp. extracts. In such embodiments, each Potentilla spp. extract is independently selected and may be the same or different from the other Potentilla spp. extracts, and each may be utilized in the amounts described above.

[0040] The Potentilla radiata extract may be utilized in any form, such as neat (i.e., without a solvent, carrier vehicle, diluent, etc.), or may be placed in a carrier vehicle, such as a solvent or dispersant. The carrier vehicle, if present, may comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or the like, or a combination thereof. When utilized, the carrier vehicle is selected based on the particular components of the botanical active ingredient and / or composition, such as the particular Potentilla radiata extract(s) utilized. It is understood that the Potentilla radiata extract, if utilized, may be combined with the carrier vehicle before, during, or after combination with the botanical active ingredient and / or other components of the composition. Pangya / Bombax ceiba

[0041] In some embodiments, the botanical active ingredient, and compositions therefrom, include an extract of Panax notoginseng, i.e., an extract containing, and optionally consisting essentially of, materials from the Panax notoginseng plant, such as flowers. The Panax notoginseng extract is not particularly limited and may include any flower extract or combination of extracts from the Panax notoginseng plant suitable for use in embodiments herein. More specifically, exemplary Panax notoginseng flower extracts include those capable of inhibiting elastase activity or eliciting / exhibiting other such activities described herein as part of the botanical active ingredient.

[0042] Bombax ceiba, also known as Bombax ceiba, has been reported to contain a variety of bioactive components, such as flavonoids, flavanols, terpenoid saponins, tannins, sterols, phenols, pyranosides, polysaccharides, glucosides, sesquiterpenes, steroids, naphthoquinones, neolignans, alkanes, fatty acids, monoterpenes, organic acids, and other compounds. Panya is sometimes simply called B. malabaricum, or by various other names, such as Panya DC., Bombax ceiba Linnaeus, Bombax ceiba Linn., Bombax ceiba L., B. ceiba, Gossampinus Malabarica, Panzhihua, Kapok tree, Hero tree, Banzhi, Qiongzhi, Malabar silk-cotton tree, Red silk-cotton, Red cotton tree, Silk-cotton, Common Bombax flower, Mu Mian Hua, [ka] or [ka] It is also sometimes called.

[0043] Specific examples of panja extracts are known in the art. As such, panja extracts may be purchased or otherwise obtained commercially from various suppliers, prepared (e.g., using any conventional extraction technique(s) known in the art, such as any of those described herein), or combinations thereof. In certain embodiments, the panja extract is obtained by alcoholic extraction (e.g., ethanolic extraction) of panja plant material, including, but not limited to, the flowers. In other embodiments, the panja extract may be obtained by water extraction (or aqueous extraction) of panja plant material.

[0044] As will be appreciated by those skilled in the art, panja is primarily cultivated for its flowers, leaves, and / or fruit. Therefore, in various embodiments, the panja extract is an extract of panja flowers. Suitable extracts include those previously described, such as ethanol and aqueous extracts of the flowers. In certain embodiments, the panja flower extract is obtained by alcoholic extraction (e.g., ethanol extraction) of panja flowers or flower-based plant material. The flowers may be from one or more plants and may be fresh, dried, or otherwise aged.

[0045] For example, a specific extract can be obtained when panya (e.g., flowers) are powdered to a uniform size using a mill. The resulting powder is then extracted using an ethanol solution. The solution is then filtered, and the filtrate is concentrated under reduced pressure to obtain a syrup. The syrup is then freeze-dried to dryness to obtain the extract.

[0046] In various embodiments, the botanical active ingredient comprises an extract of panja japonica flower. In further or alternative embodiments, the composition is substantially free of ingredients derived from plant materials other than panja japonica flower. In these embodiments, the plant materials other than panja japonica flower may be, for example, the roots, stems, bark, rhizomes, leaves, seeds, or fruit of the panja japonica plant. Without being bound by any particular theory, it is believed that panja japonica flower is most useful for elastase inhibitory effects; whereas, other parts of panja japonica (as illustrated in the Examples section below) are not.

[0047] Suitable flower extracts may be processed (e.g., defatted, partially defatted, milled, dried, precipitated, washed, filtered, mesh-screened, extracted, distilled, concentrated, etc.) to obtain panja flower extract. Similarly, panja flowers may be extracted in a raw form or may be processed prior to extraction of panja flower extract (e.g., used in a raw, suspended, dried, concentrated, etc.) In other embodiments, panja extracts are not limited to flower extracts, as they may include material from any part or combination of parts of the plant. For example, panja extracts may include materials extracted from one or more parts of the panja plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruit.

[0048] The amount of panja extract utilized in the botanical active ingredient may vary and is selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1 to 2000 mg of panja extract, e.g., 1 to 1000 mg, optionally 2 to 800 mg, optionally 20 to 750 mg, or optionally 50 to 500 mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active ingredient includes panja extract in an amount of at least 1 mg, optionally at least about 20 mg, optionally at least about 50 mg, optionally at least 100 mg, optionally at least 250 mg, optionally at least 500 mg, optionally at least 1000 mg, or optionally at least 1500 mg. In these or other embodiments, the upper boundary may be selected such that the botanical active ingredients comprise panja extract in an amount of ≦100, ≦250, ≦500, ≦750, ≦1000, ≦2000, or ≦5000 mg. In various embodiments, the botanical active ingredients can include an amount of panja extract of optionally greater than 1 wt.%, optionally greater than 5 wt.%, optionally greater than 10 wt.%, optionally greater than 25 wt.%, optionally greater than 50 wt.%, optionally greater than 75 wt.%, optionally greater than 80 wt.%, or optionally greater than 95 wt.%, based on the total weight of the botanical active ingredients. In such embodiments, the upper boundaries may be selected to be generally ≦10 wt.%, ≦20 wt.%, ≦30 wt.%, ≦40 wt.%, ≦50 wt.%, ≦60 wt.%, ≦70 wt.%, ≦80 wt.%, ≦90 wt.%, and ≦99 wt.%, respectively, based on the total weight of the botanical active ingredients.

[0049] In certain embodiments, the botanical active ingredients include two or more panja extracts, for example, 2, 3, 4, etc., or more panja extracts. In such embodiments, each panja extract is independently selected and may be the same or different from the other panja extracts, and each may be utilized in the amounts described above.

[0050] The panja extract may be utilized in any form, such as neat (i.e., without a solvent, carrier vehicle, diluent, etc.), or may be placed in a carrier vehicle, such as a solvent or dispersant. The carrier vehicle, if present, may comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or the like, or a combination thereof. When utilized, the carrier vehicle is selected based on the particular components of the botanical active ingredient and / or composition, such as the particular panja extract(s) utilized. It is understood that the panja extract, if utilized, may be combined with a carrier vehicle before, during, or after combination with the botanical active ingredient and / or other components of the composition. Amomum villosum

[0051] In some embodiments, the botanical active ingredient, and compositions therefrom, include an extract of Amomum villosum, i.e., an extract comprising, and optionally consisting essentially of, material from the Amomum villosum plant species, such as seeds. The Amomum villosum extract is not particularly limited and may include any seed extract or combination of extracts from the Amomum villosum plant suitable for use in embodiments herein. More specifically, exemplary Amomum villosum seed extracts include those capable of inhibiting elastase activity or eliciting / exhibiting other such activities described herein as part of the botanical active ingredient.

[0052] Amomum villosum has been reported to contain a variety of bioactive components, such as terpenoids, flavonoids, diarylheptanoids, and coumarins, as well as other compounds, including, but not limited to, δ-camphor, δ-borneol, δ-bornyl acetate, δ-limonene, α-pinene, phellandrene, ethyl paramethoxycinnamate, nerolidol, linalool, liquiritin, and glucobanillic acid. Amomum villosum is also known simply as A. villosum, or by various other names, such as Amomum villosum Lour, Wurbainia villosa, Malabar cardamom, Tavoy cardamom, false cardamom, Sha Ren, or [ka] It is also sometimes called.

[0053] Specific examples of Amomum villosum extracts are known in the art. As such, Amomum villosum extracts may be purchased or otherwise obtained commercially from various suppliers, prepared (e.g., using any conventional extraction technique(s) known in the art, such as any of those described herein), or combinations thereof. In certain embodiments, an extract of Amomum villosum is obtained by alcohol extraction (e.g., ethanol extraction) of Amomum villosum plant material, including, but not limited to, seeds. In other embodiments, an extract of Amomum villosum may be obtained by water extraction (or aqueous extraction) of Amomum villosum plant material.

[0054] Those skilled in the art will appreciate that Amomum villosum is primarily cultivated for its fruit and associated seeds. Therefore, in various embodiments, the extract of Amomum villosum is an extract of Amomum villosum seeds. Suitable extracts include those previously described, such as ethanol and aqueous extracts of seeds. In certain embodiments, the extract of Amomum villosum seeds is obtained by alcohol extraction (e.g., ethanol extraction) of Amomum villosum seeds or seed-based plant material. The seeds may be from one or more plants and may be fresh, dried, or otherwise aged.

[0055] For example, a specific extract can be obtained when Amomum virosum (e.g., seeds) is powdered to a uniform size using a mill. The resulting powder is then extracted using an ethanol solution. The solution is then filtered, and the filtrate is concentrated under reduced pressure to obtain a syrup. The syrup is then freeze-dried to dryness to obtain the extract.

[0056] In various embodiments, the botanical active ingredient comprises an extract of Amomum villosum seeds. In further or alternative embodiments, the composition is substantially free of ingredients derived from plant material other than Amomum villosum seeds. In these embodiments, the plant material other than Amomum villosum seeds may be, for example, the roots, stems, bark, rhizomes, leaves, flowers, or fruits of the Amomum villosum plant. Without being bound by any particular theory, it is believed that Amomum villosum seeds are most useful for elastase inhibitory effects; whereas, other parts of Amomum villosum (as illustrated in the Examples section below) are not.

[0057] Suitable seed extracts may be processed (e.g., defatted, partially defatted, milled, dried, precipitated, washed, filtered, mesh-screened, extracted, distilled, concentrated, etc.) to obtain an extract of Amomum villosum seeds. Similarly, Amomum villosum seeds may be extracted in a raw form or may be processed prior to extraction of the Amomum villosum seed extract (e.g., used in a raw, suspended, dried, concentrated, etc.) form. In other embodiments, the Amomum villosum extract is not limited to a seed extract, as it may include material from any part or combination of parts of the plant. For example, the Amomum villosum extract may include material extracted from one or more parts of the Amomum villosum plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruit.

[0058] The amount of Amomum villosum extract utilized in the botanical active ingredient may vary and is selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1 to 2,000 mg of Amomum villosum extract, e.g., 1 to 1,000 mg, optionally 2 to 800 mg, optionally 20 to 750 mg, or optionally 50 to 500 mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active ingredient includes Amomum villosum extract in an amount of at least 1 mg, optionally at least about 20 mg, optionally at least about 50 mg, optionally at least 100 mg, optionally at least 250 mg, optionally at least 500 mg, optionally at least 1,000 mg, or optionally at least 1,500 mg. In these or other embodiments, the upper boundary may be selected such that the botanical active ingredient comprises Amomum villosum extract in an amount of ≦100, ≦250, ≦500, ≦750, ≦1000, ≦2000, or ≦5000 mg. In various embodiments, the botanical active ingredient can include an amount of Amomum villosum extract of optionally greater than 1 wt.%, optionally greater than 5 wt.%, optionally greater than 10 wt.%, optionally greater than 25 wt.%, optionally greater than 50 wt.%, optionally greater than 75 wt.%, optionally greater than 80 wt.%, or optionally greater than 95 wt.% based on the total weight of the botanical active ingredient. In such embodiments, the upper boundaries may be selected to be generally ≦10 wt.%, ≦20 wt.%, ≦30 wt.%, ≦40 wt.%, ≦50 wt.%, ≦60 wt.%, ≦70 wt.%, ≦80 wt.%, ≦90 wt.%, and ≦99 wt.%, respectively, based on the total weight of the botanical active ingredients.

[0059] In certain embodiments, the botanical active ingredient comprises two or more Amomum villosum extracts, e.g., two, three, four, etc., or more Amomum villosum extracts. In such embodiments, each Amomum villosum extract is independently selected and may be the same or different from the other Amomum villosum extracts, and each may be utilized in the amounts described above.

[0060] The Amomum villosum extract may be utilized in any form, such as neat (i.e., without a solvent, carrier vehicle, diluent, etc.), or may be placed in a carrier vehicle, such as a solvent or dispersant. The carrier vehicle, if present, may comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or the like, or a combination thereof. When utilized, the carrier vehicle is selected based on the particular components of the botanical active ingredient and / or composition, such as the particular Amomum villosum extract(s) utilized. It is understood that the Amomum villosum extract, if utilized, may be combined with the carrier vehicle before, during, or after combination with the botanical active ingredient and / or other components of the composition. Amomum Kravan

[0061] In some embodiments, the botanical active ingredient, and compositions therefrom, include an extract of Amomum clavan, i.e., an extract containing, optionally consisting essentially of, material from the Amomum clavan plant species, such as fruit. The Amomum clavan extract is not particularly limited and can include any fruit extract or combination of extracts from the Amomum clavan plant suitable for use in embodiments herein. More specifically, exemplary Amomum clavan fruit extracts include those capable of inhibiting elastase activity or eliciting / exhibiting other such activities described herein as part of the botanical active ingredient.

[0062] Amomum kravanh has been reported to contain a variety of bioactive components, such as flavonoids, monoterpenoids, monoterpenes, tetracyclic diterpenes, diarylheptanoids, steroids, coumarins, and secolignans, as well as other compounds, including, but not limited to, 1,8-cineole, bornyl acetate, α-pinene, β-pinene, α-terpinene, terpineol, linalool, and limonene. Amomum kravanh is also known simply as A. kravanh, or by various other names, such as sandalwood, Amomum cardamomum, round cardamom, Cambodian cardamom, white cardamom, Bai Dou Kou, or [ka] It is also sometimes called.

[0063] Specific examples of Amomum clavan extracts are known in the art. As such, Amomum clavan extracts may be purchased or otherwise obtained commercially from various suppliers, prepared (e.g., using any conventional extraction technique(s) known in the art, such as any of those described herein), or combinations thereof. In certain embodiments, an extract of Amomum clavan is obtained by alcoholic extraction (e.g., ethanolic extraction) of Amomum clavan plant material, including, but not limited to, the fruit. In other embodiments, an extract of Amomum clavan may be obtained by water extraction (or aqueous extraction) of Amomum clavan plant material, including, but not limited to, the fruit.

[0064] As will be appreciated by those skilled in the art, Amomum clavan is primarily cultivated for its fruit and associated seeds. Therefore, in various embodiments, the extract of Amomum clavan is an extract of Amomum clavan fruit. Suitable extracts include those previously described, such as ethanol and aqueous extracts of the fruit. In certain embodiments, the extract of Amomum clavan fruit is obtained by alcohol extraction (e.g., ethanol extraction) of Amomum clavan fruit or fruit-based plant material. The fruit may be from one or more plants and may be fresh, dried, or otherwise ripened.

[0065] For example, a specific extract can be obtained when Amomum clavan (e.g., fruit) is powdered to a uniform size using a mill. The resulting powder is then extracted using an ethanol solution. The solution is then filtered, and the filtrate is concentrated under reduced pressure to obtain a syrup. The syrup is then freeze-dried to a dry state to obtain the extract.

[0066] In various embodiments, the botanical active ingredient comprises an extract of the fruit of Amomum clavan. In further or alternative embodiments, the composition is substantially free of ingredients derived from plant material other than the fruit of Amomum clavan. In these embodiments, the plant material other than the fruit of Amomum clavan can be, for example, the roots, stems, bark, rhizomes, leaves, or flowers of the Amomum clavan plant. Without being bound by any particular theory, it is believed that the fruit of Amomum clavan is most useful for elastase inhibitory effects; whereas, other parts of Amomum clavan (as illustrated in the Examples section below) are not.

[0067] Suitable fruit extracts may be processed (e.g., defatted, partially defatted, milled, dried, precipitated, washed, filtered, mesh-screened, extracted, distilled, concentrated, etc.) to obtain an extract of Amomum clavan fruit. Similarly, Amomum clavan fruit may be extracted in its raw form or may be processed prior to extraction of the extract of Amomum clavan fruit (e.g., used in its raw, suspended, dried, concentrated, etc.). In other embodiments, the extract of Amomum clavan may include material from any part or combination of parts of the plant, and is therefore not limited to an extract of the fruit. For example, the extract of Amomum clavan may include material extracted from one or more parts of the Amomum clavan plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruit.

[0068] The amount of Amomum clavan extract utilized in the botanical active ingredient may vary and is selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1-2000 mg, e.g., 1-1000 mg, optionally 2-800 mg, optionally 20-750 mg, or optionally 50-500 mg, of Amomum clavan extract. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active ingredient comprises Amomum clavan extract in an amount of at least 1 mg, optionally at least about 20 mg, optionally at least about 50 mg, optionally at least 100 mg, optionally at least 250 mg, optionally at least 500 mg, optionally at least 1000 mg, or optionally at least 1500 mg. In these or other embodiments, the upper boundary may be selected such that the botanical active ingredient comprises Amomum clavan extract in an amount of ≦100, ≦250, ≦500, ≦750, ≦1000, ≦2000, or ≦5000 mg. In various embodiments, the botanical active ingredient can include an amount of Amomum clavan extract of optionally greater than 1 wt.%, optionally greater than 5 wt.%, optionally greater than 10 wt.%, optionally greater than 25 wt.%, optionally greater than 50 wt.%, optionally greater than 75 wt.%, optionally greater than 80 wt.%, or optionally greater than 95 wt.% based on the total weight of the botanical active ingredient. In such embodiments, the upper boundaries may be selected to be generally ≦10 wt.%, ≦20 wt.%, ≦30 wt.%, ≦40 wt.%, ≦50 wt.%, ≦60 wt.%, ≦70 wt.%, ≦80 wt.%, ≦90 wt.%, and ≦99 wt.%, respectively, based on the total weight of the botanical active ingredients.

[0069] In certain embodiments, the botanical active ingredient comprises two or more Amomum clavan extracts, e.g., two, three, four, etc., or more Amomum clavan extracts. In such embodiments, each Amomum clavan extract is independently selected and may be the same or different from the other Amomum clavan extracts, and each may be utilized in the amounts described above.

[0070] The Amomum clavan extract may be utilized in any form, such as neat (i.e., without a solvent, carrier vehicle, diluent, etc.), or may be placed in a carrier vehicle, such as a solvent or dispersant. The carrier vehicle, if present, may comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or the like, or a combination thereof. When utilized, the carrier vehicle is selected based on the particular components of the botanical active ingredient and / or composition, such as the particular Amomum clavan extract(s) utilized. It is understood that the Amomum clavan extract, if utilized, may be combined with the carrier vehicle before, during, or after combination with the botanical active ingredient and / or other components of the composition. Cornus officinalis

[0071] In some embodiments, the botanical active ingredient, and compositions therefrom, include an extract of Cornus officinalis, i.e., an extract containing, optionally consisting essentially of, material from the plant species Cornus officinalis, such as fruit. Cornus officinalis extracts are not particularly limited and can include any fruit extract or combination of extracts from the Cornus officinalis plant suitable for use in embodiments herein. More specifically, exemplary Cornus officinalis fruit extracts include those capable of inhibiting elastase activity or eliciting / exhibiting other such activities described herein as part of the botanical active ingredient.

[0072] Cornus officinalis has been reported to contain a variety of bioactive components, such as iridoids, glucosides, iridoid glycosides, secoiridoid glycosides, loganin, cornusides, cornusphenosides, triterpenoids, gallotannins, 2-furancarboxaldehyde, and other compounds. Cornus officinalis is also known simply as C. officinalis or by various other names, such as Cornus officinalis (Sieb. et Zucc.), Macrocarpium officinale, Japanese Cornelian Cherry, Japanese Cornelian Dogwood, Asiatic Dogwood, Asiatic Cornelian Cherry, Shan Zhu Yu, or other names. [ka] It is also sometimes called.

[0073] Specific examples of Cornus officinalis extracts are known in the art. As such, Cornus officinalis extracts may be purchased or otherwise obtained commercially from various suppliers, prepared (e.g., using any conventional extraction technique(s) known in the art, such as any of those described herein), or combinations thereof. In certain embodiments, Cornus officinalis extracts are obtained by alcoholic extraction (e.g., ethanolic extraction) of Cornus officinalis plant material, including, but not limited to, the fruit. In other embodiments, Cornus officinalis extracts may be obtained by water extraction (or aqueous extraction) of Cornus officinalis plant material, including, but not limited to, the fruit.

[0074] Those skilled in the art will appreciate that Cornus officinalis is primarily cultivated for its fruit. Therefore, in various embodiments, the extract of Cornus officinalis is an extract of Cornus officinalis fruit. Suitable extracts include those previously described, such as ethanolic and aqueous extracts of the fruit. In certain embodiments, the extract of Cornus officinalis fruit is obtained by alcoholic extraction (e.g., ethanolic extraction) of Cornus officinalis fruit or fruit-based plant material. The fruit may be from one or more plants and may be fresh, dried, or otherwise ripened.

[0075] For example, a specific extract can be obtained when Cornus officinalis (e.g., fruit) is powdered to a uniform size using a mill. The resulting powder is then extracted using an aqueous or ethanol solution. The solution is then filtered, and the filtrate is concentrated under reduced pressure to obtain a syrup. The syrup is then freeze-dried to dryness to obtain the extract.

[0076] In various embodiments, the botanical active ingredient comprises an extract of the fruit of Cornus officinalis. In further or alternative embodiments, the composition is substantially free of ingredients derived from plant material other than the fruit of Cornus officinalis. In these embodiments, the plant material other than the fruit of Cornus officinalis can be, for example, the root, stem, bark, rhizome, leaves, flowers, or seeds of the Cornus officinalis plant. Without being bound by any particular theory, it is believed that the fruit of Cornus officinalis is most useful for elastase inhibitory effects; whereas, other parts of Cornus officinalis are not (as illustrated in the Examples section below).

[0077] Suitable fruit extracts may be processed (e.g., defatted, partially defatted, milled, dried, precipitated, washed, filtered, mesh-screened, extracted, distilled, concentrated, etc.) to obtain a Cornus officinalis fruit extract. Similarly, Cornus officinalis fruit may be extracted in its raw form or may be processed (e.g., used in its raw, suspended, dried, concentrated, etc.) prior to extraction of the Cornus officinalis fruit extract. In other embodiments, Cornus officinalis extracts are not limited to fruit extracts, as they may include material from any part or combination of parts of the plant. For example, Cornus officinalis extracts may include material extracted from one or more parts of the Cornus officinalis plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruit.

[0078] The amount of Cornus officinalis extract utilized in the botanical active ingredient may vary and is selected based on the number and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1 to 2,000 mg of Cornus officinalis extract, e.g., 1 to 1,000 mg, optionally 2 to 800 mg, optionally 20 to 750 mg, or optionally 50 to 500 mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active ingredient comprises Cornus officinalis extract in an amount of at least 1 mg, optionally at least about 20 mg, optionally at least about 50 mg, optionally at least 100 mg, optionally at least 250 mg, optionally at least 500 mg, optionally at least 1,000 mg, or optionally at least 1,500 mg. In these or other embodiments, the upper boundary may be selected such that the botanical active ingredients comprise Cornus officinalis extract in an amount of ≦100, ≦250, ≦500, ≦750, ≦1000, ≦2000, or ≦5000 mg. In various embodiments, the botanical active ingredients can include an amount of Cornus officinalis extract of optionally more than 1 wt.%, optionally more than 5 wt.%, optionally more than 10 wt.%, optionally more than 25 wt.%, optionally more than 50 wt.%, optionally more than 75 wt.%, optionally more than 80 wt.%, or optionally more than 95 wt.%, based on the total weight of the botanical active ingredients. In such embodiments, the upper boundaries may be selected to be generally ≦10 wt.%, ≦20 wt.%, ≦30 wt.%, ≦40 wt.%, ≦50 wt.%, ≦60 wt.%, ≦70 wt.%, ≦80 wt.%, ≦90 wt.%, and ≦99 wt.%, respectively, based on the total weight of the botanical active ingredients.

[0079] In certain embodiments, the botanical active ingredient comprises two or more Cornus officinalis extracts, e.g., two, three, four, etc., or more Cornus officinalis extracts. In such embodiments, each Cornus officinalis extract is independently selected and may be the same or different from the other Cornus officinalis extracts, and each may be utilized in the amounts described above.

[0080] The Cornus officinalis extract may be utilized in any form, such as neat (i.e., without a solvent, carrier vehicle, diluent, etc.), or may be placed in a carrier vehicle, such as a solvent or dispersant. The carrier vehicle, if present, may comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, or the like, or a combination thereof. When utilized, the carrier vehicle is selected based on the particular components of the botanical active ingredient(s) and / or composition, such as the particular Cornus officinalis extract(s) utilized. It is understood that the Cornus officinalis extract, if utilized, may be combined with the carrier vehicle before, during, or after combination with the botanical active ingredient(s) and / or other components of the composition. definition

[0081] In order to provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0082] The terms "ameliorating at least one sign of aging" and "ameliorating a sign of aging" are used interchangeably herein and refer to preventing, halting, reversing, ameliorating, diminishing, and / or reducing the signs of aging, including, but not limited to, lines, fine lines, wrinkles, crow's feet, dark circles, age spots, age spots, stretch marks, or a combination thereof.

[0083] The terms "improving the appearance of skin" and "improving the aesthetic appearance of skin" are used interchangeably herein and refer to aesthetic improvements in the appearance of skin. Exemplary improvements include, but are not limited to, favorable characteristics and / or properties related to skin thickness, extensibility, elasticity, moisturization, smoothness, color, texture, brightness, luster, luminosity, clarity, contour, firmness, tautness, flexibility, softness, sensitivity, pore size, or combinations thereof. The terms are also used to refer to the improvement of unhealthy skin conditions. Representative examples of undesirable symptoms that may be affected by, result from, or be caused by such unhealthy skin conditions include, but are not limited to, psoriasis, eczema, seborrhea, dermatitis, sunburn, estrogen imbalance, hyperpigmentation, hypopigmentation, discoloration, yellowing, freckles, skin atrophy, skin breakouts, brittle skin, dryness, roughness to the touch, cracking, sagging, thinning, thickening, fibrosis, enlarged pores, cellulite formation, bruising, acne, apoptosis, cell differentiation, cell dedifferentiation, tumor induction or prevention of tumor progression, viral infection, fungal infection, bacterial infection, spider veins (telangiectasia), hirsutism, rosacea, pruritus, calluses, warts, corns, or a combination of the above.

[0084] The terms "composition" and "formulation" refer to products that treat, improve, promote, increase, manage, control, maintain, optimize, modify, reduce, inhibit, or prevent a specific condition, disease, or disorder associated with a natural biological process. For example, the composition or formulation improves at least one sign of aging skin in a subject and / or minimizes or inhibits skin glycation (e.g., skin maturation). The terms composition and formulation include, but are not limited to, pharmaceutical (i.e., drug), over-the-counter (OTC), cosmetic, food, food ingredient, or dietary supplement compositions containing an effective amount of the extract, at least one component thereof, or a mixture thereof. Exemplary compositions and / or formulations include creams, cosmetic lotions, packs, or powders, or are included as emulsions, lotions, liniment foams, tablets, plasters, granules, or ointments. Preferred compositions are formulated for topical application / administration and oral administration / ingestion.

[0085] As used herein, the term "effective amount" or "therapeutically effective amount" of a pure compound, composition, extract, extract mixture, extract component, active agent or ingredient, or combination thereof refers to an amount effective at a sufficient dosage and for a sufficient period of time to achieve a desired result. For example, an "effective amount" or "therapeutically effective amount" refers to the amount of a pure compound, composition, extract, botanical extract, extract mixture, botanical extract mixture, extract component, 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 treat, for example, aging skin and / or minimize or inhibit glycation of mature skin. The amount of a composition, extract, botanical extract, extract mixture, botanical extract mixture, extract component, and / or active agent or ingredient of the present disclosure that constitutes an "effective amount" or "therapeutically effective treatment" will vary depending on the active agent or compound, the condition being treated and its severity, the method of administration, the duration of treatment, or the age of the subject being treated, but can be routinely determined by one of ordinary skill in the art given their own knowledge and this disclosure.

[0086] The term "pharmaceutically acceptable" means that those drugs, agents, extracts or inactive ingredients are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, etc., commensurate with a reasonable benefit / risk ratio.

[0087] The terms "application" and "administration" are defined as providing a composition to a subject by any route known in the art, including, but not limited to, topical, intravenous, intraarterial, oral, parenteral, buccal, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In preferred embodiments, administration of the described compositions by topical and / or oral routes is preferred.

[0088] The terms "minimize," "reduce," "suppress," "reduce," and / or "inhibit" refer to a decrease or reduction in elastase activity and / or expression, and / or its downstream effects, in the presence of a botanical (plant) ingredient or botanical extract described herein, when compared to elastase activity and / or expression in the absence of the botanical ingredient or botanical extract described herein, e.g., in a control sample. The extent of reduction or inhibition of elastase activity and / or expression and / or its downstream effects will vary depending on the nature and amount of botanical ingredient or botanical extract present, but will be evident, for example, as a detectable decrease in elastase activity and / or expression; desirably, a decrease of about 5%, about 10%, about 15%, about 20%, about 25%, about 50%, about 75%, about 90%, about 95%, or greater than about 99% (or any degree of decrease ranging from about 5% to about 99%), compared to elastase activity and / or expression in the absence of the botanical ingredient or botanical extract. For example, a composition containing one or more botanical ingredients or plant extracts of Potentilla gracilis, Panax notoginseng, Amomum villosum, Amomum clavan, and / or Cornus officinalis can minimize or reduce elastase activity in skin, such as mature skin.

[0089] As used herein, the term "subject" or "individual" includes mammals to which a 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. Composition (or Formulation)

[0090] The composition may include any amount of botanical active ingredient, which is selected based on the number and type of ingredients utilized in the composition as a whole. Generally, the botanical active ingredient is present in the composition in an amount effective to inhibit elastase in the subject's skin.

[0091] In certain embodiments, the composition contains botanical active ingredients in an amount of 1-5000, optionally 2-2000, optionally 5-1750, optionally 10-1500, optionally 15-1250, optionally 20-1000, optionally 25-750, optionally 30-500, optionally 35-500, optionally 40-500, optionally 45-450, optionally 50-450, or optionally 50-400 mg. However, amounts outside and / or overlapping these ranges may also be utilized. For example, it is understood that the ranges set forth above regarding the amount of each botanical extract in the botanical active ingredients may equally apply to the amount of each botanical extract in the composition as a whole, e.g., when the botanical active ingredients are comprised of more than one botanical extract.

[0092] In certain embodiments of the composition, the formulation comprises one or more of the following: an ethanol extract of the leaves of Atractylodes orbiculatus, an ethanol extract of the flowers of Panax notoginseng, an ethanol extract of the seeds of Atractylodes orbiculatus, an ethanol extract of the fruits of Atractylodes orbiculatus, and an aqueous and / or ethanol extract of the fruits of Cornus japonica.

[0093] Flavor essences and / or sugar substitutes may be included in the composition and can be any type of conventional ingredient understood in the art, such as flavorings. Plant (botanical) extracts can be as described above, respectively. Examples of suitable flavorings are further described below.

[0094] In general, the compositions are not limited by formulation, peripheral ingredients, form, number of functions, etc., other than comprising a botanical active ingredient and its botanical extract(s). Rather, the compositions may be varied and formulated in any manner consistent with this disclosure.

[0095] Typically, the compositions are formulated or otherwise configured for administration to a mammalian subject (e.g., a human). For example, in various embodiments, the compositions are configured to be administered topically (e.g., eye cream, mask) or consumed by a human subject, and / or administered orally.

[0096] In certain embodiments, the composition is further defined as a topical composition formulated for topical administration to a subject. In such embodiments, the composition is also referred to as a cosmetic composition, and typically may include at least one cosmetically acceptable carrier in addition to the biologically active substance composition. In certain embodiments, the cosmetically acceptable carrier is not naturally occurring. In other words, the carrier is not a natural product in these certain embodiments. In other embodiments, the carrier can be selected from conventional carriers understood in the art and used in conventional amounts.

[0097] 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 is also referred to as an ingestible composition, and typically includes at least one pharmaceutically acceptable additive in addition to the bioactive substance composition. In certain embodiments, the pharmaceutically acceptable additive is not naturally occurring. In other words, the pharmaceutically acceptable additive is not a natural product in these certain embodiments. In other embodiments, the pharmaceutically acceptable additive can be selected from conventional additives understood in the art and used in conventional amounts.

[0098] Therefore, it should be understood that the particular additives, carriers, adjuvants, fillers, etc. present in or combined with the composition may vary. Moreover, the physical form of the composition is not limited and is selected based on the particular components of the composition, the desired use of the composition, etc. Thus, in view of the description herein, it will be understood that the composition may 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, non-pyrogenic solution, suspension, coated capsule, suppository, lyophilized powder, transdermal patch, soft gel, or other known form. Other examples of suitable forms include solids, gels, liquids, creams, lotions, pomades, mousses, powders, foams, sprays, ointments, or other such preparations in which the botanical active ingredient is disposed in a suitable carrier vehicle, such as any of those described herein. In certain embodiments, the composition is formulated as an eye cream or mask for topical application, or otherwise provided.

[0099] The compositions can be prepared using a variety of methods. For example, the active agent (e.g., botanical extract(s)), and optionally one or more inactive agents (e.g., one or more conventional ingredients, additives, excipients, etc.) of the composition can be mixed or blended and then tableted or compounded using a variety of techniques well known in the art. The compositions of this disclosure are not limited to a particular order of manufacturing steps or method of manufacture.

[0100] In various embodiments, the composition is administered topically by application to the skin of a subject. The subject is typically a human and may include males and females of various ages. The methods / compositions of this disclosure are not limited to a specific subject.

[0101] 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 a subject's skin as a gel, cream, lotion, pomade, mousse, powder, or foam. In another example, the composition can be formulated to be sprayed onto a subject's skin. The composition can be formulated to be sprayed as either an aerosol spray or a pump spray. In yet another example, the composition can be formulated for application using pre-moistened wipes. In another example, the composition can be formulated as a solid to be rubbed into a subject's skin. In another example, the composition can be formulated for delivery via a patch that is adhered to a subject's skin.

[0102] Except for the botanical active ingredient (i.e., "active agent" or "active ingredient"), the composition can include pharmaceutically acceptable additives that are inert agents (or "inert ingredients"), including, but not limited to, excipients, such as diluents and binders; granulating agents; glidants (or flow aids); fillers; lubricants; preservatives; stabilizers; coatings; disintegrants; flavors; and pigments. The active ingredient and pharmaceutically acceptable additives can be combined or blended as desired to form an individual dose that, when applied topically, provides a desired amount of the active ingredient to a human subject.

[0103] Optionally, the composition may include one or more additional ingredients, such as additives. Suitable additives include, but are not limited to, those known in the art, including moisturizers, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, preservatives, drugs and active pharmaceutical ingredients, analgesic compounds, anti-neuralgic compounds, antioxidants, blood circulation promoters, antidepressant compounds, anti-anxiety compounds, anti-stress compounds, sunscreens, insect repellents, preservatives, exfoliants, fragrances, colorants, bulking agents, solvents, vehicles, carriers, other types of additives known to those skilled in the art, and combinations thereof. Such additives may be used alone or in combination. Generally, optional additives may be of any type used in personal care products and cosmetics.

[0104] Excipients can be further classified as other ingredients. Specifically, excipients used in oral solid dosage forms have been classified into groups based on their functionality, such as diluents, disintegrants, binders, tableting aids, granulating agents, glidants, lubricants, release-controlling polymers, stabilizers (such as antioxidants, chelating agents, and pH adjusters), film-coating polymers, coating agents, vehicles, plasticizers, surfactants, colorants, sweeteners, and flavoring agents.

[0105] In various embodiments, the composition includes at least one ingredient selected from the group consisting of 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, acacia, gums, waxes, glycerol monostearate, acrylic acid polymers and copolymers, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, lactose, calcium sulfate, dicalcium phosphate, sugars, microcrystalline cellulose (MCC), starch, sodium starch glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. It is understood in the art that combinations of such ingredients can be utilized, and that such ingredients can be combined with other ingredients conventionally used in tablet formulations.

[0106] As used herein, a "diluent" refers to an inert substance added to increase the volume of a composition to make tablets of a practical size for compression. Therefore, they are sometimes also referred to as bulking agents. 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, (powders) sugar, dextrose, mannitol, sorbitol, and the like. Diluents / bulking agents may be used alone or in various mixtures and may be utilized in any amount known in the art for oral compositions.

[0107] As used herein, a "flavoring agent" is a compound designed to impart a more pleasant taste to a composition. Flavoring agents vary widely in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex essential oils. Most desired types of synthetic flavors are currently available and well known in the art. An intolerable, sour, or bitter taste from the starting material may be countered by seasonings or flavoring agents, and acidifying agents (e.g., citric acid, tartaric acid, malic acid, ascorbic acid, etc.), sweeteners (e.g., saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin, etc.), or flavoring agents (e.g., lemon oil, orange oil, or various fruit flavors, including strawberry, yogurt, mint, menthol, etc.) may be included in the composition. Flavoring agents may be used alone or in various mixtures and may be utilized in any amounts known in the art for oral compositions.

[0108] As used herein, a "lubricant" is a material that performs multiple functions in the context of a composition. In certain embodiments, such as in tablet production, a lubricant performs one or more of the following functions: improving the flow rate of tablet granulation, preventing adhesion of tablet material to die and punch surfaces, reducing intergranular friction, and facilitating ejection of tablets from die cavities. Examples of suitable lubricants include, but are not limited to, zinc stearate, gum arabic powder, cocoa butter, carnauba wax, carmellose calcium, carmellose sodium, caropeptides, hydrous silicon dioxide, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, sesame oil, wheat starch, white beeswax, magnesium oxide, dimethylpolysiloxane, potassium sodium tartrate, sucrose fatty acid esters, glycerin fatty acid esters, silicone resins, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, and sucrose. Lubricants include calcium stearate, polyoxyl stearate, magnesium stearate, cetanol, gelatin, talc, magnesium carbonate, precipitated calcium carbonate, corn starch, lactose, hard fat, saccharose, potato starch, hydroxypropyl cellulose, fumaric acid, sodium stearyl fumarate, polyethylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, beeswax, magnesium aluminometasilicate, methylcellulose, wallow, glycerin monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, phosphoric acid, palmitic acid, hydrogenated vegetable oil, and fat. Lubricants can be used alone or in various mixtures and can be utilized in any amount known in the art for oral compositions.

[0109] As used herein, a "binder" is an agent used to impart cohesive qualities to powdered materials. Binders, or "granulating agents," as they are sometimes known, impart cohesive properties to tablet formulations, ensuring that tablets remain intact after compression and improving free-flowing characteristics 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; and natural and synthetic gums, such as gum arabic, sodium alginate, Irish moss extract, panwa gum, ghatti gum, isabgol bark mucus, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone (PVP), Veegum, microcrystalline cellulose, microcrystalline dextrose, amylose, larch arabogalactan, ethylcellulose, and cellulose acetate. Binders may be used alone or in various mixtures and may be utilized in any amounts known in the art for oral compositions.

[0110] As used herein, a "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 aids users in identifying the product. Any of the approved, certified, water-soluble FD&C dyes, mixtures thereof, or their corresponding lakes can be used in colored tablets. A color lake is a combination of a water-soluble dye and a heavy metal hydroxide, resulting in an insoluble form of the dye. Colorants may be used alone or in various mixtures and may be utilized in any amount known in the art for oral compositions.

[0111] Other conventional ingredients that may optionally be present in the composition include preservatives, stabilizers, anti-caking agents or silica flow conditioners, or glidants such as silicon dioxide. Such ingredients may be used alone or in various mixtures and may be utilized in any amounts known in the art for oral compositions.

[0112] It should be understood that although particular ingredients or additives may be classified under different terminologies, merely because an ingredient or additive is classified under such a term does not mean that it is limited to that function. When utilized, the additive(s) may be present in the composition in various amounts. For optional use of the composition, for example, when configured for topical or oral application, additional ingredients may be used as disclosed 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 entire disclosures of which are incorporated herein by reference. Administration method

[0113] The composition can be administered or applied daily, several times a day, or in any suitable dosage regimen as needed to achieve the desired results. In the methods of this disclosure, the frequency of administration (e.g., topical application) depends on several factors, including the desired degree of elastase inhibition. Generally, the dosage regimen involves applying the composition once or twice a day, including a morning administration and / or an evening administration. The amount and / or frequency of application of the composition depends on several factors, including the desired level of results and the particular composition.

[0114] Improved skin appearance can be achieved by administering the formulations of the present invention externally, internally, or a 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 with an acceptable carrier in the form of a gel, lotion, cream, tonic, emulsion, etc. As a further example, the formulations of the present invention can be administered internally with an acceptable carrier in the form of a pill, tablet, powder, bar, drink, etc. Accordingly, the formulations described herein are useful in a wide variety of end products, for example, pharmaceutical, food, and drink compositions. Preferably, the product is useful for providing an improved appearance to mammalian skin.

[0115] When the formulations of the present invention are orally administered as liquids, the liquid can be water-based, milk-based, tea-based, fruit juice-based, or combinations thereof. The oral solid and liquid formulations of the present invention can further comprise thickening agents, such as xanthon gum, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, methylcellulose, microcrystalline cellulose, starch, dextrin, fermented whey, tofu, maltodextrin, polyols including sugar alcohols (e.g., sorbitol and mannitol), carbohydrates including lactose, propylene glycol alginate, gellan gum, guar, pectin, tragacanth gum, acacia gum, locust bean gum, gum arabic, gelatin, and mixtures of these thickening agents. These thickening agents are typically present in the formulations of the present invention at about 0.1% or less, depending on the specific thickening agent used and the desired viscosity result.

[0116] The solid and liquid formulations (foods and beverages) of the present invention can contain, and typically contain, an effective amount 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 typically depends on the type of sweetener and the intensity of sweetness desired.

[0117] In another example, the formulations of the present invention are administered topically in the following forms: a solution, gel, lotion, cream, ointment, oil-in-water emulsion, water-in-oil emulsion, viscosity liquid, spray, paste, mousse, tonic, foundation, mask, or other form suitable for cosmetic or topical application.

[0118] Preferably, formulations of the present invention suitable for topical administration are mixed with an acceptable carrier. The acceptable carrier can act variously as a solvent, diluent, or dispersant for the components of the composition, allowing for uniform application of the components to the surface of the skin at the appropriate dilution. The acceptable carrier can also facilitate penetration of the composition into the skin.

[0119] In one example of a formulation for topical administration, the acceptable carrier comprises from about 70% to about 99.99% by weight of the total composition. In another example, the acceptable carrier comprises from about 85% to about 99.99% by weight of the total composition. The acceptable carrier can also comprise from about 90% to about 99.99% by weight of the total composition. Alternatively, the acceptable carrier can comprise from about 99.95% to about 99.999% by weight of the total composition. The acceptable carrier can form the balance of the composition, in the absence of other cosmetic adjuncts or additives.

[0120] The various components used to practice the present invention can be soluble or insoluble in the acceptable carrier. If all of the components of the formulation are soluble in the acceptable carrier, the vehicle acts as a solvent. However, if all or some of the components of the formulation are insoluble in the acceptable carrier, the components are dispersed in the vehicle by means of, for example, a suspension, emulsion, gel, cream, or paste.

[0121] Therefore, 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 include 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.

[0122] Preferably, the acceptable carrier used to practice the present invention comprises water and ethanol. Optionally, the acceptable carrier further comprises butylene glycol. For example, the acceptable carrier may comprise 2-5% butylene glycol by weight of the composition. In practicing the present invention, the acceptable carrier is preferably mixed with the formulation of the present invention to comprise 2% by weight of the total composition. In other examples, the acceptable carrier is mixed with the formulation of the present invention to comprise 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.

[0123] Generally, however, acceptable carriers for the present invention include, but are not limited to, the following: water; castor oil; ethylene glycol monobutyl ether; diethylene glycol monoethyl ether; corn oil; dimethyl sulfoxide; ethylene glycol; isopropyl alcohol; soybean oil; glycerin; soluble collagen; safflower seed oil; meadowfoam seed oil; mineral oil; squalene; shea butter; borage oil; rice bran oil; polyquaternium-10; methylparaben; PEG-8; disodium lauroamphoacetate. ;Sodium Trideceth Sulfate;Hexylene Glycol;Sodium Methyl Cocoyl Taurate;TEA Lauryl Sulfate;Lauryl Betaine;Sodium Myristoyl Sarcosinate;PEG-150 Distearate;Anhydrous Citric Acid;Sodium Citrate Dihydrate;Diazolicinyl Urea;Disodium EDTA;Propylparaben;Polysorbate 60;Isopropyl Palmitate;Octyl Palmitate;C12-15 Alkyl Benzoate;Dipropylene Glycol Dibenzoate;PPG-15 Stearyl Ether Benzoate;Isododecane;Isoethyl Eicosane; Squalane; Jojoba Oil; Dimethicone; Glyceryl Stearate; PEG-100 Stearate; Cetyl Alcohol; Butylene Glycol; Chlorphenezine; Fragrance; Polyacrylamide; C13-14 Isoparaffin; Laureth-7; Aloe Vera Powder; Aloe Vera Gel, Hydroxyethyl Acrylate; Sodium Acryloyldimethyl Taurate Copolymer; Behenyl Alcohol; Tocopheryl Acetate; Isodecyl Neopentanoate; Glyceryl Trioctanoate; Cetearyl Alcohol; Cetearyl Glucoside; Chamomile Flower Extract Biosaccharide Gum-1; Pentadecalactone; Dipropylene Glycol; Cyclomethicone; PEG / PPG-18 / 18 Dimethicone; Cyclopentasiloxane; Disteardimonium Hectorite; SD Alcohol 40; Phenoxyethanol; Ethylparaben; Trimethylsiloxysilicate; Triethoxycaprylylsilane; Micronized Titanium Dioxide; Titanium Dioxide; Zinc Oxide; Iron Oxides (Yellow; Red; Black; etc.); Caprylylsilane; Sodium Chloride; Diisopropyl Dilinoleate Dimer; Aluminum Hydroxide; Stearic Acid; Polyethylene Beads;C12-15 Alkyl Benzoate;Acrylates / C10-30 Alkyl Acrylate;Xanthan Gum;Sorbitan Laurate;Pentenol;Petrolatum;Isopropyl Isostearate;Dimethicone;Arginine;Phenoxyethanol;Acryloyldimethyl Taurate Copolymer;Isohexadecane;Polysorbate 80;Hydroxyethyl Acrylate;Sodium Acryloyldimethyl Taurate Copolymer;Octinoxate (Octyl Methoxycinnamate);Oxybenzone;Dicaprylyl Ether;Isodecyl Neopentanoate;Cetearyl Alcohol;Cetearyl Glucoside;Benzyl Alcohol;HDI / Tocopheryl Acetate Contains any of the following: methylol hexyl lactone crosspolymer; silica; isodecyl neopentanoate; coconut glucoside; C20-22 alkyl phosphate; C20-22 alcohol; palmitoyl proline; magnesium palmitoyl glutamate; sodium palmitoyl sarcosinate; C30-45 alkyl cetearyl crosspolymer; polyacrylate 13; polyisobutene; polysorbate 20; iodopropynyl butylcarbamate; sodium magnesium silicate; methyl gluceth-20; dimethyl isosorbide; silica; SD alcohol 40-B; salicylic acid; ceteth-20; fragrance; or witch hazel.

[0124] Additionally, acceptable carriers used in the present invention can optionally contain one or more humectants, including, but not limited to, the following: dibutyl phthalate; soluble collagen; sorbitol; or sodium 2-pyrrolidone-5-carboxylate. Other examples of humectants that can be used in practicing the present invention can be found in the CFTA's Cosmetic Ingredients Handbook, relevant portions of which are incorporated herein by reference.

[0125] Additionally, acceptable carriers within the present invention optionally include, but are not limited to, the following: butane-1,3 diol; cetyl palmitate; dimethylpolysiloxane; glyceryl monoricinoleate; glyceryl monostearate; isobutyl palmitate; isocetyl stearate; isopropyl palmitate; isopropyl stearate; butyl stearate; isopropyl laurate; hexyl laurate; decyl oleate; isopropyl myristate; lauryl lactate; octadecane-2-ol; caprylic / capric triglyceride; The composition may include one or more emollients, including glycerides; capric triglycerides; polyethylene glycol; propane-1,2-diol; triethylene glycol; sesame oil; coconut oil; safflower oil; isoamyl laurate; nonoxynol-9; panthenol; hydrogenated vegetable oils; 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 in the practice of the present invention can be found in the CFTA Cosmetic Ingredients Handbook, the relevant portions of which are incorporated herein by reference.

[0126] Additionally, acceptable carriers herein can optionally contain one or more penetration enhancers, including, but not limited to, the following: pyrrolidones, e.g., 2-pyrrolidone; alcohols, such as ethanol; alkanols, such as decanol; glycols, e.g., propylene glycol, dipropylene glycol, butylene glycol; surfactants; or terpenes.

[0127] Other acceptable carriers which 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.

[0128] For example, an acceptable carrier can be a topically applied lotion that can include Cabomer 981, water, glycerin, isopropyl myristate, mineral oil, shea butter, stearic acid, glycol stearate, cetyl alcohol, dimethicone, preservatives, tea, and various other ingredients of the formulations of the present invention.

[0129] The formulations of the present invention may further include various known and conventional cosmetic additives, so long as they do not adversely affect the desired skin-improving and moisturizing effects provided by the formulation. For example, the formulations of the present invention may further include one or more additives or other optional ingredients known to those skilled in the art. These include, but are not limited to, fillers (e.g., solid, semi-solid, liquid, etc.); carriers; diluents; thickeners; gelling agents; vitamins, retinoids, and retinols (e.g., vitamin B3, vitamin A, etc.); pigments; fragrances; sunscreens and sunblocks; antioxidants and radical scavengers; organic hydroxy acids; exfoliants; skin conditioners; moisturizers; ceramides, pseudoceramides, phospholipids, sphingolipids, cholesterol, glucosamine, and pharmaceutically acceptable salts thereof. Acceptable penetrating agents (e.g., n-decylmethyl sulfoxide, lecithin organogels, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids, e.g., proline, pyrrolidone carboxylic acid, its derivatives and salts, sucrose ester isomers, panthenol, and buffers used in conjunction with bases such as triethanolamine or sodium hydroxide; waxes such as beeswax, ozokerite wax, paraffin wax; extracts of aloe vera, cornflower, witch hazel, elderflower, or cucumber, and combinations thereof. Other suitable additives and / or adjuncts are described in U.S. Pat. No. 6,184,247, the entire disclosure of which is incorporated herein by reference.

[0130] The formulation may contain additional inert additives, including, but not limited to, surfactants, cosolvents, and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, may be included in the formulation. The specific surfactants used depend on the overall composition of the formulation and the intended use of the formulation. Useful surfactants include polyethoxylated (PEG) fatty acids, PEG fatty acid diesters, PEG fatty acid monoester and diester mixtures, polyethylene glycol glycerin fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, propylene glycol ester-glycerol ester mixtures, mono- and diglycerides, 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.

[0131] The formulations may include cosolvents such as alcohols and polyhydric alcohols, polyethylene glycol ethers, amides, esters, other suitable cosolvents, and mixtures thereof. The formulations may further include excipients or additives such as sweeteners, flavoring agents, coloring agents, antioxidants, preservatives, chelating agents, viscosity modifiers, isotonicity agents, flavoring agents, opacifiers, suspending agents, binders, and mixtures thereof.

[0132] Generally, the formulations of the present invention are administered topically or orally at least daily for a period sufficient to achieve the desired level of improvement in skin appearance. Topical or oral administration of the formulations of the present invention can be continued for any suitable period. More specifically, the user can notice an improvement in skin appearance within a few hours to a few days after the initial administration or ingestion. It should be recognized that the frequency with which the formulations of the present invention are administered or ingested will vary depending on the desired level of improved appearance. In particular, the degree of cosmetic improvement is directly proportional to the total amount of composition used.

[0133] 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 to produce tablet, capsule or liquid dosage forms. Industrial Applicability

[0134] The present disclosure provides new and useful elastase inhibitors, including the botanical extracts described herein. Such elastase inhibitors may offer potential preventative and therapeutic approaches for reducing the risk of skin aging, such as wrinkle formation, caused by elastase activity. Therefore, the compositions and methods described herein are useful for inhibiting elastase.

[0135] The overall lineup of compositions and products provided by the present disclosure relates to skin care and nutraceutical products utilizing such elastase inhibitors, and specific examples include eye creams, face creams, and masks utilizing such elastase inhibitors.

[0136] Left unchecked, elastase undesirably degrades elastic fibers such as elastin, resulting in reduced skin elasticity, increased wrinkles, and poor healing. Thus, the compositions and methods herein are useful for inhibiting elastase or preventing skin aging, thereby increasing skin elasticity, reducing wrinkles, and otherwise promoting skin healing. The compositions and methods disclosed herein also provide potential preventative and therapeutic approaches for reducing the risk of skin aging caused by elastase activity.

[0137] The following examples illustrating the compositions and methods of the present disclosure are intended to illustrate, but not to limit, the disclosure. [Example]

[0138] The inhibitory effects of six plant ethanol and / or aqueous extracts on elastase activity were evaluated. Specifically, three Potentilla gracilis leaf extracts, three Panya japonica flower extracts, three Amomum villosum seed extracts, three Amomum clavan fruit extracts, and six Cornus officinalis fruit extracts were evaluated for their potential to inhibit elastase activity. As illustrated in the table and figures below, 18 extracts showed inhibition. The extracts were prepared in the laboratory, but some are commercially available. Elastase inhibition

[0139] The elastase inhibitory activity of selected plant extracts was evaluated using an in vitro porcine pancreatic elastase (PPE) enzyme inhibition assay described by Cannel et al. (1988) with some modifications. The assay was performed in 0.2 M Tris-HCl buffer (pH 8.0). Porcine pancreatic elastase was dissolved in sterile water to prepare a 100-unit stock solution. The substrate, N-succinyl-Ala-Ala-Ala-p-nitroanilide (AAAPVN), was dissolved in buffer. The plant extract was incubated with the enzyme for 25 minutes, after which the substrate was added to initiate the reaction. The final reaction mixture (250 μL) contained buffer, 10 μg / mL AAAPVN, 0.001 units PPE, and 500 μg / mL plant extract. EGCG was used as a positive control, and tris-HCl was used as a blank. Measurement of inhibition rate

[0140] Maximum velocity (Vmax) was obtained at 30 second intervals over 25 minutes at a wavelength of 410 nm. Percentage inhibition was calculated by the following equation:

number

[0141] The results are illustrated in the table below. The mean percent inhibition can also be seen with reference to the figure. Table 1: [Table 1] Table 2: [Table 2] Table 3: [Table 3] Table 4: [Table 4] Table 5: [Table 5] Table 6: [Table 6] Table 7: [Table 7] Additional Embodiments

[0142] The following additional embodiments are provided, the numbering of which should not be construed as indicating any level of importance.

[0143] Embodiment 1 relates to a composition for administration to a subject, comprising at least one botanical active ingredient, wherein the botanical active ingredient comprises at least one extract selected from the group consisting of: i) Potentilla gracilis leaf extract; ii) Panax ginseng flower extract; iii) Amomum virosum seed extract; iv) Amomum clavan fruit extract; v) Cornus officinalis fruit extract; and vi) a combination of i)-v); wherein the botanical active ingredient is present in the composition in an amount effective to inhibit elastase activity in the skin of a subject.

[0144] Embodiment 2 relates to the composition of embodiment 1, wherein the botanical active ingredient comprises, or optionally consists of, an extract of Potentilla gracilis leaf.

[0145] Embodiment 3 relates to a composition according to embodiment 1 or 2, wherein the extract of Potentilla gracilis leaves is obtained by alcoholic extraction, optionally ethanolic extraction, of Potentilla gracilis leaves or leaf-based plant material.

[0146] Embodiment 4 relates to the composition of any one of embodiments 1 to 3, wherein the composition is substantially to completely free of components derived from plant material other than Potentilla gracilis leaves.

[0147] Embodiment 5 relates to a composition of any one of embodiments 1 to 4, wherein the botanical active ingredient comprises, or optionally consists of, an extract of pangolina flower.

[0148] Embodiment 6 relates to a composition according to any one of embodiments 1 to 5, wherein the extract of panax ginseng flowers is obtained by alcoholic extraction, optionally ethanolic extraction, of panax ginseng flowers or flower-based plant material.

[0149] Embodiment 7 relates to a composition according to any one of embodiments 1 to 6, wherein the composition is substantially to completely free of components derived from plant material other than the bean-jam flower-based plant material.

[0150] Embodiment 8 relates to the composition of any one of embodiments 1 to 7, wherein the botanical active ingredient comprises, or optionally consists of, an extract of Amomum virosum seeds.

[0151] Embodiment 9 relates to a composition according to any one of embodiments 1 to 8, wherein the extract of Amomum virosum seeds is obtained by alcoholic extraction, optionally ethanolic extraction, of Amomum virosum seeds or seed-based plant material.

[0152] Embodiment 10 relates to a composition according to any one of embodiments 1 to 9, wherein the composition is substantially to completely free of components derived from plant material based other than Amomum virosum seeds.

[0153] Embodiment 11 relates to a composition according to any one of embodiments 1 to 10, wherein the botanical active ingredient comprises an extract of the fruit of Amomum clavan, and optionally, the botanical active ingredient consists of an extract of the fruit of Amomum clavan.

[0154] Embodiment 12 relates to a composition according to any one of embodiments 1 to 11, wherein the extract of Amomum clavan fruit is obtained by alcoholic extraction, optionally ethanolic extraction, of Amomum clavan fruit or fruit-based plant material.

[0155] Embodiment 13 relates to a composition according to any one of embodiments 1 to 12, wherein the composition is substantially to completely free of components derived from plant material based other than the fruit of Amomum clavan. Embodiments 13 relate to the composition of any one of claims 1 to 12; wherein the composition is substantially completely free of components obtained from non-fruit-based plant material of Amomum clavan.

[0156] Embodiment 14 relates to the composition of any one of embodiments 1 to 13, wherein the botanical active ingredient comprises an extract of the fruit of Cornus officinalis, optionally further defined as an extract of the fruit of Cornus officinalis.

[0157] Embodiment 15 relates to a composition according to any one of embodiments 1 to 14, wherein the extract of Cornus officinalis fruit is obtained by water extraction (or aqueous extraction) of Cornus officinalis fruit or fruit-based plant material.

[0158] Embodiment 16 relates to a composition according to any one of embodiments 1 to 14, wherein the extract of Cornus officinalis fruit is obtained by alcoholic extraction, optionally ethanolic extraction, of Cornus officinalis fruit or fruit-based plant material.

[0159] Embodiment 17 relates to a composition according to any one of embodiments 1 to 16, wherein the composition is substantially to completely free of components derived from plant material based other than the fruit of Cornus officinalis.

[0160] Embodiment 18 relates to the composition of any one of embodiments 1 to 17, wherein the composition is further defined as a topical composition formulated for topical administration to a subject.

[0161] Embodiment 19 relates to the composition of embodiment 18, further comprising a cosmetically acceptable carrier, optionally wherein the cosmetically acceptable carrier is not naturally occurring.

[0162] Embodiment 20 relates to the use of a composition according to any one of embodiments 1 to 19 for inhibiting elastase activity in the skin of a subject. Embodiment 20a relates to the use of a composition according to any one of embodiments 1 to 19 for the manufacture of a medicament for treating skin, optionally for treating elastase activity in the skin of a subject. Embodiment 20b relates to a medicament for treating skin, optionally for treating elastase activity in the skin of a subject, comprising a composition according to any one of embodiments 1 to 19.

[0163] Embodiment 21 relates to a method of inhibiting elastase activity in the skin of a subject, comprising administering to the subject an effective amount of a composition, wherein the composition is the composition of any one of embodiments 1 to 19.

[0164] Embodiment 22 relates to the method of embodiment 21, wherein the composition is administered topically to the subject.

[0165] The terms "comprise" and "consist" are used herein in the broadest sense to mean and encompass the concepts of "comprise," "consist essentially of," and "consist." The use of "for example," "example," "such as," and "including" to list examples is not intended to limit the scope to the listed examples. Thus, "for example" or "such as" means "for example, but not limited to" or "including, but not limited to," and encompasses other similar or equivalent examples. The term "about" as used herein serves to reasonably encompass or describe slight variations in a numerical value measured by instrumental analysis or as a result of sample handling. Such slight variations may be on the order of ±0 to ±10%, ±0 to ±5, or ±0 to ±2.5% of the numerical value. Furthermore, when the term "about" is used in relation to a range of numerical values, it applies to both numerical values. Furthermore, the term "about" may be applied to and apply to a numerical value even when not explicitly stated.

[0166] Generally, as used herein, a hyphen "-" or dash "-" within a range of values ​​means "~" or "from," ">" means "greater than" or "greater than," ≥" means "at least" or "greater than or equal to," <" means "less than" or "under," 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 publications is expressly incorporated herein by reference in its entirety in one or more non-limiting embodiments.

[0167] It is understood that the appended claims are not limited to the explicit and particular compounds, compositions, or methods described in the detailed description, which may vary among specific embodiments falling within the scope of the appended claims. Furthermore, with respect to any Markush group relied upon herein to describe particular features or aspects of various embodiments, different, particular, and / or unexpected results may be obtained with each member of the respective Markush group, independent of all other Markush members. Each member of a Markush group may be relied upon individually or in combination to provide sufficient support for specific embodiments within the scope of the appended claims.

[0168] Furthermore, all ranges and subranges relied upon in describing various embodiments of the present invention are, independently and collectively, within the scope of the appended claims, and all ranges, including whole and / or fractional values, are intended to be described and contemplated therein, even if such values ​​are not expressly recited herein. Those skilled in the art will readily recognize that the recited ranges and subranges fully describe and enable various embodiments of the present invention, and that such ranges and subranges may be further subdivided into related halves, thirds, quarters, fifths, etc. By way of example only, the range "from 0.1 to 0.9" may be further subdivided into a lower third, i.e., 0.1 to 0.3, a middle third, i.e., 0.4 to 0.6, and an upper third, i.e., 0.7 to 0.9, which are individually and collectively within the scope of the appended claims and may be relied upon individually and / or collectively to provide sufficient support for particular embodiments within the scope of the appended claims. Furthermore, with respect to language defining or modifying a range, such as "at least," "greater than," "less than," "no more than," etc., it is clear that such language includes subranges and / or upper or lower limits. As another example, the range "at least 10" inherently includes subranges of at least 10 to 35, at least 10 to 25, 25 to 35, etc., each of which may be relied upon individually and / or collectively to provide sufficient support for particular embodiments within the scope of the appended claims. Finally, individual numerical values ​​within the disclosed ranges may be relied upon and provide sufficient support for particular embodiments within the scope of the appended claims. For example, the range "from 1 to 9" includes various individual integers, such as 3, as well as individual numbers containing decimal points (or fractions), such as 4.1, which may be relied upon and provide sufficient support for particular embodiments within the scope of the appended claims.

[0169] The present invention has been described herein in an illustrative manner, and it is to be understood that the terminology which has been used is intended to be in the nature of words of description rather than of limitation. Many modifications and variations of the present invention are possible in light of the above teachings. The invention may be practiced otherwise than as specifically described within the scope of the appended claims. The subject matter of all combinations of independent and dependent claims, both singular and multiple dependent claims, is expressly contemplated herein.

Claims

1. 1. A composition for administration to a subject, comprising at least one botanical active ingredient, wherein the botanical active ingredient is one of the following: i) Potentilla globulus leaf extract; ii) Panya flower extract; iii) Amomum villosum seed extract; iv) extract of the fruits of Amomum clavan; v) extract of the fruit of Cornus officinalis; and vi) a combination of i) to v); at least one extract selected from the group consisting of: wherein the botanical active ingredient is present in the composition in an amount effective to inhibit elastase activity in the skin of a subject.

2. 10. The composition of claim 1, wherein the botanical active ingredient comprises, and optionally wherein the botanical active ingredient consists of, an extract of Portulaca oleracea leaf.

3. 2. The composition of claim 1, wherein the extract of Potentilla gracilis leaves is obtained by alcoholic extraction, optionally ethanolic extraction, of Potentilla gracilis leaves or leaf-based plant material.

4. 10. The composition of claim 1, wherein the composition is substantially to completely free of components derived from plant material other than Potentilla gracilis leaves.

5. 10. The composition of claim 1, wherein the botanical active ingredient comprises an extract of panjab flower, and optionally, the botanical active ingredient consists of an extract of panjab flower.

6. 2. The composition of claim 1, wherein the pangyka flower extract is obtained by alcoholic extraction, optionally ethanolic extraction, of pangyka flowers or flower-based plant material.

7. 10. The composition of claim 1, wherein the composition is substantially to completely free of ingredients derived from plant materials other than panax ginseng flowers.

8. 10. The composition of claim 1, wherein the botanical active ingredient comprises, or optionally consists of, an extract of seeds of Amomum villosum.

9. 2. The composition of claim 1, wherein the extract of Amomum villosum seeds is obtained by alcoholic extraction, optionally ethanolic extraction, of Amomum villosum seeds or seed-based plant material.

10. 10. The composition of claim 1, wherein the composition is substantially to completely free of components obtained from plant material based other than Amomum virosum seeds.

11. 10. The composition of claim 1, wherein the botanical active ingredient comprises an extract of the fruit of Amomum clavan, optionally wherein the botanical active ingredient consists of an extract of the fruit of Amomum clavan.

12. 2. The composition of claim 1, wherein the extract of Amomum clavan fruit is obtained by alcoholic extraction, optionally ethanolic extraction, of Amomum clavan fruit or fruit-based plant material.

13. 10. The composition of claim 1, wherein the composition is substantially to completely free of ingredients derived from plant material based other than the fruit of Amomum clavan.

14. 10. The composition of claim 1, wherein the botanical active ingredient comprises an extract of the fruit of Cornus officinalis, optionally further defined as an extract of the fruit of Cornus officinalis.

15. 2. The composition of claim 1, wherein the extract of Cornus officinalis fruit is obtained by water extraction (or aqueous extraction) of Cornus officinalis fruit or fruit-based plant material.

16. 2. The composition of claim 1, wherein the extract of Cornus officinalis fruit is obtained by alcoholic extraction, optionally ethanolic extraction, of Cornus officinalis fruit or fruit-based plant material.

17. 10. The composition of claim 1, wherein the composition is substantially to completely free of ingredients derived from plant material other than the fruit of Cornus officinalis.

18. 10. The composition of claim 1, wherein the composition is further defined as a topical composition formulated for topical administration to a subject.

19. 20. The composition of claim 18, further comprising a cosmetically acceptable carrier, optionally wherein the cosmetically acceptable carrier is not naturally occurring.

20. 20. Use of a composition according to claim 1 or any one of claims 2 to 19 to inhibit elastase activity in the skin of a subject.

21. 20. A method for inhibiting elastase activity in the skin of a subject, comprising administering to the subject an effective amount of a composition, wherein the composition is a composition according to claim 1, or any one of claims 2 to 19.

22. 22. The method of claim 21, wherein the composition is administered topically to the subject.

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