Composition and method for inhibiting 5α-reductase

Abstract

A composition for administration to a subject is disclosed. The composition comprises at least one botanical active component. The botanical active component is present in the composition in an amount effective to inhibit 5α-reductase in the subject. The botanical active component comprises at least one selected from the group consisting of: i) an extract of Potentilla glabra; ii) thonningianin A; and iii) combinations of i) and ii). The composition may be in the form of an oral composition, e.g., for ingestion. The composition may also be in the form of a topical composition, e.g., for topical application. A method of inhibiting 5α-reductase in a subject is also provided. The method comprises administering an effective amount of the composition to the subject.

Description

COMPOSITION AND METHOD FOR INHIBITING 5a-REDUCTASECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of Chinese Application No. 202311552109.1, filed on 20 November 2023, the disclosure of which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION

[0002] The present invention relates generally to compositions and methods for inhibiting 5 a- reductase and, more specifically, to a botanical extract-containing composition for inhibit 5 a- reductase in a subject. Related methods are also provided.BACKGROUND OF THE INVENTION

[0003] 5a-reductase, also known as 3-oxo-5a-steroid 4-dehydrogenase, is an enzyme present in human skin and prostate tissue. The main fimction of 5a-reductase is to catalyze the reduction of testosterone to dihydrotestosterone (DHT). However, elevated levels of DHT in the human prostate can cause prostate hyperplasia, and elevated levels of DHT in human skin can cause hair loss and may also cause facial acne.

[0004] In view of the foregoing, there remains an opportunity to provide new and usefiil 5 a- reductase inhibitors. Such 5a-reductase inhibitors can offer potential preventive and therapeutic approaches for lowering the effects and risks of 5a-reductase activity and resultant DHT formation. As such, there also remains an opportunity to provide new and useful compositions and methods for inhibiting 5a-reductase activity.BRIEF SUMMARY OF THE INVENTION

[0005] A composition for administration to a subject is provided. The composition comprises at least one botanical active component. The botanical active component is generally present in the composition in an amount effective to inhibit 5a-reductase in the subject. The botanical active component comprises at least one selected from the group consisting of: i) an extract of Potentilla glabra,' ii) thonningianin A; and iii) combinations of i) and ii).

[0006] In various embodiments, the composition is a topical composition that is formulated for topical administration to the subject. In other embodiments, the composition is an oral composition that is formulated for oral administration to the subject.

[0007] The composition can be used for inhibiting 5a-reductase in a subject. A method of inhibiting 5a-reductase in a subject comprises administering an effective amount of the composition to the subject.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is a bar graph showing the inhibition rate of 5a-reductase using aqueous and ethanol extracts of Potentilla glabra in comparison to using Finasteride as a control;

[0009] Figure 2 is a plot showing the inhibition rate of 5a-reductase using Finasteride as a control; and

[0010] Figure 3 is a plot showing the inhibition rate of 5a-reductase using thonningianin A.DETAILED DESCRIPTION OF THE CURRENT EMBODIMENTS

[0011] A composition for administration to a subject is disclosed. The composition comprises at least one botanical active component. The composition is described below, followed by description of associated uses and methods.

[0012] As will be understood in view of this disclosure, the composition is not particularly limited aside from the botanical active component, including the extract(s) thereof, as well as the related components and methods. As such, the composition 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 as a unique and stand-alone therapeutic or in combination with other therapeutics compatible therewith.

[0013] The composition is usefiil for treating, preventing, and / or ameliorating various conditions, such as those associated with 5a-reductase activity. Specifically, as will be appreciated in view of the description and examples below, the composition of the present embodiments is believed to be capable of inhibiting 5a-reductase and, more specifically, inhibiting 5a-reductase in a subject.

[0014] As such, the composition may be utilized to treat (i.e., slow, prevent, reverse, etc.) conditions generally associated with 5a-reductase activity and associated DHT production, such as hair loss, facial acne, and prostate hyperplasia.

[0015] As introduced above, the composition comprises a botanical active component. More specifically, the botanical active component comprises, optionally consists essentially of, or optionally consists of at least one selected from the group consisting of: i) an extract of Potentilla glabra,' ii) thonningianin A; and iii) combinations of i) and ii).

[0016] In certain embodiments, only one of the two components i) and ii) is present in the composition. In other embodiments, both of the components i) and ii) are present in the composition. Each of the individual components i) and ii) may be referred to simply as the “botanical extract” or the “botanical active component,” or collectively as the “botanical extracts” or “botanical active components” and are described in turn below.

[0017] The term “extract” is used herein in the conventional sense to refer to a composition that has been obtained via fluid extraction from a source material. As such, the term “botanical extract” is to be understood as a composition obtained via fluid extraction (e.g., solvent extraction, gas extraction, CO2 extraction, etc.) from a botanical source (i.e., a plant material). Botanical extracts suitable for use in the composition can be obtained via any extraction method, or combination of such methods, known in the art, including water extractions, steam extractions, solvent extractions, etc. Exemplary extraction techniques are described below. However, the botanical extracts are generally not limited to a particular extraction method, or additional / adjuvant techniques used to obtain the botanical extracts, but rather may vary according to the parameters described herein. Additionally, an extraction step is not required to prepare the botanical active component and / or the composition, as suitable extracts (e.g., standardized extracts) and / or botanical active components are readily available from a number of commercial suppliers.

[0018] Botanical extracts suitable for use in, or as, the botanical active component include those obtained via solvent extraction, e.g., via use of a polar solvent such as an alcohol (e.g., methanol, ethanol, butylene glycol, etc.), ether (e.g., diethyl ether, methyl tert butyl ether, etc.), ketone (e.g., acetone), ester (e.g., ethyl acetate), phenol, water, and the like, a nonpolar solvent such as benzene, xylenes, toluene, etc., as well as derivatives, modifications, and combinations thereof (e.g., solvent- water blends, including alcohol-water, acetone-water, etc.). Additional and alternative extraction techniques include sequential fractionations, total hydro-ethanolic extractions, lump-sum extractions, supercritical fluid extractions (e.g., with CO2), and the like, as well as those utilizing sequential or secondary extractions from a first extract (e.g., a nonpolar solvent extract of a botanical extract obtained from a polar solvent extraction) or other processing techniques such as filtration, purification, distillation, dehydration, evaporation, concentration, drying, etc. Specific examples of suitable extraction methods are described in U.S. Patent No. 7,897,184, which is incorporated by reference herein.

[0019] As understood in the art, various sections or parts of plants can be used to obtain the essential oils and extracts, such as bark, berries, flowers, fruits, leaves, peels, resins, rhizomes, roots, seeds, and / or woods. Essential oils can be obtained by a number of processes, such as by distillation (e.g., using steam), expression, solvent extraction, absolute oil extraction, resin tapping, and / or cold pressing.

[0020] In various embodiments, the solvent used to obtain suitable botanical extracts for this disclosure is one in which the resulting botanical extract and / or a subsequent form thereof (e.g., botanical extract powder) is suitable for ingestion. For example, the solvent is water or ethanol.

[0021] In one example, the botanical extracts can be obtained using an organic solvent extraction technique. In another example, solvent sequential fractionation can be used to obtain the botanical extracts. Total hydro-ethanolic extraction techniques can also be used to obtain the botanical extracts. Generally, this is referred to as a lump-sum extraction. The botanical extract generated in the process will contain a broad variety of phytochemicals present in the extracted material including fat and water-soluble phytochemicals. Following collection of the botanical extract solution, the solvent will be evaporated, resulting in the botanical extract.

[0022] Total ethanol extraction may also be used. This technique uses ethanol as the solvent. This extraction technique generates a botanical extract that may include fat soluble and / or lipophilic compounds in addition to water-soluble compounds. Total methanol extraction may also be used in a similar manner with similar results.

[0023] Another example of an extraction technique that can be used to obtain the botanical extracts is supercritical fluid carbon dioxide extraction (SFE). In this extraction procedure, the material to be extracted is not exposed to any organic solvents. Rather, the extraction solvent is carbon dioxide (CO2), with or without a modifier, in super-critical conditions (e.g., >31.3°C and >73.8 bar). Those of skill in the art will appreciate that temperature and pressure conditions can be varied to obtain the best yield of botanical extract. This technique generates a botanical extract of fat soluble and / or lipophilic compounds, similar to total hexane and ethyl acetate extraction techniques, which may also be used.

[0024] Each of the extraction methods above also may include and / or be utilized in combination with one or more additional processing steps understood in the art. For example, plant material may be comminuted, smashed, ground, etc. There also may be one or more filtration steps to remove, for example, cellulosic / fibrous or other solid materials. There also may be one or more purification steps to remove, for example, certain constituents and / or contaminants. Such purification may be accomplished, for example, by distillation, evaporation, centrifugation, etc. There also may be one or more concentration and / or drying steps to remove water and / or other volatiles, e.g., alcohol, lighter compounds, VOCs, etc. Moreover, acids and / or bases may be added to adjust pH or neutralize. Depending on the desired form of the final / end botanical extract, one can also utilize various additional steps understood in the art, such as screening, pressing, milling, grinding, mixing, dispersing, etc. It is to be appreciated thatcombinations of these additional processing steps in duplicative and / or different orders is also contemplated.Potentilla glabra

[0025] In some embodiments, the botanical active component, and thus the composition, comprises the extract of Potentilla glabra, i.e., an extract comprising, optionally consisting essentially of material from the flowering plant species Potentilla glabra, such as the flower or leaf. The Potentilla glabra extract is not particularly limited, and may comprise or be any flower extract, leaf extract, or combination of flower and / or leaf extracts from a Potentilla glabra plant suitable for use in the embodiments herein. In certain embodiments, the Potentilla glabra extract comprises both flower and leaf extracts from a Potentilla glabra plant. More specifically, exemplary Potentilla glabra flower and / or leaf extracts include those capable of inhibiting 5 a- reductase or eliciting / exhibiting any other such activities described herein as part of the botanical active component.

[0026] 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 belongs to the genus Potentilla (family Rosaceae) and is mainly distributed in China, Mongolia, Soviet Union, and North Korea. Potentilla glabra may simply be referred to as P. glabra, or via various other names such as Potentilla glabra Lodd., Potentilla glabra G. Lodd., Dasiphora glabra (G. Lodd.) Sojak, Silver Dew Plum, Yinlumei,The leaves and flowers of Potentilla glabra Lodd. may be referred to as Yaowang teaor Guanyin teaIn various embodiments,Potentilla glabra may be of the variety Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand-Mazz, which may be referred to as Baimao Yinlumei,or B^^SflW(3£^). Other synonyms for Potentilla glabra include Dasiphora mandshurica (Maxim.) Juz., Potentilla davurica var. mandshurica (Maxim.) Th. Wolf, Potentilla fruticosa var. mandshurica Maxim., Potentilla fruticosa var. subalbicans Hand.-Mazz.

[0027] Specific examples of Potentilla glabra extracts are known in art. As such, the Potentilla glabra extract may be purchased or otherwise obtained commercially from various sources, 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 extract of Potentilla glabra is obtained by water extracting (or aqueous extracting) plant material of Potentilla glabra, including but not limited to the flower and / or leaf. In further or otherembodiments, the extract of Potentilla glabra is obtained by alcohol extracting (e.g., ethanol extracting), plant material of Potentilla glabra, including but not limited to the flower and / or leaf.

[0028] In certain embodiments, the extract of Potentilla glabra flower and / or leaf is obtained by water extracting (or aqueous extracting) flowers, flower-based plant material, leaves, or leafbased plant material of Potentilla glabra. In further or other embodiments, the extract of Potentilla glabra flower and / or leaf is obtained by alcohol extracting (e.g., ethanol extracting), flowers, flower-based plant material, leaves, or leaf-based plant material of Potentilla glabra. The flowers and / or leaves may be fresh or dried, typically dried to prevent decay. The dried flowers and / or leaves may then be formed into a powder, which can be used as the extract itself, or more typically, the powdered flower and / or leaf is further processed to form the extract as like described below.

[0029] As will be understood by those of skill in the art, Potentilla glabra is primarily cultivated for its flower and / or leaf. As such, in various embodiments, the extract of Potentilla glabra is an extract of Potentilla glabra flower and / or leaf. Suitable extractions include those noted above, e.g., water and ethanol extractions of flowers and / or leaves. The flowers and / or leaves can be from one or more plants, and can be fresh, dried, or otherwise aged.

[0030] By way of example, certain extracts can be obtained where Potentilla glabra (e.g., flower and / or leaf) is pulverized to a homogeneous size in a mill. Next, the resulting powder is extracted using a water or ethanol solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to yield a syrup. The syrup can then be freeze-dried to dryness to obtain extract.

[0031] In various embodiments, the botanical active component consists of the extract of Potentilla glabra flower and / or leaf. In further or other embodiments, the composition is substantially to completely free of components obtained from non-flower-based plant material and / or non-leaf-based plant material of Potentilla glabra. In these embodiments, the non-flower- based plant material and non-leaf-based plant material of Potentilla glabra can be, for example, the root, stem, bark, rhizome, or stem of a Potentilla glabra plant. Without being bound by any particular theory, it is believed that the flower and leaf of Potentilla glabra are most usefill for 5a-reductase inhibition effect; whereas other parts of Potentilla glabra are not (as illustrated in the Examples section below).

[0032] In other embodiments, the Potentilla glabra extract may comprise material from any part of the plant, or combinations of parts, and is not limited to flower and / or leaf extracts. For example, the Potentilla glabra extract may comprise material extracted from one or more parts of a Potentilla glabra plant, including the root, stem, bark, rhizome, leaf, bud, flower, seed, and / or fruit, thereof. Moreover, such extracts may be farther processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, mesh-sorted, extracted, distilled, concentrated, etc.) to obtain the Potentilla glabra extract. Likewise, the Potentilla glabra plant may be extracted in raw form, or processed prior to extraction of the Potentilla glabra extract (e.g., used in raw form, suspended form, dehydrated form, concentrated form, etc.). In certain embodiments, the botanical active component comprises a Potentilla glabra extract comprising material obtained (i.e., extracted) from flowers and / or leaves of Potentilla glabra.

[0033] The amount of the Potentilla glabra extract utilized in the botanical active component may vary, and will be selected based on the number and types of components being utilized in the botanical active component. In certain embodiments, the botanical active component comprises from 1 to 2000 mg of the Potentilla glabra extract, such as from 1 to 1000, optionally of from 2 to 800, optionally of from 20 to 750, or optionally of from 50 to 500, mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active component includes the Potentilla glabra extract in an amount of at least 1, optionally of at least about 20, optionally of at least about 50, optionally of at least 100, optionally of at least 250, optionally of at least 500, optionally of at least 1000, or optionally of at least 1500, mg. In these or other embodiments, an upper boundary may be selected such that the botanical active component comprises the Potentilla glabra extract in an amount of <100, <250, <500, <750, <1000, <2000, <5000 mg. In various embodiments, the botanical active component can include an amount of Potentilla glabra extract optionally in an amount of greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95, wt.%, based on the total weight of the botanical active component. In such embodiments, an upper boundary may be selected to be generally <10, <20, <30, <40, <50, <60, <70, <80, <90, and <99 wt.%, respectively, based on the total weight of the botanical active component.

[0034] In certain embodiments, the botanical active component comprises more than one Potentilla glabra extract, such as 2, 3, 4, or more Potentilla glabra extracts. In such embodiments, each Potentilla glabra extract is independently selected, may be the same as ordifferent from any other Potentilla glabra extract, and each utilized in an amount as described above.

[0035] The Potentilla glabra extract may be utilized in any form, such as neat (i.e., absent solvents, carrier vehicles, diluents, etc.), or disposed 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, fluid, or oil, or the like, or combinations thereof. When utilized, the carrier vehicle will be selected based on the particular components of the botanical active component and / or the composition, such as the particular Potentilla glabra extract(s) utilized. It will be appreciated that the Potentilla glabra extract may be combined with the carrier vehicle, if utilized, prior to, during, or after being combined with any other components of the botanical active component and / or composition.Thonningianin A

[0036] In some embodiments, the botanical active component, and thus the composition, comprises thonningianin A (Th A). Thonningianin A is an ellagitannin and is assigned the CAS registry number of 271579-11-4. Thonningianin A may also be known as pinocembrin dihydrochalcone or 7-O-[3"-O-galloyl-4",6"-hexahydroxydiphenoyl]-beta-D-glucoside. Thonningianin A has the chemical formula C42H34O21, a molecular weight of approximately 874.70, and the following chemical structure:

[0037] Thonningianin A may be obtained, for example, from an extract comprising, optionally consisting essentially of material from the plant species Thonningia sanguinea. Thonningia sanguinea is a dioecious herb native to Africa and may simply be referred to as T. sanguinea, or via various other names such as Thonningia sanguinea Vahl, Thonningia coccinea, Thonningia dubia, Thonningia elegans, ground pineapple, pineapple of the bush, duiker’s kolanut, and crown of the ground.

[0038] Specific examples of Thonningia sanguinea extracts are known in art. As such, thonningianin A may be purchased or otherwise obtained commercially from various sources, 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 extract of Thonningia sanguinea is obtained by water extracting (or aqueous extracting) plant material of Thonningia sanguinea. In further or other embodiments, the extract of Thonningia sanguinea is obtained by alcohol extracting (e.g., methanol or ethanol extracting), plant material of Thonningia sanguinea.

[0039] The Thonningia sanguinea extract may comprise material from any part of the plant, or combinations of parts, of the whole plant. For example, the Thonningia sanguinea extract may comprise material extracted from one or more parts of a Thonningia sanguinea plant, including the root, stem, bark, tuber, rhizome, leaf, bud, flower, seed, and / or fruit, thereof. Moreover, such extracts may be further processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, mesh-sorted, extracted, distilled, concentrated, etc.) to obtain the Thonningia sanguinea extract. Likewise, the Thonningia sanguinea plant may be extracted in raw form, or processed prior to extraction of the Thonningia sanguinea extract (e.g., used in raw form, suspended form, dehydrated form, concentrated form, etc.).

[0040] Thonningianin A may instead or in addition be obtained, for example, from an extract comprising, optionally consisting essentially of material from the plant species Penthorum Chinese Pursh. Penthorum Chinese Pursh is a plant species native to East Asia and may simply be referred to as P. Chinese, or via other names such as Penthorum Chinese L., Penthorum sedoides var. Chinese (Pursh) Maximowicz, Penthorum sedoides subsp. Chinese (Pursh) S. Y. Li & K. T. Adair, Penthorum humile Regel & Maack, Penthorum intermedium Turczaninow, Oriental penthorum, “Gan Huang Cao,” or

[0041] Specific examples of Penthorum Chinese Pursh extracts are known in art. As such, thonningianin A may be purchased or otherwise obtained commercially from various sources, 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 extract of Penthorum Chinese Pursh is obtained by water extracting (or aqueous extracting) plant material of Penthorum Chinese Pursh. In fiirther or other embodiments, the extract of Penthorum Chinese Pursh is obtained by alcohol extracting (e.g., methanol or ethanol extracting), plant material of Penthorum Chinese Pursh.

[0042] As will be understood by those of skill in the art, Penthorum Chinese Pursh is primarily cultivated for its flowers. As such, in various embodiments, the extract of Penthorum Chinese Pursh is an extract of Penthorum Chinese Pursh flower. Suitable extractions include those noted above, e.g., water and alcohol extractions of flowers. The flowers can be from one or more plants, and can be fresh, dried, or otherwise aged.

[0043] By way of example, certain extracts can be obtained where Penthorum Chinese Pursh (e.g., flower) is pulverized to a homogeneous size in a mill. Next, the resulting powder is extracted using a water or alcohol solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to yield a syrup. The syrup can then be freeze-dried to dryness to obtain extract.

[0044] The Penthorum Chinese Pursh extract may comprise material from any part of the plant, or combinations of parts, and is not limited to flower extracts. For example, the Penthorum Chinese Pursh extract may comprise material extracted from one or more parts of a Penthorum Chinese Pursh plant, including the root, stem, bark, rhizome, leaf, bud, flower, seed, and / or fruit, thereof. Moreover, such extracts may be further processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, mesh-sorted, extracted, distilled, concentrated, etc.) to obtain the Penthorum Chinese Pursh extract. Likewise, the Penthorum Chinese Pursh plant may be extracted in raw form, or processed prior to extraction of the Penthorum Chinese Pursh extract (e.g., used in raw form, suspended form, dehydrated form, concentrated form, etc.).

[0045] The amount of the thonningianin A utilized in the botanical active component may vary, and will be selected based on the number and types of components being utilized in the botanical active component. In certain embodiments, the botanical active component comprises from 1 to 2000 mg of thonningianin A, such as from 1 to 1000, optionally of from 2 to 800, optionally of from 20 to 750, or optionally of from 50 to 500, mg. However, amounts outside these ranges may also be utilized. For example, in certain embodiments, the botanical active component includes thonningianin A in an amount of at least 1 , optionally of at least about 20, optionally of at least about 50, optionally of at least 100, optionally of at least 250, optionally of at least 500, optionally of at least 1000, or optionally of at least 1500, mg. In these or other embodiments, an upper boundary may be selected such that the botanical active component comprises thonningianin A in an amount of <100, <250, <500, <750, <1000, <2000, <5000 mg. In various embodiments, the botanical active component can include an amount of thonningianin A optionally in an amount of greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionallygreater than 80, or optionally greater than 95, wt.%, based on the total weight of the botanical active component. In such embodiments, an upper boundary may be selected to be generally <10, <20, <30, <40, <50, <60, <70, <80, <90, and <99 wt.%, respectively, based on the total weight of the botanical active component.

[0046] Thonningianin A may be utilized in any form, such as neat (i.e., absent solvents, carrier vehicles, diluents, etc.), or disposed 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, fluid, or oil, or the like, or combinations thereof. When utilized, the carrier vehicle will be selected based on the particular components of the botanical active component and / or the composition, such as the particular thonningianin A utilized. It will be appreciated that thonningianin A may be combined with the carrier vehicle, if utilized, prior to, during, or after being combined with any other components of the botanical active component and / or composition.Definitions

[0047] In order to provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0048] “Improving at least one sign of hair loss,” “improving a sign of hair loss,” and “protecting hair” are used interchangeably herein to designate preventing, arresting, reversing, ameliorating, diminishing, and / or reducing hair loss. Representative signs of hair loss include, but are not limited to, thinning hair, loosening of hair, bald spots, patchy bald spots, male-pattern baldness, female-pattern baldness, patchy bald spots, traction alopecia, frontal fibrosing alopecia, fullbody hair loss, or combinations thereof.

[0049] “Improving the appearance of skin” and “improving the aesthetic appearance of skin” are used interchangeably herein to designate an aesthetic improvement in the appearance of skin. Representative improvements may include, but are not limited to, favorable characteristics and / or properties related skin thickness, elasticity, resiliency, moisturization, smoothness, tone, texture, radiance, luster, brightness, clarity, contour, firmness, tautness, suppleness, softness, sensitivity, pore size, or combinations thereof. These terms may also be used to designate an improvement in an adverse skin condition. Representative adverse conditions affecting by, resulting in or resulting from such an adverse skin condition include, but are not limited to, psoriasis, eczema, seborrhea, dermatitis, sunburn, estrogen imbalance, hyperpigmentation, hypopigmentation, discoloration, yellowing, freckles, skin atrophy, skin breakout, skin fragility, dryness, tactile roughness, chapping, sagginess, thinning, hyperplasia, fibrosis, enlarged pores,cellulite formation, bruising, acne formation, apoptosis, cellular differentiation, cellular dedifferentiation, prevention of tumor induction or tumor progression, viral infections, fungal infections, bacterial infections, spider veins (telangectasia), hirsutism, rosacea, pruritis, calluses, warts, coms, or combinations thereof.

[0050] The terms “composition” or “formulation” refer to a product that treats, improves, promotes, increases, manages, controls, maintains, optimizes, modifies, reduces, inhibits, or prevents a particular condition associated with a natural state, biological process or disease or disorder. For example, a composition or a formulation improves at least one sign of hair loss in a subject and / or minimizes or inhibits hair loss. 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 that include an effective amount of an extract, at least one component thereof, or a mixture thereof. Exemplary compositions and / or formulations include cream, cosmetic lotion, pack or powder, or as an emulsion, lotion, liniment foam, tablets, plasters, granules, or ointment. Preferred compositions are formulated for topical application / administration and for oral administration / ingestion.

[0051] As used herein, the term “effective amount” or “therapeutically effective amount” of a pure compound, composition, extract, extract mixture, component of the extract, and / or active agent or ingredient, or a combination thereof refers to an amount effective at dosages and for periods of time sufficient to achieve a desired result. For example, the “effective amount” or “therapeutically effective amount” refers to that amount of a pure compound, composition, extract, botanical extract, extract mixture, botanical extract mixture, component of the extract, and / or active agent or ingredient, or a combination thereof of this invention which, when administered to a subject (e.g., mammal, such as a human), is sufficient to effect treatment, such as improving hair loss and / or minimizing or inhibiting hair loss. The amount of a composition, extract, botanical extract, extract mixture, botanical extract mixture, component of the extract, and / or active agent or ingredient of this disclosure that constitutes an “effective amount” or “therapeutically effective treatment” will vary depending on the active agent or the compound, the condition being treated and its severity, the manner of administration, the duration of treatment, or the age of the subject to be treated, but can be determined routinely by one of ordinary skill in the art having regard to his own knowledge and to this disclosure.

[0052] The term “pharmaceutically acceptable” means those drugs, medicaments, extracts or inert ingredients, which are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, and the like, commensurate with a reasonable benefit / risk ratio.

[0053] The terms “applying” and “administering” are defined as providing a composition to a subject via a 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, topical and / or oral routes of administering the described composition are suitable.

[0054] The terms “minimize,” “reduce,” “suppress,” “decrease” and / or “inhibit” refer to a decrease or reduction in 5a-reductase activity, and / or its downstream effect, in the presence of a botanical (or plant) ingredient or botanical extract as described herein, when compared to 5 a- reductase activity in the absence of a botanical ingredient or botanical extract as described herein, such as in a control sample. The degree of decrease or inhibition of 5a-reductase activity, and / or its downstream effect, will vary with the nature and quantity of a botanical ingredient or botanical extract present, but will be evident, e.g., as a detectable decrease in 5a-reductase; desirably a degree of decrease greater than about 5%, about 10%, about 15%, about 20%, about 25%, about 50%, about 75%, about 90%, about 95% or about 99% (or any degree of decrease in the range of from about 5% to about 99%) as compared to 5a-reductase activity in the absence of the botanical ingredient or botanical extract. For example, a composition comprising a plant ingredient or plant extract of Potentilla glabra and / or thonningianin A can minimize or reduce 5a-reductase activity, which in turn can minimize or reduce hair loss as well as treat prostatic hyperplasia.

[0055] As used herein, the term “subject” or “individual” includes mammals to which a composition may be administered. Non-limiting examples of mammals include humans, nonhuman primates, rodents (including transgenic and non-transgenic mice) or the like. In some embodiments, the subject is a mammal, and in some embodiments, the subject is human. Compositions (or Formulations)

[0056] The composition may include any amount of the botanical active component, which will be selected based on the number and types of components being utilized in the composition as a whole. In general, the botanical active component is present in the composition in an amount effective to inhibit 5a-reductase activity in a subject.

[0057] In certain embodiments, the composition comprises the botanical active component in an amount of from 1 to 5000, optionally of from 2 to 2000 mg, optionally of from 5 to 1750, optionally of from 10 to 1500, optionally of from 15 to 1250, optionally of from 20 to 1000, optionally of from 25 to 750, optionally of from 30 to 500, optionally of from 35 to 500, optionally of from 40 to 500, optionally of from 45 to 450, optionally of from 50 to 450, or optionally of from 50 to 400, mg. However, amounts outside and / or overlapping with these ranges may also be utilized. For example, it is to be appreciated that the ranges described above with respect to the amount of each botanical extract in the botanical active component may equally apply to the amount of each botanical extract in the composition as a whole, such as when the botanical active component consists of but one of the botanical extracts.

[0058] In some embodiments of the composition, the formulation for hair loss prevention / hair protection and / or prostate health comprises: Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz extract and / or thonningianin A. In certain embodiments, inclusion of thonningianin A is optional and may not be included in the formulation. In other embodiments, inclusion of Potentilla glabra extract is optional and may not be included in the formulation. In specific embodiments, the formulation comprises Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz (and thonningianin A.

[0059] In general, the composition is not limited in terms of formulation, peripheral ingredients, form, number of functions, etc., aside from comprising the botanical active component and / or the botanical extract(s) thereof. Rather, the composition may be varied, and may be formulated in any fashion consistent with this disclosure.

[0060] Typically, the composition is formulated or otherwise adapted for administration to a mammalian subject (e.g., a human). For example, in various embodiments, the composition is adapted to be topically administrated or consumed and / or orally administered to a human subject.

[0061] In certain embodiments, the composition is further defined as a topical composition that is formulated for topical administration to the subject. In such embodiments, the composition may also be referred to as a cosmetic composition, and typically comprises at least one cosmetically acceptable carrier in addition to the bioactive agent composition. In specific embodiments, the cosmetically acceptable carrier is not naturally occurring. In other words, the carrier is not a product of nature in these specific embodiments. In other embodiments, the carrier is selected from conventional carriers understood in the art, and can be used in conventional amounts.

[0062] In other certain embodiments, the composition is further defined as an oral composition that is formulated for oral administration to the subject. In such embodiments, the composition may also be referred to as an ingestible composition, and typically comprises at least one pharmaceutically acceptable additive in addition to the bioactive agent composition. In specific embodiments, the pharmaceutically acceptable additive is not naturally occurring. In other words, the pharmaceutically acceptable additive is not a product of nature in these specific embodiments. In other embodiments, the pharmaceutically acceptable additive is selected from conventional additives understood in the art, and can be used in conventional amounts.

[0063] As such, it should be appreciated 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 will be selected based on the particular components of the composition, a desired use of the composition, etc. As such, as will be understood in view of the description herein, 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 liquid solution or suspension, a coated capsule, a suppository, a lyophilized powder, a transdermal patch, a softgel, or other forms are known. Other examples of suitable forms include solids, gels, liquids, creams, lotions, pomades, mousses, powders, foams, sprays, ointments, or other such preparations where the botanical active component is disposed in an appropriate carrier vehicle, such as any of those described herein. In particular embodiments, the composition is formulated or otherwise provided as a skin or scalp treatment for topical application or a liquid or capsule for oral ingestion.

[0064] The composition can be prepared using various methods. For example, actives of the composition (such as the botanical extract(s)), and optionally one or more inactives (such as one or more conventional components, additives, excipients, etc.), can be mixed or blended and compressed or compounded utilizing various techniques understood in the art. The composition of this disclosure is not limited to a particular order of manufacturing steps or method of manufacture.

[0065] In various embodiments, the composition is administered topically by application to the subject’s skin. The subject is typically a human, and can include men and women of various ages. The method / composition of this disclosure is not limited to a particular subject.

[0066] 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 as a gel, cream, lotion, pomade, mousse, powder, or foam for application to the subject’s skin. In anotherexample, the composition can be formulated for spraying onto a subject’s skin. The composition can be formulated to be sprayed as either an aerosol spray or pump spray. In still another example, the composition can be formulated for application using a pre-moistened towelette. In another example, the composition can be formulated as a solid that is rubbed onto the subject’s skin. In another example, the composition is formulated for delivery through a patch that is adhered to the subject’s skin.

[0067] Other than the botanical active component (i.e., the “actives” or “active ingredients”), the composition can include pharmaceutically acceptable additives that are inactives (or “inactive ingredients”) including, but not limited to, excipients, such as diluents and binders; granulating agents; glidants (or flow aids); fillers; lubricants; preservatives; stabilizers; coatings; disintegrants; fragrances; and pigments. The active ingredients and the pharmaceutically acceptable additives can be combined or compounded as desired to form an individual dose that provides the desired amount of active ingredient to the human subject when topically applied.

[0068] Optionally, the composition may include one or more additional components such as additives. Suitable additives include those understood in the art, including but not limited to, moisturizers, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, antiseptics, drugs and drug substances, analgesic compounds, anti-neuralgic compound, antioxidants, blood circulation promoters, antidepressant compounds, anti-anxiety compounds, antistress compounds, sunscreens, insect repellants, preservatives, exfoliants, fragrances, colors, fillers, solvents, vehicles, carriers, other types of additives known to those of skill in the art, and combinations thereof. Such additives may be utilized alone or in combination. In general, the optional additives may be of any type used in personal care products and cosmetic products.

[0069] Excipients can be further classified as other components. Specifically, excipients used in oral solid dosage forms have been classified based on their fimctionality into groups such as diluents, disintegrants, binders, compression aids, granulating agents, glidants, lubricants, release-controlling polymers, stabilizers (such as antioxidants, chelators, and pH-modifiers), film-coating polymers, coating agents, vehicles, plasticizers, surfactants, colorants, sweeteners, and flavors.

[0070] In various embodiments, the composition comprises at least one component 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, hydroxypropyl methylcellulose, ethyl cellulose, cellulose acetate phthalate, acacia, gums, wax, glycerol monostearate, acrylic acid polymers and copolymers, methacrylicacid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, lactose, calcium sulfate, calcium phosphate dibasic, sugar, microcrystalline cellulose (MCC), starch, sodium starch glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. Combinations of such components can be utilized, and such components and other components used in conventional tablets are understood in the art.

[0071] As used herein, “diluents” may be inert substances added to increase the bulk of the composition to make a tablet a practical size for consumption. As such, they may also be referred to as bulking agents. Commonly used diluents include, but are not limited to, microcrystalline cellulose (MCC), wood cellulose, com starch, modified com starch, (tri)calcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch, (powdered) sugar, dextrose, mannitol, sorbitol, and the like. The diluent / bulking agent may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0072] As used herein, “flavoring agents” are compounds designed to give the composition a more palatable taste. Flavoring agents vary considerably in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex volatile oils. Synthetic flavors of almost any desired type are now available and are well known in the art. If hard taste, acid taste or bitter taste derived from starting materials may be suppressed by seasoning or flavoring, the acidulant (e.g., citric acid, tartaric acid, malic acid, ascorbic acid, etc.), the sweetener (e.g., sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin, etc.), or the perfume (e.g., various fruit perfumes containing lemon oil, orange oil or strawberry, and yoghurt, mint, menthol, etc.) may be included in the composition. The flavoring agent may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0073] As used herein, “lubricants” are materials that perform a number of functions relating to compositions. In certain embodiments, like tablet manufacture, the lubricants perform one or more functions such as improving the rate of flow of the tablet granulation, preventing adhesion of the tablet material to the surface of dies and punches, reducing interparticle friction, and facilitating the ejection of the tablets from a die cavity. Examples of suitable lubricants include, but are not limited to, zinc stearate, gum arabic powder, cacao butter, carnauba wax, carmellosecalcium, carmellosesodium, caropeptide, aqueous silicon dioxide, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, crystalline cellulose, hardened oil, synthetic aluminum silicate, sesame oil, flour starch, white beeswax, magnesium oxide, dimethyl polysiloxane, potassium sodium tartrate, sucrose fatty acidester, glycerin fatty acid ester, silicon resin, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl stearate, magnesium stearate, cetanol, gelatin, talc, magnesium carbonate, precipitated calcium carbonate, cornstarch, lactose, hard fat, saccharose, potato starch, hydroxypropylcellulose, fumaric acid, sodium stearyl fumarate, polyethylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, beeswax, magnesium aluminometasilicate, methylcellulose, Japan wax, glycerin monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, phosphoric acid, palmitic acid, and hydrogenated vegetable oils and fats. The lubricant may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0074] As used herein, “binders” are agents used to impart cohesive qualities to powdered materials. Binders, or “granulators” as they are sometimes known, impart a cohesiveness to the tablet formulation, which ensures the tablet remaining intact after compression, as well as improving the free-flowing qualities by the formulation of granules of desired hardness and size. Materials commonly used as binders include starch, such as com starch and pregelatinized starch; gelatin; sugars, such as sucrose, glucose, dextrose, molasses, and lactose; natural and synthetic gums, such as gum acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone (PVP), Veegum, microcrystalline cellulose, microcrystalline dextrose, amylose, larch arabogalactan, ethyl cellulose, cellulose acetate, and the like. The binder may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0075] As used herein, “colorants” are agents that give the composition a more pleasing appearance, and in addition help the manufacturer to control the product during its preparation and help the user to identify the product. Any of the approved certified water-soluble FD&C dyes, mixtures thereof, or their corresponding lakes may be used to color tablets. A color lake is the combination by adsorption of a water-soluble dye to a hydrous oxide of a heavy metal, resulting in an insoluble form of the dye. The colorant may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0076] Other conventional ingredients that may optionally be present in the composition include preservatives, stabilizers, anti-adherents or silica flow conditioners or glidants, such as silicon dioxide. Such ingredients may be used alone or in various mixtures, and utilized in any amount known in the art for oral compositions.

[0077] It is to be appreciated that certain components or additives may be classified under different terms of art and just because a component or additive is classified under such a term does not mean that they are limited to that fimction. If utilized, the additive or additives may be present in the composition in various amounts. Additional ingredients for optional use in the composition, e.g., when adapted for topical or oral administration, are described in U.S. Patent Nos. 5,747,006; 5,980,904; 6,994,874; 7,060,304; 7,247,321; 7,348,034; 7,364,759; 7,700,110; 7,722,904; 8,202,556; 8,916,212; 9,445,975; 9,801,809; 10,307,366; 10,532,024; and 10,537,516; and in U.S. Publication Nos. 2006 / 0257509; 2007 / 0224154; 2008 / 0081082; 2008 / 0124409; 2013 / 0302265; 2017 / 0252293; 2017 / 0281666; 2018 / 0200285; 2019 / 0083566; 2019 / 0160117; 2020 / 0171117; 2020 / 0383898; 2021 / 0017240; and 2021 / 0212926; the disclosures of which are hereby incorporated by reference in their entirety.Method of Administration

[0078] The composition may be administered or applied as needed, daily, several times per day or in any suitable regimen such that the desired outcome is achieved. In the method of this disclosure, the frequency of administration (e.g., topical application) can depend on several factors, including the desired level of 5a-reductase inhibition. Generally, a regimen includes application of the composition once or twice daily to include an administration in the morning and / or an administration in the evening. The amount and / or frequency of application of the composition may depend on several factors, including the level of desired results and the specific composition.

[0079] Inhibition of 5a-reductase, and the associated improvement in the signs of hair loss and / or prostatic hyperplasia, can be achieved by administering the formulations of the present invention externally, internally, or some combination thereof. Preferably, the formulations of the present invention are administered with an acceptable carrier. For example, the formulation of the present invention could be externally administered with an acceptable carrier in the form of a gel, lotion, cream, tonic, emulsion, etc. As a further example, the formulation of the present invention could be internally administered with an acceptable carrier in the form of a pill, tablet, powder, bar, beverage, etc. Thus, the formulations described herein are useful in a wide variety of finished products, including pharmaceutical products, food products, and beverage compositions. Preferably, the products are useful for providing mammalian subjects with reduced hair loss and / or prostatic hyperplasia.

[0080] When the formulations of the present invention are orally administered in the form of a liquid, the liquid may be water-based, milk-based, tea-based, fruit juice-based, or some combination thereof. Solid and liquid formulations for internal administration according to the present invention can further comprise thickeners, including xanthan gum, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, methylcellulose, microcrystalline cellulose, starches, dextrins, fermented whey, tofu, maltodextrins, polyols, including sugar alcohols (e.g., sorbitol and mannitol), carbohydrates (e.g., lactose), propylene glycol alginate, gellan gum, guar, pectin, tragacanth gum, gum acacia, locust bean gum, gum arabic, gelatin, as well as mixtures of these thickeners. These thickeners are typically included in the formulations of the present invention at levels up to about 0.1%, depending on the particular thickener involved and the viscosity effects desired.

[0081] The solid and liquid (food and beverage) formulations of the present invention can, and typically will, contain an effective amount of one or more sweeteners, including carbohydrate sweeteners and natural and / or artificial no / low calorie sweeteners. The amount of the sweetener used in the formulations of the present invention will vary, but typically depends on the type of sweetener used and the sweetness intensity desired.

[0082] In another example, the formulations of the present invention are topically administered in the form of a: solution, gel, lotion, cream, ointment, oil-in-water emulsion, water-in-oil emulsion, stick, spray, paste, mousse, tonic, foundation, or other cosmetically and topically suitable form.

[0083] Preferably, formulations of the present invention that are suitable for topical administration are mixed with an acceptable carrier. An acceptable carrier may act variously as solvent, carrier, diluent or dispersant for the constituents of the composition, and allows for the uniform application of the constituents to the surface of the skin at an appropriate dilution. The acceptable carrier may also facilitate penetration of the composition into the skin.

[0084] In one example of a formulation for topical application, the acceptable carrier forms from about 70% to about 99.99% by weight of the total composition. In other examples, the acceptable carrier will form from about 85% to 99.99% by weight of the total composition. The acceptable carrier may also form from about 90% to about 99.99% by weight of the total composition; or from about 99.95% to about 99.999% by weight of the total composition. The acceptable carrier can, in the absence of other cosmetic adjuncts or additives, form the balance of the composition.

[0085] The various ingredients used in practicing the present invention may be soluble or insoluble in the acceptable carrier. If all ingredients of a formulation are soluble in the acceptable carrier, then the vehicle acts as solvent. However, if all or some ingredients of a formulation are insoluble in the acceptable carrier, then those ingredients are dispersed in the vehicle by means of, for example, a suspension, emulsion, gel, cream or paste, and the like.

[0086] Thus, it will be apparent to the skilled artisan that the range of possible acceptable carriers is very broad. For example, acceptable carriers can be emulsions, lotions, creams, or tonics. Acceptable carriers can comprise water, ethanol, butylene glycol, or other various solvents that aid in penetration of the skin. Some examples of suitable vehicles are described in U.S. Pat. Nos. 6,184,247 and 6,579,516, the entire contents of which are incorporated herein by reference.

[0087] Preferably the acceptable carrier used in practicing the present invention comprises water and ethanol. Optionally, the acceptable carrier also contains butylene glycol. For example, the acceptable carrier can comprise 2-5% butylene glycol by weight of the composition. In practicing the present invention, preferably this acceptable carrier is mixed with a formulation of the present invention comprising 2% by weight of the total composition. In other examples, the acceptable carrier is mixed with a formulation of the present invention comprising 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.

[0088] In general, however, acceptable carriers according to the present invention may comprise, but are not limited to comprising, any of the following examples: water; castor oil; ethylene glycol monobutyl ether; diethylene glycol monoethyl ether; com oil; dimethyl sulfoxide; ethylene glycol; isopropanol; soybean oil; glycerin; soluble collagen; safflower seed oil; meadowfoam seed oil; mineral oil; squalene; shea butter; borage oil; or rice bran oil; polyquatemium-10; methylparaben; PEG-8; disodium lauroamphodacetate; sodium trideceth sulfate; hexylene glycol; sodium methyl cocoyl taurate; tea-lauryl sulfate; lauryl betaine; sodium myristoyl sarcosinate; PEG- 150 distearate; citric acid-anhydrous; sodium citrate-dihydrate; diazolidinyl urea; disodium EDTA; propylparaben; polysorbate 60; isopropyl palmitate; octyl palmitate; Cl 2- 15 alkyl benzoate; dipropylene glycol dibenzoate; PPG- 15 stearyl ether benzoate; isododecane; isoeicosane; squalane; jojoba oil; dimethicone; glyceryl stearate; PEG- 100 stearate; cetyl alcohol; butylene glycol; chlorphenesin; fragrance; polyacrylamide; C13-14 isoparaffin; Laureth-7; aloe vera powder; aloe vera gel, hydroxyethylacrylate; sodium acryloyldimethyl taurate copolymer; behenyl alcohol; tocopheryl acetate; isodecyl neopentanoate; glyceryl trioctanoate; cetearyl alcohol; cetearyl glucoside; chamomilla recutitaflower extract; biosaccharide gum-1; pentadecalactone; dipropylene glycol; cyclomethicone; PEG / PPG-18 / 18 Dimethicone; cyclopentasiloxane; disteardimonium hectorite; SD alcohol 40; phenoxyethanol; ethylparaben; trimethylsiloxysilicate; triethoxycaprylysilane; micronized titanium dioxide; titanium dioxide; zinc oxide; iron oxides (yellow; red; black; etc.); caprylysilane; sodium chloride; diisopropyl dimer dilinoleate; aluminum hydroxide; stearic acid; polyethelene beads; C12-15 alkyl benzoate; acrylates / C 10-30 alkyl acrylate; xanthan gum; sorbitan laurate; panthenol; petrolatum; isopropyl isostearate; dimethicone; arginine; phenoxyethanol; acryloyldimethyl taurate copolymer; isohexadecane; polysorbate 80; hydroxyethylacrylate; sodium acryloyldimethyl taurate copolymer; octinoxate (octyl methoxycinnimate); oxybenzone; dicaprylyl ether; isodecyl neopentanoate; cetearyl alcohol; cetearyl glucoside; benzyl alcohol; HDI / trimethylol hexyllactone crosspolymer; silica; isodecyl neopentanoate; coco-glucoside; C20-22 alkyl phosphate; C20-22 alcohols; 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; dimethly isosorbide; silica; SD alcohol 40-B; salicylic acid; ceteth-20; fragrance; or witch hazel.

[0089] Additionally, acceptable carriers used in the present invention may optionally comprise one or more humectants, including but not limited to: dibutyl phthalate; soluble collagen; sorbitol; or sodium 2-pyrrolidone-5-carboxylate. Other examples of humectants that may be used in practicing the present invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0090] Additionally, acceptable carriers in the present invention may optionally comprise one or more emollients including but not limited to: butane-l,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; octadecan-2-ol; caprylic triglyceride; capric triglyceride; polyethylene glycol; propane- 1,2-diol; triethylene glycol; sesame oil; coconut oil; safflower oil; isoamyl laurate; nonoxynol-9; panthenol; hydrogenated vegetable oil; tocopheryl acetate; tocopheryl linoleate; allantoin; propylene glycol; arachis oil; castor oil; isostearic acid; palmitic acid; isopropyl linoleate; lauryl lactate; myristyl lactate; decyl oleate; or myristyl myristate. Other examples of emollients that may be used in practicing the present invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0091] Additionally, acceptable carriers used in the present invention may optionally comprise one or more penetration enhancers including but not limited to: pyrrolidones, for example 2- pyrrolidone; alcohols, such as ethanol; alkanols, such as decanol; glycols, such as propylene glycol, dipropylene glycol, butylene glycol; surfactants; or terpenes.

[0092] Other acceptable carriers that may be used in practicing the present invention will be apparent to those of skill in the art and are included within the scope of the present invention.

[0093] For example, an acceptable carrier can be a lotion that is topically applied. The lotion may comprise CARBOPOL® 981, water, glycerin, isopropyl myristate, mineral oil, shea butter, stearic acid, glycol stearate, cetyl alcohol, dimethicone, preservatives, tea, and various ingredients of the formulations of the present invention.

[0094] The formulations of the present invention may also contain various known and conventional cosmetic adjuvants so long as they do not detrimentally affect the desired 5 a- reductase and accompanying hair protection and / or prostatic hyperplasia treatment effects provided by the formulation. For example, a formulation of the present invention can further include one or more additives or other optional ingredients well known in the art, which can include but are not limited to fillers (e.g., solid, semi-solid, liquid, etc.); carriers; diluents; thickening agents; gelling agents; vitamins, retinoids, and retinols (e.g., vitamin B3, vitamin A, etc.); pigments; fragrances; sunscreens and sunblocks; anti-oxidants and radical scavengers; organic hydroxy acids; exfoliants; skin conditioners; moisturizers; ceramides, pseudoceramides, phospholipids, sphingolipids, cholesterol, glucosamine, pharmaceutically acceptable penetrating agents (e.g., n-decylmethyl sulfoxide, lecithin organogels, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids such as proline, pyrrolidone carboxylic acid, its derivatives and salts, saccharide isomerate, panthenol, buffers together with a base such as triethanolamine or sodium hydroxide; waxes, such as beeswax, ozokerite wax, paraffin wax; plant extracts, such as 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 contents of which are incorporated herein by reference.

[0095] The formulation can include additional inactive ingredients, including, but not limited to surfactants, co-solvents, and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, can be included in the formulations. Particular surfactants can be used based on the on the overall composition of the formulation and the intended delivery of the formulation. Useful surfactants include polyethoxylated (PEG) fatty acids, PEG-fatty acid diesters, PEG-fatty acid mono- and di-ester mixtures, polyethylene glycol glycerol fatty acid esters, alcohol-oiltransesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters-glycerol esters, mono- and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, polysaccharide esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants, and mixtures thereof.

[0096] The formulations can also include co-solvents such as alcohols and polyols, polyethylene glycols ethers, amides, esters, other suitable co-solvents, and mixtures thereof. The formulations can also include excipients or additives such as sweeteners, flavorants, colorants, antioxidants, preservatives, chelating agents, viscomodulators, tonicifiers, odorants, opacifiers, suspending agents, binders, and mixtures thereof.

[0097] Generally, the formulations of the present invention are topically or orally administered at least on a daily basis for a period of time sufficient to bring about the desired level of improvement in hair loss and / or treatment of prostatic hyperplasia. Topical application or oral administration of the formulations of the invention may continue for any suitable period of time. More specifically, within a few hours to within a few days of the initial application or ingestion, a user may notice an improvement in the signs of hair loss and / or prostatic hyperplasia. It should be appreciated that the frequency with which the formulations of the present invention should be applied or ingested will vary depending on the desired level of improvement. In particular, the degree of physical improvement will vary directly with the total amount of composition used.

[0098] Useful dosage forms can be prepared by methods and techniques that will be well understood by those of skill in the art and may include the use of additional ingredients in producing tablets, capsules, or liquid dosage forms.INDUSTRIAL APPLICABILITY

[0099] This disclosure provides new and usefill 5a-reductase inhibitors, including the botanical extracts described herein. Such 5a-reductase inhibitors can offer potential preventive and therapeutic approaches for lowering the risks of hair loss, prostatic hyperplasia, or other pathogenic complications caused by 5a-reductase activity. As such, the compositions and methods described herein are usefill for inhibiting 5a-reductase.

[0100] General compositions and product lines provided by this disclosure relate to hair care and nutrition-beauty products utilizing such 5a-reductase inhibitors, and specific examples include hair products, pills, or liquids / beverages utilizing such 5a-reductase inhibitors.

[0101] Left unchecked, 5a-reductase activity can result in high / elevated levels of DHT, which in turn increases the risk of hair loss, facial acne, and / or prostatic hyperplasia. Thus, the compositions and methods herein are usefiil for 5a-reductase inhibition or hair loss prevention, and therefore can protect hair, decrease hair loss, and otherwise promote hair growth. The compositions and methods of this disclosure also provide potential preventive and therapeutic approaches for lowering the risks of prostatic hyperplasia caused by DHT formation via 5 a- reductase activity.

[0102] The following examples, illustrating the compositions and methods of this disclosure, are intended to illustrate and not to limit the disclosure.EXAMPLES

[0103] The inhibition effects of botanical active components and botanical water and ethanol extracts on 5a-reductase activity (particularly the conversion of testosterone to DHT) was evaluated. Specifically, two extracts of Potentilla glabra at various concentrations and samples of thonningianin A at various concentrations were evaluated for their potential to inhibit conversion of testosterone to DHT by 5a-reductase. Both extracts of Potentilla glabra as well as thonningianin A showed inhibition as illustrated in the following Tables and Figures. The exacts were made in lab, but are also commercially available.Inhibition of 5a-reductase

[0104] The 5a-reductase inhibitory ability of samples were assessed by measuring the change of substrate testosterone content in the 5a-reductase active reaction system. The reaction solution was preincubated with or without a test sample in buffer solution (Tris-HCl, pH 7.4). Preincubated reaction solution consisted of 10 mmol / L NADPH (15 pL), 10 mol / L testosterone (1 pL) and different samples (1 pL) in a final volume of 195 pL for 5 minutes at room temperature. The reaction was started with the addition of human liver microsomes (20 mg / mL). After incubation at 37 °C for 30 minutes, the reaction solution was terminated with 200 pL acetonitrile. The upper phase was separated using a centrifugal machine, then was transferred to a tube. Testosterone and the metabolites of dihydrotestosterone (DHT) were measured by HPLC. Finasteride was used as a positive control drug.Determination of inhibition rate

[0105] The inhibition rate of 5a-reductase was calculated by the following equation:The inhibition rate (where A represents the DHT content of the blank control group, and B represents the DHT content of the sample group.Results for Potentilla glabra

[0106] The results for Potentilla glabra are illustrated in the Tables below. The rates of inhibition can also be appreciated with reference to the Figures.Table 1:* see also Fig. 1 (where each bar represents a respective concentration and the % inhibition is shown vertically)Table 2:* see also Fig. 1 (where each bar represents a respective concentration and the % inhibition is shown vertically)Table 3:* see also Fig. 1 (where each bar represents a respective concentration and the % inhibition is shown vertically)

[0107] As shown in Tables 2 and 3 above, Potentilla glabra - aqueous and ethanol extracts provide an excellent 5a-reductase inhibitory effect.Results for Thonningianin A

[0108] The results for thonningianin A are illustrated in the Tables below. The rates of inhibition can also be appreciated with reference to the Figures.Table 4:* see also Fig. 2 (where the X-axis is concentration and the Y-axis is % inhibition)Table 5:* see also Fig. 3 (where the X-axis is concentration and the Y-axis is % inhibition)

[0109] As shown in Table 5 above, thonningianin A provides an excellent 5a-reductase inhibitory effect.

[0110] The terms “comprising” or “comprise” are used herein in their broadest sense to mean and encompass the notions of “including,” “include,” “consist(ing) essentially of,” and “consist(ing) of.” The use of “for example,” “e.g.,” “such as,” and “including” to list illustrative examples does not limit to only the listed examples. Thus, “for example” or “such as” means “for example, but not limited to” or “such as, but not limited to” and encompasses other similar or equivalent examples. The term “about” as used herein serves to reasonably encompass or describe minor variations in numerical values measured by instrumental analysis or as a result of sample handling. Such minor variations may be in the order of ±0-10, ±0-5, or ±0-2.5, % of the numerical values. Further, the term “about” applies to both numerical values when associatedwith a range of values. Moreover, the term “about” may apply to numerical values even when not explicitly stated.

[0111] Generally, as used herein a hyphen or dash in a range of values is “to” or “through”; a “>” is “above” or “greater-than”; a “>” is “at least” or “greater-than or equal to”; a “<” is “below” or “less-than”; and a “<” is “at most” or “less-than or equal to.” On an individual basis, each of the aforementioned applications for patent, patents, and / or patent application publications, is expressly incorporated herein by reference in its entirety in one or more nonlimiting embodiments.

[0112] It is to be understood that the appended claims are not limited to express and particular compounds, compositions, or methods described in the detailed description, which may vary between particular embodiments which fall within the scope of the appended claims. With respect to any Markush groups relied upon herein for describing particular features or aspects of various embodiments, it is to be appreciated that different, special, and / or unexpected results may be obtained from each member of the respective Markush group independent from all other Markush members. Each member of a Markush group may be relied upon individually and or in combination and provides adequate support for specific embodiments within the scope of the appended claims.

[0113] It is also to be understood that any ranges and subranges relied upon in describing various embodiments of the present invention independently and collectively fall within the scope of the appended claims, and are understood to describe and contemplate all ranges including whole and / or fractional values therein, even if such values are not expressly written herein. One of skill in the art readily recognizes that the enumerated ranges and subranges sufficiently describe and enable various embodiments of the present invention, and such ranges and subranges may be further delineated into relevant halves, thirds, quarters, fifths, and so on. As just one example, a range “of from 0.1 to 0.9” may be farther delineated into a lower third, i.e., from 0.1 to 0.3, a middle third, i.e., from 0.4 to 0.6, and an upper third, i.e., from 0.7 to 0.9, which individually and collectively are within the scope of the appended claims, and may be relied upon individually and / or collectively and provide adequate support for specific embodiments within the scope of the appended claims. In addition, with respect to the language which defines or modifies a range, such as “at least,” “greater than,” “less than,” “no more than,” and the like, it is to be understood that such language includes subranges and / or an upper or lower limit. As another example, a range of “at least 10” inherently includes a subrange of from at least 10 to 35, a subrange of from at least 10 to 25, a subrange of from 25 to 35, and so on,and each subrange may be relied upon individually and / or collectively and provides adequate support for specific embodiments within the scope of the appended claims. Finally, an individual number within a disclosed range may be relied upon and provides adequate support for specific embodiments within the scope of the appended claims. For example, a range “of from 1 to 9” includes various individual integers, such as 3, as well as individual numbers including a decimal point (or fraction), such as 4.1, which may be relied upon and provide adequate support for specific embodiments within the scope of the appended claims.

[0114] 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 present 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 single and multiple dependent, is herein expressly contemplated.

Claims

CLAIMSWhat is claimed is:

1. A composition for administration to a subject, the composition comprising at least one botanical active component, wherein the botanical active component comprises at least one selected from the group consisting of: i) an extract of Potentilla glabra,1ii) thonningianin A; and iii) combinations of i) and ii); wherein the botanical active component is present in the composition in an amount effective to inhibit 5a-reductase in the subject.

2. The composition according to claim 1, wherein the botanical active component comprises one or both of an extract of Potentilla glabra flower and an extract of Potentilla glabra leaf.

3. The composition according to claim 2, wherein the botanical active component consists of one or both of the extract of Potentilla glabra flower and the extract of Potentilla glabra leaf.

4. The composition according to any one of claims 1 to 3, wherein the extract of Potentilla glabra is obtained by water extracting (or aqueous extracting) one or more of flowers, flowerbased plant material, leaves, and leaf-based plant material of Potentilla glabra.

5. The composition according to any one of claims 1 to 4, wherein the extract of Potentilla glabra is obtained by alcohol extracting one or more of flowers, flower-based plant material, leaves, and leaf-based plant material of Potentilla glabra.

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

7. The composition according to any one of claims 1 to 6, wherein the composition is substantially to completely free of components obtained from non-flower-based plant material and non-leaf-based plant material of Potentilla glabra.

8. The composition according to any one of claims 1 to 7, wherein Potentilla glabra is the variety Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand -Mazz.

9. The composition according to any one of claims 1 to 8, wherein the composition is farther defined as an oral composition that is formulated for oral administration to the subject.

10. The composition according to claim 9, further comprising a pharmaceutically acceptable additive.

11. The composition according to claim 10, wherein the pharmaceutically acceptable additive is not naturally occurring.

12. The composition according to any one of claims 1 to 8, wherein the composition is farther defined as a topical composition that is formulated for topical administration to the subject.

13. The composition according to claim 12, farther comprising a cosmetically acceptable carrier.

14. The composition according to claim 13, wherein the cosmetically acceptable carrier is not naturally occurring.

15. Use of the composition according to any one of claims 1 to 14, for inhibiting 5a- reductase in a subject.

16. A method of inhibiting 5a-reductase in a subject, the method comprising administering an effective amount of a composition to the subject, wherein the composition is according to any one of claims 1 to 14.

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

18. The method of claim 16, wherein the composition is administered topically to the subject.

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