Compositions and methods for inhibition of 5 alpha-reductase

Abstract

A composition for administration to a subject is disclosed. The composition comprises at least one plant active ingredient. The plant active ingredient is present in the composition in an amount effective to inhibit 5 alpha-reductase in a subject. The plant active component comprises at least one selected from the group consisting of: extract of potentilla glabra; ii) penthorum chinense pursh glycoside A; and iii) a combination of i) and ii). The composition may be in the form of an oral composition, for example for ingestion. The composition may also be in the form of a topical composition, for example for topical application. A method of inhibiting 5 alpha-reductase in a subject is also provided. The methods comprise administering to a subject an effective amount of the composition.

Description

Technical Field

[0001] The present invention generally relates to compositions and methods for inhibiting 5α - reductase, and more particularly, to compositions containing plant extracts for inhibiting 5α - reductase in a subject. Related methods are also provided. Background Art

[0002] 5α - reductase, also known as 3 - oxo - 5α - steroid 4 - dehydrogenase, is an enzyme present in human skin and prostate tissue. The main function of 5α - reductase is to catalyze the reduction of testosterone to dihydrotestosterone (DHT). However, elevated levels of DHT in the human prostate can lead to prostate hyperplasia, and elevated levels of DHT in human skin can lead to hair loss and can also lead to facial acne.

[0003] In view of the above, there remains an opportunity to provide new and useful 5α - reductase inhibitors. Such 5α - reductase inhibitors can provide potential prophylactic and therapeutic methods for reducing 5α - reductase activity and the effects and risks of the resulting DHT formation. Accordingly, there remains an opportunity to provide new and useful compositions and methods for inhibiting 5α - reductase activity. Summary of the Invention

[0004] A composition for administration to a subject is provided. The composition comprises at least one plant active ingredient. The plant active ingredient is generally present in the composition in an amount effective to inhibit 5α - reductase in the subject. The plant active ingredient comprises at least one selected from the following: i) an extract of Potentilla glabra; ii) thonningianin A; and iii) a combination of i) and ii).

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

[0006] The composition can be used to inhibit 5α - reductase in a subject. A method of inhibiting 5α - reductase in a subject comprises administering to the subject an effective amount of the composition. Brief Description of the Drawings

[0007] Figure 1 Is a bar graph showing the inhibition rate of 5α - reductase using aqueous and ethanol extracts of Potentilla glabra compared to using finasteride as a control;

[0008] Figure 2 Is a graph showing the 5α - reductase inhibition rate using finasteride as a control; and

[0009] Figure 3Graph showing the 5α-reductase inhibition rate using phyllanthoside A. Detailed implementation mode

[0010] Disclosed is a composition for administration to a subject. The composition comprises at least one botanical active ingredient. The composition is described below, followed by related uses and methods.

[0011] As should be understood in view of the present disclosure, the composition is not particularly limited except for the botanical active ingredient (including its extract) and related ingredients and methods. Thus, the composition can be formulated, for example, as a topical composition (e.g., a cosmetic composition), or as an oral composition or as a nutritional food, drug or supplement, and can be used as a unique and independent therapeutic agent or in combination with other therapeutic agents compatible therewith.

[0012] The composition can be used to treat, prevent and / or improve various conditions, such as those related to 5α-reductase activity. Specifically, as should be appreciated in view of the following description and examples, it is believed that the composition of the present embodiment is capable of inhibiting 5α-reductase, and more specifically, inhibiting 5α-reductase in a subject.

[0013] Thus, the composition can be used to treat (i.e., slow down, prevent, reverse, etc.) conditions commonly associated with 5α-reductase activity and related DHT production, such as hair loss, facial acne and prostate hyperplasia.

[0014] As introduced above, the composition comprises a botanical active ingredient. More specifically, the botanical active ingredient comprises at least one component selected from the following: i) an extract of Potentilla glabra Lodd.; ii) phyllanthoside A; and iii) a combination of i) and ii), optionally consisting essentially of or optionally consisting of the same.

[0015] In certain embodiments, only one of the two components i) and ii) is present in the composition. In other embodiments, both components i) and ii) are present in the composition. Each of the individual components i) and ii) can be simply referred to as a "botanical extract" or a "botanical active component", or collectively as "botanical extracts" or "botanical active components", and will be described in turn below.

[0016] The term "extract" is used herein in its conventional sense to refer to a composition obtained by fluid extraction from source material. Thus, the term "botanical extract" should be understood to mean a composition obtained by fluid extraction (e.g., solvent extraction, gas extraction, CO 2Compositions obtained from plant sources (i.e., plant materials) by extraction, etc. Plant extracts suitable for the compositions can be obtained by any extraction method known in the art or a combination of such methods, including water extraction, steam extraction, solvent extraction, etc. Exemplary extraction techniques are described below. However, plant extracts are generally not limited to a particular extraction method or additional / auxiliary techniques used to obtain the plant extracts, but can vary according to the parameters described herein. Additionally, the extraction step is not necessary for preparing the plant active ingredients and / or compositions, as suitable extracts (e.g., standardized extracts) and / or plant active ingredients are readily available from many commercial suppliers.

[0017] Plant extracts suitable for or as plant active ingredients include those obtained by solvent extraction, such as by using polar solvents, such as alcohols (e.g., methanol, ethanol, butanediol, etc.), ethers (e.g., diethyl ether, methyl tert-butyl ether, etc.), ketones (e.g., acetone), esters (e.g., ethyl acetate), phenols, water, etc., non-polar solvents, such as benzene, xylene, toluene, etc., and derivatives, modifiers, and combinations thereof (e.g., solvent-water blends, including alcohol-water, acetone-water, etc.). Additionally and alternatively, extraction techniques include sequential fractionations, total hydro-ethanolicextractions, lump-sum extractions, supercritical fluid extraction (e.g., with CO 2 ), etc., and those utilizing sequential or secondary extractions from a first extract (e.g., non-polar solvent extracts of plant extracts obtained by polar solvent extraction) or other processing techniques, such as filtration, purification, distillation, dehydration, evaporation, concentration, drying, etc. Specific examples of suitable extraction methods are described in U.S. Patent No. 7,897,184, which is incorporated herein by reference.

[0018] As understood in the art, various segments or parts of plants can be used to obtain essential oils and extracts, such as bark, berries, flowers, fruits, leaves, peels, resins, rhizomes, roots, seeds, and / or wood. Essential oils can be obtained by many methods, such as by distillation (e.g., using steam), pressing, solvent extraction, absolute oil extraction, resin tapping, and / or cold pressing.

[0019] In various embodiments, the solvent used to obtain the plant extracts suitable for the present disclosure is a solvent in which the resulting plant extract and / or its subsequent form (e.g., plant extract powder) is suitable for ingestion. For example, the solvent is water or ethanol.

[0020] In one instance, plant extracts can be obtained using organic solvent extraction techniques. In another instance, solvent sequential fractionation can be used to obtain plant extracts. Total water-ethanol extraction techniques can also be used to obtain plant extracts. Generally, this is referred to as single extraction. The plant extracts produced in the method will contain a wide variety of phytochemicals present in the extraction material, including both fat- and water-soluble phytochemicals. After collecting the plant extract solution, the solvent will be evaporated, thus producing the plant extract.

[0021] Total ethanol extraction can also be used. This technique uses ethanol as the solvent. The plant extracts produced by this extraction technique can include fat-soluble and / or lipophilic compounds in addition to water-soluble compounds. Total methanol extraction can be used in a similar manner with similar results.

[0022] Another example of an extraction technique that can be used to obtain plant extracts is supercritical fluid carbon dioxide extraction (SFE). In this extraction procedure, the material to be extracted is not exposed to any organic solvents. Instead, under supercritical conditions (e.g., >31.3 °C and >73.8 bar), the extraction solvent is carbon dioxide (CO 2 ), with or without a modifier. Those skilled in the art will realize that the temperature and pressure conditions can be varied to obtain the optimal yield of plant extracts. This technique produces plant extracts of fat-soluble and / or lipophilic compounds, similar to the total hexane and ethyl acetate extraction techniques that can also be used.

[0023] Each of the above extraction methods can also include and / or be combined with one or more additional processing steps understood in the art. For example, the plant material can be ground, crushed, milled, etc. There can also be one or more filtration steps to remove, for example, cellulose / fibers or other solid materials. There can also be one or more purification steps to remove, for example, certain components and / or contaminants. Such purification can be achieved, for example, by distillation, evaporation, centrifugation, etc. There can also be one or more concentration and / or drying steps to remove water and / or other volatiles, such as alcohols, lighter compounds, VOCs, etc. In addition, acids and / or bases can be added to adjust the pH or neutralize. Depending on the desired form of the final / ultimate plant extract, various additional steps understood in the art can also be utilized, such as screening, pressing, crushing, grinding, mixing, dispersing, etc. It should be realized that combining these additional processing steps in repeated and / or different sequences is also contemplated.

[0024] Potentilla glabra Lodd.

[0025] In some embodiments, the plant active ingredient and thus the composition comprises an extract of Potentilla glabra, i.e., an extract comprising material such as flowers or leaves from the flowering plant species Potentilla glabra, optionally consisting essentially of the same. The extract of Potentilla glabra is not particularly limited and can comprise or be any flower extract, leaf extract, or combination of flower and / or leaf extracts from Potentilla glabra plants suitable for the embodiments herein. In certain embodiments, the extract of Potentilla glabra comprises both flower and leaf extracts from Potentilla glabra plants. More specifically, exemplary Potentilla glabra flower and / or leaf extracts include those that are capable of inhibiting 5α-reductase or eliciting / possessing any other such activity described herein as part of the plant active ingredient.

[0026] It has been reported that Potentilla glabra contains various bioactive components such as phenolic acids, flavonoids, terpenoids, triterpenes, tannins, polyphenols, saponins, polysaccharides, and other compounds. Potentilla glabra belongs to the genus Potentilla (Rosaceae) and is mainly distributed in China, Mongolia, the Soviet Union, and Korea. Potentilla glabra can be abbreviated as Potentilla glabra (P. glabra) or various other names such as Potentilla glabra Lodd., Potentilla glabra G. Lodd., Dasiphora glabra (G. Lodd.) Soják, Silver Dew Plum, Yinlumei, or Potentilla glabra. The leaves and flowers of Potentilla glabra (Lodd.) can be called Yaowang tea or Guanyin tea. In various embodiments, Potentilla glabra can be the variety Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz, which can be called Baimao Yinlumei, white-haired Potentilla glabra, or white-haired Potentilla glabra (variety). Other synonyms of 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 L. extracts are known in the art. Thus, Potentilla glabra L. extracts can be purchased or otherwise obtained commercially from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein) or a combination thereof. In certain embodiments, the extract of Potentilla glabra L. is obtained by aqueous extraction (or water extraction) of plant material of Potentilla glabra L., including but not limited to flowers and / or leaves. In further or other embodiments, the extract of Potentilla glabra L. is obtained by alcohol extraction (e.g., ethanol extraction) of plant material of Potentilla glabra L., including but not limited to flowers and / or leaves.

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

[0029] As will be understood by those skilled in the art, Potentilla glabra L. is cultivated primarily for its flowers and / or leaves. Thus, in various embodiments, the extract of Potentilla glabra L. is an extract of Potentilla glabra L. flowers and / or leaves. Suitable extractions include those noted above, such as aqueous and ethanol extraction 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 L. (e.g., flowers and / or leaves) is ground in a mill to a uniform size. The resulting powder is then extracted using a water or ethanol solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to obtain a paste. The paste can then be lyophilized to dryness to obtain the extract.

[0031] In various embodiments, the plant active ingredient consists of an extract of Potentilla glabra L. flowers and / or leaves. In further or other embodiments, the composition is substantially to completely free of components derived from non-flower-based plant material and / or non-leaf-based plant material of Potentilla glabra L. In these embodiments, the non-flower-based plant material and non-leaf-based plant material of Potentilla glabra L. can be, for example, the roots, stems, bark, rhizomes or stolons of the Potentilla glabra L. plant. Without being bound by any particular theory, it is believed that the flowers and leaves of Potentilla glabra L. are most useful for 5α-reductase inhibitory activity; while other parts of Potentilla glabra L. are not (as illustrated in the Examples section below).

[0032] In other embodiments, the Potentilla glabra Lodd. extract may comprise materials from any part or combination of parts of the plant and is not limited to flower and / or leaf extracts. For example, the Potentilla glabra Lodd. extract may comprise materials extracted from one or more parts of the Potentilla glabra Lodd. plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. Additionally, such extracts may be further processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, sieved, extracted, distilled, concentrated, etc.) to obtain the Potentilla glabra Lodd. extract. Similarly, the Potentilla glabra Lodd. plant may be extracted in its original form or processed prior to extraction of the Potentilla glabra Lodd. extract (e.g., used in its original form, suspended form, dehydrated form, concentrated form, etc.). In certain embodiments, the plant active ingredient comprises a Potentilla glabra Lodd. extract containing materials derived from (i.e., extracted from) the flowers and / or leaves of Potentilla glabra Lodd..

[0033] The amount of Potentilla glabra Lodd. extract utilized in the plant active ingredient can vary and is selected based on the number and type of ingredients utilized in the plant active ingredient. In certain embodiments, the plant active ingredient comprises 1 - 2000 mg of Potentilla glabra Lodd. extract, such as 1 - 1000, optionally 2 - 800, optionally 20 - 750, or optionally 50 - 500 mg. However, amounts outside of these ranges may also be used. For example, in certain embodiments, the plant active ingredient comprises at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg of Potentilla glabra Lodd. extract. In these or other embodiments, the upper limit may be selected such that the plant active ingredient comprises ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, ≤5000 mg of Potentilla glabra Lodd. extract. In various embodiments, the plant active ingredient may comprise optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95 wt.% of the amount of Potentilla glabra Lodd. extract based on the total weight of the plant active ingredient. In such embodiments, the upper limit that can be selected is typically ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99 wt.% respectively based on the total weight of the plant active ingredient.

[0034] In certain embodiments, the plant active ingredient comprises more than one Potentilla glabra Lodd. extract, such as 2, 3, 4, or more Potentilla glabra Lodd. extracts. In such embodiments, each Potentilla glabra Lodd. extract is independently selected, may be the same as or different from any other Potentilla glabra Lodd. extract, and is each utilized in the amounts described above.

[0035] The Potentilla glabra Lodd. extract can be utilized in any form, such as pure (i.e., without solvents, carrier vehicles, diluents, etc.), or placed in a carrier vehicle, such as a solvent or dispersant. If present, the carrier vehicle can include aqueous solvents (e.g., water), organic solvents, fluids, or oils, etc., or combinations thereof. When utilized, the carrier vehicle should be selected based on the plant active ingredient and / or the specific components of the composition, such as the specific Potentilla glabra Lodd. extract being utilized. It should be realized that if a carrier vehicle is utilized, the Potentilla glabra Lodd. extract can be combined with the carrier vehicle before, during, or after being combined with the plant active ingredient and / or any other components of the composition.

[0036] Penthorum sachalinense A

[0037] In some embodiments, the plant active ingredient and thus the composition contain Phyllanthus amarus Schum. & Thonn. glycoside A (Th A). Phyllanthus amarus Schum. & Thonn. glycoside A is an ellagitannin and is assigned the CAS registration number 271579-11-4. Phyllanthus amarus Schum. & Thonn. glycoside A can also be referred to as inocembrindihydrochalcone or 7-O-[3”-O-galloyl-4”,6”-hexahydroxybenzoyl]-β-D-glucoside. Phyllanthus amarus Schum. & Thonn. glycoside A has the chemical formula C 42 H 34 O 21 , a molecular weight of about 874.70, and has the following chemical structure:

[0038]

[0039] Phyllanthus amarus Schum. & Thonn. glycoside A can be obtained from, for example, an extract containing materials from the plant species Thonningia sanguinea, optionally consisting essentially of the same. Thonningia sanguinea is a dioecious herb native to Africa and can be abbreviated as T. sanguinea or various other names such as Thonningia sanguinea Vahl, Thonningia coccinea, Thonningia dubia, Thonningia elegans, groundpineapple, pineapple of the bush, duiker’s kolanut, and crown of the ground.

[0040] Specific examples of the extract of *Thonningia sanguinea* are known in the art. Thus, phyllanthoside A can be purchased or otherwise obtained commercially from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein) or a combination thereof. In certain embodiments, the extract of *Thonningia sanguinea* is obtained by water extraction (or aqueous extraction) of *Thonningia sanguinea* plant material. In further or other embodiments, the extract of *Thonningia sanguinea* is obtained by alcohol extraction (e.g., methanol or ethanol extraction) of *Thonningia sanguinea* plant material.

[0041] The extract of *Thonningia sanguinea* may contain materials from any part or combination of parts of the plant from the whole plant. For example, the extract of *Thonningia sanguinea* may contain materials extracted from one or more parts of the *Thonningia sanguinea* plant, including its roots, stems, bark, tubers, rhizomes, leaves, buds, flowers, seeds, and / or its fruits. In addition, such an extract can be further processed (e.g., defatted, partially defatted, ground, dried, precipitated, washed, filtered, screened, extracted, distilled, concentrated, etc.) to obtain the extract of *Thonningia sanguinea*. Similarly, the *Thonningia sanguinea* plant can be extracted in its original form or processed prior to extraction of the *Thonningia sanguinea* extract (e.g., used in its original form, suspended form, dehydrated form, concentrated form, etc.).

[0042] Phyllanthoside A can alternatively or additionally be obtained, for example, from an extract comprising materials from the plant species *Penthorum chinese* Pursh, optionally consisting essentially of the same. *Penthorum chinese* is a plant species native to East Asia and can be abbreviated as P. chinese or 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 *Thonningia sanguinea*.

[0043] Specific examples of the extract of *Penthorum chinese* are known in the art. Thus, phyllanthoside A can be purchased or otherwise obtained commercially from a variety of sources, prepared (e.g., using any conventional extraction techniques known in the art, such as any of those described herein) or a combination thereof. In certain embodiments, the extract of *Penthorum chinese* is obtained by water extraction (or aqueous extraction) of *Penthorum chinese* plant material. In further or other embodiments, the extract of *Penthorum chinese* is obtained by alcohol extraction (e.g., methanol or ethanol extraction) of *Penthorum chinese* plant material.

[0044] As would be understood by those skilled in the art, the cultivation of Penthorum chinense Pursh is mainly for its flowers. Thus, in various embodiments, the extract of Penthorum chinense Pursh is an extract of the flowers of Penthorum chinense Pursh. Suitable extractions include those pointed out above, such as aqueous and alcoholic extractions of the flowers. The flowers can be from one or more plants and can be fresh, dried, or otherwise aged.

[0045] For example, certain extracts can be obtained where Penthorum chinense Pursh (such as the flowers) is ground in a mill to a uniform size. The resulting powder is then extracted using an aqueous or alcoholic solution. The solution is then filtered and the filtrate can be concentrated under reduced pressure to obtain a paste. The paste can then be lyophilized to dryness to obtain the extract.

[0046] The extract of Penthorum chinense Pursh can contain materials from any part or combination of parts of the plant and is not limited to flower extracts. For example, the extract of Penthorum chinense Pursh can contain materials extracted from one or more parts of the Penthorum chinense Pursh plant, including its roots, stems, bark, rhizomes, leaves, buds, flowers, seeds, and / or fruits. In addition, such extracts can be further processed (such as defatted, partially defatted, ground, dried, precipitated, washed, filtered, screened, extracted, distilled, concentrated, etc.) to obtain the extract of Penthorum chinense Pursh. Similarly, the Penthorum chinense Pursh plant can be extracted in its original form or processed prior to the extraction of the extract of Penthorum chinense Pursh (such as used in its original form, suspended form, dehydrated form, concentrated form, etc.).

[0047] The amount of swertiamarin A utilized in the botanical active ingredient can vary and is selected based on the quantity and type of ingredients utilized in the botanical active ingredient. In certain embodiments, the botanical active ingredient comprises 1 - 2000 mg of swertiamarin A, such as 1 - 1000, optionally 2 - 800, optionally 20 - 750, or optionally 50 - 500 mg. However, amounts outside of these ranges can also be used. For example, in certain embodiments, the botanical active ingredient includes an amount of swertiamarin A of at least 1, optionally at least about 20, optionally at least about 50, optionally at least 100, optionally at least 250, optionally at least 500, optionally at least 1000, or optionally at least 1500 mg. In these or other embodiments, an upper limit can be selected such that the botanical active ingredient comprises an amount of swertiamarin A of ≤100, ≤250, ≤500, ≤750, ≤1000, ≤2000, ≤5000 mg. In various embodiments, the botanical active ingredient can include an amount of swertiamarin A that is optionally greater than 1, optionally greater than 5, optionally greater than 10, optionally greater than 25, optionally greater than 50, optionally greater than 75, optionally greater than 80, or optionally greater than 95 wt.% based on the total weight of the botanical active ingredient. In such embodiments, the upper limits that can be selected are generally ≤10, ≤20, ≤30, ≤40, ≤50, ≤60, ≤70, ≤80, ≤90, and ≤99 wt.% respectively based on the total weight of the botanical active ingredient.

[0048] Swertiamarin A can be utilized in any form, such as pure (i.e., without solvents, carrier vehicles, diluents, etc.), or placed in a carrier vehicle, such as a solvent or dispersant. If present, the carrier vehicle can comprise an aqueous solvent (e.g., water), an organic solvent, a fluid, or an oil, etc., or a combination thereof. When utilized, the carrier vehicle should be selected based on the botanical active ingredient and / or the specific ingredients of the composition, such as the specific swertiamarin A being utilized. It should be appreciated that if a carrier vehicle is utilized, swertiamarin A can be combined with the carrier vehicle before, during, or after being combined with any other ingredients of the botanical active ingredient and / or the composition.

[0049] Definition

[0050] To provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0051] "Improve at least one sign of hair loss", "improve signs of hair loss", and "protect hair" are used interchangeably herein to mean prevent, stop, reverse, improve, alleviate, and / or reduce hair loss. Representative signs of hair loss include, but are not limited to, thinning hair, loosening of hair, bald patches, patchy baldness, male pattern baldness, female pattern baldness, patchy alopecia, traction alopecia, frontal fibrosing alopecia, full-body hair loss, or combinations thereof.

[0052] "Improve the appearance of the skin" and "improve the aesthetic appearance of the skin" are used interchangeably herein to mean an aesthetic improvement in the appearance of the skin. Representative improvements can include, but are not limited to, favorable properties and / or qualities related to skin thickness, elasticity, resilence, moisture retention, smoothness, tone, texture, gloss, sheen, brightness, transparency, contour, firmness, turgor, suppleness, softness, sensitivity, pore size, or combinations thereof. These terms can also be used to mean an improvement in an adverse skin condition. Representative adverse conditions affected by, resulting from, or caused by such adverse skin conditions 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, sagging, thinning, hyperplasia, fibrosis, enlarged pores, cellulite formation, contusions, acne formation, apoptosis, cell differentiation, cell dedifferentiation, prevention of tumor induction or tumor progression, viral infections, fungal infections, bacterial infections, spider veins (telangiectasias), hirsutism, rosacea, pruritus, calluses, warts, corns, or combinations thereof.

[0053] The term "composition" or "preparation" refers to a product that treats, improves, promotes, increases, manages, controls, maintains, optimizes, modifies, reduces, inhibits, or prevents a specific condition related to a natural state, biological process, or disease or disorder. For example, the composition or preparation improves at least one sign of hair loss and / or minimizes or inhibits hair loss in a subject. The terms composition and preparation include, but are not limited to, pharmaceuticals (i.e., drugs), over-the-counter (OTC) medications, cosmetics, foods, food ingredients, or dietary supplement compositions, which include an effective amount of an extract, at least one of its ingredients, or a mixture thereof. Exemplary compositions and / or preparations include creams, cosmetic lotions, packs, or powders, or are in the form of emulsions, lotions, liniment foams, tablets, plasters, granules, or ointments. Preferred compositions are formulated for topical application / administration and for oral administration / ingestion.

[0054] As used herein, the terms "effective amount" or "therapeutically effective amount" of a pure compound, composition, extract, extraction mixture, ingredient of an extract, and / or active agent or ingredient or combination thereof refer to an amount that is effective at a dosage and for a period of time sufficient to achieve the desired result. For example, an "effective amount" or "therapeutically effective amount" refers to the amount of the pure compound, composition, extract, plant extract, extraction mixture, plant extraction mixture, ingredient of an extract, and / or active agent or ingredient or combination thereof of the present invention that is sufficient to effect treatment, such as improving hair loss and / or minimizing or inhibiting hair loss, when administered to a subject (e.g., a mammal, such as a human). The amount of the compositions, extracts, plant extracts, extraction mixtures, plant extraction mixtures, ingredients of an extract, and / or active agents or ingredients that constitute an "effective amount" or "therapeutically effective treatment" will vary depending on the active agent or compound, the condition being treated and its severity, the mode of administration, the duration of treatment, or the age of the subject to be treated, but can be routinely determined by one of ordinary skill in the art based on their own knowledge and in accordance with the present disclosure.

[0055] The term "pharmaceutically acceptable" means those drugs, agents, extracts, or inert ingredients that are suitable for contact with the tissues of humans and lower animals without excessive toxicity, incompatibility, instability, irritation, etc., and that are commensurate with a reasonable benefit / risk ratio.

[0056] The terms "apply" and "administer" are defined as providing a composition to a subject by 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 a preferred embodiment, the topical and / or oral route of administration of the composition is suitable.

[0057] The terms "minimize", "reduce", "prevent", "lower" and / or "inhibit" mean a decrease or reduction in 5α-reductase activity and / or its downstream effects in the presence of a botanical (or plant) ingredient or plant extract as described herein, when compared to 5α-reductase activity (such as in a control sample) in the absence of a botanical ingredient or plant extract as described herein. The degree of decrease or inhibition of 5α-reductase activity and / or its downstream effects will vary with the nature and amount of the botanical ingredient or plant extract present, but is visibly apparent, for example, as a detectable decrease in 5α-reductase; desirably, the degree of decrease is 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 within the range of about 5% - about 99%) compared to 5α-reductase activity in the absence of the botanical ingredient or plant extract. For example, a composition comprising a botanical ingredient or plant extract containing Potentilla acaulis L. and / or Phyllanthus niruri Linn. var. glaucus (Wall.) Muell. Arg. glycoside A can minimize or lower 5α-reductase activity, which in turn can minimize or reduce hair loss and treat benign prostatic hyperplasia.

[0058] As used herein, the terms "subject" or "individual" include 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), etc. In some embodiments, the subject is a mammal, and in some embodiments, the subject is a human.

[0059] Composition (or preparation)

[0060] The composition can include any amount of the botanical active ingredient, selected based on the quantity and type of ingredients utilized in the overall composition. Generally, the botanical active ingredient is present in the composition in an amount effective to inhibit 5α-reductase activity in a subject.

[0061] In certain embodiments, the composition comprises an amount of the botanical active ingredient of 1 - 5000, optionally 2 - 2000 mg, 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 can also be utilized. For example, it should be appreciated that the ranges described above for the amount of each botanical extract of the botanical active ingredient can equally apply to the amount of each botanical extract in the overall composition, such as when the botanical active ingredient consists of only one botanical extract.

[0062] In some embodiments of the composition, the preparation for hair loss prevention / hair protection and / or prostate health comprises: Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Maz extract and / or phyllanthoside A. In certain embodiments, the inclusion of phyllanthoside A is optional and may not be included in the preparation. In other embodiments, the inclusion of Potentilla glabra extract is optional and may not be included in the preparation. In specific embodiments, the preparation comprises Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz and phyllanthoside A.

[0063] Generally, in addition to comprising plant active ingredients and / or their plant extracts, the composition has no limitations in terms of the preparation, peripheral components, form, number of functions, etc. On the contrary, the composition can vary and can be formulated in any manner consistent with the present disclosure.

[0064] Generally, the composition is formulated or otherwise adapted for administration to a mammalian subject (such as a human). For example, in various embodiments, the composition is adapted for topical administration or consumption and / or oral administration to a human subject.

[0065] In certain embodiments, the composition is further defined as a topical composition formulated for topical administration to a subject. In such an embodiment, the composition may also be referred to as a cosmetic composition and generally 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, in these specific embodiments, the carrier is not a natural product. In other embodiments, the carrier is selected from conventional carriers understood in the art and can be used in conventional amounts.

[0066] In certain other embodiments, the composition is further defined as an oral composition formulated for oral administration to a subject. In such an embodiment, the composition may also be referred to as an ingestible composition and generally 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 natural product 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.

[0067] Accordingly, it should be appreciated that the specific additives, carriers, adjuvants, fillers, etc. present in or combined with the composition can vary. Additionally, there is no limitation on the physical form of the composition, and it will be selected based on the specific ingredients of the composition, the intended use of the composition, etc. Thus, as will be understood in view of the description herein, the composition can be formulated as a liquid, dry powder, suspension, emulsion, gel, paste, etc. and combinations thereof. In certain embodiments, the composition is formulated as a sterile, pyrogen-free liquid solution or suspension, coated capsules, suppositories, lyophilized powders, transdermal patches, soft gels, or other known forms. Other examples of suitable forms include solids, gels, liquids, creams, lotions, pomades, mousses, powders, foams, sprays, ointments, or other such formulations, wherein the botanically active ingredient is placed in a suitable carrier vehicle, such as any of those described herein. In specific embodiments, the composition is formulated or otherwise provided as a skin or scalp treatment for topical application or as a liquid or capsule for oral ingestion.

[0068] The composition can be prepared using a variety of methods. For example, the active agent(s) of the composition (such as plant extracts) and optionally one or more inactive agents (such as one or more conventional ingredients, additives, excipients, etc.) can be mixed or blended and compressed or compounded using various techniques understood in the art. The compositions of the present disclosure are not limited to a particular order of manufacturing steps or manufacturing method.

[0069] In various embodiments, the composition is topically applied by being applied to the skin of a subject. The subject is generally human and can include males and females of various ages. The methods / compositions of the present disclosure are not limited to a particular subject.

[0070] 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 skin of a subject. In another example, the composition can be formulated for spraying onto the skin of a subject. The composition can be formulated for spraying as an aerosol spray or a pump spray. In still another example, the composition can be formulated for application using a pre-moistened tissue. In another example, the composition can be formulated as a solid for rubbing onto the skin of a subject. In another example, the composition is formulated for delivery via a patch that adheres to the skin of a subject.

[0071] In addition to the plant active ingredient (i.e., "active substance" or "active ingredient"), the composition may further include pharmaceutically acceptable additives as inactive substances (or "inactive ingredients"), including but not limited to excipients such as diluents and binders; granulating agents; glidants (or flow aids); fillers; lubricants; preservatives; stabilizers; coatings; disintegrants; fragrances; and pigments. The active ingredient and the pharmaceutically acceptable additives may be combined or blended as needed to form a single dose that provides the desired amount of the active ingredient to a human subject when topically applied.

[0072] Optionally, the composition may include one or more additional ingredients, such as additives. Suitable additives include those understood in the art, including but not limited to humectants, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, antibacterial agents, drugs and drug substances, pain compounds, antineuralgic compounds, antioxidants, blood circulation promoters, antidepressant compounds, anxiolytic compounds, antistress compounds, sunscreens, insect repellents, preservatives, exfoliants, fragrances, colorants, fillers, solvents, vehicles, carriers, other types of additives known to those skilled in the art, and combinations thereof. Such additives may be utilized alone or in combination. Generally, the optional additives may be of any type used in personal care products and cosmetic products.

[0073] Excipients may be further classified into other components. Specifically, excipients for oral solid dosage forms have been classified into the following groups based on their functionality: such as diluents, disintegrants, binders, compression aids, granulating agents, glidants, lubricants, controlled-release polymers, stabilizers (such as antioxidants, chelating agents, and pH regulators), film coating polymers, coating agents, vehicles, plasticizers, surfactants, colorants, sweeteners, and flavoring agents.

[0074] In various embodiments, the composition comprises at least one component selected from binders, lubricants, glidants, and combinations thereof. In certain embodiments, the composition includes one or more of the following compounds: including but not limited to methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, cellulose acetate phthalate, gum arabic, gums, waxes, glyceryl monostearate, acrylic polymers and copolymers, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, lactose, calcium sulfate, calcium hydrogen phosphate, sugars, microcrystalline cellulose (MCC), starch, sodium starch glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. Combinations of such components may be utilized, and such components and other components for conventional tablets are understood in the art.

[0075] As used herein, a "diluent" may be an inert substance added to increase the volume of a composition so that a tablet reaches a practical size for consumption. Thus, they may also be referred to as fillers. Commonly used diluents include, but are not limited to, microcrystalline cellulose (MCC), wood cellulose, corn starch, modified corn starch, tricalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch, (powdered) sugar, dextrose, mannitol, sorbitol, etc. Diluents / fillers may be used alone or in various mixtures and utilized in any amount known in the art for oral compositions.

[0076] As used herein, a "flavoring agent" is a compound intended to impart a more palatable taste to a composition. Flavoring agents vary widely in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex volatile oils. Almost any desired type of synthetic flavoring agent is now available and well known in the art. If the astringency, sourness, or bitterness derived from the starting materials can be inhibited by flavoring or taste correction, an acidifying agent (e.g., citric acid, tartaric acid, malic acid, ascorbic acid, etc.), a sweetening agent (e.g., sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin, etc.), or a fragrance (e.g., various fruit fragrances containing lemon oil, orange oil, or strawberry, as well as yogurt, mint, menthol, etc.) may be included in the composition. Flavoring agents may be used alone or in various mixtures and utilized in any amount known in the art for oral compositions.

[0077] As used herein, "lubricant" is a material that performs many functions related to the composition. In certain embodiments, such as in tablet manufacturing, the lubricant performs one or more functions, such as improving the flow rate of tablet granulation, preventing the tablet material from adhering to the surfaces of the mold and punch, reducing interparticle friction, and facilitating the ejection of the tablet from the die cavity. Examples of suitable lubricants include, but are not limited to, zinc stearate, gum arabic powder, cocoa butter, carnauba wax, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, caropeptide, aqueous silica, dried aluminum hydroxide gel, glycerin, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, crystalline cellulose, hydrogenated oils, synthetic aluminum silicate, sesame oil, flour starch, white beeswax, magnesium oxide, dimethyl polysiloxane, sodium potassium tartrate, sucrose fatty acid ester, glycerol fatty acid ester, silicone resin, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl stearate, magnesium stearate, cetyl alcohol, gelatin, talc, magnesium carbonate, precipitated calcium carbonate, corn starch, lactose, hard fat, sucrose, potato starch, hydroxypropyl cellulose, fumaric acid, sodium stearyl fumarate, polyethylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, beeswax, magnesium aluminum metasilicate, methyl cellulose, Japan wax, glycerol monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, phosphoric acid, palmitic acid, and hydrogenated vegetable oils and fats. The lubricant can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0078] As used herein, "adhesive" is a reagent used to impart cohesiveness to powdered materials. The adhesive, or sometimes referred to as "granulating agent", imparts cohesiveness to the tablet formulation to ensure that the tablet remains intact after compression and to improve free-flowability by formulating granules of the desired hardness and size. Materials commonly used as adhesives include starches such as corn starch and pregelatinized starch; gelatin; sugars such as sucrose, glucose, dextrose, molasses, and lactose; natural and synthetic gums such as acacia gum, sodium alginate, Irish moss extract, panwar gum, Indian gum, mucilage of isapol husks, carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone (PVP), colloidal magnesium aluminum silicate (Veegum), microcrystalline cellulose, microcrystalline dextrin, amylose, larch arabinogalactan, ethyl cellulose, cellulose acetate, etc. The adhesive can be used alone or in various mixtures and in any amount known in the art for oral compositions.

[0079] As used herein, a "colorant" is a reagent that imparts a more pleasant appearance to the composition and also helps the manufacturer control the product during its preparation and helps the user identify the product. Any approved certified water-soluble FD&C dye, mixtures thereof, or their corresponding lakes can be used to color the tablets. Lakes are combinations obtained by adsorbing water-soluble dyes onto hydrated oxides of heavy metals, thereby producing insoluble forms of the dyes. The colorants can be used alone or in various mixtures and are utilized in any amounts known in the art for oral compositions.

[0080] Other conventional ingredients that may optionally be present in the composition include preservatives, stabilizers, anti-adhesion agents or silica flow regulators or glidants, such as silica. Such ingredients can be used alone or in various mixtures and are utilized in any amounts known in the art for oral compositions.

[0081] It should be appreciated that certain ingredients or additives may be classified under different technical terms and just because an ingredient or additive is classified under such a term does not mean that they are limited to that function. If utilized, one or more additives can be present in the composition in various amounts. For example, when suitable for topical or oral administration, additional ingredients optionally used in the composition are described in U.S. Patent Nos. 5,747,006; 5,980,904; 6,994,874; 7,060,304; 7,247,321; 7,348,034; 7,364,759; 7,700,110; 7,722,904; 8,202,556; 8,916,212; 9,445,975; 9,801,809; 10,307,366; 10,532,024; and 10,537,516; and U.S. Publication Nos. 2006 / 0257509; 2007 / 0224154; 2008 / 0081082; 2008 / 0124409;

[0082] 2013 / 0302265; 2017 / 0252293; 2017 / 0281666; 2018 / 0200285;

[0083] 2019 / 0083566; 2019 / 0160117; 2020 / 0171117; 2020 / 0383898;

[0084] 2021 / 0017240; and 2021 / 0212926; the disclosures of which are hereby incorporated by reference in their entirety.

[0085] Method of Administration

[0086] The composition can be administered or applied as needed, daily, several times a day, or according to any suitable regimen such that the desired result is achieved. In the methods of the present disclosure, the frequency of administration (e.g., topical administration) can depend on several factors, including the desired level of 5α-reductase inhibition. Generally, the regimen includes applying the composition once or twice a day, including applying in the morning and / or in the evening. The amount and / or frequency of applying the composition can depend on several factors, including the level of the desired result and the specific composition.

[0087] Inhibition of 5α-reductase and associated improvements in signs of hair loss and / or prostate 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 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 another example, the formulations of the present invention can be administered internally with an acceptable carrier in the form of a pill, tablet, powder, stick, beverage, etc. Thus, the formulations described herein can be used in a wide variety of finished products, including pharmaceutical, food, and beverage compositions. Preferably, the product can be used to provide reduced hair loss and / or prostate hyperplasia for mammalian subjects.

[0088] When the formulations of the present invention are administered orally in liquid form, the liquid can be water-based, milk-based, tea-based, juice-based, or some combination thereof. The solid and liquid formulations for internal administration according to the present invention can further contain thickeners, including xanthan gum, carboxymethyl cellulose, carboxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, microcrystalline cellulose, starch, dextrin, fermented whey, tofu, maltodextrin, polyols, including sugar alcohols (e.g., sorbitol and mannitol), carbohydrates (e.g., lactose), propylene glycol alginate, gellan gum, guar gum, pectin, tragacanth gum, gum acacia, locust bean gum, gum arabic, gelatin, and mixtures of these thickeners. These thickeners are generally included in the formulations of the present invention at levels up to about 0.1%, depending on the particular thickener involved and the desired viscosity effect.

[0089] The solid and liquid (food and beverage) formulations of the present invention can, and generally do, contain an effective amount of one or more sweeteners, including carbohydrate sweeteners and natural and / or artificial non / low-calorie sweeteners. The amount of sweetener used in the formulations of the present invention varies, but generally depends on the type of sweetener used and the desired intensity of sweetness.

[0090] In another example, the formulations of the present invention are topically administered in the form of a solution, gel, lotion, cream, ointment, water-in-oil emulsion, oil-in-water emulsion, stick, spray, paste, mousse, tonic, foundation, or other cosmetic and topically suitable forms.

[0091] Preferably, the formulations of the present invention suitable for topical application are mixed with an acceptable carrier. The acceptable carrier can variously serve as a solvent, vehicle, diluent, or dispersant for the components of the composition and allows the components to be uniformly applied to the skin surface at an appropriate dilution. The acceptable carrier can also facilitate the penetration of the composition into the skin.

[0092] In one example of a formulation for topical application, the acceptable carrier constitutes from about 70% to about 99.99% by weight of the total composition. In other examples, the acceptable carrier constitutes from about 85% to 99.99% by weight of the total composition. The acceptable carrier can also constitute from about 90% to about 99.99% by weight of the total composition; or from about 99.95% to about 99.999% by weight of the total composition. The acceptable carrier can constitute the balance of the composition in the absence of other cosmetic adjuvants or additives.

[0093] The various components used to practice the present invention can be soluble or insoluble in the acceptable carrier. If all the components of the formulation are soluble in the acceptable carrier, the vehicle serves as a solvent. However, if all or some of the components of the formulation are insoluble in the acceptable carrier, these components are dispersed in the vehicle by means of, for example, suspensions, emulsions, gels, creams, or pastes.

[0094] Thus, it is obvious 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 skin care liquid. The acceptable carrier can contain water, ethanol, butylene glycol, or other various solvents that facilitate skin penetration. 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.

[0095] Preferably, the acceptable carrier used to practice the present invention contains water and ethanol. Optionally, the acceptable carrier also contains butylene glycol. For example, the acceptable carrier can contain 2 - 5% by weight of butylene glycol of the composition. In practicing the present invention, it is preferred to mix such an acceptable carrier with 2% by weight of the formulation of the present invention that constitutes the total composition. In other examples, the acceptable carrier is mixed with 0.001% - 30% by weight of the formulation of the present invention that constitutes the total composition; 1% - 5% by weight of the total composition; 0.01% - 15% by weight of the total composition; or 0.5% - 1.0% by weight of the total composition.

[0096] However, generally, acceptable carriers according to the present invention may include, but are not limited to, any of the following examples: water; castor oil; ethylene glycol monobutyl ether; diethylene glycol monoethyl ether; corn oil; dimethyl sulfoxide; ethylene glycol; isopropyl alcohol; soybean oil; glycerol; soluble collagen; safflower oil; meadowfoam seed oil; mineral oil; squalene; shea butter; borage oil; or rice bran oil; polyquaternium-10; methylparaben; PEG-8; disodium lauroamphodiacetate; sodium laureth sulfate; hexylene glycol; sodium methyl cocoyl taurate; TEA-lauryl sulfate; lauryl betaine; sodium myristoyl sarcosinate; PEG-150 distearate; anhydrous citric acid; sodium citrate dihydrate; diazolidinyl urea; disodium EDTA; propylparaben; polysorbate 60; isopropyl palmitate; octyl palmitate; C12-15 alkyl benzoate; dipropylene glycol dibenzoate; PPG-15 stearyl ether benzoate; isododecane; isoeicosane; squalane; jojoba oil; dimethicone; glyceryl stearate; PEG-100 stearate; cetyl alcohol; butylene glycol; chlorphenesin; fragrance; polyacrylamide; C13-14 isoparaffin; laureth-7; aloe powder; aloe gel, hydroxyethyl acrylate; acryloyldimethyltaurate copolymer; behenyl alcohol; tocopheryl acetate; isodecyl neopentanoate; glyceryl trioctanoate; cetearyl alcohol; cetearyl glucoside; chamomilla recutita flower extract; biosaccharide gum-1; pentadecanolide; dipropylene glycol; cyclomethicone; PEG / PPG-18 / 18 dimethicone; cyclopentasiloxane; dimethyldistearylammonium hectorite; SD alcohol 40; phenoxyethanol; ethylparaben; trimethylsilyoxysilicate; triethoxysilane; micronized titanium dioxide; titanium dioxide; zinc oxide; iron oxides (yellow; red; black; etc.); octyl silane; sodium chloride; diisopropyl dimer dilinoleate; aluminum hydroxide; stearic acid; polyethylene beads; C12-15 alkyl benzoate; acrylate / C10-30 alkyl acrylate; xanthan gum; sorbitan laurate; panthenol; petrolatum; isopropyl isostearate; dimethicone; arginine; phenoxyethanol; acryloyldimethyltaurate copolymer; isocetane; polysorbate 80; hydroxyethyl acrylate; acryloyldimethyltaurate copolymer; octyl methoxycinnamate (octinoxate); oxybenzone; diisooctyl ether; isodecyl neopentanoate; cetearyl alcohol; cetearyl glucoside; benzyl alcohol; HDI / trimetylolhexylactone cross polymer; silica; isodecyl neopentanoate; cocoyl-glucoside; C20-22 alkyl phosphate; C20-22 alcohol; palmitoyl proline; magnesium palmitoyl glutamate; sodium palmitoyl sarcosinate; C30-45 alkyl cetearyl cross polymer; polyacrylate 13; polyisobutene; polysorbate 20; iodopropynyl butylcarbamate; magnesium sodium silicate;Methylgluceth-20; Isosorbide Dimethyl Ether; Silica; SD Alcohol 40-B; Salicylic Acid; Ceteth-20; Fragrance; or Witch Hazel.

[0097] In addition, the acceptable carrier for use in the present invention may optionally contain one or more humectants, including but not limited to: Dibutyl Phthalate; Soluble Collagen; Sorbitol; or Sodium 2-Pyrrolidone-5-Carboxylate. Other examples of humectants that can be used to practice the present invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0098] In addition, the acceptable carrier in the present invention may optionally contain one or more emollients, including but not limited to: Butane-1,3-diol; Cetyl Palmitate; Dimethicone; 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; Triglyceride Caprylic; Triglyceride Capric; 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; Peanut Oil; Castor Oil; Isostearic Acid; Palmitic Acid; Isopropyl Linoleate; Lauryl Lactate; Myristyl Lactate; Decyl Oleate; or Myristyl Myristate. Other examples of emollients that can be used to practice the present invention can be found in the CFTA Cosmetic Ingredient Handbook, the relevant portions of which are incorporated herein by reference.

[0099] In addition, the acceptable carrier for use in the present invention may optionally contain one or more penetration enhancers, including but not limited to: Pyrrolidone, such as 2-Pyrrolidone; Alcohols, such as Ethanol; Alkanols, such as Decanol; Diols, such as Propylene Glycol, Dipropylene Glycol, Butylene Glycol; Surfactants; or Terpenes.

[0100] Other acceptable carriers that can be used to practice the present invention will be apparent to those skilled in the art and are included within the scope of the present invention.

[0101] For example, the acceptable carrier can be a topically applied lotion. The lotion may contain Carbomer 981, water, glycerin, isopropyl myristate, mineral oil, shea butter, stearic acid, stearic acid diol ester, cetyl alcohol, polydimethylsiloxane, preservatives, triethanolamine (tea) and various components of the preparation of the present invention.

[0102] The formulations of the present invention may also contain various known and conventional cosmetic adjuvants, provided that they do not detrimentally affect the desired 5α-reductase and the concomitant hair protection and / or prostate hyperplasia treatment effects provided by the formulation. For example, the formulations of the present invention may further include one or more additives or other optional ingredients well known in the art, which may include, but are not limited to, fillers (such as solids, semi-solids, liquids, etc.); carriers; diluents; thickeners; gelling agents; vitamins, vitamin A-like substances, and retinol (such as vitamin B 3 6, vitamin A, etc.); pigments; fragrances; chemical sunscreens and physical sunblocks; antioxidants and free radical scavengers; organic hydroxy acids; exfoliants; skin conditioners; moisturizers; ceramides, pseudo-ceramides, phospholipids, sphingolipids, cholesterol, glucosamine, pharmaceutically acceptable penetrants (such as n-decyl methyl sulfoxide, lecithin organogel, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids, such as proline, pyrrolidone carboxylic acid, its derivatives and salts, sugar isomers, panthenol, buffers with bases such as triethanolamine or sodium hydroxide; waxes, such as beeswax, ozokerite, paraffin wax; plant extracts, such as aloe vera, cornflower, witch hazel, elderflower or cucumber and combinations thereof. Other suitable additives and / or adjuvants are described in U.S. Patent No. 6,184,247, the entire content of which is incorporated herein by reference.

[0103] The formulation may include additional inactive ingredients, including but not limited to surfactants, co-solvents, and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, may be included in the formulation. Specific surfactants may be used based on the overall composition of the formulation and the intended delivery of the formulation. Useful surfactants include polyethoxylated (PEG) fatty acids, PEG-fatty acid diesters, mixtures of PEG-fatty acid mono- and diesters, polyglycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerolated fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters-glycerol esters, glycerol mono- and diesters, sterols and sterol derivatives, polyethyleneglycol sorbitan fatty acid esters, polyethyleneglycol alkyl ethers, polysaccharide esters, polyethyleneglycol alkylphenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants, and mixtures thereof.

[0104] The formulation may also include co-solvents, such as alcohols and polyols, polyethyleneglycol ethers, amides, esters, other suitable co-solvents, and mixtures thereof. The formulation may also include excipients or additives, such as sweeteners, flavoring agents, coloring agents, antioxidants, preservatives, chelating agents, viscosity regulators, tonicity regulators, odorants, emulsifying agents, suspending agents, binders, and mixtures thereof.

[0105] Typically, the formulations of the present invention are administered topically or orally at least daily for a period of time sufficient to bring about a desired level of improvement in hair loss and / or treatment of prostate hyperplasia. The topical or oral administration of the formulations of the present invention can continue for any suitable period of time. More specifically, within hours to days of initial administration or ingestion, the user may notice improvement in the signs of hair loss and / or prostate hyperplasia. It should be appreciated that the frequency of administration or ingestion of the formulations of the present invention should vary according to the desired level of improvement. In particular, the degree of physical improvement will vary directly with the total amount of the composition used.

[0106] Useful dosage forms can be prepared by methods and techniques well understood by those skilled in the art and can include the use of additional ingredients in the production of tablets, capsules or liquid dosage forms.

[0107] Industrial Applicability

[0108] The present disclosure provides novel and useful 5α-reductase inhibitors, including the plant extracts described herein. Such 5α-reductase inhibitors can provide potential prophylactic and therapeutic methods for reducing the risk of hair loss, prostate hyperplasia or other pathogenic complications caused by 5α-reductase activity. Thus, the compositions and methods described herein can be used to inhibit 5α-reductase.

[0109] The general compositions and product lines provided by the present disclosure relate to hair care and nutricosmetic products that utilize such 5α-reductase inhibitors, and specific examples include hair products, pills or liquids / drinks that utilize such 5α-reductase inhibitors.

[0110] If left uncontrolled, 5α-reductase activity can lead to high / elevated levels of DHT, which in turn increases the risk of hair loss, facial acne and / or prostate hyperplasia. Thus, the compositions and methods herein can be used for 5α-reductase inhibition or prevention of hair loss and can therefore protect hair, reduce hair loss or otherwise promote hair growth. The compositions and methods of the present disclosure also provide potential prophylactic and therapeutic methods for reducing the risk of prostate hyperplasia caused by the formation of DHT via 5α-reductase activity.

[0111] The following examples illustrating the compositions and methods of the present disclosure are intended to illustrate and not limit the present disclosure.

[0112] Examples

[0113] The inhibitory effects of plant active ingredients and aqueous and ethanol extracts of plants on 5α-reductase activity (specifically, the conversion of testosterone to DHT) were evaluated. Specifically, the potential of two Potentilla acaulis L. extracts at various concentrations and a sample of penthorin A at various concentrations to inhibit the conversion of testosterone to DHT via 5α-reductase was evaluated. As shown in the following table and figures, both Potentilla acaulis L. extracts and penthorin A showed inhibition. The extracts were prepared in the laboratory but are also commercially available.

[0114] Inhibition of 5α-reductase

[0115] The 5α-reductase inhibitory ability of the samples was evaluated by measuring the change in the content of the substrate testosterone in the 5α-reductase activity reaction system. The reaction solution was pre-incubated in a buffer solution (Tris-HCl, pH 7.4) with or without the test sample. The pre-incubated reaction solution consisted of 10 mmol / L NADPH (15 μL), 10 mmol / L testosterone (1 μL), and different samples (1 μL), with a final volume of 195 μL, and was incubated at room temperature for 5 minutes. The reaction was started by adding human liver microsomes (20 mg / mL). After incubation at 37 °C for 30 minutes, the reaction solution was terminated with 200 μL of acetonitrile. The upper layer was separated using a centrifuge and then transferred to a test tube. Testosterone and its metabolite dihydrotestosterone (DHT) were measured by HPLC. Finasteride was used as a positive control drug.

[0116] Determination of inhibition rate

[0117] The inhibition rate of 5α-reductase was calculated using the following equation:

[0118] Inhibition rate (%) = (A - B) / A × 100%

[0119] where A represents the DHT content in the blank control group, and B represents the DHT content in the sample group.

[0120] Results of Potentilla glabra Lodd.

[0121] The results for Potentilla acaulis L. are shown in the following table. The inhibition rate can also be understood with reference to the figures.

[0122] Table 1:

[0123]

[0124] * Also see Figure 1 (where each bar represents the corresponding concentration and the inhibition % is shown vertically)

[0125] Table 2:

[0126]

[0127] *See also Figure 1 (where each bar represents the corresponding concentration and the inhibition % is shown vertically)

[0128] Table 3:

[0129]

[0130] *See also Figure 1 (where each bar represents the corresponding concentration and the inhibition % is shown vertically)

[0131] As shown in Tables 2 and 3 above, Potentilla acaulis L. - aqueous and ethanol extracts provide excellent 5α - reductase inhibitory activity.

[0132] Results of Penthorum sachalinense A

[0133] The results of Phyllanthus niruri Linn. glycoside A are shown in the table below. The inhibition rate can also be understood with reference to the attached drawings.

[0134] Table 4:

[0135]

[0136] *See also Figure 2 (where the X - axis is the concentration and the Y - axis is the inhibition %)

[0137] Table 5:

[0138]

[0139] *See also Figure 3 (where the X - axis is the concentration and the Y - axis is the inhibition %)

[0140] As shown in Table 5 above, Phyllanthus niruri Linn. glycoside A provides excellent 5α - reductase inhibitory activity.

[0141] The term "comprising" or "comprise" is used herein in its broadest sense to mean and encompass the concepts of "including", "include", "consisting essentially of", and "consisting of". The use of "for example", "e.g.", "such as", and "including" to list illustrative examples is not limited to the examples listed. Thus, "for example" or "such as" means "for example but not limited to" or "such as but not limited to" and encompasses other similar or equivalent examples. The term "about" as used herein is intended to reasonably encompass or describe minor variations in values measured by instrumental analysis or as a result of sample processing. Such minor variations can be about ±0 - 10, ±0 - 5, or ±0 - 2.5% of the value. Further, when associated with a numerical range, the term "about" applies to both values. Additionally, even when not explicitly stated, the term "about" can apply to a numerical value.

[0142] Generally, the hyphen "-" or dash "-" in a numerical range as used herein means "to" or "until"; ">" means "higher than" or "greater than"; "≥" means "at least" or "greater than or equal to"; "<" means "lower than" or "less than"; and "≤" means "at most" or "less than or equal to". On an individual basis, each of the above patent applications, patents is incorporated herein by reference in its entirety.

[0143] It should be understood that the appended claims are not limited to the specific and definite compounds, compositions, or methods described in the detailed description, and they may vary between specific embodiments that fall within the scope of the appended claims. With respect to any Markush group of specific features or aspects relied upon herein to describe various embodiments, it should be recognized that different, special, and / or unexpected results can be obtained by each member of the corresponding Markush group independently of all other Markush members. Each member of the Markush group can be relied upon individually and / or in combination to provide sufficient support for specific embodiments within the scope of the appended claims.

[0144] It should also be understood that any ranges and sub-ranges used to describe various embodiments of the present invention independently and jointly fall within the scope of the appended claims, and it should be understood to describe and contemplate all ranges including integer and / or fractional values therein, even if such values are not explicitly written herein. Those skilled in the art can easily recognize that the enumerated ranges and sub-ranges are sufficient to describe and implement various embodiments of the present invention, and such ranges and sub-ranges can be further depicted as related 1 / 2, 1 / 3, 1 / 4, 1 / 5, etc. By way of example only, the range of "0.1 - 0.9" can be further depicted as the lower 1 / 3, i.e., 0.1 - 0.3, the middle 1 / 3, i.e., 0.4 - 0.6, and the upper 1 / 3, i.e., 0.7 - 0.9, which independently and jointly fall within the scope of the appended claims and can independently and / or jointly provide sufficient support for specific embodiments within the scope of the appended claims. Additionally, with respect to words defining or modifying ranges, such as "at least", "greater than", "less than", "not more than", etc., it should be understood that such words include sub-ranges and / or upper or lower limits. As another example, the range of "at least 10" inherently includes sub-ranges of at least 10 - 35, at least 10 - 25, 25 - 35, etc., and can independently and / or jointly rely on each sub-range and provide sufficient support for specific embodiments within the scope of the appended claims. Finally, individual numerical values within the disclosed ranges can be relied upon and provide sufficient support for specific embodiments within the scope of the appended claims. For example, the range of "1 - 9" includes various individual integers, such as 3, and individual numerical values (or fractions) including a decimal point, such as 4.1, which can be relied upon to provide sufficient support for specific embodiments within the scope of the appended claims.

[0145] The present invention has been described in an illustrative manner, and it should be understood that the terms used are intended to be descriptive rather than restrictive words. Many modifications and variations of the present invention are possible in light of the above teachings. The present invention may be practiced differently than specifically described within the scope of the appended claims. All combinations of the subject matter of the independent and dependent claims (including single and multiple dependencies) are explicitly contemplated herein.

Claims

1. A composition for administration to a subject, the composition comprising at least one botanical active ingredient, wherein the botanical active ingredient comprises at least one selected from the group consisting of: i) an extract of Herba Lycopodii; ii) chrysanthemumin A; and iii) a combination of i) and ii); The botanical active ingredient is present in the composition in an amount effective to inhibit 5α-reductase in a subject.

2. A composition according to claim 1, wherein the plant active ingredients comprise one or both of an extract of Prunus armeniaca flower and an extract of Prunus armeniaca leaf, optionally wherein the plant active ingredients consist of one or both of an extract of Prunus armeniaca flower and an extract of Prunus armeniaca leaf.

3. A composition according to claim 1 or 2, wherein the extract of Herba Lycopodii is obtained by water extraction (or aqueous extraction) of one or more of the flowers, flower-based plant materials, leaves and leaf-based plant materials of Herba Lycopodii.

4. The composition according to claim 1 or 2, wherein the extract of Potentilla argentea is obtained by alcohol extraction, optionally ethanol extraction, of one or more of the flowers, flower-based plant materials, leaves and leaf-based plant materials of Potentilla argentea.

5. A composition according to any one of claims 1 to 4, wherein the composition is substantially to completely free of components derived from non-flower-based plant materials and non-leaf-based plant materials of Prunus armeniaca.

6. A composition according to any one of claims 1 to 5, wherein the Potentilla glabra is the variety Potentilla glabra Lodd. var. mandshurica (Maxim.) Hand.-Mazz.

7. The composition according to any one of claims 1-6, wherein said composition is further defined as an oral composition formulated for oral administration to said subject.

8. The composition according to claim 7, further comprising a pharmaceutically acceptable additive, optionally wherein the pharmaceutically acceptable additive is not naturally occurring.

9. The composition according to any one of claims 1-6, wherein said composition is further defined as a topical composition formulated for topical administration to said subject.

10. A composition according to claim 9, further comprising a cosmetically acceptable carrier, optionally wherein the cosmetically acceptable carrier is not naturally occurring.

11. Use of a composition according to any one of claims 1 to 10 for inhibiting 5-alpha-reductase in a subject.

12. A method of inhibiting 5-alpha-reductase in a subject, the method comprising administering to the subject an effective amount of a composition, wherein the composition is according to any one of claims 1-10.

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

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

Images