Compositions for hair treatment with rhapontigenin and derivatives thereof

Abstract

Various actives have been identified which may be used to promote hair growth or otherwise improve keratin fibers. These compositions typically contain at least one of a rhapontigenin, a polyphenol such as poliumoside, and nicotinamide mononucleotide. In various embodiments the rhapontigenin is provided from an extract of the plant species Rheum and the polyphenol is provided as an extract from the plant species Callicarpa.

Description

COMPOSITIONS FOR HAIR TREATMENT WITH RHAPONTIGENIN ANDDERIVATIVES THEREOFCROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to and the benefit of U.S. App. No. 63 / 665.838, filed June 28, 2024, which is hereby incorporated by reference in its entirety.FIELD OF DISCLOSURE

[0002] The present disclosure is related to hair grow th compositions which may comprise rhapontigenin and one or more additional active components such as polyphenols or nicotinamide mononucleotide.BACKGROUND

[0003] Tens of millions of Americans suffer from some type of hair loss. A wide variety of conditions cause hair loss, including androgenic alopecia, or common pattern baldness, anagen effluvium a chemotherapy -induced hair loss, telogen effluvium, induced by stress, fever and drugs and alopecia areata, an autoimmune disease which afflicts an estimated four million people.

[0004] Typical drug treatments relating to hair growth such as Minoxidil and finasteride both stimulate hair regrowth in some patients, but only for the duration of drug use: new hair growth ends, and hair loss resumes shortly after the patient stops treatment. After several months of use, minoxidil successfully induces limited hair growth for approximately 1 in 3 patients and slows hair loss for roughly 9 in 10 patients. Oral finasteride is generally more effective than topical minoxidil at inducing hair growth, but both treatments are far less than 100% effective. Around half of treated patients achieve some hair regrowth, and approximately one-third of patients experience cosmetically important hair regrowth after two years of continuous use. There exists a significant need for improved compositions and methods for promoting hair growth.SUMMARY

[0005] In accordance with the foregoing objectives and others, the present disclosure provides compositions and methods for promoting hair growth. Typically these compositions comprise an active, optionally present in a liposome such as a coated liposome. The present application is partially premised on the discovery' of the activity7of certain components, suchas rhapontigenin, Rheum extracts, Callicarpa extracts, and nicotinamide mononucleotide are able to promote hair growth. Moreover, these actives may act synergistically providing unexpectedly increased hair growth when used in combination.

[0006] Topical compositions are provided which may comprise one or more topically acceptable excipients, rhapontigenin (5-[(E)-2-(3-hydroxy-4- methoxyphenyl)ethenyl]benzene-l,3-diol) and derivatives thereof and less than 5% anthranoids by weight of the rhapontigenin (e.g., a weight ratio of rhapontigenin: anthranoids of from 10: 1-5000: 1, 10: 1-100: 1, 100: 1-1000: 1, 1000: 1-5000: 1). In certain implementations, the topical composition comprises an extract of a plant from the genus Rheum and said extract of Rheum provides said rhapontigenin and / or derivatives thereof. For example, the plant may be Rheum rhaponticum. In various implementations, the extract of Rheum is an alcohol / water extract (e.g., lower alcohol / water (e.g., C1-C4 alcohol) such as methanol / water. ethanol / water, propanol / water, isopropanol / water. butanol / water, or combinations thereof). In some embodiments In various embodiments, the extract is aqueous alkaline extract (e.g. , a Ca(OH)2 extract). The Rheum extract may be a root extract. In various implementations, the rhapontigenin derivative is a glycosylated rhapontigenin. For example, the glycosylated rhapontigenin has the structure:wherein R1-R3 are independently selected from hydrogen and glucosyl, wherein at least one (e.g, one, two, three) of R1-R3 is glucosyl.

[0007] The rhapontigenin (or plant extract such as a Rheum extract) may be complexed with cyclodextrin (e.g, hydroxypropyl cyclodextrin, hydroxypropyl-P-cyclodextrin). In various implementations, the rhapontigenin (or said extract) is present in a liposome (e.g, a coated liposome). For example, the coated liposome is a cyclodextrin (e.g., hydroxypropyl cyclodextrin): phospholipids liposome coated with a starch such as a modified starch (e.g.. a liposome coated with rhapontigenin in a weight ratio of rhapontigenin:cyclodextrin:phospholipids:modified starch of 0.1-2:50-70: 10-15:1-7). For example, the ratio of rhapontigenin to cyclodextrin may be 1 :50-1 :75 and / or the ratio ofrhapontigenin to phospholipid may be 1 :10-1: 15 and / or the ratio of sodium starch octenylsuccinate (e.g., low viscosity starch such as starch viscosity of less than 500 mPas or less than 200 mPas or less than 100 mPas or less than 75 mPas) may be from 1:3-1 :5. The modified starch may be sodium starch octenyl succinate. In some embodiments, the starch (e.g., modified starch) has a viscosity' of less than (or from 1 mPas to) 100 mPas (e.g., less than 75 mPas. less than 50 mPas. less than 25 mPas) as measured by a 10% w / w water solution at 20°C with a Brookfield viscometer spindle LV-1. The liposome (e.g.. coated liposome) may have a Z-average particle size of from 100-200 nm (e.g., 125-175 nm) as measured by' dynamic light scattering. In some embodiments, the liposome (e.g., coated liposome) have polydispersity index of from 0.2-0.3. The topical composition may comprise from 0.01% to 50% (e.g., from 0.01% to 20%. from 0.01% to 10%, from 0.01% to 5%, from 0.1% to 5%. from 0.5% to 3%, 2%) liposome (e.g, coated liposome) by weight of the composition.

[0008] In various implementations, the topical composition comprises an extract from a plant of the genus Callicarpa (e.g, the Callicarpa extract provides one or more polyphenols such as poliumoside). For example, the Callicarpa extract may be a is Callicarpa japonica extract. In various implementations, the Callicarpa extract is a water extract. The Callicarpa extract may be from the fruit of the plant.

[0009] The actives may be present in the topical composition in a variety of ratios such ath the benefits to hair are provided. For example, the topical composition may have a weight ratio of the rhapontigenin or derivative thereof to extract from a plant of the genus Callicarpa of from 250: 1 to 1:250 (e.g., 250: 1 to 1 : 1, 200:1 to 1: 1, 70: 1 to 1: 1, 70: 1 to 2:1, 25: 1 to 1: 1, 25:1 to 2: 1, 20: 1 to 2: 1).

[0010] In some embodiments, the rhapontigenin (or said extract) is present in a coated liposome and said extract from a plant of the genus Callicarpa is present in a continuous phase.

[0011] The topical composition may comprise less than (or from 0.0001% to) 10% Callicarpa extract by weight of the composition (e.g, less than 5% Callicarpa extract by weight of the composition, less than 2% Callicarpa extract by weight of the composition, less than 1% Callicarpa extract by weight of the composition, less than 0.5% Callicarpa extract by weight of the composition, less than 0.2% Callicarpa extract by weight of the composition, less than 0.1% Callicarpa extract by weight of the composition, less than 0.01% Callicarpa extract by weight of the composition). In various embodiments, the Callicarpa extract contains more than 90% (e.g., more than 95%, more than 99%) water and / or butylene glycol by' weightof the Callicarpa extract. In some embodiments, the weight ratio of rhapontigenin to Callicarpa extract is from 1 : 1 to 10: 1 (e.g, 2: 1 to 8: 1, 3: 1 to 5: 1, 4: 1).

[0012] The topical composition may comprise nicotinamide mononucleotide. For example, the topical composition may comprise less than (or from 0.0001% to) 10% nicotinamide mononucleotide by weight of the composition (e.g. , less than 5% nicotinamide mononucleotide by weight of the composition, less than 2% nicotinamide mononucleotide by weight of the composition, less than 1% nicotinamide mononucleotide by weight of the composition, less than 0.5% nicotinamide mononucleotide by weight of the composition, less than 0.2% nicotinamide mononucleotide by weight of the composition). In various embodiments, the rhapontigenin (or said extract) is present in a coated liposome and said nicotinamide mononucleotide is present in a continuous phase.

[0013] The topical composition may comprises less than (or from 0.0001% to or from 0.001% to or from 0.01% to) 10% rhapontigenin by weight of the composition (e.g, less than 5% rhapontigenin by weight of the composition, less than 2% rhapontigenin by weight of the composition, less than 1% rhapontigenin by weight of the composition, less than 0.5% rhapontigenin by weight of the composition, less than 0.2% rhapontigenin by weight of the composition, less than 0.05% rhapontigenin by weight of the composition, less than 0.1% rhapontigenin by weight of the composition, less than 0.01% rhapontigenin by weight of the composition. 0.001% to 0.006% by weight of the composition, 0.004% by weight of the composition).

[0014] Typically, the topical compositions are formulated for del i \ erx to the hair or to the skin surrounding the hair. For example, the topical composition is a shampoo, conditioner, gel, mousse, lotion, cream, serum, or pomade. In some embodiments, the composition is formulated for deliver)’ to the hair or scalp.

[0015] The topical compositions of the present disclosure may comprise: a) rhapontigenin or a derivative thereof (e.g, from 0.001% to 1%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1% by weight of the composition); b) Callicarpa extract (e.g., from 0.0001% to 1%, from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%. from 0.1% to 1%, from 0.0001% to 0.5% by weight of the composition); and one or more topically acceptable excipients. The topical compositoin may be a hair care composition.

[0016] The topical composition may comprise: a) Rheum rhaponticum root extract (e.g, from 0.001% to 1%, from 0.001% to 0.02%, from 0.01% to 0.1%. from 0.1% to 1%, from 0.0025% to 0.015%, 0.010%, by weight of the composition); b) Callicarpa Japonica fruit extract (e.g., from 0.0001% to 1%. from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1%, from 0.0001% to 0.5%); and one or more topically acceptable excipients. In various embodiments, the topical composition is a hair care composition.

[0017] Topical compositions are provided which may comprise coated liposomes dispersed in a continuous (e.g., aqueous phase) wherein: the coated liposomes are cyclodextrin and / or phospholipid liposomes comprising rhapontigenin or a derivative thereof (e.g., from 0.001% to 1%, from 0.001% to 0.01%, from 0.01% to 0. 1%, from 0.1% to 1% by weight of the composition) coated with a modified starch (e.g., sodium starch octenyl succinate); and the continuous phase comprises a Callicarpa extract and / or nicotinamide mononucleotide.

[0018] Exemplary descriptions of active content in the compositions of the present disclosure may be found in Table 1Table 1

[0019] Methods for promoting hair growth and / or otherwise improving keratin fibers in a subject are provided. These methods comprise administering the topical compositions of thepresent disclosure to a subject. In various implementations, the topical composition is administered to the scalp, face, or hair of the subject. In some embodiments, the topical composition is administered more once a week or more (e.g., daily, twice a week, every other day).

[0020] Methods for inducing proliferation of hair follicle dermal papilla cells are also provided comprising contacting a population of hair follicle dermal papilla cells with the topical composition according to any one of claims 1-32 to induce proliferation of the hair follicle dermal papilla cells. The method may be in vitro, in vivo, or ex vivo. The compositions may be characterized such that the number of hair follicle dermal papilla cells after proliferation is from 25% to 100% greater (e.g., 50% to 100% greater, 75% to 100% greater) than the number of hair follicle dermal papilla cells in the population.BRIEF DESCRIPTION OF FIGURES

[0021] FIG. 1 (FIG. 1A-D) provide the results of the Human Hair Follicle Dermal Papilla Cell (HFDPC) proliferation assay for individual administration of test compositions. Minoxidil (positive control), finasteride, poliumoside, and rhapontigenin are provided in FIG. 1A, minoxidil, salvionic acid A. engeletin, farrerol, and liquiritigenin are provided in FIG. IB, minoxidil and nicotinamide mononucleotide are provided in FIG. 1C, and minoxidil, corilagin, helichry setin, didymin, and 9-O-methylnissolin-3-O-glucoside are provided in FIG. ID.

[0022] FIG. 2 (FIG. 2A-F) provide the results of the Human Hair Follicle Dermal Papilla Cell (HFDPC) proliferation assay for combination administration of test compositions involving 1 pg / mL rhapontigenin. Combination treatment with polyphenol rich Calicarpa jciponica extract (Japanese Beautv Berry (JBB) polyphenols) is provided in FIG. 2A, combination treatment with salvianolic acid A is provided in FIG. 2B, combination treatment with engeletin is provided in FIG. 2C, combination treatment with farrerol is provided in FIG. 2D, combination treatment with liquiritigenin is provided in FIG. 2E. and combination treatment with nicotinamide mononucleotide (NMN) is provided in FIG. 2F.DETAILED DESCRIPTION

[0023] Detailed embodiments of the present disclosure are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the disclosure that may be embodied in various forms. In addition, each of the examples given in connection with the various embodiments of the disclosure is intended to be illustrative, and not restrictive.

[0024] All terms used herein are intended to have their ordinary meaning in the art unless otherwise provided. All concentrations are in terms of percentage by weight of the specified component relative to the entire weight of the topical composition, unless otherwise defined.

[0025] As used herein, "a” or “an” shall mean one or more. As used herein when used in conjunction with the word “comprising,” the words “a” or “an” mean one or more than one. As used herein “another” means at least a second or more.

[0026] As used herein, all ranges of numeric values include the endpoints and all possible values disclosed between the disclosed values. The exact values of all half integral numeric values are also contemplated as specifically disclosed and as limits for all subsets of the disclosed range. For example, a range of from 0.1% to 3% specifically discloses a percentage of 0.1%, 1%, 1.5%, 2.0%, 2.5%, and 3%. Additionally, a range of 0.1 to 3% includes subsets of the original range including from 0.5% to 2.5%, from 1% to 3%, from 0.1% to 2.5%, etc. It will be understood that the sum of all weight % of individual components will not exceed 100%.

[0027] By “consist essentially” it is meant that the ingredients include only the listed components along with the normal impurities present in commercial materials and with any other additives present at levels which do not affect the operation of the embodiments disclosed herein, for instance at levels less than 5% by weight or less than 1% or even 0.5% by weight.

[0028] The term “keratin fiber” typically refers to any hair of the body, including hair of the scalp, eyelashes, hair of the face (e.g., moustache, beard, eyebrows), and the like.

[0029] Typically, the compositions of the present disclosure include at least one plant extract that includes rhapontigenin. For example, the plant extract may be an extract from the genus Rheum such as Rheum acuminatum, Rhum alexandrae, Rhuem austral. Rheum compactum, Rheum cordatum, Rheum coreanum, Rheum darvasicum, Rheum delavayi. Rheum fedtschenkoi, Rhum forrestii, Rheum globulosum, Rhum hissaricum, Rheum hotaoense, Rheum x hybridum, Rhum inopinatum, Rheum khorasanicum, Rheum kialense, Rheum lacinatum, Rheum lhasaense. Rheum likiangense, Rheum lucidum, Rheum macrocarpum, Rheum maculatum, Rhum maximowiczii, Rhum moorcroftianum. Rheum nanum. Rheum nyeshabourense, Rheum nobile, Rhum officinale, Rheum palaestinum, Rheum palmatum, Rheum persicum. Rheum platylobum, Rheum przewalskyi, Rheum pumilum, Rheum raceferum, Rheum reticulatum, Rheum rhabarbarum, Rheum rhaponticum, Rheum rhizostachyum, Rheum rhoboideum, Rheum ribes, Rheum spicifiorme. Rheum subacaule, Rheum sublanceolatum,Rheum x svetlanae, Rheum tanguticum, Rheum tataricum. Rheum tibeticum, Rheum turkestancium, Rheum univerve, Rheum webbianum, Rheum wittrockii, or Rheum yunnanense .The topical compositions may include one or more other (or additional) plant extracts, typically plant extracts comprising a polyphenol such as poliumoside. For example, the topical composition may comprise an extract from the genus Callicarpa. In some embodiments, the composition comprises an extract from the species Callicarpa aculeolaia. Callicarpa acuminata, Callicarpa acutidens, Callicarpa acutifolia, Callicarpa albidotomentella, Callicarpa alongensis, Callicarpa americana. Callicarpa ampla, Callicarpa angusta, Callicarpa angustifolia, Callicarpa anisodonta, Callicarpa anisophylla, Callicarpa anomala, Callicarpa apoensis, Callicarpa arborea, Callicarpa areolata, Callicarpa argentii, Callicarpa badipilosa, Callicarpa barbata, Callicarpa basilanensis , Callicarpa basitruncata, Callicarpa baviensis, Callicarpa bicolor, Callicarpa bodinieri, Callicarpa bodinieroides, Callicarpa borneensis, Callicarpa bracteata. Callicarpa brevipes. Callicarpa brevipetiolata. Callicarpa brevistyla, Callicarpa bucheri, Callicarpa candicans, Callicarpa cathayana, Callicarpa caudata, Callicarpa cinnamomea, Callicarpa collina, Callicarpa coriacea, Callicarpa crassinervis, Callicarpa cubensis. Callicarpa cuneifolia. Callicarpa denticulata, Callicarpa dentosa, Callicarpa dichotoma, Callicarpa dolichophylla, Callicarpa endertii, Callicarpa erioclona, Callicarpa erythrosticta, Callicarpa fasciculiflora, Callicarpa ferruginea, Callicarpa flavida, Callicarpa floccosa, Callicarpa fulva, Callicarpa fulvohirsuta, Callicarpa furfuracea, Callicarpa gibaroana, Callicarpa giraldii, Callicarpa glabra, Callicarpa glabrifolia. Callicarpa gracilipes, Callicarpa grandiflora, Callicarpa grisebachii, Callicarpa havilandii. Callicarpa heterotricha, Callicarpa hispida. Callicarpa hitchcockii, Callicarpa homoeophylla, Callicarpa hungtaii, Callicarpa hypoleucophylla, Callicarpa inaequalis, Callicarpa integerrima, Callicarpa involucrata, Callicarpa japonica, Callicarpa kerrii, Callicarpa kinabaluensis, Callicarpa kochiana, Callicarpa kwangtungensis, Callicarpa laciniata, Callicarpa lamii, Callicarpa lancifolia. Callicarpa leonis, Callicarpa lingh, Callicarpa loboapiculata, Callicarpa longibracteata, Callicarpa longifolia, Callicarpa longipes, Callicarpa longipetiolata, Callicarpa luteopunctata, Callicarpa macrophylla, Callicarpa madagascariensis, Callicarpa magnifolia, Callicarpa maingayi, Callicarpa membranacea, Callicarpa mendumiae, Callicarpa micrantha, Callicarpa moana, Callicarpa moldenkeana, Callicarpa mollis, Callicarpa nipensis, Callicarpa nishimurae, Callicarpa nudiflora, Callicarpa oblanceolata, Callicarpa oligantha, Callicarpa oshimensis, Callicarpa pachyclada, Callicarpa paloensis, Callicarpa parvifolia, Callicarpa pauciflora, Callicarpapedunculata, Callicarpa peichieniana, Callicarpa pentandra. Callicarpa petelotii, Callicarpa phuluangensis . Callicarpa pilosissima. Callicarpa pingshanensis, Callicarpa platyphylla, Callicarpa plumose. Callicarpa prolifera, Callicarpa pseudorubella, Callicarpa pseudoverticillata, Callicarpa psilocalyx, Callicarpa pullei, Callicarpa quaternifolia, Callicarpa ramiflora, Callicarpa randaiensis, Callicarpa remotiflora, Callicarpa remotiserrulata, Callicarpa resinosa, Callicarpa reticulata, Callicarpa revoluta, Callicarpa ridleyi. Callicarpa roigii, Callicarpa rubella, Callicarpa rudis, Callicarpa ruptofoliata. Callicarpa saccata, Callicarpa salicifolia, Callicarpa scandens, Callicarpa selleana, Callicarpa shaferi, Callicarpa shikokiana, Callicarpa x shirasawana, Callicarpa simondii, Callicarpa siongsaiensis , Callicarpa sordida, Callicarpa stapfii, Callicarpa subaequalis , Callicarpa subalbida, Callicarpa subglandulosa, Callicarpa subintegra. Callicarpa subpubescens , Callicarpa superposita, Callicarpa surigaensis, Callicarpa takakumensis, Callicarpa teneriflora, Callicarpa thozetii, Callicarpa tikusikensis , Callicarpa tingwuensis, Callicarpa toaensis, Callicarpa tomentosa, Callicarpa x tosaensis, Callicarpa vansteenisii, Callicarpa vestita, Callicarpa woodii, Callicarpa wrightii, or Callicarpa yunnanensis .

[0030] The plant materials may be in any form including, but not limited to, the whole plant, a dried plant, a ground plant, or parts thereof, including but not limited to, seeds, needles, leaves, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, flowers, and meristems, or components and / or constituents found in, or isolated from, the natural plant material, and / or portions of the plant, or any combinations thereof. In one embodiment, the natural plant material is in the form of an extract derived from the whole plant or from a select portion of the plant, such as the leaves of the plant. It is to be understood that "natural plant materiak’ also includes an ingredient, component, constituent, or extract derived from the natural plant material. Specifically, the botanical component is derived from raw materials collected from the plants, which may contain the desired constituent(s), such as seeds, needles, leaves, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, organs and organ systems, and meristems. In certain embodiments, the raw materials collected from the plants are ground to small particle sizes. In addition, the raw materials may be dried to reduce water content. The raw materials may be dried by a number of different means, such as, for example, air-dried, oven-dried, rotary evaporated under vacuum or lyophilized.

[0031] The extract of the above-noted plants may be obtained by distilling the raw materials with a stripping agent. The stripping agent may be a liquid that is miscible, immiscible, or partially miscible with the desired extract from the plants. Suitable stripping agents include,but are not limited to, water; alcohols (such as methanol, ethanol, propanol, butanol and the like); glycols; ethers (such as diethyl ether, dipropyl ether, and the like); esters (such as butyl acetate, ethyl acetate, and the like); ketones (such as acetone, ethyl methyl ketone, and the like); dimethyl sulfoxide; acetonitrile; other organic solvents; and combinations thereof. In one embodiment, the stripping agent is immiscible with the desired extract (e.g., essential oil) from the plant. In one embodiment, the stripping agent is water. More In one embodiment, the extract is obtained by steam distillation. The extract (e.g., essential oil) may be collected by phase separation from the stripping agent. It is believed that the stripping agent increases the overall vapor pressure of a distillation system for obtaining an extract and thereby reducing the boiling point of the desired product, the extract.

[0032] In other embodiments, the botanical component may be in the form of an extract obtained by solvent extraction. In one embodiment the botanical material is obtained by organic solvent extraction(s) mixtures of organic solvents with water. Briefly, the solvent extraction method involves washing and extracting the raw materials, which may be whole or ground into small particle sizes, using an solvent which may be an organic solvent, water, or a combination thereof. In some embodiments, the solvent may be an alkaline solvent, such as a water and inorganic hydroxide e.g., Ca(OH)2) mixture. Non-limiting examples of organic solvents include methanol, ethanol, isopropanol, dichloromethane, chloroform, hexane, xylene, and petroleum ether. An extracting machine may be used for organic solvent extraction as is well known in the field. The raw materials are pushed in the extracting machine by a thruster, which slowly moves the plant raw materials forward. Organic solvent (e.g., methanol, ethanol) may be added into the machine through a solvent inlet at the top of a waste discharge outlet. Due to the difference in gravity and equilibrium, the solvent flows toward the raw material inlet, soaks the materials and flows out from the opposite side of the solvent inlet. Since the plant materials and the solvent move in opposite directions against each other, the plant materials are constantly immersed in a solution that contains a low-concentration of extract. As a result of equilibrium, high yield of plant constituent(s) may be achieved by continuously extracting the plant material against the low-concentration solution.

[0033] An extraction time suitable to extract the plant constituents is used, typically between 1-10 hours is suitable, in one embodiment is between 2-8 hours, in one embodiment is between 3-6 hours. The temperature of extraction is between 30° C-100° C. in one embodiment between 40° C-70° C. and in one embodiment between 50° C-60° C. The collected extract is then fine filtered to remove debris, and may be used directly, or is concentrated, for example by distillingthe solvent or by other conventional processing. The solution of extract actives may be rotary evaporated under vacuum or lyophilized. A typical extract's actives content is above 25%, in one embodiment above 50%, and the extract can also be provided an essential oil or a concentrate having a semi-solid or solid consistency.

[0034] Similarly, aqueous-organic solvent extraction involves initially collecting raw materials from the plants, which may be whole or ground into small particle sizes. The ground plant material is soaked in aqueous solution that is acidic or alkaline, depending on the solubility and stability of the desired extract under acidic or alkaline (basic) conditions. For extraction under acidic conditions, an acid such as hydrochloric acid or sulfuric acid is added to water, e.g., at a concentration of 3% (w / v). For extraction under alkaline conditions, an alkali such as sodium hydroxide, sodium carbonate, calcium hydroxide is added to water. The extraction time and temperature of extraction are typically similar to that used in the organic solvent extraction method described above. The extract is then collected and fine-fdtered to remove debris. Alkaline agents (e.g., ammonia) or acidifying agents (e.g, sulfuric acid) may be added to the extract to neutralize the solution by adjusting the pH, depending on the acidity7or alkalinity of the collected extract. The aqueous extract may be used directly, concentrated or dried. Alternatively, organic solvent may then be added to the neutralized solution to transfer the extract from an aqueous phase to an organic phase. Examples of such organic solvents include, but are not limited to, ethanol, isopropanol, butanol, pentanol, hexanol and xylene. The extract comprising the transferred extract actives dissolved in organic solvent may be used directly as an essential oil or a concentrate, or dried by a number of different means, such as, for example, air-dried, oven-dned, rotary evaporated under vacuum or lyophilized to a semisolid or solid consistency.

[0035] In one embodiment, the efficacy of the extract of the present invention may be optimized by adjusting the relative presence of various extract fractions present in the extract by, for example, altering the identity' and / or relative proportions of the solvents used in the extraction process. In another embodiment, the temperatures and / or other conditions utilized in solvent extraction may be optimized so as to yield an effective extract.

[0036] The compositions of the invention may also optionally comprise one or more antioxidants, which can protect against free radicals that can contribute to keratin fiber loss, as well as protect keratin fibers from the drying effects of the sun and other photodamage. Examples of useful antioxidants include, but are not limited to ginkgo-biloba. beta carotene, green tea, ascorbic acid and derivatives thereof, such as. for example sodium ascorbylphosphate and magnesium ascorbyl phosphate, camosic acid (rosemary ), resveratrol and derivatives thereof, N-acetyl cysteine, and BHT and BHA. Green tea, as well as other antioxidants, may be in the form of an extract or any other known form of the antioxidant, as well as the active components of extracts, e.g., catechin based flavonoids such as EGCG (epigallcatechin gallate) from green tea, rosemary extract, and the like. Antioxidants, if used, will be present in an amount of from 0.0001 to 10%, based on the total weight of the composition.

[0037] The compounds for use in the invention are used in the form of a topical formulation for application to any area of the body that contains keratin fiber follicles. The vehicle in which the active ingredients are applied can be in any form typically used for application to keratin fibers. The compositions of the invention may be applied to keratin fibers that are either wet or dry.

[0038] The compositions will typically include a topically acceptable vehicle, by which is meant a diluent, solvent, or carrier that is generally safe and non-irritating when applied to a human integument, in particular, for application to hair or scalp.

[0039] It is contemplated that any cosmetically acceptable vehicle may be useful (added to the extract and / or to the composition itself). The vehicle may comprise water and / or hydrophobic and / or hydrophilic organic solvents. Suitable hydrophilic solvents include but are not limited to, alcohols and poly ols (e.g., ethanol, isopropanol, propanol, butanol, benzy l alcohol, phenylethyl alcohol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, glycerin, etc.), carbitol, glycol ethers such as, for example, ethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monobutyl ether, dipropylene glycol and diethylene glycol alkyl ethers such as, for example, diethylene glycol monoethyl ether or monobutyl ether, and any combinations thereof . Water is an exemplary vehicle component.

[0040] Typically, the amount of water in the vehicle is 5% to 100%, more typically from 20% to 99% by weight, or from 50% to 97% by weight. The vehicle may also comprise a hydroalcoholic solution, which includes an amount of a lower alcohol (e.g, ethanol, isopropanol) in combination with water. For example, the vehicle may comprise from 20% to 99% by weight water, and from 1% to 80% by weight alcohol, typically ethanol or isopropanol.

[0041] The vehicle may also be in the form of an emulsion. Emulsions include oil-in-water, silicone-in-water, water-in-oil, water-in-silicone, and the like. When formulated as an emulsion, an emulsifier is typically included.

[0042] The compositions may be applied as a shampoo, a hair rinse, a hair conditioner, a pomade, a hair gel, a mousse, a hydroalcoholic tonic, a cream, a spray, an emulsion, a liquid, or any other form that is normally used for treatment of keratin fibers.

[0043] Suitable other ingredients that may be optionally included in the compositions of the invention include, but are not limited to, amino acids, antioxidants, colorants, emollients, emulsifiers, excipients, fillers, humectants, minerals, photostabilizing agents (e.g., UV absorbers), stabilizers, staining agents, surfactants, viscosity and / or rheology modifiers, vitamins, waxes and mixtures thereof. It is contemplated that the compositions of the present invention can also include anti-dandruff, deodorant, sunscreen and / or antiperspirant ingredients. The formulations may contain suitable adjuvants such as organic solvents, humectants, emollients, rheology modifiers, stabilizers, and thickeners, gelling agents, waxes, film forming polymers, shine agents, detanglers, skin and hair conditioning agents, emulsifiers, anti-oxidants, botanicals, peptides, amino acids, sunscreens, colorants, fillers, vitamins and minerals, fragrances, pH adjusters, chelating agents, preservatives, and the like. The compositions may have the form of a mascara, shampoo, hair rinse, hair conditioner, pomade, hair gel, mousse, hydroalcoholic tonic, cream, spray, emulsion, serum / liquid, or any other form that is suitable for treatment of keratin fibers. The compositions may further comprise additional bioactive agents, such as anti-dandruff agents, antiperspirants, retinoids, alphahydroxy acids (e.g., glycolic acid), oxa-acids, salicylic acid, anti-acne agents, ascorbic acid, etc. The additional hair growth agents, bioactive agents, and adjuvants may be present, individually or in the aggregate in amounts from 0.0001% to 25%, typically from 0.001% to 10%, based on the total weight of the composition. The vehicle may comprise from 1% to 99.9%, typically from 5% to 95% by weight of the composition.

[0044] The compositions according to the invention may be formulated in a variety' of forms for topical application and will typically independently comprise from 0.00001% by weight to 20% by weight of one or more of the active agents (e.g., rhapontigenin, Rheum extract, Callicarpa extract). More typically, the active will be present from 0.0001% by weight to 10% by weight, or from 0.0001% by weight to 5% by weight of the composition or from 0.0001% to 1% by weight of the composition. In one embodiment, the active will be present in an amount from 0.001% by weight to 1% by weight or from 0.0001% by weight to 0.1% by weightof the composition. The compositions may comprise an effective amount of the actives, by which is meant an amount which may be sufficient to stimulate hair matrix cell proliferation, keratin production, and / or proliferation of hair follicle dermal papilla cells. In other embodiments, the amount of active thereof will be sufficient to promote hair grow th and / or thicken the hair shafts and / or strengthen hair when topically applied to the hair and / or scalp daily (e.g, for a period of at least four, or at least eight weeks).

[0045] The compositions of the present invention can be incorporated into all types of vehicles. Non-limiting examples of suitable vehicles include emulsions (e.g., water-in-oil, ■water-in-oil-in-water, oil-in-water, oil-in-water-in-oiL oil-in-water-in-silicone emulsions), creams, lotions, solutions (both aqueous and hydro-alcoholic), anhydrous bases (such as lipsticks and powders), gels, and ointments or by other method or any combination of the forgoing. In certain aspects, it is important that the concentrations and combinations of the compounds, ingredients, and agents be selected in such a way that the combinations are chemically compatible and do not form complexes which precipitate from the finished product.

[0046] It is also contemplated that ingredients identified throughout this specification, including but not limited to rhapontigenin, Rheum extracts, Callicarpa extracts can be individually or combinatorially encapsulated for delivery to a target area such as skin or hair. Non-limiting examples of encapsulation techniques include the use of liposomes, vesicles, and / or nanoparticles that can be used as delivery vehicles to deliver the ingredient as disclosdin U.S. Pat. No. 6,387,398; U.S. Pat. No. 6,203,802; and U.S. Pat. No. 5,411,744 each of which are herein incorporated by reference in their entirety’.

[0047] In various implementations the liposome which may be formulated in, for example, an emulsion such as an oil-in-water emulsion, serum, or cream, is a coated liposome. The coated liposome may be formed from a mixture of

[0048] The cyclodextrin (CD) may be a cyclic oligomer of glucose having, for example, six (a-cyclodextrins. a-CDs), seven [3-cyclodextrins. 0-CDs), or eight (y-cyclodextrins, y-CDs) glucose units. Cylclodextrins include a hydrophobic interior portion (cavity) capable of binding hydrophobic molecules. In embodiments, cyclodextrins of the present disclosure include a lipophilic central cavity and a hydrophilic outer surface. Non-limiting examples of cyclodextrins which can be incorporated in the cyclodextrin-lipid complexes of the present disclosure include, but are not limited, a-cyclodextrins. Non-limiting examples of a- cyclodextrins include methyl-a-cyclodextrins (e.g., a species of a-cyclodextrins with a methylgroup or methyl groups attached to the glucose rings of a cyclodextrin, such as dimethyl-a- cyclodextrin and randomly methylated alpha cyclodextrins), sulfo-a-cyclodextrin. and hydroxypropyl-a-cyclodextrin, carboxy ethyl-a-cyclodextrin, succinyl-a-cyclodextrin, hydroxyethyl-a-cyclodextrin, ethyl-a-cyclodextrin, and n-butyl-a-cyclodextrin. In embodiments, cyclodextrins which can be incorporated in the cyclodextrin-lipid complexes of the present disclosure include, but are not limited, a-cyclodextrins, 0-cyclodextrins. y- cyclodextrins, or combinations thereof. Examples of cyclodextrins and chemically modified cyclodextrins useful in the present compositions, and particularly for the liposome or coated liposome, include alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, randomly methylated beta-cyclodextrin, sulfoxide beta-cyclodextrin, and hydroxypropyl beta- cyclodextrin.

[0049] The lipids used in the liposomes may include one or more phospholipids, including but are not limited to. phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylinositol (PI) or combinations thereof.

[0050] In some embodiments, the liposome comprises egg phospholipids, soy phospholipids, egg phosphatidylcholine (EPC), egg phosphatidylglycerol (EPG), egg phosphatidylethanolamine (EPE), egg phosphatidylserine (EPS), egg phosphatidic acid (EP A), egg phosphatidylinositol (EPI), soy phosphatidylcholine (SPC). soy phosphatidylglycerol (SPG), soy phosphatidylethanol amine (SPE), soy phosphatidylserine (SPS), soy phosphatidic acid (SPA), soy phosphatidylinositol (SPI) or combinations thereof. In another embodiments, the lipid mixture comprises dipalmitoylphosphatidylcholine (DPPC), 1,2-dioleoyl-sn-glycero- 3-phosphatidylcholine (DOPC), dimyristoylphosphatidylcholine (DMPC), dip almitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylglycerol (DOPG), dimyristoylphosphatidylglycerol (DMPG), hexadecylphosphocholine (HEPC), hydrogenated soy phosphatidylcholine (HSPC), distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), dioleoylphosphatidylethanolamine (DOPE), palmitoylstearoylphosphatidyl choline (PSPC), palmitoylstearoylphosphatidylglycerol (PSPG), monooleoylphosphatidylethanolamine (MOPE), l-palmitoyl-2-oleoyl-sn-glycero-3- phosphatidylcholine (POPC), polyethyleneglycol distearoylphosphatidylethanolamine (PEG- DSPE), dipalmitoylphosphatidylserine (DPPS), l,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), dipalmitoylphosphatidic acid (DPP A), l,2-dioleoyl-sn-glycero-3 -phosphatidic acid (DOPA),dimyristoylphosphatidic acid (DMPA). distearoylphosphatidic acid (DSPA), dipalmitoylphosphatidylinositol (DPPI), l,2-dioleoyl-sn-glycero-3-phosphatidylinositol (DOPI), dimyristoylphosphatidylinositol (DMPI), distearoylphosphatidylinositol (DSPI), or combinations thereof.

[0051] In particular embodiments, the liposome (which may contain an extract or active compound of the present disclosure such as rhapontigenin or a Rheum extract) may comprise one or more phospholipids and one or more cyclodextrins.

[0052] The liposome may be coated with a compound providing a hydrophobic medium stabilizing agent such as modified natural polymers. For example, the modified natural polymers may be generally regarded as safe. The coating may be wheat protein isolates, vital wheat gluten, gelatin, casein, caseinates, soy protein isolates, maltodextrin, high gluten content flours, durum wheat or semolina, pregelatinized or modified starch, com flour, wheat flour, rice flour, barley flour, oat flour, and rye flour, and whey protein isolates. In particular embodiments, the coating may comprise a modified starch such as starch sodium octenyl succinate.

[0053] Methods for forming the compositions of the present application are also provided. The method may comprise the addition any indicated component and suitable mixing (e.g., until a homogeneous mixture is created). In some embodiments, the method may comprise: a) combining one or more liposome forming components (e.g., cyclodextrin) with an active (e.g., rhapontigenin) and / or extract of the present disclosure (e.g., Rheum extract) optionally in an aqueous solvent; b) optionally subjecting the combined mixture to homogenization (e g., high-pressure homogenization); c) optionally adding a second liposome forming component (e.g., phospholipids) and / or a coating (e.g., modified starch such as sodium starch octenylsuccinate) to the homogenized mixture; d) optionally subjecting the mixture to a second homogenization procedure (e.g., high-pressure homogenization); and e) optionally mixing a second aqueous composition containing a second active (e.g., Ccillicarpci extract, nicotinamide mononucleotide) to the liposome formulation.In these systems one active may be present in the liposome (e.g., rhapontigenin, Rheum extract) and one active may be present in the continuous phase (e.g., Callicarpa extract).

[0054] In another aspect, methods are provided for improving health and appearance of human keratin fibers and / or promoting growth of human keratin fibers and / or thickening the shaft of keratin fibers and / or strengthening human keratin fibers. In some embodiments, the keratin fibers are eyelashes. In some embodiments, the keratin fibers are hair of the scalp. In some embodiments, the keratin fibers are hair of the face (e.g. , moustache or beard). In some embodiments, the keratin fibers are hair of the scalp that has been damaged, for example, by sun damage, chlorine and other chemicals from swimming pools, bleaching or lightening agents (e.g., peroxide), and / or treatment with colorants (e.g., reactive dyes, such as two-part oxidative dyes). The actives are typically applied to human keratin fibers and / or to the follicles and / or to the skin surrounding the follicles (e.g., the eyelid or the scalp). Application is typically at least once daily for as long as necessary to achieve the desired results (e.g.. at least one, two, four, eight, twelve weeks or longer).

[0055] Frequency of application of the compositions to the desired area of keratin fiber follicles may occur at least once a week. The compositions of the invention may also be applied three to five times a week, or they may be applied daily. The compounds of the invention maybe applied once daily, twice daily, three times daily, four times daily, five times daily, or more, as needed to obtain the desired result.

[0056] The timing of its usage will be determined according to the cause of the keratin fiber loss, thinning, or poor appearance; a temporary keratin fiber loss, due for example to drug exposure, may require only regular use on a temporary basis, until after the removal of the harmful stimulus and subsequent re-growth of hair to a satisfactory- level. However, for pattern or age-related baldness or thinning keratin fibers, where the causative agent is a constant presence, a chronic application is contemplated, e.g. the application will be regularly applied over the lifetime of the user. The period of topical application may7be over the lifetime of the user such as for a period of at least one week to eight weeks, or from three months to twenty years, or from six months to ten years, or from one year to five years, or for as long as the user is interested in treating their keratin fibers. The period of topical application may also be from two months to three months, three months to one year, or from one month to two years. The amount of product applied will vary7according to the form of the product but will normally be in accordance with the industry accepted methodology for the use of a product of the same type. A representative application procedure will involve application of the formulation to thearea in need of treatment once or twice a day and leaving the formulation in place for a period of between several minutes to several hours.

[0057] In particular embodiments, embodiments, the compositions are applied to scalp or to the hair of the scalp. The compositions of the present disclosure may be used for the promotion of hair growth and / or improving keratin fibers in a subject. In some embodiments, the topical compositions may be used for preparation of a medicament for the promotion of hair grow th and / or improving keratin fibers in a subject.

[0058] Non-limiting examples of improvements in keratin fibers imparted by use of the compositions of the invention comprise:(a) improvement in root sheath thickness;(b) improvement in fiber anchorage;(c) decrease in keratin fiber loss;(d) reduction in keratin fiber breakage;(e) increase in keratin fiber strength;(1) improvement in keratin fiber growth rate;(g) improvement in shine;(h) improvement in the number of visible keratin fibers;(i) improvement in keratin fiber length; and / or(j) improvement in keratin fiber volume.EXAMPLES

[0059] The following examples illustrate specific aspects of the instant description. The examples should not be constmed as limiting, as the example merely provides specific understanding and practice of the embodiments and its various aspects.

[0060] Example 1 : Rheum rhaponticum Root Extract

[0061] Extracts of Rheum rhaponticum roots were prepared and characterized with high- performance liquid chromatography (HPLC). Rheum rhaponticum roots were macerated and placed in extraction solvents for 15 hours at 40 °C. Tested extraction solvents were water / Ca(OH)2 having a weight ratio of H2O:Ca(OH)2 of from 95:5 to 80:20; and methanol / water having a weight ratio of CH3OH H2O of 70:30.The water / Ca(OH)2 extract was further acidified by adding an acid, such as an organic acid or HC1. Following extraction, the solid material was removed and the liquid extract was dried (e.g., to form a crystalline powder) and subsequently analyzed with HPLC to characterize the extracts. Based on HPLC, the extracts had from 30%-60% rhapontigenin-glucosides by weight and less than 0.5% anthraquinones by weight. Table 2 provides the ratio of herbal drug to extract (the amount of roots required for the amount of final extract, for example, a drug / extract ratio of 30: 1 means 30kg of roots need to be extracted for 1kg of extract) for each extract.Table 2

[0062] Example 2: Coated Liposome Formation

[0063] Hydroxypropyl-P-cyclodextrin was dissolved in water under stirring. Rheum rhaponticum extract was added and stirred under identical conditions until the extract was dissolved. Subsequently, soy phospholipids, glycerin, and pentylene glycol were added and stirred until a homogenous mixture was obtained. The homogenous mixture was that treated with high-pressure homogenization to form liposomes comprising extract / phospholipids / glycerin / pentylene glycol. The homogenization (for liposome) was done at 600-800bar for 3 cycles.

[0064] Mixtures of sodium starch octenylsuccinate was then added under stirring to coat the liposomes. Each mixture was formed of one of three different sodium starch octenylsuccinates each having different viscosities. As shown by 10% w / w of each starch (20g of each starch in 180ml distilled w ater) on a Brookfield DVPlus viscometer at 20°C with Spindle LV-1, Starch 1 had a viscosity of 3-8 mPas, Starch 2 had a viscosity of 50-75 mPas. and Starch 3 had viscosity of 8000-15000 mPas. Following coating, the coated liposome compositions weresubjected to another high-pressure homogenization. This homogenization step was carried out at lower pressure (400bar) for 3 cycles.

[0065] The liposomal compositions formed had the components as indicated in Table 3.Table 3As measured by HPLC, the rhapontigenin-glucoside content of the liposomal composition is typically 0.2%-0.3% by weight of the composition. The coated liposomes have an average particle size (Z-average as measured by dynamic light scattering using a Malvern Panalytics Zetasizer 173° refractive angle) of between 100-200 nm and a polydispersibility’ index (PDI) of between 0.2 and 0.3.

[0066] Example 3: Penetration Enhancement Assay

[0067] A penetration enhancement assay was performed to compare of various serums to the coated liposomes similar to as described in Example 2. Serum formulations were prepared for penetration testing. To prepare these serums, pentylene glycol was triturated with the gelling agent hydroxypropyl methylcellulose (I4PMC, 3800-5300 mPas, Carl Roth) in a mortar. The water content and the native extract or coated liposome were then mixed and homogenized with the triturated pentylene glycol / HPMC while stirring in the mortar. The serums were triturated until no lumps were visible and a uniform consistency was achieved. Serums were prepared containing1 % Rheum rhaponticum extract native;0.05% Rheum rhaponticum extract in coated liposomal form,0.05% Rheum rhaponticum in hydroxypropyl-P-cyclodextrin liposomes, and0.05% Rheum rhaponticum in phospholipid liposomes.Table 4 provides the components for each of the serum concentrations tested.Table 4In the coated liposomes, a serum was prepared with each individual starch (as opposed a combination of starches as described in Example 2).

[0068] The serum formulations were analyzed to determine skin penetration in a vertical amber glass Franz diffusion cell (PermeaGear 6 position Franz cell stirrer containing 6 jacketed Franz cells 11.28mm diameter, 8 mL volume, 1.00 cm2membrane area). The diffusion cell was contained in a water bath heated to 32°C and the lower compartment of the cells contained 0.1% Tween 80 in HPLC grade water with the PermeaPad Skin membrane separating the upper and lower compartments. After applying each serum formulation to the upper compartment, the sampling arm and upper compartments were sealed with parafilm. Tests were carried out in triplicates and the average values were calculated.

[0069] After Ih 2h, 3h, 4h and 24h, 300pL were withdrawn from the lower compartment using a syringe and replaced with fresh, pre-tempered solution (0.1% Tween80 in HPLC grade water). The samples were analyzed undiluted by HPLC (Agilent 1260 Infinity II DAD). The concentration (C) in the lower compartment in pg / mL was determined cumulatively (taking into account the 300 pL samples withdrawal at each time interval).

[0070] The cumulative final concentration in the lower compartment after 24 h was particularly relevant and w as used to calculate the apparent permeability (Papp). This value is a concentration-independent measure of permeability, w hich indicates that the permeability' of the formulations can also be compared at different active ingredient concentrations. Papp was calculated Papp = (Volume in ml / Area x time in sec) x (Drug concentration lower compartment / Initial drug concentration upper compartment). Table 5 provides the concentration (C) andApparent Permability (Papp) for each tested formulation. All values are statistically significant (p< 0.05) with respect to control (native Rheum rhaponticuni).Table 5

[0071] As can be seen, coated liposomes containing hydroxypropyl-P-cyclodextrin shows a statistically significant increase which is further enhanced when low-viscosity sodium octenylsuccinate starches are used to coat the liposome (e.g., starches 1 and 2 and a combination thereof). Liposomes formed starches 1 and 2 provided statistically significant increased Papp with respect to starch 3 formed liposomes as well.

[0072] The control samples containing only hydroxylpropyl-P-cyclodextrin or phospholipids in the identical concentration show only a slight increase in permeability (factor 1.5 for hydrxypropyl-P-cyclodextrin and factor 1.2 of phospholipids). This suggests specific overadditive synergy' between the excipients when they are processed in the form of the coated liposomes as described.

[0073] The order of preparation (pre-dissolution of the active ingredient in the cyclodextrin solution, subsequent addition of the phospholipids and preparation of liposomes, subsequent coating) as well as the final particle size (e.g., 100-200 nm such as 125 nm -175 nm) and the poly dispersibility index (e.g., between 0.2 and 0.3) are also important and may have effect on the system and product stability and permeability.

[0074] These results also suggest optimum ratios for various components in the coated liposomes. For example, the ratio of rhapontigenin to cyclodextrin may be 1 :50-1:75 and / or the ratio of rhapontigenin to phospholipid may be 1: 10-1: 15 and / or the ratio of sodium starch octenylsuccinate (e.g., low viscosity starch such as starch viscosity of less than 500 mPas or less than 200 mPas or less than 100 mPas or less than 75 rnPas or less than 50 mPas or less than 25 mPas or less than 10 mPas) may be from 1 :3-l :5.

[0075] Example 4: Callicarpa iaponica Fruit extract

[0076] Extracts of Callicarpa japonica fruit were prepared and the polyphenol content was determined as gallic acid equivalents via UV / VIS with either the Folin-Ciocalteu method of the liquid extract or the Folin-Ciocalteu method of the dry extract. Callicarpa japonica fruit was macerated and placed in extraction solvents (e.g., water or water / ethanol, water and at least 20% short chain alcohol) for 20 hours at 35 °C. It was identified that short chain alcohols (e.g., C1-C4 alcohols such as methanol, ethanol, propanol, isopropanol, or butanol) with more than 20% may decrease the polyphenol content of the extract.

[0077] The polyphenol content of the liquid extract was measured to be 0.015% to 0.05% (Folin-Ciocalteu method of the liquid extract) or 7.5%-25% (Folin-Ciocalteu method of the dry extract). The extracts were formulated and used subsequently as a mixture with butylene glycol and water (solid Callicarpa japonica extract was present in an amount of 0.2% by weight, buty lene glycol, added to prevent microbiological spoilage, was present in an amount of 30% by weight, and water was present in an amount of 69.8% by weight)

[0078] Example 5: Human Hair Follicle Dermal Papilla Cell (HFDPC) Proliferation Assay

[0079] Human Hair Follicle Dermal Papilla Cells (HFDPC, Promocell) were used as an in vitro test system. The cells were cultured according to manufacturer’s instructions. Briefly, HFDPC (C 12071) were culctured at 10,000 cells / cm2form passage 2 to passage 6 in 75 cm2T-flasks in Follical Dermal Papilla Cell Growth Medium (C26501, Promocell), which contains fetal calf serum, bovine pituitary' extract, bFGF and insulin, supplemented with L-Glutamine (X0550, Biowest) and 1% (w / v) penicillin / streptomycin (P / S) (L0022, Biowest). Cultures were maintained at 37°C and 5% CO2 in a humidified atmosphere and passaged at 80% confluency. HFDPCs were seeded at a density of 5000 cells / cm2in 96-well plates. After 24 hours of incubation, the cell culture medium was replaced by a new medium containing various concentrations of the test substances (six replicates per compound and concentration, n=6). The cells were further incubated for 72 hours in order to proliferate. The supernatant was removed and the remaining cells were assayed using the CyQUANT™ NF Cell Proliferation assay.

[0080] The cells were incubated with either individual substances (minoxidil (Sigma Aldrich, CAS: 38304-91-5), finasteride (Thermo Fisher Scientific, CAS: 98319-26-7), rhapontigenin (Phyproof®, CAS: 500-65-2), poliumoside (Phyproof®, CAS: 94079-87-9), salvionic acid A (Phy proof®, CAS: 96574-01-5), engeletin (Phyproof®, CAS 572-31-6),farrerol (Phyproof®, CAS: 95403-16-0), liquiritigenin (Phyproof®, CAS: 69097-97-8), corilagin (Phyroof®, CAS: 23094-69-7), didymin (Phyproof®, CAS: 14259-47-3), helichrysetin (Phyproof®, CAS: 62014-87-3), 9-O-methylnissolin-3-O-glucoside (Phyproof®, CAS: 94367-42-7)) or with a combination of rhapontigenin and either1 ) Cctllicarpa japonica polyphenol rich extract (e.g., as described in Example 4),2) salvianohc acid A,3) engeletin,4) farrerol,5) liquiritgenin, or6) nicotinamide-mononucleotide (NMN).The cell count was determined after 72 hours using a fluorescent dye (CyQUANT® NF dye). Combination testing was only performed with compounds, which exhibited cell proliferation enhancement individually.

[0081] FIGS. 1A-D provide the results of the cellular proliferation assay for single substance administration. All cell population percentages in these figures are provided in reference to the untreated vehicle control. Table 6 provides the data represented in FIGS. 1 A-D.Table 6

[0082] FIGS. 2A-F provide the results of the cellular proliferation assay for combinations of various actives with 1 pg / mL rhapontigenin. Cell population percentages in these figures are expressed relative to the 1 pg / mL rhapontigenin alone. Minoxidil at a concentration of 5 pM served as a positive control. Table 7 provides the data represented in FIGS. 2A-F.Table 7

[0083] Cell proliferation-promoting effects were observed from the single test substances minoxidil and finasteride, as well as for the polyphenols poliumoside and rhapontigenin. The other single substances (salvianolic acid A, engeletin, farrerol, liquiritegnin) exhibited proliferation promoting effects as well. Corilagin, didymin, helichiysetin, and 9-0- methylnissolin-3-O-glucoside did not show proliferation enhancing effects, with helichhry setin decreasing cell proliferation at higher concentrations.

[0084] Combination treatment of rhapontigenin and polyphenols from Callicarpa japonica extract and rhapontigenin and nicotinamide mononucleotide resulted in unexpectedly increased cellular proliferation in a statistically significant manner (0<0.05) as compared to rhapontigenin control. For example, administration of 0. 16 pg / mL poliumoside resulted in no change as compared to positive control as shown in FIG. 1 A. However, administration of 0. 158 pg / mL Japanese Beauty Berry (JBB) polyphenols, the Cctlicarpa japonica extract, with 1 pg / mL rhapontigenin resulted in increased cellular proliferation, with statistical significance,as compared to rhapontigenin alone as shown in FIG. 2A. The unexpected increase was seen across a range of rhapontigenin: JBB polyphenol weight ratios including from 20: 1 to 2: 1.

[0085] Similarly, nicotinamide (NMN) mononucleotide administration alone provided minimal, if any increase in cellular proliferation as shown in FIG. 1C. However, across all concentrations tested, NMN and rhapontigenin provided unexpectedly increased statistically significant cellular proliferation as compared to rhapontigenin administration alone.

[0086] No synergy was observed for the combination with rhapontigenin with salvianolic acid A, engeletin, farrerol, or liquiritigenin, despite those compounds showing enhancing effects individually. Combinations with salvianolic acid A at several concentrations decreased the proliferative effect afforded by rhapontigenin alone as shown in FIG. 2B.SPECIFIC EMBODIMENTS

[0087] Non-limiting specific embodiments are described below each of which is considered to be within the present disclosure.

[0088] Specific Embodiment 1. A topical composition comprising one or more topically acceptable excipients, rhapontigenin (5-[(E)-2-(3-hydroxy-4- methoxyphenyl)ethenyl]benzene-l,3-diol) and derivatives thereof and less than 5% anthranoids by weight of the rhapontigenin (e.g., a weight ratio of rhapontigenin: anthranoids of from 10: 1-5000:1. 10:1-100: 1, 100: 1-1000: 1, 1000: 1-5000: 1).

[0089] Specific Embodiment 2. The topical composition according to Specific Embodiment1, wherein the topical composition comprises an extract of a plant from the genus Rheum and said extract of Rheum provides said rhapontigenin and / or derivatives thereof.

[0090] Specific Embodiment 3. The topical composition according to Specific Embodiment2, wherein the plant is Rheum rhaponticum.

[0091] Specific Embodiment 4. The topical composition according to Specific Embodiment 2 or 3, wherein the extract of Rheum is an alcohol / water extract (e.g., lower alcohol / water such as methanol / water, ethanol / water, propanol / water, isopropanol / water, butanol / water, or combinations thereof).

[0092] Specific Embodiment 5. The topical composition according to any one of Specific Embodiments 2-4, wherein the extract is aqueous alkaline extract (e.g., a Ca(OH)2 extract).

[0093] Specific Embodiment 6. The topical composition according to any one of Specific Embodiments 2-5, wherein the extract of Rheum is a root extract.

[0094] Specific Embodiment 7. The topical composition according to any one of Specific Embodiments 1-5, wherein the rhapontigenin derivative is a glycosylated rhapontigenin.

[0095] Specific Embodiment 8. The topical composition according to Specific Embodiment 7, wherein the glycosylated rhapontigenin has the structure:wherein R1-R3 are independently selected from hydrogen and glucosyl, wherein at least one (e.g, one, two, three) of R1-R3 is glucosyl.

[0096] Specific Embodiment 9. The topical composition according to any one of Specific Embodiments 2-8, wherein said extract is complexed with cyclodextrin (e.g., hydroxypropyl cyclodextrin).

[0097] Specific Embodiment 10. The topical composition according to any one of Specific Embodiments 1 -9, wherein said rhapontigenin (or said extract) is present in a liposome (e.g. , a coated liposome).

[0098] Specific Embodiment 11. The topical composition according to Specific Embodiment 10, wherein said coated hposome is a cyclodextrin (e.g., hydroxypropyl cyclodextrin): phospholipids liposome coated with a starch such as a modified starch (e.g, a liposome coated with rhapontigenin in a weight ratio of rhapontigenin:cyclodextrin:phospholipids:modified starch of 0.1-2:50-70: 10-15: 1-7). For example, the ratio of rhapontigenin to cyclodextrin may be 1 :50-1 :75 and / or the ratio of rhapontigenin to phospholipid may be 1 :10-1: 15 and / or the ratio of sodium starch octenylsuccinate (e.g., low viscosity starch such as starch viscosity of less than 500 mPas or less than 200 mPas or less than 100 mPas or less than 75 mPas) may be from 1 : 3-1 :5.

[0099] Specific Embodiment 12. The topical composition according to Specific Embodiment 11, wherein said modified starch is sodium starch octenyl succinate.

[0100] Specific Embodiment 13. The topical composition according to Specific Embodiment 11 or 12, wherein the starch (e.g., modified starch) has a viscosity of less than (orfrom 1 mPas to) 100 mPas (e.g., less than 75 mPas, less than 50 mPas, less than 25 mPas) as measured by a 10% w / w water solution at 20°C with a Brookfield viscometer spindle LV-1.

[0101] Specific Embodiment 14. The topical composition according to any one of Specific Embodiments 10-13, wherein the liposome (e.g., coated liposome) have a Z-average particle size of from 1 0-200 nm (e.g, 125-175 nm) as measured by dynamic light scattering.

[0102] Specific Embodiment 15. The topical composition according to any one of Specific Embodiments 10-14, wherein the liposome (e.g., coated liposome) have polydispersity index of from 0.2-0.3.

[0103] Specific Embodiment 16. The topical composition according to any one of Specific Embodiments 10-15 wherein said composition comprises from 0.01% to 50% (e.g., from 0.01% to 20%. from 0.01% to 10%. from 0.01% to 5%, from 0.1% to 5%. from 0.5% to 3%, 2%) liposome (e.g., coated liposome) by weight of the composition.

[0104] Specific Embodiment 17. The topical composition according to any one of Specific Embodiments 1-16, wherein said topical composition further comprises an extract from a plant of the genus Callicarpa (e.g, the Callicarpa extract provides one or more polyphenols such as poliumoside).

[0105] Specific Embodiment 18. The topical composition according to SpecificEmbodiment 17, wherein said genus of Callicarpa is Callicarpa japonica.

[0106] Specific Embodiment 19. The topical composition according to SpecificEmbodiment 17 or 18, wherein the extract is a water extract.

[0107] Specific Embodiment 20. The topical composition according to any one of Specific Embodiments 17-19. wherein the extract is from the fruit of the plant.

[0108] Specific Embodiment 21. The topical composition according to any one of Specific Embodiments 17-20, wherein the weight ratio of the rhapontigenin or derivative thereof to extract from a plant of the genus Callicarpa is from 250: 1 to 1 :250 (e.g. , 250: 1 to 1: 1, 200: 1 to 1: 1, 70: 1 to 1: 1, 70: 1 to 2: 1, 25: 1 to 1: 1, 25:1 to 2: 1, 20:1 to 2: 1).

[0109] Specific Embodiment 22. The topical composition according to any one of Specific Embodiments 17-21, wherein said rhapontigenin (or said extract) is present in a coated liposome and said extract from a plant of the genus Callicarpa is present in a continuous phase.

[0110] Specific Embodiment 23. The topical composition according to any one of Specific Embodiments 1-22, wherein the composition comprises less than (or from 0.0001% to) 10%Callicarpa extract by weight of the composition (e.g., less than 5% Callicarpa extract by weight of the composition, less than 2% Callicarpa extract by weight of the composition, less than 1% Callicarpa extract by weight of the composition, less than 0.5% Callicarpa extract by weight of the composition, less than 0.2% Callicarpa extract by weight of the composition, less than 0.1% Callicarpa extract by weight of the composition, less than 0.01% Callicarpa extract by weight of the composition).

[0111] Specific Embodiment 24. The topical composition according to any one of Specific Embodiments 1-23, wherein the Callicarpa extract contains more than 90% (e.g., more than 95%, more than 99%) water and / or butylene glycol by weight of the Callicarpa extract.

[0112] Specific Embodiment 25. The topical composition according to any one of Specific Embodiments 1-24, wherein the weight ratio of rhapontigenin to Callicarpa extract is from 1 : 1 to 10: 1 (e.g, 2:1 to 8: 1, 3: 1 to 5:1, 4: 1).

[0113] Specific Embodiment 26. The topical composition according to any one of Specific Embodiments 1-24, further comprising a nicotinamide mononucleotide.

[0114] Specific Embodiment 27. The topical composition according to Specific Embodiment 26, wherein said rhapontigenin (or said extract) is present in a coated liposome and said nicotinamide mononucleotide is present in a continuous phase.

[0115] Specific Embodiment 28. The topical composition according to any one of Specific Embodiments 1-27, wherein the topical composition comprises less than (or from 0.0001% to or from 0.001% to or from 0.01% to) 10% rhapontigenin by weight of the composition (e.g, less than 5% rhapontigenin by weight of the composition, less than 2% rhapontigenin by weight of the composition, less than 1% rhapontigenin by weight of the composition, less than 0.5% rhapontigenin by weight of the composition, less than 0.2% rhapontigenin by weight of the composition, less than 0.05% rhapontigenin by weight of the composition, less than 0.1% rhapontigenin by weight of the composition, less than 0.01% rhapontigenin by weight of the composition, 0.001% to 0.006% by weight of the composition, 0.004% by weight of the composition).

[0116] Specific Embodiment 29. The topical composition according to any one of Specific Embodiments 1-28, wherein the topical composition is a shampoo, conditioner, gel, mousse, lotion, cream, serum, or pomade.

[0117] Specific Embodiment 30. The topical composition according to any one of Specific Embodiments 1-29, wherein the composition is formulated for delivery to the hair or scalp.

[0118] Specific Embodiment 31. A topical composition comprising: a) rhapontigenin or a derivative thereof (e.g, from 0.001% to I %. from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1% by weight of the composition); b) Callicarpa extract (e.g., from 0.0001% to 1%, from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1%. from 0.0001% to 0.5%) by weight of the composition); and one or more topically acceptable excipients; wherein said topical composition is a hair care composition.

[0119] Specific Embodiment 32. A topical composition comprising: a) Rheum rhaponticum root extract (e.g., from 0.001% to 1%, from 0.001% to 0.02%, from 0.01% to 0.1%. from 0.1% to 1%, from 0.0025% to 0.015%, 0.010%, by weight of the composition); b) Callicarpa japonica fruit extract (e.g., from 0.0001% to 1%. from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1%, from 0.0001% to 0.5%); and one or more topically acceptable excipients; wherein said topical composition is a hair care composition.

[0120] Specific Embodiment 33. A topical composition comprising coated liposomes dispersed in a continuous (e.g., aqueous phase) wherein: the coated liposomes are cyclodextrin and / or phospholipid liposomes comprising rhapontigenin or a derivative thereof (e.g, from 0.001% to 10% liposomes, from 0.001% to 5% liposomes, from 0.1% to 5% liposomes, from 0.1% to 1% liposomes, from 0.5% to 3% liposomes, by weight of the composition) coated with a modified starch (e.g.. sodium starch octenyl succinate); and the continuous phase comprises a Callicarpa extract and / or nicotinamide mononucleotide.

[0121] Specific Embodiment 34. A method for promoting hair growth comprising administering the topical composition according to any one of Specific Embodiments 1-33 to a subject.

[0122] Specific Embodiment 35. The method according to Specific Embodiment 34, wherein the topical composition is administered to the scalp, face, or hair of the subject.

[0123] Specific Embodiment 36. The method according to 34 or 35, wherein the topical composition is administered more once a week or more (e.g.. daily, twice a week, every other day).

[0124] Specific Embodiment 37. A method inducing proliferation of hair follicle dermal papilla cells comprising contacting a population of hair follicle dermal papilla cells with the topical composition according to any one of Specific Embodiments 1 -32 to induce proliferation of the hair follicle dermal papilla cells.

[0125] Specific Embodiment 38. The method according to Specific Embodiment 37, wherein the number of hair follicle dermal papilla cells after proliferation is from 25% to 100% greater (e.g., 50% to 100% greater, 75% to 100% greater) than the number of hair follicle dermal papilla cells in the population.

[0126] As various changes can be made in the above-described subject matter without departing from the scope and spirit of the present disclosure, it is intended that all subject matter contained in the above description, or defined in the appended claims, be interpreted as descriptive and illustrative of the present disclosure. Many modifications and variations of the present disclosure are possible in light of the above teachings. Accordingly, the present description is intended to embrace all such alternatives, modifications and variances which fall within the scope of the appended claims.

[0127] All documents cited or referenced herein, and all documents cited or referenced in the herein cited documents, together with any manufacturer's instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated by reference, and may be employed in the practice of the disclosure.

Claims

CLAIMS1. A topical composition comprising one or more topically acceptable excipients, rhapontigenin (5-[(E)-2-(3-hydroxy-4-methoxyphenyl)ethenyl]benzene-l,3-diol) and derivatives thereof and less than 5% anthranoids by weight of the rhapontigenin (e.g, a weight ratio of rhapontigenimanthranoids of from 10: 1 -5000: 1, 10: 1 -100: 1 , 100: 1-1000: 1, 1000: 1-5000: 1).

2. The topical composition according to claim 1 , wherein the topical composition comprises an extract of a plant from the genus Rheum and said extract of Rheum provides said rhapontigenin and / or derivatives thereof.

3. The topical composition according to claim 2, wherein the plant is Rheum rhaponticum.

4. The topical composition according to claim 2 or 3, wherein the extract of Rheum is an alcohol / water extract (e.g.. lower alcohol / water such as methanol / water, ethanol / water. propanol / water, isopropanol / water, butanol / water. or combinations thereof).

5. The topical composition according to any one of claims 2-4, wherein the extract is aqueous alkaline extract (e.g, a Ca(OH)2 extract).

6. The topical composition according to any one of claims 2-5. wherein the extract of Rheum is a root extract.

7. The topical composition according to any one of claims 1-5. wherein the rhapontigenin derivative is a glycosylated rhapontigenin.

8. The topical composition according to claim 7, wherein the glycosylated rhapontigenin has the structure:wherein R1-R3 are independently selected from hydrogen and glucosyl, wherein at least one (e.g, one, two, three) of R1-R3 is glucosyl.

9. The topical composition according to any one of claims 2-8, wherein said extract is complexed with cyclodextrin (e.g, hydroxypropyl cyclodextrin).

10. The topical composition according to any one of claims 1-9, wherein said rhapontigenin (or said extract) is present in a liposome (e.g., a coated liposome).

11. The topical composition according to claim 10, wherein said coated liposome is a cyclodextrin (e.g, hydroxypropyl cyclodextrin): phospholipids liposome coated with a starch such as a modified starch (e.g., a liposome coated with rhapontigenin in a weight ratio of rhapontigenin:cyclodextrin:phospholipids:modified starch of 0.1-2:50-70: 10-15: 1-7). For example, the ratio of rhapontigenin to cyclodextrin may be 1:50-1:75 and / or the ratio of rhapontigenin to phospholipid may be 1 : 10-1: 15 and / or the ratio of sodium starch octenylsuccinate (e.g., low viscosity starch such as starch viscosity of less than 500 mPas or less than 200 mPas or less than 100 mPas or less than 75 mPas) may be from 1 : 3-1 :5.

12. The topical composition according to claim 11, wherein said modified starch is sodium starch octenyl succinate.

13. The topical composition according to claim 11 or 12, wherein the starch (e.g., modified starch) has a viscosity7of less than (or from 1 mPas to) 100 mPas (e.g., less than 75 mPas, less than 50 mPas, less than 25 mPas) as measured by a 10% w / w water solution at 20°C with a Brookfield viscometer spindle LV-1.

14. The topical composition according to any one of claims 10-13, wherein the liposome (e.g., coated liposome) have a Z-average particle size of from 100-200 nm (e.g., 125-175 nm) as measured by dynamic light scattering.

15. The topical composition according to any one of claims 10-14, wherein the liposome (e.g., coated liposome) have poly dispersity index of from 0.2-0.3.

16. The topical composition according to any one of claims 10-15 wherein said composition comprises from 0.01% to 50% (e.g., from 0.01% to 20%, from 0.01% to 10%, from 0.01% to 5%, from 0.1% to 5%, from 0.5% to 3%, 2%) liposome (e.g, coated liposome) by weight of the composition.

17. The topical composition according to any one of claims 1-16, wherein said topical composition further comprises an extract from a plant of the genus Callicarpa (e.g., the Callicarpa extract provides one or more polyphenols such as poliumoside).

18. The topical composition according to claim 17, wherein said genus of Callicarpa is Callicarpa japonica.

19. The topical composition according to claim 17 or 18, wherein the extract is a water extract.

20. The topical composition according to any one of claims 17-19, wherein the extract is from the fruit of the plant.

21. The topical composition according to any one of claims 17-20, wherein the weight ratio of the rhapontigenin or derivative thereof to extract from a plant of the genus Callicarpa is from 250: 1 to 1:250 (e.g, 250: 1 to 1 : 1, 200:1 to 1 : 1, 70: 1 to 1: 1, 70: 1 to 2: 1, 25: 1 to 1 :1, 25:1 to 2: 1, 20: 1 to 2: 1).

22. The topical composition according to any one of claims 17-21, wherein said rhapontigenin (or said extract) is present in a coated liposome and said extract from a plant of the genus Callicarpa is present in a continuous phase.

23. The topical composition according to any one of claims 1-22, wherein the composition comprises less than (or from 0.0001% to) 10% Callicarpa extract by weight of the composition (e.g, less than 5% Callicarpa extract by weight of the composition, less than 2% Callicarpa extract by weight of the composition, less than 1% Callicarpa extract by weight of the composition, less than 0.5% Callicarpa extract by weight of the composition, less than 0.2% Callicarpa extract by weight of the composition, less than 0. 1% Callicarpa extract by weight of the composition, less than 0.01% Callicarpa extract by weight of the composition).

24. The topical composition according to any one of claims 1-23, wherein the Callicarpa extract contains more than 90% (e.g, more than 95%, more than 99%) water and / or butylene glycol by weight of the Callicarpa extract.

25. The topical composition according to any one of claims 1-24, wherein the weight ratio of rhapontigenin to Callicarpa extract is from 1 : 1 to 10: 1 (e.g., 2: 1 to 8:1, 3: 1 to 5: 1, 4:1).

26. The topical composition according to any one of claims 1-24, further comprising a nicotinamide mononucleotide.

27. The topical composition according to claim 26, wherein said rhapontigenin (or said extract) is present in a coated liposome and said nicotinamide mononucleotide is present in a continuous phase.

28. The topical composition according to any one of claims 1-27, wherein the topical composition comprises less than (or from 0.0001% to or from 0.001% to or from 0.01% to) 10% rhapontigenin by weight of the composition (e.g, less than 5% rhapontigenin by weightof the composition, less than 2% rhapontigenin by weight of the composition, less than 1% rhapontigenin by weight of the composition, less than 0.5% rhapontigenin by weight of the composition, less than 0.2% rhapontigenin by weight of the composition, less than 0.05% rhapontigenin by weight of the composition, less than 0.1% rhapontigenin by weight of the composition).

29. The topical composition according to any one of claims 1-28, wherein the topical composition is a shampoo, conditioner, gel, mousse, lotion, cream, serum, or pomade.

30. The topical composition according to any one of claims 1-29, wherein the composition is formulated for delivery to the hair or scalp.

31. A topical composition comprising: a) rhapontigenin or a derivative thereof (e.g., from 0.001% to 1%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1% by weight of the composition); b) Callicarpa extract (e.g., from 0.0001% to 1%, from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1%. from 0.0001% to 0.5%) by weight of the composition); and one or more topically acceptable excipients; wherein said topical composition is a hair care composition.

32. A topical composition comprising: a) Rheum rhaponticum root extract (e.g., from 0.001% to 1%, from 0.001% to 0.02%, from 0.01% to 0.1%, from 0.1% to 1%, from 0.0025% to 0.015%, 0.010%, by weight of the composition); b) Callicarpa japonica fruit extract (e.g., from 0.0001% to 1%. from 0.0001% to 0.001%, from 0.001% to 0.01%, from 0.01% to 0.1%, from 0.1% to 1%, from 0.0001% to 0.5%); and one or more topically acceptable excipients; wherein said topical composition is a hair care composition.

33. A topical composition comprising coated liposomes dispersed in a continuous (e.g., aqueous phase) wherein:the coated liposomes are cyclodextrin and / or phospholipid liposomes comprising rhapontigenin or a derivative thereof (e.g.. from 0.001% to 10% liposomes, from 0.001% to 5% liposomes, from 0. 1% to 5% liposomes, from 0. 1% to 1% liposomes, from 0.5% to 3% liposomes, by weight of the composition) coated with a modified starch (e.g., sodium starch octenyl succinate); and the continuous phase comprises a Callicarpa extract and / or nicotinamide mononucleotide.

34. A method for promoting hair growth comprising administering the topical composition according to any one of claims 1-33 to a subject.

35. The method according to claim 34, wherein the topical composition is administered to the scalp, face, or hair of the subject.

36. The method according to 34 or 35, wherein the topical composition is adminstered more once a week or more (e.g., daily, twice a week, every other day).

37. A method inducing proliferation of hair follicle dermal papilla cells comprising contacting a population of hair follicle dermal papilla cells with the topical composition according to any one of claims 1-32 to induce proliferation of the hair follicle dermal papilla cells.

38. The method according to claim 37, wherein the number of hair follicle dermal papilla cells after proliferation is from 25% to 100% greater (e.g., 50% to 100% greater, 75% to 100% greater) than the number of hair follicle dermal papilla cells in the population.

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