Composition for modulating hair growth, production process, uses and methods

Abstract

The present invention relates to novel cosmetic, dermatological or pharmaceutical compositions containing an apolar extract of black-jack (Bidens pilosa), which are effective for stimulating hair growth in humans or animals.

Description

COMPOSITION FOR MODULATION OF HAIR GROWTH, PRODUCTION PROCESS, USES AND METHODS Technical Field of the Invention

[0001] The present invention discloses new cosmetic, dermatological, or pharmaceutical compositions containing apolar extract of black thistle (Bidens pilosá) that are effective in stimulating hair growth in humans or animals. The present invention is in the technical fields of cosmetic compositions for modulating hair growth and topical cosmetic compositions. Background of the Invention

[0002] Hair is divided into two distinct structures: the hair bulb and the hair shaft. The hair bulb corresponds to the part below the skin, while the shaft is a filament that extends from the part below the skin to the surface.

[0003] Hair strands originate from a dermal indentation called a hair follicle. Anchored to this follicle is the hair root, which terminates at the hair bulb and includes a layer of mitotically active basal cells called the hair matrix.

[0004] The hair follicle can be divided into three segments: lower, middle, and upper. The lower segment is the area from the base of the follicle to the insertion of the arrector pili muscle and consists of the bulb and suprabulb regions. The bulb consists of the dermal papilla and the surrounding matrix, with the lower portion of the papilla fused to the fibrous root sheath, which surrounds the hair follicle. The size of the bulb and papilla determines the diameter of the hair strand.

[0005] The middle segment, also known as the isthmus, is short and extends from the insertion of the arrector pili muscle to the meatus of the sebaceous gland duct. The upper segment of the follicle, also called the infundibulum, extends from the meatus of the sebaceous gland duct to the follicular orifice. The surface of the epidermis lines the infundibulum and contains melanocytes. active pigmented cells. The basal layer contains inactive melanocytes, which are kept in reserve and can become melanin-producing cells after skin injury.

[0006] Hair follicle development

[0007] Hair follicles begin to form in the skin of a human embryo at 8 â the 12th â week of gestation, with its development and differentiation classically divided into eight stages during embryogenesis.

[0008] Follicle formation requires a complex, and still largely unexplained, sequence of autocrine, paracrine, and endocrine signals that occur within and between the epidermis and dermis. Although the mechanism is not fully understood, it is known that multiple signal transduction pathways are activated for the correct development and distribution of hair follicles in the skin.

[0009] In particular, Wnt gene products and the intracellular mediators associated with cell signaling, β-catenin and LEF1 (lymphoid enhancer binding factor 1), have been shown to be critical for hair follicle embryogenesis. Wnt is the first essential signal for the induction of hair follicle development. Wnt secretion by its producing cells is facilitated by the multipass transmembrane protein Wntless (Wls), and although its role in developmental induction is unclear, Wnt is known to be expressed in the developing embryonic epidermis and in hair follicle compartments after the completion of hair morphogenesis.

[0010] Wnts can be classified as primary Wnts, examples being Wnts 3, 4, and 6, and secondary Wnts, such as Wnts 2, 7b, 10a, and 10b. Primary Wnts are essential for hair follicle initiation, while secondary Wnts are important in development. In an essential step for hair follicle induction, which is fibroblast aggregation, Wnts also play an important role, as this process is driven by the Wnt / β-catenin signaling pathway.

[0011] The subsequent activation cascade of the signaling pathway mediated by [3-catenin and LEF1, includes the molecules EDA (ectodysplasin A), NOG protein (noggin), TGF- [32 (transforming growth factor 2), TGF|3R-II (transforming growth factor 2 receptor), integrin [3-1 and NCAM (cell adhesion molecule), among others.

[0012] Hair Growth Cycle

[0013] In mammals, the hair growth process is cyclically controlled and consists of three distinct phases: anagen (growth phase), catagen (regression phase) and telogen (resting phase).

[0014] The growth phase lasts on average 2 to 7 years, while the regression phase lasts approximately 2 to 4 weeks and the resting phase, approximately 3 months. Approximately 84% of scalp hair is in the anagen phase, 1% to 2% in the catagen phase, and 10% to 15% in the telogen phase.

[0015] During the anagen phase, active hair growth occurs, during which hair fibers are produced and the hair root elongates. During this phase, germinal epithelial cells at the base of the follicle rapidly proliferate and differentiate, producing elongation of the hair fiber and inner root sheath layers. As mitotic activity in the terminal bulb decreases and eventually ceases, the hair follicle enters the catagen phase, which is characterized by the apoptosis of epithelial cells in the lower, transient section of the follicle and the formation and anchoring of the tubular fiber. The dermal papilla moves to the base of the permanent section of the follicle. In the telogen phase, the hair follicle regresses to less than half its anagen-phase size.

[0016] Hair growth regulatory mediators

[0017] The interaction between epithelial and mesenchymal cells, called epithelial-mesenchymal interaction (EMI), is involved in the formation of various organs, including hair follicles. EMI has a strong influence on the hair growth cycle, especially on the induction of the anagen phase.

[0018] The cell cycle is governed by a signaling cascade between the follicular keratinocyte stem cells in the bulge committed to the specific differentiation of the hair follicle and the dermal papilla. At the beginning of the anagen phase induction, the follicular stem cells and the degenerated cells of the dermal papilla (epithelial cells) come into close proximity, so that this proximity allows interaction between these two cell types.

[0019] Studies cite some molecules as inducing epithelial-mesenchymal interaction, such as BMP (bone morphogenic protein) factors, belonging to the transforming growth factor (TGF-a) superfamily; the signaling protein Shh (sonic hedgehog); the factors bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), IGF-1 (insulin-like growth factor 1) and VEGF (vascular endothelial growth factor); and the proteins Wnt 3a, 7 and 10a.

[0020] Among these factors, BMPs and the Shh protein stand out. BMPs are secreted signaling molecules that belong to the transforming growth factor (TGF-[3) superfamily and exert their biological activities through interaction with specific BMP receptors. These factors control cell proliferation, differentiation, and apoptosis in various organs, including the skin. BMPs also interact with members of other growth factor families, such as Wnt, Shh, TGF-[3 (transforming growth factor-3), EGF (epidermal growth factor), FGF (fibroblast growth factor), Notch, and neutrophins, to control cell proliferation, differentiation, and apoptosis in the developing skin and appendages.

[0021] Signaling via the Shh (sonic hedgehog) protein regulates the proliferation and development of tissues, including the hair follicle. This protein is essential for hair development and hair cycle, so alterations in the function of members of this signaling pathway alter hair follicle formation and generate epidermal neoplasia. Shh is expressed in the follicle matrix and is essential for controlling hair follicle morphogenesis, in addition to being involved in controlling the initiation of the hair cycle in primary and secondary follicles.

[0022] Other factors are also identified as regulators of the hair cycle, being important in the promotion and maintenance of the anagen phase, such as FGF-2 (fibroblast growth factor 2), FGF-7 (fibroblast growth factor 7), LEF1 (lymphoid enhancer binding factor 1), MSP (macrophage stimulating factor), PDGF (platelet-derived growth factor), TGF-a (transforming growth factor a), NOG (noggin) and PRL (prolactin).

[0023] Regulators of the promotion and maintenance of the catagen and telogen phases include BDNF (brain-derived neurotrophic factor), BMP-2 (bone morphogenetic protein 2), BMP-4 (bone morphogenetic protein 4), EGF (epidermal growth factor), FGF-5 (fibroblast growth factor 5), IL-1 (interleukin 1), IL-6 (interleukin 6), IFN-y (interferon y), NT3 (neutrophin 3), OSM (oncostatin M), PTH (parathyroid hormone); TAC-1 (protachykinin-1 precursor), TGF-[31 (transforming growth factor

[31] , TGF-[32 (transforming growth factor [32).

[0024] Hair Loss - Factors Causing Hair Loss

[0025] Several factors are associated with hair loss, known as alopecia. The causes are generally attributed to male hormones (androgens), genetic factors, and age.

[0026] Some of the factors that cause hair loss are: reduced hair follicle function due to male hormones, reduced metabolic functions of the follicle and hair bulb, reduced physiological functions in the scalp, and local circulation damage due to tension in the scalp.

[0027] Androgenetic alopecia

[0028] Of all alopecias, the most common is androgenetic alopecia, caused by a genetically determined shortening of the anagen phase. Androgen hormones have profound effects on the scalp and body hair, with testosterone being the primary hormone responsible for these effects. Inadequate blood flow to the scalp is also cited as a major contributing factor. hair loss.

[0029] The scalp has androgen-independent and androgen-sensitive hair follicles, with sensitive follicles located at the front and top of the scalp, while independent follicles are located at the sides and back. This distribution reflects the classic pattern of hair loss seen in patients with androgenetic alopecia.

[0030] The androgen hormones testosterone and dihydrotestosterone (DHT) act on androgen-sensitive receptors in the dermal papilla, located in the hair bulb. DHT, a more potent hormone than testosterone, binds to androgen-sensitive receptors, shortening the anagen phase of the growth cycle and causing hair follicle miniaturization. It is suggested that DHT atrophies the hair follicle through a pro-apoptotic mechanism via caspase 3. Hair continues to grow but becomes thinner and eventually falls out.

[0031] In fact, studies have shown that there is a direct relationship between DHT and androgenetic alopecia, with high levels of this hormone being found in men affected by this condition.

[0032] Main targets against androgenetic alopecia

[0033] Studies have shown that patients with androgenetic alopecia have high levels of the enzyme 5a-reductase, which converts testosterone into DHT. Considering this, one approach used in products aimed at preventing hair loss is the use of 5a-reductase inhibitors.

[0034] Three types of 5α-reductase have been identified (types 1, 2, and 3): type 1 is predominantly expressed in the skin and appendages such as sebaceous glands; type 2 is expressed in the epididymis, seminal vesicles, prostate, and genital fibroblasts; and type 3 is expressed in benign and neoplastic prostate tissue (Ceirut et al., 2018). Studies have shown that type 2 was also found in dermal papilla cells of the frontal scalp.

[0035] In addition to 5a-reductase inhibitors, vasomodulators, with the intention of increasing local blood circulation to stimulate hair growth.

[0036] Currently, only two FDA-approved synthetic drugs are available for the treatment of androgenetic alopecia: minoxidil and finasteride, which act by opening the potassium channel and inhibiting 5α-reductase type 2, respectively. Both drugs have side effects and are effective in <50% of patients. Therefore, the search for new drugs to treat AGA is necessary, and to achieve this, it is important to understand the underlying mechanism of androgen action within PD cells.

[0037] Minoxidil is a vasodilator that promotes the opening of potassium channels and is known to prolong the anagen phase and convert vellus hair into terminal hair. This effect is seen through the upregulation of VEGF and FGF-7 within dermal papilla cells and through growth-promoting activity in hair epithelial cells. Furthermore, it is the only drug used to treat androgenetic alopecia in women. However, it is only effective in 30–35% of treated patients, and treatment must be continued for life. Furthermore, side effects of 2% and 5% minoxidil solutions include scalp irritation, pruritus, dryness, scaling, itching, redness, contact dermatitis, and hypertrichosis.

[0038] Finasteride, a synthetic azosteroid, is a type 2 5α-reductase inhibitor. It is known to irreversibly bind to the enzyme and inhibit the conversion of testosterone to DHT. This inhibition reduces serum DHT concentrations by 68%, with observed side effects including impotence, abnormal ejaculation, abnormal sexual function, myalgia, testicular pain, and gynecomastia. It can cause malformation of the external genitalia in male fetuses if taken by women who are or may become pregnant. Furthermore, it is known to be effective in only 48% of treated patients.

[0039] During searches carried out on the state of the art, the following documents were detected.

[0040] JP2001233727 discloses a hair tonic composition for use in the prevention of hair loss containing the polar fraction of the Bidens pilosa plant extract using ethanol.

[0041] JP4627107 discloses a composition for promoting hair growth containing the polar fraction of the Bidens pilosa plant extract using ethanol, or, 1,3-butylene glycol.

[0042] Dieamant et al. (2015) evaluated the anti-aging effects of a supercritical CO2 extract. However, they indicated that such a composition can only be used as an anti-aging or skin repair agent.

[0043] Hughes et al. (2019) discloses compositions to promote hair growth containing polar fractions of the Bidens pilosa plant extract using EtOAc, EHO (1:1 Ethanol / Water) or H2O.

[0044] Hughes et al. (2020) reveals a composition to promote hair growth containing polar fractions of the Bidens pilosa plant extract using EtOAc.

[0045] Hughes et al. (2022) reveals a composition to promote hair growth containing polar fractions of the Bidens pilosa plant extract using EtOAc.

[0046] Therefore, the discovery of new safe and effective compositions for promoting hair growth is of particular interest for the treatment of these conditions. Summary of the Invention

[0047] In this sense, the patent application presents new compositions effective in significantly stimulating the growth of human hair follicles. Surprisingly, the new composition for modulating hair growth comprises an extract with the nonpolar fraction of the Bidens pilosa plant.

[0048] In one embodiment of the present invention, said extract is obtained by supercritical fluid extraction of carbon dioxide (CO2) from Bidens pilosa.

[0049] In one embodiment of the present invention said composition additionally comprises: 20% to 85%, by mass, of triglycerides containing saturated fatty acids, mono and polyunsaturated fatty acids, selected from palm oil, coconut oil, shea butter, capric / caprylic acid triglycerides, linseed oil, cottonseed, sunflower, macadamia, sesame, avocado, rice, olive, corn, soybean, peanut, castor oil, preferably a combination of 30% to 60% sunflower triglycerides and 10% to 30% castor oil triglycerides; and / or; 1% to 30% by mass of phytosterols, preferably between 5% to 25% of phytosterols; and / or; 1% to 10%, by mass, of free fatty acids, which may be linoleic, caprylic, or rhinonicloeic acid; and / or; 0.1% to 10% by mass of diterpene, such as retinol, phytol, abietic acid, gibberellic acid cembrene and taxadiene, preferably 0.1% to 10% of phytol; and / or; 0.1% to 10% by mass of hydroxycinnamic acid derivative, such as ferulic, caffeic, coumaric and sinapic acid derivative, preferably 0.10% to 10% of ethyl caffeate; and / or; 0.01% to 0.5% by mass of antioxidant, preferably pentaerythrityl tetra-dibutyl hydroxycinnamate.

[0050] In one embodiment of the present invention the composition comprises from 0.01% to 20% of non-polar extract of Bidens pilosa or non-polar supercritical extract of Bidens pilosa.

[0051] In one embodiment of the present invention said modulation of hair growth is by topical application of the composition to a human or animal in a region comprising hair follicles.

[0052] In one embodiment of the present invention said composition is a cosmetic, dermatological or pharmaceutical composition.

[0053] A process for producing the composition defined herein is also presented, which comprises supercritical extraction with carbon dioxide. (CO2) from the aerial parts of the Bidens pilosa plant, previously dehydrated and crushed.

[0054] The use of the composition defined herein for modulating hair growth in a human or animal is also presented.

[0055] Furthermore, a method is presented for modulating hair growth in a human or animal, comprising the topical application of a composition as defined herein in a cosmetically, dermatologically or pharmaceutically effective amount to a region of the skin comprising hair follicles. Description of Figures

[0056] Figure 1: Bar graph representing the measurement of increased length (mm) of human hair follicles after 7 days of treatment with the hair growth composition (test product), comparator product (benchmark) or Fetal Bovine Serum as a positive control. * Represents statistical significance with a p-value <0.05. **** Represents statistical significance with a p-value <0.0001. Detailed Description of the Invention

[0057] This detailed description of the invention establishes some non-limiting definitions of the main terminologies and technical characteristics used throughout this patent application, as well as providing examples of some of the embodiments of the present invention so that it can be reproduced by a person skilled in the art.

[0058] The present invention relates to the use of a cosmetic composition containing non-polar extract of black thistle (Bidens pilosa), preferably obtained by extraction with supercritical fluid of carbon dioxide (CO2) and optionally associated with phytosterols; phytosterol esters; hydroxycinnamic acid ester; triglycerides containing saturated fatty acids, mono and polyunsaturated fatty acids, which may be palm oil, coconut oil, shea butter, capric / caprylic acid triglycerides, linseed oil, cottonseed oil, sunflower oil, macadamia oil, sesame oil, avocado oil, rice oil, olive oil, corn oil, soybean oil, peanut and castor oil, free fatty acids and diterpene or a fraction thereof, for the preparation of a cosmetic, dermatological or pharmaceutical composition for topical use, intended to stimulate hair growth or prevent hair loss.

[0059] Supercritical fluid extraction is considered a green extraction method because it was developed to reduce energy and solvent consumption, shorten processing times, and replace conventional solvents with environmentally friendly substitutes. This ensures a safe, high-quality extract / product, and represents a sustainable alternative to traditional extraction systems. This method can prevent or minimize the use of organic solvents, reduce storage problems associated with organic solvents, and consequently minimize environmental problems by avoiding the release of toxic substances into the environment and also contribute to reducing the carbon footprint. Carbon dioxide (CO2) is widely used as a supercritical fluid for extraction purposes due to its critical properties (Tc = 31.1 SC; Pc = 73.8 bar), which makes it an excellent solvent for extracting heat-sensitive bioactive compounds. It is chemically inactive, economical, readily available, separable from extracts, and non-toxic. Another advantage of using CO2 is its ability to produce extracts free of solvent residues, as CO2 is a gas at ambient temperature and pressure. It also minimizes thermal damage to bioactive compounds due to its low critical temperature.

[0060] The plant Bidens pilosa L., popularly known as Picão-preto, is a small, erect herb that can reach 1 m in height. It has bright green leaves with serrated, spiny edges and produces small yellow flowers and black fruits. It is widely distributed throughout the Amazon Rainforest and other tropical areas, such as other parts of South America, Africa, the Caribbean, and the Philippines. In some countries, due to its high prevalence, it is considered a weed.

[0061] The phytochemical composition of Bidens pilosa is widely diversified, characterized mainly by the presence of flavonoids, terpenes, phenylpropanoid compounds, lipids and benzenoids. The main chemical constituents described for Bidens pilosa are: berhenic, docosahexaenoic (DHA), butanedioic, caffeolic, capric, eladic, erythronic, lauric, linoleic, myristic, palmitic, palmitoleic, α-coumaric, titanic, phytenoic, tannic, vanillic, ricinoleic acids and derivatives, β-sitosterol, borneol, butoxylinoleates, cadinols, caffeine, ethyl caffeate, esculetin, daucosterol, friedelanes, germacrene D, glucopyranoses, glucopyranosides, inositol, isoquercitrin, limonene, lupeol, luteolin, muurolol, phenylheptatrienols, phytol, phytol heptanoate, pilosola A, polyacetylenes, precocene I, pyranoses, quercetin, squalene, stigmasterols, tetrahydroxyaurones, tocopherolquinones, tridecapentainenes.

[0062] Black picão has been widely used in traditional medicine for a wide variety of treatments, such as topical and internal inflammatory processes, wounds, insect bites, and fungal infections. It has anti-inflammatory, immunomodulatory, antimalarial, antitumor, antioxidant, antibacterial, antihypertensive, and antiaging properties.

[0063] The black picão has been the subject of scientific research that supports its applications in herbal and folk medicine. Various research groups have demonstrated the anti-inflammatory and immunomodulatory potential of Bidens pilosa, particularly through its ability to inhibit the production of pro-inflammatory cytokines, as well as prevent prostaglandin synthesis and induced cyclooxygenase activity. Research shows that extracts obtained from the aerial parts or the entire Bidens pilosa plant exhibit antimicrobial and antioxidant activities.

[0064] Chemical compounds of interest for cosmetic use can be separated by high-performance liquid chromatography and other conventional extraction techniques, varying the polarity of the solvent. However, the use of more sophisticated techniques such as supercritical CO2 extraction favors the production and separation of more purified compounds. and in higher concentrations.

[0065] Fluids near their critical points have densities close to those of liquids and compressibilities comparable to those of gases. Their properties are particularly sensitive to temperature and pressure. Therefore, it is very easy to modify the solubilization of compounds through small variations in the thermodynamic process conditions. In a typical supercritical extraction process, the material containing the constituents of interest is fed to the extractor, where a supercritical solvent stream flows at a specific pressure, temperature, and flow rate, thus extracting some components depending on their solubility. Extraction and fractionation of products with supercritical fluids can be performed in two operating modes: selective extraction and / or selective separation.The first involves tuning the solvation capacity of the fluid used in the extraction by manipulating the thermodynamic conditions of temperature and pressure and / or modifying the chemical nature of the solvent used with the addition of a co-solvent. In the second mode of operation, selective separation is achieved through depressurization or gradual heating or cooling of the extract, thus allowing controlled fractionation of the extractable products. Selective separation can also be achieved by coupling the extraction process to another separation process, such as adsorption. After extraction, one or more dissolved components precipitate in the separator vessel upon decompression of the system. Manipulating the operating conditions can make the solvent more selective for specific components.The solubilizing power of a solvent such as CO2 can be modified by adding small amounts of polar substances called modifiers or co-solvents.

[0066] Extraction with supercritical fluids presents advantages over conventional processes for obtaining active ingredients from the plant matrix, as these processes are mostly based on extraction with chemical solvents, and have drawbacks such as high operating temperatures and therefore the possibility of thermal degradation of the assets, the presence of toxic residues in the final product and the possibility of human and environmental contamination due to the use of organic solvents that are dangerous to handle.

[0067] The cosmetic composition containing apolar extract of black thistle (Bidens pilosa) proved to be surprisingly effective in promoting hair growth, as shown in the results presented in example 3. It is understood that some of its compounds may play an important role in morphogenesis, differentiation and cell development, possibly through interaction with nuclear receptors, called RARs and RXRs, and thus enable the stimulation of hair follicle development, through mechanisms that have not yet been fully elucidated.

[0068] In one embodiment of the present invention, the cosmetic composition containing the non-polar supercritical extract of Bidens pilosa may be associated with triglycerides, in the form of oils and fats, which may be obtained from fruits, grains, nuts, and seeds, through cold-pressing or solvent extraction processes. While oils are composed primarily of unsaturated fatty acids and are in liquid form at room temperature, fats are solid or semi-solid at room temperature and have a high concentration of saturated fatty acids in their composition. Both are composed primarily of triglycerides or glycerol triesters (95-98%), also containing small amounts of mono- and diglycerides (1%), free fatty acids, and unsaponifiable materials, such as tocopherols, tocotrienols, polyphenols, terpenes, phospholipids, carotenoids, and phytosterols.

[0069] The main activity of vegetable oils and butters is emollient, which results in better skin hydration due to reduced transepidermal water loss (TEWL). Unsaponifiable substances can be responsible for specific effects, such as antimicrobial, anti-inflammatory, antioxidant, and enhance the permeation of other substances.

[0070] In hair products, vegetable oils and butters can be Used as shine enhancers and emollients, they form films on the hair's surface, sealing the cuticle and retaining moisture within the fiber. They are lubricants and provide greater glide between strands of hair, which aids in detangling, thus improving hair health and appearance. They can also fill gaps between cuticle cells and prevent the penetration of aggressive substances such as surfactants into the follicle. Additionally, some vegetable oils may also play a role in preventing protein loss from hair fibers.

[0071] Oils also play an important role in protecting hair from damage. Some oils can penetrate hair fibers, reducing the amount of water absorbed, leading to reduced swelling.

[0072] In one embodiment of the present invention, the cosmetic composition containing the non-polar supercritical extract of Bidens pilosa may also be associated with phytosterols, which are plant metabolites belonging to the triterpene family, with a chemical structure similar to cholesterol, and can be found in vegetable oils. [3-sitosterol, campesterol, and stigmasterol are the main phytosterols found in plants. Phytosterols are essential components of membranes and alter their properties such as permeability and fluidity, also possessing anti-inflammatory properties.

[0073] In cosmetics, it has been used for photo-protective, anti-aging, humectant, barrier protection and antioxidant effects.

[0074] In one embodiment of the present invention, the cosmetic composition containing the non-polar supercritical extract of Bidens pilosa may also be associated with diterpenes, such as retinol, phytol, abietic acid, gibberellic acid, cembrene, and taxadiene, preferably phytol, an important phytoconstituent, which consists of an acyclic diterpene alcohol, found abundantly in nature as part of the chlorophyll molecule. It is produced by almost all photosynthetic organisms, such as algae, plants, and Cyanobacteria. It is primarily used as a fragrance component, but it also has anti-inflammatory, antioxidant, and antimicrobial properties. Its chemical structure and anti-aging mechanism of action are similar to retinoids, and it can be considered a natural RXR ligand.

[0075] In one embodiment of the present invention, the cosmetic composition containing the nonpolar supercritical extract of Bidens pilosa may be combined with a hydroxycinnamic acid derivative, such as ferulic, caffeic, coumaric, and sinapic acids, preferably ethyl caffeate, a phenolic compound with anti-inflammatory, antioxidant, and antimicrobial activity. It may be obtained naturally or synthesized through the esterification of caffeic acid to increase the lipophilicity of this natural antioxidant. Caffeic acid is a phenolic compound, a secondary metabolite naturally present in plants, specifically a hydroxycinnamic acid found in plants, fruits, and vegetables, with several biological properties, such as antioxidant and antimicrobial.

[0076] In one embodiment of the present invention, a hair composition is presented comprising the apolar supercritical extract of Bidens pilosa, which may be associated in any proportion with oils and other active ingredients such as phytosterol, diterpene and hydroxycinnamic acid derivative, such as, for example, in the following composition:

[0077] from 20% to 85%, by mass, of at least one triglyceride containing saturated, monounsaturated and polyunsaturated fatty acids; and / or

[0078] from 1% to 30%, by mass, of at least one phytosterol or its derivatives in esterified form; and / or

[0079] from 1% to 10%, by mass, of free fatty acids, which may be linoleic, caprylic and rhincycloeic acid; and / or

[0080] from 0.01% to 20%, by mass, of the non-polar supercritical extract of Bidens pilosa; and / or

[0081] from 0.10% to 10%, by mass, of a diterpene; and / or

[0082] from 0.10% to 10%, by mass, of a derivative of the acid hydroxycinnamic acid; and / or

[0083] from 0.01% to 0.5% by mass of an antioxidant.

[0084] In a preferred embodiment of the present invention, the concentration of the non-polar supercritical extract of Bidens pilosa within the composition for modulating hair growth is between 0.01% and 20%. Optionally, between 0.01% and 10%. Optionally, between 0.01% and 5%. Optionally, between 0.01% and 1%.

[0085] In one embodiment of the present invention, the composition of the hair composition additionally comprises from 20% to 85%, by mass, of triglycerides containing saturated fatty acids, mono and polyunsaturated fatty acids, which may be palm oil, coconut oil, shea butter, capric / caprylic acid triglycerides, linseed oil, cottonseed, sunflower, macadamia, sesame, avocado, rice, olive, corn, soybean, peanut, castor oil, preferably being a combination of 30 to 60% of sunflower triglycerides and 10 to 30% of castor oil triglycerides; 1 to 30% of phytosterols, preferably between 5 to 25% of phytosterols; 1% to 10%, by mass, of free fatty acids, which may be linoleic, caprylic, rhinicloeic acid, preferably 1 to 5% of caprylic and linoleic acid; 0.1 to 10% of diterpene, preferably 0.1 to 10% of phytol; 0.1 to 10% of hydroxycinnamic acid derivative, preferably 0.10 to 10% of ethyl caffeate;0.01 to 0.5% antioxidant, preferably pentaerythrityl tetra-dibutyl hydroxycinnamate.;

[0086] Production of a Hair Growth Composition

[0087] Example 1: Obtaining supercritical extract of Bidens pilosa

[0088] In one embodiment of the present invention, the process for obtaining the supercritical extract of Bidens pilosa comprises the following steps: i. 1.00 to 5.00 kg of crushed Bidens pilosa plant are loaded into the stainless steel extraction vessel. ii. The vessel is connected to the supercritical carbon dioxide (CO2) extractor and hermetically sealed. iii. Carbon dioxide (CO2) is cooled and pressurized under pressure of 200 - 400 kgf / cm2 and under temperature of 30 - 60 SC. iv. After the system is stabilized under the conditions previously defined, the extraction is initiated and the process is carried out for approximately 20 hours in a cycle. v. After the extraction time is completed, the supercritical CO2 originally transforms into gaseous CO2, being expelled, and the pure concentrated supercritical extract of Bidens pilosa is obtained in the extraction chamber.

[0089] Example 2: Obtaining a Hair Growth Composition (“test product”): In one embodiment of the present invention, the process for obtaining the test product comprises the following steps: i. In a container of suitable volume, coupled with a mechanical stirrer and nitrogen bubbler, 20 to 85 g of at least one triglyceride containing saturated, monounsaturated, and polyunsaturated fatty acids is added; ii. The mechanical stirring is turned on and adjusted between 100 and 500 RPM. Open the nitrogen flow, adjusting it between 2 and 20 liters / min; iii. The heating is turned on and the temperature is adjusted between 60 and 90 sC; iv. Add 1 to 30 g of at least one phytosterol or its derivatives in esterified form; v. Keep the system under stirring for 30 to 100 minutes; vi. Add 0.10 to 10 g of diterpene; vii. Keep the system under stirring for 10 to 20 minutes; viii. Add 0.10 to 10 g of a hydroxycinnamic acid derivative; ix. Add 1.00 to 10 g of free fatty acid; x. Add 0.01 to 20 g of supercritical extract of Bidens pilosa; xi. Add 0.01 to 0.5 g of pentaerythrityl tetradibutylhydroxycinnamate. xii. Keep the system under stirring for 20 to 30 minutes.

[0090] Example 3: Ex vivo evaluation of the stimulatory effects of hair growth

[0091] Material and methods

[0092] Human hair follicles from the occipital region (nape) of volunteers were isolated by manual extraction. Hair follicles in the anagen phase, six per condition, were selected by morphological discrimination and maintained in growth medium supplemented with Fungizone, penicillin, and streptomycin. Baseline images (Oh time) were obtained immediately after isolation using a stereomicroscope. The follicles were individually placed in 24-well plates (1 follicle / well) and kept free-floating in culture medium containing or not (control) the test product, a comparator (benchmark = minoxidil - 0.01% w / w), and a positive control (fetal bovine serum). The plates were placed in an incubator at 37°C in a 5% CO2 / 95% air atmosphere and maintained under these conditions for 7 days.

[0093] At the end of the incubation period, new images of the hair follicles were recorded under conditions identical to the previous images. Image analysis was performed using ImageJ software, measuring the length (mm) of each follicle. The growth rate (increased length) of each follicle after 7 days of treatment was calculated by subtracting the length at time 0 h (before the start of treatment) from the length after 7 days of treatment, and expressed in millimeters (mm).

[0094] Results

[0095] Hair follicles treated with the hair growth composition, identified as the test product at a concentration of 0.01% w / w, surprisingly increased hair length by 119.8% compared to the control group (no treatment). The positive control, under the same conditions, stimulated hair growth by 246.5%, while the comparator product (benchmark) promoted a statistically non-significant increase of 29.5% (Figure 1).

[0096] As seen in Figure 1, the composition for growth The test product was able to intensely stimulate hair growth in culture. The measurement of hair length indicated a statistically significant increase of 119.8% compared to the control group, while the benchmark was able to stimulate hair growth by 29.5%, under the same experimental conditions.

[0097] Industrial Application

[0098] The products can be used as cosmetic, dermatological, or pharmaceutical compositions for topical use capable of modulating hair growth. These compositions may, for example, consist of creams for cleansing, protection, treatment, or care, lotions, gels, or mousses for skin and / or scalp care, such as cleansing or disinfecting lotions, or bath compositions. They can also be used for the skin and / or scalp in the form of solutions, tonics, creams, gels, emulsions, mousses, or in the form of aerosol compositions also containing a pressurized propellant.

[0099] The examples revealed here are intended to merely exemplify some of the numerous forms of realization and use of the present invention, without limiting the interpretation of its scope and breadth, as well as, on possible alternative forms and variations thereof, which will be defined based on the claims presented here.

Claims

Claims 1. Composition for modulating hair growth characterized by comprising the non-polar fraction of extract from the Bidens pilosa plant.

2. Composition according to claim 1, characterized in that the non-polar fraction of the extract is obtained by supercritical fluid extraction of Bidens pilosa.

3. Composition according to claim 2, characterized in that the supercritical fluid is Carbon Dioxide (CO2).

4. Composition according to any one of the preceding claims, characterized in that it comprises between 0.01% and 20% by mass of non-polar extract of Bidens pilosa.

5. Composition according to any one of the preceding claims, characterized in that it comprises between 0.01% and 10% by mass of non-polar extract of Bidens pilosa; optionally between 0.01% and 5% by mass of non-polar extract of Bidens pilosa; or; optionally between 0.01% and 1% by mass of non-polar extract of Bidens pilosa.

6. Composition according to any one of the preceding claims, characterized in that it additionally comprises at least one of: 20% to 85%, by mass, of triglycerides containing saturated fatty acids, mono and / or polyunsaturated fatty acids; 1% to 30% by mass of phytosterols; 0.1% to 10% by mass of diterpenes; 1% to 10% by mass of free fatty acids; 0.1% to 10% by mass of hydroxycinnamic acid derivative; and / or; 0.01% to 0.5% by mass of antioxidant.

7. Composition according to any one of the preceding claims, characterized in that said modulation of hair growth is by topical application of the composition to a human or animal in a region comprising hair follicles.

8. Composition according to any one of the preceding claims, characterized in that it is a cosmetic, dermatological or pharmaceutical composition.

9. Process for producing a composition as defined in any of the preceding claims, characterized by comprising the supercritical extraction with carbon dioxide (CO2) of the aerial parts of the Bidens pilosa plant, previously dehydrated and crushed.

10. Use of a composition as defined in any one of claims 1 to 8, characterized in that it is for modulating hair growth in a human or animal. 1 1. Method for modulating hair growth in a human or animal, characterized by comprising the topical application of a composition as defined in any one of 1 to 8 in a cosmetic, dermatological or pharmaceutically effective amount on a region of the skin comprising hair follicles.

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