Oral composition comprising extracts of epilobium, nigella and boswellia, for improving hair growth and hair health

Abstract

It relates to an oral composition comprising Epilobium parviflorum extract, Nigella sativa extract, and Boswellia serrata extract in specific amounts and ratios. It also relates to the oral composition for use in the treatment of hair loss. The present invention also relates to the use of the oral composition for improving brightness, hydration, elasticity, firmness, and / or hair shine; or for improving brightness, hydration, elasticity, and firmness of the skin.

Description

[0001] ORAL COMPOSITION COMPRISING EXTRACTS OF EPILOBIUM, NIGELLA AND BOSWELLIA, FOR IMPROVING HAIR GROWTH AND HAIR HEALTH

[0002] This application claims the benefit of European Patent Application EP24382855 filed 01 August 2024.

[0003] Technical Field

[0004] It relates to the field of compositions and its uses for improving hair appearance, restoration of hair growth and prevention of hair loss.

[0005] Background Art

[0006] Hair loss is a prevalent condition affecting millions of individuals globally. The causes of hair loss are multifaceted, ranging from genetic predispositions and hormonal imbalances to environmental factors, age-related oxidative stress and lifestyle choices. Among the most common forms of hair loss are androgenetic alopecia (male and female pattern baldness), telogen effluvium, and alopecia areata.

[0007] Understanding the underlying mechanisms of hair loss is crucial for developing effective treatments. Hair growth is a complex biological process regulated by the hair follicle cycle, which includes phases of growth (anagen), regression (catagen), and rest (telogen). Disruptions in this cycle can lead to various forms of hair loss. For instance, although not the only cause, psychological or physiological stress is one of the major factors driving telogen effluvium, as it leads to elevated cortisol levels that disrupt the hair growth cycle, resulting in thinner hair and eventual hair loss. Elevated cortisol has also been shown to contribute to the pathogenesis of androgenetic alopecia and alopecia areata (Thom, 2016). In contrast, androgenetic alopecia is primarily driven by dihydrotestosterone (DHT), a derivative of testosterone that shrinks hair follicles, leading to thinner hair and eventual hair loss.

[0008] The market for hair loss treatments encompasses a wide array of products and methods, each aiming to target different aspects of the condition. Pharmaceutical formulations, such as minoxidil and finasteride, are widely recognized for their efficacy in promoting hair growth and reducing hair loss. Minoxidil is a topical solution that stimulates hair growth although its mechanism of action remains poorly understood, while finasteride is an oral medication that inhibits human 5-alpha-reductase type II in the hair follicle, inhibiting the conversion of testosterone to dihydrotestosterone (DHT).

[0009] Treatments with minoxidil or finasteride present significant challenges that hinder their widespread adoption as hair growth treatments due to side effects or indication limitations. For instance, finasteride is not indicated in women and users can suffer from sexual dysfunction. There are also potential long-term safety concerns with finasteride, such as risks of prostate cancer and depression.

[0010] Cosmetic products, including specialized shampoos, conditioners, and serums, offer another approach by nourishing the scalp and hair follicles, potentially improving hair health and growth. Many of these products incorporate ingredients like biotin, caffeine, and ketoconazole, which are believed to support hair strength and vitality. However, cosmetics are often restricted to superficial action.

[0011] Herbal extracts, essential oils and dietary supplements are nowadays highly demanded natural products that include or combine vitamins, minerals, herbal extracts or other natural actives that are commonly used to address hair loss, especially when consumed together with a healthy diet and lifestyle. For example, saw palmetto extract and green tea extract inhibit DHT production, while essential oils like rosemary and lavender improve scalp circulation and hair growth.

[0012] For instance, US10688037B1 provides a nutraceutical supplement composition that simultaneously inhibits the molecular triggers of hair loss associated with stress and androgens and further addresses the concurrent cascade of disordered cytokine signaling, inflammation and oxidative damage that is brought on by their activity, thereby preventing damage and shrinkage to hair follicles and promoting more follicles to enter a healthy hair cycle in a multi-targeted, comprehensive manner. Accordingly, the patent provides a composition for promoting hair growth and reducing hair loss, comprising an extract of Curcuma longa, an extract of the roots and leaves of Withania somnifera, saw palmetto extract, and Iodine.

[0013] Natural treatments for hair growth include supplements comprising biotin, saw palmetto extract, iron, niacin, selenium, or collagen peptides.

[0014] In some cases, there are difficulties in preparing formulations of supplements, especially in a liquid format and when using herbal extracts with low solubility, making it challenging to develop effective compositions.

[0015] Despite the wide array of existing treatments for hair loss, there remains a significant unmet need for a comprehensive natural solution that effectively combines efficacy, safety, and user convenience. It is therefore desirable to find solutions that enhance the overall treatment efficacy and user experience and improving the bioavailability to meet the unmet needs of individuals struggling with hair loss, offering a solution that is both effective and user-friendly.

[0016] Summary of Invention

[0017] The oral composition of the present invention has been shown to reduce hair loss and promote hair growth in individuals suffering from various types and degrees of hair loss. It addresses the main underlying causes of hair loss using natural remedies without pharmacological side effects while providing the necessary nutrition for improved hair growth.

[0018] Inventors have found that a combination of herbal extracts in specific amounts, specifically Epilobium parviflorum extract Nigella sativa extract, and Boswellia serrata extract, when administered orally, allow maximization of positive effects on hair treatment while avoiding the usual side effects of the common pharmacological treatments indicated for hair loss, further enhancing the overall treatment efficacy and user experience.

[0019] Therefore, in a first aspect, the present invention relates to an oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 25:1 to 1 :30; the Epilobium parviflorum extract is a dry extract from the herb which comprises phenolic acids, tannins, flavonoids, and a content of polyphenols of at least 5% by weight; the Nigella sativa extract is a powder extracted from the seeds of the plant, and which comprises thymoquinone; and the Boswellia serrata extract is dry extract derived from the resin of Boswellia serrata trees comprising a minimum of 12% total boswellic acids by weight.

[0020] The oral composition may be combined with vitamins, amino acids, minerals, proteins, carbohydrates, fats, flavorings, prebiotics, probiotics, postbiotics, herbal extracts, sweeteners, and antioxidants. The inventors have found that such oral composition provides several benefits for the treatment of hair, including also cosmetic benefits.

[0021] In a second aspect, the present invention relates to an oral composition as defined above, for use in the prevention and / or treatment of hair loss.

[0022] This oral composition can also be used to enhance hair health and improve skin appearance. Specifically, it targets the hair follicle and skin appendages, which are components derived from both the epidermis and dermis, including hair. Thus, in a third aspect, the present invention relates to the use of the oral composition as defined above, either for improving brightness, hydration, elasticity, firmness, and / or hair shine; or for improving brightness, hydration, elasticity, and firmness of the skin.

[0023] In a fourth aspect, the present invention relates to the use of an oral composition as defined above, for the prevention and / or treatment of natural hair loss.

[0024] Brief Description of Drawings

[0025] FIG. 1: Graphical representation of the results showing the ALPL (alkaline phosphatase gene) expression of HFDPC after treatment with Nigella sativa (N) Epilobium parviflorum

[0026] (E) + Boswellia serrata (B) mixture (4:1) and Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) compared to the cortisone control. Asterisks represent statistical significance as follows: ** p-value < 0.01.

[0027] FIG. 2: Graphical representation of the results showing the recovery percentage of ALPL

[0028] (alkaline gene) expression of HFDPC after treatment with Nigella sativa (N),

[0029] Epilobium parviflorum (E) + Boswellia serrata (B) mixture (4:1) and Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) compared to the cortisone control. The recovery percentage was calculated considering the decrease in expression induced by cortisol as a reference and represents how much of that negative effect was reversed by the extracts. Asterisks represent statistical significance as follows: ** p-value < 0.01.

[0030] FIG. 3: Graphical representation of the results showing the cell viability of HFDPC after treatment with Nigella sativa for 72 hours compared to the cortisone control. Asterisks represent statistical significance as follows: ** p-value < 0.01 and **** p-value < 0.0001.

[0031] FIG. 4: Graphical representation of the results showing the cell viability of HFDPC after treatment with Epilobium parviflorum + Boswellia serrata (4:1) for 72 h compared to the cortisone control. Asterisks represent statistical significance as follows: * p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001 and **** p-value < 0.0001.

[0032] FIG. 5: Graphical representation of the results showing the cell viability of HFDPC after treatment with Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) for 72 h compared to the cortisone control. Asterisks represent statistical significance as follows: * p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001 and **** p-value < 0.0001. FIG. 6: Graphical representation of the results showing the growth rate (normalized length) of each follicle after 7 days of treatment with (A) Epidermal Growth Factor (EGF) 20 ng / ml and (B) Nigella sativa (Nig) and Epilobium parviflorum (Epi) + Boswellia serrata (Bos). Statistical significance is depicted as * for p < 0.05.

[0033] FIG. 7: Graphical representation of the results showing the growth rate (normalized length) of each follicle after 7 days of treatment with (A) EGF 20 ng / ml and (B) Nig. Statistical significance is depicted as * for p < 0.05.

[0034] FIG. 8: Graphical representation of the results showing the growth rate (normalized length) of each follicle after 7 days of treatment with (A) EGF 20 ng / ml and (B) Nig+Epi+Bos. Statistical significance is depicted as * for p < 0.05.

[0035] Detailed description of the invention

[0036] All terms as used herein in this application, unless otherwise stated, shall be understood in their ordinary meaning as known in the art. Other more specific definitions for certain terms as used in the present application are as set forth below and are intended to apply uniformly throughout the specification and claims unless an otherwise expressly set out definition provides a broader definition.

[0037] For the purposes of the invention, any ranges given include both the lower and the upper endpoints of the range. Ranges given, such as temperatures, quantities, times, sizes, and alike, should be considered approximate, unless specifically stated.

[0038] The oral composition of the present invention is considered a food supplement. The term “food supplement” refers to concentrated sources of nutrients (i.e. minerals and vitamins) or other substances with a nutritional or physiological effect that are marketed in “dose” form. A wide range of nutrients and other ingredients might be present in food supplements, including, but not limited to, vitamins, minerals, amino acids, essential fatty acids, fiber and various plants and herbal extracts. The food supplement for hair loss of the present invention refers to a composition comprising phytochemical ingredients, designed to promote hair growth and reduce hair loss without the use of synthetic drugs. The term “phytochemical ingredients” refers to naturally occurring chemical compounds in plants.

[0039] The oral composition of the present invention may also be considered a nutraceutical.

[0040] For the purposes of the invention, commercial extracts can be used for any of the extracts present in the composition.

[0041] The term “room temperature” as disclosed herein refers to a temperature of the environment, without heating or cooling, and is generally comprised from 20 to 25 °C.

[0042] The expression "effective amount for use in the treatment of hair loss”, refers to the amount of a compound that, when administered, is sufficient mainly to reduce hair loss and promote hair growth. It can be an effective amount to be used in a complementary therapy to pharmacological treatments.

[0043] The expression "effective amount” when used for cosmetic purposes, refers to the amount of a compound that, when administered, is sufficient to provide cosmetic benefits such as improves brightness, hydration, elasticity, firmness, and / or hair shine.

[0044] The expression “natural hair loss” refers to the physiological shedding of hair that occurs as part of the normal hair growth cycle, in the absence of any pathological, chemical, mechanical or environmental insult.

[0045] The expression “non-therapeutic treatment” refers to any method applied to the human or animal body whose intended effect is achieved without the administration of a pharmacologically active agent (e.g. a drug, medicament, or vaccine) to obtain its result.

[0046] When the intended used is for improving brightness, hydration, elasticity, and firmness of the skin; an effective amount is the amount of a compound that, when administered, is sufficient to provide such cosmetic benefits. The safe and effective amount of the active ingredients will vary with the age of the consumer, the condition of the skin, the duration of the treatment, the nature of any concurrent treatment, the specific combination of active ingredients employed, the particular cosmetically acceptable carrier utilized, and like factors.

[0047] As mentioned above, one aspect of the present invention relates to an oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 25:1 to 1 :30; the Epilobium parviflorum extract is a dry extract from the herb which comprises phenolic acids, tannins, flavonoids, and a content of polyphenols of at least 5% by weight; the Nigella sativa extract is a powder extracted from the seeds of the plant, and which comprises thymoquinone; and the Boswellia serrata extract is dry extract derived from the resin of Boswellia serrata trees comprising a minimum of 12% total boswellic acids by weight.

[0048] As used herein, “dry extract” denotes an extract from which the extraction solvent has been removed to yield a solid material (e.g., powder, granules or flakes). Minor residual moisture typical of such materials may be present. Unless stated otherwise, all quantitative amounts for the extract refer to the dry matter of the extract. The dry extract may be used as such to prepare the oral composition of the present invention or dissolved or dispersed prior its use in a food-acceptable carrier, for example water, glycerol (glycerin) or mixtures thereof. Both are considered equivalent embodiments of the present invention and fall within the scope of the invention.

[0049] In a particular embodiment, the combination of herbal extracts in specific amounts, specifically Epilobium parviflorum hydro-alcoholic extract containing >5% polyphenols, Nigella sativa seed water extract, and Boswellia serrata extract containing >30% acetyl- keto-beta-boswellic acid, when administered orally, allows maximization of positive effects on hair treatment. The percentages are by weight.

[0050] Epilobium parviflorum is the herbaceous perennial plant of the Onagraceae family. This plant occurs in most parts of Europe, Northern Africa and Western Asia. Willowherb tea exhibits anti-inflammatory, diuretic and antioxidative properties. It is used for gastrointestinal and prostate disorders, mucous membrane lesions and improving wound healing. Epilobium parviflorum species comprise or contain phenolic acids (e.g., gallic acid, chlorogenic acid, (Z)-p-coumaric acids), tannins, flavonoids (e.g., myricetin, catechin, koempherol), steroids and terpenes. Particularly, depending on the herb species and plant parts, the content of polyphenols in lyophilizate from an aqueous solution is 9-19%, along with tannins 6-32% and flavonoids. The percentages are by weight.

[0051] In particular, the Epilobium parviflorum extract may be a dry extract presented as a brown powder. The part of the plant used for this extract is the herb. The solvents employed in the extraction process are generally water and alcohol, particularly a hydroalcoholic solvent. The extract is partially soluble, with an extraction ratio generally around 10:1. Extraction ratios may be in a range from 4:1 to 20:1. The ratios given are by weight. It contains polyphenols in a concentration of at least 5% by weight. The content of polyphenols may be measured by UV spectrophotometry. The particle size of the extract generally is at least around 80 MESH. In a particular embodiment, the particle size may be at least 80 MESH. In a particular embodiment, the purity parameters include a total ash content of not more than 10% and a loss on drying of not more than 5%. The relative density of the extract generally ranges from 40 to 60 grams per 100 milliliters. Additionally, the extract is generally GMO-free and has not been irradiated.

[0052] In a particular embodiment, the Epilobium parviflorum extract is a dry extract which comprises phenolic acids, tannins, flavonoids, a content of polyphenols is 9-19% by weight and the content of tannins is 6-32% by weight;

[0053] Boswellia serrata is derived from the resin of Boswellia serrata trees. It has been used for centuries in traditional medicine for its anti-inflammatory properties. The key bioactive components responsible for these effects are boswellic acids. The Boswellia serrata extract is an oleoresin derived from the resin of Boswellia serrata trees comprising a minimum of 12% by weight total boswellic acids with low solubility. The extract may be obtained using a solvent selected from methanol, ethanol, supercritical carbon dioxide, water, and ethilacetate. It is characterized by its brown color and turbid dilution in water. The part of the plant used for this extract is the oleoresin from the tree. The extract is standardized to contain a minimum of 12% total boswellic acids and is partially soluble. Particularly, the content may be in a range comprised from 12 to 65% total boswellic acids. Additionally, the extract is generally GMO-free and has not been irradiated. All the percentages are given by weight.

[0054] Nigella sativa, also known as black seed or black cumin, has been used in traditional medicine for its broad range of therapeutic properties, including anti-inflammatory effects. The primary active component is thymoquinone. The Nigella sativa L. extract is presented as a brown-yellow powder. The part of the plant used for this extract is the seeds. The extract may have a content of at least 0.5% of thymoquinone. Maltodextrin (carrier, typically 10-60% w / w) is generally present. Generally, the extraction solvent used is water and ethanol. Typically, the extract has a total content of polyphenols of 1.4% by weight using the Folin-Ciocalteu colorimetric method (A760 nm). The extract is partially soluble, with an extraction ratio generally of 4:1. Extraction ratios may be in a range from 4:1 to 20:1. The ratios given are by weight. The relative density of the extract generally ranges from 40 to 60 grams per 100 milliliters, and the particle size is generally at least around 80 MESH. The loss on drying is not more than 5%. Additionally, the extract is generally GMO-free and non-irradiated.

[0055] The colorimetric method indicated above is well-known for the skilled person in the art.

[0056] In a particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 15:1 to 1:20. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 10:1 to 1:15. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 5:1 to 1 :10. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in ratio of 4:3.

[0057] In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 20 to 400 mg; b) Nigella sativa extract in an amount from 20 to 700 mg; and c) Boswellia serrata extract in an amount from 20 to 500 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 10:1 to 1 :20. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 20 to 300 mg; b) Nigella sativa extract in an amount from 20 to 500 mg; and c) Boswellia serrata extract in an amount from 20 to 400 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 15:1 to 1 :20. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 20 to 200 mg; b) Nigella sativa extract in an amount from 20 to 200 mg; and c) Boswellia serrata extract in an amount from 20 to 200 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 15:1 to 1:20. In another particular embodiment, the oral composition comprising: a) Epilobium parviflorum extract in an amount from 25 to 100 mg; b) Nigella sativa extract in an amount from 25 to 100 mg; and c) Boswellia serrata extract in an amount from 25 to 100 mg; is that where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 5:1 to 1 :8.

[0058] In a particular embodiment, the oral composition as defined above, is that where the weight ratio Nigella sativa extract : Boswellia serrata extract are in range from 20:1 to 1:20 In another particular embodiment, the oral composition as defined above, is that where the weight ratio of Nigella sativa extract : Boswellia serrata extract are in a range from 10:1 to 1:10 In another particular embodiment, the oral composition as defined above, is that where the weight ratio of Nigella sativa extract : Boswellia serrata extract are in a range from 5:1 to 1:5. In another particular embodiment, the oral composition as defined above, is that where the weight ratio of Nigella sativa extract : Boswellia serrata extract are in a range from 2:1 to 1 :2.

[0059] Salvia officinalis L. extract is known for its beneficial effects on hormonal balance, as it contributes to the alleviation of menopausal symptoms by potentially modulating estrogen levels. This can result in a reduction in hair loss, a common issue faced by women undergoing menopause. In a particular embodiment, the oral composition as defined above, further comprises Salvia officinalis L. extract from the leaves and stems of the plant.

[0060] The Salvia officinalis L. extract is a dry extract presented as a brown-yellow powder. The parts of the plant used for this extract are the aerial parts, specifically the leaves and stems. The solvents employed in the extraction process are selected from water, ethanol, water with ethanol, and supercritical carbon dioxide. Extraction ratios may be in a range from 5:1 to 20:1. In particular, the extraction ratio is around 5:1 , and the extract contains at least 2.5% rosmarinic acid. In particular, the extract contains rosmarinic acid in an amount from 2.5% to 10% of the extract. It is partially soluble. Maltodextrin is included in the formulation at a concentration of less than 10%. The total ash content is not more than 10%, and the loss on drying is not more than 5%. The relative density of the extract ranges from 40 to 60 grams per 100 milliliters, and the particle size is at least 80 MESH. Additionally, the extract is GMO-free and has not been irradiated. All the percentages are given by weight.

[0061] In another particular embodiment, the oral composition as defined above is that which comprises Salvia officinalis L. extract in an amount from 10 to 500 mg, wherein the extract is a dry extract which comprises at least 2.5% rosmarinic acid. In another particular embodiment, the oral composition as defined above is that which comprises Salvia officinalis L. extract in an amount from 25 to 300 mg, wherein the extract is a dry extract which comprises at least 2.5% rosmarinic acid. In another particular embodiment, the oral composition as defined above is that which comprises Salvia officinalis L. extract in an amount from 50 to 200 mg, wherein the extract is a dry extract which comprises at least 2.5% rosmarinic acid. In another particular embodiment, the oral composition as defined above is that which comprises Salvia officinalis L. extract in an amount of 100 mg, wherein the extract is a dry extract which comprises at least 2.5% rosmarinic acid. The extract of these embodiments may be further characterized as defined above.

[0062] Postbiotics, which are a preparation of inanimate microorganisms and / or their components that confer a health benefit on the host, play a significant role in enhancing scalp health and promoting hair growth. Postbiotics help maintain a balanced scalp microbiome, reduce inflammation, and support the natural hair growth cycle. In a particular embodiment, the oral composition as defined above, further comprises postbiotics.

[0063] In another particular embodiment, the oral composition as defined above, is that where the postbiotics, when are present, are in an amount equal to or less than 50 mg. In another particular embodiment, the oral composition as defined above, is that where the postbiotics, when are present, are in an amount equal to or less than 40 mg. In another particular embodiment, the oral composition as defined above, where the postbiotics, when are present, are in an amount equal to or less than 30 mg. In another particular embodiment, the oral composition as defined above is that where the postbiotics, when are present, are in an amount equal to or less than 20 mg. In another particular embodiment, the oral composition as defined above, is that where the postbiotics, when are present, are in an amount equal to or less than 10 mg. In another particular embodiment, the oral composition as defined above, is that where the postbiotics, when are present, are in an amount equal to or less than 5 mg.

[0064] Examples of appropriate postbiotics are Lactobacillus plantarum tyndallized, Lactobacillus paracasei tyndallized, Lactobacillus reuteri tyndallized, Lactobacillus acidophilus tyndallized, Bifidobacterium longum tyndallized, and Bifidobacterium lactis tyndallized.

[0065] In a particular embodiment, the oral composition as defined above, is that where the postbiotics are selected from the group consisting of Lactobacillus plantarum tyndallized, Lactobacillus paracasei tyndallized, Lactobacillus reuteri tyndallized, Lactobacillus acidophilus tyndallized, Bifidobacterium longum tyndallized, Bifidobacterium lactis tyndallized, Bacillus subtilis, and mixtures thereof.

[0066] Other examples of appropriate antiinflamatories for the purpose of the present invention are Curcuma longa, omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), green tea extract, ginger extract, quercetin, ashwagandha extract, bromelain, rosemary extract, resveratrol, black cumin seed oil, licorice root extract, garlic extract, holy basil extract, and white willow bark extract.

[0067] Thus, in a particular embodiment, the oral composition as defined above, comprises a further antiinflamatory compound selected from the group consisting of: Curcuma longa, omega-3 fatty acids (EPA and DHA), green tea extract, ginger extract, quercetin, bromelain, rosemary extract, resveratrol, black cumin seed oil, licorice root extract, garlic extract, holy basil extract, and white willow bark extract, and mixtures thereof.

[0068] Other examples of appropriate 5-alpha reductase inhibitors for the purpose of the present invention are saw palmetto extract, pygeum extract, green tea extract (EGCG), reishi mushroom extract, pumpkin seed oil, nettle root extract, beta-sitosterol, flaxseed lignans, black cohosh extract, soy isoflavones, linoleic acid, oleic acid, zinc, and lycopene.

[0069] In a particular embodiment, the oral composition as defined above, comprises a further 5- alpha reductase inhibitor selected from the group consisting of: saw palmetto extract, pygeum extract, and mixtures thereof; wherein the Saw Palmetto extract is a dry extract from the berry which comprises at least 45 % total free fatty acids by weight; and the Pygeum extract is a dry extract from the inner bark of Prunus africana which comprises at least 12 % total phytosterols by weight.

[0070] In particular, the Saw Palmetto extract may be an off-white to light-brown dry powder or an oil. The part of the plant used is the berry (fruit). The extraction process may use water and alcohol, particularly a hydroalcoholic solvent. It may also use supercritical fluids as extraction solvents. Extraction ratios may be in a range from 4:1 to 200:1. In particular, the extraction ratio may be 5:1. The extraction ratio may also be 8:1 to 10:1. It is standardised to contain > 45 % total free fatty acids. The extract may have a content of at least 0,1 % total sterols expressed as beta-sitosterols. The particle size generally corresponds to at least 80 MESH. In particular, quality parameters include a total ash content of not more than 5 % and a loss on drying of not more than 5 %. The density of the powder typically ranges from 40 to 60 g / 100 mL, with a tapped density of 60-90 g / 100 mL. Additionally, commercial grades are supplied as GMO-free, non-irradiated material. The percentages are by weight.

[0071] The Pygeum extract may be a brown-yellow to reddish-brown dry powder obtained from the inner bark of Prunus africana. The extraction process may use a solvent selected from water, ethanol, water with ethanol, and supercritical fluids such as supercritical carbon dioxide. Extraction ratios may be in a range from 4:1 to 200:1. In particular, the extraction ratios may be in a range from 5:1-20:1. The extract is standardised to contain at least 10 % total phytosterols (P-sitosterol, campesterol, stigmasterol). In particular, it may contain 12% total phytosterols. Particle size is at least around 80 MESH. Density for the powder generally falls in the 40-60 g / 100 mL range. The Pygeum extract may be GMO-free and non-irradiated. The percentages are by weight.

[0072] In a particular embodiment, the oral composition as defined above further comprising additional components selected from the group consisting of vitamins, amino acids, amino acids precursors, minerals, proteins, carbohydrates, prebiotics, probiotics, herbal extracts, fats, flavorings, sweeteners, antioxidants, and a mixture thereof.

[0073] Example of appropriate vitamins are Vitamin C, Vitamin E, Biotin, Vitamin D3, Niacinamide (Vitamin B3), Calcium Pantothenate (Vitamin B5), Pyridoxine Hydrochloride (Vitamin B6), Folic Acid (Vitamin B9), Cyanocobalamin (Vitamin B12).

[0074] Examples of appropriate amino acids are Arginine, Aspartic acid, Alanine, Serine, Valine, Proline, Threonine, Isoleucine, Histidine, Phenylalanine, Cysteine, and Glutamine.

[0075] Examples of appropriate minerals are zinc, iron, magnesium, selenium, copper, calcium, manganese, potassium, silicon, chromium, iodine, phosphorus, molybdenum, sulfur, and sodium.

[0076] Examples of appropriate carbohydrates are fructose, glucose, maltodextrin, inulin, betaglucan, xylitol, D-ribose, arabinogalactan, isomaltulose, pectin, oligofructose, trehalose, starch, cyclodextrin, galactooligosaccharides (GOS), polydextrose, sorbitol, erythritol, lactose, and mannitol.

[0077] Examples of appropriate proteins are hydrolyzed collagen, keratin, whey protein, pea protein, rice protein, soy protein isolate, hemp protein, bone broth protein, egg white protein, fish protein, beef protein isolate, spirulina, chlorella, and casein protein, collagen peptides, silk protein, quinoa protein, oat protein, milk protein concentrate, pumpkin seed protein, sunflower seed protein, almond protein, and fava bean protein.

[0078] Examples of appropriate fats are sucrose esters of fatty acids, omega-3 fatty acids (EPA and DHA), omega-6 fatty acids (linoleic acid), omega-9 fatty acids (oleic acid), mediumchain triglycerides (MCTs), evening primrose oil, borage oil, flaxseed oil, chia seed oil, coconut oil, avocado oil, walnut oil, pumpkin seed oil, hemp seed oil, black currant seed oil, conjugated linoleic acid (CLA), phospholipids (such as phosphatidylcholine), lecithin, and fish oil.

[0079] Examples of appropriate flavorings are natural vanilla extract, natural strawberry flavor, natural blueberry flavor, natural raspberry flavor, natural lemon flavor, natural orange flavor, natural mint flavor, natural cherry flavor, natural peach flavor, natural apple flavor, natural pineapple flavor, natural mango flavor, natural grape flavor, natural watermelon flavor, natural coconut flavor, natural cinnamon flavor, natural chocolate flavor, natural caramel flavor, and natural almond flavor.

[0080] Examples of appropriate antioxidants are Turmeric (Curcuma longa), Resveratrol, Astaxanthin, Licorice (Glycyrrhiza glabra), Bilberry (Vaccinium myrtillus) green tea extract (Camellia sinensis), quercetin, coenzyme Q10, alpha-lipoic acid, selenium, Zinc bisglycinate, N-acetylcysteine, grape seed extract (Vitis vinifera), lutein, zeaxanthin, betacarotene, lycopene, pycnogenol (pine bark extract), curcumin, melatonin, glutathione, rosemary extract (Rosmarinus officinalis), pomegranate extract (Punica granatum), olive leaf or fruit extract (Olea europaea), and tocotrienols.

[0081] In a particular embodiment, the oral composition as defined above is a liquid oral composition.

[0082] The oral composition of the present invention overcomes the challenges associated with poor aqueous solubility and limited bioavailability, as well as inconsistent efficacy of the extracts from Boswellia serrata, Nigella sativa, and Epilobium parviflorum extracts when administered in oral dosage forms.

[0083] These botanical extracts are known for their anti-inflammatory, antioxidant, or healthpromoting properties. However, their efficacy in traditional solid oral dosage forms is hampered by their limited solubility and subsequent poor absorption in the gastrointestinal tract. By providing these active ingredients in a liquid oral composition, the invention significantly enhances the solubility and absorption of the active ingredients in the gastrointestinal tract. This improvement leads to higher and more consistent plasma concentrations, resulting in better efficacy in reducing hair loss and promote hair growth as a complementary therapy to pharmacological treatments and more predictable pharmacokinetic profiles.

[0084] The liquid oral compositions of the present invention offer a more rapid onset of action and consistent effect, particularly beneficial for patients who have difficulty swallowing pills or require faster relief. This can be achieved by the combination of active ingredients and excipients of the present liquid oral composition of the present invention, specifically, the excipients used in these compositions allow the formulation to deliver these botanical extracts, Boswellia Serrata, Nigella sativa, and Epilobium parviflorum extracts, in a more bioavailable form, resulting in improved outcomes compared to traditional solid oral dosage forms. The liquid oral compositions of the present invention may comprise a broad spectrum of excipients such as surfactants, cosolvents, taste-masking agents, diluents to adjust the concentration and viscosity of the formulation, ensuring ease of administration and consistent dosing.

[0085] Appropriate surfactants may be non-ionic surfactants, ionic surfactants, and amphoteric surfactants.

[0086] Examples of appropriate non-ionic surfactants are: Polysorbates (e.g., Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 80), Polyoxyl 35 castor oil, Polyoxyl 40 hydrogenated castor oil (Cremophor EL), Sorbitan esters (e.g., Sorbitan monolaurate, Sorbitan monooleate, Sorbitan monopalmitate), Polyethylene glycol (PEG) esters, Sucroesters, Poloxamers (e.g., Poloxamer 188, Poloxamer 407), and Lauryl macrogolglycerides.

[0087] Examples of appropriate ionic surfactants are Sodium lauryl sulfate (SLS), Sodium dodecyl sulfate (SDS), Sodium stearate, Sodium oleate, Sodium cetostearyl sulfate, and Sodium caprylate.

[0088] Examples of appropriate amphoteric surfactants are Cocamidopropyl betaine, Cocamphocarboxyglycinate, Cocamidopropyl hydroxysultaine, Lauryl betaine, and Lauryl dimethylamine oxide.

[0089] Examples of appropriate cosolvents are Glycerol, Propylene glycol, Polyethylene glycol (PEG) 400, PEG 600, Diethylene glycol monoethyl ether (Transcutol), Isopropanol, 1,2- Propylene glycol, Polyethylene glycol (PEG) 2000, PEG 3350, PEG 6000, Caprylic / capric triglyceride (MCT oil), N-Methyl-2-pyrrolidone (NMP).

[0090] Examples of appropriate taste-masking agents are natural sweeteners (e.g., stevia, monk fruit extract, licorice root extract), artificial sweeteners (e.g., sucralose, aspartame, saccharin, acesulfame potassium), sugar alcohols (e.g., xylitol, sorbitol, maltitol, erythritol), flavors (e.g., fruit flavors like cherry, orange, lemon; mint; vanilla; chocolate), essential oils (e.g., peppermint oil, lemon oil), acidulants (e.g., citric acid, malic acid, tartaric acid), salts (e.g., sodium chloride, potassium chloride), masking agents (e.g., cyclodextrins, tannins), aromatic compounds (e.g., vanillin, ethyl vanillin, menthol), or texturizers (e.g., glycerin, xanthan gum).

[0091] Examples of appropriate diluents include water or aqueous solutions. Thus, in a particular embodiment, the oral composition as defined above is a liquid oral composition comprising water as diluent.

[0092] The extracts of the oral liquid composition of the present invention may be used in encapsulated form. The inclusion of carriers such as liposomes, nanoparticles, or micelles serves to encapsulate such extracts, facilitating enhanced absorption and bioavailability. Examples of appropriate carriers are liposomes, nanoparticles, micelles, cyclodextrins, phospholipid complexes, solid lipid nanoparticles, nanostructured lipid carriers (NLCs), self-emulsifying drug delivery systems (SEDDS), microemulsions, nanoemulsions, hydrophilic polymers, biodegradable polymers, surfactant-stabilized emulsions, phytosomes, nanosuspensions, carrageenan, alginates, film-coating cellulose derivates or waxes, and colloidal dispersions.

[0093] The nanoparticles also may offer improved stability. The solid lipid nanoparticles (SLNs), and the nanostructured lipid carriers (NLCs) also may offer controlled release and protection of the extracts.

[0094] The liposomes according to the present invention are phospholipid-based carriers.

[0095] Examples of appropriate cyclodextrins are as p-cyclodextrin, hydroxypropyl-p- cyclodextrin, and methyl-p-cyclodextrin. They form inclusion complexes with the active ingredients to enhance solubility.

[0096] Appropriate phospholipid complexes can be those that use phospholipids such as phosphatidylcholine to enhance the bioavailability of the extracts.

[0097] Examples of appropriate hydrophilic polymers are hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), and are used to increase the viscosity and stability of the formulation.

[0098] Examples of appropriate biodegradable polymers are polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), used for controlled release.

[0099] Additionally, the use of taste-masking agents ensures that the formulation is palatable, thus improving patient compliance. Therefore, this invention provides a novel and effective solution for enhancing the bioavailability and efficacy of Boswellia serrata, Nigella sativa, and Epilobium parviflorum extracts.

[0100] The oral composition of the present invention may be used for prevention and / or treatment of hair loss. Thus, an oral composition as defined above, for use in the prevention and / or treatment of hair loss is part of the present invention.

[0101] This oral composition may be used in a subject whose hair loss is caused by a condition selected from androgenetic alopecia, alopecia areata, alopecia mucinosa, telogen effluvium, chronic inflammation, extreme and / or chronic stress, hair treatments, hereditary disorders, hormonal changes, malnutrition, aging and trichotillomania. The treatment of hair loss comprises administering an effective amount of the composition for the treatment in a subject in need thereof.

[0102] The previous use may be also formulated as the use of a combination comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; bj Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; where the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 25:1 to 1 :30. For the manufacture of an oral composition as defined for the prevention and / or treatment of hair loss. It may also be formulated as a method for the treatment of hair loss, the method comprising administering an effective amount of an oral composition as defined above to a subject in need of such treatment.

[0103] In a particular embodiment, the oral composition for use as defined above is that where the prevention and / or treatment comprises reducing hair loss and promoting hair growth as a complementary therapy to pharmacological treatments.

[0104] The oral composition can also be used for improving hair brightness, hydration, elasticity, firmness, and shine.

[0105] It may also be used for cosmetic purposes or for improving brightness, hydration, elasticity, and firmness of the skin.

[0106] The use of antioxidants contributes to protecting the hair from aging and environmental factors primarily and to improve brightness. Antioxidants such as green tea extract, quercetin, and resveratrol help to enhance the overall health and appearance of the hair by reducing oxidative stress, which can otherwise make the hair appear dull.

[0107] Healthy fats, including omega-3 fatty acids (EPA and DHA) and flaxseed oil, help maintain the scalp and hair's moisture levels. Certain carbohydrates, like hyaluronic acid if included, can also aid in retaining moisture and contribute to the hydration. Additionally, proteins like hydrolyzed collagen and silk protein attract and retain moisture, contributing significantly to hair hydration. Amino acids such as L-Glutamine, L-Threonine, and L-Valine play a vital role in contributing to maintaining the hair's elasticity. Precursor amino acids are essential as they facilitate the synthesis of proteins, which are critical for improving hair structure and elasticity.

[0108] Proteins such as keratin and hydrolyzed collagen help to strengthen the hair, making it firmer and more resilient. Minerals such as zinc (for example, Zinc bisglycinate) and other trace minerals are also important as they contribute to the overall strength and structure of the hair.

[0109] The combination of vitamins, fats, and antioxidants also contribute to hair shine. Vitamins such as Vitamin E and biotin (Vitamin B7) are known to enhance hair shine. Healthy oils like argan oil, coconut oil, and omega-3 fatty acids add a natural shine to the hair. Antioxidants such as resveratrol and green tea extract help maintain the natural luster of the hair by protecting it from environmental damage. While flavorings are primarily included for taste, some natural extracts, such as coconut extract, may also have beneficial properties that enhance hair shine.

[0110] Accordingly, the combination of further ingredients of the oral composition of the present invention is especially useful for the intended uses. Thus, it is also part of the present invention the use of the oral composition as defined above, for improving brightness, hydration, elasticity, firmness, and / or hair shine. Particularly, this use comprises administering an effective amount of the oral composition for providing improved brightness, hydration, elasticity, firmness, and / or hair shine.

[0111] In a particular embodiment, the oral composition for any of the intended uses as defined above, is that where the subject is a female. In a particular embodiment, the oral composition for use as defined above, is that where the subject is a male. In another particular embodiment, the oral composition for use as defined above, is that where the subject is over 45 years old, in particular over 50 years old.

[0112] In another particular embodiment, the oral composition for use as defined above, is that which is adapted to be administered once a day.

[0113] It is also an aspect of the present invention the use of an oral composition as defined above, for the prevention and / or treatment of natural hair loss.

[0114] In a particular embodiment, the use of the oral composition as defined above is that where the prevention and / or treatment comprises reducing hair loss and promoting hair growth as a complementary treatment to a non-therapeutic treatment.

[0115] In another particular embodiment, the use of the oral composition as defined above is that where the subject is over 45 years old.

[0116] In another particular embodiment, the use of the oral composition as defined above is that where the subject is a woman.

[0117] In another particular embodiment, the use of the oral composition as defined above is that where the composition is adapted to be administered once a day.

[0118] Throughout the description and claims the word "comprise" and variations of the word, are not intended to exclude other technical features, additives, components, or steps. Furthermore, the word “comprise” encompasses the case of “consisting of”. Additional objects, advantages and features of the invention will become apparent to those skilled in the art upon examination of the description or may be learned by practice of the invention. The following examples and drawings are provided by way of illustration, and they are not intended to be limiting of the present invention. Reference signs related to drawings and placed in parentheses in a claim, are solely for attempting to increase the intelligibility of the claim and shall not be construed as limiting the scope of the claim. Furthermore, the present invention covers all possible combinations of particular and preferred embodiments described herein.

[0119] For reasons of completeness, various aspects of the invention are set out in the following numbered clauses:

[0120] Clauses

[0121] 1. An oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; wherein the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 25:1 to 1:30.

[0122] 2. The oral composition according to clause 1 , wherein the weight ratio of Nigella sativa extract: Boswellia serrata extract are in range from 20:1 to 1 :20. 3. The oral composition according to any of the clauses 1-2, which is a liquid oral composition.

[0123] 4. The oral composition according to any of the clauses 1-3, further comprising Salvia officinalis L. extract.

[0124] 5. The oral composition according to clause 4, wherein the Salvia officinalis L. extract is in an amount from 10 to 500 mg.

[0125] 6. The oral composition according to any of the clauses 1-5, further comprising postbiotics in an amount equal to or less than 50 mg.

[0126] 7. The oral composition according to clause 6, wherein the postbiotics are selected from the group consisting of Lactobacillus plantarum tyndallized, Lactobacillus paracasei tyndallized, Lactobacillus reuteri tyndallized, Lactobacillus acidophilus tyndallized, Bifidobacterium longum tyndallized, Bifidobacterium lactis tyndallized, and mixtures thereof.

[0127] 8. The oral composition according to any of the clauses 1-7, comprises a further 5-alpha reductase inhibitor selected from the group consisting of: Saw Palmetto extract, Pygeum extract, and mixtures thereof.

[0128] 9. The oral composition according to any of the clauses 1-8, comprising additional components selected from the group consisting of vitamins, amino acids, amino acids precursors, minerals, proteins, carbohydrates, prebiotics, probiotics, herbal extracts, fats, flavorings, sweeteners, antioxidants, and a mixture thereof.

[0129] 10. The oral composition according to any of the clauses 1-9, comprising additional excipients selected from the group consisting of surfactants, cosolvents, taste-masking agents, diluents, and mixtures thereof, and, optionally, carriers selected from the group consisting of liposomes, nanoparticles, micelles, cyclodextrins, phospholipid complexes, solid lipid nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, selfemulsifying drug delivery systems, microemulsions, nanoemulsions, hydrophilic polymers, biodegradable polymers, surfactant-stabilized emulsions, phytosomes, nanosuspensions, colloidal dispersions, and mixtures thereof.

[0130] 11. An oral composition as defined in any of the clauses 1-10, for use in the prevention and / or treatment of hair loss. 12. The oral composition for use according to clause 11, wherein the prevention and / or treatment comprises reducing hair loss and promoting hair growth as a complementary therapy to pharmacological treatments.

[0131] 13. The oral composition for use according to any of the clauses 11-12, wherein the subject is over 45 years old.

[0132] 14. The oral composition for use according to any of the clauses 11-13, wherein the composition is adapted to be administered once a day.

[0133] 15. Use of the oral composition according to any of the clauses 1-10, either for improving brightness, hydration, elasticity, firmness, and / or hair shine; or for improving brightness, hydration, elasticity, and firmness of the skin.

[0134] Examples

[0135] The main extracts used in the examples are characterized as follows:

[0136] NIG: Nigella sativa extract is a seed extract with a ratio 4:1 using water and ethanol as extraction solvents. It was measured a total content of polyphenols of 1.4% using the Folin-Ciocalteu colorimetric method (A760 nm). The particle size is at least 80 MESH (177 pm) according to USP 36-786. The relative density is between 40-60g / mL according to Eu.Pharm.7.0-(2.9.34) validated in 2022. It has equal to or less than 10% total ash according to Eu.Pharm.7.0-(2.4.16) validated in 2022. The loss on drying is equal to or less than 5% according to Eu.Pharm.7.0-(2.8.17) validated in 2022.

[0137] EPI: Epilobium parviflorum herb extract with a ratio 10:1 using water and ethanol as solvents with at least 5 % of polyphenols measured by UV spectrophotometry. The particle size is at least 80 MESH. The relative density is between 40-60g / mL according to Eu.Pharm.7.0-(2.9.34) validated in 2024. It has equal to or less than 10% total ash according to Eu.Pharm.7.0-(2.4.16) validated in 2024. The loss on drying is equal to or less than 5% according to Eu.Pharm.7.0-(2.8.17) validated in 2024.

[0138] BOS: Boswellia serrata oleoresin extract 5:1 using methanol as solvent with 65 % boswellic acids measured by titration. The particle size passed 90% through 40 MESH (420 pm). The relative density is between 0.3-0.6g / mL according to USP 616 validated in 2024. It has equal to or less than 10% total ash according to IP-2014. The loss on drying is equal to or less than 5% according to IP-2014. of an oral of extract, sativa extract, and Boswellia serrata extract

[0139] In a 100 ml round bottom flask, 100 mg of Epilobium parviflorum extract, 25 mg of Boswellia serrata extract, and 50 mg Black cumin extract (Nigella sativa extract) were added in 18 ml of H2O and 3 ml of Glycerin, and 3 ml of grape fructose. The mixture was stirred until complete homogenization at room temperature.

[0140] Example 2. Preparation of an oral composition of Epilobium parviflorum extract, Nigella sativa extract, and Boswellia serrata extract with further ingredients

[0141] In a 100 ml round bottom flask, 100 mg of Epilobium parviflorum extract, 25 mg of Boswellia serrata extract, 50 mg Black cumin extract (Nigella sativa extract), 100 mg of Curcuma longa extract, 250 mg of saw palmetto, 30 mg of Zinc bisglycinate (30% Zinc), 10mg of Copper gluconate (14% copper), 80 mg of L-ascorbic acid, 3 mg of D-Biotin, 40 mg of Bilberry extract, 50 mg of Hyaluronic acid, 50 mg of Millet extract, 100 mg of Salvia officinalis L. extract, 100 mg of Ashwagandha extract, 200 mg of L-Glycine, 120 mg of L- Proline, 30 mg of L-Serine, 3 mg of Lactobacillus plantarum tyndallized, 3 mg of Lactobacillus paracasei tyndallized, and 3 mg of Lactobacillus reuteri tyndallized were added in 18 ml of H2O and 3 ml of Glycerin, and 3 ml of grape fructose. The mixture was stirred until complete homogenization at room temperature.

[0142] Example 3. Evaluation of a product according to the present invention for hair treatment Volunteers.

[0143] Women and men aged 45-65.

[0144] Volunteers with Initial Female Pattern Hair Loss (FPHL), potentially with symptom of Telogen Effluvium (TE).

[0145] Commitment not to use systemic, topical, or oral products with an effect similar to that of the product to be evaluated throughout the study period.

[0146] Do not change the daily routine regarding the use of cosmetic products and eating habits.

[0147] Availability to comply with all study visits.

[0148] Product: Oral composition of example 1.

[0149] Mode of Ingestion: Oral Duration: 6 months.

[0150] Results of the treatment after 6 months

[0151] Visual inspection

[0152] In the visual inspection test, the response is classified qualitatively in five categories: 5- points Likert scale (1 = very little; 2 = little; 3 = neutral; 4 = much; and 5 very much). Comb test: results are shown as a percentage of reduction of hair loss.

[0153] Evaluation of side effects

[0154] The patients have not reported any side effects or discomfort either during or after the use of the compositions throughout the entire clinical study.

[0155] Example 4. Evaluation of ALPL (alkaline phosphatase gene) expression analysis by qRT- PCR

[0156] Gene expression analysis of ALPL by qRT-PCR is critical for evaluating hair growth and maintenance of healthy hair follicle function. ALPL upregulates Wnt / p-catenin pathway, one of the main regulators of the hair follicle growth. It is strongly expressed in dermal papilla (DP) cells during the anagen phase of the hair cycle. It is considered a marker of inductive activity and structural integrity within the follicle. Previous studies have shown that cortisol reduces alkaline phosphatase activity in human dermal papilla cells, suggesting that ALPL expression is functionally responsive to glucocorticoid-mediated stress (Lee et al., 2017).

[0157] Analytical equipment

[0158] Inverted microscope, laminar flow hood, cell culture incubator (37°C, 5 % CO2, 90 % relative humidity (RH), Burker chamber, pipettes, rack, plate reader spectrophotometer, Nano-Drop spectrophotometer, vortex, Quant studio 5 (Applied Biosystem) Quantitative real-time PCR, heating block, thermocycler and consumables, statistical analysis software.

[0159] Reagents

[0160] Distilled Water (Braun), HFDPC specific culture medium and supplements (PromoCell), PBS (Gibco), Trypan Blue (Bio-Rad), Trypsin (Sigma-Aldrich), Dimethylsulfoxide (DMSO, SigmaAldrich), MTT reagent [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide](lnvitrogen), RNeasy extraction kit (Qiagen), DNAse-l (Qiagen), PrimeScript RT reagent kit (Perfect Real Time- (TaKaRa)).

[0161] Gene expression analysis by qRT-PCR

[0162] For the gene expression assay, HFDP cells were cultured in supplemented growth medium at a density of 150,000 cells / well in 24-well plates at 37°C, 5 % CO2. 24 hours later the medium was replaced with fresh medium containing cortisone 10'3M and the tested products for 24 hours. Afterwards, cells were collected in lysis buffer to proceed with the RNA extraction. Total RNA was extracted using RNeasy kit (Qiagen) and treated with DNAsel to remove any contamination from genomic DNA. RNA quality and quantity were checked in a Nano-Drop spectrophotometer, and 0.5 g of total RNA was used to synthesize cDNA, using First-strand Synthesis kit (TaKaRa). Finally, quantitative PCR (qPCR) was performed in a real time PCR machine (QuantStudio 5, Applied BioSystem). To perform raw data analysis, we used the 2'AACtmethod (Livak & Schmittgen, 2001) to calculate the gene relative expression ratio to non-treated control (C). Actin (ACT) was used as a reference housekeeping gene. Mathematical model of relative expression ratio in real-time PCR is shown in the equation below.

[0163] The ratio of a target gene is expressed in a treated versus a non-treated control in comparison to a reference gene. CtGO1is the Ct of the Gene of Interest, CtACTis the Ct of the reference housekeeping gene.

[0164] Controls

[0165] C: Negative control=cells at a density of 150.000 cells / well without treatment.

[0166] Cortisone: cells at a density of 150.000 cells / well+cortisone 10'3M. Cortisone is the insult to the cells and decreases the expresion of ALPL gene.

[0167] Samples

[0168] Table 1. Component mixtures concentrations (mg / mL) of Nigella sativa (NIG), Epilobium parviflorum (EPI), and Boswellia serrata (BOS) extracts as described herein In the following table, the concentration of each active at 0.001% of the sample is shown.

[0169] Table 2. Component diluted mixtures at 0.001% of Nigella sativa (NIG), Epilobium parviflorum (EPI), and Boswellia serrata (BOS)

[0170] Results

[0171] Treatment with Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) at 0.001 % for 24 hours significantly increased ALPL gene expression (28.5 ± 9.8%), a well-known marker of dermal papilla cell activity associated with follicular inductive capacity. Nigella sativa by itself under the same conditions as the mixture does not increase the ALPL gene expression. Epilobium parviflorum + Boswellia serrata mixture does show an increase in ALPL gene expression but is markedly lower than the mixture of three. Therefore, it is clearly shown to have a synergistic effect on the ALPL gene expression when combining the three extracts (See FIG. 1).

[0172] Treatment with a mixture of Nigella sativa, Epilobium parviflorum, and Boswellia serrata (2:4:1) at 0.001% restored cortisone-reduced ALPL gene expression levels by 95.6 ± 24.7%. The combination of the three shows significantly more recovery compared to Nigella sativa by itself and the mixture of Epilobium parviflorum and Boswellia (See FIG. 2).

[0173] Gene expression analysis by qRT-PCR revealed a higher upregulation of the ALP gene following treatment with the combination. Given that ALP is known to be involved in establishing and maintaining follicular structure during the anagen (growth) phase and in activating one of the main hair growth pathways, the Wnt / p-catenin signalling pathway, these results support the technical advantage of the combination over individual components in stimulating hair growth and maintaining follicular function. Example 5. Analysis of the proliferation capacity in human follicle dermal papilla cells (HFDPC)

[0174] Cortisol, released in response to psychological or physical stress, has been shown to disrupt the normal hair growth cycle by promoting premature entry into the telogen phase (resting phase), contributing to hair loss conditions such as telogen effluvium, androgenetic alopecia, and alopecia areata (Thom, 2016).

[0175] The present study evaluated the effects of the different extracts on the proliferation of human follicle dermal papilla cells under cortisone-induced conditions.

[0176] Analytical equipment

[0177] Laminar flow hood, CO2incubator, inverted microscope with integrated camera, Burker chamber, centrifuge tubes, micropipettes, pipettes, freezer -20°C, freezer -80°C, rack, plate reader spectrophotometer, statistical analysis software and other equipment frequently used in the laboratory.

[0178] Reagents

[0179] Follicle Dermal Papilla cells culture medium and supplements (Promocell), phosphate buffer solution (PBS, Gibco), trypan blue solution (Bio-Rad), dimethyl sulfoxide (DMSO, Sigma-Aldrich), trypsin-EDTA (Gibco) and MTT reagent [3-(4,5-Dimethylthiazol-2-yl)-2,5- Diphenyltetrazolium Bromide] (Sigma).

[0180] Cell proliferation procedure

[0181] Cell numbers and viability were determined using Trypan-Blue staining and counting in a Burker chamber under the microscope. For the MTT proliferation assay, HFDPC were cultured overnight at a 10.000 cells / well density in a 96 well plate, in supplemented growth medium. 24 hours later, the culture medium was replaced with fresh low-nutrient medium containing Nigella sativa, Epilobium parviflorum + Boswellia serrata Mixture (4:1) and Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) for 72 hours. The experiments were conducted with continuous cortisone (10-3M) exposure for 72 hours, EGF (20 ng / ml) was added as a proliferative control. After the incubation, the medium was removed, and MTT solution was added to each well. Plates were incubated at 37°C for 3h. MTT reagent was removed and DMSO at 100 % was added to each well to solubilize formazan crystals, then the absorbance was measured at 550 nm on a scanning multi-well spectrophotometer. Controls

[0182] C: Negative control=cells at a density of 150.000 cells / well without treatment.

[0183] Cortisone: cells at a density of 150.000 cells / well+cortisone 10'3M.

[0184] Samples

[0185] Table 3. Component mixtures concentrations (mg / mL) of Nigella sativa (NIG), Epilobium parviflorum (EPI), and Boswellia serrata (BOS)

[0186] In the following table, the concentration of each active at 0.0001% of the sample is shown.

[0187] Table 4. Component diluted mixtures at 0.0001% of Nigella sativa (NIG), Epilobium parviflorum (EPI), and Boswellia serrata (BOS)

[0188] In this proliferation analysis, we used a concentration ten times lower than that employed in Example 4.

[0189] This design shows both the effect of the combination itself and whether the composition remains effective at concentrations below those of Example 4. If the effect is observed at these lower concentrations, it can reasonably be expected to occur at the higher concentrations used in Example 4 as well.

[0190] Results

[0191] Epidermal Growth Factor (EGF) consistently promoted cell proliferation, confirming assay sensitivity and serving as a reliable positive control. The treatment with Nigella sativa at 0.0001% did not reduce cell proliferation after 72 hours of cortisone exposure in HFDPC (See FIG. 3).

[0192] The treatment with the Epilobium parviflorum + Boswellia serrata mixture (4:1) at 0.0001% did not reduce cell proliferation after 72 hours of cortisone exposure in HFDPC (See FIG. 4).

[0193] The treatment with Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) at 0.0001% increased cell viability by 17.0 ±2.7% after 72 hours of cortisone exposure in HFDPC (See FIG. 5).

[0194] In conclusion, in the in vitro model of HFDPC subjected to cortisone-induced stress, the Nigella sativa, Epilobium parviflorum, and Boswellia serrata mixture, enhanced cell viability at 0.0001%, suggesting a potential proliferative or protective effect under hormonal stress conditions, which is associated with follicle miniaturization and hair loss.

[0195] Example 6. Analysis of the hair growth-stimulating effects using Philpott test

[0196] Philpott test is a useful ex vivo model that uses isolated human hair follicles explants to assess hair growth by measuring hair shaft elongation. It allows direct testing of how hair follicles respond to active ingredients in controlled conditions that closely resemble the human scalp.

[0197] Analytical eguipment

[0198] Stereoscopic microscope with camera, cell culture incubator (37°C, 5 % CO2, 90 % relative humidity (RH), statistical analysis software, laminar flow hood, micropipettes, pipettes, propipette and other eguipment freguently used in the laboratory.

[0199] Reagents

[0200] Penicillin - streptomycin (Fisher), Phosphate buffered saline (Gibco), fungizone® (Fisher), EGF (Sigma) and Williams’ medium (Sigma).

[0201] Philpott test procedure

[0202] Human hair follicles explants were isolated by manual extraction from the human nape. Hair follicles in the anagen phase were selected through morphologic discrimination and maintained in growth medium with Fungizone®, penicillin and streptomycin supplements as previously described (Philpott et al., 1994). Follicles were maintained free-floating in individual wells of 24-well plates, at 37°C in an atmosphere of 5 % CO2 / 95 % air. Basal images (Oh) were taken immediately after isolation using a stereomicroscope. After that, tested samples and positive control (EGF, Epidermal Growth Factor, 20 ng / ml) were added to each well and plates were incubated at 37°C for 7 days. Images were taken after 7 days of treatment, under identical conditions. Finally, data analysis was performed using Imaged software.

[0203] Controls

[0204] C: Negative control= human hair explant without treatment.

[0205] EGF: Positive control= Epidermal Growth Factor (20 ng / mL).

[0206] Samples

[0207] Table 3. Component diluted mixtures at 0.001% of Nigella sativa (NIG), Epilobium parviflorum (EPI), and Boswellia serrata (BOS)

[0208] Results

[0209] Treatment with the Boswellia serrata + Epilobium parviflorum mixture (4:1) at 0.0001 % stimulated hair growth by 96.6 ± 40.0 % on human hair follicles explants during 7 days. Positive control: EGF (epidermal growth factor) at 20 ng / ml stimulated hair growth by 114.5 ± 46.5 % on human hair follicles explants during 7 days (See FIG. 6A and FIG. 6B).

[0210] Treatment with the Nigella sativa stimulated hair growth by 34.2 ± 30.6 % on human hair follicles explants during 7 days, but this change was not statistically significant. Positive control: EGF at 20 ng / ml stimulated hair growth by 114.5 ± 46.5 % on human hair follicles explants during 7 days (See FIG. 7A and FIG. 7B).

[0211] Treatment with the Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) at 0.0001 % significantly stimulated hair growth by 101.9 ± 43.6 % on human hair follicles explants during 7 days. Positive control: EGF at 20 ng / ml stimulated hair growth by 142.4 ± 57.5 % on human hair follicles explants during 7 days (See FIG. 8A and FIG. 8B). Table 4. Treatment comparison between the mixtures and negative control

[0212] The Philpott assay conducted on human hair follicles explants cultured ex vivo, treatment with the Boswellia serrata + Epilobium parviflorum mixture (4:1) and Nigella sativa + Epilobium parviflorum + Boswellia serrata mixture (2:4:1) resulted in significantly greater hair shaft elongation compared to the individual extract of Nigella sativa, indicating a hair growth-promoting effect on human hair follicles explants attributable to the interactions of the extracts.

[0213] Citation List

[0214] Patent Literature

[0215] US10688037B1

[0216] Non-patent literature Philpott MP, Sanders D, Westgate GE, Kealey T. Human hair growth in vitro: a model for the study of hair follicle biology. J Dermatol Sci. 1994 Jul;7 Suppl:S55- 72. doi:10.1016 / 0923-1811(94)90036-1. PMID: 7999676.

[0217] Thom, E. (2016). Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption. Journal of Drugs in Dermatology, 15(8), 1001-1004. Lee SE, Lee EY, Kang SJ, Lee SH. 1 ip-Hydroxysteroid dehydrogenase type 1 inhibition attenuates the adverse effects of glucocorticoids on dermal papilla cells. Yonsei Med J. 2017 Nov;58(6):1204-1210. doi:10.3349 / ymj.2017.58.6.1204. PMID: 29047245; PMCID: PMC5653486.

Claims

Claims1. An oral composition comprising: a) Epilobium parviflorum extract in an amount from 10 to 500 mg; b) Nigella sativa extract in an amount from 10 to 1200 mg; and c) Boswellia serrata extract in an amount from 10 to 700 mg; wherein: the weight ratio of Epilobium parviflorum extract and the sum of Nigella sativa extract and Boswellia serrata extract are in range from 25:1 to 1 :

30. the Epilobium parviflorum extract is a dry extract from the herb which comprises phenolic acids, tannins, flavonoids, and a content of polyphenols of at least 5% by weight; the Nigella sativa extract is a powder extracted from the seeds of the plant, and which comprises thymoquinone; and the Boswellia serrata extract is dry extract derived from the resin of Boswellia serrata trees comprising a minimum of 12% total boswellic acids by weight.

2. The oral composition according to claim 1, wherein the weight ratio of Nigella sativa extract: Boswellia serrata extract are in range from 20:1 to 1 :

203. The oral composition according to any of the claims 1-2, which is a liquid oral composition.

4. The oral composition according to any of the claims 1-3, further comprising Salvia officinalis L. extract, wherein the extract is a dry extract from leaves and stems which comprises at least 2.5% rosmarinic acid by weight.

5. The oral composition according to claim 4, wherein the Salvia officinalis L. extract is in an amount from 10 to 500 mg6. The oral composition according to any of the claims 1-5, further comprising postbiotics in an amount equal to or less than 50 mg.

7. The oral composition according to claim 6, wherein the postbiotics are selected from the group consisting of Lactobacillus plantarum tyndallized, Lactobacillus paracasei tyndallized, Lactobacillus reuteri tyndallized, Lactobacillus acidophilus tyndallized, Bifidobacterium longum tyndallized, Bifidobacterium lactis tyndallized, and mixtures thereof.

8. The oral composition according to any of the claims 1-7, comprises a further 5-alpha reductase inhibitor selected from the group consisting of: Saw Palmetto extract, Pygeum extract, and mixtures thereof; wherein the Saw Palmetto extract is a dry extract from the berry which comprises at least 45 % total free fatty acids by weight; and the Pygeum extract is a dry extract from the inner bark of Prunus Africana which comprises at least 12 % total phytosterols by weight.

9. The oral composition according to any of the claims 1-8, comprising additional components selected from the group consisting of vitamins, amino acids, amino acids precursors, minerals, proteins, carbohydrates, prebiotics, probiotics, herbal extracts, fats, flavorings, sweeteners, antioxidants, and a mixture thereof.

10. The oral composition according to any of the claims 1-9, comprising additional excipients selected from the group consisting of surfactants, cosolvents, taste-masking agents, diluents, and mixtures thereof, and, optionally, carriers selected from the group consisting of liposomes, nanoparticles, micelles, cyclodextrins, phospholipid complexes, solid lipid nanoparticles, nanostructured lipid carriers, self-emulsifying drug delivery systems, microemulsions, nanoemulsions, hydrophilic polymers, biodegradable polymers, surfactant-stabilized emulsions, phytosomes, nanosuspensions, carrageenan, alginates, film-coating cellulose derivates or waxes, colloidal dispersions, and mixtures thereof.

11. An oral composition as defined in any of the claims 1-10, for use in the prevention and / or treatment of hair loss due to a condition selected from androgenetic alopecia, alopecia areata, alopecia mucinosa, telogen effluvium, chronic inflammation, extreme and / or chronic stress, hair treatments, hereditary disorders, hormonal changes, malnutrition, aging, and trichotillomania.

12. The oral composition for use according to claim 11, wherein the prevention and / or treatment comprises reducing hair loss and promoting hair growth as a complementary therapy to pharmacological treatments.

13. The oral composition for use according to any of the claims 11-12, wherein the subject is over 45 years old.

14. The oral composition for use according to any of the claims 11-13, wherein the composition is adapted to be administered once a day.

15. Use of the oral composition according to any of the claims 1-10, either for improvingbrightness, hydration, elasticity, firmness, and / or hair shine; or for improving brightness, hydration, elasticity, and firmness of the skin.

16. Use of an oral composition as defined in any of the claims 1-10, for the prevention and / or treatment of natural hair loss.

17. Use of the oral composition according to claim 16, wherein the prevention and / or treatment comprises reducing hair loss and promoting hair growth as a complementary treatment to a non-therapeutic treatment.

18. Use of the oral composition according to any of the claims 16-17, wherein the subject is over 45 years old.

19. Use of the oral composition according to any of the claims 16-18, wherein the subject is a woman.

20. Use of the oral composition according to any of the claims 16-19, wherein the composition is adapted to be administered once a day.

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