Topical neurocosmetic compositions and methods for modulating skin-neuron interactions

Abstract

A topical neurocosmetic composition comprising a first component including one or more of bakuchiol, allantoin, squalane, or Morinda citrifolia extract; a second component including one or more of hyaluronic acid, vitamin E, Zanthoxylum alatum fruit extract, Coriandrum sativum seed oil, Vitex agnus-castus extract, Helianthus annuus sprout extract, niacinamide, resveratrol, or an ascorbyl ester; and a cosmetically acceptable oil-in-water vehicle configured to deliver both lipophilic and hydrophilic actives through the skin to dermal neurons. The composition improves measurable skin parameters such as hydration and elasticity and supports psychophysiological comfort. Methods of manufacture and use are also described

Description

[0001] TOPICAL NEUROCOSMETIC COMPOSITIONS AND METHODS FOR MODULATING SKIN-NEURON INTERACTIONS

[0002] CROSS-REFERENCE TO RELATED APPLICATION

[0003] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 716,583, filed on November 5, 2024. The disclosure of the above U.S. application is incorporated herein by reference in its entirety.

[0004] TECHNICAL FIELD

[0005] This application relates generally to topical cosmetic and pharmacognostic compositions comprising various ingredients and associated methods of making and using them to enhance cognitive function together with enhancing the skin of a subject. More particularly, the application includes, for example, topical compositions that not only enhance a subject's skin health but utilize the skin- brain connection to regulate a subject’s well-being (e.g, improve mood, improve measurable skin parameters such as hydration and elasticity, support psychophysiological comfort, promote cognitive well-being, and support neuronal homeostasis).

[0006] BACKGROUND

[0007] The disclosure relates to topical compositions configured to improve skin condition and to support well-being through modulation of cutaneous neuronal activity. Cosmetic and dermatologic formulations containing botanical and synthetic actives are well known. Conventional skin-care products typically combine humectants, emollients, antioxidants, exfohants, and vitamins within water- or oil-based vehicles such as creams, serums, or emulsions. The formulation art also includes teachings directed to emulsion stabilization, surfactant selection by hydrophilic-lipophilic balance, and sensorial attributes of finished products. These known systems, however, focus primarily on epidermal hydration or visual improvement and do not address coordinated delivery of defined lipophilic and hydrophilic actives to cutaneous neurons.

[0008] Certain publications describe “neurocosmetic” concepts, including topical compositions said to act on sensory neurons to reduce stress or promote comfort. Representative examples include formulations based on Scutellaria alpina and coconut derivatives used to attenuate stress responses in the skin. Such references disclose different botanical combinations and mechanisms than those described herein and do not teach the multi-blend composition architecture, the specific sets of actives, or the delivery approach recited in the present claims.

[0009] Other disclosures relate to bakuchiol-based cosmetic formulations for improving skin appearance or providing “sensory' enhancement.” These references typically combine bakuchiol with routine emollient oils or esters to address dermal texture or pigmentation. None of them disclose the combination of bakuchiol with Morinda citrifolia, Vitex agnus- caslus. Zanthoxylum alatum, Coriandrum sativum seed oil, Helianthus annuus sprout extract, or resveratrol within a single composition configured as an oil-in-water emulsion capable of influencing neuronal signaling pathways.

[0010] Generic cosmetic compositions using individual actives such as vitamin E, glycolic acid, niacinamide, or ceramides are also known. These teachings describe conventional ingredient use in isolation or in random mixtures without establishing the coordinated “first- component / second-component” blend structure now claimed. None require or suggest the specific pairing of lipophilic and hydrophilic actives drawn from the ingredient groups defined in the claims and implemented in the Examples.

[0011] Accordingly, while prior work recognizes skin-care formulations and even the general concept of skin-brain communication, the presently described compositions differ in both composition and function. They provide a defined two-component system incorporating precise combinations of actives selected to act synergistically on cutaneous neurons and skin cells, in vehicles capable of concurrently delivering hydrophilic and lipophilic constituents. No known disclosure teaches or suggests this composition architecture, the particular ingredient constellation, or the functional configuration claimed herein.

[0012] DISCLOSURE

[0013] Described is a composition configured for topical administration to a subject, the composition comprising: a first component comprising an admixture of at least four natural products selected from the group consisting of bakuchiol, allantoin, squalene, squalane, and Morinda citrifolia extract, a second component comprising an admixture of at least four natural products selected from the group consisting of hyaluronic acid, sodium hyaluronate, vitamin E, Zanthoxylum alatum fruit extract, glycolic acid, Coriandrum sativum seed oil, biotin, salicylic acid, ferulic acid, Vitex agnus-castus extract, ceramides, ascorbic acid, green tea extract, Helianthus annuus sprout extract, retinol, niacinamide, and resveratrol, and a vehicle suitable for topical administration of the first and second components to the subject when the first and second components are incorporated into the vehicle.

[0014] In certain embodiments, the composition has, as the first component, bakuchiol and, as the second component, at least one ingredient selected from the group consisting of hyaluronic acid, sodium hyaluronate, vitamin E, Z. alatum fruit extract, and glycolic acid.

[0015] In certain embodiments, the composition has, as the first component, allantoin, and, as the second component, at least one ingredient selected from the group consisting of C. sativum seed oil, biotin, salicylic acid, and ferulic acid.

[0016] In certain embodiments, the composition has, as the first component, squalene and / or squalane, and, as the second component, at least one ingredient selected from the group consisting of V. agnus-castus extract, ceramides, ascorbic acid, and / or green tea extract.

[0017] In certain embodiments, the composition has, as the first component, M. citrifolia extract, and, as the second component, at least one ingredient selected from the group consisting of H. annuus sprout extract, retinol, niacinamide, and / or resveratrol.

[0018] Also described is a composition configured for topical administration to a subject, the composition comprising: a first blend comprising: bakuchiol in an amount of 0.15 - 0.85% (w / w) of the composition and hyaluronic acid (0.1 - 0.6%, w / w of the composition), sodium hyaluronate (0.1 - 0.6%, w / w of the composition), vitamin E (0.05 - 2.5%, w / w of the composition), Zanthoxylum alatum fruit extract (0.02 - 0. 19%, w / w of the composition), and / or glycolic acid (4 - 7%. w / w of the composition); a second blend comprising: allantoin in an amount of 0.2 - 0.7% (w / w) of the composition, and Coriandrum sativum seed oil (0.8 - 2%, w / w of the composition), biotin (0.01 - 0.05%, w / w of the composition), salicylic acid (0.3 - 0.8%, w / w of the composition), and / or ferulic acid (0.2 - 0.5%, w / w of the composition); a third blend comprising: squalene and / or squalane in an amount of 0.9 - 1.6% (w / w) of the composition, and Vitex agnus-castus extract (0.015 - 0.029%, w / w of the composition), ceramides (0.6 - 1.1%, w / w of the composition), ascorbic acid (7 - 10%, w / w of the composition), and / or green tea extract (0.003 - 0.007%, w / w of the composition); a fourth blend comprising: Morinda citrifolia extract in an amount of 0.002 - 0.007% (w / w) of the composition, and Helianthus annuus sprout extract (0.009 - 0.015%, w / w of the composition), retinol (0.01 - 0.03%, w / w of the composition), niacinamide (2 - 3%, w / w of the composition), and / or resveratrol (0.5 - 0.8%, w / w of the composition); and a vehicle suitable for topical administration of the composition to the subject when the first, second, third, and fourth blends are incorporated into the vehicle. Also described is a method of manufacturing the described compositions, the method comprising: mixing the components and the vehicle(s) so as to create a formulation that, upon topical application, delivers components through the dermis and / or epidermis to a mammalian subject.

[0019] In certain embodiments, the composition is a lotion, cream, serum, cleanser, toner, emulsion, or facial mask.

[0020] In certain embodiments, the composition is a water-based formulation. In certain embodiments, the composition is an oil-based formulation. In certain embodiments, the composition is an emulsion.

[0021] In certain embodiments, the composition further comprises a humectant, emollient, occlusive, antioxidant, exfoliant, cleansing agent, skin-whitening ingredient, anti-aging ingredient, sunscreen agent, wound-healing-ingredient, and / or acne-fighting ingredient.

[0022] In certain embodiments, the composition consists essentially of the first component, the second component, and the vehicle.

[0023] In certain embodiments, the composition consists of the first component, the second component, and the vehicle.

[0024] The present invention provides topical neurocosmetic compositions and related methods designed to promote measurable improvement in skin appearance while supporting the skin-brain interaction pathway. In certain embodiments, the composition comprises: a first component including at least one of bakuchiol, allantoin, squalane (or squalene), and Morinda citrifolia extract; a second component including at least one of hyaluronic acid, sodium hyaluronate, vitamin E, Zanthoxylum alatum fruit extract, glycolic acid, Coriandrum sativum seed oil, biotin, salicylic acid, ferulic acid, Vitex agnus-castus extract, ceramides, ascorbic acid, green-tea extract, Helianthus annuus sprout extract, retinol, niacinamide, and resveratrol; and a cosmetically acceptable vehicle, preferably an oil-in-water emulsion or serum configured to deliver both lipophilic and hydrophilic actives to dermal neurons and adjacent skin cells.

[0025] In preferred embodiments, the first and second components are admixed in ratios effective to enhance skin elasticity, hydration, and firmness while promoting neuronal communication within the skin. The compositions may optionally include additional actives such as Acmella oleracea extract, tetrahexyldecyl ascorbate, Camellia sinensis leaf extract, Fucus vesiculosus extract, acetyl hexapeptide-8, and Plantago major leaf extract, all within cosmetically acceptable concentrations.

[0026] Described is the use of the composition in the manufacture of a topical cosmetic product for promoting in promoting cognitive well-being or psychological comfort in a subject.

[0027] Also described are the compositions for use in enhancing cognitive health of a mammalian or human subject. After application of the compositions to a subject topically, the described compositions promote both skin and cognitive health. These compositions open the door to the creation of more powerful topical skincare products with integrated cosmetic and neurocosmetic benefits.

[0028] BRIEF DESCRIPTION OF THE DRAWINGS

[0029] FIG. 1 depicts a schematic of the skin-brain connection and the pathways by which both skin and cognitive health can be enhanced.

[0030] FIG. 2 depicts a cross-section of human skin showing diffusion of actives from topical application to cutaneous neurons.

[0031] FIG. 3 is a flowchart of emulsion preparation process.

[0032] MODE(S) FOR CARRYING OUT THE INVENTION

[0033] Described herein are mixtures of molecules from plants (such as those listed as Blends A-D in the Examples) that include flavonoids, phenolic acids, stilbenes, lignans, coumarins, alkaloids, sulforaphanes, polysaccharides, peptides, and microRNAs (see, FIG. 1, portion (A)). These molecules, when applied to a subject’s skin over a sufficient period of time and at a sufficient concentration as described herein, surprisingly act to enhance a subject’s cognitive health. As used herein, a subject is a mammal, such as an adult human.

[0034] As used herein, “neurocosmetic” refers to a composition configured to influence biochemical communication between cutaneous neurons and skin cells without treating or diagnosing disease. “Cognitive well-being” denotes physiological or psychological comfort associated with modulation of skin neuronal pathways, measured through biochemical or functional markers. “Cosmetically acceptable vehicle” means a water-based, oil-based, or emulsion system suitable for topical application to human skin. “First component” refers to a lipophilic or amphiphilic group of actives drawn from bakuchiol, allantoin, squalane, and Morinda citrifolia extract. “Second component” refers to a hydrophilic or antioxidant group of actives drawn from hyaluronic acid, sodium hyaluronate, vitamin E, Zanthoxylum alatum fruit extract, Coriandrum sativum seed oil, biotin, salicylic acid, ferulic acid, Vitex agnus- castus extract, ceramides, ascorbic acid, green-tea extract, Melianthus annuus sprout extract, retinol, niacinamide, and resveratrol.

[0035] Existing (prior art) cosmetic formulations enhance the appearance of the skin but do not coordinate defined lipophilic and hydrophilic actives to modulate cutaneous neuronal pathways or skin-neuron signaling. The disclosed compositions provide simultaneous improvement in skin condition and neuronal communication using a dual-phase, multi-blend architecture that delivers defined actives through the epidermis and dermis to dermal neurons. The specific combination of lipophilic and hydrophilic actives enables bidirectional signaling between the skin and the brain that is not achieved by conventional formulations.

[0036] While not intending to be bound by theory, the following might help explain the surprisingly good results obtainable by application of the described compositions. As described by Fergus et al. (2021), infra “The ‘skin-brain axis' communication network [is] a mechanism by which the central nervous system (CNS) response to psychological stress results in an afferent relay and physiological outcome in the skin. Stress, through a CNS- mediated mechanism, has been shown to exacerbate peripheral cutaneous manifestations of atopic dermatitis, psoriasis, and even hair growth. However, in addition to the skin being a target for stress responses, bi-directional signaling is described wherein the skin itself, through the localized production of neuroimmunomodulators and stress catecholamines, can initiate stress signaling to the brain. [Citations omitted].”

[0037] The described composition is believed to activate cutaneous neurons via synergistic interaction between bakuchiol, Vitex agnus-castus, and Morinda citrifolia. promoting local neurotransmitter signaling and feedback to dermal fibroblasts.

[0038] Further provided are methods of manufacturing such compositions by separately preparing lipophilic and hydrophilic blends (as described in Examples I-IV, Blends A-D) and combining them with the vehicle under controlled emulsification conditions. Upon topical administration, the resulting formulation delivers its components through the epidermis and dermis to interact with cutaneous neurons, leading to improved skin condition and user w ell-being as depicted schematically in FIG. 1.

[0039] The present claims therefore encompass compositions characterized by: a coordinated multi-blend structure linking defined ingredient groups (Blends A-D); specific combinations and concentration ranges of actives not taught in prior art; and a dual-phase delivery system capable of modulating cutaneous neuronal signaling.

[0040] Exemplary Ranges and Ratios (Table 1)

[0041] These distinguishing features collectively differentiate the claimed subject matter from previously known cosmetic or neurocosmetic formulations, providing a new class of compositions that integrate skincare and neuro-responsive benefits within a single topical system.

[0042] As shown in FIGS. 1 and 2, the described formulations are applied to the subject’s skin and believed to first deliver the first and second component to neurons embedded within the subject’s epidermis 10, dermis 12, and hypodermis 14, where they interact with the skinbased neurons 16 and activate neural networks that send a neurochemical signal up to the brain (FIG. 1, portion (B)).

[0043] Such a neurochemical signal, upon reaching the brain 18. upregulates expression of neurotransmitters including, but not limited to, dopamine, serotonin, and dehydroepiandrosterone (DHEA) (FIG. 1, portion (C)). Neurotransmitters thus expressed (or produced) in the brain react through well-established neurochemical pathway s to improve mood, increase happiness, promote productivity’, and elevate overall emotional well-being, thus enhancing cognitive health. They also improve measurable skin parameters such as hydration and elasticity, support psychophysiological comfort, promote cognitive wellbeing, and support neuronal homeostasis.

[0044] This improved brain chemistry and overall cognitive health results in the subject sending signals back to the skin, via signal transduction cascades (STCs), which signals can activate genes in the skin related to collagen production / degradation, matrix metalloprotease expression, elastin production, melanin maintenance, and skin moisturization (FIG. 1, portion (D)). Thus, these neurocosmetic molecules are believed to lead to the creation of a bidirectional signaling between skin and the central nervous system.

[0045] In certain preferred embodiments, the first component of the composition comprises bakuchiol, allantoin, squalene (or squalane), and / or Morinda citrifolia extract.

[0046] Bakuchiol is readily commercially available. It is a meroterpene phenol obtainable from the seeds of the Psoralea corylifolia plant. Bakuchiol is relatively lipophilic (as used herein) and is soluble in organic solvents (e.g.. ethanol and dimethyl sulfoxide (DMSO)) and sparingly soluble in aqueous solutions. Bakuchiol’s aqueous solubility can be increased by first making a stock solution with ethanol and bakuchiol, and then diluting it with aqueous buffers. One method is extraction with 80% ethanol, followed by silica column chromatography. It has been used in topical applications since 2007 when it was introduced to the market under as SYTENOL A™ by Sytheon Ltd. (Boulogne-Billancourt, FR). It is preferably present in the composition in an amount of 0.15 - 0.85% (w / w of the total composition). Bakuchiol supports collagen, reduces UV effects, smooths and hydrates skin, minimizes appearance of fine lines and wrinkles, provides antioxidants, all without irritation.

[0047] Allantoin (C4H6N4O3) is readily commercially available and is a diureide of glyoxylic acid. As used herein, allantoin is relatively hydrophilic, being soluble in boiling water, slight soluble in cold water, and insoluble in most organic solvents. Allantoin is used topically for its moisturizing and keratolytic effects. When present in the composition, it is preferably present in the composition in an amount of 0.2 - 0.7% (w / w of the total composition). Allantoin enhances skin’s moisture retention, providing a smoothing effect that visually minimizes the appearance of aging.

[0048] Squalene is readily commercially available and is a polyunsaturated triterpenoid compound having multiple biological activities. It is lipophilic. For practical purposes (e.g., low extraction efficiency, high cost, and environmental issues), squalane may be substituted for (or combined with) squalene herein. Squalane is the hydrogenated and more stable version of squalene, created to enhance its effectiveness in skincare products by preventing oxidation. It too is readily commercially available. Squalene (or squalane) is preferably present in the composition in an amount of 0.9 - 1.6% (w / w of the total composition). Squalane promotes moisture retention, enhances suppleness, and provides a silky -smooth texture. Morinda citrifolia extract (or "noni" fruit extract) is readily commercially available. It is relatively hydrophilic as used herein. It is preferably present in the composition in an amount of 0.002 - 0.007% (w / w of the total composition).

[0049] In certain preferred embodiments, the second component comprises at least one of hyaluronic acid (or sodium hyaluronate), vitamin E, Zanthoxylum alatum fruit extract, glycolic acid, Coriandrum salivum seed oil. biotin, salicylic acid, ferulic acid, Vilex agnus- castus extract, ceramides, ascorbic acid, green tea extract. Helianthus annuus (sunflower) sprout extract, retinol, niacinamide, and resveratrol.

[0050] In certain preferred embodiments, the composition comprises Coriandrum sativum, Zanthoxylum alatum, Helianthus annuus, and Vitex agnus-castus. C. sativum supports skin comfort and wellness, enhancing resilience to environmental factors. Z. alatum nourishes and hydrates, which promotes a healthy glow and appearance. H. annuus naturally supports the longevity molecule NAD+ and supports skin health and vitality, promoting natural rejuvenation processes. V. agnus-castus enhances skin elasticity and hydration supporting collagen production.

[0051] Hyaluronic acid (or sodium hyaluronate) is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 0.1 - 0.6% (w / w of the total composition).

[0052] Vitamin E is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 0.05 - 2.5% (w / w of the total composition).

[0053] Zanthoxylum alatum fruit extract is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 0.02 - 0.19% (w / w of the total composition).

[0054] Glycolic acid is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 4 - 7% (w / w of the total composition).

[0055] Coriandrum sativum (coriander) seed oil is readily commercially available and is relatively lipophilic. It is preferably present in the composition in an amount of 0.8 - 2% (w / w of the total composition).

[0056] Biotin is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 0.01 - 0.05% (w / w of the total composition).

[0057] Salicylic acid is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 0.3 - 0.8% (w / w of the total composition). Ferulic acid is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 0.2 - 0.5% (w / w of the total composition).

[0058] Vitex agnus-castus extract is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 0.015 - 0.029 (w / w of the total composition).

[0059] Ceramides are readily commercially available and are lipophilic. They are preferably present in the composition in an amount of 0.6 - 1.1% (w / w of the total composition).

[0060] Ascorbic acid is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 7 - 10% (w / w of the total composition).

[0061] Green tea extract is readily commercially available and is hydrophilic. It can also be dissolved in alcohol and glycerol. It is preferably present in the composition in an amount of 0.003 - 0.007% (w / w of the total composition).

[0062] Helicinthus annuus (sunflower) sprout extract is readily commercially available and is relatively hydrophilic. It is preferably present in the composition in an amount of 0.009 - 0.015% (w / w of the total composition).

[0063] Retinol is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 0.01 - 0.03% (w / w of the total composition).

[0064] Niacinamide is readily commercially available and is hydrophilic. It is preferably present in the composition in an amount of 2 - 3% (w / w of the total composition).

[0065] Resveratrol is readily commercially available and is lipophilic. It is preferably present in the composition in an amount of 0.5 - 0.8% (w / w of the total composition).

[0066] Other ingredients may also be included. For example, vitamin C enhances the skin’s appearance by giving a brightening effect, supporting collagen production, and providing antioxidant support against environmental stressors.

[0067] Vehicles and bases and their use to create formulations configured for topical application are well known to those of ordinary skill in the art. For example, as described at DermNet, topical formulations are ty pically applied directly to the skin or mucosa. They typically comprise a vehicle or base (e.g., water, ethanol, glycerin, and petrolatum), which has been preferably selected and optimized for the active ingredient(s) and the particular site of application of the body or ty pe of skin. Thus, the end-product (the formulation or composition) may be, e.g., designed or configured to be moisturizing and / or to maximize the penetration of an active ingredient into or through the skin. The amount of the active ingredient that is absorbed through the skin after application depends upon various factors, such as the thickness of the skin (thin skin absorbs more than thick skin), which varies with, e.g. , age and body site. Another important factor is skin barrier function, which may be disrupted by dermatitis, ichthyosis, and keratolytic agents (including potential ingredients hereof, such as, e.g., salicylic acid, ascorbic acid, or allantoin). More active ingredient(s) may be absorbed through damaged skin than with intact skin. Occlusion may be used to increase the absorption of the active ingredient, such as by application in skin folds, under dressings, or when an ointment formulation is used. Also, smaller molecules are more easily absorbed through the skin than larger molecules and lipophilic compounds are better absorbed than hydrophilic compounds. Higher concentrations of the active ingredient may increase penetration over lower concentrations. Other ingredients in the formulation (e.g., permeation enhancers) may also increase absorption rates.

[0068] The choice of vehicle depends upon various factors such as the thickness of the application, the total area of topical application, the frequency of application, and the duration of the treatment course. For example, one gram of a cream spreads out over a 10 cm2area of skin; an ointment spreads a little further. The fingertip unit (~ 0.5 g) is a guide to the amount of a cream or ointment needed to treat an area for a certain time. One fingertip unit covers one side of two flat hands, and one gram covers both sides of the subject’s two hands. At the other extreme, it typically takes 20-30 g of cream or ointment to cover an adult's total body once.

[0069] Vehicles used for topical formulations vary. Topical formulations include active ingredient(s) and a vehicle. The vehicle usually comprises water, oil, alcohol or propylene glycol mixed with preservatives, emulsifiers, permeation enhances (e.g., a keratolytic or DMSO), and fragrances.

[0070] Particular topical formulations are known to those of skill in the art. For example, a solution is a water or alcoholic solution containing the active ingredient(s). A lotion is usually thicker than a solution and more likely to contain oil, water, and / or alcohol. A cream is thicker than a lotion, maintaining its shape, for example, a 50 / 50 emulsion of oil and water, and is often moisturizing. The composition is typically configured as a lotion or a cream when both the first component(s) and the second component(s) are hydrophilic.

[0071] An ointment is a semi-solid, water-free or nearly water-free (e.g., 80% oil). Ointments are typically emollient, protective, and occlusive. With ointments, there is typically no need for preservatives, thus reducing the risk of contact allergies. Ointments typically include a hydrocarbon (paraffin), wool fat, beeswax, macrogols, emulsifying wax, cetrimide or vegetable oil (e.g., olive oil, arachis oil, coconut oil). The composition is typically configured as an ointment when both the first component(s) and the second component(s) are hydrophilic.

[0072] Ointments, balms, and salves typically include petrolatum or oils together with optional ingredients like cocoa butter, shea butter, and essential oils.

[0073] As is known to one of skill in the art of cosmetic chemistry, an emulsion is a dispersion of two or more immiscible materials, where one phase, also known as the internal phase, is dispersed in the continuous or external phase. Cosmetic emulsions are classified as oil in water (“O / W”), water in oil (“W / O”), and water in silicone (“W / Si”). Further emulsions such as oil in water in oil (W / O / W) are also possible.

[0074] Oil in water emulsions are typically preferred due to better cost and light skin feel. To create an oil in water emulsion (one that remains stable for a long enough time), the interfacial tension between the two phases must be overcome, which can be achieved by mixing. However, mixing even at very high rates may not be enough to provide long term stability of the composition. An emulsifier or combination of emulsifiers may be used to stabilize droplets of the dispersed phase.

[0075] Surfactants are often used to create emulsions. Surfactants are molecules that have a lipophilic (oil soluble) and an effective hydrophilic (water soluble) portion. Surfactants act as emulsifiers by significantly lowering the interfacial tension and decreasing the coalescence of dispersed droplets.

[0076] In certain embodiments, the emulsion exhibits droplet sizes of 100-500 nm to facilitate dermal neuronal uptake.

[0077] A gel is an aqueous or alcoholic monophasic semisolid emulsion, often based on cellulose, which liquefies upon contact with skin. Gels often include preservatives and fragrances. A paste is a concentrated suspension of oil, water and powder. An aerosol foam or spray is typically a solution or gel with pressurized propellant.

[0078] A cosmetic serum is typically a skincare product that's designed to target specific skin concerns with a high concentration of active ingredients. Serums contain ingredients such as vitamins, minerals, antioxidants, and amino acids. Serums are lightweight, oil- or water-based liquids that are easily absorbed by the skin. They often are dispense in small bottles with a dropper. A powder is a solid, such as talc or com starch. A solid is ty pically a “stick,"’ which may melt upon reaching body temperature (e.g., a suppository).

[0079] A transdermal patch is a well-known delivery' system that allows precise dosing of the active ingredient(s) and typically includes an adhesive for adhesion to the skin.

[0080] To be compounded, the crude ingredients may be added to a selected vehicle and mixed, generally to uniformity.

[0081] When the subject’s skin is wet or oozing, creams, lotions, and drying pastes are typically utilized. When the subject’s skin is dry and / or scaly, ointments and oils are preferably used. When the subject’s skin is inflamed, creams or ointments are ty pically used. If the subject’s skin is cracked and sore, alcohol and acidic preparations are to be avoided.

[0082] As a general rule, for application to the subject’s palms and soles, an ointment or cream may be preferred. For application to skin folds, a cream or a lotion is preferably used. For hairy' areas, a lotion, solution, gel, or foam is typically used. For mucosal surfaces, nonirritating formulations are preferably used.

[0083] For particular compositions, particular topical formulations may be used. For example, when the composition has bakuchiol as the first component, which is lipophilic, and has, vitamin E as the second component, which is also lipophilic, then an ointment may readily be used as the formulation.

[0084] However, when the composition has bakuchiol as the first component and has hyaluronic acid (and / or sodium hyaluronate), Z. alatum fruit extract, and / or glycolic acid as the second component, which are hydrophilic, then an emulsion formulation may advantageously be used.

[0085] When the composition has allantoin as the first component, which is hydrophilic, and the second component is biotin and / or salicylic acid, a cream or lotion may be readily utilized.

[0086] When the composition has allantoin as the first component and has C. sativum seed oil and / or ferulic acid as the second component, then an emulsion or surfactant dosage form may be used.

[0087] When the composition has squalene and / or squalane as the first component, which are lipophilic, and has, as the second component, V. agnus-castus extract and / or ceramides, then an ointment formulation may be used. When the composition has squalene and / or squalane as the first component, and ascorbic acid and / or green tea extract as the second component, then an emulsion or surfactant formulation may be used.

[0088] When the composition has M. citrifolia extract as the first component, which is relatively hydrophilic, and has, as the second component, retinol and / or resveratrol, then an emulsion or surfactant-based formulation may advantageously be used.

[0089] When the composition has M. citrifolia extract as the first component, and / / , annuus sprout extract and / or niacinamide as the second component, then a cream or lotion formulation may advantageously be used.

[0090] Other topical formulations and their methods of making will be clear to those of ordinary skill in the art.

[0091] Typical dosages per application used herein are from 0.5 to 1.0 grams of the composition, preferably 0.5 grams.

[0092] The composition may be applied to the subject’s skin (e.g., the subject’s face, neck, fingers, palms, elbows, ears, arms, legs, behind the knees, or feet) from one to four times a day, preferably twice a day separated by approximately 12 hours. In certain embodiments, the skin is cleansed with a cleaner and optional toner before application of the composition. The treatment continues for as long as desired, but the cognitive enhancement typically occurs after one or two weeks.

[0093] While measures of a subject's cognitive health may be done by. for example, selfreporting, various common cognitive screening tests exist and are known in the art. For example, the ENCOMPASS® test is typically used. Other tests are the Montreal Cognitive Assessment (“MoCA’ ), a test involving memorizing a short list of words, naming objects shown in pictures, copying shapes, and performing other tasks. The Mini -Mental State Exam C’MMSE”) test involves counting backwards, identifying objects in the room, and stating the date and other common, well-known facts. The Mini-Cog involves memorizing and recalling a three-word list of unrelated words and drawing a circle clock — adding all time points, then drawing hands to show a specific time. Other screening tests include the Memory Impairment Screen (MIS) / MIS by Telephone (MIS-T), Mental Status Questionnaire (MSQ), 8-item Informant Interview (AD8), Functional Activities Questionnaire (FAQ), 7- Minute Screen (7MS), Abbreviated Mental Test (AMT), St Louis University' Mental Status Examination (SLUMS), Telephone Instrument for Cognitive Status (TICS), and Informant Questionnaire on Cognitive Decline in the Elderly. Preferred embodiments employ combinations of botanical and synthetic actives that interact with dermal neuronal pathways to yield non-additive enhancement in both visible skin parameters and molecular markers of well-being. The compositions may be formulated as emulsions, serums, or creams using cosmetically acceptable vehicles as described. The disclosure is further described with the aid of the following illustrative Examples.

[0094] EXAMPLES

[0095] Example

[0096] Blend A is made by admixing the selected ingredients in an appropriate vehicle.

[0097] Example

[0098] Blend B is made by admixing the selected ingredients in an appropriate vehicle.

[0099] Example III Blend C is made by admixing the selected ingredients in an appropriate vehicle.

[0100] Example IV

[0101] Blend D is made by admixing the selected ingredients in an appropriate vehicle.

[0102] Example V

[0103] An oil in water emulsion for topical administration to a subject’s skin is made comprising Blend A, Blend B, Blend C, and Blend D of Examples I - IV. The emulsion is applied twice daily to a subject's face and neck in 0.5-gram amounts (droplet sizes of 100- 500 nm to facilitate dermal neuronal uptake). After two weeks, the subject experiences enhanced cognitive health (e.g., improved mood, increased happiness, and boosted productivity) all while improving the subject’s skin health.

[0104] Example VI

[0105] A serum was made containing water, propanediol, maltodextrin, pentylene glycol, coco-caprylate, glyceryl caprylate, glycerin, Coriandrum sativum seed oil, squalane, glyceryl stearate, bakuchiol, allantoin, xanthan gum, sodium acrylates copolymer, capry lie / capric triglyceride, triethyl citrate, caprylhydroxamic acid, Acmella oleracea extract, citric acid, tetrahexyldecyl ascorbate, Zanthoxylum alatum fruit extract, lecithin, linalool, vitex agnus castus extract, Helianthus annuus sprout extract, phenoxyethanol, linalyl acetate, Camellia sinensis leaf extract, Fiicus vesiculosus extract, Jasminum officinale flower / leaf extract, Morinda citrifolia extract, Rosmarinus officinalis leaf extract, Salvia officinalis leaf extract, Salvia triloba leaf extract, vanilla planifolia fruit extract. Lavandula angustifolia flower / leaf / stem extract, Rosa damascena flower extract, Lactobacillus ferment, potassium sorbate, tocopherol, acetyl hexapeptide-8, Plantago major leaf extract, and acetic acid in the amounts described herein. The serum was directed to be applied morning and evening to a subject's face and neck in 0.5-gram amounts. After cleansing, the serum was massaged onto the subject’s damp face and neck using a gentle upward motion until fully absorbed. The follow up was with a moisturizer.

[0106] After two weeks, the subjects experienced revitalization of the appearance of the skin and supported the subject’s natural rejuvenation processes and promoted skin elasticity and suppleness — all while enhancing the subject’s overall sense of well-being with every application.

[0107] All of the subjects saw an immediate boost in hydration to the skin. A vast majority noticed a visible improvement in firmness and elasticity in one week. A vast majority recognized a visual reduction in fine lines and wrinkles after four weeks. A vast majority felt a noticeable difference in skin texture and softness.

[0108] Example VII

[0109] Preliminary in vitro studies indicate that compositions according to the disclosure up- regulate expression of genes associated with cutaneous neuronal activity (e.g., DHEA synthase and serotonin receptor 1A) and increase collagen lai expression. These effects exceed the sum of corresponding single-component controls and support the neurocosmetic functionality of the compositions.

[0110] INDUSTRIAL APPLICABILITY

[0111] The compositions described herein are industrially applicable in the manufacture of cosmetic and personal-care products, including creams, serums, emulsions, and lotions, for improving skin condition and promoting psychophysiological comfort in human subjects.

[0112] These formulations are suitable for large-scale production using conventional cosmetic-processing equipment and have clear commercial relevance in the skincare, cosmetic, and wellness industries.

[0113] REFERENCES

[0114] (The contents of the entirety of each of which is incorporated herein by this reference.)

[0115] Akhtar N., Ali M., Alam M.S. “Chemical Constituents from the Seeds of Zanthoxylum alatumf Journal of Asian Natural Products Research (2009) 11(1): 91-95. doi: 10.1080 / 10286020802514622. PMID: 19177245.

[0116] Ascsillan A. A., Kemeny L.V. “The Skin-Brain Axis: From UV and Pigmentation to Behaviour Modulation,” International ' Journal of Molecular Sciences (2024) 25(11): 6199. doi: 10.3390 / ijms25116199.

[0117] Blatt N.L., Khaiboullin T.I., Lombardi V.C., Rizvanov A. A., Khaiboullina S.F. “The Skin-Brain Connection Hypothesis: Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain,” Frontiers in Immunology (2017) 7: 683. doi: 10.3389 / fimmu.2016.00683.

[0118] Boujbiha M.A., Chahdoura H., Adouni K. et al. “Wild Vitex agnus-castus L. Phytochemical Characterization, Acute Toxicity, and Bioactive Properties,” Molecules (2023) 28(13): 5096. doi: 10.3390 / molecules28135096.

[0119] Chen Y., Lyga J. “Brain-Skin Connection: Stress, Inflammation and Skin Aging,” Inflammation & Allergy Drug Targets (2014) 13(3): 177-190. doi: 10.2174 / 1871528113666140522104422.

[0120] EP 4389136 Al (2024). “Neurocosmetic Composition for Preventing Stress Effects,” Applicant: Laboratoires Mibelle AG Biochemistry. Describes compositions containing Scutellaria alpina and coconut extract for stress reduction via cutaneous neuronal pathways.

[0121] FR 3143372 Al (2024). “Neurocosmetic Composition for Alleviating Stress Effects on the Skin.” Applicant: Laboratoires Mibelle AG Biochemistry. Discloses formulations of coconut and Alpine skullcap extracts for modulating skin sensory neurons.

[0122] Fregoso D.R., Hadian Y., Gallegos A.C. et al. “Skin-Brain Axis Signaling Mediates Behavioral Changes after Skin Wounding,” Brain Behavior and Immunity - Health (2021) 15: 100279. doi: 10.1016 / j bbih.2021.100279.

[0123] Griffin W.C. “Calculation of HLB Values ofNon-Ionic Surfactants,” Journal of the Society of Cosmetic Chemists (1954) 5: 249-253.

[0124] Maqbool S., Ihtesham A., Langove M.N. et al. “Neurodermatological Association between Psoriasis and Depression: An Immune-Mediated Inflammatory Process Validating the Skin-Brain Axis Theory,” AIMS Neuroscience (2021) 8(3): 340-354. doi: 10.3934 / Neuroscience.2021018. Rizzi V., Gubitosa J., Fini P., Cosma P. “Neurocosmetics in Skincare — The Fascinating World of Skin-Brain Connection: A Review to Explore Ingredients. Commercial Products for Skin Aging, and Cosmetic Regulation,’’ Cosmetics (2021) 8(3): 66. doi: 10.3390 / cosmetics8030066.

[0125] SinaH., Dramane G., TchekounouP. et al. “Phytochemical Composition and In Vitro Biological Activities o Morinda cilrifolia Fruit Juice,” Saudi Journal of Biological Sciences (2021) 28(2): 1331-1335. doi: 10. 1016 / j.sjbs.2020. 11.059.

[0126] Sobhani Z., Mohtashami L , Amiri M.S. et al. “Ethnobotanical and Phytochemical Aspects of the Edible Herb Coriandrum sativum L.f Journal of Food Science (2022) 87(4): 1386-1422. doi: 10.1111 / 1750-3841.16085.

[0127] US 2011 / 0223267 Al (2011). “Bakuchiol Compositions and Uses Thereof.” Discloses bakuchiol in cosmetic formulations for anti-aging and anti-inflammatory effects.

[0128] US 2020 / 0030256 Al (2020). “Bakuchiol Compositions for Topical Application.” Describes bakuchiol-containing creams for improving skin appearance.

[0129] US 2022 / 0273538 Al (2022). “Skin Care Compositions Containing Bakuchiol and Oil-Based Conditioning Agents for Sensory Enhancement.” Applicant: Procter & Gamble. Relates to cosmetic compositions providing enhanced sensory perception.

[0130] Vaughan C.D., Rice D.A. “Predicting O / W Emulsion Stability by the Required HLB Equation,” Journal of Dispersion Science and Technology (1990) 11(1): 83-91.

[0131] WO 2024 / 096259 Al (2024). “Cosmetic Compositions Containing Bakuchiol. Milk Thistle Extract, and Fruit Extracts for Skin Care Applications.”

[0132] WO 2017 / 009206 Al (2017). “Compositions for Topical Use Comprising Pharmacological or Cosmetic Actives in Stable Emulsions.”

[0133] Yang J., Zhang S., Wu Q. et al. “T Cell-Mediated Skin-Brain Axis: Bridging the Gap between Psoriasis and Psychiatric Comorbidities,” Journal of Autoimmunity (2024) 144: 103176. doi: 10.1016 / j.jaut.2024.103176.

Claims

1. CLAIMSWhat is claimed is:

1. A topical composition configured to modulate cutaneous neuronal signaling, comprising: a. a first component comprising at least one compound selected from bakuchiol, allantoin, squalane, and Morindci citrifolia extract; b. a second component comprising at least one compound selected from Coriandrum sativum seed oil, Zanthoxylum alatum fruit extract, Vitex agnus-castus extract, Helianthus annuus sprout extract, niacinamide, resveratrol, or an ascorbyl ester; and c. a cosmetically acceptable vehicle configured as an oil-in-water emulsion that delivers both hydrophilic and lipophilic actives to dermal neurons.

2. The composition of claim 1, wherein the first component and the second component are each present in defined ratios effective to enhance both skin appearance and user well-being.

3. The composition of claim 1 or 2, wherein topical application increases expression of at least one cutaneous biomarker selected from dopamine receptor D2, serotonin receptor 1A, or DHEA synthase.

4. The composition of any of the preceding claims, wherein bakuchiol and Vitex agnus-castus extract are co-formulated in a weight ratio of 3: 1-10: 1.

5. The composition of any of the preceding claims, wherein Morinda citrifolia extract and Helianthus annuus sprout extract are present in a combined concentration of 0.002-0.02 % w / w.

6. The composition of any of the preceding claims, wherein the emulsion exhibits droplet sizes of 100-500 nm to facilitate dermal neuronal uptake.

7. The composition of any of the preceding claims, wherein the composition excludes Scutellaria or Cocos extracts.

8. The composition of any of the preceding claims further comprising one or more of: Acmella oleracea extract, tetrahexyldecyl ascorbate, Camellia sinensis leaf extract, Fucus vesiculosus extract, acetyl hexapeptide-8, and Plantago major leaf extract.

9. A method of enhancing cutaneous neuronal activity and improving skin condition, comprising topically administering to a subject a composition according to any of claims 1-8, wherein the application results in up-regulation of cutaneous neurotransmitter receptor expression relative to untreated control skin.

10. A method of supporting psychological comfort or cognitive well-being in a human subject, comprising topically administering to the subject a composition according to any one of claims 1-8.1 1. A composition according to any one of claims 1-8 for use in promoting cognitive well-being or psychological comfort in a subject.

12. The composition for use according to claim 11, wherein the improvement in well-being correlates with measurable enhancement of skin-condition parameters.

13. The composition of any one of claims 1-12, wherein the vitamin E, ascorbic acid, or retinoid components are present as functional derivatives or esters selected from ascorbyl palmitate, tetrahexyldecyl ascorbate, tocopheryl acetate, or retinyl palmitate.

Images