Atomic Scale Topical Composition with Enhanced Interstitial Cellular Uptake for Increased Moisturizing, Fluidity, Antioxidant and Radiation Protection, Antimicrobial Cleansing and Therapeutics for Optimal Dermal Integrity and Homeostasis.

Abstract

This invention proposes a multifunctional topical composition that integrates halogen-functionalized fullerenes (halo-fullerenes and halo-endofullerenes) and metallic nanoparticles (NPs) to provide comprehensive skin protection and sanitizing, cosmetic enhancement and in some embodiments, treatment for various conditions. Leveraging the atomic scale and physical characteristics of halogenated fullerenes for deeper tissue penetration, the composition can provide antioxidant, antimicrobial, and UV protective benefits to foster cellular integrity, proliferation, and differentiation as healthy tissue. The proposed formulation can penetrate the stratum corneum and diffuse into underlying skin layers due to atomic-scale NPs that can readily deliver active ingredients through the skin via the pores of sweat glands; the lipid matrix of the stratum corneum; and hair follicles, sebaceous glands, and pilosebaceous pores. This composition uses stable inorganic antibacterial agents with a robust safety profile. Furthermore, it can provide UV protection from harmful radiation. The formulation comprises active ingredients that are specific, safe, stable and effectiveand can be produced economically, making it suitable for a broad range of skin protection, sanitizing, enhancement and therapeutic products that promote skin health and wellbeing.

Claims

1: A topical composition comprising: (a) an active ingredient comprising halo-fullerenes coordinated to silver nanoparticles, and (b) a delivery vehicle.

2: The topical composition of claim 1, which is for application to the skin.

3: The topical composition of claim 1, wherein the delivery vehicle is selected from the group consisting of a lotion, a cream, a gel, a hydrogel, a serum, a micellar-based formulation, a nano-emulsion, a liposomal formulation, an ointment, an aerosolized spray, and an aerosolized foam.

4: The topical composition of claim 1, wherein the delivery vehicle comprises one or more bases, penetration enhancers, pH adjusters, thickening agents, film formers, gelling agents, preservatives, surfactants, humectants, foaming agents, aerosolizing agents, emulsifiers, emollients and fragrances.

5: The topical composition of claim 1, wherein, when the composition is applied to skin, it provides antimicrobial activity at the application site on the skin.

6: The topical composition of claim 1, wherein the halo-fullerene has the chemical structure C.sub.nX.sub.m, wherein n is an integer from 60 to 84; X is a halogen selected from the group consisting of fluorine, chlorine, bromine, and iodine; m is an integer representing the number of halogen atoms.

7: The topical composition of claim 1, wherein the silver nanoparticles-coordinated halo-fullerene has the chemical structure C.sub.nX.sub.mAg.sub.x, wherein n is an integer from 60 to 84; X is halogen selected from the group consisting of fluorine, chlorine, bromine, and iodine; m is an integer representing the number of halogen atoms; Ag is a silver nanoparticle; x is an integer representing the number of silver nanoparticles.

8: The topical composition of claim 1, further comprising zinc oxide nanoparticles-coordinated halo-fullerene has the chemical structure C.sub.nX.sub.m(ZnO).sub.y, wherein n is an integer from 60 to 84; X is halogen selected from the group consisting of fluorine, chlorine, bromine, and iodine; m is an integer representing the number of halogen atoms; ZnO is a zinc oxide nanoparticle; y is an integer representing the number of zinc oxide nanoparticles.

9: The topical composition of claim 1, further comprising silver nanoparticles- and zinc oxide nanoparticles-coordinated halo-fullerene has the chemical structure C.sub.nX.sub.mAg.sub.x(ZnO).sub.y, wherein n is an integer from 60 to 84; X is halogen selected from the group consisting of fluorine, chlorine, bromine, and iodine; m is an integer representing the number of halogen atoms; Ag is a silver nanoparticle; x is an integer representing the number of silver nanoparticles; ZnO is a zinc oxide nanoparticle; y is an integer representing the number of zinc oxide nanoparticles.

10: The topical composition of claim 8 or 9, wherein the active ingredients are present in effective concentrations to provide antimicrobial activity, antioxidant properties and UV radiation protection at the application site on the skin.

11: The topical composition of claim 1, wherein the active ingredient is present in an effective concentration to provide antimicrobial activity as a dermal sanitizer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] FIG. 1 is a molecular representation of an exemplary halo-fullerene of 60 carbons functionalized with halogens (X).

[0035] FIG. 2 is a molecular representation of an exemplary halo-fullerene of 60 carbons functionalized with halogens (X) and anti-bacterial NPs (i.e., AgNPs; gray circle) that are coordinated to the outside the fullerene cage.

[0036] FIG. 3 is a molecular representation of an exemplary halo-fullerene of 60 carbons functionalized with halogens (X) and UV-blocking NPs (i.e., ZnO NPs; black circle) coordinated outside the fullerene cage.

[0037] FIG. 4 is a molecular representation of an exemplary halo-fullerene of 60 carbons functionalized with halogens (X) and containing anti-bacterial NPs (i.e., AgNPs; gray circle) and UV-blocking NPs (i.e., ZnO NPs; black circle) coordinated outside the fullerene cage.

DETAILED DESCRIPTION OF THE INVENTION

[0038] The object of this invention is to create a composition using functionalized fullerenes and NPs in a stable form for use as a topical skin protectant/moisturizer, antioxidant, therapeutic and broad-spectrum antimicrobial. This innovation combines halogen-functionalized fullerenes (halo-fullerenes) and halogen-functionalized endohedral fullerenes (halo-endofullerenes) enriched with silver nanoparticles (AgNPs), zinc oxide nanoparticles (ZnO NPs), or combinations thereof. In the present invention, the fullerene functions as a platform, whereby the external cage can be chemically altered to achieve different functionalities, depending on specific performance objectives to enhance the biochemical interactions with skin, thereby enhancing cellular hydration, mitigating microbial activity, scavenging free radicals and providing protection from UV and other harmful radiation.

[0039] A primary embodiment of the present invention comprises halo-fullerenes, halo-endofullerenes and optionally functional silver (Ag) and zinc oxide (ZnO) NPs capable of penetrating the skin barrier. This permeable membrane has characteristic, semi-circular channels that vary in diameter from 0.4 nm to 36.0 nm. The atomic-scale NPs can readily deliver active ingredients through the skin via the pores of sweat glands, with diameters ranging from 60-80 m; the lipid matrix of the stratum corneum; and hair follicles, sebaceous glands, and pilosebaceous pores, which possess a diameter of 10-70 m. Topical delivery of the composition can thus traverse the skin via the trans-follicular pathway, which employs skin appendages, or through the intercellular and intracellular channels within the stratum corneum.

[0040] A second embodiment of the present invention comprises: halo-fullerenes, a delivery vehicle and optionally a penetration enhancer, cosmetic, nutritive, or therapeutically active ingredient(s) and water. Wherein the halo-fullerene represents a fullerene of C.sub.20, whereby n=10, 12, 13, 14, 15, . . . , 360, that contains multiple side-chain halogens attached to the carbon cage. As shown in FIG. 1, an exemplary molecule of the present invention relates to the C.sub.60 fullerene functionalized with eight halogen molecules. In alternative embodiments, the halo-fullerene may comprise the three typical functionalization patterns including: C.sub.60X.sub.6, C.sub.60X.sub.8 (FIG. 1), and Co.sub.60X.sub.24; whereby X=a halogen molecule (e.g., iodine, bromine, chlorine or fluorine); whereas the composition may also comprise halo-fullerenes further modified with antimicrobial NPs (FIG. 2) on the exterior of the cage structure, such as metallic NPs (e.g., AgNPs). The halo-fullerene possesses an inherent molecular affinity for pathogenic species, augmented by the introduction of broad-spectrum antimicrobial halogens, which are capable of prolonged microbial neutralization.

[0041] In FIG. 2 a molecular representation of an exemplary halo-fullerene comprised of a 60-carbon atom sphere is depicted, wherein each carbon atom is denoted as a vertex on the geometric structure. The fullerene is functionalized with halogens, represented by the symbol X; these halogens are covalently bonded to the carbon cage at designated positions. Additionally depicted are anti-bacterial nanoparticles (NPs), indicated by gray circles, which are AgNPs (silver nanoparticles). These nanoparticles are coordinated to the fullerene cage, and quantified to form a stable complex wherein the silver atoms engage in directional bonding with specific carbon atoms on the fullerene cage surface.

[0042] FIG. 3 shows a molecular representation of an exemplary halo-fullerene consisting of a 60-carbon atom framework. Herein, the halogens symbolized as X are functionalized on the carbon structure. UV-blocking nanoparticles, indicated by black circles, which are ZnO NPs (zinc oxide nanoparticles), are coordinated outside the fullerene cage. This coordination implies a stable interaction between the ZnO NPs and the carbon cage with a quantified number of the NPs, facilitating the fullerene's ability to block ultraviolet radiation, thereby enhancing its potential use in photoprotective applications.

[0043] FIG. 4 illustrates a molecular representation of another exemplary halo-fullerene with 60 carbon atoms forming the spherical structure, functionalized with halogens marked as X. This fullerene shows dual functionalization, whereby the carbon cage of the fullerene is simultaneously coordinated with anti-bacterial AgNPs, displayed as gray circles, and UV-blocking ZnO NPs, shown as black circles. The nanoparticles are positioned outside the fullerene cage and bound through coordination chemistry. The presence of a quantified number of both AgNPs and ZnO NPs on the fullerene imparts it with multiple properties for antimicrobial efficacy and ultraviolet radiation blocking, respectively.

[0044] This invention presents a composition resulting from chemical functionalization of fullerenes with chlorine and the coordination of AgNPs and/or ZnNPs attached to the external surface of the fullerene cages using a one-step process. The invention indicates that the silver nanoparticles are attached to the cage rather than simply juxtaposed due to forces during the mixing process. This attachment results in a notable alteration of the overall charge distribution within the fullerene molecule, distinct from a mere physical association.

[0045] In this embodiment, the addition of nutritive agents can leverage the extended dermal cellular life cycle to deliver enhanced interstitial benefits. While nutritive agents enhance cellular formation and growth, the halo-fullerenes combine surface and interstitial antimicrobial activity with reduced exposure to toxins and radiation, leading to overall improved skin health and appearance. These properties can help to maintain appropriate moisture levels throughout keratinization, creating a visibly smooth complexion via improved cellular integrity.

[0046] In addition to antimicrobial activity in the present invention, the halo-fullerenes harness unique capabilities as scavengers of free radicals and neutralize the damaging effects of ROS that cause oxidative stress, cellular degradation, premature skin aging, and a host of skin disorders. The atomic scale of the halo-fullerenes also enables exceptional penetration through complex skin architecture to deliver antioxidant effects deep into epidermal layers, where they can have the greatest benefits through earlier introduction in cell flattening and dermal layering cycles. Ultimately, as the halo-fullerenes perform deep in the epidermis throughout its 30-day cellular cycle, the particles will be pushed outward and shed as atomic dust with expired skin cells.

[0047] The utility of the present invention is derived in part from the distinctive structure of the fullerene that confers unparalleled stability to this molecule. The carbon cage forms an electron reservoir, which not only scavenges but also releases electrons as needed. This allows for continuous free radical scavenging and ROS-neutralizing performance for sustained defense against oxidative stress and pathogenic material. The stability of this halo-fullerene also affords consistent antimicrobial activity as a key component of the present invention.

[0048] In a third embodiment of the present invention, the composition may comprise endohedral halo-fullerenes with UV blocking NPs inside of the cage structure (FIG. 3). The process of loading fullerenes with metallic NPs requires attention to both the size of the fullerenes and that of the metallic nanoparticles. Encapsulation of the metallic NPs of the present invention is accomplished via chemical reduction or sonication. In the chemical reduction method, fullerenes are introduced into a recently synthesized solution of metallic NPs. This solution contains a suitable reducing agent, which facilitates the incorporation of metallic NPs into the fullerenes. Alternatively, as implied, the sonication method employs sonication of fullerenes, giving rise to cavitation bubbles to induce high pressure and temperatures that lead to formation of transient hotspots to permit loading of metallic NPs into the fullerenes. Knowhow for optimization of reaction conditions, such as concentration of reagents, temperature, pressure, and reaction time is imperative to ensure successful NP encapsulation and integration into the fullerene.

[0049] In a fourth embodiment of the present invention, the composition may comprise a halo-endofullerene chemically functionalized with antimicrobial NPs attached to the exterior of the cage structure with UV blocking NPs inside the cage structure (FIG. 4). In another aspect of the present invention, the composition may comprise a combination of the functional fullerene and endohedreal fullerenes as previously described.

[0050] The incorporation of penetration enhancers into a topical composition is common in the skincare industry. Their inclusion can enhance the delivery of active ingredients, particularly in NP-based compositions, by employing a combination of mechanisms. These include but are not limited to altering the lipid structure of the stratum corneum, enhancing solubilization, and reducing surface tension, which in the present invention would facilitate deeper uptake and absorption of halo-fullerenes and NPs, thereby improving the overall effectiveness of the formulation. Other penetration enhancers are often used in anti-aging products or treatments for specific skin concerns to alter the barrier function of the skin, allowing active ingredients to penetrate more deeply. It would be obvious to one skilled in the art that an acceptable penetration enhancer at a safe concentration would increase NP absorption. An exemplary list of penetration enhancers is described below, claimed in various embodiments and may be utilized separately or in combination to achieve desired penetration characteristics in the final product: [0051] 1) Dimethyl Sulfoxide (DMSO): Used in skin creams and serums to enhance penetration by creating spaces between skin cells, allowing other ingredients to sink deeper. [0052] 2) Ethanol: Used in toners, aftershaves, and perfumes to temporarily disrupt the skin barrier and allow active ingredients to penetrate more rapidly. [0053] 3) Glycerol: Used in lotions, creams, and soaps to act as a humectant that facilitates the penetration of substances into the skin. [0054] 4) Hyaluronic Acid: Used in serum, moisturizers, and anti-aging products to function as a humectant that binds water to the skin, helping active ingredients penetrate more effectively. [0055] 5) Lecithin: Used in creams, lotions, and lipsticks to help to reduce surface tension and allow better mixing and absorption of active substances. [0056] 6) Menthol: Used in shampoos, conditioners, and balms to enhance penetration via increasing blood flow to the site of application. [0057] 7) Oleic Acid: Used in creams and lotions and comprises a fatty acid that increases the fluidity of cell membranes to enable better absorption of active compounds. [0058] 8) Polysorbates: Used in cleansers, emulsifiers in creams and lotions to act as a surfactant that reduces surface tension and aids in the dispersion and absorption of active compounds. [0059] 9) Propylene Glycol: Used in moisturizers, sunscreens, and makeup products to act as a humectant and increases absorption of active ingredients. [0060] 10) Sorbitol: Used in toothpaste, mouthwash, and anti-aging skincare composition to act as a humectant that draws water into the skin and enhances absorption of active ingredients.

[0061] Topical delivery vehicles and solutions for halo-fullerenes and NP-based cosmetics are diverse and can be tailored to various skin types, conditions, and application sites. Each formulation offers unique characteristics including texture, appearance, absorption rate, and moisturizing properties. In the present invention, the selection of the appropriate vehicle or solution is determined by the desired release profile, target skin area, and consumer or patient preferences. An exemplary list of delivery vehicles or solutions for the proposed halo-fullerene and NP-based composition is described below and may be employed individually or in combination to attain the intended performance and effects of a given topical embodiment: [0062] 1) Aerosol Foam Formulation: A foam formulation typically comprises a propellant, emulsifiers, and stabilizers. Aerosol foam formulations can provide unique textures, increased solubility, and allow for uniform application of active ingredients over large skin regions. [0063] 2) Cream Formulation: A cream-based formulation is especially suited for application on dry or damaged skin. Cream formulations are thick emulsions that typically consist of oils and waxes. This vehicle can create a barrier that may help slow the release of active ingredients for prolonged action at the site of administration. [0064] 3) Gel Formulation: A gel-based formulation is a semi-solid composition consisting of dispersions of small or large molecules in an aqueous liquid phase and thickened with gelling agents, such as carbomer or hydroxyethyl cellulose. Gel formulations are usually transparent, non-greasy and allow for rapid absorption of active components. [0065] 4) Hydrogel Formulation: A hydrogel-based formulation is comprised of a three-dimensional network of hydrophilic polymers. Hydrogel formulations can bind a significant amount of water, enhance hydration at the site of application, and allow for controlled and sustained delivery of active ingredients. [0066] 5) Liposomal Formulation: A liposomal formulation is comprised of spherical vesicles made of phospholipid bilayers that can encapsulate and protect active ingredients, facilitating targeted and controlled release. Liposomal formulations enhance the stability and bioavailability of the active ingredient. [0067] 6) Lotion Formulation: A lotion-based vehicle typically provides a lightweight and non-greasy application, suitable for all skin types. Lotion formulations typically consist of an emulsion of oils and water and optionally the inclusion of stabilizers, emulsifying agents, and viscosity modifiers to allow for even dispersion of active ingredients. [0068] 7) Micellar Solution: A micellar-based solution comprises surfactants that can encapsulate active ingredients within their micelle structure. Micellar solution vehicles provide gentle and effective delivery and are particularly beneficial for sensitive skin applications. [0069] 8) Nano-emulsion Formulation: A nano-emulsion formulation is a stabilized emulsion comprising nano sized droplets that function to enhance surface area and allow for improved dissolution and penetration of active ingredients. [0070] 9) Ointment Formulation: An ointment formulation provides a moisture barrier and facilitates prolonged release of active ingredients at the site of application. These anhydrous formulations are rich in lipids and waxes and ideal for applying to dry or compromised skin. [0071] 10) Serum Formulation: A serum-based formulation is a typically lightweight, fast-absorbing vehicle designed to deliver more concentrated active ingredients directly to the site of application, compared to cream and lotion-based vehicles.

[0072] The described penetration enhancers and delivery vehicles for the application of a halo-fullerene and halo-endofullerene, with or without metallic and metallic oxide chemically functionalized side chain groups or encapsulated moieties, is deemed illustrative, expansive, and non-restrictive. The description provides an adaptable framework to facilitate the controlled release, dispersion, stability, and safety of the active ingredients within various cosmetic or therapeutic formulations. The integration of other or additional ingredients commonly employed within the cosmetics or alternatively, the pharmaceuticals industry, may be judiciously selected, with specific considerations as to physicochemical compatibility with the halo-fullerene structure, optimal efficacy in promoting deeper skin penetration, and adherence to relevant safety standards and regulatory guidelines. The precise composition may be tailored to align with the targeted therapeutic or aesthetic goals, and to conform to the quality and performance requirements pertinent to the intended consumer or therapeutic application. Such materials would include the use of pH adjustors, thickening agents, film formers, gelling agents, preservatives, surfactants, humectants, foaming agents, aerosolizing agents, emulsifiers, emollients, and fragrances common to cosmetics or pharmaceuticals industries.

[0073] The proposed topical embodiments leverage the antimicrobial, antioxidant, UV blocking and penetration capabilities of halo-fullerenes and halo-endofullerenes with and without metallic and metallic oxide chemically functionalized side chain groups or encapsulated moieties. As referenced for therapeutic applications herein, it would be obvious to one skilled in the art that the composition presents a multitude of potential applications beyond cosmetics. By example, the deep penetration and persistent antimicrobial activity of halo-fullerenes could facilitate faster, cleaner wound healing by eliminating pathogenic species within the wound and thereby mitigate infection risk. Moreover, the oxidative stress relief afforded by the free-radical scavenging capability of halo-fullerenes could promote the proliferation and differentiation of cells crucial for tissue regeneration and wound closure. Similarly, halo-fullerenes could be incorporated in therapeutics following chemical peels or laser resurfacing. The soothing, hydrating, and antimicrobial properties of the formulation could help expedite healing while reducing the risk of complications.

[0074] The antioxidant and radical scavenging properties of the halo-fullerene composition would also be beneficial for mitigating the symptoms of chronic inflammatory skin conditions such as psoriasis or eczema. The targeted, deep-layer action of halo-fullerenes could provide relief by reducing inflammatory oxidative stress and enhancing dermal integrity. Additionally, UV protective properties provided by the AgNPs and ZnO NPs in the cosmetic composition would be useful as a potent, lasting sunscreen, providing superior skin protection against harmful UV radiation. This could reduce the risk of premature skin aging and skin cancers associated with UV damage. Its potential as a sunscreen is enhanced by the fact that the halo-fullerenes can remain active for extended periods until gradually shed from the surface with expired cells, providing prolonged sun protection from deeper penetration.