Insect repellent formulations and methods making and using thereof

Abstract

Described herein are repellent compositions and methods of making and using thereof. For instance, such repellent compositions can be formed from a combination of an alkyl lactate, a fatty acid, and a base oil which form an emulsion that can be used, for example, to repel various insects, such as mosquitoes.

Description

[0001] INSECT REPELLENT FORMULATIONS AND METHODS MAKING AND USING THEREOF

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 624,151 filed January 23, 2024, which is herein incorporated by reference in its entirety.

[0004] FIELD OF THE INVENTION

[0005] The disclosed invention is generally in the field of insect repellent formulations, and methods of making and using thereof.

[0006] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0007] This invention was made with government support under DC 007864 and Al 165575 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.

[0008] BACKGROUND OF THE INVENTION

[0009] The insect repellent DEET represents the gold standard for insect repellents, and has been available to the public since the 1957.

[0010] Despite the common use of DEET as an insect repellent, DEET has limitations, including potential for eye irritation and rashes. DEET should not be ingested. Therefore, DEET should not be applied near the mouth or eyes. DEET can damage certain types of clothing (synthetics such as rayon and Spandex), and therefore should not be used underneath some types of clothing. Moreover, DEET has to be applied at high concentrations to provide adequate repellency effectiveness. For example, a 10% DEET repellent only lasts about 2 hours and 25% DEET repellent typically lasts about 5 hours (Lupi, E., Hatz, C. and Schlagenhauf, P. The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp. - A literature review. Travel Medicine and Infectious Disease 11, 374-411 (2013)).

[0011] Accordingly, there remains a need for improved insect repellents.

[0012] Therefore, it is an object of the present invention to provide improved insect repellent formulations.

[0013] It is a further object of the present invention to provide methods of preparing such repellent formulations. It is still a further object of the present invention to provide methods of using such repellent formulations.

[0014] SUMMARY OF THE INVENTION

[0015] Various repellent formulations are described that can provide long-lasting protection from insects, such as for repelling mosquitoes. In one non-limiting instance, a repellent formulation is in the form of an emulsion which includes:

[0016] (i) a base oil that is skin impermeable or substantially skin impermeable;

[0017] (ii) a C2-C12 alkyl lactate; and

[0018] (iii) a C6-C18 fatty acid,

[0019] In some instances, the emulsions can be microemulsions or nanoemulsions. In some instances, the repellent formulation can further include a cargo.

[0020] In yet another non-limiting instance, a repellent formulation is in the form of an emulsion and includes:

[0021] (i’) a base oil which is a paraffin oil;

[0022] (ii’) a C2-C12 alkyl lactate at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or at a concentration ranging from about 5 v% to 10 v% of the total volume of the emulsion; and

[0023] (iii’) a Ce-Cis fatty acid at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion, where the emulsion is an inverse microemulsion.

[0024] In one non-limiting instance, the repellent formulations can be prepared according to a method including the step of:

[0025] (a) preparing a mixture of a C2-C12 alkyl lactate, a Ce-Cis fatty acid, and a base oil to form an emulsion including self- assembled micelles therein.

[0026] As indicated, the repellent formulations can be used to repel arthropods, such as insects. In some instances, the formulations can repel arachnids. In one non-limiting instance, a method of repelling an insect (or arachnid) includes the steps of:

[0027] (a’) applying a repellent formulation, in the form of an emulsion, as described herein, to at least a portion of a skin surface of a subject; wherein following step (a’), the portion of the skin surface to which the emulsion was applied provides a complete protection time (CPT) of at least about 12 hours, and optionally provides a CPT of about 12 hours or longer. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 shows a non- limiting illustration of an inverted micelle, as found in a surfactant free microemulsion repellent formulation, where the micelle self-assembles from ethyl L-lactate and lauric acid and is surrounded by paraffin oil.

[0029] Figure 2 shows a non- limiting illustration of a slow-release mechanism of inverted micelles from paraffin oil, when the repellent formulation is applied onto a skin surface.

[0030] Figure 3 shows a non- limiting illustration of an arm-in-cage method. In step 1 , a cage contains mosquitoes at a density of about 30 mosquitoes per 30 cubic centimeters. In step 2, a forearm, which has exposed skin that has been treated with a repellent formulation or is untreated (acting as a control), is inserted into the cage for a period of time. In step 3, complete protection time (CPT) is calculated from the time between repellent application to the exposed skin and insertion into the cage and the first confirmed mosquito bite.

[0031] Figure 4 shows a bar graph of percent blood fed (y-axis) as a function of weight percentage (1% - 10%) ethyl L-lactate (ELL) in the formulation applied to artificial skin and exposed to mosquitoes, where the control is 0% ELL.

[0032] Figure 5 shows a bar graph demonstrating repellent properties of ethyl L-lactate (ELL) and lauric acid (LA) using artificial blood feeders. In Figure 5, the y-axis is percent blood fed and the x-axis corresponds with five different tested formulations with different concentrations (wt %) of ELL and LA, individually and in combination, applied to artificial skin and exposed to mosquitoes, where the control is 0% ELL, 6% ELL alone in ethanol, 7% LA alone in ethanol, the combination of 6% ELL with 7% LA (“6% +7% LA”) in ethanol, and IR007 is 6% ELL plus 7% LA in light paraffin oil.

[0033] Figure 6 shows a bar graph of percent blood fed (y-axis) as a function of percentage (1% - 7%) lauric acid (LA) applied to artificial skin and exposed to mosquitoes, where the control is 0% LA.

[0034] DETAILED DESCRIPTION OF THE INVENTION

[0035] Various repellent compositions and methods of making and using thereof are described herein.

[0036] I. Definitions

[0037] “Generally regarded as safe for topical application to skin,” as used herein refers to substances that are considered safe for use in cosmetic products which are applied to the skin of a mammalian subject, such as a human. Such substances are generally understood in the field of cosmetics to be safe under the conditions of their intended use. In some instances, such substances may be reviewed by the Cosmetics Ingredient Review (CIR) and deemed safe for personal skincare products and categorized as safe to use, at specified concentrations, as may be applicable. See, for example: On-Line INFOBASE - ingredients - regulations - labeling - cosmetics - personal care products. International Journal of Toxicology 17(Suppl. 1 ): 1 — 3, 199s Copyright 1998 Cosmetic Ingredient Review, 1-3 (1998).

[0038] “Complete Protection Time,” or “CPT,” as used herein refers to the duration of time during which a repellent provides an effective defense against landing, biting, and / or contact of an insect species on an area or surface, such as when applied to skin, clothing, or other surfaces. The effectiveness of a repellent is typically measured by its ability to provide protection for a specific period and indicates how long the repellent can effectively prevent landing, biting, and / or contact by the insect species with the treated area. For example, CPT can be calculated from the time between repellent application to the exposed skin and insertion into the cage and the first confirmed mosquito bite. A mosquito bite can be confirmed when after the bite occurs a second bite occurs within 30 minutes of the first bite. If a second bite does not occur within 30 minutes of the first bite, the first bite is not a “confirmed mosquito bite” and is dismissed and volunteer continues testing. Subsequently, if the volunteer receives another bite at any point of the testing, this subsequent bite is considered the first bite and they leave their arm in the cage for up to at least 30 minutes or until a confirmation bite is recorded (if it occurs in less than 30 minutes) to determine if the subsequent bite is confirmed. The test continues until a set time period is reached without a confirmed bite or until the first confirmed bite is achieved. See, e.g. Luker, et al. 2023. Sci Rep 13, 1705.

[0039] “Repellency,” as used herein is a measurement of the ability of a repellent to repel an insect, expressed as a percentage. Repellency (R%) is calculated using the formula:

[0040] R(%) = ( c - ) X 100% where C is the number of insect (such as mosquito) bites) on a control and T is the number of insect bites on a repellent treated equivalent of the control. For example, an area of skin without any treatment may serve as a control (C) and the same area of skin treated with a repellent formulation may serve as treated (T). See Schreck C. E. Techniques for evaluation of insect repellents: a critical review. Annual Review of Entomology. 1977;22:101-119.

[0041] “Alkyl lactate,” as used herein refers to a chemical compound derived from lactic acid, which is a naturally occurring organic acid. In the context of alkyl lactates, the term "alkyl" refers to a hydrocarbon chain, which can vary in length.

[0042] “Fatty Acid,” as used herein refers to a chemical compound that consists of a hydrocarbon chain and a carboxylic acid group (-COOH) at one end. The hydrocarbon chain may be saturated (with hydrogen atoms on the hydrocarbon chain) or unsaturated (having one or more carbon-carbon double bonds in the hydrocarbon chain).

[0043] “Hydrophilic,” as used herein refers to substances, molecules, and agents having an affinity for and demonstrating solubility or dispersibility in water, facilitated by interactions such as hydrogen bonding and electrostatic attractions between the molecules and water molecules.

[0044] "Lipophilic," as used herein refers to substances, molecules, and agents that have an affinity for, or a tendency to dissolve in, lipids or fats. Such substances, molecules, and agents typically exhibit little to no solubility in water due to their non-polar nature.

[0045] Numerical ranges disclosed in the present application include, but are not limited to, ranges of temperatures, ranges of concentrations, ranges of times, amongst other ranges disclosed below. The disclosed ranges, disclose individually each possible number that such a range could reasonably encompass, as well as any sub-ranges and combinations of sub-ranges encompassed therein. For example, disclosure of a range of concentrations is intended to disclose individually every possible value that such a range could encompass, consistent with the disclosure herein. For example, a concentration range of about 5 wt% to 10 wt% also discloses each weight concentration within the range individually (i.e., 5, 5.6, 6, 6.8, 7, 7.1 , 8, 8.4, 9, 9.9,

[0046] 10, 10.11 wt%, amongst others), as well as any sub-range contained therein (about 5 to 7.5 wt%).

[0047] Use of the term "about" is intended to describe values either above or below the stated value, which the term “about” modifies, in a range of approx. + / - 10%; in other instances, the values may range in value either above or below the stated value in a range of approx. + / - 5%. When the term "about" is used before a range of numbers (i.e., about 1-5) or before a series of numbers (i.e., about 1, 2, 3, 4, etc.) it is intended to modify both ends of the range of numbers and / or each of the numbers recited in the entire series, unless specified otherwise.

[0048] 11. Repellent Compositions

[0049] To address limitations and issues with currently known insect repellents, such as DEET, various repellent formulations were developed using a combination of safe natural compounds that together provide long-lasting protection from insects. In some instances, the formulations can repel mosquito bites for at least about 10, 11, or 12 hours, and optionally longer than 12 hours. Typically, the formulations can repel mosquito bites for at least about 12 hours, for greater than about 12 hours, or for 12 hours or longer.

[0050] In one non- limiting instance, a repellent formulation is in the form of an emulsion which includes:

[0051] (i) a base oil that is skin impermeable or substantially skin impermeable;

[0052] (ii) a C2-C12 alkyl lactate; and (iii) a C6-C18 fatty acid, wherein components (i), (ii), and (iii) are generally regarded as safe for topical application to skin. “Skin impermeable,” refers to the skin acting as a barrier blocking the passage, absorption, or entry of the base oil through the skin entirely. Skin impermeability is understood to be maintained by the outermost layer of the skin, known as the stratum comeum, which consists of dead skin cells and lipids that form a protective barrier. “Substantially skin impermeable,” refers to the skin acting as a barrier blocking the nearly all passage, absorption, or entry of the base oil through the skin, where less than about 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, or less by weight of the base oil applied to a skin surface is able to pass through skin.

[0053] In certain instances, the base oil is at a concentration ranging from about 50 wt% to 95 wt% or about 70 wt% to 90 wt% of the total weight of the emulsion, or at any individual concentration values or sub-ranges contained within the aforementioned ranges. In some instances, the base oil can be selected from a paraffin oil, mineral oil, petroleum, and silicone oil, or a combination thereof. The paraffin oil does not permeate skin, is stable and does not become rancid at standard ambient temperature and pressure (SATP) (i.e. 25 °C and 1 atm). Tn some instances, the paraffin oil is a light paraffin oil, a heavy paraffin oil, or a combination thereof. A “light paraffin oil” is a highly refined and purified paraffin oil having a viscosity of less than or equal to 0.86 g mL such as in the range of between about 0.83 to less than or equal to about 0.86 g mL-1and is typically odorless. A “heavy paraffin oil” is a paraffin oil having a viscosity of greater than about 0.86 g mL1, such as in a range of greater than about 0.86 to about 0.89 g mL-1and typically has a slight odor.

[0054] In some instances, the C2-C12 alkyl lactate is at a concentration ranging from about 2.5 wt% to 20 wt% or about 5 wt% to 10 wt% of the total weight of the emulsion, or at any individual concentration values or sub-ranges contained within the aforementioned ranges. In some instances, the C2-C12 alkyl lactate is at a concentration ranging from about 2.5 v% to 20 v% or about 5 v% to 10 v% of the total volume of the emulsion. In certain instances, the C2-C12 alkyl lactate is selected from ethyl L-lactate, methyl lactate, myristyl lactate, cetyl lactate, lauryl lactate, menthyl lactate, and isopropyl lactate, or a combination thereof, optionally the C2-C12 alkyl lactate is ethyl L-lactate.

[0055] In some instances, the Ce-Cis fatty acid is at a concentration ranging from about 2.5 wt% to 20 wt% or about 5 wt% to 15 wt% of the total weight of the emulsion, or at any individual concentration values or sub-ranges contained within the aforementioned ranges. In some instances, the Ce-Cis fatty acid is selected from lauric acid, oleic acid, myristic acid, and stearic acid, or combinations thereof, optionally the Ce-Cis fatty acid is lauric acid.

[0056] In most instances, the repellent formulations are inverse emulsions (also referred to as reverse emulsions). In some instances, the emulsions or inverse emulsions contain micelles or droplets that have an average diameter on the nanometer scale and range from about 10 to 500 nanometers, about 10 to 450 nanometers, about 10 to 400 nanometers, about 10 to 350 nanometers, about 10 to 300 nanometers, about 10 to 250 nanometers, about 10 to 200 nanometers, about 10 to 150 nanometers, about 10 to 100 nanometers, about 10 to 75 nanometers, about 10 to 50 nanometers, or about 10 to 25 nanometers in diameter, or any individual value or sub-range contained therein. Techniques for evaluating the size and diameters of micelles or droplets in an emulsion are known in the art.

[0057] In certain instances, the emulsions form a microemulsion having self-assembled inverted micelles therein (see Figure 1). Microemulsions demonstrate thermodynamic stability and form spontaneously. In other words, the micelles contained therein self-assemble spontaneously. The viscosity of the microemulsion is dependent on the dispersion of the micelles and the base medium in which they are dispersed in, wherein the heavier the base oil, the more viscous the microemulsion. Microemulsions can be transparent, translucent, or milky in appearance depending on droplet size and concentration. Microemulsions can be monodisperse or substantially monodisperse. “Monodisperse,” refers to microemulsions where the micelles or droplets have a uniform size distribution and “substantially monodisperse,” refers to microemulsions where the majority (i.e., 90% or greater) of the micelles or droplets have a uniform size distribution.

[0058] In certain instances, the emulsion is a microemulsion, where the average diameter of the micelles or droplets are typically on the nanometer scale and range from about 10 to 100 nanometers, 10 to 75 nanometers, about 10 to 50 nanometers, about 10 to 25 nanometers, about 10 to 20 nanometers, or any individual value or sub-range contained therein.

[0059] In certain other instances, the emulsion is a nanoemulsion. In contrast to microemulsions, nanoemulsions generally have higher dispersities than microemulsions and are typically not monodisperse. Nanoemulsions demonstrate kinetic stability and usually require steps, such as high shear mixing and / or sonication, for their formation. Nanoemulsions are prone to separation over time and surfactant(s) or emulsifying agent(s) can be used to stabilize them. Nanoemulsions can have a range of viscosities, from low to high, depending on composition and concentration.

[0060] For nanoemulsions, the average diameter of the micelles or droplets contained therein can be on the nanometer scale and may range from about 20 to 400 nanometers in diameter, about 50 to 400 nm, about 100 to 400 nm, about 100 to 350 nm, about 100 to 300 nm, about 100 to 250 nm, about 100 to 200 nm, about 100 to 150 nm, or about 100 to 125 nm, or any individual value or sub-range contained therein.

[0061] In some instances, the repellent formulations further include one or more surfactants and / or emulsifying agents that are generally regarded as safe for topical application to skin, such as human skin, therein. Suitable surfactants include SPAN™ 20-80 (such as SPAN™ 80) and / or TWEEN® 20-80. Other surfactants and / or emulsifying agents can include sodium lauryl sulfate (SLS), cocoamidopropyl betaine, cetearyl alcohol, ceteareth-20, sorbitan oleate, glyceryl stearate, PEG- 100 stearate, emulsifying wax NF, lecithin, beeswax, carbomer, dimethicone copolyol, and / or PEG- 8 dimethicone. In certain instances, the repellent formulations are free or substantially free of any surfactants and / or emulsifying agents. “Substantially free,” as used herein refers to a formulation having less than about 3%, 2%, 1%, 0.0%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, or less by weight of the total weight of the formulation.

[0062] In some instances, the repellent formulation can further include a cargo selected from insect repellent agents (such as DEET), sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof. In some instances, the cargo is hydrophilic. In some other instances, the cargo can be lipophilic and can be suspended in a continuous oil phase, such as formed by the base oil of the emulsion.

[0063] In yet another non-limiting instance, a repellent formulation is in the form of an emulsion and includes:

[0064] (i’) a base oil which is a paraffin oil;

[0065] (ii’) a C2-C12 alkyl lactate at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or at a concentration ranging from about 5 v% to 10 v% of the total volume of the emulsion; and

[0066] (iii’) a Ce-Cis fatty acid at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion, where the emulsion is an inverse microemulsion.

[0067] Details of the base oil, C2-C12 alkyl lactate, and Cr.-Cis fatty acid are the same as described above. In some instances, such a repellent formulation further includes one or more surfactants and / or emulsifying agents therein. In certain instances, the repellent formulation is free or substantially free of any surfactants and / or emulsifying agents. “Substantially free,” as used herein refers to a formulation having less than about 3%, 2%, 1%, 0.0%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, or less by weight of the total weight of the formulation. In some instances, such a repellent formulation further includes a cargo selected from insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof. In some instances, the cargo can be hydrophilic. In some other instances, the cargo can be lipophilic and can be suspended in a continuous oil phase, such as formed by the base oil of the emulsion. In some instances, the insect repellent agents may include or exclude DEET.

[0068] In certain instances, the base oil is selected from a paraffin oil (either heavy, light, or in its less processed state mineral oil) and ethyl L-lactate (ELL; a C2-C12 alkyl lactate) and lauric acid (LA; a Ce-Cis fatty acid) serve simultaneously as the emulsifier and the cargo. It is believed that the fatty acid, such as LA, can interact with the non-polar ends of alkyl lactate, such as ELL to self-assemble and form into an inverted micelle, where the polar ends of the alkyl lactate, such as ELL, congregate and pack together, as shown in Figure 1. The inverted micelles are surrounded by the base oil, such as paraffin oil. The paraffin oil can be an unscented (light) paraffin oil. The alkyl lactate ELL is readily obtained from peas and red grapes (and other sources), is biodegradable, known to be FDA approved and safe for use in low concentrations with no irritation on skin. The fatty acid LA can be derived from coconuts (and other sources), has been shown to have antibacterial properties, and is FDA approved and safe for use at up to 100% concentrations with no irritation on skin.

[0069] Without being bound by theory, it is believed that physical interactions between the C2- C12 alkyl lactate, such as ELL, and the C6-Cis fatty acid, such as LA, can create a s low-release method of repellent delivery. See Figure 2, which shows a microemulsion of inverted micelles dispersed in a layer of base oil (paraffin oil) on a skin surface. The paraffin oil provides for low skin permeation of the emulsion, which allows for a slow release of the inverted micelles from the layer surface.

[0070] The repellent formulations are typically stable for at least one month, at least two months, three months, four months, five months, 6 months or longer, or at least one year, and optionally longer at a range of temperatures, such as temperatures ranging from about 10-70°C at 1 atm pressure. The repellent formulations can remain stable at temperatures ranging from about 10-70 °C, such as from about 20-70 °C, from about 20-50 °C, from about 20-40 °C, or from about 20- 30 °C for time periods of at least 7 days, at least 4 weeks, or at least 6 months, or at least 1 year, optionally longer than 1 year, such as for at least 1.5 years, or at least 2 years at a temperature of about 70°C at 1 atm. In some instances, when frozen the micelles may separate. However, when thawed to a temperature within the temperature range at which the micelles are stable, the micelles selfassemble.

[0071] In certain instances, the formulations include one or more water-absorbing compounds to enhance stability, rheological properties, and / or overall functionality. In certain instances, the water-absorbing compounds are alginates, chitosan derivatives, carboxymethyl cellulose (CMC), polyacrylates, or other hydrocolloids. In some instances, the water-absorbing compound is CMC. In certain instances, the water absorbing compounds are incorporated into the formulation at concentrations ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt%, or individual values or sub-ranges of the aforementioned ranges, in order to help absorb water and maintain structural integrity in varying humidity conditions. The inclusion of one or more water-absorbing compounds, for example CMC, can reduce water mobility within the formulation, thereby mitigating phase separation and preventing viscosity shifts of about 5% - 65%, 5% - 60%, 5% - 55%, 5% - 50%, 10% - 50%, 15% - 50%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50%, or more, or individual values or subranges of the aforementioned ranges, from the baseline viscosity value under standard temperature and pressure (STP) conditions. The inclusion of water-absorbing compounds can facilitate a uniform distribution of active components when the formulation is stored or applied under conditions involving temperature which are below about 5 °C or above about 40 °C, or humidity conditions which are below about 20% relative humidity (RH) or above about 80% RH.

[0072] In some instances, the formulations may contain one or more stabilizers to improve the emulsion’s physical integrity and reduce phase separation. In certain instances, the stabilizer is glycerol oleate, a safe nonionic surfactant or co-emulsifier. Other suitable stabilizers are known. In certain instances, the one or more stabilizers are incorporated into the formulation at concentrations ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0. 1 wt% to 3.5 wt%, or about 0. 1 wt% to 3.0 wt%, or individual values or sub-ranges of the aforementioned ranges,. The stabilizers may help form a stabilized interface between the continuous (oil) and dispersed (micellar) phases. Such stabilizers enhance the longterm shelf life of the formulation, particularly under elevated temperature or fluctuating humidity conditions.

[0073] In some instances, the formulation may contain one or more antioxidants to reduce oxidative degradation of the formulation over time. In some instances, the one or more antioxidants can include tocopherols and / or butylated hydroxytoluene (BHT). Other suitable antioxidants are known. In some instances, the one or more antioxidants are incorporated into the formulation at concentrations ranging from about 0.05 wt% to 3.0 wt%, about 0.05 wt% to 2.5 wt%, about 0.05 wt% to 2.0 wt%, about 0.05 wt% to 1.5 wt%, or about 0.05 wt% to 1.0 wt%, or individual values or sub-ranges of the aforementioned ranges. The addition of antioxidants can extend the product’s shelf life, preserve product color and / or odor, and maintain the potency of lipophilic ingredients (e.g., fatty acids and base oils).

[0074] In certain instances, the formulation contains one or more humectants to enhance user comfort by retaining moisture on the skin on which it is applied. In some instances, the one or more humectants can be glycerin and / or sorbitol. Other suitable humectants are known. In certain instances, the one or more humectants are added at concentrations between about 0.5 wt% to 7.0 wt%, about 0.5 wt% to 6.5 wt%, about 0.5 wt% to 6.0 wt%, about 0.5 wt% to 5.5 wt%, about 0.5 wt% to 5.0 wt%, about 0.2 wt% to 5 wt% or about 0.1 wt% to 5 wt%, or individual values or sub-ranges of the aforementioned ranges. The presence of humectants helps counteract dryness or irritation, improving the overall sensory attributes of the formulation during topical application.

[0075] III. Methods of Preparing Repellent Compositions

[0076] In one non-limiting instance, the repellent formulations can be prepared according to a method including the step of:

[0077] (a) preparing a mixture of a C2-C12 alkyl lactate, a C6-Cis fatty acid, and a base oil to form an emulsion including self- assembled micelles therein.

[0078] Details of the base oil, C2-C12 alkyl lactate and Ce-Cis fatty acid, are the same as already described in Section II above. The three components (C2-C12 alkyl lactate, Ce-Ci8 fatty acid, and base oil) can be mixed in any order. In certain instances, the C2-C12 alkyl lactate and Cs-Cis fatty acid are mixed first and then the combination may be added into the base oil. Optionally, the preparing step (a) is performed with heating. In some instances, heating is applied to heat the mixture to a temperature of at least about 70 °C or higher. Heating is typically applied to promote complete dissolution of all components and could also promote micelle formation.

[0079] Heating may be applied for any suitable amount of time needed to ensure dissolution of any solid components of the mixture, such as for a period of at least about 5 seconds to about five minutes, or longer. The length of heating time can be impacted by the volume of the mixture. In certain instances, the heating can applied for a short period of time ranging from about 30 to 60 seconds. In certain instances, heating is not performed using a water-based heating bath to avoid or minimize exposure of the mixture to water vapor. In the event that a water bath is used, the contents can be sealed and vented to prevent or minimize exposure to water vapor.

[0080] In certain instances, the emulsion formed can further include a cargo and the method further includes adding the cargo into the mixture of the C2-C12 alkyl lactate, the Ce-Cis fatty acid, and the base oil. In some instances, the cargo is selected from insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof. In some instances, the cargo is hydrophilic. In some other instances, the cargo can be lipophilic and can be suspended in a continuous oil phase, such as formed by the base oil of the emulsion.

[0081] In some instances of the method, following step (a), a step (b) of sonicating and / or shaking the emulsion formed can be performed to promote formation or increase rate of the formation of micelles.

[0082] In certain instances, the method further includes a step (c) of heating the formed emulsion to promote formation or increase the rate of formation of micelles. This heating may be a continuation of the heating applied for purposes of dissolution of any solid components of the mixture, where the heating may be continued to be applied to the mixture after all solid components have been dissolved. In some instances, heating is applied to heat the mixture to a temperature of at least about 70 C or higher. Heating may be applied for any suitable amount of time needed to promote formation or increase the rate of formation of the self-assembled micelles, such as for a period of time ranging from about 10 to 90 seconds, 20 to 60 seconds, or 30 to 60 seconds.

[0083] In certain instances of the method, the mixture further includes at least one surfactant and / or emulsifying agent and the mixture can be sonicated, typically with cooling (such as by exposing the mixture to an ice-water bath or other cooling solution). Without limitation, the at least one surfactant can include SPAN™ 20-80 (such as SPAN™ 80) and / or TWEEN® 20-80. Other suitable surfactants and / or emulsifying agents include, without limitation, sodium lauryl sulfate (SLS), cocoamidopropyl betaine, cetearyl alcohol, ceteareth-20, sorbitan oleate, glyceryl stearate, PEG- 100 stearate, emulsifying wax NF, lecithin, beeswax, carbomer, dimethicone copolyol, and / or PEG- 8 dimethicone. The surfactant and / or emulsifying agent may be present at weight concentrations in a range from about 0.01 wt% to 30 wt% based on the total weight of the mixture, as well as any individual weight percentage or sub-range contained within. In some instances, the sonication can be performed with an ultrasonic probe, where the probe tip is placed in the mixture. In some instances, sonication is not applied by means of an ultrasonic water bath. The ultrasonic probe is typically pulsed and each pulse can have an amplitude of about 40% and / or the ultrasonic probe is pulsed with a plurality of pulses having about 3 seconds of sonication time and about 3 seconds of no sonication time per pulse. Other amplitudes and pulse times are possible. For instance, the amplitude can be in a range from about 15 to 50% or 20 to 40% and the pulse time may range from about 1 to 5 seconds or 2 to 4 seconds, as well as individual values or sub-ranges contained within the aforementioned ranges.

[0084] IV. Methods of Using Repellent Compositions

[0085] The repellent formulations can be used to repel arthropods, such as insects. In some instances, the formulations can repel arachnids. The repellent formulations can be used to repel one or more types of insects, such as fleas, ticks, mites, mosquitoes, flies, lice, blowflies, bed bugs, stable flies, hom flies, or black flies, and combinations thereof. Specific examples include, but are not limited to, cat and dog fleas, ticks, and mites, lice (Trichodectes spp., Cheyletiella spp., Linognathus spp., and the like), mosquitoes (Aedes spp., Culex spp., Anopheles spp., and the like) and flies (Haematobia spp., Musca spp., Stomoxys spp., Dermatobia spp., Cochliomyia spp. , and the like). In some instances, the arachnid is a spider. In certain instances, the mosquito is a blood- feeding species from any of the known Aedes or Anopheles subspecies, or may be from other species including, without limitation, Culex and Culiseta, and their respective subspecies. In some instances, the mosquito is an Aedes aegypti or Anopheles stephensi mosquito.

[0086] In one non- limiting instance, a method of repelling an insect (or arachnid) includes the steps of:

[0087] (a’) applying a repellent formulation, in the form of an emulsion, as described in Section II above, to at least a portion of a skin surface of a subject; wherein following step (a’), the portion of the skin surface to which the emulsion was applied provides a complete protection time (CPT) of at least about 12 hours, and optionally provides a CPT of at least about 12 hours.

[0088] For the methods described, the subject can be any mammal. In some instances, the subject is a human. In some instances, the mammal is a livestock or farm animal (such as a cow, horse, etc.) or can be a domesticated animal (such as a dog, cat, etc.). In some instances, the complete protection time (CPT) is provided for at least 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 hours, or longer. In some instances, the complete protection time (CPT) is provided for a period of time ranging from at least about 12 to 24 hours, or individual time values or sub-ranges contained within the aforementioned range. Although there are different criteria used for CPT depending on the organism, for mosquitoes, a non-limiting example of a test to determine CPT using the arm-in-cage testing method, is shown in Figure 3. The same method can be used for testing other biting insects, however the time period to determine a confirmed bite may vary, depending on insect of interest. The arm-in-cage method involves step 1 , where a cage containing mosquitoes, such as at a density of about 30 mosquitoes per 30 cubic centimeters; followed by step 2, inserting a forearm, which has exposed skin that has been treated with the repellent formulation to be tested, or is untreated (acting as a control), into the cage for a period of time. Lastly, in step 3 of the method, the complete protection time (CPT) is calculated from the time between repellent application to the exposed skin and insertion into the cage and the first confirmed mosquito bite. A mosquito bite can be confirmed when after the bite occurs a second bite occurs within 30 minutes of the first bite. If a second bite does not occur within 30 minutes of the first bite, the first bite is not a “confirmed mosquito bite” and is dismissed and volunteer continues testing. Subsequently, if the volunteer receives another bite at any point of the testing, this subsequent bite is considered the first bite and they leave their arm in the cage for up to at least 30 minutes or until a confirmation bite is recorded (if it occurs in less than 30 minutes) to determine if the subsequent bite is confirmed. The test continues until a set time period is reached without a confirmed bite or until the first confirmed bite is achieved. See, e.g. Luker et al. 2023. Sci Rep 13, 1705.

[0089] In some instances, the repellent formulations demonstrate a Repellency (7?%) of at least about 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or up to 100%. In some instances, the repellency ranges from about 25 to 100%, 50 to 100%, or 75 to 100%, or any individual percentage value or sub-range contained within the aforementioned ranges.

[0090] In some instances, the repellent formulations can be stored inside a container that blocks out or substantially blocks ambient light from reaching the formulation. “Substantially blocks,” refers to blocking out at least about 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% of ambient light present outside of the container.

[0091] The presently disclosed subject matter will be better understood by reference to the following number paragraphs and Examples, which are provided as exemplary of the invention, and not by way of limitation.

[0092] 1. An emulsion comprising:

[0093] (i) a base oil that is skin impermeable or substantially skin impermeable;

[0094] (ii) a C2-C12 alkyl lactate; and

[0095] (iii) a Ce-Ci8 fatty acid, wherein components (i), (ii), and (iii) are generally regarded as safe for topical application to skin.

[0096] 2. The emulsion of paragraph 1 , wherein the base oil is selected from the group consisting of paraffin oil, mineral oil, petroleum, and silicone oil, and a combination thereof. 3. The emulsion of paragraph 2, wherein the base oil is paraffin oil, and wherein the paraffin oil is a light paraffin oil, a heavy paraffin oil, and a combination thereof.

[0097] 4. The emulsion of any one of paragraphs 1-3, wherein the C2-C12 alkyl lactate is selected from the group consisting of ethyl L-lactate, methyl lactate, myristyl lactate, cetyl lactate, lauryl lactate, menthyl lactate, and isopropyl lactate, and a combination thereof.

[0098] 5. The emulsion of any one of paragraphs 1-4, wherein the Ce-Ci8 fatty acid is selected from the group consisting of lauric acid, oleic acid, myristic acid, and stearic acid, and combinations thereof.

[0099] 6. The emulsion of any one of paragraphs 1-5, wherein the C2-C12 alkyl lactate is at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or about 5 v% to 10 v% of the total volume of the emulsion.

[0100] 7. The emulsion of any one of paragraphs 1-6, wherein the Ce-Cis fatty acid is at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion.

[0101] 8. The emulsion of any one of paragraphs 1-7, wherein the base oil is at a concentration ranging from about 70 wt% to 90 wt% of the total weight of the emulsion.

[0102] 9. The emulsion of any one of paragraphs 1-8, wherein the emulsion is a microemulsion comprising self-assembled micelles therein.

[0103] 10. The emulsion of paragraph 9, wherein the microemulsion is an inverse microemulsion.

[0104] 11. The emulsion of any one of paragraphs 1-8, wherein the emulsion is an inverse nanoemulsion.

[0105] 12. The emulsion of any one of paragraphs 1-11, wherein the emulsion further comprises one or more surfactants.

[0106] 13. The emulsion of any one of paragraphs 1-11, wherein the emulsion is free or substantially free of surfactants.

[0107] 14. The emulsion of any one of paragraphs 1-13, wherein the emulsion further comprises (iv) a cargo, wherein the cargo is hydrophilic and is selected from the group consisting of insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof.

[0108] 15. The emulsion of any one of paragraphs 1-14, wherein the emulsion further comprises one or more water- absorbing compounds optionally selected from the group consisting of carboxymethyl cellulose (CMC), alginate, chitosan, polyacrylates, and combinations thereof.

[0109] 16. The emulsion of paragraph 15, wherein the one or more water-absorbing compounds are present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

[0110] 17. The emulsion of any one of paragraphs 1-16, wherein the emulsion further comprises at least one stabilizer optionally selected from the group consisting of glycerol oleate, sorbitan oleate, and combinations thereof.

[0111] 18. The emulsion of paragraph 17, wherein the at least one stabilizer is present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

[0112] 19. The emulsion of any one of paragraphs 1-18, wherein the emulsion further comprises one or more antioxidants optionally selected from the group consisting of tocopherols, butylated hydroxytoluene (BHT), and combinations thereof.

[0113] 20. The emulsion of paragraph 19, wherein the one or more antioxidants are present at a concentration ranging from about 0.05 wt% to 3.0 wt%, about 0.05 wt% to 2.5 wt%, about 0.05 wt% to 2.0 wt%, about 0.05 wt% to 1.5 wt%, or about 0.05 wt% to 1.0 wt% of the total weight of the emulsion.

[0114] 21. The emulsion of any one of paragraphs 1-20, wherein the emulsion further comprises one or more humectants optionally selected from the group consisting of glycerin, sorbitol, and combinations thereof.

[0115] 22. The emulsion of paragraph 21, wherein the one or more humectants are present at a concentration ranging from about 0.5 wt% to 7.0 wt%, about 0.5 wt% to 6.5 wt%, about 0.5 wt% to 6.0 wt%, about 0.5 wt% to 5.5 wt%, about 0.5 wt% to 5.0 wt%, about 0.2 wt% to 5 wt% or about 0.1 wt% to 5 wt% of the total weight of the emulsion.

[0116] 23. An emulsion comprising: a base oil which is a paraffin oil; a C2-C12 alkyl lactate at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or about 5 v% to 10 v% of the total volume of the emulsion; and a Ce-Cis fatty acid at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion, wherein the emulsion is an inverse microemulsion.

[0117] 24. The emulsion of paragraph 23, wherein the paraffin oil comprises a light, a heavy paraffin oil, or a combination thereof. 25. The emulsion of any one of paragraphs 23-24, wherein the C2-C12 alkyl lactate is selected from the group consisting of methyl lactate, myristyl lactate, cetyl lactate, lauryl lactate, menthyl lactate, and isopropyl lactate, or a combination thereof.

[0118] 26. The emulsion of any one of paragraphs 23-25, wherein the Cs-C'ix fatty acid is selected from the group consisting of lauric acid, oleic acid, myristic acid, and stearic acid, or a combination thereof.

[0119] 27. The emulsion of any one of paragraphs 23-26, wherein the emulsion is free or substantially free of surfactants.

[0120] 28. The emulsion of any one of paragraphs 23-27, wherein the emulsion further comprises a cargo, wherein the cargo is hydrophilic and is selected from the group consisting of insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof.

[0121] 29. The emulsion of any one of paragraphs 23-28, wherein the emulsion further comprises one or more water-absorbing compounds optionally selected from the group consisting of carboxymethyl cellulose (CMC), alginate, chitosan, polyacrylates, and combinations thereof.

[0122] 30. The emulsion of paragraph 29, wherein the one or more water-absorbing compounds are present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

[0123] 31. The emulsion of any one of paragraphs 23-30, wherein the emulsion further comprises at least one stabilizer optionally selected from the group consisting of glycerol oleate, sorbitan oleate, and combinations thereof.

[0124] 32. The emulsion of paragraph 31, wherein the at least one stabilizer is present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

[0125] 33. The emulsion of any one of paragraphs 23-32, wherein the emulsion further comprises one or more antioxidants optionally selected from the group consisting of tocopherols, butylated hydroxytoluene (BHT), and combinations thereof.

[0126] 34. The emulsion of paragraph 33, wherein the one or more antioxidants is present at a concentration ranging from about 0.05 wt% to 3.0 wt%, about 0.05 wt% to 2.5 wt%, about 0.05 wt% to 2.0 wt%, about 0.05 wt% to 1.5 wt%, or about 0.05 wt% to 1.0 wt% of the total weight of the emulsion. 35. The emulsion of any one of paragraphs 23-34, wherein the emulsion further comprises one or more humectants optionally selected from the group consisting of glycerin, sorbitol, and combinations thereof.

[0127] 36. The emulsion of paragraph 35, wherein the one or more humectants are present at a concentration ranging from about 0.5 wt% to 7.0 wt%, about 0.5 wt% to 6.5 wt%, about 0.5 wt% to 6.0 wt%, about 0.5 wt% to 5.5 wt%, about 0.5 wt% to 5.0 wt%, about 0.2 wt% to 5 wt% or about 0.1 wt% to 5 wt% of the total weight of the emulsion.

[0128] 37. A method of making the emulsion of any one of paragraphs 1-36, the method comprising:

[0129] (a) preparing a mixture of the C2-C12 alkyl lactate, the Ce-Cis fatty acid, and the base oil to form an emulsion comprising micelles.

[0130] 38. The method of paragraph 37, wherein the preparing step (a) is performed with heating of the mixture to a temperature of about 70 °C.

[0131] 39. The method of paragraph 37, wherein the emulsion further comprises a cargo and the method further comprises the cargo being present in the mixture of the C2-C12 alkyl lactate, the Ce-Ci8 fatty acid, and the base oil.

[0132] 40. The method of any one of paragraphs 37-39, wherein the method further comprises a step

[0133] (b) of sonicating and / or shaking the emulsion formed to increase formation of the micelles.

[0134] 41. The method of any one of paragraphs 37-39, wherein the method further comprises a step

[0135] (c) of heating the emulsion formed to increase formation of the micelles.

[0136] 42. The method of paragraph 37, wherein the mixture further comprises at least one surfactant and the mixture is sonicated optionally with cooling.

[0137] 43. The method of paragraph 42, wherein the at least one surfactant is selected from the group consisting of SPAN™ 80, sodium lauryl sulfate (SLS), cocoamidopropyl betaine, cetearyl alcohol, ceteareth-20, sorbitan oleate, glyceryl stearate, PEG- 100 stearate, emulsifying wax NF, lecithin, beeswax, carbomer, dimethicone copolyol, PEG-8 dimethicone, and combinations thereof.

[0138] 44. The method of any one of paragraphs 42-43, wherein the sonication is performed with an ultrasonic probe.

[0139] 45. A method of repelling an insect or an arachnid, the method comprising the steps of: (a’) applying the emulsion of any one of paragraphs 1-28 to at least a portion of a skin surface of a subject; wherein following step (a’), the portion of the skin surface to which the emulsion was applied provides a complete protection time of at least about 9 hours, optionally at least about 10 hours.

[0140] 46. The method of paragraph 45, wherein the insect or arachnid is selected from the group consisting of a mosquito, tick, spider, bed bug, stable fly, horn fly, and black fly, and combinations thereof.

[0141] 47. The method of paragraph 46, wherein the mosquito is an Aedes aegypti or Anopheles stephensi mosquito.

[0142] 48. The method of any one of paragraphs 46-47, wherein the subject is a mammal.

[0143] 49. The method of any one of paragraphs 46-48, wherein the subject is a human.

[0144] The present invention will be further understood by reference to the following nonlimiting examples.

[0145] Examples

[0146] Example 1A: Repellent Microemulsions

[0147] Materials and Repellent Emulsion Preparation:

[0148] Table 1.

[0149] Lab-Scale Preparation of Micro emulsions: 10 mL 6 wt% ELL / 7% LA microemulsions were prepared from the ingredients listed in Table 1 using the following steps:

[0150] 1. 0.6 mL or 0.62 g of ethyl L-lactate and 0.7 g of lauric acid were measured and combined to form a mixture.

[0151] 2. The mixture was heated to 70 °C on a hotplate for 5 minutes.

[0152] 3. The heated mixture was added to 8.6 mL of unscented light paraffin oil.

[0153] 4. Vortex / shake liquid mixture for 10 seconds to speed up the self-assembly process. Repellent Microemulsion Evaluation'.

[0154] The microemulsions prepared above were evaluated for their ability to repel Aedes aegypti mosquitoes using arm-in-cage studies. Figure 3 shows an schematic of the arm-in-cage method.

[0155] Table 2.

[0156] Discussion'.

[0157] As shown in Table 2, the emulsions studied were able to provide at least 12 hours of complete protection time (CPT), depending on the repellent composition. This was much higher than the CPT time found for the industry standard repellent DEET (7V,A-Diethyl-meta- toluamide). The experiment using 6% ELL / 7% LA in paraffin oil was stopped after 12 hours with no bites on the arm. Table 2 further discloses comparative protection times for the test formulation (containing 6% ELL and 7%LA) and 25% DEET (OFF! Deep Woods) against Aedes aegypti and Anopheles stephensi. Complete Protection Time (CPT) is reported in hours, with the test formulation (6%ELL, 7%LA, Light Paraffin Oil) delivering >12 hours of repellency in each trial. DEET exhibited shorter mean protection windows (5.3+0.4 and 6.3+0.3 hours, respectively). The number of trials for each test condition are indicated in the final column.

[0158] Notably, the 6% ELL / 7% LA unscented paraffin oil (light) repellent formulation did not require any surfactants to create micelles. Instead, in this formulation ELL acts as a solvent; ELL is slightly amphiphilic, and is stable at high temperatures. Without being bound by theory, it is believed that the non-polar ends of ELL and LA can interact while the polar ends of ELL congregate forming micelles. The self-assembled micelles were then slowly introduced into the paraffin oil to provide a microemulsion which is stable in a wide range of temperatures, such as ranging from about 20°C until about 70°C, at 1 atm. Due to its self-assembling nature, even if the solution is destabilized through freezing, it can reform itself into a stable microemulsion once it reaches its stable temperature range.

[0159] Example IB: Repellent Nanoemulsions

[0160] Nanoemulsions can be prepared with the ingredients of Table 1 above and a surfactant. An exemplary method of preparation is described below.

[0161] Preparation of Nanoemulsions'. 10 mL 6 wt% ELL / 7% LA nanoemulsions were prepared from SPAN™ 80 (Sigma Aldrich in liquid form) and the ingredients listed in Table 1 using the following steps:

[0162] 1 ’. An Ultrasonic (Ultrasonic Homogenizer Sonicator Lab Cell Disruptor 950W, 21 Khz) <D6 mm probe was cooled in a cold water bath.

[0163] 2’. 0.6 mL or 0.62 g of ethyl L-lactate, 0.7 g of lauric acid, 3 mL or 3.18 g of

[0164] SPAN™ 80, and 5.6 mL of Unscented light Paraffin oil were combined in a vial.

[0165] 3 ’ . The vial was placed in the cold water bath and the ultrasonic probe was positioned in the vial.

[0166] 4’. The mixture in the vial was sonicated a. Sonication Parameters: 40% amplitude, 40 min total time, 3 seconds sonication with 3 second gaps in between (20 min working time).

[0167] Discussion:

[0168] The nanoemulsions include a surfactant and a formed using sonication. Such nanoemulsions can also be evaluated for their ability to repel Aedes aegypti mosquitoes using arm-in-cage studies, such as those discussed in Example 1A, and using an arm-in-cage method (Figure 3). Testing under such conditions, the nanoemulsions would be expected to provide CPT times similar to the microemulsions, such as IR007. CPT times would be expected to remain consistent since the active components, such as ethyl L-lactate (ELL) and lauric acid (LA), are the same. As long as these components are incorporated into a system that reduces evaporation and limits skin penetration, such as a paraffin or silicone oil base, their efficacy would be expected to be preserved. The inclusion of surfactant(s), or other additives, are unlikely to negatively impact the CPT, as they are inert and can be used at minimal concentrations.

[0169] Example 2: Evaluation of Ethyl L-Iactate (ELL) alone, Lactic acid (LA) alone, combinations of ELL and LA (in ethanol or oil) tested on Artificial Skin

[0170] Tests were conducted on artificial skin, which was integrated into a blood feeder system. Artificial skin is a membrane made of a dessicated chitosan mixture that absorbs hydrophilic compounds when rehydrated. This apparatus holds approximately 2 mL of blood, maintaining it at a temperature of 36°C to mimic human conditions. Due to the risk of coagulation, tests were limited to a maximum of 20 minutes.

[0171] The following five formulations were tested: The Control was ethanol (alone) (containing 0% ELL); 6% ELL alone in ethanol; 7% LA alone in ethanol; 6% ELL and 7% LA in light paraffin oil (referred to as “IR700”); and the combination of 6% ELL and 7% LA in ethanol. Ethanol was chosen as a solvent based on its ability to solubilize LA.

[0172] Results:

[0173] Figure 5 shows a bar graph demonstrating repellent properties of ethyl L-lactate (ELL) and lauric acid (LA) using artificial blood feeders. In Figure 5, the y-axis is percent blood fed and the x-axis corresponds with the 5 different tested formulations described above.

[0174] Example 3: Evaluation of Ethyl L-lactate (ELL) on Artificial Skin

[0175] Materials and Methods'.

[0176] Tests were conducted on artificial skin, which was integrated into a blood feeder system. Artificial skin is a membrane made of a dessicated chitosan mixture that absorbs hydrophilic compounds when rehydrated. This apparatus holds approximately 2 mL of blood, maintaining it at a temperature of 36°C to mimic human conditions. Due to the risk of coagulation, tests were limited to a maximum of 20 minutes.

[0177] 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10% ELL formulations were prepared and applied directly to the artificial skin. A control having no ELL was also prepared.

[0178] The artificial skin treated with the above samples was exposed to Aedes aegypti mosquitoes and the percent blood fed was evaluated.

[0179] Discussion:

[0180] As shown in Figure 4, as the concentration of ELL alone increased the percentage of blood feeding by the mosquitoes decreased significantly. ELL by itself, however, is readily absorbed by skin and metabolized, which renders its use alone inadequate for effective repellency. As shown in Example 1, ELL in combination with lauric acid is effective at inhibiting mosquito blood feeding, and was even more effective than a commercially available product containing 25% DEET. After achieving zero blood feeding in the artificial skin setup, attributed to IR007 (6% ELL and 7% LA in light paraffin oil), arm-in-cage assays were conducted for further evaluation.

[0181] Example 4: Evaluation of Ethyl Laurate as Substitute for Lauric Acid

[0182] Materials and Methods:

[0183] Ethyl laurate was tested as a substitute for lauric acid in a paraffin oil base combined with ethyl lactate. Formulations containing about 5-10 wt% ethyl laurate, 5-10 wt% ethyl lactate, and 80-90 wt% paraffin oil were prepared and evaluated via artificial feeders and arm-in-cage assays. Although initial findings with artificial blood feeders were promising, this ethyl laurate- based emulsion proved ineffective in arm-in-cage assays. The first mosquito bites occurred within approximately 3 minutes of introducing the treated arm into a cage of Aedes aegypti mosquitoes.

[0184] Discussion:

[0185] These results indicated that ethyl laurate lacks the critical interactions and selfassembling properties of lauric acid with ethyl lactate, thereby failing to provide the extended complete protection time (CPT) observed with the formulations described herein. Figure 4 and Figure 6 show that ELL and LA alone are not sufficient to provide complete protection from mosquito bites (i.e., 0% blood feeding).

[0186] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed invention belongs. Publications cited herein and the materials for which they are cited are specifically incorporated by reference.

[0187] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

CLAIMSWe claim:

1. An emulsion comprising:(i) a base oil that is skin impermeable or substantially skin impermeable;(ii) a C2-C12 alkyl lactate; and(iii) a Ce-Ci8 fatty acid, wherein components (i), (ii), and (iii) are generally regarded as safe for topical application to skin.

2. The emulsion of claim 1, wherein the base oil is selected from the group consisting of paraffin oil, mineral oil, petroleum, and silicone oil, and a combination thereof.

3. The emulsion of claim 2, wherein the base oil is paraffin oil, and wherein the paraffin oil is a light paraffin oil, a heavy paraffin oil, and a combination thereof.

4. The emulsion of claim 1, wherein the C2-C12 alkyl lactate is selected from the group consisting of ethyl L-lactate, methyl lactate, myristyl lactate, cetyl lactate, lauryl lactate, menthyl lactate, and isopropyl lactate, and a combination thereof.

5. The emulsion of claim 1, wherein the Ce-Cis fatty acid is selected from the group consisting of lauric acid, oleic acid, myristic acid, and stearic acid, and combinations thereof.

6. The emulsion of claim 1, wherein the C2-C12 alkyl lactate is at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or about 5 v% to 10 v% of the total volume of the emulsion.

7. The emulsion of claim 1, wherein the Ce-Ci8 fatty acid is at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion.

8. The emulsion of claim 1, wherein the base oil is at a concentration ranging from about 70 wt% to 90 wt% of the total weight of the emulsion.

9. The emulsion of claim 1 , wherein the emulsion is a microemulsion comprising selfassembled micelles therein.

10. The emulsion of claim 9, wherein the microemulsion is an inverse microemulsion.

11. The emulsion of claim 1 , wherein the emulsion is an inverse nanoemulsion.

12. The emulsion of claim 1, wherein the emulsion further comprises one or more surfactants.

13. The emulsion of claim 1, wherein the emulsion is free or substantially free of surfactants.

14. The emulsion of claim 1, wherein the emulsion further comprises (iv) a cargo, wherein the cargo is hydrophilic and is selected from the group consisting of insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof.

15. The emulsion of claim 1, wherein the emulsion further comprises one or more waterabsorbing compounds, optionally selected from the group consisting of carboxymethyl cellulose (CMC), alginate, chitosan, poly acrylates, and combinations thereof.

16. The emulsion of claim 15, wherein the one or more water-absorbing compounds are present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

17. The emulsion of claim 1, wherein the emulsion further comprises at least one stabilizer, optionally selected from the group consisting of glycerol oleate, sorbitan oleate, and combinations thereof.

18. The emulsion of claim 17, wherein the at least one stabilizer is present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0. 1 wt% to 3.0 wt% of the total weight of the emulsion.

19. The emulsion of claim 1, wherein the emulsion further comprises one or more antioxidants optionally selected from the group consisting of tocopherols, butylated hydroxytoluene (BHT), and combinations thereof.

20. The emulsion of claim 19, wherein the one or more antioxidants are present at a concentration ranging from about 0.05 wt% to 3.0 wt%, about 0.05 wt% to 2.5 wt%, about 0.05 wt% to 2.0 wt%, about 0.05 wt% to 1.5 wt%, or about 0.05 wt% to 1.0 wt% of the total weight of the emulsion.

21. The emulsion of claim 1, wherein the emulsion further comprises one or more humectants optionally selected from the group consisting of glycerin, sorbitol, and combinations thereof.

22. The emulsion of claim 21, wherein the one or more humectants are present at a concentration ranging from about 0.5 wt% to 7.0 wt%, about 0.5 wt% to 6.5 wt%, about 0.5 wt% to 6.0 wt%, about 0.5 wt% to 5.5 wt%, about 0.5 wt% to 5.0 wt%, about 0.2 wt% to 5 wt% or about 0.1 wt% to 5 wt% of the total weight of the emulsion.

23. An emulsion comprising: a base oil which is a paraffin oil; a C2-C12 alkyl lactate at a concentration ranging from about 5 wt% to 10 wt% of the total weight of the emulsion or about 5 v% to 10 v% of the total volume of the emulsion; and a Ce-Cis fatty acid at a concentration ranging from about 5 wt% to 15 wt% of the total weight of the emulsion, wherein the emulsion is an inverse microemulsion.

24. The emulsion of claim 23, wherein the paraffin oil comprises a light, a heavy paraffin oil, or a combination thereof.

25. The emulsion of claim 23, wherein the C2-C12 alkyl lactate is selected from the group consisting of methyl lactate, myristyl lactate, cetyl lactate, lauryl lactate, menthyl lactate, and isopropyl lactate, or a combination thereof.

26. The emulsion of claim 23, wherein the Ce-Ci8 fatty acid is selected from the group consisting of lauric acid, oleic acid, myristic acid, and stearic acid, or a combination thereof.

27. The emulsion of claim 23, wherein the emulsion is free or substantially free of surfactants.

28. The emulsion of claim 23, wherein the emulsion further comprises a cargo, wherein the cargo is hydrophilic and is selected from the group consisting of insect repellent agents, sun blocking agents, antibacterial agents, skin repair agents, wound repair agents, and fragrances, or a combination thereof.

29. The emulsion of claim 23, wherein the emulsion further comprises one or more waterabsorbing compounds optionally selected from the group consisting of carboxymethyl cellulose (CMC), alginate, chitosan, poly acrylates, and combinations thereof.

30. The emulsion of claim 29, wherein the one or more water-absorbing compounds are present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

31. The emulsion of claim 23, wherein the emulsion further comprises at least one stabilizer optionally selected from the group consisting of glycerol oleate, sorbitan oleate, and combinations thereof.

32. The emulsion of claims 31, wherein the at least one stabilizer is present at a concentration ranging from about 0.1 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, or about 0.1 wt% to 3.0 wt% of the total weight of the emulsion.

33. The emulsion of claim 23, wherein the emulsion further comprises one or more antioxidants optionally selected from the group consisting of tocopherols, butylated hydroxytoluene (BHT), and combinations thereof.

34. The emulsion of claim 33, wherein the one or more antioxidants is present at a concentration ranging from about 0.05 wt% to 3.0 wt%, about 0.05 wt% to 2.5 wt%, about 0.05 wt% to 2.0 wt%, about 0.05 wt% to 1.5 wt%, or about 0.05 wt% to 1.0 wt% of the total weight of the emulsion.

35. The emulsion of claim 23, wherein the emulsion further comprises one or more humectants optionally selected from the group consisting of glycerin, sorbitol, and combinations thereof.

36. The emulsion of claim 35, wherein the one or more humectants are present at a concentration ranging from about 0.5 wt% to 7.0 wt%, about 0.5 wt% to 6.5 wt%, about 0.5 wt% to 6.0 wt%, about 0.5 wt% to 5.5 wt%, about 0.5 wt% to 5.0 wt%, about 0.2 wt% to 5 wt%, or about 0.1 wt% to 5 wt% of the total weight of the emulsion.

37. A method of making the emulsion of claim 1 , the method comprising:(a) preparing a mixture of the C2-C12 alkyl lactate, the Ce-Cis fatty acid, and the base oil to form an emulsion comprising micelles.

38. The method of claim 37, wherein the preparing step (a) is performed with heating of the mixture to a temperature of about 70 °C.

39. The method of claim 37, wherein the emulsion further comprises a cargo and the method further comprises the cargo being present in the mixture of the C2-C12 alkyl lactate, the Ce-Cis fatty acid, and the base oil.

40. The method of claim 37, wherein the method further comprises a step (b) of sonicating and / or shaking the emulsion formed to increase formation of the micelles.

41. The method of claim 37, wherein the method further comprises a step (c) of heating the emulsion formed to increase formation of the micelles.

42. The method of claim 37, wherein the mixture further comprises at least one surfactant and the mixture is sonicated optionally with cooling.

43. The method of claim 42, wherein the at least one surfactant is selected from the group consisting of SPAN™ 80, sodium lauryl sulfate (SLS), cocoamidopropyl betaine, cetearyl alcohol, ceteareth-20, sorbitan oleate, glyceryl stearate, PEG- 100 stearate, emulsifying wax NF, lecithin, beeswax, carbomer, dimethicone copolyol, PEG-8 dimethicone, and combinations thereof.

44. The method of claim 42, wherein the sonication is performed with an ultrasonic probe.

45. A method of repelling an insect or an arachnid, the method comprising the steps of: (a’) applying the emulsion of claim 1 to at least a portion of a skin surface of a subject; wherein following step (a’), the portion of the skin surface to which the emulsion was applied provides a complete protection time of at least about 9 hours, optionally at least about 10 hours.

46. The method of claim 45, wherein the insect or arachnid is selected from the group consisting of a mosquito, tick, spider, bed bug, stable fly, horn fly, and black fly, and combinations thereof.

47. The method of claim 46, wherein the mosquito is an Aedes aegypti or Anopheles stephensi mosquito.

48. The method of claim 45, wherein the subject is a mammal.

49. The method of claim 45, wherein the subject is a human.

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