# US 2026/0090982 A1 · Transdermal delivery formulations

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- Number: US 2026/0090982 A1
- Document ID: US20260090982A1
- Status: Published application
- Kind: A1
- Application number: 19/411,130
- Filed: 2025-12-05
- Published: 2026-04-02
- Earliest claimed: 2023-06-06
- Assignees: LifeActive, Inc.
- Applicants: LifeActive, Inc.
- Inventors: Calvin Dexter MORRIS; Burgess A. THOMASSON, JR.; Scott A. JENKINS
- Web page: https://patentgrep.com/patent/US20260090982A1

## CPC

- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 31/047: having two or more hydroxy groups, e.g. sorbitol
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/07: Retinol compounds, e.g. vitamin A (retinoic acids A61K31/203)
- A61K 31/121: acyclic
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/205: Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof
- A61K 31/401: Proline; Derivatives thereof, e.g. captopril
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/405: Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- A61K 31/4172: Imidazole-alkanecarboxylic acids, e.g. histidine
- A61K 31/4188: condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
- A61K 31/455: Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
- A61K 31/51: Thiamines, e.g. vitamin B1
- A61K 31/525: Isoalloxazines, e.g. riboflavins, vitamin B2
- A61K 31/593: 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
- A61K 31/714: Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
- A61K 35/60: Fish, e.g. seahorses; Fish eggs
- A61K 36/21: Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
- A61K 36/9066: Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
- A61K 38/063: {Glutathione}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided are transdermal delivery formulations, and methods for the manufacture thereof, for the epicutaneous administration of therapeutic agents, drugs, and nutrients to human subjects; veterinary animals; domesticated or undomesticated animals, plants or insects; or agricultural animals, plants, or insects. Transdermal delivery formulations disclosed herein comprise a homogenous mixture of (a) a transdermal accelerant comprising a weak organic acid having a pKa greater than 2.0 and (b) a microemulsion comprising a nonionic emulsifier, water, and a cis-unsaturated long-chain fatty acid. Fatty acid microemulsions are combined with the acidified transdermal accelerants having a pH greater than 1.0 (typically from 1.5 to 2.5) to yield a homogenous transdermal delivery formulation comprising fatty acid micelles and/or liposomes that encapsulate one or more compound, such as a nutrient or a drug, and incorporate one or more cis-unsaturated fatty acid having a 12 to 26 carbon chain that includes one or more double bond in a cis configuration. Transdermal delivery formulations exhibit ideal solubility and absorption properties in high humidity conditions, such as in a warm to hot shower or sauna.

## Claims

### Claim 1

A transdermal delivery formulation, comprising:
at least one weak organic acid present in total in an amount from 2.0% to 45.0% w/w of the formulation;
at least one active agent;
water, present in a weight percentage in the range of 15% to 70% of the formulation;
one or more oils comprising at least one unsaturated long-chain fatty acid selected from oleic acid and linoleic acid, wherein the one or more oils in total have a weight percentage in the range of 5% to 35% of the formulation; and
polysorbate 80 present in a weight percentage in the range of 15% to 40% of the formulation,
wherein the transdermal delivery formulation has a pH in the range of 2.0 to 6.0,
wherein the polysorbate 80, the one or more oils in total, and the water comprises a weight ratio in the range of X:Y:Z, wherein X is =1-5, Y is =1-6, and Z is =1-6, and
wherein the transdermal delivery formulation is capable of delivering the at least one agent to the blood stream of a subject when applied to the skin of the subject.

### Claim 2 (depends on 1)

The transdermal delivery formulation of claim 1, wherein the at least one active agent comprises arginine, citrulline, citrulline malate, beetroot, creatine, glutamine, leucine, norvaline, ornithine, histidine, beta-alanine, phenylalanine, agmatine, betaine, L-theanine, glutathione, or any nitrate or any nitrite, any nitro, or any nitroso or salt thereof, or any combination thereof.

### Claim 3 (depends on 1)

The transdermal delivery formulation of claim 1, wherein the at least one active agent further comprises ascorbic acid or its derivative.

### Claim 4 (depends on 1)

The transdermal delivery formulation of claim 1, wherein at least one weak organic acid is present in total in an amount from 4.5% to 45.0% w/w.

### Claim 5 (depends on 1)

The transdermal delivery formulation of claim 1, wherein the at least one weak organic acid is present in total in an amount from 10.0% to 45.0% w/w.

### Claim 6

The transdermal delivery formulation of any one of claim, wherein the transdermal delivery formulation comprises about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or about 80% (w/w) of the at least one weak organic acid.

### Claim 7

The transdermal delivery formulation of any one of claim, wherein the transdermal delivery formulation comprises about 60%, about 65%, about 70%, about 75%, or about 80% w/w of the total of the polysorbate 80, the one or more oils in total, and water.

### Claim 8

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises 2 weak organic acids at a ratio by weight of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1::8, 1:9, 1:10, 1:100 or 1:1000 relative to each other.

### Claim 9

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises about 80%, about 85%, about 90%, about 95%, about 97%, about 99% (w/w) of one or more weak organic acids.

### Claim 10

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid has a median pKa of from 3.0 to 5.5.

### Claim 11

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid has a median pKa of from 4.0 to 5.0.

### Claim 12

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid has a median pKa of about 4.6.

### Claim 13

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises a mono, di or tri carbonic acid of chain length (R) between 1-16.

### Claim 14

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises a mono or poly hydroxy moiety of 0-14.

### Claim 15

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises lactic acid, acetic acid, formic acid, citric acid, oxalic acid, gallic acid, malic acid, maleic acid, malonic acid, succinic acid, tartaric acid, fumaric acid, or any combination thereof.

### Claim 16

The transdermal delivery formulation of any one of claim, wherein said weak organic acid is citric acid or acetic acid.

### Claim 17

The transdermal delivery formulation of any one of claim, wherein the at least one weak organic acid comprises citric acid and acetic acid.

### Claim 18 (depends on 17)

The transdermal delivery formulation of claim 17, wherein the acetic acid is apple cider vinegar.

### Claim 19

The transdermal delivery formulation of any one of claim, wherein the formulation comprises two oils comprising an unsaturated long-chain fatty acid, wherein the two oils are in a ratio by weight of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:100 or 1:1000 relative to each other.

### Claim 20

The transdermal delivery formulation of any one of claim, wherein said at least one unsaturated long-chain fatty acid comprises a chain of from 12 to 26 carbons.

### Claim 21 (depends on 20)

The transdermal delivery formulation of claim 20, wherein said at least one unsaturated long-chain fatty acid comprises one or more double bonds in a cis configuration.

### Claim 22 (depends on 20)

The transdermal delivery formulation of claim 20, wherein said at least one unsaturated long-chain fatty acid comprises adrenic acid, arachidonic acid, arachidic acid, behenic acid, brassidic acid, cervonic acid, cis-vaccenic acid, dihomo-γ-linolenic acid, docosadienoic acid, eicosadienoic acid, eicosapentaenoic acid, eicosatetraenoic acid, eicosenoic acid, elaidic acid, erucic acid, gadoleic acid, gondoic acid, herring acid, lauric acid, lignoceric acid, linoleic acid, linolelaidic acid, margaric acid, margoleic acid, mead acid, myristoleic acid, nervonic acid, oleic acid, ozubondo acid, palmitic acid, palmitoleic acid, trans-palmitoleic acid, paullinic acid, petroselinic acid, pinolenic acid, sapienic acid, sardine acid, stearic acid, stearidonic acid, tetracosapentaenoic acid, α-linolenic acid, γ-linolenic acid, or any combination thereof.

### Claim 23 (depends on 22)

The transdermal delivery formulation of claim 22, wherein said at least one unsaturated long-chain fatty acid is oleic acid or linoleic acid.

### Claim 24 (depends on 22)

The transdermal delivery formulation of claim 22, wherein said at least one long-chain fatty acid comprises oleic acid and linoleic acid.

### Claim 25

The transdermal delivery formulation of any one of claim, wherein the one or more oils comprising an unsaturated long-chain fatty acid is one or more plant or animal oils.

### Claim 26 (depends on 25)

The transdermal delivery formulation of claim 25, wherein said one or more plant oils is selected from the group consisting of vegetable oil, nut oil and seed oil.

### Claim 27 (depends on 25)

The transdermal delivery formulation of claim 25, wherein said one or more plant or animal oils comprises macadamia oil, maracuja (passion fruit) oil, safflower oil, sunflower oil, olive oil, avocado oil, canola oil, coconut oil, corn oil, cottonseed oil, flaxseed/linseed oil, grape seed oil, hemp seed oil, palm oil, peanut oil, rice bran oil, sesame oil, soybean oil, brazil nut oil, almond oil, walnut oil, pecan oil, jojoba oil, chia seed oil, wallflower seed, mustard oil, borage oil, black currant oil, evening primrose oil, chicken fat, cartilage oil, cod liver oil, herring oil, mackerel oil, salmon oil, menhaden oil, sardine oil, or any combination thereof.

### Claim 28 (depends on 27)

The transdermal delivery formulation of claim 27, wherein said one or more plant or animal oils is macadamia oil or maracuja (passion fruit) oil, or a combination thereof.

### Claim 29 (depends on 27)

The transdermal delivery formulation of claim 27, wherein said one or more plant or animal oils comprises macadamia oil and maracuja (passion fruit) oil.

### Claim 30

The transdermal delivery formulation of any one of claim, wherein the transdermal delivery formulation comprises a lotion, a gel, a cream, an ointment, a liniment, a paste, a film, an encapsulation, or a liquid.

### Claim 31

The transdermal delivery formulation of any one of claim, wherein the formulation comprises a nitrate source.

### Claim 32 (depends on 31)

The transdermal delivery formulation of claim 31, wherein said nitrate source is a plant-based nitrate source.

### Claim 33 (depends on 32)

The transdermal delivery formulation of claim 32, wherein said plant-based nitrate source comprises from the group consisting of arugula, spinach, leafy green vegetables, beetroot, or any combination thereof.

### Claim 34 (depends on 33)

The transdermal delivery formulation of claim 33, wherein said plant-based nitrate source is beetroot, and wherein the beetroot is a dried beetroot powder.

### Claim 35 (depends on 34)

The transdermal delivery formulation of claim 34, wherein the formulation comprises about 2.0%, about 2.5%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, about 5.0%, about 5.5%, about 6.0%, about 6.5%, about 7.0%, about 7.5%, or about 8.0% w/w dried beetroot powder.

### Claim 36

The transdermal delivery formulation of any one of claims, further comprising a viscosity enhancer, a nutrient, a plant powder or extract, an amino acid, a vitamin, or any combination thereof.

### Claim 37 (depends on 36)

The transdermal delivery formulation of claim 36, wherein said formulation comprises a viscosity enhancer selected from the group consisting of lecithin, aloe vera, glycerin, a plant oil, an animal oil, and collagen.

### Claim 38 (depends on 36)

The transdermal delivery formulation of claim 36, wherein said formulation comprises a nutrient selected from the group consisting of acetyl-L-carnitine, alpha lipoic acid, arginine, potassium, NALT-Acetyl Tyrosine, NAC, PEA, resveratrol, taurine, palmitate, calcium carbonate, choline bitartrate B-4, creatine, resveratrol, citrulline malate, taurine, magnesium glycinate, carnitine, CoQ10, humic, hyaluronic acid, magnesium, selenium, and zinc oxide.

### Claim 39 (depends on 36)

The transdermal delivery formulation of claim 36, wherein said formulation comprises a plant powder or extract selected from the group consisting of bacopa powder, bamboo extract powder, beet powder, blueberry extract, ginkgo biloba, ginger, grape seed extract, green tea, jojoba, nutmeg, olive leaf, pomegranate, and turmeric.

### Claim 40 (depends on 36)

The transdermal delivery formulation of claim 36, wherein said formulation comprises an amino acid selected from the group consisting of alanine, arginine, leucine, isoleucine, valine, glutamine, glycine, histidine, leucine, lysine, methionine, proline, serine, threonine, and valine.

### Claim 41 (depends on 36)

The transdermal delivery formulation of claim 36, wherein said formulation comprises a vitamin selected from the group consisting of vitamin A, vitamin B-1, vitamin B-2, vitamin B-3, vitamin B-7 & 8 inositol, vitamin B-9 (folic acid), vitamin B-12, vitamin C, vitamin D-3, and vitamin E.

### Claim 42

The transdermal delivery formulation of any one of claim, wherein said transdermal formulation has a pH of from 3.0 to 5.0.

### Claim 43

The transdermal delivery formulation of any one of claim, wherein said transdermal formulation has a pH of from 3.5 to 4.5.

### Claim 44

The transdermal delivery formulation of any one of claim, wherein said transdermal formulation has a viscosity at 20° C. of from 500 to 10,000 centipoise (cP) or from 1,000 to 5,000 cP, or from 1,500 to 4,000 cP, or from 2,000 to 3,000 cP.

### Claim 45

The transdermal delivery formulation of any one of claim, wherein the transdermal delivery formulation forms an emulsion comprising a population of droplets from about 10 nm to about 300 nm in diameter.

### Claim 46

The transdermal delivery formulation of any one of claims, further comprising one or more components for enhancing nutrition and optimizing health, immune support, restful sleep, exercise performance and nitric oxide metabolism, cognitive function, or any combination thereof.

### Claim 47 (depends on 46)

The transdermal delivery formulation of claim 46, further comprising one or more of a hydration electrolyte, cinnamic acid, phenylalanine, resveratrol, carnitine.

### Claim 48 (depends on 46)

The transdermal delivery formulation of claim 46, further comprising one or more of gamma-aminobutyric acid (GABA), melatonin, and tryptophan.

### Claim 49 (depends on 46)

The transdermal delivery formulation of claim 46, further comprising one or more of vitamin D, vitamin C, citrulline, ribose ATP blood carrier, beetroot, curcumin (turmeric), fish oil, and threonine.

### Claim 50 (depends on 46)

The transdermal delivery formulation of claim 46, further comprising one or more of silicon, leucine, lysine, isoleucine, valine, threonine, phenylalanine, methionine, histidine, tryptophan, vitamin B-5 (pantothenic acid), vitamin B-7 (biotin), vitamin K, acetyl L carnitine, palmitoyl-ethanolamide (PEA), taurine, periwinkle, artichoke, bacopa, ginkgo biloba, nutmeg, alanine, and tyrosine.

### Claim 51 (depends on 1)

The transdermal delivery formulation of claim 1, wherein the formulation comprises:
about 12.0% (w/w) citric acid powder;
about 20.5% (w/w) apple cider vinegar;
about 1.4% (w/w) beetroot powder;
about 23.8% (w/w) polysorbate 80;
about 22.5% (w/w) distilled water;
about 9.9% (w/w) macadamia oil; and
about 9.8% (w/w) maracuja oil.

### Claim 52 (depends on 1)

The transdermal delivery formulation of claim 1, wherein the formulation comprises:
about 374 g citric acid powder;
about 640 g apple cider vinegar;
about 44.4 g beetroot powder;
about 742 g polysorbate 80;
about 700 g distilled water;
about 308 g macadamia oil; and
about 308 g maracuja oil.

### Claim 53

The transdermal delivery formulation of any one of claims, further comprising one or more additional ingredients, wherein the additional ingredients comprise: acetyl-l-carnitine (alc), alanine, alpha lipoic acid, arginine, artichoke extract, ashwagandha, bacopa powder, bamboo extract powder, basil powder, beet powder, calcium carbonate, blueberry extract, aloe vera, choline bitartrate, collagen protein peptides, collagen powder, citrulline malate, curcumin powder, creatine, CoQ10, kale powder, folic acid, gingko biloba, glutamine, glycerin, ginger, glycine, grape seed extract, green tea, inositol (vitamins B7/B8), histidine, jojoba, pomegranate powder, magnesium glycinate, leucine, lysine, lecithin (sun flower), niacinamide (vitamin B3), nutmeg powder, niacin, methionine, NALT (acetyl tyrosine), NAC, lutein, olive leaf, pea powder, periwinkle, phenylalanine, potassium, proline, ribose, DAA (d-aspartic acid), serine, hyaluronic acid, taurine, threonine, tryptophan, turmeric, theanine, valine (amino acid), valerian root powder, zinc oxide, vitamin A, vitamin B complex, vitamin B-1, vitamin B-2, vitamin B-5, vitamin B-6 (pyridoxine), vitamin B-7&8, vitamin B-9 (folic acid), vitamin B-12, vitamin C (ascorbic acid), vitamin D-3 (cholecalciferol), vitamin E, vitamin K-2, ginseng, isoleucine, almond oil, broccoli seed oil, collagen liquid, avocado oil, chamomile liquid, vitamin E oil, glycerin (conditioning), grapefruit seed, grape seed oil, gotu kola oil, kava liquid, virgin algae oil (fish oil), jojoba extract oil (organic), lavender oil, macadamia nut oil, meadowfoam seed oil, peppermint oil, maracuja oil (passionfruit), primrose oil, pomegranate oil, BCAA, GABA, collagen oil, virgin algae oil, ashwagandha powder, collagen peptides, guarana powder, and huperzine.

### Claim 54 (depends on 53)

The transdermal delivery formulation of claim 53, wherein the transdermal delivery formulation comprises more than one, more than 2, more than 3, more than 4, more than 5, more than 6, more than 7, more than 8, more than 9, more than 10, more than 11, more than 12, more than 13, more than 14, more than 15, more than 16, more than 17, more than 18, more than 19, more than 20 of the additional ingredients.

### Claim 55

The transdermal delivery formulation of any one of claim, wherein the one or more active agents comprises a therapeutic agent, a nutraceutical, or a combination thereof.

### Claim 56 (depends on 55)

The transdermal delivery formulation of claim 55, wherein the therapeutic agent comprises a biologic, a protein, a peptide, a small molecule, a macromolecule, a nucleic acid, another pharmaceutically or physiologically active ingredient, or any combination thereof.

### Claim 57 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)

A method of transdermal delivery to a subject, comprising epicutaneous application of the transdermal delivery formulation of any one of claims 1-56 to the subject.

### Claim 58 (depends on 57)

The method of claim 57, further comprising overlaying an ionized water on to the epicutaneously-applied transdermal delivery formulation.

### Claim 59 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)

A method of treatment of a disease or condition in a subject, comprising epicutaneous application of the transdermal delivery formulation of any one of claims 1-56 and one or more active agents to the subject.

### Claim 60 (depends on 59)

The method of claim 59, wherein the one or more active agents comprises a therapeutic agent, a nutraceutical, or a combination thereof.

### Claim 61 (depends on 59)

The method of claim 59, wherein the therapeutic agent comprises a biologic, a protein, a peptide, a small molecule, a macromolecule, a nucleic acid, another pharmaceutically or physiologically active ingredient, or any combination thereof.

### Claim 62 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)

A method of enhancing a feature or condition in a subject, comprising epicutaneous application of the transdermal delivery formulation of any one of claims 1-56 to the subject.

### Claim 63 (depends on 62)

The method of claim 62, wherein the feature is a cosmetic feature.

### Claim 64 (depends on 62)

The method of claim 62, wherein the condition is nutrition, general health, quality of sleep, exercise performance, nitric oxide metabolism, cognitive function, or any combination thereof.

### Claim 65 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)

A method of systemic delivery of an active agent to a subject, comprising epicutaneous application of the transdermal delivery formulation of any one of claims 1-56 and one or more active agents to the subject.

### Claim 66 (depends on 65)

The method of systemic delivery of claim 65, further comprising overlaying an ionized water on to the epicutaneously-applied transdermal delivery formulation.

### Claim 67 (depends on 65)

The method of claim 65, wherein the one or more active agents comprises a therapeutic agent, a nutraceutical, or a combination thereof.

### Claim 68 (depends on 65)

The method of claim 65, wherein the therapeutic agent comprises a biologic, a protein, a peptide, a small molecule, a macromolecule, a nucleic acid, another pharmaceutically or physiologically active ingredient, or any combination thereof.
