TRANSDERMAL AND/OR DERMAL DELIVERY OF LIPOPHILIC ACTIVE AGENTS
Aspects described herein relate to improved compositions and methods for transdermal and/or dermal delivery of lipophilic active agents, particularly without the need for added penetration enhancers.
1 . A transdermal and/or dermal composition comprising a lipophilic active agent, wherein the transdermal and/or dermal composition comprises a dehydrated mixture, and wherein the dehydrated mixture comprises a therapeutically effective amount of the lipophilic active agent and an edible oil comprising long chain fatty acids and/or medium chain fatty acids.
2 . The transdermal and/or dermal composition of claim 1 , wherein the composition does not comprise added penetration enhancers.
3 . The transdermal and/or dermal composition of any one of claim 1 or 2 , wherein the transdermal and/or dermal composition comprises an oil-in-water emulsion comprising an aqueous phase and an oil phase, wherein the oil phase comprises the dehydrated mixture.
4 . The transdermal and/or dermal composition of claim 3 , wherein the dehydrated mixture is obtainable by the steps of:
i) combining the therapeutically effective amount of the lipophilic active agent with the edible oil comprising long chain fatty acids and/or medium chain fatty acids; and
ii) dehydrating the product of step (i), thereby producing the dehydrated mixture.
5 . The transdermal and/or dermal composition of any one of claims 1 to 4 , wherein the bioavailability of the lipophilic active agent in a subject is at least 2 times greater than the bioavailability of the lipophilic active agent in the subject in the absence of the edible oil comprising long chain fatty acids and/or medium chain fatty acids.
6 . The transdermal and/or dermal composition of any one of claims 1 to 4 , wherein the bioavailability of the lipophilic active agent in a subject is at least 5 times greater than the bioavailability of the lipophilic active agent in the subject in the absence of the edible oil comprising long chain fatty acids and/or medium chain fatty acids.
7 . The transdermal and/or dermal composition of any one of claims 1 to 4 , wherein the bioavailability of the lipophilic active agent in a subject is at least 10 times greater than the bioavailability of the lipophilic active agent in the subject in the absence of the edible oil comprising long chain fatty acids and/or medium chain fatty acids.
8 . The transdermal and/or dermal composition of any one of claims 1 to 7 , wherein the edible oil comprising long chain fatty acids and/or medium chain fatty acids is substantially free of omega-6 fatty acids.
9 . The transdermal and/or dermal composition of any one of claims 1 to 8 , wherein the long chain fatty acids and/or medium chain fatty acids are selected from the group consisting of oleic acid, undecanoic acid, valeric acid, heptanoic acid, pelargonic acid, capric acid, lauric acid, and eicosapentaenoic acid.
10 . The transdermal and/or dermal composition of any one of claims 1 to 9 , wherein the lipophilic active agent is selected from the group consisting of: cannabinoids, terpenes and terpenoids, non-steroidal anti-inflammatory drugs (NSAIDs), vitamins, nicotine or an analog thereof, phosphodiesterase 5 (PDE5) inhibitors, Maca extract, hormones, fentanyl or an analog thereof, buprenorphine or an analog thereof, scopolamine or an analog thereof, and antioxidants.
11 . The transdermal and/or dermal composition of claim 10 , wherein the cannabinoid is a psychoactive cannabinoid.
12 . The transdermal and/or dermal composition of claim 10 , wherein the cannabinoid is a non-psychoactive cannabinoid.
13 . The transdermal and/or dermal composition of claim 10 , wherein the NSAID is acetylsalicylic acid, ibuprophen, acetaminophen, diclofenac, indomethacin, piroxicam, or a COX inhibitor.
14 . The transdermal and/or dermal composition of claim 10 , wherein the vitamin is vitamin A, D, E, or K.
15 . The transdermal and/or dermal composition of claim 10 , wherein the PDE5 inhibitor is avanafil, lodenafil, mirodenafil, sildenafil, tadalafil, vardenafil, udenafil, acetildenafil, thiome-thisosildenafil, or analogs thereof.
16 . The transdermal and/or dermal composition of claim 10 , wherein the hormone is an estrogen, an anti-estrogen, an androgen, an anti-androgen, or a progestin.
17 . The transdermal and/or dermal composition of claim 10 , wherein the antioxidant is astaxanthin, Superoxide Dismusase, beta-carotene, selenium, lycopene, lutein, Coenzyme Q10, phytic acid, flavonoids, a polyphenol, a substituted 1,2-dihydroquinoline, ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomer, N-acetylcysteine, benzyl isothiocyanate, o-, m- or p-amino benzoic acid (o is anthranilic acid, p is PABA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid, canthaxantin, alpha-carotene, beta-carotene, beta-caraotene, beta-apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate, chlorogenic acid, citric acid and its salts, clove extract, coffee bean extract, p-coumaric acid, 3,4-dihydroxybenzoic acid, N,N′-diphenyl-p-phenylenediamine (DPPD), dilauryl thiodipropionate, distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, sodium erythorbate, esculetin, esculin, 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eucalyptus extract, eugenol, ferulic acid, flavonoids, flavones (e.g., apigenin, chrysin, luteolin), flavonols (e.g., datiscetin, myricetin, daemfero), flavanones, fraxetin, fumaric acid, gallic acid, gentian extract, gluconic acid, glycine , gum guaiacum, hesperetin, alpha-hydroxybenzyl phosphinic acid, hydroxycinammic acid, hydroxyglutaric acid, hydroquinone, N-hydroxysuccinic acid, hydroxytryrosol, hydroxyurea, ice bran extract, lactic acid and its salts, lecithin, lecithin citrate; R-alpha-lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxy tryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate; morin, beta-naphthoflavone, nordihydroguaiaretic acid (NDGA), octyl gallate, oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphates, phytic acid, phytylubichromel, pimento extract, propyl gallate, polyphosphates, quercetin, trans-resveratrol, rosemary extract, rosmarinic acid, sage extract, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e., alpha-, beta-, gamma- and delta-tocopherol), tocotrienols (i.e., alpha-, beta-, gamma- and delta-tocotrienols), tyrosol, vanilic acid, 2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., lonox 100), 2,4-(tris-3′,5′-bi-tert-butyl-4′-hydroxybenzyl)-mesitylene (i.e., lonox 330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tertiary butyl hydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10, wheat germ oil, zeaxanthin, or combinations thereof.
18 . The transdermal and/or dermal composition of any one of claims 1 to 17 , further comprising an additional formulation component selected from the group consisting of Penetration Enhancers, Essential Oils, Plant Extracts, Thickening Agents, Neutralizing Agents, Wetting Agents (Surfactants), Lubricants, Emollients, Emulsifying Agents, Solubilizers, Oils and Waxes, Higher Fatty Acids, Higher Alcohols, Cosmetic Ingredients, UV Absorption Agents, Moisturizing Agents, Antioxidants, Structuring Agents, Emulsifiers, Silicone Containing Compounds, Preservatives, and Conditioning Agents.
19 . A process for making a transdermal and/or dermal composition comprising a lipophilic active agent in an oil-in-water emulsion comprising an aqueous phase and an oil phase, the steps comprising:
i) combining a therapeutically effective amount of the lipophilic active agent with an edible oil comprising long chain fatty acids and/or medium chain fatty acids;
ii) dehydrating the product of step (i), thereby producing a dehydrated mixture; and
iii) combining the aqueous phase with the oil phase, wherein the oil phase comprises the dehydrated mixture of step (ii).
20 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the condition is a skin condition selected from the group consisting of skin ageing, elastosis, laxity (sagging), rhytids (wrinkles), skin infection, skin damage, skin burn, pain, and muscle tightness, and combinations thereof.
21 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is a cannabinoid and the condition is selected from the group consisting of cardiac diseases such as heart disease, ischemic infarcts, and cardiometabolic disorders; neurological diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia, and Human Immunodeficiency Virus (HIV) dementia; obesity; metabolic disorders such as insulin related deficiencies and lipid profiles, hepatic diseases, diabetes, and appetite disorders; cancer chemotherapy; benign prostatic hypertrophy; irritable bowel syndrome; biliary diseases; ovarian disorders; marijuana abuse; alcohol, opioid, nicotine, or cocaine addiction; and sexual dysfunction such as erectile dysfunction.
22 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is a non-steroidal anti-inflammatory drug (NSAID), and wherein the condition is selected from the group consisting of asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, inflammatory bowel disease, irritable bowel syndrome, inflammatory pain, fever, migraine, headache, low back pain, fibromyalgia, myofascial disorders, viral infections (e.g. influenza, common cold, herpes zoster, hepatitis C and AIDS), bacterial infections, fungal infections, dysmenorrhea, burns, surgical or dental procedures, malignancies (e.g. breast cancer, colon cancer, and prostate cancer), hyperprostaglandin E syndrome, classic Bartter syndrome, atherosclerosis, gout, arthritis, osteoarthritis, juvenile arthritis, rheumatoid arthritis, rheumatic fever, ankylosing spondylitis, Hodgkin's disease, systemic lupus erythematosus, vasculitis, pancreatitis, nephritis, bursitis, conjunctivitis, iritis, scleritis, uveitis, wound healing, dermatitis, eczema, psoriasis, stroke, diabetes mellitus, neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis, autoimmune diseases, allergic disorders, rhinitis, ulcers, coronary heart disease, sarcoidosis and any other disease with an inflammatory component.
23 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is a vitamin, and wherein the condition is selected from the group consisting of a vitamin deficiency, vitamin malabsorption, and cystic fibrosis.
24 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is nicotine, and wherein the condition is selected from the group consisting of tobacco dependence/addiction, Parkinson's disease, ulcerative colitis, Alzheimer's disease, schizophrenia, Attention Deficit Hyperactivity Disorder (ADHD), Tourette's syndrome, ulcerous colitis, and post-smoking-cessation weight control.
25 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is a phosphodiesterase 5 (PDE5) inhibitor, and wherein the condition is erectile dysfunction.
26 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is Maca extract and wherein the condition is selected from the group consisting of inflammatory cytokine production, the effects of chronic inflammation, discomfort related to menstruation, the symptoms of menopause, the symptoms of andropause, the symptoms of HIV, the symptoms of anemia, discomfort related to chemotherapy, the symptoms of tuberculosis, the symptoms of osteoporosis, sexual dysfunction, and combinations thereof.
27 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is a hormone and wherein the condition is a hormone deficiency.
28 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is fentanyl and wherein the condition is pain.
29 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is buprenorphine and wherein the condition is pain.
30 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is scopolamine and wherein the condition is selected from the group consisting of nausea, vomiting, motion sickness, muscle spasms, and Parkinson-like conditions.
31 . A method of treating a condition comprising administering the transdermal and/or dermal composition of any one of claims 1 to 18 to a subject in need thereof, wherein the lipophilic active agent is an antioxidant and wherein the condition is oxidative stress in a mammalian cell.
32 . A kit comprising the transdermal and/or dermal composition of any one of claims 1 to 18 and instructions for use thereof.