A method for transdermal delivery of a formulation having an active ingredient to a mammal, said mammal having a body surface that comprises a stratum corneum, an epidermis, a basement membrane, and a dermis;
- the method comprises:
- a) applying the formulation to the body surface, wherein formulation comprises:
- i) at least one penetration agent comprising a solvent, a lipophilic agent, a hydrophilic agent, or a combination thereof,
- (1) wherein the solvent is selected from the group consisting of:
- (a) one or more polar solvents, selected from the group consisting of:
- ethyl acetate, dimethyl sulfoxide water, methanol, isopropanol, acetic acid, methanol, ethanol, n-propanol, n-butanol and a combination thereof;
- (b) one or more limonenes selected from the group consisting of:
- D-limonene, L-limonene and a combination thereof and a combination thereof, or
- at least one penetration agent selected from the group consisting of:
- fatty acids, fatty acid esters, oleic acids, polyols, amides, sodium laurate, sodium lauryl sulfate, phospholipids, cholesterol, cholesterol derivatives, m-pyrrole, dimethyl acetamide, sphingo lipids, ceramides, terpenes, alkanones, menthol, salicylic acid, citric acid, succinic acid, prostaglandins, decyl-methyl sulfoxide, sulfoxide alcohols, vitamins and a combination thereof;
- (2) at least one basement membrane disruptor that reversibly denatures the basement membrane, wherein the basement membrane disruptor is present in an amount ranging from about 0.2% w/w and about 10% w/w;
- ii) at least one vaso-modulator, wherein the vaso-modulator comprises a vasodilator or vasoconstrictor,
- wherein the vasodilator allows for the active ingredient to be delivered systemically or to local tissue, wherein the vasodilator is selected from the group consisting of:
- amrinone, arginine, bamethan sulphate, bencyclane fumarate, benfurodil hemisuccinate, benzyl nicotinate, buflomedil hydrochloride, buphenine hydrochloride, butalamine hydrochloride, cetiedil citrate, ciclonicate, cinepazide maleate, cyclandelate, di isopropylammonium dichloroacetate, ethyl nicotinate, hepronicate, hexyl nicotinate, ifenprodil tartrate, inositol nicotinate, isoxsuprine hydrochloride, kallidinogenase, methyl nicotinate, naftidrofuryl oxalate, nicametate citrate, niceritrol, nicoboxil, nicofuranose, nicotinyl alcohol, nicotinyl alcohol tartrate, nitric oxide, nonivamide, oxpentifylline, papaverine, papaveroline, pentifylline, peroxynitrite, pinacidil, pipratecol, propentofyltine, raubasine, suloctidil, teasuprine, thymoxamine hydrochloride, tocopherol nicotinate, tolazoline, papaverine, xanthinol nicotinate, diazoxide, hydralazine, minoxidil, and sodium nitroprusside, clonidine, quanaberz, methyl dopa, alpha adrenoceptor, indoramin, phenoxybenzamine, phentolamine, prazosin, PDE-5 inhibitors, sildenafil, tadalafil, adrenergic neuron blocking agents, bedmidine, debrisoquine, guanethidine, ACE inhibitors, benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, ganglion blocking agents, pentolinium, trimetaphan, calcium channel blockers, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, verapamil, prostaglandins, prostacyclin, thrombuxane A2, leukotrienes, PGA, PGA1, PGA2, PGE1, PGE2, PGD, PGG, PGH, angiotensin II analogs, saralasin, nitroglycerin, labetalol, thrazide, isosorbide dinitrate, pentaerythritol tetranitrate, digitalis, hydralazine, diazoxide, sodium nitroprusside, and a combination thereof;
- wherein the vasoconstrictor allows for the active ingredient to be delivered to the dermis, wherein the vasoconstrictor is selected from the group consisting of:
- adenosine triphosphate, amphetamine, antazoline, asymmetric dimethylarginine, cocaine, dopamine, endothelin, ephedrine, epinephrine, ergine, hydroxyamphetamine, isoproterenol, levonordefrin, metaraminol, methamphetamine, methoxamine, methylphenidate, neuropeptide Y, naphazoline, norepinephrine, oxymetazoline, phenylephrine, pseudoephedrine, tetrahydozoline, thromboxane, tramazoline, tyramine, and a combination thereof;
- and
- iii) at least one active ingredient;
- wherein the formulation allows for penetration of the active ingredient to the dermis, wherein the basement membrane disruptor denatures one or more molecules of the basement membrane to allow for passage of the active ingredient, and wherein the one or more molecules of the basement membrane renature once the active ingredient is delivered to the dermis.