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AssigneesMassachusetts Institute of Technology Massachusett s, Children's Medical Center Corporation Massachusett s
InventorsDaniel S. Kohane, Itay Sagie, Emmanuel J. Simons
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Chemical permeation enhancers (CPEs) improve access of local anesthetics to the nerve, thereby improving their performance. Surfactants, representing three CPE sub-groups: anionic, cationic, and nonionic surfactants, were co-injected with tetrodotoxin (TTX) or bupivacaine at the sciatic nerve of Sprague-Dawley rats. All enhancers produced marked concentration-dependent improvements in the frequency and duration of block with TTX but not bupivacaine. An in vitro toxicity assay showed a wide range of CPE myotoxicity, but in vivo histological assessment showed no signs of muscle or nerve damage at concentrations of CPEs that produced a half-maximal increase in the duration of block of TTX. There was no systematic relationship between the enhancers' charge or hydrophobicity and their enhancement of block duration or potency. Thus, CPEs can provide marked prolongation of nerve blockade from TTX, without apparent local tissue toxicity, and therefore enhance the clinical applicability of TTX for prolonged-duration local anesthesia.
A method for enhancing nerve blockade without significant cytotoxicity comprising administering a site I sodium channel local anesthetic in combination with an effective amount of chemical permeation enhancer selected from the group consisting of surfactants, terpenes, amino amides, amino esters, azide-like compounds and alcohols, to increase blockade more than the additive effect of the local anesthetic or chemical permeation enhancer alone.
An anesthetic composition for enhancing nerve blockade without significant cytotoxicity comprising a site I sodium channel local anesthetic in combination with an effective amount of chemical permeation enhancer selected from the group consisting of surfactants, terpenes, amino amides, amino esters, azide-like compounds and alcohols, to increase blockade more than the additive effect of the local anesthetic or chemical permeation enhancer alone.
A method for providing local anesthesia comprising providing an effective amount of a site I sodium channel blocker in combination with a local anesthetic selected from the group consisting of a charged local anesthetic selected from the group consisting of amino-amide or amino-ester local anesthetics or derivatives thereof, at least partly amphiphilic local anesthetics, local anesthetics that act not on the surface of the cell, and at least partly charged local anesthetics.
A composition for providing local anesthesia comprising an effective amount of a site I sodium channel blocker in combination with a local anesthetic selected from the group consisting of a charged local anesthetic selected from the group consisting of amino-amide or amino-ester local anesthetics or derivatives thereof, at least partly amphiphilic local anesthetics, local anesthetics that act not on the surface of the cell, and at least partly charged local anesthetics.
Dependencies are inferred from the claim text.