Chemical permeation enhancers enhance nerve blockade by toxins
US8658699B2 · kind B2 · utility
Assignees
Inventors
Key dates
| Filing date | May 19, 2009 |
| Grant date | Feb 25, 2014 |
| Priority date | — |
| Expiry date | Oct 18, 2029 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K9/0024
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.