Development of Thermally and Photochemically Stable Anesthetic Components

Period of Performance: 12/14/2001 - 12/13/2002

$120K

Phase 1 SBIR

Recipient Firm

Polium Technologies, Inc.
2155 Stonington Ave., Suite 119
Hoffman Estates, IL 60195
Principal Investigator

Abstract

Low photo- and thermal stability of (R)-epinephrine (vasoconstrictor) in local anesthetic formulations compromises their anesthetic afficacy in field austere environments. The overall objective of this proposal (Phase I and Phase II combined) is to synthesize potentially stable vasoconstrictors, study their stability, and prove their anesthetic efficacy. Toward this end, Phase I focuses on the synthesis of ring-fluorinated analogs of (R)-epinephrine and (R)-phenylephrine using Polium Technologies proprietary biocatalyst, Finezyme-H1. Synthesis of chiral fluorinated derivatives of (R)-phenylephrine by any methods has not been described. Published methods of the synthesis of chiral fluorinated epinephrine derivatives use harsh conditions that are difficult for the scale-up. Contrary to this, Finezyme-H1 catalyzed reactions use mild conditions and the method is easily scaleable. The literature data suggest that these fluorinated analogs may possess required biological properties. Phase I focuses on the synthesis of these compounds using proprietary technology and stability studies of fluorinated analogs. If candidate compounds synthesized during Phase I show higher stability than existing vasoconstrictors, during Phase II we will test these compounds in local anesthetic formulations, perform biological affinity receptor assays and perform toxicology studies. Successful candidates will be commercialized in DOD and private sector Many third world countries do not have climate-controlled environments to safely store pharmaceuticals. Transport and storage of anesthetic to these regions, especially in hot climates, may compromise the efficacy of the drug. Development of new anesthetic components would be of great benefit to the oral care of many civilians in these nations, as well as military personnel deployed in austere environments