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Abstract

Grant Number:	5R44AR046396-03
PI Name:	CIOFALO, VINCENT B.
PI Email:	glsyn@glsynthesis.com
PI Title:
Project Title:	New Dermal Anesthetics

Abstract: DESCRIPTION (provided by applicant): Dermal anesthetics are used to anesthetize the skin of patients for various reasons, ranging from minor cutaneous surgery and needle inserts to skin grafts. The dermal anesthetic market is dominated by a single preparation, called EMLA (AstraZeneca), which consists of a eutectic mixture of lidocaine and prilocaine bases. EMLA?s principal drawback is a long onset time for dermal anesthesia, requiring up to two hours for full effect. The results of our Phase I studies demonstrate that we have arrived at compounds that are superior to EMLA in every respect. The new compounds offer faster onset of anesthetic activity, deeper local anesthesia, and longer duration of anesthesia than EMLA. We have selected a lead compound - racemic TAC-34 - and a backup compound - TAC-HP. (The enantiomers of TAC-34 possessed similar activity.) Both lead and backup compounds meet and exceed our original selection criteria. The goal of the phase II project is to acquire the data package needed to select the Candidate Drug, and to prepare the Investigational New Drug Application (IND) for submission to the Food and Drug Administration. Specific aims designed to meet this goal include: 1. to develop scale-up synthesis methods, analytical procedures, and formulations of both isomeric TAC-34 and the backup compound TAC-HP to further evaluate efficacy and toxicity for selection of the Candidate Drug; 2. to carry out the preclinical toxicity testing and to prepare the Chemistry, Manufacturing and Control information necessary to support the IND application for the Candidate Drug. After the first-in-man studies, we intend to license out this project to one of the pharmaceutical companies that has already expressed strong interest in this project.

Thesaurus Terms:
carbopolycyclic compound, chemical synthesis, drug design /synthesis /production, local anesthetic, skin pharmacology
chemical structure function, drug adverse effect, drug screening /evaluation, pain, pharmacokinetics, skin absorption
guinea pig

Institution:	GLSYNTHESIS, INC.
	1 INNOVATION DR
	WORCESTER, MA 01605
Fiscal Year:	2003
Department:
Project Start:	27-SEP-1999
Project End:	31-AUG-2004
ICD:	NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG:	ZRG1

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