Sepracor Inc. announced last week that it has been awarded aU.S. patent on toothpaste and mouthwash formulations ofsingle-isomer non-steroidal anti-inflammatory drugs (NSAIDS)for treating periodontal disease.

The patent, No. 5,190,981, covers the NSAIDS S-ketoprofen andS-flurbiprofen. In preclinical studies, both compounds haveproven effective in reducing inflammation and bone loss, themanifestations of periodontal disease, which affects almost 80percent of all adults.

The two drugs, ketoprofen and flurbiprofen, are currentlymarketed as analgesics in racemic mixtures, 50/50combinations of two chemical molecules known as R- and S-isomers, which are mirror images of each other. The isomersare chemically identical but structurally different; frequentlythey also have distinct differences in biological activity, withone exhibiting the desired therapeutic effect while the othercauses side effects or is ineffective.

Sepracor (NASDAQ:SEPR) of Marlborough, Mass., is developingS-isomers of these drugs. "These compounds prevent the boneloss associated with periodontal disease," explained Nancy Gray,project manager at Sepracor. It's known that anti-inflammatorynon-steroidal drugs (the racemic mixes) do this by inhibitingprostaglandin synthesis. "The bone loss/growth activity isbelieved to be retained by the S-isomer," Gray added.

Sepracor expects to begin early human clinical trials with atoothpaste formulation of S-ketoprofen this year, according toTimothy Barberich, the company's president and chiefexecutive officer.

"Toothpaste is a very effective dosage form," Gray toldBioWorld. "You do get very acceptable system bioavailabilityby brushing the teeth. The compound is readily absorbedthrough the membranes." And using only the S-isomer of theracemic pair reduces the volume of experimental drug that hasto be added to the toothpaste. Otherwise, "there's anorganoleptic problem," Gray said. "It tastes very bad."

Sepracor is also working on a mouthwash formulation of itsNSAIDS for treating gingivitis, but "still needs to evaluate anappropriate clinical profile," Gray told BioWorld.

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.