Method and compositions for administering resveratrol and pterostilbene

Abstract

Resveratrol and / or pterostilbene are added to a chewable carrier, to enhance absorption of resveratrol and / or pterostilbene buccally or through the mucous membranes of the mouth. The composition containing the resveratrol and / or pterostilbene is designed to be retained in the mouth for at least 20 seconds and up to 20 minutes to ensure absorption of the resveratrol and / or pterostilbene through the mucous membranes of the mouth.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]The present application claims priority from provisional application 61 / 019,745, filed Jan. 8, 2008.FIELD OF THE INVENTION [0002]The present invention relates to methods and compositions for administering resveratrol and pterostilbene.BACKGROUND OF THE INVENTION [0003]Resveratrol and its analogs, pterostilbene (3,5-dimethoxy-4′-hydroxy-trans-stilbene), TMS (3,4′,5-reimwrhoxzy-trans-stilbene), 3,4′,4-DH-5-MS (3,4′-dihydroxy5-methoxy-trans-stilbnene) and 3,5-DH-4′MS(3,5-dihydroxy-4′-,ethoxy-trans-stilbene), have been shown to have chemopreventaive activity against cardiovascular disease and a variety of cancers in model systems. However, it is not clear whether the drugs reach the proposed sites of action in vivo after oral administration, especially in humans.[0004]Walle et al., in Drug Metabolism and Disposition 32: 1377-1382, 2004, examined the absorption, bioavailability and metabolism of 14C-resveratrol after oral and intravenous dose...

AI Technical Summary

Benefits of technology

[0016]Pterostilbene has been found to be equal in potency to resveratrol as a cancer-preventive agent (Rimando et al., Cancer Chemopreventive and Antioxidant Activities of Pterostilbene, a Naturally Occurring Analogue of Resveratrol, Ars.usda.gov). Antioxidants destroy free radicals, highly reactive molecules whose excess has been linked to cancer, which may account for the effectiveness of resveratrol and pterostilbene against cancer. Animal studies have also found that pterostilbene can lower blood glucose and may be a potent antidiabetic agent.

[0020]Some compounds are not carcinogenic until they have been metabolized in the body by cytochrome P450 enzymes (2). By inhibiting the expression and activity of certain cytochrome P450 enzymes (20,21), resveratrol could help prevent cancer by decreasing exposure to these activated carcinogens. In contrast, increasing the activity of phase II biotransformation enzymes generally promotes the excretion of potentially toxic or carcinogenic chemicals. Resveratrol has been found to increase the expression and activity of the phase II enzyme NAD(P)H:quinine reductase in cultured cells (5, 22).

[0038]Another method of incorporating resveratrol and / or pterostilbene into a chewable form for transmucosal delivery is by incorporating the resveratrol and / or pterostilbene into a dissolvable matrix material. This dissolvable matrix material may include carbohydrates, fats, proteins such as gelatin, waxes (natural and synthetic), hydrocarbons and other materials that safely dissolve in the oral cavity. The combination of resveratrol and / or pterostilbene and the matrix material can be compressed, poured into a mold cavity, dehydrated, freeze dried or otherwise formed into an integral delivery system. Specific confectionery components can be combined in order for the mixture to form an integral solid mass. These components include, for example, compressible confectioner's sugar, sorbitol, mannitol and maltodextrin. Any food-safe flavoring and / or coloring materials may be incorporated into the product.

Problems solved by technology

However, it is not clear whether the drugs reach the proposed sites of action in vivo after oral administration, especially in humans.

However, the resveratrol is rapidly transformed in the liver to the glucurunide, which makes the resveratrol not bioavailable.

However, it is not clear if the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans.

Extremely rapid sulfate conjugation by the intestine / liver appears to be the rate-limiting step in the bioavailability of resveratrol and related compounds such as pterostilbene.