Pharmaceutical composition comprising a curcumin derivative

Abstract

The present invention is directed to a pharmaceutical composition comprising:

Description

RELATED APPLICATION(S)[0001]This application is a continuation application of U.S. application Ser. No. 12 / 571,303, filed Sep. 30, 2009, which is a continuation-in-part of International Application No. PCT / US2008 / 060569, which designated the United States and was filed on Apr. 17, 2008, published in English, which claims priority to and is a CIP of, both U.S. application Ser. No. 12 / 029,904, filed Feb. 12, 2008 and U.S. application Ser. No. 11 / 736,278, filed Apr. 17, 2007.[0002]The entire teachings of the above applications are incorporated herein by reference.BACKGROUND OF THE INVENTION[0003]In Alzheimer's Disease (AD), the abnormal cleavage of beta amyloid protein precursor from the intracellular membrane often produces a protein Aβ 1-42 which is incompletely removed by normal clearance processes. It has been reported that soluble beta amyloid oligomers are highly neurotoxic. Moreover, over time, this soluble protein assemblage is deposited as a beta amyloid protein Aβ plaque with...

AI Technical Summary

Benefits of technology

The present invention relates to improving the brain bioavailability of curcumin by administering it through the nasal route. This mode of delivery allows curcumin to pass through the olfactory mucosa and enter olfactory neurons, resulting in higher brain levels and fewer side effects. Intranasal delivery also reduces the dose required and avoids extensive hepatic first-pass metabolism, making the drug more tolerable and effective. The nasal route of administration is believed to preferentially deposit curcumin in the brain regions associated with Alzheimer's Disease. Overall, this invention provides a method for delivering curcumin to the brain of a mammal by applying a pharmaceutical composition to the nasal cavity.

Problems solved by technology

Despite the beneficial effects of curcumin, the present inventors have noted that there are many bioavailability problems associated with the oral delivery of curcumin.

First, because curcumin does not easily penetrate the human digestive tract and is subject to intestine-based metabolism and rejection, less than 1% of oral curcumin enters the plasma.

Second, the small amount of curcumin that enters the bloodstream is rapidly metabolized by the liver and kidney.

Third, it has been reported that high oral doses of curcumin in the range of 4,000-8,000 mg / day cause problems such as headache, rash and diarrhea, likely produced by metabolites of curcumin.

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