High penetration composition and uses thereof

Abstract

The present invention relates to compositions and uses of novel high penetration compositions or high penetration prodrugs (HPP), in particular HPPs for 4-aminophenol derivatives, which are capable of crossing biological barriers with high penetration efficiency. The HPPs herein are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, due to the ability of penetrating biological barriers, the HPPs herein are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs herein can be administered to a subject through various administration routes. For example, the HPPs can be locally delivered to an action site of a condition with a high concentration due to their ability of penetrating biological barriers and thus obviate the need for a systematic administration. For another example, the HPPs herein can be systematically administer to a biological subject and enter the general circulation with a faster rate.

Description

PRIORITY CLAIM[0001]The present application is a continuation-in-part application of International Application PCT / IB2006 / 053091, with an international filing date of Sep. 3, 2006, and designating the U.S.; and a continuation-in-part application of U.S. application Ser. No. 12 / 351,804, filed on Jan. 9, 2009, both of which are incorporated herein by reference in their entirety. The present application also claims priority to U.S. Provisional Application 61 / 120,052, filed Dec. 4, 2008, which is incorporated herein by reference in its entirety. The U.S. application Ser. No. 12 / 351,804, filed on Jan. 9, 2009, is a continuation-in-part application of International Application PCT / IB2006 / 052318, with an international filing date of Jul. 9, 2006; a continuation-in-part application of International Application PCT / IB2006 / 052461, with an international filing date of Jul. 18, 2006; a continuation-in-part application of International Application PCT / IB2006 / 052549, with an international filing ...

AI Technical Summary

Benefits of technology

The present invention relates to a method of treating various conditions by using a high potency prodrug (HPP) or high potency c prodrug (HPC) which can be administered locally or systemically. The HPPs or HPCs can be designed to have higher concentrations at the target site with lower dosages and reduced side effects. They can also be used to penetrate biological barriers and treat previously difficult-to-reach areas. This approach allows for faster and more efficient bioavailability, as well as the potential to treat new indications.

Problems solved by technology

Active agents or drugs that are effective in vitro may not be as effective in vivo due to the delivery difficulties in vivo, in particular, their limited penetration ability across one or more biological barriers (BBs) before reaching the site of action where diseases occur in vivo.

Since a higher dosage of a drug is required to reach a distal location in the systematic administration, drugs delivered by such a route may cause adverse reactions.

Although acetaminophen is used to relieve fever as well as the signs and symptoms of rheumatoid arthritis and osteoarthritis, a number of side effects are associated with the use of acetaminophen and the related compounds.

Acute overdosage of acetaminophen may result in dose-dependent and potentially fatal hepatic necrosis as well as renal tubular necrosis and hypoglycemia.

It is very difficult, however, to deliver therapeutically effective plasma levels of these drugs by the known formulations.

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