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

[0147]In certain embodiments, since a HPP of the present invention is capable of crossing one or more biological barriers, the HPP can be administered locally (e.g., typically or transdermally) to reach a location where a condition occurs without the necessity of a systematic administration (e.g., oral or parenteral administration). The local administration and penetration of a HPP or HPC allow the HPP or HPC to reach the same level of local concentration of an agent or drug with much less amount or dosage of HPP in comparison to a systematic administration of a parent agent or drug; alternatively, a higher level of local concentration which may not be afforded in the systematic administration, or if possible, requires significantly higher dosage of an agent in the systematic administration. The high local concentration of a HPP or HPC or its parent agent if being cleaved enables the treatment of a condition more effectively or much faster than a systematically delivered parent agent and the treatment of new conditions that may not be possible or observed before. The local administration of a HPP or HPC may allow a biological subject to reduce potential sufferings from a systemic administration, e.g., adverse reactions associated with the systematic exposure to the agent, gastrointestinal / renal effects. Additionally, the local administration may allow a HPP or HPC to cross a plurality of biological barriers and reach systematically through, for example, general circulation and thus avoid the needs for systematic administration (e.g., injection) and obviate the pain associated with the parenteral injection.

[0148]In certain embodiments, a HPP or HPC according to the present invention can be administered systematically (e.g., orally or parenterally). The HPP or the active agent (e.g., drug or metabolite) of the HPP may enter the general circulation with a faster rate than the parent agent and gain faster access to the action site of a condition. Additionally, the HPP can cross a biological barrier (e.g., BBB) which has not been penetrated if a parent agent is administered and thus offer novel treatment of conditions that may not be possible or observed before.

[0149]The following examples are provided to better illustrate the claimed invention and are not to be interpreted as limiting the scope of the invention. All specific compositions, materials, and methods described below, in whole or in part, fall within the scope of the present invention. These specific compositions, materials, and methods are not intended to limit the invention, but merely to illustrate specific embodiments falling within the scope of the invention. One skilled in the art may develop equivalent compositions, materials, and methods without the exercise of inventive capacity and without departing from the scope of the invention. It will be understood that many variations can be made in the procedures herein described while still remaining within the bounds of the present invention. It is the intention of the inventors that such variations are included within the scope of the invention.

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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