Convalent conjugates of biologically-active compounds with amino acids and amino acid derivatives for targeting to physiologically-protected sites

Abstract

This invention herein describes a method of facilitating the entry of drugs into cells and tissues at physiologically protected sites at pharmacokinetically useful levels and also a method of targeting drugs to physiologically protected sites in vivo. Also provided are drug conjugates with an amino acid or derivative thereof for facilitating such targeted drug delivery. The conjugates and methods of this invention provide an advance over other drug targeting methods known in the prior art, because the invention provides drug concentrations in such physiologically protected sites that can reach therapeutically-effective levels after administration of systemic levels much lower than are currently administered to achieve a therapeutic dose. This technology is appropriate for use with psychotropic, neurotropic, neurological, antibiotic, antibacterial, antimycotic, antiviral, antiproliferative or antineoplastic drugs, agents and conjugates, for rapid and efficient introduction of such agents across, e.g., the blood-brain barrier. Further, the invention provides means for retention and prolonged enzymatic release of such drugs, agents and conjugates comprising the conjugates of the invention, in the brain and central nervous system and other physiologically-protected sites.

Description

[0001] This application claims priority to U.S. Ser. No. 09 / 993,976, filed Nov. 5, 2001, now U.S. Pat. No. 7,045,543, granted May 16, 2006, which is incorporated by reference in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] This invention is related to specific targeting of biologically-active compounds to specific cells, tissues and organs in vivo. The invention specifically provides conjugates of biologically-active compounds and methods of effecting the uptake and accumulation of biologically active compounds into organs, tissues and cells, particularly at physiologically protected sites, at pharmacokinetically useful levels. The conjugates of this invention permit drug concentrations to be achieved, especially at physiologically protected sites, at levels at which such compounds are therapeutically effective after administration of systemic levels much lower than currently attainable otherwise. This technology is appropriate for rapid and effic...

AI Technical Summary

Benefits of technology

"The present invention is about a method for delivering biologically-active compounds to specific sites in an animal's body. This is done by attaching the compounds to specific amino acids or amino acid derivatives that are transported into these protected sites. The method allows for efficient and specific intracellular concentration of the compounds, which can be achieved through a spacer molecule that links the compounds to the amino acid or amino acid derivative. The invention also provides pharmaceutical compositions and compositions of matter comprising the biologically-active compounds covalently linked to the amino acid or amino acid derivative. The invention has the advantage of facilitating the entry of the compounds into cells and tissues protected by the blood-brain barrier."

Problems solved by technology

In the pharmacological and neurologic arts, it is well-recognized that the inability to deliver effective amounts of neurotropic, psychotropic and anticonvulsant drugs and agents across the blood-brain barrier severely limits the therapeutic efficacy of such pharmaceutical compounds and can prevent treatment of neurologic disease.

In addition, the use of even effective neurologic agents is further limited by systemic toxicity resulting from the high systemic concentrations that must be administered to achieve a therapeutic concentration of such agents in the brain, central nervous system and other neurological structures.

An additional challenge in designing an appropriate drug delivery scheme is to include within the drug conjugate a functionality that could either accelerate or reduce the rate at which the drug is released upon arrival at the desired site.

An additional challenge in designing an appropriate drug delivery scheme is to include within the drug conjugate a functionality that could either accelerate or reduce the rate at which the drug is released upon arrival at the desired site.

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