Compositions and methods of delivery of pharmacological agents

Abstract

The present invention relates to a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, which carrier comprises a protein, for example, human serun albumin and / or deferoxamine. The human serum albumin is present in an amount effective to reduce one or more side effects associated with administration of the pharmaceutical composition. The invention also provides methods for reducing one or more side effects of administration of the pharmaceutical composition, methods for inhibiting microbial growth and oxidation in the pharrmaceutical composition, and methods for enhancing transport and binding of a pharmaceutical agent to a cell.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS [0001] This patent application is a continuation of patent application Ser. No. 10 / 731,224, which claims the benefit of U.S. Provisional Patent Application No. 60 / 432,317 filed December 9, 2002, U.S. Provisional Patent Application 60 / 526,544 filed Dec. 3, 2003, U.S. Provisional Patent Application 60 / 526,773 filed Dec. 4, 2003, and U.S. Provisional Patent Application 60 / 527,177 filed Dec. 5, 2003. FIELD OF THE INVENTION [0002] This invention pertains to pharmaceutical compositions comprising pharmaceutically active agents for parenteral or other internal use, which have the effect of reducing certain undesirable side effects upon administration when compared with available formulations of similar drugs. BACKGROUND OF THE INVENTION [0003] It is well recognized that many drugs for parenteral use, especially those administered intravenously, cause undesirable side effects such as venous irritation, phlebitis, burning and pain on injection, ...

AI Technical Summary

Benefits of technology

[0010] The invention provides a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises a protein, such as albumin, more preferably human serum albumin, in an amount effective to reduce one or more side effects of administration of the pharmaceutical composition into a human, and wherein the pharmaceutically acceptable carrier comprises deferoxamine in an amount effective to inhibit microbial growth in the pharmaceutical composition. The invention also provides a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises a protein, such as albumin, in an amount effective to reduce one or more side effects of administation of the pharmaceutical composition into a human, and wherein the pharmaceutically acceptable carrier comprises deferoxamine in an amount effective to inhibit oxidation m the pharmaceutical composition.

[0011] The invention provides a method for reducing one or more side effects associated with administration of a pharmaceutical composition to a human comprising (a) administering to a human a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrer, wherein the pharmaceutically acceptable carrier comprises albumin and deteroxamine. Also provided are methods for inhibiting microbial growth or for inhibiting oxidation, or for inhibiting microbial growth and oxidation in a pharmaceutical composition. These methods comprise preparing a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmacutically acceptable carrier comprises deferoxamine in an amount effective for inhibiting microbial growth or an amount effective for inhibiting oxidation in the pharmaceutical composition.

Problems solved by technology

It is well recognized that many drugs for parenteral use, especially those administered intravenously, cause undesirable side effects such as venous irritation, phlebitis, burning and pain on injection, venous thrombosis, extravasation, and other administration related side effects.

Often, the free drug present in the formulation induces pain or irritation upon administration.

Another problem associated with the manufacture of drugs for injection, particularly water insoluble drugs, is the assurance of sterility.

However, such methods are time consuming and expensive.

In addition, the oxidation of drug formulations by exposure to air during manufacture or storage can lead to, for example, reduced pH, drug degradation, and discoloration, thereby destabilizing the drug formulation and / or reducing shelf life.

These formulations, however, induce other side effects (e.g., cardiovascular complications), or cause destabiliztion of propofol emulsions.

Since edetate and pentetate are metal ion chelators, however, they have the potential to be dangerous by scavenging the essential metal ions from the body system.

Moreover, the addition of sulphites to drug formulations presents potential adverse effects to the periatric population and for those in the general population who are allergic to sulphur.