American Bioscience, Inc.

Vivorx Pharmaceuticals, Inc.

Abraxis Bioscience, LLC

Zhiwen Yao

Patrick Soon-Shiong

Neil P Desai

Shlomo Magdassi

Chunlin Tao

Andrew Yang

Leslie Louie

Tianli Zheng

In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful election of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof

In accordance with the present invention, there are provided stabilized total nutrient admixture (TNA) compositions which are useful for the in vivo parenteral delivery of pharmacologically acceptable lipids or fats, as well as methods for the preparation thereof. In particular, the pharmacologically acceptable lipid or fat is contained within a protein walled shell. In a particular embodiment of the invention, a TNA composition using human serum albumin (HSA) as a stabilizer has been prepared as a convenient three-in-one formulation (i.e., containing a fat emulsion, dextrose, and amino acids plus electrolytes). This &ldquo;three-in-one&rdquo; formulation can be prepared in liquid form or in dry form (comprising submicron-sized nanoparticles). The dried material is stable, even under long term storage, and is easily reconstituted immediately before use by simply adding sterile water (with or without vitamin supplementation) This serves to rehydrate the powder into a TNA suitable for injection. The long shelf life, ease of reconstitution, and single-component injectability of invention compositions provide significant cost savings, as such compositions can be reconstituted and administered safely, even in the home. In addition, HSA, the stabilizing agent of choice for use in the practice of the present invention, has been shown to improve survival and wellness when given as a supplement to patients receiving conventional forms of total nutrient admixtures.

Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof

In accordance with the present invention, there are provided stabilized total nutrient admixture (TNA) compositions which are useful for the in vivo parenteral delivery of pharmacologically acceptable lipids or fats, as well as methods for the preparation thereof. In particular, the pharmacologically acceptable lipid or fat is contained within a protein walled shell. In a particular embodiment of the invention, a TNA composition using human serum albumin (HSA) as a stabilizer has been prepared as a convenient three-in-one formulation (i.e., containing a fat emulsion, dextrose, and amino acids plus electrolytes). This 'three-in-one' formulation can be prepared in liquid form or in dry form (comprising submicron-sized nanoparticles). The dried material is stable, even under long term storage, and is easily reconstituted immediately before use by simply adding sterile water (with or without vitamin supplementation). This serves to rehydrate the powder into a TNA suitable for injection. The long shelf life, ease of reconstitution, and single-component injectability of invention compositions provide significant cost savings, as such compositions can be reconstituted and administered safely, even in the home. In addition, HSA, the stabilizing agent of choice for use in the practice of the present invention, has been shown to improve survival and wellness when given as a supplement to patients receiving conventional forms of total nutrient admixtures.

Total nutrient admixtures as stable multicomponent liquids or dry

In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful selection of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

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Culver City, CA, United States of America

Zhiwen Yao