Methods for in vivo delivery of nutriceuticals and compositions useful therefor

• US 5,650,156 A
• Filed: 06/07/1995
• Issued: 07/22/1997
• Est. Priority Date: 02/22/1993
• Status: Expired due to Term

• Current Assignee: Abraxis Bioscience LLC (Bristol-Myers Squibb Company)
• Original Assignee: Vivorx Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Wong, Michael, Suslick, Kenneth S., Soon-Shiong, Patrick, Desai, Neil P., Grinstaff, Mark W., Sandford, Paul A.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US08/482,272
• Time in Patent Office: 776 Days
• Field of Search: 424/400, 424/450, 424/451, 424/9
• US Class Current: 424/400
• CPC Class Codes: A23L 33/40 Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 47/6927 the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 49/126 Linear polymers, e.g. dextran, inulin, PEG
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 49/1818 particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 49/1863 the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
• CPC Class Codes: A61K 49/222 characterised by a special physical form, e.g. emulsions, liposomes
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/226 Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: A61K 9/5052 Proteins, e.g. albumin
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

In accordance with the present invention, there are provided compositions useful for the in vivo delivery of a biologic, wherein the biologic is associated with a polymeric shell formulated from a biocompatible material. The biologic can be associated with the polymeric shell itself, and/or the biologic, optionally suspended/dispersed in a biocompatible dispersing agent, can be encased by the polymeric shell. In another aspect, the biologic associated with polymeric shell is administered to a subject, optionally dispersed in a suitable biocompatible liquid.

Claims

1. A method for the preparation of articles for in vivo delivery of nutriceuticals, said method comprising subjecting aqueous medium containing biocompatible material capable of being crosslinked by disulfide bonds and a nutriceutical to high intensity ultrasound conditions for a time sufficient to promote crosslinking of said biocompatible material by disulfide bonds;

wherein said nutriceutical is substantially contained within a polymeric shell, and

wherein the largest cross-sectional dimension of said shell is no greater than about 10 microns.

2. The method according to claim 1, wherein said biocompatible material is a naturally occurring polymer, a synthetic polymer, or a combination thereof,

wherein said polymer, prior to crosslinking, has covalently attached thereto sulfhydryl groups or disulfide linkages.

3. The method according to claim 1, wherein said nutriceutical is selected from amino acids, sugars, proteins, carbohydrates, fat-soluble vitamins, fat, or combinations of any two or more thereof.

4. The method according to claim 1, wherein said nutriceutical within said shell is dissolved or suspended in a biocompatible dispersing agent.

5. A method for the delivery of a nutriceutical to a subject in need thereof, said method comprising administering to said subject the articles prepared by the method of claim 1 by oral, intravenous, subcutaneous, intraperitoneal, intrathecal, intramuscular, intracranial, inhalational, topical, transdermal, suppository (rectal), or pessary (vaginal) routes of administration.

9. A method for the delivery of a nutriceutical to a subject in need thereof, said method comprising administering to said subject the articles prepared by the method of claim 1 by oral, intravenous, subcutaneous, intraperitoneal, intrathecal, intramuscular, intracranial, inhalational, topical, transdermal, suppository (rectal), or pessary (vaginal) routes of administration.

6. A method for the preparation of articles for in vivo delivery of nutriceuticals, said method comprising subjecting aqueous medium containing a nutriceutical capable of being crosslinked by disulfide bonds to high intensity ultrasound conditions for a time sufficient to promote crosslinking of said biocompatible material by disulfide bonds to form a polymeric shell;

wherein the largest cross-sectional dimension of said shell is no greater than about 10 microns.

7. The method according to claim 6, wherein said nutriceutical is a naturally occurring polymer, a synthetic polymer, or a combination thereof,

wherein said polymer, prior to crosslinking, has covalently attached thereto sulfhydryl groups or disulfide linkages.

8. The method according to claim 6, wherein said nutriceutical is selected from amino acids, sugars, proteins, carbohydrates, fat-soluble vitamins, fat, or combinations of any two or more thereof.