Compositions and methods for altering the biodistribution of biological agents

• US 7,198,949 B2
• Filed: 09/22/2003
• Issued: 04/03/2007
• Est. Priority Date: 06/28/1996
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Nebraska
• Original Assignee: Board of Regents of the University of Nebraska
• Inventors: Iversen, Patrick L., Porter, Thomas R.
• Primary Examiner(s): ZARA, JANE J
• Application Number:
  US10/668,448
• Publication Number:
  US 20040057946A1
• Time in Patent Office: 1,289 Days
• Field of Search: 435/6, 435/455, 435/91.7, 435/91.1, 514/44, 536/23.1, 536/24.5, 530/300, 530/350, 530/362
• US Class Current: 435/455
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics

Abstract

The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic or diagnostic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in improved utility for agents such as oligonucleotides and polynucleotides which are plagued with problems with biodistribution.

Claims

1. A method for delivering a biological agent to the site of a tumor in a subject, comprising:

administering to a subject having said tumor a composition comprising said agent and a suspension of microbubbles which are encapsulated with a filmogenic protein selected from the group consisting of albumin, human gamma globulin, human apotransferrin, beta lactase and urease and contain a gas selected from a perfluorocarbon and SF₆.

2. The method of claim 1, wherein said composition is formed by incubating said agent with said suspension of microbubbles.

3. The method of claim 1, wherein the gas is a perfluorocarbon selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, and perfluoropentane.

4. The method of claim 1, wherein said administration is carried out without application of ultrasound to said composition during or following administration.

5. The method of claim 1, wherein said composition is administered intravenously.

6. A composition comprising

a suspension of microbubbles which are encapsulated with a filmogenic protein selected from the group consisting of albumin, human gamma globulin, human apotransferrin, beta lactase and urease and contain a gas selected from a perfluorocarbon and SF₆, and

a medicament which binds to said filmogenic protein.

7. The composition of claim 6, wherein said composition is formed by incubating said medicament with said suspension of microbubbles.

8. The composition of claim 7, wherein the gas is a perfluorocarbon selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, and perfluoropentane.