Targeted thermal release of drug-polymer conjugates

• US 5,490,840 A
• Filed: 09/26/1994
• Issued: 02/13/1996
• Est. Priority Date: 09/26/1994
• Status: Expired due to Term

• Current Assignee: InSightec Ltd.
• Original Assignee: General Electric Company
• Inventors: Anthony, Thomas R., Uzgiris, Egidijus E., Opsahl, Lorinda R., Vosburgh, Kirby G., Cline, Harvey E.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): SMITH, CHALIN A
• Application Number:
  US08/312,362
• Time in Patent Office: 505 Days
• Field of Search: 128/653.2, 128/653.4, 128/662.02, 128/660.03, 604/20, 604/22, 424/9, 601/2, 601/15, 601/3, 607/97, 607/901
• US Class Current: 604/22
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

Thermal drug treatment of tumor tissue is obtained by attaching a thermally active drug to carrier molecules which have an affinity to tumor tissue. Localized heating is performed on the tumor tissue, thereby activating the drug in the tumor tissue. The end result may be concentrated delivery of a drug to a chosen tissue, or, in the case where the drug creates a toxin when heated, selective tissue destruction of a selected locations heated. The localized heat may be applied by focused ultrasound heating.

Claims

1. A method of thermal drug treatment of tumor tissue of a subject comprising the steps of:

a) selecting drug molecules used in tumor tissue treatment of living subjects;

b) selecting a polypeptide carrier molecule of a size such that it will pass freely into tumor tissue but substantially none will pass into normal tissue;

c) binding drug molecules to carrier molecules to result in combined carrier/drug molecules;

d) introducing the carrier/drug molecules into a blood vessel of said subject having said tumor tissue desired to be destroyed causing the carrier/drug molecules to infuse into the tumor tissue; and

e) heating the tumor tissue employing focused ultrasound and the carrier/drug molecules within the tumor tissue to cause the carrier/drug molecules to produce a toxin having a relatively increased concentration in the tumor tissue as compared with the concentration in other tissues of said subject.

2. The method of thermal drug treatment of claim 1 wherein the polypeptide carrier molecules are chosen to have a plurality of residues such that the combined charge of molecules of the selected polypeptide and selected drug is a net negative charge.

3. The method of thermal drug treatment of claim 1 wherein the polypeptide carrier molecules and drug molecules have a combined molecular size chosen to selectively accumulate in the tumor tissue.

4. The method of thermal drug treatment of claim 1 wherein the polypeptide carrier molecules are selected to be polylysine molecules having a plurality of attached residues.

5. The method of thermal drug treatment of claim 1 wherein the drugs are chosen to be chemotherapy drugs.