Ultrasound therapy for selective cell ablation

• US 6,821,274 B2
• Filed: 03/29/2002
• Issued: 11/23/2004
• Est. Priority Date: 03/07/2001
• Status: Expired due to Fees

• Current Assignee: Gendel Limited
• Original Assignee: Gendel Limited
• Inventors: McHale, Anthony Patrick, Haro, Anna Maria Rollan
• Primary Examiner(s): PEFFLEY, MICHAEL F
• Application Number:
  US10/113,173
• Publication Number:
  US 20020193784A1
• Time in Patent Office: 970 Days
• Field of Search: 606/1, 606/27, 606/28, 606/41, 604/21, 604/22, 435/461, 435/450, 435/173.1, 435/173--17
• US Class Current: 606/41
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• 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: A61N 2007/0008 Destruction of fat cells
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

The invention provides a method of sensitizing target cells to ultrasound energy using a stimulus such as an electric field. This “electrosensitisation” enables target cells to be disrupted by ultrasound at frequencies and energies of ultrasound which do not cause disruption of non-sensitized (i.e., non-target) cells. As a consequence, the method increases the selectivity of ultrasound therapy, providing a way to ablate undesired cells, such as diseased cells (e.g., tumor cells) while minimizing harm to neighboring cells. In another aspect, however, ultrasound can be used to sensitize cells while the electrical field is used to disrupt cells. The invention also provides an apparatus for performing the method and assays for identifying gene products and other molecules involved in apoptosis.

Claims

1. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said one or more target cells comprise tumor cells, wherein said target site is within the body of an organism, wherein said target site is accessed using a medical access device which brings a source of electrical energy and ultrasound energy in sufficient proximity to the target site, to disrupt said one or more target cells and wherein said medical access device is selected from the group consisting of a catheter, an endoscope, and a laparoscope.

2. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said target site comprises a wart, a papiloma, a psoriatic region of skin, a region of skin with eczema, or a mole.

3. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said target site comprises an unwanted fatty deposit.

4. The method according to claim 3, wherein said fatty deposit is a lipoma.

5. The method according to claim 3 or 4, wherein said one or more target cells comprise adipose cells.

6. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said exposing is used to debulk tissue.

7. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said one or more cells are at the site of a wound.

8. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said one or more cells are within a blood vessel.

9. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said target site comprises benign granulomatous tissue.

10. A method for selectively disrupting one or more target cells at a target site comprising a plurality of cells comprising:

(a) exposing the one or more cells to an electric field; and

(b) exposing the one or more cells to ultrasound;

wherein said exposing in steps (a) and (b) disrupts said one or more target cells, wherein said one or more target cells comprise tumor cells, wherein said target site is within the body of an organism and wherein disrupted cells are removed from the body of the organism.

11. The method according to claim 10, wherein removal of cells is effected by immune response cells.

12. The method according to claim 11, further comprising administering to the organism an agent which modulates an immune response.