Compositions and methods for enhancing the biological response to chemical agents and physical stimuli

• US 10,029,089 B2
• Filed: 10/14/2011
• Issued: 07/24/2018
• Est. Priority Date: 10/15/2010
• Status: Active Grant

• Current Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York), University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Rubin, Clinton, Rubin, Janet
• Primary Examiner(s): Gilbert, Samuel
• Application Number:
  US13/879,551
• Publication Number:
  US 20130288260A1
• Time in Patent Office: 2,475 Days
• Field of Search: 128898
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 2/00 Magnetotherapy
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

The present invention relates to compositions and methods configured to deliver a stimulus (e.g., a therapeutic agent or a therapeutically beneficial signal) to a cell, tissue, organ, or organism. The stimulus is applied at least twice, and the first and second applications are separated by a rest period in which no further stimulus is actively applied. The rest period is of a duration (e.g., about 1-6 hours) sufficient to provoke an enhanced response to the second stimulus.

Claims

1. A method of enhancing a cell response to a high frequency, low magnitude physical stimulus, the method comprising:

providing a cultured cell;

providing a device configured to deliver the high frequency, low magnitude physical stimulus toward the cultured cell;

exposing the cultured cell to the physical stimulus, wherein the physical stimulus is applied to the cultured cell for a first session comprising about one second to about one hour;

providing for a refractory period wherein the same cultured cell is free of the physical stimulus for about the next 1-3 hours; and

exposing the same cultured cell to the physical stimulus for a second session comprising about one second to about one hour immediately after the about 1-3 hours of being free of the physical stimulus,

wherein the response is enhanced relative to a cultured cell receiving the same stimulus without the refractory period, and wherein the cultured cell is a purified tissue culture.

2. The method of claim 1, wherein the cultured cell comprises a mammalian cell.

3. The method of claim 1, wherein the physical stimulus is delivered by vibration.

4. The method of claim 1, wherein the frequency is about 5-1,000 Hz and wherein the magnitude is about 0.01-10.0 g.

5. The method of claim 1, further comprising providing the cultured cell in the device, wherein the device is a cell culture incubator.

6. The method of claim 1, wherein a response by the cultured cell to the physical stimulus is an increase in cellular proliferation.

7. The method of claim 1, wherein the device is configured to deliver the high frequency, low magnitude, physical stimulus toward the cultured cell when the cultured cell is disposed in an in vitro growth medium.

8. The method of claim 1, wherein the cultured cell is disposed in an in vitro growth medium.

9. The method of claim 1, wherein the cultured cell is in tissue culture.

10. The method of claim 1, wherein the time period of the physical stimulus are selected from the group consisting of about 2, 5, 10, 15, 20, 30, 45 or 60 minutes.

11. The method of claim 1, wherein the frequency of the physical stimulus is about 15 to about 200 Hz.

12. The method of claim 1, wherein the frequency of the physical stimulus is about 5 to about 100 Hz.

13. The method of claim 1, wherein the magnitude of the physical stimulus is about 0.1 to 1.0 g.