Transdermal active drug delivery system and method

• US 6,564,093 B1
• Filed: 08/23/2001
• Issued: 05/13/2003
• Est. Priority Date: 04/23/1995
• Status: Expired due to Fees

• Current Assignee: Electromagnetic Bracing Systems, Inc.
• Original Assignee: Electromagnetic Bracing Systems, Inc.
• Inventors: Koops, Geert-Henk, Tannenbaum, Joseph, Ostrow, Alvin
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US09/807,698
• Time in Patent Office: 628 Days
• Field of Search: 604/20, 604/501, 607/152-153, 600/362, 600/573
• US Class Current: 604/20
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0452 Specially adapted for transcutaneous muscle stimulation [TMS]
• CPC Class Codes: A61N 1/0456 Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36021 for treatment of pain
• CPC Class Codes: A61N 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals

Abstract

A transdermal drug delivery system having at least one patch (20) with an electrosmotic, electro porous membrane (26) comprised of an inert biochemical substance which becomes actively electro-osmotic when an electric charge is passed through the membrane enabling a drug solution passing through to a skin surface to create an electroporative effect. The patch may be powered by a battery, an external power source (82), or self-powered by an auto-bio-fuel cell which acts as a battery during drug solution saturation. Multiple patches may be configured as a linked patch unit for use with a flexible cuff apparatus (70) to provide circumferential treatment of a body part. A network of supply tubes (66) may be connected to an external reservoir (68) to provide a slow supply of medicated fluid to each patch. A titration regulator (72) is in communication with the transdermal patch to regulate permanent flow to the skin.

Claims

1. A transdermal patch device for delivery of a pharmaceutical medium comprising:

a stored energy source for generating an electrical current;

means for generating an electromagnetic field having at least one predetermined frequency,

means for activating said energy source to generate said current producing said electromagnetic field;

a layer of permeable foam for retaining therein a quantity of pharmaceutical medium exhibiting at least partial ionization; and

an electroconductive membrane disposed under said foam layer through which the pharmaceutical medium passes,

said electromagnetic field driving said ionized pharmaceutical medium by active transport through said membrane to provide drug treatment therapy via the skin.

2. The device of claim 1 further comprising an electrophoretic tubing port in fluid communication with said layer of permeable foam defining a refillable storage reservoir, said port introducing the pharmaceutical medium into said patch device.

3. The device of claim 2 wherein said port is shaped to accommodate a drug-filled syringe for injecting pharmaceutical medium into said foam.

4. The device of claim 1 further comprising a biosensor integrated within said electroconductive membrane for sensing a quantity of the pharmaceutical medium passing therethrough and developing a responsive signal.

5. The device of claim 4 wherein said biosensor comprises:

a set of spaced apart electrode plates, comprising a reference electrode, an analyzing electrode, and a comparison electrode, said analyzing electrode disposed proximate a treatment area,

said reference electrode disposed away from said treatment area, and said comparison electrode disposed between said analyzing and reference electrodes closer to said reference electrode, said responsive signal being a voltage representing the difference in voltage differentials measured between said reference electrode and each of said analyzing and comparison electrodes.

6. The device of claim 4 wherein said biosensor additionally monitors levels of chemicals in the blood so as to determine and justify delivery of drug dosages.

7. The device of claim 1 wherein said electroconductive membrane further comprises a dense coating layer disposed on said membrane having at least one of fixed negative and positive charges in a mosaic pattern for controlling said drug delivery through said membrane.

8. The device of claim 1 wherein said dense coating layer is at least partially comprised of at least one of sulfonated polysulfone and polyetheretherketone.

9. The device of claim 1 wherein said patch can adhere to a skin surface for local area drug delivery.

10. The device of claim 1 wherein said stored energy source is provided as a fuel cell.

11. The device of claim 10 wherein said means for activating comprises a depressable activator button which activates said fuel cell.

12. The device of claim 1 wherein said stored energy source is provided as a battery.

13. The device of claim 12 wherein said means for activating comprises a depressable activator button which completes an electrical circuit for generating said current.

14. The device of claim 1 wherein said means for generating an electromagnetic field is provided as an impermeable conductive plate providing a barrier for preventing leaching of components of said energy source through said membrane to a treatment area.

15. The device of claim 1 in which said electric current generates magnetic and electric fields providing a drive mechanism for transdermal magnetophoresis and iontophoresis of the pharmaceutical medium.

16. The device of claim 1 in which said electric current is combined with said electromagnetic field to develop transdermal electro-infusion of the pharmaceutical medium.

17. The device of claim 1 in which said electric current provides electrostimulation therapy.

18. The device of claim 1 in which said pharmaceutical medium is a chemotherapy drug for electrochemotherapy.

19. The device of claim 1 wherein a multiple quantity of said transdermal patch devices are linked together as a cuff for cumulative drug treatment of a limb.

20. The device of claim 19 configured within an electrophoretic cuff apparatus, said apparatus comprising:

an applicator wrap of single or multiple connecting patch units each containing a plurality of said transdermal patch devices;

means for simultaneously generating an electric current in each of said patch devices, and

a network of electrophoretic tubing adjacent to a surface of said patch devices for delivering a selected pharmaceutical medium to said patch devices, said patch devices being selectively energized by said electric current for providing drug treatment therapy.

21. The device of claim 20 wherein said patch units are connected to a slow drip liquid drug reservoir through a pump connected to said electrophoretic tubing with a system of duct distribution to each and every individual porous patch unit to deliver a drug through the skin and surface tissues.

22. The device of claim 21 further comprising a computerized control system for regulating flow from said slow drip liquid reservoir through said pump to said electrophoretic tubing, in accordance with said responsive signal.

23. The device of claim 1 further comprising regulation means for controlling passage of said pharmaceutical medium through said membrane in accordance with said responsive signal, to regulate and permeate said pharmaceutical medium in a treatment area by active transport transdermally.

24. The device of claim 23 wherein said regulation means comprises a computerized control system.

25. The device of claim 23, wherein said computerized control system comprises a display readout of a flow rate of said pharmaceutical medium.

26. A method of providing transdermal therapy of a pharmaceutical medium comprising the steps of:

providing a transdermal patch device comprising;

a stored energy source for generating an electrical current, means for generating an electromagnetic field having at least one predetermined frequency;

means for activating said energy source to generate said current producing said electromagnetic field;

a layer of permeable foam for retaining therein a quantity of pharmaceutical medium exhibiting at least partial ionization; and

an electroconductive membrane disposed under said foam layer through which the pharmaceutical medium passes, and

activating said energy source for generating said current to produce said electromagnetic field,

said electromagnetic field driving said ionized pharmaceutical medium through said membrane by active transport to provide drug treatment therapy via the skin.

27. The method of claim 26 wherein said step of activating said energy source generates electrical and electromagnetic field intensities having alternating polarities and predetermined sequential intervals programmed to correspond to selected drug characteristics.

28. The method of claim 27 wherein said various modulated electrical and electromagnetic fields are generated on a scale of intensities.

29. The method of claim 26 wherein the pharmaceutical medium is provided within said layer of permeable foam by a method comprising the steps of:

providing an electrophoretic tubing port in fluid communication with said layer of foam; and

inserting the pharmaceutical medium into said layer of foam via said port.

30. The method of claim 29 wherein said step of inserting is performed using a pharmaceutical medium administered in at least one of combinational and sequential forms.

31. The method of claim 26 further comprising the steps of:

providing an electrophoretic cuff apparatus comprising;

an applicator wrap of single or multiple connecting patch units containing a plurality of said transdermal patch devices;

means for simultaneously generating an electric current in each of said patch devices, and

a network of electrophoretic tubing adjacent to a surface of said patch devices;

delivering a selected pharmaceutical medium to said patch devices, said patch devices being connected to a controlled slow drip liquid reservoir through said network of tubing with a system of duct distribution to each and every individual patch device; and

selectively energizing said patch devices by said electric current to provide said drug treatment therapy through the skin and surface tissues.

32. The method of claim 31 wherein said delivering step is performed by a computerized control system in accordance with said responsive signal.

33. The method of claim 32 wherein said step of selectively energizing said patch devices establishes at least one of anode and cathode drug delivery modes.

34. The method of claim 31 wherein said step of selectively energizing said patch devices provides a DC current modulated in at least one of trapezoidal, square and sinusoidal wave pulses from 0-50 volts with alternating and continuous wave pulses modulated between 50 and 200 Hz and the electrical current ranging from 0 to 50 mA, within a current range of 0 to 15 mA.

35. The method of claim 31 wherein said step of selectively energizing said patch devices provides a DC electromagnetic current modulated in a format of at least one of trapezoidal, square and sinusoidal wave pulses from 0-50 volts with alternating and continuous pulses modulated between 0 to 200 Hz and the electrical current ranging from 0 to 50 mA, within a gauss range from 0-100 Gauss.

36. The method of claim 34, wherein said pulses are generated as at least one of two types, combined and individual.

37. The method of claim 35, wherein said pulses are generated as at least one of two types, combined and individual.

38. The method of claim 31 further comprising the step of providing a computerized control system for regulating flow from said slow drip liquid reservoir through said tubing.