System and method for biphasic transdermal iontophoretic therapeutic agents

Patent metadata

Field	Value
Publication number	US-10780266-B2
Application number	US-201715679924-A
Country	US
Kind code	B2
Filing date	Aug 17, 2017
Priority date	Feb 12, 2009
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

Abstract

Various embodiments provide methods and systems for the biphasic iontophoretic transdermal delivery of therapeutic agents. An embodiment of a method for such delivery comprises positioning at least one electrode assembly in electrical communication with a patient's skin. The assembly includes a solution comprising a therapeutic agent which passively diffuses into the skin. A dose of agent is delivered from the assembly into the skin during a first period using a first current having a characteristic e.g., polarity and magnitude, to repel the agent out of the assembly. During a second period, a second current having a characteristic to attract the agent is used to retain the agent in the assembly such that delivery of agent into skin is minimized. A dose of agent may be delivered on demand by an input from the patient. Embodiments may be used for delivery of agents which cause adverse effects from unwanted passive diffusion.

First claim

What is claimed is:

1. An apparatus for iontophoretic transdermal delivery of a therapeutic agent to a patient, the apparatus comprising:
a) an electrode assembly having a tissue contacting side for coupling to a skin of the patient at a tissue site, a therapeutic agent reservoir and at least one electrode, the at least one electrode being electrically coupled to the therapeutic agent reservoir and having a tissue contacting layer at the tissue contacting side and configured to be positioned adjacent the skin tissue site;
b) a current source coupled to the electrode assembly and electrically coupled to the at least one electrode; and
c) a controller coupled to the current source for controlling the iontophoretic transdermal delivery of the therapeutic agent;
d) the controller comprising a processor and application programming executable on the processor for performing the steps of:
i) delivering a dose of therapeutic agent from the therapeutic agent reservoir into the skin during a first period using a first current having a polarity and magnitude to repel the therapeutic agent out of the therapeutic agent reservoir; and
ii) retaining or lowering a rate of delivery of the therapeutic agent from the therapeutic agent reservoir during a second period using a second current having a polarity and magnitude to minimize or lower delivery of the therapeutic agent into the skin during the second period, wherein the first period and the second period together comprise a delivery cycle.

2. The apparatus of claim 1 , wherein the first period comprises a delivery period and the second period comprises a non-delivery period where the therapeutic agent is not delivered from the therapeutic agent reservoir to the skin.

3. The apparatus of claim 1 , wherein at least one of the first period and second period comprise a ramp-up period or ramp-down period during which a magnitude of a corresponding current varies between the first current and the second current.

4. The apparatus of claim 1 , wherein the tissue contacting layer comprises a first electrode, the apparatus further comprising:
a second electrode disposed to contact a second skin tissue site spaced apart from the first electrode; and
wherein the first and second electrodes are coupled so as to form an active electrode and return electrode.

5. The apparatus of claim 4 :
wherein the electrode assembly is coupled to or integrated with a patch having the tissue contacting side;
wherein at least one of the current source and controller is positioned in a housing coupled to a non-tissue contacting side of the patch, the housing having sufficient flexibility such that the housing is engaged with the patch to form the apparatus;
wherein the patch is adhered at tissue contacting side the to the skin tissue site; and
wherein the patch and housing have sufficient flexibility to deform with movement or fluctuation of the skin tissue site so as to remain sufficiently adhered to the skin tissue site over an extended period of time to transdermally deliver the therapeutic agent.

6. The apparatus of claim 5 , wherein the extended period of time is up to about seven days.

7. The apparatus of claim 1 , wherein the tissue contacting layer comprises a porous layer to allow for the therapeutic agent to pass from the therapeutic agent reservoir through the tissue contacting layer and into the skin tissue site.

8. The apparatus of claim 2 , further comprising:
an input device and associated logic coupled to the controller for initiating a delivery cycle, wherein the application programming executable is further configured to allow for patient initiation of the delivery cycle.

9. The apparatus of claim 2 , wherein the application programming executable is further configured for limiting a maximum number of delivered doses of therapeutic agent over a selected period.

10. The apparatus of claim 2 , wherein the controller includes logic for controlling a start of a second delivery period until after a refractory period.

11. The apparatus of claim 10 , wherein the refractory period comprises a period of time spanning from an end of the delivery period to an end of the non-delivery period.

12. The apparatus of claim 2 , wherein at least one of the delivery period and non-delivery period are selected to maintain a plasma concentration of the therapeutic agent within a therapeutic index.

13. The apparatus of claim 1 , wherein the therapeutic agent reservoir includes at least one of a therapeutic agent or a therapeutic agent solution.

14. The apparatus of claim 13 , wherein the therapeutic agent comprises an opioid.

15. The apparatus of claim 14 , wherein the opioid comprises a fentanyl salt or a fentanyl analogue.

16. The apparatus of claim 15 , wherein the fentanyl salt is selected from the group consisting of fentanyl hydrochloride, fentanyl citrate and fentanyl pamoate and wherein the fentanyl analogue is selected from the group consisting of alfentanil, sufentanil and remifentanil.

17. The apparatus of claim 13 , wherein the therapeutic agent comprises iron for treatment of iron deficient anemia.

18. The apparatus of claim 13 , wherein the therapeutic agent comprises insulin or various glucagon like peptides for treatment of diabetes or other blood sugar regulation disorder.

19. The apparatus of claim 13 , wherein the therapeutic agent comprises one or more chemotherapeutic agents for treatment of cancer.

20. The apparatus of claim 1 , wherein the current source and controller are configured to deliver an alternating current to the at least one electrode.

Assignees

• Incube Labs Llc

Inventors

• Imran Mir
• Hashim Mir
• Mclaughlin Glen
• Arastu Huma
• Vaidyanathan Rekha
• Harris Joel
• Korupolu Radhika
• Mangogna Andrew
• Ong Chang
• Patel Sanjay
• Wang Lu
• Williams Timothy

Classifications

• A61N1/044

  Shape of the electrode · CPC title

• A61K31/5415

  ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam · CPC title

• A61N1/0448

  Drug reservoir · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61N1/325 Primary

  for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body (electrodes for external use A61N1/0428) · CPC title