Methods and systems for glucose regulation

• US 9,333,340 B2
• Filed: 11/20/2012
• Issued: 05/10/2016
• Est. Priority Date: 04/04/2008
• Status: Active Grant

• Current Assignee: ReShape LifeSciences, Inc.
• Original Assignee: EnteroMedics, Inc. (ReShape LifeSciences, Inc.)
• Inventors: Thornton, Arnold W., Kim, Dennis Dong-won, Knudson, Mark B., Tweden, Katherine S., Wilson, Richard R.
• Primary Examiner(s): Dietrich, Joseph
• Application Number:
  US13/681,581
• Publication Number:
  US 20130079745A1
• Time in Patent Office: 1,267 Days
• Field of Search: 607/40, 607/41, 607/133
• US Class Current: 1/1
• 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 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36167 Timing, e.g. stimulation onset
• CPC Class Codes: A61N 1/37211 Means for communicating with stimulators
• CPC Class Codes: A61N 1/37235 Aspects of the external programmer

Abstract

Various methods and apparatus for treating a condition associated with impaired glucose regulation in a subject comprising in one embodiment, applying a neural conduction block to a target nerve at a blocking site with the neural conduction block selected to at least partially block nerve pulses. In another embodiment, combinations of down-regulating and or up-regulating with or without pharmaceutical agents are used to treat impaired glucose regulation. In other embodiments, up-regulation or down-regulation of various nerves, such as the vagus and its branches, and the splanchnic is used to modify the production of GLP-1 and GIP, thereby controlling glucose levels. In yet further embodiments, combinations of down-regulating and or up-regulating with or without pharmaceutical agents are used to modify the production of GLP-1 and GIP, to treat impaired glucose regulation.

Claims

1. A method of modifying the amount of GLP1, comprising:

applying a first intermittent electrical signal to an electrode positioned on a vagus nerve with said electrical signal selected to down-regulate afferent and efferent neural activity on the vagus nerve and to restore neural activity on the nerve upon discontinuance of said signal, and has a frequency of 500 Hz to 5000 Hz, wherein the first electrical signal is applied intermittently in a cycle including an on time of application of the signal followed by an off time during which the signal is not applied to the nerve, wherein the on and off times are applied multiple times per day over multiple days;

wherein the on time is selected to have a duration of about 30 seconds to about 5 minutes; and

wherein the electrical signal is selected to increase the amount of GLP1.

2. The method according to claim 1, wherein the electrical signal is applied on the hepatic branch of the vagus nerve.

3. The method according to claim 1, wherein the electrical signal is applied on the celiac branch of the vagus nerve.

4. The method according to claim 1, further comprising applying a second electrical signal to a second target nerve or organ, wherein the second electrical signal is selected for frequency, pulse width, amplitude and timing to upregulate or down-regulate neural activity.

5. The method of claim 4, wherein the downregulating and upregulating signals are applied at the same time or different times.

6. The method of claim 4, wherein the second target nerve is the splanchnic nerve or the celiac branch of the vagus nerve.

7. The method of claim 4, wherein the second target organ is the duodenum or ileum.

8. The method of claim 1, further comprising detecting the level of GLP1 to determine whether to apply an electrical signal treatment.

9. The method according to claim 1, further comprising administering an agent that improves glucose control.

10. The method of claim 9, wherein the agent increases the amount of insulin and/or increases the sensitivity of cells to insulin.

11. The method of claim 10, wherein the agent that increases the amount of insulin is selected from the group consisting of insulin, insulin analogs, sulfonylureas, meglitinides, GLP-1 analogs, and DPP4 inhibitors.

12. The method of claim 10, wherein the agent that increases the sensitivity of cells to insulin is a PPAR alpha, gamma, or delta agonist.