Patent Application
20080004671
The present invention is hereinafter described in conjunction with the appended drawings, in which:
Before describing several exemplary embodiments of the invention, it is to be understood that the invention is not limited to the details of construction or process steps set forth in the following description. The invention is capable of other embodiments and of being practiced or being carried out in various ways.
Embodiments of the present invention provide methods, apparatus and systems for vagus nerve stimulation in a patient. An exemplary embodiment of an apparatus for vagus nerve stimulation is shown in
Further details of the stimulation apparatus are shown in
Referring now to
Referring now to
The power and electrical parameters of the apparatus will now be described. The power needs will be dominated by dissipation through the system resistance is given by Vrms2/R, where Vrms is the root-mean square excitation voltage provided by the system between Electrode A and Electrode B, and R is the lumped resistance between these electrodes.
The system resistance R is given by
R=ρ*b/Area,
where τ is resistivity of the medium, Area is the cross sectional area of conduction, and b is the electrode spacing. Based on tissue measurements, it is estimated that the resistivity of the gastric wall as 1 kΩ cm. See M. R. Prausnitz, Advanced Drug Delivery Reviews 18 (1996) 395-425, wherein based on values are given as the deeper tissue resistance on page 397, the area-based resistivity of deep skin tissues is 100-200 Ωcm2. The resistivity is given by 100-200 Ωcm2/0.1 cm=1-2 kΩ cm.
Also, it is estimated that the resistivity of the gastric fluid is 1 kΩcm. Gastric fluids are essentially HCl with a pH of 1 to 3. (J. DeSesso and C. Jacobson, Food and Chemical Toxicology 39 (2001) 209-228). The molar conductivity of gastric fluid is 391, 412, and 421Ω−1 cm2 mol−1 (CRC Handbook of Chemistry and Physics, 82nd Edition, D. R. Lide, ed. (2001) Page 5-92), giving an average resistivity of 880 Ωcm.
Assuming an electrode spacing of 1 cm, and an Area of 1 cm2, the resulting system resistance R=1 kΩ. This estimate compares favorably with data in U.S. Pat. No. 6,684,104, which is incorporated herein by reference, where 300-800 ohms was reportedly measured between patches attached to the gastric wall (where the electrode spacing is 0.5-2 cm and each patch diameter is 1 to 3 cm).
Therefore, assuming Vrms=1.2 V and R=1 kΩ, the ohmic power dissipation is 1.4 mW. This gives a power dissipation of 1.4 mW per electrode array. A typical apparatus would include up to about five arrays, and multiplying by five arrays per apparatus yields a 7 mW system power dissipation when energized. It will be understood, however, that the invention is not limited to a particular number of arrays. The average power requirements will be lower because of the stimulation duty cycle, and the possibility of deactivating the system during meals and at night. Optimal duty cycle stimulation is reported to be 1:1.8, or on 36% of the time, as disclosed in U.S. Pat. No. 6,587,719. This translates to an average system power (during periods of activation) of 2.5 mW.
The power source is selected so as to be an appropriate size for packaging in an orally ingestible capsule. Alternatively, the power source could be provided by an externally applied electromagnetic field, such as by using inductive coupling.
Existing battery technology has been optimized for other applications to deliver the similar system power. Hearing aid batteries have evolved from mercury cells to zinc-air cells with a very high capacity. While the zinc air batteries offer the best size-performance fit for this application, it is not clear whether there is sufficient air in the gastric cavity for operating a zinc air battery. Alternatives include silver oxide cells, custom batteries, and supercapacitors. Table 1 lists examples of types of batteries, dimensions, capacities and life cycle of the battery at 2.5 mW, based on the calculations above reflecting a 1:1.8 duty cycle.
Alternatively, an open battery cell can be utilized in which gastric fluids act as electrolytes. In another alternative, the power source can be an external power source based on a capacitive system or inductive coupling. For example, the power source could be strapped to the outside of the patient's abdomen to supply power to the apparatus.
Referring now to
The controller 204 can provide control signals to control the duty cycle of the wave generated by the oscillator 202, programmed stimulation, and intensity control of the wave generated by the oscillator 202. The controller 204 and the oscillator 202 can be integrated into one component as shown in the Figures. Alternatively, these components can be discrete elements. Communications 208 may be provided to provide induced or generated power. Antenna 210 may be provided to send and receive signals from communications to the apparatus. The communications 208 may be integrated into the stimulation apparatus, or alternatively, they may be remote from the apparatus to provide for control of the device outside of the body of the patient.
The excitation frequency can be any suitable frequency, and an exemplary range of frequencies is between about 0.1 to 20 Hz. The duty cycle of the apparatus according to one embodiment is between about 1:1 and 100:1. Programmed stimulation can be provided according to one or more embodiments of the invention wherein the apparatus can be programmed to simulate during meal time on a daily basis or based on a custom program according to the patient's needs. The communications can continually monitor the intensity, cycle time, and programming of the apparatus.
The oscillator, controller, and communications can be readily integrated into a microchip as is known in the art. For example, radio frequency identification (RFID) tags include an RF transceiver and coded reporting functions in a package the size of a grain of rice. Also, FPGA (field-programmable gate array) and ASIC (application specific IC) technologies provide for over about 5,000 circuit elements per square cm. For example, Xilinx 4VFX12 FPGA (field programmable gate array) incorporates over 12,000 logic cells in an area 17×17 mm.
In use, the apparatus of the present invention can be administered to a patient by administering a capsule containing the apparatus or by endoscopic delivery as discussed above. When the apparatus is in place inside the patient's stomach, the electrical components are placed in communication and are adapted to generate an electrical output signal in the form of a sequence of pulses, with either predetermined parameter values or values programmable by the attending physician within predetermined, programmed ranges for treating the disorder. The electrodes, which are adjacent the vagus nerve of the patient when the apparatus is deployed in the stomach, apply the programmed output signal to the patient's vagus nerve. Calibration of the overall treatment system for a particular patient can be performed by telemetry by means of an external programmer to and from the implant. The apparatus may be externally programmed for activation upon occurrence of a predetermined detectable event, or, instead might be periodically or continuously activated, to generate the desired output signal with parameter values programmed to treat obesity by modulating vagal activity so as to produce a sensation of satiety. If adjustment to the stimulation is required, the frequency of the stimulation can be adjusted.
Suitable methods, devices and systems for controlling system for stimulation of the vagus nerve are disclosed in U.S. Pat. Nos. 5,263,480 and 6,587,719, the entire contents of which are incorporated herein by reference.
After the system has been utilized for an extended period of time, for example, about a few days or as long as about one to two weeks or longer, the apparatus can be removed using an endoscope. Alternatively, the apparatus can be designed to be excreted through GI tract after use by manufacturing portions of the apparatus using bioerodible elements. Bioerodible elements can be provided which dissolve inside the patient's stomach after a predetermined period of time. Examples of bioerodible elements, include, but are not limited to, polyglycolide (PGA), polylactide (PLA), poly-caprolactone, poly-dioxanone, and poly-lactide-co-glycolide, either alone or combined as co-polymers. Of these, PGA has the strongest flexural modulus (7.0 Gpa). Additional examples of which are disclosed in aforementioned U.S. Pat. Nos. 4,758,436 and 5,047,464. Once the device has been dosed, it will deploy and retain in the GI tract, preferably the stomach. During this retention period the system will be in contact with the lining of the GI tract. During this contact period, electrical energy can be pulsed through the wall thus stimulating the vagal nerve.
Suitable materials to manufacture the apparatus according to the present invention include polymers such as polyethylene, polypropylene and similar materials. Bioerodible materials such as the materials listed above may also be utilized. As noted above, the electromechanical linkages can be made from a suitable conductive shape memory metal such as nickel titanium. The expandable element could be in a variety of forms such as the polygonal expandable element comprised of elongate members linked by electromechanical linkages. Alternatively, the expandable element could be in the form of an inflatable tube or ring. Additional examples of expandable elements that are retained inside the patient's stomach over a controlled, predictable and extended period of time are described in U.S. Pat. Nos. 5,062,829; 4,758,436; 5,047,464, the entire contents of which are incorporated by reference. As used herein, the term “expandable” refers to an element or a member that can increase in dimensions in at least one direction. Expandable elements could further be provided by balloon type structures, and polymer sheets.
In addition to the expandable elements described immediately above, the apparatus of the present invention could be retained in the stomach using a suitable gastric retention system used in drug delivery. Thus, the gastric retention system could include floating systems based on one or more hydrodynamically balanced system incorporating buoyant materials enabling the device to float; effervescent systems that use gas-generating material such as carbonates incorporated into the element which react with gastric acid and produce carbon dioxide, which allows them to float; raft systems incorporating alginate gels which have a carbonate component that reacts with gastric acid to form bubbles in the gel, enabling floating.
In one embodiment, the diameter of the device when deployed and expanded in the stomach is from about 7 to 20 cm. According to one or more embodiments, the elongate members are about 0.5 to 5 cm in length and preferably approximately 1.8 cm in length (0.7 inches to fit into size 000 or smaller capsule, for example size 0 capsule L=0.85″). Other suitably sized capsules such as size 00 capsules may be utilized, which have been used for imaging of the gastrointestinal tract.
Thus, according to embodiments of the present invention, apparatus, methods and systems for controlling appetite in a reversible and noninvasive or minimally invasive manner by stimulating the vagus nerve from the inside of the stomach are provided. The apparatus can be an orally delivered electronic device that provides an electrical field to the surrounding tissue and thereby stimulates the vagus nerve to suppress appetite. The structure of the apparatus can be in the form of a compressible and expandable ring structure comprised of elongate members connected by electrical or electromechanical linkages. Once the device is deployed in the stomach, it will be retained in place, similar to a gastric retained drug delivery device. The expanded ring structure will contact the stomach walls to provide for retention of the device.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.
This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application Ser. No. 60/806,065, filed Jun. 28, 2006, which is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 60806065 | Jun 2006 | US |
