Iontophoretic drug delivery system with two-stage delivery profile

• US 5,207,752 A
• Filed: 03/21/1991
• Issued: 05/04/1993
• Est. Priority Date: 03/30/1990
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Badzinski, John D., Lattin, Gary A., McNichols, Larry A., Sorenson, Paul D.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US07/671,306
• Time in Patent Office: 775 Days
• Field of Search: 604/20, 604/21, 128/419 R, 128/803
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• 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

Abstract

A two-stage iontophoretic drug delivery system provides that iontophoretic current is delivered at a first level for a first predetermined interval to rapidly introduce a therapeutic agent into the bloodstream and thereafter reduced to a second lower level to maintain a desired steady-state therapeutic level of the agent. One embodiment provides that the initial interval is maintained sufficiently long to provide a peak dosage, thereafter which the current is shut off to allow concentration of the agent to subside in the bloodstream, whereupon a maintenance level of iontophoretic current is initiated. Another embodiment provides that the patient may selectively initiate a brief interval of increased iontophoretic current level to attain a brief interval of increased dosage.

Claims

1. A method of iontophoretic drug delivery wherein there is provided at least two electrodes carrying or in contact with an ionized therapeutic agent and wherein the electrodes and agent are positioned against body tissue to form an electrical path for an iontophoretic current traveling from one electrode to the other, said method comprising the steps of:

(a) inducing a first level of iontophoretic current between said electrodes wherein the ionized therapeutic agent is delivered into the tissue at a first rate and maintaining said first level for a predetermined interval so that the agent is rapidly introduced into the tissue; and

(b) reducing said first level to a second lower level of iontophoretic current at a time when the concentration of therapeutic agent is substantially near that desired for a maintenance level, said lower level of current being sufficient to maintain said desired concentration level.

2. The method of iontophoretic drug delivery according to claim 1 wherein the predetermined interval for maintaining the first level of iontophoretic current is a time sufficient to achieve an initial concentration level higher than the maintenance level and further comprising the steps of:

shutting off the first level of iontophoretic current for a predetermined delay period following the predetermined interval, the delay period sufficient to allow the initial concentration level to reduce the maintenance level; and

including the second level of iontophoretic current after the predetermined delay period to maintain the desired concentration level.

3. The method of iontophoretic drug delivery according to claim 1 further comprising the steps of:

stepping up the iontophoretic current, for a second predetermined interval, from the maintenance level to a higher level of iontophoretic current for increasing the concentration of the therapeutic agent in the body; and

reducing the iontophoretic current back to the lower level of iontophoretic current after the second predetermined interval expires for maintaining the desired concentration level.

4. The method of iontophoretic drug delivery according to claim 3 wherein stepping up the iontophoretic current is user controlled.

5. The method of iontophoretic drug delivery according to claim 3 wherein the higher level of iontophoretic current is the first level of iontophoretic current.

6. Apparatus for introducing an ionized therapeutic agent into the body, comprising:

at least two electrodes;

iontophoretic current generation means for;

(i) driving a first level of iontophoretic current through said electrodes and the body tissue said electrodes are attached to, said first level applied for a predetermined interval; and

(ii) driving a second, lower level of iontophoretic current through said electrodes and the associated body tissue beginning after said predetermined interval, said predetermined interval being timed so that the concentration of therapeutic agent in the body obtains approximately the desired concentration level during the predetermined interval and so that said second current level substantially maintains the desired concentration level thereafter.

7. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the predetermined interval for driving the first level of iontophoretic current through the electrodes and the body tissue is a time sufficient to achieve an initial concentration level higher than the desired concentration level;

and the iontophoretic current generation means further comprises;

means for timing a predetermined delay period following the predetermined interval, the delay period sufficient to allow the initial concentration level to reduce to the desired concentration level; and

means for activating the iontophoretic current generation means for driving the second iontophoretic current after the predetermined delay period to maintain the desired concentration level.

8. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the iontophoretic current generation means further comprises:

means for stepping up the iontophoretic current from the desired concentration level to a higher level of iontophoretic current for increasing the concentration of the therapeutic agent in the body, said means for stepping up responsive to a control signal generated by a user activated timer; and

the user-activated timer producing the control signal for a second predetermined interval in response to user activation.

9. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first level of iontophoretic current is a first and second battery, the first battery only supplying power for the predetermined interval, after which the means for driving the second level of iontophoretic current is the second battery which provides the power for maintaining the desired concentration level.

10. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first level of iontophoretic current is a first and second battery, the first battery mainly supplying power for the predetermined interval, after which the means for driving the second level of iontophoretic current is the second battery which mainly provides the power for maintaining the desired concentration level.

11. The apparatus for introducing an ionized therapeutic agent into the body according to claim 10 wherein the first battery depletes its energy supply during the predetermined interval so that at the end of the predetermined interval, it no longer supplies an appreciable amount of current.

12. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first level of iontophoretic current is a first and second constant current source, the first constant current source powered by a first battery and the second constant current source powered by a second battery, the first battery only supplying power to the first constant current source for the predetermined interval, after which the means for driving the second level of iontophoretic current is the second constant current source which provides the power for maintaining the desired concentration level.

13. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first level of iontophoretic current is a first and second constant current source, the first constant current source powered by a first battery and the second constant current source powered by a second battery, the first battery mainly supplying power to the first constant current source for the predetermined interval, after which the means for driving the second level of iontophoretic current is the second constant current source which mainly provides the power for maintaining the desired concentration level.

14. The apparatus for introducing an ionized therapeutic agent into the body according to claim 13 wherein the first battery depletes its energy supply during the predetermined interval so that at the end of the predetermined interval, it no longer supplies an appreciable amount of current.

15. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first and second levels of iontophoretic current comprises:

a power source;

a first plurality of constant current diodes for regulating current from the power source to a first output node;

a second plurality of constant current diodes for regulating current from the power source to a second current output node;

a plurality of switching means which may be selectively closed for selectively connecting selected ones of the first and second plurality of constant current diodes with the power source so that the first level of current can be programmed to be delivered to the first node and the second level of current can be programmed to be delivered to the second node; and

a timed switch connecting the first and second nodes for the predetermined interval, after which time the second node is switched out.

16. The apparatus for introducing an ionized therapeutic agent into the body according to claim 15 wherein the selectively closed switching means are fused closed.

17. The apparatus for introducing an ionized therapeutic agent into the body according to claim 15 further comprising:

a cover to the plurality of switching means with a plurality of holes, each hole associated with one of the plurality of switching means so that

a stiletto may be selectively punched into the holes to selectively close the switching means.

18. The apparatus for introducing an ionized therapeutic agent into the body according to claim 6 wherein the means for driving the first and second levels of iontophoretic current comprises:

a first iontophoretic current source for, with a control input for activation thereof, producing a first current;

a second iontophoretic current source for producing a second current, the output of the first and second sources connected to the electrodes;

a timer for producing an activation signal for the predetermined interval, the activation signal connected to the control input of the first iontophoretic current source;

a power source applied to the first and second iontophoretic current sources;

the first and second current sources active in response to the supplied power to produce in combination the first level of iontophoretic current while the activation signal is applied thereto; and

whereby the first level of iontophoretic current is applied to the tissue by the first and second iontophoretic current sources when the first current source is active for the predetermined interval and the second, lower level of iontophoretic current is applied to the tissue by the second iontophoretic current source after the predetermined interval.

19. The apparatus for introducing an ionized therapeutic agent into the body according to claim 18 wherein the timer includes a user switch for activating the timer for a predetermined time, whereby the user is permitted to activate the first iontophoretic current source to increase the iontophoretic current level.

20. The apparatus for introducing an ionized therapeutic agent into the body according to claim 18 further comprising a deactivation timer means for deactivating the second iontophoretic current source for a predetermined deactivation period and for reactivating the second iontophoretic current source after the expiration of the predetermined deactivation period.

21. The apparatus for introducing an ionized therapeutic agent into the body according to claim 20 wherein the deactivation timer means deactivates the second iontophoretic current source after the predetermined interval.

22. Apparatus for introducing an uncharged therapeutic agent into the body, comprising:

at least two electrodes;

a drug reservoir for storing a liquid solvent containing the uncharged therapeutic agent;

iontophoretic current generation means for;

(i) driving a first level of iontophoretic current through said electrodes and the body tissue said electrodes are attached to, said first level applied for a predetermined interval; and

(ii) driving a second, lower level of iontophoretic current through said electrodes and the associated body tissue beginning after said predetermined interval, said predetermined interval being timed so that the concentration of therapeutic agent in the body obtains approximately the desired concentration level during the predetermined interval and so that said second current level substantially maintains the desired concentration level thereafter.