Biosynchronous transdermal drug delivery

• US 7,780,981 B2
• Filed: 09/13/2005
• Issued: 08/24/2010
• Est. Priority Date: 09/13/2004
• Status: Active Grant

• Current Assignee: Morningside Venture Investments Ltd. (Morningside Group Ltd.)
• Original Assignee: Chrono Therapeutics Inc.
• Inventors: Giannos, Steven A., DiPierro, Guy
• Primary Examiner(s): Krass; Frederick
• Assistant Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US11/162,525
• Publication Number:
  US 20060062838A1
• Time in Patent Office: 1,806 Days
• Field of Search: 424/449
• US Class Current: 424/449
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/0266 Shape memory materials
• CPC Class Codes: A61M 2205/3337 Controlling, regulating pressure or flow by means of a valve by-passing a pump
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61M 39/22 Valves or arrangement of valves A61M39/02, A61M39/0247, A61M39/16 take precedence; regulating valves in infusion systems A61M5/16881; in devices worn by the patient for the reception of urine, faeces, catamenial or other discharge, or in colostomy devices A61F5/4405
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

Systems and methods for treating diseases, addictions and disorders in humans and animals involving synchronizing and tailoring the administration of drug compounds with the body'"'"'s natural circadian rhythms, in order to counteract symptoms when they are likely to be at their worst. Automated and pre programmable transdermal drug administration system are used. This system can also utilize a pump or pressurized reservoir, and/or a system for removing depleted carrier solution, or other modulated dispensing actuator, in conjunction with micro-fabricated structures commonly referred to as Micro-needles, or heat, or iontophoresis, sonophoresis, or a wide range of chemical permeation enhancers.

Claims

1. A method for delivering a bioactive agent to a human or animal comprising:

(a) providing a transdermal drug delivery device coupled to the human or animal, the transdermal drug delivery device comprising;

(i) a drug reservoir comprising the bioactive agent,

(ii) a membrane in contact with the skin of the human or animal;

(iii) an electronic programmable timing mechanism;

(iv) a mechanism for causing the bioactive agent to be delivered from the drug reservoir to the membrane in response to the timing mechanism, the bioactive agent being delivered transdermally by passive diffusion from the membrane into the skin of the human or animal; and

(v) an expandable waste reservoir for controlled discontinuance of the delivery of the bioactive agent;

(b) providing timing routines implemented by the timing mechanism, wherein the timing routines are selected to deliver the bioactive agent at a time, rate, sequence and/or cycle that is synchronized with a biological rhythm of the human or animal;

(c) delivering the bioactive agent from the drug reservoir to the membrane in response to the timing mechanism;

(d) transdermally delivering the bioactive agent from the membrane into the skin of the human or animal by passive diffusion; and

(e) removing the bioactive agent and/or a carrier solution from the membrane via the expandable waste reservoir to discontinue delivery of the bioactive agent to the human or animal;

wherein the device is maintained in contact with the skin during removal of the bioactive agent and/or carrier solution via the expandable waste reservoir.

2. The method of claim 1 wherein the bioactive agent comprises a stimulant and the timing routines are selected to deliver the stimulant immediately before the human or animal wakes up.

3. The method of claim 1 wherein the bioactive agent comprises nicotine and the timing routines are selected to deliver the nicotine at times that are associated with nicotine cravings.

4. The method of claim 3 wherein at least one of the selected times corresponds to a time at which the human or animal experiences a morning nicotine craving.

5. The method of claim 1 wherein the bioactive agent comprises an antihistamine and the timing routines are selected to deliver the antihistamine while the human or animal sleeps.

6. The method of claim 1 wherein the time routines are selected to deliver the bioactive agent immediately before the human or animal wakes up.

11. The method of claim 3 wherein the timing routine results in a plurality of nicotine delivery pulses with a most sustained pulse beginning during a one-hour period prior to waking in the morning.

12. The method of claim 3 wherein the timing routines include a cessation of nicotine dosage from after midnight to during a one-hour period prior to the time the human or animal wakes in the morning.

13. The method of claim 12 wherein the timing routines further include pulses associated with waking up and mid-day and evening meals.

14. The method of claim 3 wherein the timing routines include at least five preprogrammed pulses during the course of 24 hours.

15. The method of claim 3 wherein amplitudes of preprogrammed pulses in the afternoon are less than amplitudes of a first preprogrammed pulse in the morning and a preprogrammed pulse in the evening.

16. The method of claim 1 wherein the timing routines schedule no delivery of the bioactive agent in a time period from after midnight to 1 hour before waking in the morning and schedule a first delivery of the bioactive agent in the morning in a pulse which has an initial peak at from 1 to 4 hours after waking and a pulse peak width of from 1-6 hours.

17. The method of claim 1 wherein the bioactive agent and/or carrier solution is removed from the membrane via evaporation into the expandable waste reservoir.

18. The method of claim 1 wherein the expandable waste reservoir comprises a hydrophilic substance.

7. A method for delivering a drug to a human or animal comprising:

(a) providing a transdermal drug delivery device comprising;

(i) a source of the drug;

(ii) a membrane in contact with the skin of the human or animal;

(iii) an electronic programmable timing mechanism;

(iv) a mechanism for causing the drug to be delivered from the source to the membrane in response to the timing mechanism, the drug being delivered transdermally by passive diffusion from the membrane into the skin of the human or animal;

(v) a solvent removal system comprising an expandable waste reservoir for removing carrier solution and/or remaining drug;

(b) providing timing routines implemented by the timing mechanism, wherein the timing routines are selected to deliver the drug at a time when the human or animal is expected to be asleep;

(c) delivering the drug from the source to the membrane in response to the timing mechanism;

(d) transdermally delivering the drug from the membrane into the skin of the human or animal by passive diffusion; and

(e) removing carrier solution and/or remaining drug from the membrane via the expandable waste reservoir to discontinue delivery of the drug to the human or animal; and

wherein the device is maintained in contact with the skin during removal of the carrier solution and/or remaining drug via the expandable waste reservoir.

8. The method of claim 7 wherein the timing routines terminate drug delivery at a time when the human or animal is expected to be asleep.

9. The method of claim 7 wherein the time routines increase the dosage of drug delivered at a time when the human or animal is expected to be asleep.

10. The method of claim 7 wherein the timing routines decrease the dosage of drug delivered at a time when the human or animal is expected to be asleep.