Diagnosis, evaluation and treatment of coronary artery disease by exercise simulation using closed loop drug delivery of an exercise simulating agent beta agonist

• US 5,460,605 A
• Filed: 12/07/1993
• Issued: 10/24/1995
• Est. Priority Date: 02/19/1988
• Status: Expired due to Fees

• Current Assignee: SICOR, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: SICOR, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Tuttle, Ronald R., Browne, Clinton E.
• Primary Examiner(s): Maglione, Corrine M.
• Assistant Examiner(s): WILKENS, FRANK
• Application Number:
  US08/163,839
• Time in Patent Office: 686 Days
• Field of Search: 604/50-53, 604/65-67, 128/DIG. 12, 128/DIG. 13
• US Class Current: 604/67
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0448 Drug reservoir
• 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
• 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
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 215/60 the chain having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/62 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 237/30 having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 45/305 with halogenochromate reagents, e.g. pyridinium chlorochromate
• CPC Class Codes: C07C 47/277 containing ether groups, groups, groups, or groups
• CPC Class Codes: Y10S 128/13 Infusion monitoring

Abstract

Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.

Claims

1. A device for eliciting cardiovascular responses in a mammal similar to cardiovascular responses elicited by aerobic exercise which comprises:

(a) drug delivery system for administering an exercise simulating agent into said mammal'"'"'s bloodstream;

(b) infusion control system for controlling infusion of said exercise simulating agent into the bloodstream of said mammal which is operatively connected to said delivery system; and

(c) monitoring system connected to said mammal to measure response level of said mammal to said exercise simulating agent which is operatively connected to said drug delivery system and infusion control system such that infusion of exercise simulating agent may be feedback-controlled to obtain a preselected range of responses of said mammal to said exercise simulating agent, said preselected range of responses being varied as a function of time by the infusion control system.

2. A device according to claim 1 wherein said control system includes a discontinuing system for discontinuing infusion of exercise simulating agent into said mammal'"'"'s bloodstream when a preselected time period has expired or when said cardiovascular responses are outside said preselected range and which is operatively connected to said drug delivery system.

3. A device according to claim 2 wherein said control system includes a termination system for terminating absorption of said exercise simulating agent into said mammal'"'"'s bloodstream operatively connected to said discontinuing system which is actively activated simultaneously with said discontinuing system.

4. The device according to claim 1 wherein the monitoring system includes an electrocardiographic monitor.

5. The device according to claim 2 wherein the drug delivery system includes a transdermal iontophoretic element.

6. The device according to claim 5 wherein the discontinuing system includes a switching element which stops or reverses current to the iontophoretic element.

7. The device for eliciting cardiovascular responses of claim 1 wherein the infusion control system includes a microprocessor.

8. A system for the closed-loop administration of a drug which causes a physical response in a mammal comprising:

(a) a drug delivery system connected to the mammal;

(b) a monitor connected to the mammal capable of determining the physical response of the mammal, and

(c) a control system to control the drug infusion to the mammal so as to vary the physical response as a function of time for diagnosis, the control system being connected in closed-loop fashion to the monitor and the drug delivery system.

9. The system of claim 8 wherein the physical response of the mammal is the heart rate.

10. The system of claim 9 wherein the drug is an exercise simulating agent.

11. The system of claim 10 wherein the drug is a catecholamine.

12. The system of claim 8 wherein the monitor includes an electrocardiograph.

13. The system of claim 8 wherein the drug delivery system is a transdermal drug delivery device.

14. The system of claim 8 wherein the drug delivery system is an intravenous drug delivery device.

15. The system of claim 8 further including:

(d) a display for providing an indication of the physical response.

16. The system of claim 8 wherein the control system includes a microprocessor.

17. The system of claim 8 wherein the control system includes means to vary the physical response as a linear function of time.

18. The system of claim 8 wherein the control system includes means to vary the physical response as a step function.

19. The system of claim 8 further including:

(d) a user input device for specifying the desired response of the physical response as a function of time.

20. The system of claim 19 wherein the user input device includes means to specify the rate of increase of a linear increase in the physical response.

21. The system of claim 19 wherein the user input device includes means to specify the time and size of a step function increase in the physical response.

22. The system of claim 19 wherein the user input device includes means to specify patient specific data.

23. The system of claim 19 further including:

(d) an input operatively connected to the control system for initiating a hold of the physical response at the then current value.

24. The system for the closed-loop administration of a drug of claim 8 wherein the control system includes a microprocessor.