Regulation of drug delivery through flow diversion

• US 6,638,263 B1
• Filed: 10/12/1999
• Issued: 10/28/2003
• Est. Priority Date: 10/12/1999
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Brown, James E., Theeuwes, Felix
• Primary Examiner(s): Hayes, Michael J.
• Application Number:
  US09/416,379
• Time in Patent Office: 1,477 Days
• Field of Search: 604/167-1-1, 604/256, 604/264, 604/27, 604/500, 604/523, 604/508, 604/511, 604/515, 604/516, 604/517, 604/521, 604/246-250, 137/625, 137/625.47, 137/872, 137/874, 137/861-864
• US Class Current: 604/500
• CPC Class Codes: A61M 2205/3523 using telemetric means
• 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: A61M 39/28 Clamping means for squeezing flexible tubes, e.g. roller clamps tube strippers A61M1/83
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/16804 Flow controllers
• CPC Class Codes: A61M 5/16813 by controlling the degree of opening of the flow line

Abstract

The present invention features methods and devices for modulating the rate of delivery of a drug formulation from a drug delivery device by diverting drug away from a drug delivery pathway. In one embodiment, a flow regulator is positioned relative to a drug delivery pathway of a drug delivery system so that adjustment of the flow regulator can provide for diversion of drug away from the drug delivery pathway. Diverted drug can be either delivered into the systemic circulation of the subject, or can be captured in a waste reservoir.

Claims

1. A method for delivering a desired amount of a drug to a localized treatment site of a subject, the method comprising:

causing a therapeutically effective quantity of drug to exit from a drug reservoir of a drug delivery device into a first delivery conduit comprising a first outlet and in a direction toward a localized treatment site; and

diverting a portion of the drug exiting the drug delivery device away from the first conduit and into a separate second conduit having a second outlet, wherein drug that flows through the second outlet is delivered to a site within the subject other than a treatment site and away from the localized treatment site such that said diverted portion does not reach the localized treatment site in a therapeutically effective amount;

wherein said diverting results in delivery of a desired amount of drug to the localized treatment site.

2. The method of claim 1, wherein the localized treatment site is a biologically confined treatment site.

3. The method of claim 1, wherein the desired amount of drug is delivered to the localized treatment site by varying the amount of drug diverted from the drug delivery device.

4. The method of claim 1, wherein said diverting is on an intermittent basis.

5. The method of claim 1, wherein the first delivery conduit is suitable for delivery of the drug at a low volume rate.

6. The method of claim 1, wherein the first delivery conduit provides two delivery outlets to provides for delivery of drug to at least two localized treatment sites.

7. The method of claim 1, wherein the localized treatment site is subcutaneous, percutaneous, intravenous, intramuscular, intra-arterial, intravascular, intraperitoneal, intraspinal, epidural, intrathecal, intracranial, intracardial, peritumoral, or intratumoral.

8. The method of claim 1, wherein the localized treatment site is a site within a kidney, liver, pancreas, heart, lung, eye, ear, lymph node, breast, prostate, ovary, testicle, thyroid, spleen, central nervous system, skeletal muscle, bone, lymph vessel, artery, arteriole, capillary bed, blood vessel, vein, peripheral nervous system, digestive system, gastrointestinal tract, urinary bladder, gall bladder, adrenal gland, adipose tissue, parathyroid gland, uterus, fallopian tube, skin, tumorous growth, autologous graft, synthetic graft, or site of microbial infection.

9. The method of claim 1, wherein the drug delivery device is a constant rate drug delivery device.

10. The method of claim 1, where drug diverted from the first conduit is delivered to the subject systemically.

11. The method of claim 1, wherein a distal end of the first drug delivery conduit is attached to a drug delivery catheter, wherein at least the catheter distal end is implanted at the localized treatment site.

12. The method of claim 11, wherein the catheter is adapted for delivery of drug to two localized treatment sites.

13. The method of claim 1, wherein said diverting is provided by adjusting a diversion element, the diversion element being positioned so as to facilitate diversion of flow of drug out of the first conduit and into the second conduit.

14. The method of claim 13, wherein said diverting is by adjusting the diversion element for a first time period so as to facilitate flow through the first conduit, and for a second time period so as to divert flow through the second conduit, wherein varying the length of the first and second time periods results in alteration in the amount of drug delivered to the localized treatment site.

15. The method of claim 13, wherein the diversion element is adjusted so that the delivery conduit and the diversion conduit are each partially open.

16. The method of claim 13, wherein the diversion element is adjusted to simultaneously divert a portion of the drug away from the delivery pathway and toward a site other than a treatment site.

17. The method of claim 1, wherein the localized treatment site is intraspinal, epidural, intrathecal, or intracranial.

18. The method of claim 1, wherein the localized treatment site is intrapericardial.

19. The method of claim 1, wherein the localized treatment site is intratumoral.

20. The method of claim 1, wherein the localized treatment site is within a kidney, liver, pancreas, heart, lung, eye, ear, lymph node, prostate, ovary, testicle, thyroid, spleen, bone, urinary bladder, gall bladder, adrenal gland, parathryoid gland, or uterus.

21. The method of claim 1, wherein the localized treatment site is within the central nervous system.

22. The method of claim 1, wherein drug diverted from the drug delivery pathway is delivered to the subject systemically.

23. A method of controlling an amount of drug administered to a treatment site in a subject with a drug delivery system comprising:

a flow regulator comprising;

a delivery conduit comprising a proximal delivery inlet, a distal delivery outlet, a delivery lumen extending between the proximal delivery inlet and the distal delivery outlet, the delivery conduit lumen defining a delivery pathway, and a diversion element positioned so as to facilitate diversion of flow of drug in a direction away from the delivery pathway, and

a diversion conduit comprising a diversion inlet, a diversion outlet, and a diversion lumen extending between the diversion inlet and diversion outlet, the diversion conduit lumen defining a diversion pathway;

a drug delivery device, wherein the drug delivery device is attached to the flow regulator to facilitate delivery of a drug from the drug delivery device through the delivery conduit lumen and out the distal delivery outlet; and

a waste reservoir positioned for receiving drug diverted away from the delivery pathway by the diversion element;

wherein the diversion conduit is in fluid communication with the waste reservoir such that drug diverted away from the delivery pathway by the diversion element flows into the diversion pathway defined by the diversion conduit and into the waste reservoir;

the method comprising;

implanting the drug delivery device;

introducing a drug into the flow regulator proximal delivery inlet, said introducing resulting in drug flowing through the drug delivery pathway and to a treatment site in a subject at which a distal end of the drug delivery conduit is implanted; and

adjusting the diversion element so that the delivery conduit and the diversion conduit are each partially open, thus diverting a portion of the drug away from the drug delivery pathway such that the diverted portion is delivered into the waste reservoir and does not reach the treatment site in a therapeutically effective amount;

wherein said adjusting alters the amount of drug that is delivered to the treatment site in the subject.

24. The method of claim 23, wherein the drug delivery device is a constant rate drug delivery device.

25. The method of claim 23, wherein the distal end of the drug delivery conduit is attached to a drug delivery catheter to provide for extension of the drug delivery pathway to a catheter delivery outlet at the catheter distal end, and wherein the catheter distal end is implanted at the treatment site.

26. The method of claim 25, wherein the catheter is adapted for delivery of drug to two treatment sites.

27. The method of claim 23, wherein the treatment site is subcutaneous, percutaneous, intravenous, intrathecal, intramuscular, intra-arterial, intravascular, intraperitoneal, intrapericardial, intraspinal, epidural, intracranial, intracardial, peritumoral, or intratumoral.

28. The method of claim 23, wherein the treatment site is a site within a kidney, liver, pancreas, heart, lung, eye, ear, lymph node, breast, prostate, ovary, testicle, thyroid, spleen, central nervous system, skeletal muscle, bone, lymph vessel, artery, arteriole, capillary bed, blood vessel, vein, peripheral nervous system, digestive system, gastrointestinal tract, urinary bladder, gall bladder, adrenal gland, adipose tissue, parathyroid gland, uterus, fallopian tube, skin, tumorous growth, autologous graft, synthetic graft, or site of microbial infection.

29. The method of claim 23, wherein the diversion element is adjusted for a first time period so as to facilitate flow through the delivery conduit, and for a second time period so as to divert flow through a diversion element, wherein varying the length of the first and second time periods results in alteration in the amount of drug delivered to the treatment site.

30. A method of administering drug to a treatment site in a subject, the method comprising:

implanting a flow regulator for use at a treatment site within a subject, wherein the flow regulator comprises;

a delivery conduit comprising a proximal delivery inlet, a distal delivery outlet, and a delivery lumen extending between the proximal delivery inlet and the distal delivery outlet, the delivery lumen defining a delivery pathway;

a diversion element positioned so as to facilitate diversion of flow of drug in a direction away from the delivery pathway; and

a waste reservoir positioned for receiving drug diverted away from the delivery pathway by the diversion element;

wherein said implanting of the flow regulator comprises implanting at least the distal end of the flow regulator delivery conduit at the treatment site; and

delivering drug from a drug delivery device, through the drug delivery pathway of the flow regulator, and to the treatment site;

wherein the drug is administered to the treatment site in the subject and wherein the amount of drug delivered to the treatment site is modulated by adjusting the diversion element of the flow regulator to simultaneously divert a portion of the drug away from the drug delivery pathway such that the diverted portion is delivered to the waste reservoir and does not reach the treatment site in a therapeutically effective amount.

32. The method of claim 30, wherein the drug delivery device is a constant rate drug delivery device.

31. A method of controlling an amount of drug administered to a treatment site in a subject with a drug delivery system comprising:

a flow regulator comprising a delivery conduit comprising a proximal delivery inlet, a distal delivery outlet, a delivery lumen extending between the proximal delivery inlet and the distal delivery outlet, the delivery conduit lumen defining a delivery pathway, and a diversion element positioned so as to facilitate diversion of flow of drug in a direction away from the delivery pathway;

a drug delivery device, wherein the drug delivery device is attached to the flow regulator to facilitate delivery of a drug from the drug delivery device through the delivery conduit lumen and out the distal delivery outlet; and

a waste reservoir positioned for receiving drug diverted away from the delivery pathway by the diversion element;

the method comprising;

implanting the drug delivery device;

introducing a drug into the flow regulator proximal delivery inlet, said introducing resulting in drug flowing through the drug delivery pathway and to a treatment site in a subject at which a distal end of the drug delivery conduit is implanted; and

adjusting the diversion element of the flow regulator to simultaneously divert a portion of the drug away from the drug delivery pathway and toward a site other than the treatment site such that the diverted portion is delivered into the waste reservoir and does not reach the treatment site in a therapeutically effective amount;

wherein said adjusting alters the amount of drug that is delivered to the treatment site in the subject.

33. The method of claim 31, wherein the distal end of the drug delivery conduit is attached to a drug delivery catheter, and wherein the catheter distal end is implanted at the treatment site.

34. The method of claim 31, wherein the catheter is adapted for delivery of drug to two treatment sites.

35. The method of claim 31, wherein the treatment site is subcutaneous, percutaneous, intravenous, intrathecal, intramuscular, intra-arterial, intravascular, intraperitoneal, intrapericardial, intraspinal, epidural, intracranial, intracardial peritumoral, or intratumoral.

36. The method of claim 31, wherein the treatment site is a site within a kidney, liver, pancreas, heart, lung, eye, ear, lymph node, breast, prostate, ovary, testicle, thyroid, spleen, central nervous system, skeletal muscle, bone, lymph vessel, artery, arteriole, capillary bed, blood vessel, vein, peripheral nervous system, digestive system, gastrointestinal tract, urinary bladder, gall bladder, adrenal gland, adipose tissue, parathyroid gland, uterus, fallopian tube, skin, tumorous growth, autologous graft, synthetic graft, or site of microbial infection.

37. The method of claim 31, wherein the diversion element is adjusted for a first time periods as to facilitate flow through the delivery conduit, and for a second time period so as to divert flow through a diversion element, wherein varying the length of the first and second time periods results in alteration in the amount of drug delivered to the treatment site.

38. The method of claim 31, wherein the flow regulator further comprises:

a diversion conduit comprising a diversion inlet, a diversion outlet, and a diversion lumen extending between the diversion inlet and diversion outlet, the diversion conduit lumen defining a diversion pathway;

wherein the diversion conduit is in fluid communication with the waste reservoir such that drug diverted by the diversion element flows into the diversion pathway defined by the diversion conduit and into the waste reservoir.