Drug delivery methods with tracer

• US 10,806,396 B2
• Filed: 01/26/2015
• Issued: 10/20/2020
• Est. Priority Date: 01/26/2015
• Status: Active Grant

• Current Assignee: Alcyone Therapeutics, Inc.
• Original Assignee: Alcyone Lifesciences, Inc.
• Inventors: Singh, Deep Arjun, Anand, PJ, Brady, Martin Lee
• Primary Examiner(s): Kish, James M
• Application Number:
  US14/604,826
• Publication Number:
  US 20160213312A1
• Time in Patent Office: 2,094 Days
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 6/032 Transmission computed tomography [CT]
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61M 2025/0004 having two or more concentrically arranged tubes for forming a concentric catheter system
• CPC Class Codes: A61M 2025/0008 having visible markings on its surface, i.e. visible to the naked eye, for any purpose, e.g. insertion depth markers, rotational markers or identification of type
• CPC Class Codes: A61M 2025/0042 Microcatheters, cannula or the like having outside diameters around 1 mm or less
• CPC Class Codes: A61M 2202/206 Viruses
• CPC Class Codes: A61M 2205/33 Controlling, regulating or measuring
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 25/001 Forming the tip of a catheter, e.g. bevelling process, join or taper
• CPC Class Codes: A61M 5/007 for contrast media
• CPC Class Codes: A61M 5/145 using pressurised reservoirs, e.g. pressurised by means of pistons
• CPC Class Codes: A61M 5/172 electrical or electronic A61M5/16804, A61M5/16831 take precedence

Abstract

Systems and methods for delivering a drug with a tracer or contrast agent are disclosed herein, as are systems and methods that generally involve CED devices with various features for reducing or preventing backflow. In some embodiments, CED devices include a tissue-receiving space disposed proximal to a distal fluid outlet. Tissue can be compressed into or pinched/pinned by the tissue-receiving space as the device is inserted into a target region of a patient, thereby forming a seal that reduces or prevents proximal backflow of fluid ejected from the outlet beyond the tissue-receiving space. In some embodiments, CED devices include a bullet-shaped nose proximal to a distal fluid outlet. The bullet-shaped nose forms a good seal with surrounding tissue and helps reduce or prevent backflow of infused fluid.

Claims

1. A method of administering a therapy to an anatomy or delivering a drug to a subject, comprising:

advancing a convection-enhanced delivery (CED) device having a first fluid lumen and a second fluid lumen into tissue to position an outlet port of the first fluid lumen and an outlet port of the second fluid lumen at a target site within the tissue;

delivering a tracer under positive pressure through the first fluid lumen and into the target tissue to produce a distribution of the tracer within the tissue; and

delivering a fluid containing the drug under positive pressure through the second fluid lumen and into the previously-delivered tracer such that the drug displaces the tracer radially outward to expand the distribution of the tracer; and

visualizing using an imaging technique the radially outward displacement of the tracer resulting from delivery of the fluid containing the drug into the distribution.

2. The method of claim 1, wherein the delivery of the fluid containing the drug and its distribution within and around the target site can be visualized during said delivery of the fluid containing the drug.

3. The method of claim 1, further comprising delivering the tracer through the first fluid lumen while delivering the fluid containing the drug through the second fluid lumen.

4. The method of claim 1, wherein displacing the tracer radially outward produces a hollow distribution of the tracer.

5. The method of claim 1, wherein the tracer comprises gadolinium.

6. The method of claim 1, wherein the drug comprises at least one of adenovirus and adeno-associated virus.

7. The method of claim 1, further comprising monitoring the distribution of the tracer using the imaging technique to determine the distribution of the drug.

8. The method of claim 7, wherein the imaging technique comprises at least one of magnetic resonance imaging (MRI), single-photon emission computerized tomography (SPECT), and positron emission tomography (PET).

9. The method of claim 1, wherein delivery of the tracer is stopped before delivery of the fluid containing the drug is started.

10. The method of claim 1, wherein delivery of the tracer is stopped throughout the delivery of the fluid containing the drug.

11. The method of claim 1, wherein delivering the fluid containing the drug comprises delivering a volume of the fluid that is at least 2 times greater than the volume of tracer that is delivered.

12. The method of claim 1, wherein delivering the fluid containing the drug comprises delivering a volume of the fluid that is at least 5 times greater than the volume of tracer that is delivered.

13. The method of claim 1, wherein delivering the fluid containing the drug comprises delivering a volume of the fluid that is at least 10 times greater than the volume of tracer that is delivered.

14. The method of claim 1, wherein the tracer and the fluid containing the drug are not mixed prior to delivery into the tissue.

15. The method of claim 1, wherein the tissue comprises brain tissue.

16. The method of claim 1, wherein the fluid containing the drug is delivered at a flow rate of at least about 5 μ

L/minute.

17. The method of claim 1, wherein the fluid containing the drug is delivered at a flow rate of at least about 15 μ

L/minute.

18. The method of claim 1, wherein the fluid containing the drug is delivered at a flow rate of at least about 50 μ

L/minute.

19. The method of claim 1, further comprising controlling delivery of the fluid containing the drug based on an output of a microsensor embedded in the CED device.

20. The method of claim 1, wherein the method is used to treat at least one condition selected from central-nervous-system (CNS) neoplasm, intractable epilepsy, Parkinson'"'"'s disease, Huntington'"'"'s disease, stroke, lysosomal storage disease, chronic brain injury, Alzheimer'"'"'s disease, amyotrophic lateral sclerosis, balance disorders, hearing disorders, tumors, glioblastoma multiforme (GBM), and cavernous malformations.

21. The method of claim 1, wherein the CED device comprises a micro-tip coupled to a distal end of a catheter and wherein the method further comprises:

inserting the catheter through an incision;

positioning the micro-tip in proximity to the target site using stereotactic targeting;

removing a stylet inserted through the catheter or a sheath disposed over the catheter;

tunneling a proximal end of the catheter beneath the scalp of the patient; and

coupling one or more proximal fluid connectors of the catheter to a fluid delivery system.

22. The method of claim 1, wherein the first fluid lumen is concentric with the second fluid lumen.

23. A method of administering a therapy to an anatomy or delivering a drug to a subject, comprising:

advancing a convection-enhanced delivery (CED) device having at least one fluid lumen into tissue to position an outlet port of the at least one fluid lumen at a target site within the tissue;

delivering a tracer under positive pressure through the at least one fluid lumen and into the target tissue; and

thereafter, delivering a fluid containing the drug under positive pressure through the at least one fluid lumen and into the previously-delivered tracer such that the drug displaces the tracer radially outward to expand the distribution of the tracer; and

visualizing using an imaging technique the radially outward displacement of the tracer resulting from delivery of the fluid containing the drug into the distribution.

24. The method of claim 23, wherein visualizing the radially outward displacement of the tracer occurs during delivery of the fluid containing the drug.

25. The method of claim 23, wherein delivering the tracer produces a cloud-shaped distribution of tracer within the tissue and delivering the drug displaces the tracer radially outward to expand the cloud-shaped distribution of the tracer.

26. The method of claim 23, wherein delivering the tracer produces a cloud-shaped distribution of tracer within the tissue and delivering the drug displaces the tracer radially outward to produce a hollow cloud-shaped distribution of the tracer.

27. The method of claim 23, wherein delivery of the tracer is stopped before delivery of the fluid containing the drug is started.

28. The method of claim 23, wherein delivery of the tracer is stopped throughout the delivery of the fluid containing the drug.

29. The method of claim 23, wherein delivering the fluid containing the drug comprises delivering a volume of the fluid that is at least 2 times greater than the volume of tracer that is delivered.

30. The method of claim 23, wherein the tracer and the fluid containing the drug are not mixed prior to delivery into the tissue.

31. The method of claim 23, wherein the fluid containing the drug is delivered at a flow rate of at least about 5 μ

L/minute.

32. The method of claim 23, wherein the CED device comprises a micro-tip coupled to a distal end of a catheter and wherein the method further comprises:

inserting the catheter through an incision;

positioning the micro-tip in proximity to the target site using stereotactic targeting;

removing a stylet inserted through the catheter or a sheath disposed over the catheter;

tunneling a proximal end of the catheter beneath the scalp of the patient; and

coupling one or more proximal fluid connectors of the catheter to a fluid delivery system.