Drug delivery systems and methods

• US 9,682,193 B2
• Filed: 05/11/2016
• Issued: 06/20/2017
• Est. Priority Date: 05/11/2015
• Status: Active Grant

• Current Assignee: Alcyone Therapeutics, Inc.
• Original Assignee: Alcyone Lifesciences, Inc.
• Inventors: Brophy, Morgan, Anand, PJ, Eberl, Greg, Singh, Deep Arjun
• Primary Examiner(s): BERDICHEVSKY, AARTI
• Application Number:
  US15/151,585
• Publication Number:
  US 20160331897A1
• Time in Patent Office: 405 Days
• CPC Class Codes: A61M 2202/0464 Cerebrospinal fluid
• CPC Class Codes: A61M 2210/0687 Skull, cranium
• CPC Class Codes: A61M 2210/1003 Spinal column
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

Drug delivery systems and methods are disclosed herein. In some embodiments, a drug delivery system can be configured to deliver a drug to a patient in coordination with a physiological parameter of the patient (e.g., the patient'"'"'s natural cerebrospinal fluid (CSF) pulsation or the patient'"'"'s heart or respiration rate). In some embodiments, a drug delivery system can be configured to use a combination of infusion and aspiration to control delivery of a drug to a patient. Catheters, controllers, and other components for use in the above systems are also disclosed, as are various methods of using such systems.

Claims

1. A method of delivering a drug to a patient, comprising:

inserting a catheter or needle into an intrathecal space of the patient;

measuring or estimating a natural intrathecal pulsation of the patient using a sensor; and

with a controller, controlling a pump to coordinate infusion of a drug through the catheter or needle with the measured or estimated natural intrathecal pulsation to override the natural intrathecal pulsation and move the drug cranially within the intrathecal space.

2. The method of claim 1, further comprising synchronizing infusion frequency with a frequency of the patient'"'"'s natural intrathecal pulsation as measured by the sensor.

3. The method of claim 1, further comprising synchronizing infusion phase with a phase of the patient'"'"'s natural intrathecal pulsation as measured by the sensor.

4. The method of claim 1, further comprising establishing a sinusoidal approximation of the patient'"'"'s natural intrathecal pulsation as measured by the sensor and synchronizing infusions with an ascending wave of the sinusoidal approximation.

5. The method of claim 1, further comprising establishing a sinusoidal approximation of the patient'"'"'s natural intrathecal pulsation as measured by the sensor and synchronizing infusions with a descending wave of the sinusoidal approximation.

6. The method of claim 1, wherein the sensor is configured to measure intrathecal pressure.

7. The method of claim 1, wherein the catheter or needle comprises first and second fluid lumens, and wherein the method includes controlling the pump to alternately aspirate fluid through the first fluid lumen and infuse fluid through the second fluid lumen in coordination with the patient'"'"'s natural intrathecal pulsation as measured by the sensor.

8. The method of claim 1, wherein the sensor is configured to measure at least one of heart rate, intrathecal pressure, intrathecal pulsation rate, respiration rate, lung capacity, chest expansion, chest contraction, intrathoracic pressure, and intraabdominal pressure.

9. The method of claim 1, wherein catheter or needle is inserted such that it extends along the spinal cord of the patient with at least a portion of the catheter or needle being disposed in the cervical region of the patient'"'"'s spine and at least a portion of the catheter or needle being disposed in the lumbar region of the patient'"'"'s spine.

10. The method of claim 1, further comprising delivering a plurality of different drugs through the catheter or needle, each of the drugs being delivered through a respective fluid lumen of the catheter or needle.

11. The method of claim 1, further comprising, with the controller, controlling the pump to aspirate fluid through the catheter or needle.

12. The method of claim 1, wherein the catheter or needle includes a plurality of outlet ports spaced in a cranial-caudal direction along the length of the catheter or needle and wherein the method includes infusing a drug through a first port of the catheter or needle and aspirating fluid through a second port of the delivery device, the second port being cranial to the first port.

13. The method of claim 1, wherein the drug is infused through a port of the catheter or needle disposed in the cervical region of the patient'"'"'s spine to propel the infused drug into the cranial space.

14. The method of claim 1, wherein the catheter or needle is inserted through a percutaneous lumbar puncture in the patient.

15. The method of claim 1, wherein the infusion comprises alternating between infusing a first volume of the drug and aspirating a second volume of the drug, the second volume being less than the first volume.

16. The method of claim 1, wherein the drug is delivered to a target region, the target region being at least one of an intrathecal space of the patient, a subpial region of the patient, a cerebellum of the patient, a dentate nucleus of the patient, a dorsal root ganglion of the patient, and a motor neuron of the patient.

17. The method of claim 1, wherein the drug includes at least one of an antisense oligonucleotide, a stereopure nucleic acid, a virus, adeno-associated virus (AAV), non-viral gene therapy, vexosomes, and liposomes.

18. The method of claim 1, wherein the method includes at least one of performing gene therapy by delivering the drug, performing gene editing by delivering the drug, performing gene switching by delivering the drug, and performing non-viral gene therapy by delivering the drug.

19. The method of claim 1, further comprising determining a total CSF volume of the patient and tailoring the infusion based on the total CSF volume.

20. The method of claim 1, wherein the sensor comprises a first sensor configured to measure intrathecal pressure and a second sensor configured to measure heart rate.

21. The method of claim 20, further comprising:

establishing a correlation between heart rate and intrathecal pressure based on the output of the first and second sensors when no infusion is performed; and

coordinating infusion of the drug through the catheter or needle with the intrathecal pulsation of the patient based on the output of the second sensor.

22. A method of delivering a drug to a patient, comprising:

inserting a catheter or needle into an intrathecal space of the patient;

measuring a physiological parameter of the patient using a sensor; and

with a controller, controlling a pump to coordinate delivery of a drug through the catheter or needle with the physiological parameter measured by the sensor, wherein said delivery comprises;

aspirating a volume of CSF from the patient;

infusing a drug through a first, proximal port of the catheter or needle while aspirating CSF through a second, distal port of the catheter or needle to form a bolus of drug between the first and second ports; and

infusing the previously-extracted CSF at a location proximal to the bolus to urge the bolus in a distal direction.

23. The method of claim 22, wherein the volume of CSF aspirated from the patient comprises about 10% by volume of the patient'"'"'s total CSF.

24. The method of claim 22, wherein the physiological parameter comprises a natural intrathecal pulsation of the patient.