Drug delivery systems and methods

• US 10,406,285 B2
• Filed: 05/25/2017
• Issued: 09/10/2019
• Est. Priority Date: 05/11/2015
• Status: Active Grant

• Current Assignee: Alcyone Therapeutics, Inc.
• Original Assignee: Alcyone Lifesciences, Inc.
• Inventors: Anand, PJ, Brophy, Morgan, Singh, Deep Arjun, Eberl, Greg
• Primary Examiner(s): Mehta, Bhisma
• Assistant Examiner(s): Engel, Matthew A
• Application Number:
  US15/605,449
• Publication Number:
  US 20170258996A1
• Time in Patent Office: 838 Days
• CPC Class Codes: A61M 2202/0464 Cerebrospinal fluid
• 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 delivery device into an intrathecal space of the patient;

measuring a respiration rate of the patient;

infusing a drug through the delivery device and into the intrathecal space, wherein the drug is infused in a pulsatile manner in coordination with or to override a natural cerebrospinal fluid (CSF) pulsation based on the respiration rate of the patient to urge the drug towards a target side within the patient; and

after infusing the drug, infusing a fluid out of the drug delivery device into the intrathecal space of the patient proximal to the drug such that infusion of the fluid moves the drug distally towards the target site within the patient.

2. The method of claim 1, wherein the infusion of the fluid overrides the natural CSF pulsation of the patient to urge the drug towards the target site.

3. The method of claim 1, wherein the infusion of the fluid coordinates with the natural CSF pulsation of the patient to urge the drug towards the target site.

4. The method of claim 1, wherein the fluid comprises at least one of a drug, a buffer solution, and CSF aspirated from the patient through the delivery device.

5. The method of claim 1, wherein at least one of the infusion of the drug and the infusion of the fluid is coordinated with a physiological parameter of the patient.

6. The method of claim 5, wherein the physiological parameter is at least one of heart rate, intrathecal pressure, intrathecal pulsation rate, respiration rate, lung capacity, chest expansion, chest contraction, intrathoracic pressure, and intraabdominal pressure.

7. The method of claim 1, further comprising aspirating a volume of CSF from the patient, wherein the infused fluid comprises the aspirated CSF.

8. The method of claim 1, wherein the target site is 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.

9. The method of claim 1, wherein the target site is a neuronal structure of the patient.

10. 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.

11. 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.

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

13. The method of claim 1, further comprising measuring a physiological parameter of the patient using a sensor and, with a controller, controlling a pump to coordinate infusion of the fluid through the delivery device with the physiological parameter measured by the sensor.

14. The method of claim 13, further comprising synchronizing infusion frequency with a frequency of the patient'"'"'s natural intrathecal pulsation as measured by the sensor.

15. The method of claim 13, further comprising synchronizing infusion phase with a phase of the patient'"'"'s natural intrathecal pulsation as measured by the sensor.

16. The method of claim 13, 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.

17. The method of claim 13, 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.

18. The method of claim 13, wherein the sensor is configured to measure intrathecal pressure.

19. The method of claim 13, wherein the sensor comprises a first sensor configured to measure intrathecal pressure and a second sensor configured to measure heart rate.

20. The method of claim 13, wherein the delivery device comprises a catheter including a plurality of lumens, the sensor comprises a pressure sensor, and one of the plurality of lumens comprises a lumen for the pressure sensor.

21. The method of claim 1, wherein the delivery device is inserted through a percutaneous lumbar puncture in the patient.

22. The method of claim 1, wherein the delivery device comprises a catheter and wherein inserting the delivery device comprises positioning a first port of the catheter in a lumbar region of the patient'"'"'s spine and positioning a second port of the catheter in a cervical region of the patient'"'"'s spine.

23. The method of claim 1, wherein the delivery device comprises a catheter including a lumen having an opening at a distal end with a tapered, nozzle configuration to direct the drug distally towards the target site within the patient.

24. The method of claim 1, further comprising extracting a volume of CSF from the patient using the delivery device;

and wherein infusing the fluid into the intrathecal space of the patient comprises infusing the previously-extracted CSF proximal to the drug until a predetermined CSF pressure reached.

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

inserting a delivery device into an intrathecal space of the patient;

measuring a respiration rate of the patient;

infusing a drug through the delivery device and into the intrathecal space, wherein the drug is infused in a pulsatile manner in coordination with or to override a natural cerebrospinal fluid (CSF) pulsation based on the respiration rate of the patient to urge the drug towards a target site within the patient, the pulsatile manner created by infusing a first volume of the drug into the patient and withdrawing a second, smaller volume of the drug in a repeated process until a desired dose of the drug is delivered; and

after infusing the drug, infusing a fluid out of the drug delivery device behind the drug such that infusion of the fluid enhances distribution of the drug or moves the drug towards the target site within the patient;

wherein the drug and the fluid are infused as part of an infusion profile, and wherein a total volume of the fluid infused in the infusion profile is greater than a total volume of the drug infused in the infusion profile.