THERAPY FOR KIDNEY DISEASE AND/OR HEART FAILURE BY INTRADERMAL INFUSION

• US 20150080844A1
• Filed: 03/15/2013
• Published: 03/19/2015
• Est. Priority Date: 04/02/2012
• Status: Abandoned Application

• Current Assignee: Capricor Therapeutics, Inc.
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Donovan, Maura, van Antwerp, William J. L., Wieneke, Chad A., Kaytor, Mike, Grovender, Eric
• Application Number:
  US14/390,227
• Publication Number:
  US 20150080844A1
• Time in Patent Office: Days
• US Class Current: 604/505
• CPC Class Codes: A61K 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/3334 Measuring or controlling the flow rate
• CPC Class Codes: A61M 2205/3344 Measuring or controlling pressure at the body treatment site
• CPC Class Codes: A61M 2205/3355 Controlling downstream pump pressure
• CPC Class Codes: A61M 2205/3561 local, e.g. within room or hospital
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/3592 using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2205/52 with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2209/01 Remote controllers for specific apparatus
• CPC Class Codes: A61M 2210/04 Skin
• CPC Class Codes: A61M 2210/1082 Kidney
• CPC Class Codes: A61M 2210/125 Heart
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/16854 by monitoring line pressure

Abstract

Intradermal delivery devices, systems and methods thereof for the administration of a natriuretic or chimeric peptide are described. The described delivery devices, systems and methods provide for the treatment of pathological conditions such as kidney disease alone, heart failure alone, concomitant kidney disease and heart failure, or cardiorenal syndrome by delivery of a natriuretic or chimeric peptide through a microneedle array using a delivery pump. The described delivery devices, systems and methods can provide for greater availability of a natriuretic or chimeric peptide and improved pharmacokinetics.

Claims

1. An intradermal delivery device, comprising:

a drug provisioning component having a pumping apparatus to administer a therapeutically effective amount of a therapeutic composition from a reservoir;

a microneedle array having a substrate with plural microneedles projecting from a surface of the substrate, the microneedles in fluid communication with the reservoir and an intra-substrate space;

a catheter for transporting the composition from the reservoir to the intra-substrate space;

a first pressure sensor for sensing a pressure within the catheter; and

a controller for controlling a pumping rate of the pump and for monitoring a pressure within the catheter to determine if flow through the microneedle array is within an expected range.

2. The device of claim 1, further comprising a second pressure sensor for sensing a pressure within the intra-substrate space, wherein the controller monitors a pressure difference between the first pressure sensor and the second pressure sensor and determines if the flow rate between individual microneedles of the microneedle array is substantially equal.

3. The device of claim 1, wherein the therapeutic composition comprises one or more natriuretic peptides selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and vessel dilator (VD).

4. The device of claim 1, wherein the therapeutic composition comprises one or more chimeric natriuretic peptides selected from any one of CD-NP (SEQ ID No. 9), CU-NP (SEQ ID No. 10), DNP (SEQ ID No. 8), and CNP (SEQ ID No. 7).

5. The device of claim 3, wherein the composition has a concentration of the natriuretic peptide from 0.5 to 10 mg/mL.

6. The device of claim 1, wherein the drug provisioning component administers the composition at a rate from 1 to 100 μ

L/min.

7. The device of claim 1, wherein a distal end of the catheter for attachment to the intra-substrate space is divided into plural attachment members, the plural attachments attached to separate ports on the microneedle array

8. The device of claim 1, wherein the intra-substrate space is divided into one or more compartments.

9. The device of claim 1, wherein one or more intra-substrate space members are disposed within the intra-substrate space to reduce the volume of the intra-substrate space.

10. The device of claim 3, wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide at a rate (ng/kg of body weight) from any one of 0.5 to 10 μ

g/min, from 1 to 10 μ

g/min or from 1 to 5 μ

g/min.

11. The device of claim 3, wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide to maintain a plasma level of the natriuretic peptide at a steady state concentration from 0.5 to 200 pmol/L.

12. The device of claim 3, wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide to maintain a plasma level of the natriuretic peptide at a steady state concentration or maximum plasma concentration in the range represented by n to (n+i) pmol/L, where n={xε

Z|0<

x≦

200} and i={ yε

Z|0≦

y≦

(200−

n)}.

13. The device of claim 3, wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide to maintain a plasma level of the natriuretic peptide at a steady state concentration or maximum plasma concentration from any one of 10 to 150 pmol/L, 5 to 100 pmol/L, from 10 to 75 pmol/L, from 5 to 55 pmol/L, from 10 to 60 pmol/L, from 5 to 40 pmol/L or from 5 to 50 pmol/L, from more than 0 to 55 pmol/L, from 0.5 to 55 pmol/L, from 2 to 55 pmol/L or from 5 to 55 pmol/L.

14. The device of claim 1, wherein the microneedles have a length selected from any of 300 to 1500 μ

m, from 500 to 900 μ

m, from 200 to 1200 μ

m, from 300 to 1000 μ

m, from 400 to 900 μ

m, from 600 to 800 μ

m and from 700 to 900 μ

m.

15. The device of claim 3, wherein the drug provisioning component delivers a composition comprising the natriuretic peptide at a rate selected from any of 1 to 200 μ

L/min, 5 to 150 μ

L/min, 3 to 100 μ

L/min, from 1 to 50 μ

L/min, from 1 to 75 μ

L/min, from 1 to 20 μ

L/min, from 1 to 15 μ

L/min and from 1 to 10 μ

L/min.

16. The device of claim 1, wherein the drug provisioning component delivers the therapeutic composition at a fixed, pulsed, continuous or variable rate.

17. The device of claim 1, wherein the drug provisioning component delivers an intermittent bolus of the therapeutic composition.

18. A method, comprising the steps of:

administering a therapeutic composition by intradermal administration to a patient suffering from kidney disease alone, heart failure, concomitant kidney disease and heart failure, or cardiorenal syndrome using a drug provisioning component, and

maintaining a plasma concentration of the composition within a specified range, wherein the bioavailability of the natriuretic peptide is increased or the half-life of absorption of the composition is decreased as compared to the composition delivered by subcutaneous administration.

19. The method of claim 18, wherein the drug provisioning component has a pumping apparatus to administer an amount of the composition from a reservoir, the drug provisioning component in fluid communication with a microneedle array having a substrate with plural microneedles projecting from a surface of the substrate, the microneedles in fluid communication with the reservoir and an intra-substrate space;

transporting the composition from the reservoir to the intra-substrate space with a catheter;

sensing a first pressure within the catheter using a first pressure sensor; and

monitoring a pressure within the catheter to determine if flow through the microneedle array is within an expected range.

20. The method of claim 19, further comprising sensing a second pressure within the intra-substrate space using a second pressure sensor and monitoring a difference between the first pressure and the second pressure and determining if the flow rate between individual microneedles of the microneedle array is substantially equal.

21. The method of claim 18, wherein the composition is a natriuretic peptide selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and vessel dilator (VD).

22. The method of claim 18, wherein the composition comprises one or more chimeric natriuretic peptides selected from any one of CD-NP (SEQ ID No. 9), CU-NP (SEQ ID No. 10), DNP (SEQ ID No. 8), and CNP (SEQ ID No. 7).

23. The method of claim 18, wherein the drug provisioning component is capable of delivering the natriuretic peptide at a fixed, pulsed, continuous or variable rate.

24. The method of claim 18, further comprising the step of collecting data and transmitting the data via radio frequency to an external controller.

25. The method of claim 18, further comprising the step of collecting and transmitting data and returning digital instructions to a control unit via the Internet.

26. The method of claim 18, wherein the drug provisioning component and a control unit are connected or controlled wirelessly.

27. The method of claim 19, wherein the microneedles have a length selected from any of from 300 to 1500 μ

m, from 500 to 900 μ

m, from 200 to 1200 μ

m, from 300 to 1000 μ

m, from 400 to 900 μ

m, from 600 to 800 μ

m and from 700 to 900 μ

m.

28. The method of claim 18, wherein the drug provisioning component delivers a composition comprising the composition at a rate selected from any of 1 to 200 μ

L/min, 5 to 150 μ

L/min, 3 to 100 μ

L/min, from 1 to 50 μ

L/min, from 1 to 75 μ

L/min, from 1 to 20 μ

L/min, from 1 to 15 μ

L/min and from 1 to 10 μ

L/min.

29. The method of claim 18, wherein the composition comprises brain natriuretic peptide (BNP).