Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin

Patent metadata

Field	Value
Publication number	US-11679075-B2
Application number	US-202016911070-A
Country	US
Kind code	B2
Filing date	Jun 24, 2020
Priority date	Sep 18, 2013
Publication date	Jun 20, 2023
Grant date	Jun 20, 2023

Abstract

There is disclosed a method for administration of a formulation of resiniferatoxin (RTX) to provide cardiac sympathetic afferent denervation when applied in an amount and concentration sufficient to chemically denervate vanilloid 1 receptor (TRPV1)-expressing CSAR (cardiac sympathetic afferent reflex) afferents. There is further disclosed a method for treating heart failure or hypertension and its related indications selected from the group consisting of increased sympatho-excitation, cardiac hypertrophy, increased left ventricular end diastolic pressure (LVEDP), lung edema, and combinations thereof, comprising administering an effective amount of RTX directly to a tissue site selected from the group consisting of epicardium, a T1-T4 dorsal root ganglion and intrathecally to the T1-T4 region of the spinal column.

First claim

We claim:

1. A method for administering a formulation comprising resiniferatoxin (RTX) to a patient, the method comprising administering the formulation via catheter-based administration into the coronary artery circulation or pericardiocentesis, wherein the patient has or is at risk of having one or more of: heart failure, cardiac inflammation, or cardiac fibrosis, which are induced by myocardial infarction.

2. The method of claim 1 , wherein the formulation is administered as a single dose.

3. The method of claim 1 , wherein the formulation is administered over a length of time from about 1 minute to about 5 minutes.

4. The method of claim 1 , wherein the formulation is delivered as one or more boluses.

5. The method of claim 1 , wherein the concentration of RTX in the formulation is about 100 ng/ml to about 500 μg/ml.

6. The method of claim 1 , wherein the concentration of RTX in the formulation is about 5 μg/ml to about 80 μg/ml.

7. The method of claim 1 , wherein the concentration of RTX in the formulation is about 20 μg/ml to about 60 μg/ml.

8. The method of claim 1 , wherein the patient is an adult human patient.

9. A method for reducing cardiac inflammation induced by myocardial infarction in a patient, comprising administering a formulation comprising resiniferatoxin (RTX) via catheter-based administration into the coronary artery circulation or pericardiocentesis.

10. The method of claim 9 , wherein the concentration of RTX in the formulation is about 100 ng/ml to about 500 μg/ml.

11. The method of claim 9 , wherein the concentration of RTX in the formulation is about 5 μg/ml to about 80 μg/ml.

12. The method of claim 9 , wherein the concentration of RTX in the formulation is about 20 μg/ml to about 60 μg/ml.

13. A method for treating heart failure induced by myocardial infarction or a myocardial infarction-related condition in a patient, comprising administering a formulation comprising resiniferatoxin (RTX) via catheter-based administration into the coronary artery circulation or pericardiocentesis; wherein the related condition is increased sympatho-excitation, cardiac hypertrophy, increased left ventricular end diastolic pressure (LVEDP), lung edema, or a combination thereof.

14. The method of claim 13 , wherein the concentration of RTX in the formulation is about 100 ng/ml to about 500 μg/ml.

15. The method of claim 13 , wherein the concentration of RTX in the formulation is about 5 μg/ml to about 80 μg/ml.

16. The method of claim 13 , wherein the concentration of RTX in the formulation is about 20 μg/ml to about 60 μg/ml.

17. The method of claim 1 , wherein a cardiac sympathetic afferent reflex (CSAR) is attenuated for a period of at least one week after the administration.

18. The method of claim 17 , wherein the CSAR is attenuated for a period of four weeks after the administration.

19. The method of claim 9 , wherein a cardiac sympathetic afferent reflex (CSAR) is attenuated for a period of at least one week after the administration.

20. The method of claim 19 , wherein the CSAR is attenuated for a period of four weeks after the administration.

21. The method of claim 13 , wherein a cardiac sympathetic afferent reflex (CSAR) is attenuated for a period of at least one week after the administration.

22. The method of claim 21 , wherein the CSAR is attenuated for a period of four weeks after the administration.

Assignees

• Univ Nebraska

Inventors

• Zucker Irving H
• Wang Hanjun

Classifications

• A61K9/0085

  Brain, e.g. brain implants; Spinal cord · CPC title

• A61K31/357

  having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title