Treatment of renal hypertension or carotid sinus syndrome with adventitial pharmaceutical sympathetic denervation or neuromodulation

• US 9,199,065 B2
• Filed: 03/18/2015
• Issued: 12/01/2015
• Est. Priority Date: 04/22/2009
• Status: Active Grant

• Current Assignee: Mercator MedSystems, Inc.
• Original Assignee: Mercator MedSystems, Inc.
• Inventors: Seward, Kirk Patrick
• Primary Examiner(s): Minnifield, Nita M
• Application Number:
  US14/661,320
• Publication Number:
  US 20150224289A1
• Time in Patent Office: 258 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61M 2025/009 the needle having a bent tip, i.e. the needle distal tip is angled in relation to the longitudinal axis of the catheter
• CPC Class Codes: A61M 25/00 Catheters; Hollow probes dilators A61M29/00; peritoneal catheters A61M1/285; tracheal tubes A61M16/04; for drainage A61M27/00; for uterus, vagina or rectum A61M31/00 ; for measuring or testing A61B; materials for catheters A61L29/00
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/1002 characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: A61M 5/007 for contrast media
• CPC Class Codes: A61M 5/44 having means for cooling or heating the devices or media
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

Sympathetic nerves run through the adventitia surrounding renal arteries and are critical in the modulation of systemic hypertension. Hyperactivity of these nerves can cause renal hypertension, a disease prevalent in 30-40% of the adult population. Hypertension can be treated with neuromodulating agents (such as angiotensin converting enzyme inhibitors, angiotensin II inhibitors, or aldosterone receptor blockers), but requires adherence to strict medication regimens and often does not reach target blood pressure threshold to reduce risk of major cardiovascular events. A minimally invasive solution is presented here to reduce the activity of the sympathetic nerves surrounding the renal artery by locally delivering neurotoxic or nerve-blocking agents into the adventitia. Extended elution of these agents may also be accomplished in order to tailor the therapy to the patient.

Claims

1. A device for the treatment of hypertension comprising:

an inflatable balloon that, when inflated, positions a needle within a vessel wall for the delivery of fluids outside and around the vessel wall;

an electrically resistive heating element positioned along the pathway of the injected fluid, wherein the heating element is connected to a proximal energy source and control circuitry; and

a thermosensor positioned distal to the resistive heating element, wherein the thermosensor is connected to a proximal energy source and is capable of feeding back a signal to the control circuitry for the purpose of controlling the temperature of the resistive heating element.

2. The device of claim 1, wherein the heating element heats the fluids.

3. The device of claim 1, wherein the thermosensor is configured to control a temperature of the fluids such that nerves within the vessel wall are heated from 42 C to 50 C.

4. The device of claim 1, wherein the thermosensor is configured to heat the fluids to a temperature of at least from 42 C to 50 C.

5. The device of claim 1, wherein the vessel is a blood vessel.

6. The device of claim 5, wherein the inflatable balloon and needle are configured to position the needle into tissue bound on the inside by the external elastic lamina of said blood vessel and bound on the outside by the outer extent of the adventitial and perivascular connective tissues that surround the blood vessel.

7. The device of claim 5, wherein the blood vessel is a vein or an artery.

8. The device of claim 5, wherein the blood vessel is a renal vein or a renal artery.

9. The device of claim 8, wherein the inflatable balloon and needle are configured to position the needle into tissue bound on the inside by the external elastic lamina of said renal artery or renal vein and bound on the outside by the outer extent of the adventitial and perivascular connective tissues that surround the renal artery or renal vein.

10. The device of claim 2, comprising a fluid source that comprises the fluids to be heated by the heating element upon contact therewith, thereby making the fluid therapeutically effective in treating hypertension.

11. The device of claim 10, wherein the fluids comprise a diagnostic agent.

12. The device of claim 10, comprising a source of a diagnostic agent.

13. The device of claim 12, wherein the diagnostic agent comprises a radio-opaque contrast medium.

14. A system for treating hypertension, said system comprising:

a catheter adapted to be introduced into a patient'"'"'s vasculature;

a needle adapted to be deployed from the catheter through a blood vessel wall into the adventitia surrounding the blood vessel; and

a source of a neuromodulating agent which can be delivered through the needle into the adventitia to lower the systemic blood pressure of the patient by a therapeutically beneficial amount.

15. The system of claim 14, wherein the needle is advanceable in a direction substantially normal to the blood vessel wall to a depth in the range from 300 μ

m to 3 mm.

16. The system of claim 14, wherein the catheter is configured to deliver an amount of the neuromodulating agent that is effective to lower systemic blood pressure by a therapeutically beneficial amount.

17. The system of claim 14, wherein the neuromodulating agent comprises a neurotoxin or neurotoxin fragment.

18. The system of claim 17, wherein the neurotoxin is a botulinum neurotoxin or fragment thereof.

19. The system of claim 18, wherein system is configured to deliver an amount of the neurotoxin, wherein the neurotoxin comprises active botulinum neurotoxin, and wherein the amount is between 10 picograms and 25 nanograms of active botulinum neurotoxin, between 50 picograms and 10 nanograms of active botulinum neurotoxin, or between 100 picograms and 2.5 nanograms of active botulinum neurotoxin.

20. The system of claim 14, wherein the source of neuromodulating agent is also a source of a diagnostic agent, wherein the neuromodulating agent is mixed with the diagnostic agent.

21. The system of claim 14, comprising a source of a diagnostic agent.

22. The system of claim 21, wherein the source of diagnostic agent is configured to allow delivery of the diagnostic agent into adventitial prior to the delivery of the neuromodulating agent.

23. The system of claim 21, wherein the diagnostic agent comprises a radio-opaque contrast medium.

24. The system of claim 14, wherein the blood vessel is an artery or a vein.

25. The system of claim 24, wherein the artery is a renal artery, or the vein is a renal vein.