Methods and systems for inhibiting vascular inflammation

• US 10,441,747 B2
• Filed: 01/26/2015
• Issued: 10/15/2019
• Est. Priority Date: 01/22/2002
• Status: Expired due to Term

• Current Assignee: Mercator MedSystems, Inc.
• Original Assignee: Mercator MedSystems, Inc.
• Inventors: Seward, Kirk Patrick
• Primary Examiner(s): Patel, Shefali D
• Application Number:
  US14/605,865
• Publication Number:
  US 20150141959A1
• Time in Patent Office: 1,723 Days
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/4833 Assessment of subject's compliance to treatment
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2005/1588 having means for monitoring, controlling or visual inspection, e.g. for patency check, avoiding extravasation
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/0087 Multiple injection needles protruding laterally from the distal tip
• CPC Class Codes: A61M 2025/0092 Single injection needle protruding laterally from the distal tip
• CPC Class Codes: A61M 2025/0093 wherein at least one needle is a microneedle
• CPC Class Codes: A61M 2025/0096 being laterally outward extensions or tools, e.g. hooks or fibres
• CPC Class Codes: A61M 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 2210/12 Blood circulatory system
• CPC Class Codes: A61M 25/0043 characterised by structural features
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/10 : Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 37/0015 : by using microneedles
• CPC Class Codes: A61M 5/158 : Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body

Abstract

Methods and kits for delivering pharmaceutical agents to an adventitia and other regions outside an external elastic lamina (EEL) surrounding a blood vessel utilize a catheter having a needle. The needle is positioned in up to 5 mm beyond the EEL and delivers an amount of a pharmaceutical agent sufficient to circumferentially permeate around the blood vessel and, in many cases, extend longitudinally and radially along the blood vessel. Confirmation that a delivery aperture of the needle lies beyond the EEL may be required before delivering the pharmaceutical agent. In one example, catheters are used to deliver dexamethasone and other anti-inflammatory agents to a peripheral vasculature and other vasculature to treat peripheral vascular disease and other conditions.

Claims

1. A method for inhibiting inflammation in a patient'"'"'s vasculature, said method comprising:

positioning a catheter within a lumen of a blood vessel of the patient, the blood vessel having had a revascularization procedure performed thereon;

advancing a needle radially outwardly from the catheter through a wall of the blood vessel and into an adventitial tissue surrounding the blood vessel; and

delivering an anti-inflammatory agent into the adventitial tissue and a perivascular tissue through the needle advanced into the adventitial tissue in an amount sufficient to inhibit inflammation of the blood vessel after the revascularization procedure, wherein the anti-inflammatory agent consists essentially of dexamethasone or dexamethasone phosphate,

wherein the inhibition or a reduction of inflammation is characterized by a detectable lack of a significant increase or a detectable reduction, respectively, in monocyte chemotractive protein-1 (MCP-1) levels in circulating blood.

2. The method of claim 1, wherein the patient is at risk of or suffering from peripheral artery disease.

3. The method of claim 2, wherein the blood vessel is an artery selected from the group consisting of iliac arteries, femoral arteries, and popliteal arteries.

4. The method of claim 1, wherein the anti-inflammatory agent is delivered at a dosage of 3.2 mg to 24 mg.

5. The method of claim 1, wherein the anti-inflammatory agent is delivered at a dosage of 0.5 to 2.7 mg per cm of lesion.

6. The method of claim 1, wherein the anti-inflammatory agent is delivered at a dosage of 2.4 mg to 8.0 mg per infusion.

7. The method of claim 1, wherein the delivered anti-inflammatory agent distributes completely circumferentially through the adventitial tissue surrounding the blood vessel at a delivery site.

8. The method of claim 1, wherein the anti-inflammatory agent is delivered right after revascularization.

9. The method of claim 1, further comprising delivering a contrast agent for visualization through the needle advanced into the adventitial tissue.

10. The method of claim 9, wherein the anti-inflammatory agent is delivered with the contrast agent at a primary therapeutic agent to contrast agent ratio of 4:

1.

11. The method of claim 1, wherein the anti-inflammatory agent is incorporated into a lipophilic carrier or adjuvant.

12. The method of claim 1, wherein the anti-inflammatory agent is delivered with saline.

13. The method of claim 1, wherein the anti-inflammatory agent is incorporated into liposomes.

14. The method of claim 1, wherein the anti-inflammatory agent is delivered with an erodable polymer.

15. The method of claim 1, wherein the anti-inflammatory agent is delivered with a solubilizer.

16. The method of claim 1, wherein the anti-inflammatory agent is provided as microparticles or nanoparticles.

17. The method of claim 1, wherein the method further comprises withdrawing the needle from the adventitial tissue and withdrawing the catheter out of the blood vessel of the patient after delivering the anti-inflammatory agent.

18. A method for inhibiting inflammation in a patient'"'"'s vasculature, said method comprising:

positioning a catheter within a lumen of a blood vessel of the patient, the blood vessel having had a revascularization procedure performed thereon;

advancing a needle radially outwardly from the catheter through a wall of the blood vessel and into an adventitial tissue surrounding the blood vessel; and

delivering an anti-inflammatory agent into the adventitial tissue and a perivascular tissue through the advanced needle in an amount sufficient to inhibit inflammation of the blood vessel after the revascularization procedure, wherein the anti-inflammatory agent comprises dexamethasone or dexamethasone phosphate, and wherein the dexamethasone or the dexamethasone phosphate is delivered into the adventitial tissue and the perivascular tissue at a dosage of 0.5 to 2.7 mg per cm of lesion,

wherein the inhibition or a reduction of inflammation is characterized by a detectable lack of a significant increase or a detectable reduction, respectively, in monocyte chemotractive protein-1 (MCP-1) levels in circulating blood.

19. The method of claim 18, wherein the patient is at risk of or suffering from peripheral artery disease.

20. The method of claim 19, wherein the blood vessel is an artery selected from the group consisting of iliac arteries, femoral arteries, and popliteal arteries.

21. The method of claim 18, wherein the anti-inflammatory agent is delivered at a dosage of 3.2 mg to 24 mg.

22. The method of claim 18, wherein the anti-inflammatory agent is delivered at a dosage of 2.4 mg to 8.0 mg per infusion.

23. The method of claim 18, wherein the delivered anti-inflammatory agent distributes completely circumferentially through the adventitial tissue surrounding the blood vessel at a delivery site.

24. The method of claim 21, wherein the anti-inflammatory agent is delivered right after revascularization.

25. The method of claim 18, further comprising delivering a contrast agent for visualization through the needle advanced into the adventitial tissue.

26. The method of claim 25, wherein the anti-inflammatory agent is delivered with the contrast agent at a primary therapeutic agent to contrast ratio of 4:

1.

27. The method of claim 18, wherein the anti-inflammatory agent is incorporated into a lipophilic carrier or adjuvant.

28. The method of claim 18, wherein the anti-inflammatory agent is delivered with saline.

29. The method of claim 18, wherein the anti-inflammatory agent is incorporated into liposomes.

30. The method of claim 18, wherein the anti-inflammatory agent is delivered with an erodable polymer.

31. The method of claim 18, wherein the anti-inflammatory agent is delivered with a solubilizer.

32. The method of claim 18, wherein the anti-inflammatory agent is provided as microparticles or nanoparticles.

33. The method of claim 18, wherein the method further comprises withdrawing the needle from the adventitial tissue and withdrawing the catheter out of the blood vessel of patient after delivering the anti-inflammatory agent.