# US 10,441,747 B2 · Methods and systems for inhibiting vascular inflammation

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- Number: US 10,441,747 B2
- Document ID: US10441747B2
- Status: Granted
- Kind: B2
- Application number: 14/605,865
- Filed: 2015-01-26
- Published: 2015-05-21
- Granted: 2019-10-15
- Earliest claimed: 2002-01-22
- Assignees: Mercator MedSystems, Inc.
- Applicants: Mercator MedSystems, Inc.
- Inventors: Kirk Patrick Seward
- Web page: https://patentgrep.com/patent/US10441747B2

## CPC

- A61M 25/0084: {being one or more injection needles}
- A61B 5/01: Measuring temperature of body parts {; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue} (clinical contact thermometers G01K13/20)
- A61B 5/021: Measuring pressure in heart or blood vessels
- A61B 5/053: Measuring electrical impedance or conductance of a portion of the body
- A61B 5/14539: {for measuring pH}
- A61B 5/4833: {Assessment of subject's compliance to treatment}
- A61L 29/16: Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2300/41: Anti-inflammatory agents, e.g. NSAIDs
- A61L 2300/43: Hormones, e.g. dexamethasone
- A61M 5/158: Needles {for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body}
- A61M 25/0043: {characterised by structural features}
- 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})
- A61M 37/0015: {by using microneedles}
- A61M 2005/1588: {having means for monitoring, controlling or visual inspection, e.g. for patency check or for avoiding extravasation}
- A61M 2025/0057: {Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings}
- A61M 2025/0087: {Multiple injection needles protruding laterally from the distal tip}
- A61M 2025/0092: {Single injection needle protruding laterally from the distal tip}
- A61M 2025/0093: {wherein at least one needle is a microneedle}
- A61M 2025/0096: {being laterally outward extensions or tools, e.g. hooks or fibres}
- A61M 2025/1086: {having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves}
- A61M 2210/12: Blood circulatory system
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)

## 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

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 2)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 9)

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.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 1)

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

### Claim 16 (depends on 1)

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

### Claim 17 (depends on 1)

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.

### Claim 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.

### Claim 19 (depends on 18)

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

### Claim 20 (depends on 19)

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.

### Claim 21 (depends on 18)

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

### Claim 22 (depends on 18)

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.

### Claim 23 (depends on 18)

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.

### Claim 24 (depends on 21)

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

### Claim 25 (depends on 18)

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

### Claim 26 (depends on 25)

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.

### Claim 27 (depends on 18)

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

### Claim 28 (depends on 18)

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

### Claim 29 (depends on 18)

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

### Claim 30 (depends on 18)

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

### Claim 31 (depends on 18)

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

### Claim 32 (depends on 18)

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

### Claim 33 (depends on 18)

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.