# US 2016/0354522 A1 · Drug-eluting device for prophylaxis or treatment of a disease or pathology

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- Number: US 2016/0354522 A1
- Document ID: US20160354522A1
- Status: Published application
- Kind: A1
- Application number: 15/149,006
- Filed: 2016-05-06
- Published: 2016-12-08
- Earliest claimed: 2015-05-06
- Assignees: Fluid Biotech Inc.
- Applicants: Fluid Biotech Inc.
- Inventors: ALIM P. MITHA; JOHN H. WONG; PALLAVI BHAMBRI
- Web page: https://patentgrep.com/patent/US20160354522A1

## CPC

- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61L 31/022: {Metals or alloys}
- A61L 31/10: Macromolecular materials
- A61L 31/148: {Materials at least partially resorbable by the body}
- C08L 67/04: Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence)
- A61L 2300/604: Biodegradation
- A61L 2300/606: Coatings
- A61L 2300/608: having two or more layers
- 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)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The invention disclosed herein generally relates to particular intravascular drug-eluting delivery devices and methods for manufacture and use in either the prophylaxis or treatment of a disease or pathology. In one aspect, the intravascular device may comprise a verapamil eluting stent with polymeric coating designed for the controlled release of a vasodilating drug in the prophylactic or remedial treatment of cerebral vasospasm.

## Claims

### Claim 1

A drug eluting prosthesis for the controlled release of one or more drugs in the remedial or prophylactic treatment of a disease, the prosthesis comprising:
a prosthesis body having an inner surface and an outer surface;
at least one layer of biodegradable polymeric material bonded to at least one surface of the prosthesis body, the polymeric material being capable of absorbing and releasing the one or more drugs;
at least one drug dispersed within at least one layer of the polymeric material;
wherein the controlled release comprises control over initiation time for drug elution, control over duration time for drug elution, and control over quantity of drug being eluted.

### Claim 2 (depends on 1)

The prosthesis of claim 1, wherein the prosthesis is a drug eluting stent or scaffold having a lumen and capable of radial expansion, the prosthesis body formed from a material comprising metals, ceramics, polymers, or combinations thereof.

### Claim 3 (depends on 2)

The prosthesis of claim 2, wherein the material forming the prosthesis body is at least partially biodegradable.

### Claim 4 (depends on 3)

The prosthesis of claim 3, wherein the material comprises nitinol.

### Claim 5 (depends on 3)

The prosthesis of claim 3, wherein at least a first drug is contained within a polymeric base layer bonded to at least one surface of the prosthesis body.

### Claim 6 (depends on 5)

The prosthesis of claim 5, comprising a second polymeric layer that does not comprise a drug, the second polymeric layer built upon the base layer, and permitting the initiation of drug release from the base layer to be delayed.

### Claim 7 (depends on 5)

The prosthesis of claim 5, comprising a second polymeric layer that comprises at least one drug, the second polymeric layer built upon the base layer, and permitting the initiation of drug release from the second polymeric layer prior to drug release from the base layer.

### Claim 8 (depends on 6)

The prosthesis of claim 6, comprising a third polymeric layer that comprises at least one drug, the third polymeric layer built upon the second polymeric layer, the third polymeric layer permitting the initiation of drug release from the third layer prior to drug release from the base layer, the second polymeric layer permitting drug release from the base layer to be delayed.

### Claim 9 (depends on 1)

The prosthesis of claim 1, wherein the polymeric material is selected from the group consisting of polylactides (PLA), polyglycolides (PGA), polycaprolactone (PCL), polylactide-co-glycolides (PLGA), polyanhydrides, polyorthoesters, poly(N-(2-hydroxypropyl) methacrylamide), poly(l-aspartamide), including the derivatives DLPLA—poly(dl-lactide); LPLA—poly(l-lactide); PDO—poly(dioxanone); PGA-TMC—poly(glycolide-co-trimethylene carbonate); PGA-LPLA—poly(l-lactide-co-glycolide); PGA-DLPLA—poly(dl-lactide-co-glycolide); LPLA-DLPLA—poly(l-lactide-co-dl-lactide), PDO-PGA-TMC-poly(glycolide-co-trimethylene carbonate-co-dioxanone), and copolymers, derivatives, and combinations thereof.

### Claim 10 (depends on 9)

The prosthesis of claim 9, wherein the polymeric material comprises poly(lactic-co-glycolic acid) (“PLGA”).

### Claim 11 (depends on 1)

The prosthesis of claim 1, wherein the at least one drug is selected from the group consisting of an antibiotic agent, antiviral agent, analgesic, muscle relaxant, chemotherapeutic agent, intra-arterial vasodilating agent, calcium channel inhibitor, calcium channel antagonist, calcium channel blocker, transient receptor potential protein blocker, endothelin antagonist, and combinations thereof.

### Claim 12 (depends on 11)

The prosthesis of claim 11, wherein the at least one drug is selected from the group consisting of amlodipine, aranidipine, azelnidipine, bamidipine, benidipine, bepridil, cinaldipine, diltiazem, efonidipine, felodipine, gallopamil, isradipine, lacidipine, lamivudine (3TC), lemildipine, lercanidipine, milrinone, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, manidipine, pranidipine, papaverine, temozolamide, vancomycin, verapamil, and combinations thereof.

### Claim 13 (depends on 12)

The prosthesis of claim 12, wherein the at least one drug comprises verapamil.

### Claim 14

A verapamil eluting stent for the controlled delivery of verapamil in the prophylactic or remedial treatment of cerebral vasospasm, the stent comprising:
a stent body having a lumen with a diameter, an inner surface and an outer surface. at least one layer of biodegradable polymeric material bonded to at least one surface of the stent body;
verapamil dispersed within at least one layer of the polymeric material;
wherein the controlled delivery of verapamil comprises control over initiation time for verapamil elution, control over duration time for verapamil elution, and control over quantity of verapamil being eluted.

### Claim 15 (depends on 14)

The stent of claim 14 wherein at least one polymeric layer comprises polylactic-co-glycolic acid) (PLGA).

### Claim 16 (depends on 15)

The stent of claim 15, comprising a base layer coating of PLGA and verapamil, verapamil being present at a concentration of between about 50% and about 5% by weight of verapamil to PLGA.

### Claim 17 (depends on 15)

The stent of claim 15, wherein verapamil is present at a concentration of between about 35% and about 27% by weight of verapamil to PLGA, and wherein the controlled delivery of verapamil comprises an initial burst release phase followed by a sustained release phase.

### Claim 18 (depends on 16)

The stent of claim 16, wherein verapamil is present at a concentration of between about 22% and about 15% by weight of verapamil to PLGA, and wherein the controlled release of verapamil by the stent comprises an initial burst release phase followed by dampened sustained release phase.

### Claim 19 (depends on 16)

The stent of claim 16, comprising a second layer of PLGA that does not comprise a drug, the second PLGA layer built upon the base layer, and permitting the initiation of verapamil release to be delayed.

### Claim 20 (depends on 19)

The stent of claim 19, wherein verapamil is present at a concentration of about 30% by weight of verapamil to PLGA, and the delay prior to initial onset of verapamil release is about 48 hours.

### Claim 21 (depends on 19)

The stent of claim 19, wherein verapamil is present at a concentration of about 20% by weight of verapamil to PLGA, and the delay prior to the initial onset of verapamil release is about 72 hours.

### Claim 22

Use of a drug eluting prosthesis for the controlled release of one or more drugs in the remedial or prophylactic treatment of a disease, the prosthesis comprising a prosthesis body having an inner surface and an outer surface, at least one layer of polymeric material bonded to at least one surface of the prosthesis body, at least one drug dispersed within at least one layer of the polymeric material, wherein the controlled release comprises control over initiation time for drug elution, control over duration time for drug elution, and control over quantity of drug being eluted.

### Claim 23 (depends on 22)

Use of the prosthesis of claim 22, further comprising the steps of:
determining a typical drug requirement for the disease, determining a typical time course for the disease, and determining any typically delayed clinical manifestations for the disease;
implanting the prosthesis at a target location of a patient; and
contacting the prosthesis with one or more biological tissues or fluids in vivo to cause the at least one layer of polymeric material to degrade, controlling release of the drug into the patient;
wherein type and concentration of the drug corresponds to the typical drug requirement for the disease, and wherein drug release occurs substantially over the typical time course for the disease, and wherein any delay in the initial onset of drug release corresponds with any typical delayed clinical manifestations of the disease.

### Claim 24 (depends on 23)

Use of the prosthesis of claim 23, wherein the disease is selected from the group consisting of cancer, infections or cerebral vasospasm.

### Claim 25 (depends on 23)

The use of the drug eluting prosthesis of claim 23 wherein the at least one drug is selected from the group consisting of antibiotic agents, antiviral agents, analgesics, muscle relaxants, chemotherapeutic agents, intra-arterial vasodilating agents, calcium channel inhibitors, calcium channel antagonists, calcium channel blockers, transient receptor potential protein blockers, endothelin antagonists, and combinations thereof.

### Claim 26 (depends on 23)

The use of the prosthesis of claim 23, wherein the at least one layer of polymeric material comprises a base layer comprising at least a first drug contained within the polymeric material, and a second polymeric layer that does not comprise a drug built upon the base layer, comprising:
contacting the second polymeric layer with one or more biological tissues or fluids in vivo to cause the second polymeric layer to degrade prior to degradation of the base layer, causing an initial delay in the release of the drug from the base layer;
contacting the base layer with one or more biological tissues or fluids in vivo to cause the base layer to degrade after substantial degradation of the second layer, thereby releasing the drug into the patient.

### Claim 27

Use of a verapamil eluting prosthesis for the controlled delivery of verapamil in the prophylactic or remedial treatment of cerebral vasospasm, the prosthesis comprising a prosthesis body having an inner surface and an outer surface, at least one layer of biodegradable polymeric material bonded to at least one surface of the prosthesis body, verapamil dispersed within at least one layer of the polymeric material; wherein the controlled delivery of verapamil comprises control over initiation time for verapamil elution, control over duration time for verapamil elution, and control over quantity of verapamil being eluted.

### Claim 28 (depends on 27)

Use of the prosthesis of claim 27, wherein the prosthesis has a release profile comprising an immediate burst release and subsequent sustained release, an immediate sustained release, or a sustained release after a delay in the initial onset of release.

### Claim 29 (depends on 28)

Use of the prosthesis of claim 28, further comprising selecting a desired release profile for the verapamil, the release profiles comprising an immediate burst release and subsequent sustained release, an immediate sustained release, or a sustained release after a delay in the initial onset of release;
placing the prosthesis proximal to blood vessels in spasm, the prosthesis release profile corresponding with the desired release profile for the verapamil;
contacting the at least one layer of polymeric material with one or more biological tissues or fluids in vivo to cause degradation of the polymeric material, thereby releasing verapamil into the patient in accordance with the release profile.

### Claim 30 (depends on 29)

Use of the prosthesis of claim 29, wherein the release of verapamil comprises a time period of up to about twenty-one days from the initial onset of verapamil release.

### Claim 31 (depends on 29)

Use of the prosthesis of claim 29, wherein the release of verapamil substantially plateaus after about thirteen days from the initial onset of verapamil release.

### Claim 32 (depends on 29)

Use of the prosthesis of claim 29, wherein the at least one polymeric layer comprises a base layer coating of PLGA and verapamil, wherein the verapamil present at a concentration of between about 35% and about 27% by weight of verapamil to PLGA, and wherein the delivery of verapamil comprises an initial burst release phase followed by a sustained release phase.

### Claim 33 (depends on 29)

Use of the prosthesis of claim 29, wherein the at least one polymeric layer comprises a base layer coating of PLGA and verapamil, wherein the verapamil is present at a concentration of between about 22% and about 15% by weight of verapamil to PLGA, and wherein the delivery of verapamil comprises an initial burst release phase and followed by an dampened sustained release phase.

### Claim 34 (depends on 29)

The use of the verapamil eluting prosthesis of claim 29 wherein the at least one polymeric layer comprises a base layer coating of PLGA and verapamil present at a concentration of about 30% by weight of verapamil to PLGA, and a second layer of PLGA that does not comprise a drug, the second PLGA layer built upon the base layer, wherein the delay prior to initial onset of verapamil release is about 48 hours.

### Claim 35 (depends on 29)

The use of the verapamil eluting prosthesis of claim 29 wherein the at least one polymeric layer comprises a base layer coating of PLGA and verapamil present at a concentration of about 20% by weight of verapamil to PLGA, and a second layer of PLGA that does not comprise a drug, the second PLGA layer built upon the base layer, wherein the delay prior to initial onset of verapamil release is about 72 hours.

### Claim 36 (depends on 1)

A method for manufacturing the drug eluting prosthesis of claim 1, comprising
preparing a solution comprising a polymeric material, a drug and a solvent;
coating at least a portion of a surface of the prosthesis body, wherein the coating method is selected from the group consisting of dip coating, spin coating, electrospinning, and spray coating.

### Claim 37 (depends on 36)

The method of claim 36, wherein the coating method comprises electrospinning.