Drug delivery system making use of a hydrogel polymer coating

Claim 3

The method of claim 1 further comprising introducing said catheter to an artery.

Claim 4

The method of claim 1 or 2 wherein said expandable portion is adapted for application of heat to said polymer material to control the rate of administration.

Claim 5

The method of claim 1 or 2 wherein said expandable portion includes a stent, placeable in said lumen by expansion thereof.

Claim 6

The method of claim 6 including a binding of said drug and said hydrogel polymer in a coating upon said stent for slow time release of drug remaining in said hydrogel polymer on said stent after compression of said hydrogel polymer by said expansion.

Claim 7

The method of claim 4 wherein said stent is balloon-expandable stent and said expandable portion is a stent positioned about said balloon.

Claim 8

The method of claim 6 wherein said stent and balloon both include said swellable hydrogel polymer coating incorporating said drug.

Claim 9

The method of claim 1 further comprising positioning said expandable portion at a point of occlusion in said vascular lumen and expanding said expandable portion at pressures sufficient to simultaneously dilate said vessel and deliver said drug by compression of said hydrogel polymer coating.

Claim 10

The method of claim 8 wherein said expandable portion is a dilatation balloon expandable to pressures in the range of about 1 to 20 atmospheres.

Claim 11

The method of claim 9 further comprising delivering about 20% or more of said drug during said compression.

Claim 12

The method of claim 10 wherein said drug is delivered in about ten minutes or less and the expandable portion is thereafter deflated.

Claim 13

The method of claim 11 wherein said hydrogel polymer is selected from the group consisting of polycarboxylic acids, cellulosic polymers, gelatin polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, and polyethylene oxides.

Claim 14

The method of claim 12 wherein said hydrogel polymer is polyacrylic acid.

Claim 17

A vascular catheter for rapidly delivering drug into tissue or occlusive formation at a desired location of the wall of a vascular lumen, effective to reduce blood clotting problems or proliferation of smooth muscle cells that may impede blood flow, comprising: a catheter constructed for insertion into a vascular lumen having a catheter shaft and an expandable portion mounted on said catheter shaft, said expandable portion being expandable in response to controlled inflation pressure to fill the cross-section of the vascular lumen and engage the tissue or occlusive formation of said vascular lumen, at least a part of the exterior surface of the expandable portion being defined by a coating of a tenaciously adhered swellable hydrogel polymer, and incorporated within said hydrogel polymer, a preselected aqueous-mobile drug to be delivered to said tissue or occlusive formation, said drug selected from the groups of drugs that reduce vascular lumen occlusion problems caused by blood clots or tissue cell proliferation, said hydrogel polymer selected to cause the coating to reach a characteristic swollen state of a thickness a number of times thicker than the thickness of the coating in its dry state as a result of absorption of aqueous fluid, and, when in said swollen state, said coating having characteristic compressibility, in response t compressive pressure within said expandable portion elevated above said inflation pressure, to squeeze the coating against said tissue or occlusive formation sufficiently to immediately, substantially, reduce the coating thickness, and force a substantial portion of said aqueous-mobile drug into said tissue or occlusive formation, thereby to enable rapid administration of a desired dose of said drug into said tissue or occlusive formation.

Claim 18

A vascular catheter for rapidly delivering drug into tissue or occlusive formation at a desired location of the wall of a vascular lumen, effective to reduce blood clotting problems or proliferation of smooth muscle cells that may impede blood flow, comprising: a catheter constructed for insertion into a vascular lumen having a catheter shaft and an expandable portion mounted on said catheter shaft, said expandable portion being expandable in response to controlled inflation pressure to fill the cross-section of the vascular lumen and engage the tissue or occlusive formation of said vascular lumen, at least a part of the exterior surface of the expandable portion being defined by a coating of a tenaciously adhered swellable hydrogel polymer, and incorporated within said hydrogel polymer, a preselected aqueous-mobile drug to be delivered to said tissue or occlusive formation, said drug selected from the groups of drugs that reduce vascular lumen occlusion problems caused by blood clots or tissue cell proliferation, said hydrogel polymer selected to cause the coating to reach a characteristic swollen state of a thickness a number of times thicker than the thickness of the coating in its dry state as a result of absorption of aqueous fluid, and, when in said swollen state, said coating having characteristic compressibility, in response t compressive pressure within said expandable portion elevated above said inflation pressure, to squeeze the coating against said tissue or occlusive formation sufficiently to immediately, substantially, reduce the coating thickness, and force a substantial portion of said aqueous-mobile drug into said tissue or occlusive formation, thereby to enable rapid administration of a desired dose of said drug into said tissue or occlusive formation.

Claim 19

The catheter of claim 16 wherein said catheter is a dilatation catheter sized, constructed and arranged for insertion in a stenosed vascular lumen, and said expandable portion is an inflatable dilatation balloon adapted for brief inflation at pressures in the range for effecting widening of said stenosed vascular lumen, said elevated compressive pressure being in a range effective to simultaneously cause, with said compression of said hydrogel a administration of said drug, widening of said vascular lumen.

Claim 20

The catheter of claims 17 or 16 wherein said hydrogel polymer is selected from the group consisting of polycarboxylic acids, cellulosic polymers, gelatin, polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, and polyethylene oxides.

Claim 21

The catheter of claim 18 wherein said hydrogel polymer is polyacrylic acid.

Claim 22

The catheter of claim 17 or 16 wherein said drug is an anti-thrombogenic drug selected from the group consisting of heparin, PPACK, enoxaprin, aspirin and hirudin.

Claim 23

The catheter of claim 17 or 16 wherein said drug is an anti-proliferative drug selected from the group consisting of monoclonal antibodies, capable of blocking smooth muscle cell proliferation, heparin, angiopeptin and enoxaprin.

Claim 24

The catheter of claim 17 or 16 wherein said expandable portion is adapted for application of heat to said polymer material to control the rate of administration.

Claim 25

The catheter of claim 17 or 16 wherein said catheter further comprises a member, extending over said expandable portion to inhibit release of said drug into body fluids during placement of said catheter.

Claim 26

The catheter of claim 23 wherein said member is a retractable sheath.

Claim 27

The catheter of claim 17 or 16 wherein said expandable portion is constructed to withstand sufficient inflation pressure that application of said pressure to rapidly administer said drug simultaneously facilitates delivery of said drug into and through cracks in plaque formed by balloon angioplasty to reach smooth muscle tissue.

Claim 28

The catheter of claim 17 wherein said pressure 2 is in the pressure range of about 1 to 20 atmospheres.

Claim 29

The catheter of claim 17 or 26 wherein said hydrogel polymer is effective to release about 20% or more of said drug during inflation in said pressure range.

Claim 30

The catether of claims 17 or 26 wherein said expandable portion is constructed to withstand sufficient inflation pressure that application of said pressure to rapidly administer said drug simultaneously facilitates delivery of said drug into tissue or occlusive formation that lies deeper than the surface portion of the tissue or occlusive formation directly engaged by said expandable portion

Claim 31

The catheter of claim 28 wherein the response characteristic of said hydrogel to said compressive pressure is effective to deliver said dose of said drug over a duration of about 10 minutes or less.

Claim 32

The catheter of claim 28 wherein said hydrogel polymer coating is about 10 to 50 microns thick in the swelled, uncompressed state.

Claim 33

The catheter of claim 28 wherein said expandable portion includes a stent, placeable in said body lumen by expansion thereof.

Claim 34

The catheter of claim 28 wherein the hydrogel releases about 50% of the drug upon compression.

Claim 35

The catheter of claim 28 wherein the drug is precipitated into the hydrogel.

Claim 36

The catheter of claim 17 wherein said catheter is constructed as a perfusion catheter having an expandable balloon.

Claim 37

The catheter of any one of claims 16 wherein said expandable portion is constructed to withstand sufficient inflation pressure that application of said pressure to rapidly administer said drug simultaneously facilitates delivery of said drug into tissue or occlusive formation that lies deeper than the surface portion of the tissue or occlusive formation directly engaged by said expandable portion.

Claim 38

The catheter of claim 16 or 35 wherein said expandable portion includes a stent, placeable in said body lumen by expansion thereof.

Claim 39

The catheter of claim 36 including a binding of said drug and hydrogel polymer in a coating upon said stent for slow time release of drug remaining in said hydrogel polymer on said stent after said compression of said hydrogel polymer by said expansion.

Claim 40

The catheter of claim 37 wherein said hydrogel polymer coating on said stent is a polyacrylic acid including an ammonium anion, said drug is heparin and said binding is an electrostatic binding.

Claim 41

The catheter of claim 36 wherein said stent is a balloon-expandable stent and said expandable portion is a stent positioned about said balloon.

Claim 42

The catheter of claim 39 wherein said stent and balloon both include said swellable hydrogel coating incorporating said drug.

Claim 43

The catheter of claim 39 wherein said drug is an anti-thrombogenic drug selected from the group consisting of heparin, PPacK enoxaprin aspirin and hirudin.

Claim 44

The catheter of claim 39 wherein said drug is an anti-proliferative drug selected from the group consisting of monoclonal antibodies, capable of blocking smooth muscle cell proliferation, heparin, angiopeptin and enoxaprin.

Claim 45

The catheter of any one of claims 2, 16 or 35 wherein the response characteristic of said hydrogel to said compressive pressure is effective to deliver said dose of said drug over a duration of about 10 minutes or less.

Claim 46

The catheter of any one of claims 17, 16 or 35 wherein said hydrogel polymer coating is about 10 to 50 microns thick in the swelled, uncompressed state.

Claim 47

A vascular balloon catheter for rapidly delivering a dose of a preselected aqueous-mobile drug into tissue or occlusive formation at a desired location of the wall of a vascular lumen, comprising: a catheter constructed for insertion into a vascular lumen having a catheter shaft and an expandable dilatation balloon mounted on said catheter shaft, said expandable balloon being expandable by an expansion controller to press against said tissue or occlusive formation at a compressive pressure in the range of about 1 to 20 atmospheres, said compressive pressure being elevated above the inflation pressure needed to fill the cross-section of the vascular lumen and engage the tissue or occlusive formation of said vascular lumen, at least a portion of the exterior surface of the expandable balloon being defined by a coating of a tenaciously adhered swellable hydrogel polymer having said dose of said aqueous-mobile drug incorporated therein, said hydrogel polymer selected to cause the coating to reach a characteristic swollen state of a thickness a number of times thicker than the thickness of the coating in its dry state as a result of absorption of aqueous fluid, and, when in said swollen state, said coating having characteristic compressibility, in response to said compressive pressure within said expandable balloon elevated above said inflation pressure, to squeeze the coating against said tissue or occlusive formation sufficiently to immediately, substantially, reduce the coating thickness, and force a substantial portion of said dose of said aqueous-mobile drug into said tissue or occlusive formation, said hydrogel polymer coating further characterized by having the capacity to incorporate a predetermined substantial amount of aqueous fluid and said drug and by being swellable by a factor of about 6 or more from a dried state to have a thickness in the range of about 10 to 50 microns in the swelled state, whereby rapid site specific release of a desired dose of about 20% or more of said aqueous-mobile drug from said hydrogel polymer coating is achieved during a brief interval of compression of said hydrogel polymer coating against the wall of the lumen when said expandable balloon is expanded in said pressure range.

Claim 48

A vascular balloon catheter for rapidly delivering a dose of a preselected aqueous-mobile drug into tissue or occlusive formation at a desired location of the wall of a vascular lumen, comprising: a catheter constructed for insertion into a vascular lumen having a catheter shaft and an expandable dilatation balloon mounted on said catheter shaft, said expandable balloon being expandable by an expansion controller to press against said tissue or occlusive formation at a compressive pressure in the range of about 1 to 20 atmospheres, said compressive pressure being elevated above the inflation pressure needed to fill the cross-section of the vascular lumen and engage the tissue or occlusive formation of said vascular lumen, at least a portion of the exterior surface of the expandable balloon being defined by a coating of a tenaciously adhered swellable hydrogel polymer having said dose of said aqueous-mobile drug incorporated therein, said hydrogel polymer selected to cause the coating to reach a characteristic swollen state of a thickness a number of times thicker than the thickness of the coating in its dry state as a result of absorption of aqueous fluid, and, when in said swollen state, said coating having characteristic compressibility, in response to said compressive pressure within said expandable balloon elevated above said inflation pressure, to squeeze the coating against said tissue or occlusive formation sufficiently to immediately, substantially, reduce the coating thickness, and force a substantial portion of said dose of said aqueous-mobile drug into said tissue or occlusive formation, said hydrogel polymer coating further characterized by having the capacity to incorporate a predetermined substantial amount of aqueous fluid and said drug and by being swellable by a factor of about 6 or more from a dried state to have a thickness in the range of about 10 to 50 microns in the swelled state, whereby rapid site specific release of a desired dose of about 20% or more of said aqueous-mobile drug from said hydrogel polymer coating is achieved during a brief interval of compression of said hydrogel polymer coating against the wall of the lumen when said expandable balloon is expanded in said pressure range.

Claim 49

The catheter of claim 45 wherein said hydrogel polymer is selected from the group consisting of polycarboxylic acids, cellulosic polymers, gelatin, polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, and polyethylene oxides.

Claim 50

The catheter of claim 45 wherein said hydrogel polymer is polyacrylic acid.

Claim 51

The catheter of claim 39 wherein said catheter further comprises a sheath member, extendable over said balloon to inhibit release of said drug into body fluids during placement of said catheter.

Claim 52

The catheter of claim 45 wherein said drug is an anti-thrombogenic drug selected from the group consisting of heparin, Pebac, enoxaprin, aspirin and hirudin.

Claim 53

The catheter of claim 45 wherein the drug is an anti-proliferative drug selected from the group consisting of monoclonal antibodies, capable of blocking smooth muscle cell proliferation, heparin, angiopeptin and enoxaprin.

Claim 54

The catheter of any one of claims 45, 16 or 35 or the method of claim 1 wherein the hydrogel releases about 50% of the drug upon compression.

Claim 55

The catheter or method of claim 51 wherein the polymer is polyacrylic acid.

Claim 56

The catheter of method of claim 52 wherein the drug is heparin.

Claim 57

The catheter or method of claim 50 wherein the hydrogel includes up to about 20-30 mg of aqueous drug solution.

Claim 58

The catheter of any one of claims 45, 16 or 35 or the method of claim 1 wherein the drug is precipitated into the hydrogel.