US6179817B1 — Hybrid coating for medical devices

Claim 1

Independent Claim 107 words

A coating composition for rendering substrates bio-compatible and delivering therapeutic agents in vivo comprising: i. an aqueous dispersion or emulsion of an organic acid functional group-containing polymer and an excess of a polyfunctional crosslinker which is reactive with said organic acid functional groups of said polymer; ii. a therapeutic agent dispersed within said aqueous dispersion or emulsion, said therapeutic agent being substantially non-reactive with said polymer or said crosslinker; and iii. an aqueous solution or dispersion of an organic acid functional group-containing bio-active agent or equivalent thereof, said polymer covalently bonded to said organic acid functional groups on said bio-active agent through said unreacted excess polyfunctional crosslinker.

Claim 2

Dependent Claim 107 words

A coating composition for rendering substrates bio-compatible and delivering therapeutic agents in vivo comprising: i. an aqueous dispersion or emulsion of an organic acid functional group-containing polymer and an excess of a polyfunctional crosslinker which is reactive with said organic acid functional groups of said polymer; ii. a therapeutic agent dispersed within said aqueous dispersion or emulsion, said therapeutic agent being substantially non-reactive with said polymer or said crosslinker; and iii. an aqueous solution or dispersion of an organic acid functional group-containing bio-active agent or equivalent thereof, said polymer covalently bonded to said organic acid functional groups on said bio-active agent through said unreacted excess polyfunctional crosslinker.

Claim 3

Dependent Claim 32 words

The coating composition of claim 1 , wherein said organic acid functional groups are selected from the group consisting of free carboxylic acid, free sulfonic acid, free phosphoric acid, and combinations thereof.

Claim 4

Dependent Claim 20 words

The coating composition of claim 1 , wherein said polyfunctional crosslinking agent has more than two functional groups per molecule.

Claim 5

Dependent Claim 21 words

The coating composition of claim 1 , wherein said polymer is one of an organic acid functional group-containing homo- and copolymer.

Claim 6

Dependent Claim 28 words

The coating composition of claim 1 , wherein said polymer is selected from the group consisting of polyurethanes, polyacrylates, poly(meth)acrylates, polyisocrotonates, epoxy resins, (meth)acrylate-urethane copolymers and combinations thereof.

Claim 7

Dependent Claim 14 words

The coating composition of claim 1 , wherein said polymer is a (meth)acrylate-urethane copolymer.

Claim 8

Dependent Claim 13 words

The coating composition of claim 1 , wherein said polymer is a polyurethane.

Claim 9

Dependent Claim 28 words

The coating composition of claim 1 , wherein said bio-active agent is selected from the group consisting of anti-thrombogenic agents, antibiotic agents, anti-inflammatory agents, equivalents and mixtures thereof.

Claim 10

Dependent Claim 44 words

The coating composition of claim 1 , wherein said therapeutic agent is selected from the group consisting of anti-tumor agents, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, angiostatin agents, endostatin agents, cell cycle regulatory agents, genetic agents, growth hormones, equivalents and mixtures thereof.

Claim 11

Dependent Claim 18 words

The coating composition of claim 1 , wherein said bio-active agent is an organic acid functional group-containing polysaccharide.

Claim 12

Dependent Claim 13 words

The coating composition of claim 10 , wherein said polysaccharide is a glycosaminoglycan.

Claim 13

Dependent Claim 35 words

The coating composition of claim 11 , wherein said glycosaminoglycan is selected from the group consisting of heparin, hirudin, heparin sulfate, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratin sulfate, prostoctein, reopro, integrin and equivalents thereof.

Claim 14

Dependent Claim 27 words

The coating composition of claim 1 wherein said bio-active agent is heparin or a chemically modified equivalent thereof and said therapeutic agent is paclitaxel or equivalent thereof.

Claim 15

Dependent Claim 24 words

The coating composition of claim 1 , wherein the concentration of said polymer is from about 1% to about 60% by weight solids content.

Claim 16

Dependent Claim 24 words

The coating composition of claim 1 , wherein the concentration of said polymer is from about 1% to about 40% by weight solids content.

Claim 17

Dependent Claim 31 words

The coating composition of claim 1 , wherein the concentration of said polyfunctional crosslinker in i. is from about 0.2% to about 40% by weight solids content of said first coating.

Claim 18

Dependent Claim 28 words

The coating composition of claim 1 , wherein said polymer is covalently bonded to said bio-active agent via said polyfunctional crosslinker at a temperature below about 120° C.

Claim 19

Dependent Claim 32 words

The coating composition of claim 1 , wherein said polymer is covalently bonded to said bio-active agent via said polyfunctional crosslinker at a temperature between about 10° C. and about 70° C.

Claim 20

Dependent Claim 12 words

An implantable device coated with a composition according to claim 1 .

Claim 21

Dependent Claim 143 words

A medical device having a coating on at least a portion of a surface thereof, said coating comprising: i. a first layer formed from (a) an aqueous dispersion or emulsion of an organic acid functional group-containing polymer, (b) an excess of a polyfunctional crosslinker which is reactive with said organic acid groups and (c) a therapeutic agent dispersed within said aqueous dispersion or emulsion, wherein said therapeutic agent is substantially non-reactive with (a) or (b); and ii. a second coating of an aqueous solution or dispersion containing an organic acid functional group-containing bio-active agent or equivalent thereof, said first coating covalently bonded to said second coating through said excess crosslinker and said organic acid functional groups on said bio-active coating, wherein said therapeutic agent is releasable from said first coating and said bio-active agent substantially remains on a surface of said medical device.

Claim 22

Dependent Claim 143 words

A medical device having a coating on at least a portion of a surface thereof, said coating comprising: i. a first layer formed from (a) an aqueous dispersion or emulsion of an organic acid functional group-containing polymer, (b) an excess of a polyfunctional crosslinker which is reactive with said organic acid groups and (c) a therapeutic agent dispersed within said aqueous dispersion or emulsion, wherein said therapeutic agent is substantially non-reactive with (a) or (b); and ii. a second coating of an aqueous solution or dispersion containing an organic acid functional group-containing bio-active agent or equivalent thereof, said first coating covalently bonded to said second coating through said excess crosslinker and said organic acid functional groups on said bio-active coating, wherein said therapeutic agent is releasable from said first coating and said bio-active agent substantially remains on a surface of said medical device.

Claim 23

Dependent Claim 24 words

The medical device of claim 20 , wherein said surface is selected from the group consisting of polymeric compositions, non-polymeric compositions and combinations thereof.

Claim 24

Dependent Claim 46 words

The medical device of claim 20 , wherein said surface is selected from the group of consisting of olefin polymers, polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, polyvinyl acetate, polystyrene, poly(ethylene terephthalate), polyurethane, polyurea, silicone rubbers, polyamides, polycarbonates, polyaldehydes, natural rubbers, polyether-ester copolymers, styrene-butadiene copolymers and combinations thereof.

Claim 25

Dependent Claim 23 words

The medical device of claim 20 , wherein said surface is selected from the group consisting of ceramics, metals, glasses and combinations thereof.

Claim 26

Dependent Claim 13 words

The medical device of claim 20 , wherein said device is an endoprosthesis.

Claim 27

Dependent Claim 22 words

The medical device of claim 24 , wherein said endoprosthesis is selected from the group consisting of grafts, stents and graft-stent devices.

Claim 28

Dependent Claim 23 words

The medical device of claim 24 , wherein said endoprosthesis is selected from the group consisting of catheters, guidewires, trocars and introducer sheaths.

Claim 29

Dependent Claim 28 words

The medical device of claim 20 , wherein said bio-active agent is selected from the group consisting of anti-thrombogenic agents, antibiotic agents, anti-inflammatory agents, equivalents and mixtures thereof.

Claim 30

Dependent Claim 44 words

The medical device of claim 20 , wherein said therapeutic agent is selected from the group consisting of anti-tumor agents, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, angiostatin agents, endostatin agents, cell cycle regulatory agents, genetic agents, growth hormones, equivalents and mixtures thereof.

Claim 31

Dependent Claim 28 words

The medical device of claim 20 , wherein said bio-active agent is heparin or a chemically modified equivalent thereof and said therapeutic agent is paclitaxel or equivalent thereof.

Claim 32

Dependent Claim 95 words

A multi-layer coating composition for rendering substrates bio-compatible and delivering therapeutic agents in vivo comprising a reaction product of: i. a first layer comprising an aqueous polymer dispersion or emulsion, a crosslinker and a therapeutic agent physically dispersed within said dispersion or emulsion, wherein said therapeutic agent is releasable from said first layer and is substantially non-reactive with said polymer or said crosslinker; and ii. a second layer comprising an aqueous solution or dispersion containing a bio-active agent, wherein said polymer of said first layer is covalently bonded to said bio-active agent through said crosslinker.

Claim 33

Dependent Claim 95 words

A multi-layer coating composition for rendering substrates bio-compatible and delivering therapeutic agents in vivo comprising a reaction product of: i. a first layer comprising an aqueous polymer dispersion or emulsion, a crosslinker and a therapeutic agent physically dispersed within said dispersion or emulsion, wherein said therapeutic agent is releasable from said first layer and is substantially non-reactive with said polymer or said crosslinker; and ii. a second layer comprising an aqueous solution or dispersion containing a bio-active agent, wherein said polymer of said first layer is covalently bonded to said bio-active agent through said crosslinker.

Claim 34

Dependent Claim 18 words

The coating composition of claim 30 , wherein said polymer and bio-active agent contain organic acid functional groups.

Claim 35

Dependent Claim 31 words

The coating composition of claim 30 , wherein said crosslinker is a polyfunctional crosslinker which is reactive with said organic acid functional groups of said polymer but not said therapeutic agent.

Claim 36

Dependent Claim 25 words

The coating composition of claim 30 , wherein said therapeutic agent is paclitaxel or equivalent thereof and said bio-active agent is heparin or equivalent thereof.

Claim 37

Dependent Claim 46 words

An implantable medical device having at least a portion of said device coated with said coating according to claim 30 , wherein said bio-active agent remains permanently attached to a surface of said medical device while said therapeutic agent is controllably releasable from said first layer.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2004-01-30	2004-07-31	2005-01-30	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2008-01-30	2008-07-31	2009-01-30	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2012-01-30	2012-07-31	2013-01-30	$7700.00	Window Closed / Lapsed

Hybrid coating for medical devices

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