Barriers for polymeric coatings

• US 20040111144A1
• Filed: 12/06/2002
• Published: 06/10/2004
• Est. Priority Date: 12/06/2002
• Status: Abandoned Application

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Boucha-Rayle, Michelle C., Lawin, Laurie R., Kloke, Timothy M.
• Application Number:
  US10/313,234
• Publication Number:
  US 20040111144A1
• Time in Patent Office: Days
• US Class Current: 623/1.11
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A barrier adapted to be positioned between a first surface provided in the form of a polymeric, bioactive agent-containing coating upon a medical device, and a second surface provided by another material positioned in apposition, and preferably moveable apposition, to the first surface. The barrier, as provided by block copolymers or photoderivatized polymers, provides protection to the polymeric composition from mechanical damage and/or delamination during fabrication, storage, delivery or deployment, and/or residence of the device within the body. A combination that includes a medical device, such as a stent, and another device, such as a surrounding sheath or internal expandable balloon, between which is positioned a barrier of the type described.

Claims

1. A barrier adapted to be positioned between a first surface provided in the form of a polymeric, bioactive agent-containing coating upon a medical device, and a second surface provided by another material positioned in apposition, and preferably moveable apposition, to the first surface, the barrier being selected from the group consisting of block copolymers and polymers bearing latent reactive groups.

2. A barrier according to claim 1 wherein the polymeric, bioactive agent-containing coating comprises a plurality of polymers.

3. A barrier according to claim 1 wherein the block copolymers are selected from ethylene oxide/propylene oxide block copolymers.

4. A barrier according to claim 1 wherein the polymers bearing latent reactive groups are selected from natural polymers selected from photoderivatized polysaccharides and polypeptides, and synthetic polymers selected from photoderivatized polyolefins, vinyl chloride polymers, fluorine-containing polymers, poly(vinyl acetates), poly(vinyl alcohols), poly(vinyl acetals), polyacrylates and polymethacrylates, styrene polymers and copolymers, vinyl thermoplastics, polyamides and polyimides, polyacetals, polycarbonates, thermoplastics containing p-phenylene groups, polyesters, polyurethanes, polyisocyanurates, and silicones.

5. A barrier according to claim 4 wherein the photoderivatized polymer is selected from photoderivatized polysaccharides, photoderivatized polyamides, and photoderivatized vinyl thermoplastics.

6. A barrier according to claim 5 wherein the photoderivatized polysaccharides are selected from photohyaluronic acid and photoheparin.

7. A barrier according to claim 5 wherein the photoderivatized polyamides comprise photoderivatized polyacrylamide copolymers, and the photoderivatized vinyl thermoplastics comprise photopolyvinylpyrrolidone.

8. A barrier according to claim 1 wherein the medical device comprises an implantable medical device.

9. A barrier according to claim 8 wherein the medical device is selected from the group consisting of vascular devices, orthopedic devices, dental devices, drug delivery devices, ophthalmic devices, urological devices, and synthetic prostheses, and the second surface is provided by another contacting portion of the same device or as a different material contained within or surrounding the device.

10. A barrier according to claim 9 wherein the medical device comprises a balloon-expandable stent, and the second surface is provided by an expandable balloon contained within the stent.

11. A barrier according to claim 1 wherein the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition.

12. A barrier according to claim 11 wherein the bioactive agent within the polymeric coatings is present at a concentration of at least 30% based on the weight of the coated composition.

13. A barrier according to claim 12 wherein the bioactive agent within the polymeric coatings is present at a concentration of at least 40% based on the weight of the coated composition.

14. A barrier according to claim 1 wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

15. A barrier according to claim 2 wherein the plurality of polymers comprises a first polymer selected from the group consisting of polyalkyl(meth)acrylate, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate).

16. A barrier according to claim 15 wherein the polyalkyl(meth)acrylates comprise poly(n-butyl methacrylate) and the polyaryl(meth)acrylates are selected from poly-9-anthracenylmethacrylate, polychlorophenylacrylate, polymethacryloxy-2-hydroxybenzophenone, polymethacryloxybenzotriazole, polynaphthylacrylate, polynaphthylmethacrylate, poly-4-nitrophenylacrylate, polypentachloro(bromo, fluoro)acrylate and methacrylate, polyphenylacrylate and methacrylate, the polyaralkyl(meth)acrylates are selected from polybenzylacrylate and methacrylate, poly-2-phenethylacrylate and methacrylate, poly-1-pyrenylmethylmethacrylate, and the polyaryloxyalkyl(meth)acrylates are selected from polyphenoxyethylacrylate and methacrylate, polyethyleneglycolphenylether acrylates and methacrylates with varying polyethyleneglycol molecular weights.

17. A barrier according to claim 1 wherein:

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers,

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups are selected from photoderivatized polysaccharides and photoderivatized polyolefins, vinyl chloride polymers, fluorine-containing polymers, poly(vinyl acetates), poly(vinyl alcohols), poly(vinyl acetals), polyacrylates and polymethacrylates, styrene polymers and copolymers, vinyl thermoplastics, polyamides and polyimides, polyacetals, polycarbonates, thermoplastics containing p-phenylene groups, polyesters, polyurethanes, polyisocyanurates, and silicones,

d) the medical device comprises an implantable medical device,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition, and

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

18. A barrier according to claim 17 wherein:

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylate, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate),

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups are selected from photoderivatized heparin, photoderivatized polyamides and photoderivatized vinyl thermoplastics,

d) the medical device is selected from the group consisting of vascular devices, orthopedic devices, dental devices, drug delivery devices, ophthalmic devices, urological devices, and synthetic prostheses,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition, and

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

19. A barrier according to claim 1 wherein:

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate),

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups comprise a photoderivatized heparin, polyacrylamide, or polyvinylpyrrolidone,

d) the medical device comprises an implantable medical device selected from the group consisting of vascular devices, orthopedic devices, dental devices, drug delivery devices, ophthalmic devices, urological devices, and synthetic prostheses, and the second surface is provided by another contacting portion of the same device or as a different material contained within or surrounding the device,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition,

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

20. A barrier according to claim 1, wherein:

a) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

b) the polymers bearing latent reactive groups are selected from photoderivatized polysaccharides, polyolefins, vinyl chloride polymers, fluorine-containing polymers, poly(vinyl acetates), poly(vinyl alcohols), poly(vinyl acetals), polyacrylates and polymethacrylates, styrene polymers and copolymers, vinyl thermoplastics, polyamides and polyimides, polyacetals, polycarbonates, thermoplastics containing p-phenylene groups, polyesters, polyurethanes, polyisocyanurates, and silicones,

c) the medical device comprises a balloon-expandable stent, and the second surface is provided by an expandable balloon contained within the stent,

d) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition,

e) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents, and

f) the polymeric, bioactive agent-containing coating comprises a plurality of polymers, comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate), wherein the polyalkyl(meth)acrylates comprise poly(n-butyl methacrylate) and the polyaryl(meth)acrylates are selected from poly-9-anthracenylmethacrylate, polychlorophenylacrylate, polymethacryloxy-2-hydroxybenzophenone, polymethacryloxybenzotriazole, polynaphthylacrylate, polynaphthylmethacrylate, poly-4-nitrophenylacrylate, polypentachloro(bromo, fluoro)acrylate and methacrylate, polyphenylacrylate and methacrylate, the polyaralkyl(meth)acrylates are selected from polybenzylacrylate and methacrylate, poly-2-phenethylacrylate and methacrylate, poly-1-pyrenylmethylmethacrylate, and the polyaryloxyalkyl(meth)acrylates are selected from polyphenoxyethylacrylate and methacrylate, polyethyleneglycolphenylether acrylates and methacrylates with varying polyethyleneglycol molecular weights.

31. A method of minimizing the damage caused to a first surface comprising polymeric, bioactive agent-containing composition upon a medical device surface, by a second surface provided by another material and positioned in apposition to the first surface, the method comprising the step of providing a barrier according to claim 1.

21. A combination comprising:

a) a medical device having a first surface bearing a polymeric, bioactive agent-containing coating, b) a second surface provided by another material positioned in apposition to the medical device, and c) a barrier positioned between the first surface and the second surface, the barrier being selected from the group consisting of block copolymers and polymers bearing latent reactive groups.

22. A combination according to claim 21 wherein the barrier is provided in the form of a coating upon the polymeric coating, a coating upon the second surface, and/or a discrete layer positioned between the two.

23. A combination according to claim 21 wherein the barrier is itself comprised of one or more layers of the same or different materials, and positioned in any suitable combination upon the first and/or second surfaces, or separately provided between the two.

24. A combination according to claim 21 wherein the barrier is applied in the course of fabrication, storage, delivery or deployment, and/or residence of the device within the body.

25. A combination according to claim 21 wherein the polymeric, bioactive agent-containing coating is positioned upon the surface of an implantable medical device, the second surface is provided by the surface of an different material in apposition to the device, and the barrier comprises a barrier in the form of an anti-adherent coating adapted to facilitate the placement of the medical device surface and the different material in stable and separable apposition to each other.

26. A combination according to claim 25 wherein the medical device comprises a balloon-expandable stent, and the different material is in the form of an expandable balloon within the stent, and the barrier is selected from the group consisting of block copolymers and polymers bearing latent reactive groups.

27. A combination according to claim 21, wherein

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers,

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups are selected from photoderivatized polysaccharides and photoderivatized polyolefins, vinyl chloride polymers, fluorine-containing polymers, poly(vinyl acetates), poly(vinyl alcohols), poly(vinyl acetals), polyacrylates and polymethacrylates, styrene polymers and copolymers, vinyl thermoplastics, polyamides and polyimides, polyacetals, polycarbonates, thermoplastics containing p-phenylene groups, polyesters, polyurethanes, polyisocyanurates, and silicones,

d) the medical device comprises an implantable medical device,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition, and

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

28. A composition according to claim 27 wherein:

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate),

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups are selected from photoderivatized heparin, photoderivatized polyamides and photoderivatized vinyl thermoplastics,

d) the medical device is selected from the group consisting of vascular devices, orthopedic devices, dental devices, drug delivery devices, ophthalmic devices, urological devices, and synthetic prostheses,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition, and

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

29. A composition according to claim 21 wherein:

a) the polymeric, bioactive agent-containing coating comprises a plurality of polymers comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate),

b) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

c) the polymers bearing latent reactive groups comprise a photoderivatized heparin, polyacrylamide, or polyvinylpyrrolidone,

d) the medical device comprises an implantable medical device selected from the group consisting of vascular devices, orthopedic devices, dental devices, drug delivery devices, ophthalmic devices, urological devices, and synthetic prostheses, and the second surface is provided by another contacting portion of the same device or as a different material contained within or surrounding the device,

e) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition,

f) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

30. A combination according to claim 21, wherein:

a) the block copolymers are selected from ethylene oxide/propylene oxide block copolymers,

b) the polymers bearing latent reactive groups are selected from photoderivatized polysaccharides, polyolefins, vinyl chloride polymers, fluorine-containing polymers, poly(vinyl acetates), poly(vinyl alcohols), poly(vinyl acetals), polyacrylates and polymethacrylates, styrene polymers and copolymers, vinyl thermoplastics, polyamides and polyimides, polyacetals, polycarbonates, thermoplastics containing p-phenylene groups, polyesters, polyurethanes, polyisocyanurates, and silicones,

c) the medical device comprises a balloon-expandable stent, and the second surface is provided by an expandable balloon contained within the stent,

d) the bioactive agent within the polymeric coatings is present at a concentration of at least 20% based on the weight of the coated composition,

e) the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives (including antiangiogenesis agents), anticancer chemotherapeutic agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents, and

f) the polymeric, bioactive agent-containing coating comprises a plurality of polymers, comprising a first polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer selected from the group consisting of poly(ethylene-co-vinyl acetate), wherein the polyalkyl(meth)acrylates comprise poly(n-butyl methacrylate) and the polyaryl(meth)acrylates are selected from poly-9-anthracenylmethacrylate, polychlorophenylacrylate, polymethacryloxy-2-hydroxybenzophenone, polymethacryloxybenzotriazole, polynaphthylacrylate, polynaphthylmethacrylate, poly-4-nitrophenylacrylate, polypentachloro(bromo, fluoro)acrylate and methacrylate, polyphenylacrylate and methacrylate, the polyaralkyl(meth)acrylates are selected from polybenzylacrylate and methacrylate, poly-2-phenethylacrylate and methacrylate, poly-1-pyrenylmethylmethacrylate, and the polyaryloxyalkyl(meth)acrylates are selected from polyphenoxyethylacrylate and methacrylate, polyethyleneglycolphenylether acrylates and methacrylates with varying polyethyleneglycol molecular weights.