MEDICAL DEVICES FOR CONTROLLED DRUG RELEASE

• US 20080057101A1
• Filed: 08/15/2007
• Published: 03/06/2008
• Est. Priority Date: 08/21/2006
• Status: Active Grant

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Roorda, Wouter
• Granted Patent: US 9,248,121 B2
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B22F 10/14 by jetting of binder onto a bed of metal powder
• CPC Class Codes: B22F 2003/1051 by electric discharge
• CPC Class Codes: B22F 2003/1054 by microwave
• CPC Class Codes: B22F 3/105 by using electric current other than for infrared radiant energy, laser radiation or plasma B22F3/11 takes precedence; by ultrasonic bonding B22F3/115 takes precedence
• CPC Class Codes: Y02P 10/25 Process efficiency

Abstract

The present invention is a medical device for controlling the release of an active agent. The medical device has a supporting structure having a porous body disposed therein. At least one elution rate controlling matrix containing an effective amount of at least one active agent is disposed within the pores of the porous body in a manner that protects the matrix from mechanical damage. The medical device may therefore be used for controlled drug release applications. Additionally, the present invention discloses a method for using the medical device for the treatment and prevention of diseases in mammals. This invention further relates to a method for using the medical device for treating and preventing vascular diseases.

Claims

1. A medical device for controlling the release of an active agent, the medical device comprising:

a supporting structure configured and dimensioned to be used within a body of an animal;

a porous body disposed on and at least partially covering the supporting structure, said porous body including a first biocompatible material having a plurality of pores;

a therapeutically effective amount of an active agent disposed within at least a portion of the pores; and

an elution rate controlling matrix disposed on at least one surface of the porous body so as to contain the active agent within said at least a portion of the pores, said matrix including a second biocompatible material that controls an elution rate of the active agent from the pores.

2. A medical device according to claim 1, wherein the porous body has a thickness ranging from about 10 nanometers to about 1 millimeter.

3. A medical device according to claim 1, wherein the porous body comprises pores having a diameter of from about 10 nanometers to about 1 millimeter.

4. A medical device according to claim 1, wherein the elution rate controlling matrix is disposed within the pores such that substantially none of the matrix protrudes from the pores and the porous body protects the matrix.

5. A medical device according to claim 1, wherein the medical device is selected from the group consisting of endoprostheses, drug delivery stents, drug delivery catheters, grafts, drug delivery balloons, guidewires, orthopedic implants, dental implants, fixation screws, indwelling catheters, ocular implants, pharmacotherapeutic implants, blood-contacting components of extracorporeal devices, staples, filters, needles, tubes, coils, wires, clips, screws, sensors, plates, conduits, portions thereof, and combinations thereof.

6. A medical device according to claim 1, wherein said second biocompatible material is biodegradable.

7. A medical device according to claim 1, wherein said second biocompatible material includes at least one polymeric material comprised of phosphorylcholines, phosphorylcholine linked macromolecules, polyolefins, poly(meth)acrylates, polyurethanes, polyesters, polyanhydrides, polyphosphazenes, polyacrylates, acrylic polymers, poly(lactide-coglycolides) (PLGA), polylactic acids (PLA), poly(hydroxybutyrates), poly(hydroxybutyrate-co-valerates), polydioxanones (PDO), polyorthoesters, polyglycolic acids (PGA), polycaprolactones (PCL), poly(glycolic acid-co-trimethylene carbonates), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyiminocarbonates, aliphatic polycarbonates, fibrins, fibrinogens, celluloses, starchs, collagens, polycarbonate urethanes, polyisoprenes, polyisobutylenes, polybutadienes, polyethylenes, plasticized polyethylene terephthalates, polyethylene terepthalates, polymethylmethacrylates, ethylene ethylacrylates, polyethyl hexylacrylates, plasticized ethylene vinylacetates, polyvinyl acetates, ethylene vinyl acetates, ethylene vinyl alcohols, polyvinyl alcohols, cross-linked polyvinyl alcohols, cross-linked polyvinyl butyrates, polyvinylbutyrates, polybutylmethacrylates, polyvinyl chlorides, ethylene vinylchloride copolymers, silicones, polysiloxanes, substituted polysiloxanes, polyethylene oxides, polyethylene glycols (PEG), polybutylene terepthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, polyvinyl acetals, polyvinyl acetates, polyamides, polyvinyl pyrrolidones, polyacrylamides, polyvinyl esters, copolymers thereof, polymer derivatives thereof, or combinations thereof.

8. A medical device according to claim 1, wherein said active agent comprises at least one of analgesics, antipyretics, antiasthamatics, antibiotics, antidepressants, antidiabetics, antifungal agents, antihypertensive agents, anti-inflammatories including non-steroidal and steroidal, antineoplastics, antianxiety agents, immunosuppressive agents, antimigraine agents, sedatives, hypnotics, antianginal agents, antipsychotic agents, antimanic agents, antiarrhythmics, antiarthritic agents, antigout agents, anticoagulants, thrombolytic agents, antifibrinolytic agents, hemorheologic agents, antiplatelet agents, anticonvulsants, antiparkinson agents, antihistamines, anti-restenosis agents, antipruritics, agents useful for calcium regulation, antibacterial agents, antiviral agents, antimicrobials, anti-infectives, bronchodilators, steroidal compounds or hormones, and combinations thereof.

9. A medical device according to claim 1, wherein said active agent comprises at least one of rapamycin, rapamycin analog, zotarolimus, sirolimus, everolimus, dexamethasone, prednisone, hydrocortisone, estradiol, acetaminophen, ibuprofen, naproxen, sulidac, heparin, taxol, paclitaxel, or combinations thereof.

10. A medical device according to claim 1, wherein said porous body is integrated with the supporting structure.

11. A medical device for controlling the release of an active agent, the medical device comprising:

a supporting structure configured and dimensioned to be used within a body of a human;

a porous body disposed on and at least partially covering the supporting structure, said porous body including a first biocompatible material having a plurality of pores;

a therapeutically effective amount of an active agent disposed within said pores;

an elution rate controlling matrix disposed within the porous body so as to contain said active agent within said pores, said matrix including a polymeric biocompatible material that at least partially determines an elution rate of the active agent from the pores; and

said pores each having a dimension that is configured to at least partially determine said elution rate.

12. A medical device according to claim 11, wherein the porous body has a thickness ranging from about 10 nanometers to about 1 millimeter.

13. A medical device according to claim 11, wherein the porous body comprises pores having a diameter of from about 10 nanometers to about 1 millimeter.

14. A medical device according to claim 11, wherein the elution rate controlling matrix is disposed within the pores such that substantially none of the matrix protrudes from the pores and the porous body protects the matrix.

15. A medical device according to claim 11, wherein the medical device is selected from the group consisting of endoprostheses, drug delivery stents, drug delivery catheters, grafts, drug delivery balloons, guidewires, orthopedic implants, dental implants, fixation screws, indwelling catheters, ocular implants, pharmacotherapeutic implants, blood-contacting components of extracorporeal devices, staples, filters, needles, tubes, coils, wires, clips, screws, sensors, plates, conduits, portions thereof, and combinations thereof.

16. A medical device according to claim 11, wherein said polymeric biocompatible material is biodegradable.

17. A medical device according to claim 11, wherein said polymeric biocompatible material includes at least one polymeric material comprised of phosphorylcholines, phosphorylcholine linked macromolecules, polyolefins, poly(meth)acrylates, polyurethanes, polyesters, polyanhydrides, polyphosphazenes, polyacrylates, acrylic polymers, poly(lactide-coglycolides) (PLGA), polylactic acids (PLA), poly(hydroxybutyrates), poly(hydroxybutyrate-co-valerates), polydioxanones (PDO), polyorthoesters, polyglycolic acids (PGA), polycaprolactones (PCL), poly(glycolic acid-co-trimethylene carbonates), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyiminocarbonates, aliphatic polycarbonates, fibrins, fibrinogens, celluloses, starchs, collagens, polycarbonate urethanes, polyisoprenes, polyisobutylenes, polybutadienes, polyethylenes, plasticized polyethylene terephthalates, polyethylene terepthalates, polymethylmethacrylates, ethylene ethylacrylates, polyethyl hexylacrylates, plasticized ethylene vinylacetates, polyvinyl acetates, ethylene vinyl acetates, ethylene vinyl alcohols, polyvinyl alcohols, cross-linked polyvinyl alcohols, cross-linked polyvinyl butyrates, polyvinylbutyrates, polybutylmethacrylates, polyvinyl chlorides, ethylene vinylchloride copolymers, silicones, polysiloxanes, substituted polysiloxanes, polyethylene oxides, polyethylene glycols (PEG), polybutylene terepthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, polyvinyl acetals, polyvinyl acetates, polyamides, polyvinyl pyrrolidones, polyacrylamides, polyvinyl esters, copolymers thereof, polymer derivatives thereof, or combinations thereof.

18. A medical device according to claim 11, wherein said active agent comprises at least one of analgesics, antipyretics, antiasthamatics, antibiotics, antidepressants, antidiabetics, antifungal agents, antihypertensive agents, anti-inflammatories including non-steroidal and steroidal, antineoplastics, antianxiety agents, immunosuppressive agents, antimigraine agents, sedatives, hypnotics, antianginal agents, antipsychotic agents, antimanic agents, antiarrhythmics, antiarthritic agents, antigout agents, anticoagulants, thrombolytic agents, antifibrinolytic agents, hemorheologic agents, antiplatelet agents, anticonvulsants, antiparkinson agents, antihistamines, antipruritics, agents useful for calcium regulation, antibacterial agents, antiviral agents, antimicrobials, anti-infectives, bronchodilators, steroidal compounds and hormones, or combinations thereof.

19. A medical device according to claim 11, wherein said active agent comprises at least one of rapamycin, rapamycin analog, zotarolimus, sirolimus, everolimus, dexamethasone, prednisone, hydrocortisone, estradiol, acetaminophen, ibuprofen, naproxen, sulidac, heparin, taxol, paclitaxel, or combinations thereof.

20. A medical device according to claim 11, wherein said porous body is integrated with the supporting structure.

21. A drug eluting stent for controlling the release of an active agent, the stent comprising:

an expandable supporting structure configured and dimensioned as a stent to be used within a lumen of an animal, said expandable supporting structure having a delivery orientation and a deployed orientation;

a porous body disposed on and at least partially covering the supporting structure, said porous body including a first biocompatible material having a plurality of pores;

a therapeutically effective amount of an active agent disposed within at least a portion of the pores; and

an elution rate controlling matrix disposed on at least one surface of the porous body so as to contain the active agent within said at least a portion of the pores, said matrix including a second biocompatible material that determines an elution rate of the active agent from the pores.

22. A stent according to claim 21, wherein the porous body has a thickness ranging from about 10 nanometers to about 1 millimeter.

23. A stent according to claim 21, wherein the porous body comprises pores having a diameter of from about 10 nanometers to about 1 millimeter.

24. A stent according to claim 21, wherein the elution rate controlling matrix is disposed within the pores such that substantially none of the matrix protrudes from the pores and the porous body protects the matrix.

25. A stent according to claim 21, wherein the medical device is selected from the group consisting of endoprostheses, drug delivery stents, drug delivery catheters, grafts, drug delivery balloons, guidewires, orthopedic implants, dental implants, fixation screws, indwelling catheters, ocular implants, pharmacotherapeutic implants, blood-contacting components of extracorporeal devices, staples, filters, needles, tubes, coils, wires, clips, screws, sensors, plates, conduits, portions thereof, and combinations thereof.

26. A stent according to claim 21, wherein said second biocompatible material is biodegradable.

27. A stent according to claim 21, wherein said second biocompatible material includes at least one polymeric material comprised of phosphorylcholines, phosphorylcholine linked macromolecules, polyolefins, poly(meth)acrylates, polyurethanes, polyesters, polyanhydrides, polyphosphazenes, polyacrylates, acrylic polymers, poly(lactide-coglycolides) (PLGA), polylactic acids (PLA), poly(hydroxybutyrates), poly(hydroxybutyrate-co-valerates), polydioxanones (PDO), polyorthoesters, polyglycolic acids (PGA), polycaprolactones (PCL), poly(glycolic acid-co-trimethylene carbonates), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyiminocarbonates, aliphatic polycarbonates, fibrins, fibrinogens, celluloses, starchs, collagens, polycarbonate urethanes, polyisoprenes, polyisobutylenes, polybutadienes, polyethylenes, plasticized polyethylene terephthalates, polyethylene terepthalates, polymethylmethacrylates, ethylene ethylacrylates, polyethyl hexylacrylates, plasticized ethylene vinylacetates, polyvinyl acetates, ethylene vinyl acetates, ethylene vinyl alcohols, polyvinyl alcohols, cross-linked polyvinyl alcohols, cross-linked polyvinyl butyrates, polyvinylbutyrates, polybutylmethacrylates, polyvinyl chlorides, ethylene vinylchloride copolymers, silicones, polysiloxanes, substituted polysiloxanes, polyethylene oxides, polyethylene glycols (PEG), polybutylene terepthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, polyvinyl acetals, polyvinyl acetates, polyamides, polyvinyl pyrrolidones, polyacrylamides, polyvinyl esters, copolymers thereof, polymer derivatives thereof, or combinations thereof.

28. A stent according to claim 21, wherein said active agent comprises at least one of analgesics, antipyretics, antiasthamatics, antibiotics, antidepressants, antidiabetics, antifungal agents, antihypertensive agents, anti-inflammatories including non-steroidal and steroidal, antineoplastics, antianxiety agents, immunosuppressive agents, antimigraine agents, sedatives, hypnotics, antianginal agents, antipsychotic agents, antimanic agents, antiarrhythmics, antiarthritic agents, antigout agents, anticoagulants, thrombolytic agents, antifibrinolytic agents, hemorheologic agents, antiplatelet agents, anticonvulsants, antiparkinson agents, antihistamines, antipruritics, agents useful for calcium regulation, antibacterial agents, antiviral agents, antimicrobials, anti-infectives, bronchodilators, steroidal compounds and hormones, or combinations thereof.

29. A stent according to claim 21, wherein said active agent comprises at least one of rapamycin, rapamycin analog, zotarolimus, sirolimus, everolimus, dexamethasone, prednisone, hydrocortisone, estradiol, acetaminophen, ibuprofen, naproxen, sulidac, heparin, taxol, paclitaxel, or combinations thereof.

30. A stent according to claim 21, wherein said porous body is integrated with the supporting structure.