Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS20050100609 A1
Publication typeApplication
Application numberUS 11/015,617
Publication date12 May 2005
Filing date16 Dec 2004
Priority date30 Mar 2001
Also published asUS6780424, US7364748, US20020142039, US20040191293, WO2002078668A2, WO2002078668A3
Publication number015617, 11015617, US 2005/0100609 A1, US 2005/100609 A1, US 20050100609 A1, US 20050100609A1, US 2005100609 A1, US 2005100609A1, US-A1-20050100609, US-A1-2005100609, US2005/0100609A1, US2005/100609A1, US20050100609 A1, US20050100609A1, US2005100609 A1, US2005100609A1
InventorsCharles Claude
Original AssigneeClaude Charles D.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Phase-separated polymer coatings
US 20050100609 A1
Abstract
The present invention includes a drug release system. The drug release system comprises a bulk polymer phase and a polymeric drug-enriched phase within the bulk polymer phase. At least one, drug is incorporated into the drug-enriched phase.
Images(1)
Previous page
Next page
Claims(43)
1-43. (canceled)
44. a drug-delivery stent comprising a coating, wherein the coating includes:
a first-polymer phase comprising a first-polymer, a second-polymer phase comprising a second-polymer, and a drug; wherein, the second-polymer phase is substantially or completely immiscible in the first-polymer phase, and the drug is preferentially incorporated in the second-polymer phase.
45. The stent of claim 44, wherein the first-polymer phase has a film forming property.
46. The stent of claim 44, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.
47. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely disconnected in the coating, such that elution of the drug from the coating occurs through transport of the drug across both the second-polymer phase and the first-polymer phase.
48. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely connected in the coating, such that elution of the drug from the coating includes transport of the drug primarily through the second-polymer phase.
49. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely connected in the coating, such that elution of the drug from the coating includes transport of the drug exclusively through the second-polymer phase.
50. The stent of claim 44, wherein the concentration of the second-polymer phase in the coating is less than or equal to about 30% by volume.
51. The stent of claim 44, wherein the concentration of the second-polymer phase in the coating is greater than or equal to about 30% by volume.
52. The stent of claim 44, wherein the coating comprises the second-polymer phase in a concentration that is less than or equal to a percolation threshold of the coating.
53. The stent of claim 44, wherein the coating comprises the second-polymer phase in a concentration that is greater than or equal to a percolation threshold of the coating.
54. The stent of claim 44, wherein the second-polymer phase has a glass-transition temperature of less than about 37 C.
55. The stent of claim 44, wherein the drug has a preferential solubility for the second-polymer phase, such that the drug becomes preferentially incorporated in the second-polymer phase in the coating.
56. The stent of claim 44, wherein the drug has a preferential solubility in a solvent used to form the coating, the solvent preferentially solubilizes the second polymer over the first polymer, and the drug becomes preferentially incorporated in the second-polymer phase upon removing the solvent to form the coating.
57. A method of coating a stent comprising incorporating a drug preferentially in a second-polymer phase during a coating process, wherein the coating process comprises:
forming a coating composition comprising a first polymer for a first polymer phase, a second polymer for a second polymer phase, a drug, and a solvent; wherein the second polymer is substantially or completely immiscible in the first polymer;
applying the composition to a stent; and
removing the solvent from the composition to form a coating including the first-polymer phase, the second-polymer phase, and the drug, wherein the drug is preferentially in the second-polymer phase.
58. The method of claim 57, wherein the incorporating includes selecting a drug with a preferential solubility in the second-polymer phase, such that the drug becomes preferentially incorporated in the second-polymer phase in the coating.
59. The method of claim 57, wherein the incorporating includes selecting a drug with a preferential solubility in the solvent, and the solvent preferentially solubilizes the second polymer over the first polymer, such that the drug becomes preferentially incorporated in the second-polymer phase upon removing the solvent to form the coating.
60. The method of claim 57, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.
61. The method of claim 57, wherein the second-polymer phase has a glass-transition temperature of less than about 37 C.
62. The method of claim 57, wherein the coating comprises the second-polymer phase in a concentration that is less than or equal to a percolation threshold of the coating composition.
63. The method of claim 57, wherein the coating comprises the second-polymer phase in a concentration that is greater than or equal to a percolation threshold of the coating composition.
64. The method of claim 57, wherein the concentration of the second-polymer phase in the coating is less than or equal to about 30% by volume.
65. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely disconnected throughout the coating, such that elution of the drug from the second-polymer phase occurs through transport of the drug across both the second-polymer phase and the first-polymer phase.
66. The method of claim 57, wherein the concentration of the second-polymer phase in the coating is greater than or equal to about 30% by volume.
67. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely connected throughout the coating, such that elution of the drug from the second-polymer phase includes transport of the drug primarily through the second-polymer phase.
68. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely connected throughout the coating, such that elution of the drug from the second-polymer phase includes transport of the drug exclusively through the second-polymer phase.
69. The method of claim 57, wherein the first polymer constitutes more in amount than the second polymer in the composition.
70. The method of claim 57, wherein the forming comprises:
blending the first polymer with the second polymer in the solvent to form a solution; and
adding the drug to the solution such that the drug is preferentially incorporated in the second-polymer phase in the coating.
71. A drug-delivery stent comprising a coating, wherein the coating includes:
a first-polymer phase comprising a first-polymer, a second-polymer phase comprising a second-polymer, and a drug; wherein, the second-polymer phase is partially or substantially phase-separated from the first-polymer phase, and the drug is preferentially incorporated in the second-polymer phase.
72. A method of coating a stent comprising incorporating a drug preferentially in a second-polymer phase during a coating process, wherein the coating process comprises:
forming a coating composition comprising a first polymer for a first-polymer phase, a second polymer for a second-polymer phase, a drug, and a solvent;
applying the composition to a stent; and
removing the solvent from the composition to form a coating with the drug preferentially in the second-polymer phase, wherein the second-polymer phase is partially or substantially phase-separated from a first-polymer phase.
73. A therapeutic composition for coating stents comprising:
a first polymer component;
a second polymer component, wherein the second polymer component at least partially separates from the first polymer component when a coating is formed from the composition; and
a drug being preferentially enriched in the second polymer component when the coating is formed from the composition.
74. The composition of claim 73, wherein the first-polymer component has a film forming property.
75. The composition of claim 73, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.
76. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely disconnected when a coating is formed from the composition, such that elution of the drug from the coating occurs through transport of the drug across both the second-polymer component and the first-polymer component.
77. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely connected when a coating is formed from the composition, such that elution of the drug from the coating includes transport of the drug primarily through the second-polymer component.
78. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely connected when a coating is formed from the composition, such that elution of the drug from the coating includes transport of the drug exclusively through the second-polymer component.
79. The composition of claim 73, wherein the concentration of the drug-enriched second-polymer component in the coating is less than or equal to about 30% by volume.
80. The composition of claim 73, wherein the concentration of the drug-enriched second-polymer component in the coating is greater than or equal to about 30% by volume.
81. The composition of claim 73, wherein the coating comprises the drug-enriched second-polymer component in a concentration that is less than or equal to a percolation threshold of the coating.
82. The composition of claim 73, wherein the coating comprises the drug-enriched second-polymer component in a concentration that is greater than or equal to a percolation threshold of the coating.
83. The composition of claim 73, wherein the drug-enriched second-polymer component has a glass-transition temperature of less than about 37 C.
84. The composition of claim 73, wherein the drug has a preferential solubility for the second-polymer component, such that the drug becomes preferentially incorporated in the second-polymer component when the coating is formed from the composition.
85. The composition of claim 73 additionally including a solvent used to form the coating, such that the drug has a preferential solubility in the solvent, and the solvent preferentially solubilizes the second polymer over the first polymer, wherein the drug becomes preferentially incorporated in the second-polymer component upon removing the solvent to form the coating.
Description
    BACKGROUND OF THE INVENTION
  • [0001]
    The present invention relates to a system for controlled drug release within a vessel lumen, and to a method and to a device for controlled drug release.
  • [0002]
    A device for providing a continuous release of drugs over an extended period of time following from a single administration of a drug releasing material has wide application in treating disease. One type of continuous drug release mechanism is based upon degradation of biodegradable polymers. The biodegradable polymers have drugs incorporated within them. As the biodegradable polymers hydrolyze over time, the drugs are released. Hydroxycarboxylic acid polymers have been used to release drugs in this manner.
  • [0003]
    One other modality of drug release is a prolonged, though discontinuous release of drugs. Frequently, with a discontinuous release, there is a lag phase of no or negligible drug release when a drug delivery device is delivered to an in situ site for drug release.
  • [0004]
    One problem with sustaining drug release is that when drugs, particularly water soluble drugs, are incorporated into polymers, it is difficult to prevent a rapid, uncontrolled release of the drugs. As used herein, the term “water soluble drug” is defined as a hydrophilic compound with a solubility in water greater than 1 percent (w/v) and that is practically insoluble in nonpolar organic solvents such as ethyl acetate, methylene chloride, chloroform, toluene, or hydrocarbons. This rapid, uncontrolled release from a drug-polymeric matrix is known as a “burst effect.” The burst effect is particularly troublesome with high drug loading.
  • [0005]
    One other type of uncontrolled drug release is characterized by a “lag effect.” The lag effect occurs when the rate of drug release decreases to a negligible value.
  • [0006]
    The degree of drug release from a polymeric-drug matrix is, in part, controlled by the morphology of the polymeric-drug matrix. The morphology is, for some embodiments, a single-phase dispersion and for other embodiments, is a multi-phase dispersion. A single-phase dispersion is typically transparent when viewed in natural light. The single phase dispersion is clear and transparent because both the drug and the polymer have a mutual miscibility. A multi-phase dispersion has micro domains that give the dispersion a cloudy appearance. For some multi-phase dispersions, drugs are embedded in a polymeric matrix as particles.
  • [0007]
    Drug release is also controlled by the degree of drug loading. Matrices that have dispersed drug particles that do not contact each other tend to have a slow release of drug. A drug carrier such as blood is typically required to move the drug through the matrix and into the bloodstream of a living being.
  • [0008]
    Drug-polymeric matrices have been used to deliver drugs in situ through a vehicle such as a stent. The drug-polymeric matrix has been applied as a coating or a wrap to the stent. U.S. Pat. No. 5,605,696, which issued Feb. 25, 1997, describes a drug loaded polymeric material that is applied to an intravascular stent. The drug-polymeric matrix defines pores, multilayered to permit a combination of different drugs in a single stent. The stent also includes a rate controlling membrane that controlled retention and delivery of selected drugs to the affected blood vessel. The drug is dispersed as small particles, having a maximum cross-sectional dimension of 10 microns.
  • DESCRIPTION OF THE DRAWINGS
  • [0009]
    FIG. 1 is a perspective view of one embodiment of the drug delivery system of the present invention wherein a system component is below the percolation threshold.
  • [0010]
    FIG. 2 is a perspective view of one embodiment of the drug delivery system of the present invention wherein a system component is above the percolation threshold.
  • [0011]
    FIG. 3 a is a perspective view of the drug delivery system of the present invention wherein the pore structure is discontinuous.
  • [0012]
    FIG. 3 b is a perspective view of the drug delivery system of the present invention wherein the pore structure is semi-continuous.
  • [0013]
    FIG. 3 c is a perspective view of another embodiment of the drug delivery system of the present invention wherein the pore structure is continuous.
  • SUMMARY OF THE INVENTION
  • [0014]
    One embodiment of the present invention includes a drug release system. The drug release system releases one or more drugs when implanted in a human being or other vertebrate but does not display a substantial release of drugs when outside of the human being or other vertebrates. The drug release system comprises a bulk polymer phase and a polymeric drug-enriched phase within the bulk polymer phase. The drug release system also includes at least one drug that is incorporated in the polymeric drug-enriched phase. The drug release system of the present invention releases one or more drugs in situ while decreasing the rate of release of the drug when the device is not in situ. The drug profile release is predictable and preselectable.
  • [0015]
    Another embodiment of the present invention includes a coating that comprises a drug release system. The drug release system has desirable film properties which render it useful as a coating for an implantable device. The present invention also includes an implantable device with a coating that is adhered to the implantable device. The coated implantable device releases one or more drugs in a predictable and preselectable manner when implanted in a human being or other vertebrate.
  • [0016]
    Another embodiment of the present invention includes a method for substantially continuously releasing drugs. The method includes attaching or adhering a drug delivery system to an implantable medical device. The drug delivery system comprises a bulk polymer phase and a polymeric drug-enriched phase within the bulk polymer phase. The drug release system also includes one or more drugs that are incorporated in the polymeric drug-enriched phase.
  • [0017]
    One other embodiment includes a device for continuously and predictably releasing drugs. The device comprises a drug release system that comprises a bulk polymer phase. The drug release system also includes a drug-enriched polymeric phase within the bulk polymer phase. The drug release system also includes at least one drug which is incorporated into the polymeric drug-enriched phase wherein the drug-enriched phase comprises sites within the bulk polymer phase that are continuous in both cross-section and longitudinal directions. Other embodiments of the device include implantable devices, such as a stent, catheter or guidewire, to which the drug release system is attached or adhered.
  • [0018]
    Another embodiment of the present invention includes a method for making a device for a continuous release of drugs. The method comprises providing a bulk phase polymer and providing a drug that is substantially insoluble in the bulk phase polymer. The method also includes providing a drug enriched polymer. The drug enriched polymer is substantially insoluble in the bulk polymer. One or more of the drugs are soluble in the drug-enriched polymer. The method further comprises providing a solvent. The bulk phase polymer, the drug enriched polymer and the drug or drugs are blended in the solvent so that the drug or drugs are incorporated into the drug receiving polymer and the drug enriched polymer is dispersed within the bulk polymer.
  • DETAILED DESCRIPTION
  • [0019]
    One embodiment of the present invention includes a drug release system comprising two or more polymers that are insoluble in each other. The polymers are blended in a solvent to form two polymer phases which create a polymer blend. At least one drug is added to the polymer blend. The drug or drugs are soluble in one of the polymer phases, hereinafter referred to as the “drug-enriched polymer” or “drug enriched polymer phase.” The polymer blend with the drug enriched polymer phase is removed from the solvent and is allowed to set. Once set, this drug release system has a morphology that has a predictable and preselectable drug release profile with desirable film properties. The desirable film properties include adherence or attachment to a polymeric or metal surface of an implantable device. Thus, the drug release system serves a dual function of predictable, preselectable drug delivery and coating an implantable device.
  • [0020]
    The term “preselectable” as used herein refers to an ability to preselect one or more drugs to be released. “Preselectable,” for some embodiments, also refers to a rate of drug release.
  • [0021]
    The polymer phase that includes the soluble drug, the drug-enriched polymer phase, preferably has a glass transition temperature, Tg, less than human body temperature of about 37 degrees Centigrade. This polymer phase shall be referred to herein as a “drug-enriched polymer.” Upon incorporating one or more drugs into the polymer, the polymer is kept at a temperature that is lower than the glass transition temperature. The term “glass transition temperature” as used herein refers to a temperature at which the polymer chain undergoes long range motion characterized by a transition from a glassy state to a rubbery state. The glass transition temperature is also the temperature at which the rate of diffusion within the polymer phase changes by several orders of magnitude as the polymer goes from the glassy state to the rubbery state.
  • [0022]
    A polymer with a Tg that is less than 37 degrees Centigrade is used as the drug-enriched polymer because the diffusion rate of molecules, such as drug molecules within the polymer, decreases one to two orders of magnitude when the polymer is exposed to a temperature that is below the Tg. The Tg features of the drug enriched polymer impart to the polymer features that allow additional control of the drug delivery rate. For instance, when the polymer is at a temperature below its Tg, it will not be within a living being, such as a human being: At these lower temperatures, the drug diffusion is suppressed and the drug does not prematurely diffuse through the bulk polymer. This is desirable because outside of a human being, drug diffusion through the polymer is problematic. Once the drug-enriched polymer phase is implanted, the temperature of the polymer approaches its Tg and the rate of diffusion of drug through the polymer increases. The drug or drugs are deliverable to a predetermined site, such as to a lesion in a blood vessel. Once at this site, the drugs diffuse through the drug-enriched polymer. Polymers which can be used as the drug enriched phase include polyethylene oxide, PEO, and poly n-vinyl pyrrolidone.
  • [0023]
    The drug enriched polymer is at a concentration greater than the percolation threshold concentration, which is about 33-36%, assuming a morphology of spherical domains, to form a continuous drug enriched phase within the bulk polymer film. The term “percolation threshold” as is used herein refers to a state achieved when an aqueous drug enriched phase forms a continuous, interconnecting network throughout the bulk polymer thickness. The continuous drug enriched phase is one where the drug-enriched polymer phase is substantially uniformly distributed within the bulk phase, such as is shown generally, in one perspective view, at 10, in FIG. 1.
  • [0024]
    The-continuous drug-enriched polymer phase, is illustrated at 11 in FIG. 1, for one embodiment. The bulk polymer 12 forming the phase which is not drug-enriched, referred to herein as the “bulk phase” or “bulk matrix” has acceptable film properties. One suitable polymer for use in the drug release system, as a bulk phase polymer, is poly(ethylene-co-vinyl)alcohol, which is also known as EVAL. EVAL is a thermoplastic polymer, manufactured by EVAL Company of America (EVALCA), of Lisle, Ill. This polymer 12 has a formulation which is the following:
    The drug-enriched polymer containing the drug has, for one embodiment, the formula:
  • [0025]
    One drug delivery system is composed of two components: one, a hydrophobic component, including but not limited to poly(ethylene-co-vinyl alcohol), and two, a hydrophilic component, which includes but is not limited to polyethylene glycol. The dissimilarity of solubility parameters of the components results in a phase separation of the two polymer phases. The two polymers are blended in a common solvent, such as dimethyl sulfoxide or N,N-dimethylacetamide, to forn a solution. At least one therapeutic drug is added to the solution, such as the therapeutic drug, actinomycin D. However, the therapeutic drug or drugs are not limited to the antiproliferative class of drugs which has preferential solubility in the hydrophilic phase.
  • [0026]
    For some embodiments, the drug delivery system comprising the drug and polymer solution is applied to an implantable device to form a coating on the device. The coated device is dried to remove the solvent, by vacuum or by convection processing. The drying allows the polymers within the applied solution to form phases and to separate. Once dried, the coating retains flexibility.
  • [0027]
    If the volume percent of the drug enriched hydrophilic phase is less than about 30%, the hydrophilic polymer and drug will exhibit a discontinuous pore structure, as shown at 10 in FIG. 1. The discontinuous pore structure shown in FIG. 1 is defined as being below the percolation threshold.
  • [0028]
    If the volume percent of the drug enriched hydrophilic phase is greater than about 30%, the hydrophilic polymer and drug will exhibit a pore structure 22 that is continuous throughout the volume of the bulk polymer 24, as shown generally at 20 in FIG. 2. The continuous pore structure 22 within the bulk polymer volume of the polymer 24 is defined as being above the percolation threshold.
  • [0029]
    The elution of the drug from a drug release coating, such as is shown in FIG. 1, below the percolation threshold, is dependent upon the diffusion of the drug within the drug-enriched polymer 11 through the hydrophobic bulk polymer 12. This is contrary to the diffusion of the drug from a drug release coating above the percolation threshold, such as is illustrated in FIG. 2, which is dependent upon the diffusion of the drug from the pore network 22, and upon the mean pore length.
  • [0030]
    Common solvents and co-solvents usable for the blending of the polymers include dimethyl sulfoxide, N,N-dimethylacetamide, dimethyl sulfoxide-tetrahydrfuran, and isopropanol-water.
  • [0031]
    Once the polymers are blended and the drug is incorporated in the drug-enriched polymer, the solvent is evaporated. The evaporation is carried out, for some embodiments, at a reduced pressure and at a temperature that is as close to ambient temperature as possible.
  • [0032]
    Examples of such drugs include antiproliferative substances as well as antineoplastic, anti-inflammatory antiplatelet, anticoagulant, antifigrin, antithrombin, antimitotic, antibiotic, antioxidant, and combinations thereof. A suitable example of an antiproliferative substance includes actinomycin D, or derivatives and analogs thereof, manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I1, actinomycin X1, and actinomycin C1. Examples of suitable antineoplastics include paclitaxel and docetaxel. Examples of suitable antiplatelets, anticoagulants, antifibrins, and antithrombins, include sodium heparin, low molecular weight heparin, hirudin, argatroban, forskolin, vapisprost, prostacyclin and prostacyclin analogs, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein Iib/IIIa platelet membrane receptor antagonist, recombinant hirudin, thrombin inhibitor, available from Biogen, and 7E-3B, an antiplatelet drug from Centocore. Examples of suitable antimitotic agents include methotrexate, azathioprine, vincristine, vinblastine, antiproliferative agents include angiopeptin (a somatostatin analog from Ibsen), angiotensin converting enzyme inhibitors such as CAPTOPRIL, available from Squibb, CILAZAPRIL, available form Hoffman-LaRoche, or LISINOPRIL, available form Merck, calcium channel blockers such as Nifedipine, colchicine, fibroblast growth factor (FGF) antagonists, fish oil, omega 3-fatty acid, histamine antagonists, LOVASTATIN, an inhibitor of AMG-CoA reductase, a cholesterol lowering drug from Merck, a cholesterol lowering drug, monoclonal antibodies such as PDGF receptors, nitroprusside, phosphodies terase, inhibitors, prostaglandin inhibitor, Seramin, a PDGF antagonist, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, a PDGF antagonist, and nitric oxide. Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, and dexamethasone.
  • [0033]
    In-another embodiment, the drug delivery system comprises a polymer film doped with one or more therapeutic drugs. The polymer film is comprised of a graft copolymer, the copolymer having segments that differ significantly in their solubility parameters. The solubility differences result in phase separation of the two segments. In this embodiment, the hydrophobic polymer is poly(ethylene-co-vinyl alcohol), commercially known as EVAL. In the embodiment, a hydrophilic copolymer such as a polyethylene oxide with a molecular weight between 3200 and 20,000 with an isocyanate functionality is grafted as a side chain, in the following chemical reaction:
  • [0034]
    The graft copolymer with a molecular weight of 3200 daltons is functionalized with 0.27 mol percent of the hydroxyl functionalities of the poly(ethylene-co-vinyl alcohol) and has an average of two ethylene oxide polymers grafted to the polymer. The total volume fraction of hydrophilic polymer and drug occupies approximately 35% of the polymer matrix and assumes a cylindrical-like pore morphology. The grafted co-polymer with a molecular weight of 3200 daltons functionalized with 0.68 mole percent of the hydroxyl functionalities has an average of five co-polymer segments attached to any given polymer chain. The hydrophilic graft polymer volume containing the polyethylene oxide functionality and the drug, forming a drug enriched polymer, are present at approximately 50 volume percent. The drug enriched polymer assumes a lamellar structure as is shown at 40 c in FIG. 3 c.
  • [0035]
    The morphologies of the drug enriched graft polymer 32 within the bulk polymer substrate 34, are shown at 40 a, 40 b and 40 c, respectively, in FIGS. 3 a, 3 b and 3 c. These different morphologies are due to an increasing concentration of the drug enriched polymer phase 32 a, 32 b and 32 c, respectively, in which one or more drugs is incorporated. At higher concentrations, the drug enriched polymer phase coalesces to form a lamellar morphology. The drug release embodiment 40 a, shown in FIG. 3 a, is a discontinuous pore structure, with the drug-enriched polymer phase 32 a discretely dispersed in the bulk phase 34 a.
  • [0036]
    The drug-enriched polymer structure 32 b in FIG. 3 b has a semi-continuous phase and in FIG. 3 c, the drug-enriched polymer 32 c has a continuous phase in which the drug is soluble and diffusible from the continuous phase, when implanted into a living being. The semi-continuous phase 32 b comprises sites that are discrete in cross-section but continuous in a longitudinal direction, as is shown in FIG. 3 b. The continuous phase 32 c, shown in FIG. 3 c, defines a channel 33 c in which the drug is diffusible from the bulk polymer 34 c to the polymer interface 35. The drug-enriched sites are continuous in both cross-section and in a longitudinal direction.
  • EXAMPLE 1
  • [0037]
    One exemplary composition that produces the drug release morphology of FIG. 3 c includes an EVAL polymer with 66 weight percent ethylene groups, 43.32 weight percent vinyl alcohol functionalities and 0.68 weight percent vinyl ether groups. The weight percent refers to the percent of the total drug release system weight. The vinyl ether groups were functionalized with PEO-isocyanate, which forms a urethane linkage, using groups that have a molecular weight of a side group of 3200 g/mol. The side groups comprise 33 weight percent of the total EVAL/PEO polymer. The composition of the PEO-isocyanate blend is 75 weight percent functionalized EVAL and 25 weight percent drug. This composition gives rise to a 50 weight percent hard, bulk phase and a 50 weight percent drug/PEO side chain phase. The final structure is a lamellar structure.
  • [0038]
    The chemical reaction is as follows:
  • [0039]
    (x)=66 weight %; (y)=44 weight %. M is approximately equal to 70 units. Molecular weight is approximately 3200 units. With the drug release system such as is shown at 40 c in FIG. 3 c, drug release is substantially continuous within a human being.
  • [0040]
    The drug release system of the present invention is deliverable to a treatment site by attachment to a device such as a stent or catheter or guidewire. For other embodiments, the drug release system is encapsulated and ingested or subcutaneously injected. For other embodiments, the drug release system is adhered to a prosthetic device or a graft or other implantable device by methods known to those skilled in the art.
  • [0041]
    Once positioned within a living being by one of the implantable devices, the drug release system commences delivering drugs because the polymer component of the drug-laden phase is at a temperature below its glass transition temperature. The release of drugs is substantially continuous.
  • [0042]
    While specified embodiments of the invention have been herein described, it is to be appreciated that various changes, rearrangements and modifications may be made therein without departing from the scope of the invention as defined by the appended claims.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2072303 *14 Oct 19332 Mar 1937Chemische Forschungs GmbhArtificial threads, bands, tubes, and the like for surgical and other purposes
US2386454 *22 Nov 19409 Oct 1945Bell Telephone Labor IncHigh molecular weight linear polyester-amides
US4226243 *27 Jul 19797 Oct 1980Ethicon, Inc.Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
US4343931 *17 Dec 197910 Aug 1982Minnesota Mining And Manufacturing CompanySynthetic absorbable surgical devices of poly(esteramides)
US4529792 *6 May 198216 Jul 1985Minnesota Mining And Manufacturing CompanyProcess for preparing synthetic absorbable poly(esteramides)
US4611051 *31 Dec 19859 Sep 1986Union Camp CorporationNovel poly(ester-amide) hot-melt adhesives
US4656242 *7 Jun 19857 Apr 1987Henkel CorporationPoly(ester-amide) compositions
US4733665 *7 Nov 198529 Mar 1988Expandable Grafts PartnershipExpandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4800882 *13 Mar 198731 Jan 1989Cook IncorporatedEndovascular stent and delivery system
US4931287 *14 Jun 19885 Jun 1990University Of UtahHeterogeneous interpenetrating polymer networks for the controlled release of drugs
US4941870 *30 Dec 198817 Jul 1990Ube-Nitto Kasei Co., Ltd.Method for manufacturing a synthetic vascular prosthesis
US5100992 *3 May 199031 Mar 1992Biomedical Polymers International, Ltd.Polyurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same
US5133742 *14 Nov 199128 Jul 1992Corvita CorporationCrack-resistant polycarbonate urethane polymer prostheses
US5219980 *16 Apr 199215 Jun 1993Sri InternationalPolymers biodegradable or bioerodiable into amino acids
US5292516 *8 Nov 19918 Mar 1994Mediventures, Inc.Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
US5298260 *9 Jun 199229 Mar 1994Mediventures, Inc.Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality
US5300295 *13 Sep 19915 Apr 1994Mediventures, Inc.Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
US5306501 *8 Nov 199126 Apr 1994Mediventures, Inc.Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers
US5306786 *16 Dec 199126 Apr 1994U C B S.A.Carboxyl group-terminated polyesteramides
US5328471 *4 Aug 199312 Jul 1994Endoluminal Therapeutics, Inc.Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens
US5330768 *5 Jul 199119 Jul 1994Massachusetts Institute Of TechnologyControlled drug delivery using polymer/pluronic blends
US5380299 *30 Aug 199310 Jan 1995Med Institute, Inc.Thrombolytic treated intravascular medical device
US5447724 *15 Nov 19935 Sep 1995Harbor Medical Devices, Inc.Medical device polymer
US5455040 *19 Nov 19923 Oct 1995Case Western Reserve UniversityAnticoagulant plasma polymer-modified substrate
US5462990 *5 Oct 199331 Oct 1995Board Of Regents, The University Of Texas SystemMultifunctional organic polymers
US5485496 *22 Sep 199416 Jan 1996Cornell Research Foundation, Inc.Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties
US5605696 *30 Mar 199525 Feb 1997Advanced Cardiovascular Systems, Inc.Drug loaded polymeric material and method of manufacture
US5607467 *23 Jun 19934 Mar 1997Froix; MichaelExpandable polymeric stent with memory and delivery apparatus and method
US5609629 *7 Jun 199511 Mar 1997Med Institute, Inc.Coated implantable medical device
US5610241 *7 May 199611 Mar 1997Cornell Research Foundation, Inc.Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers
US5616338 *19 Apr 19911 Apr 1997Trustees Of Columbia University In The City Of New YorkInfection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5624411 *7 Jun 199529 Apr 1997Medtronic, Inc.Intravascular stent and method
US5644020 *10 May 19961 Jul 1997Bayer AktiengesellschaftThermoplastically processible and biodegradable aliphatic polyesteramides
US5649977 *22 Sep 199422 Jul 1997Advanced Cardiovascular Systems, Inc.Metal reinforced polymer stent
US5658995 *27 Nov 199519 Aug 1997Rutgers, The State UniversityCopolymers of tyrosine-based polycarbonate and poly(alkylene oxide)
US5667767 *27 Jul 199516 Sep 1997Micro Therapeutics, Inc.Compositions for use in embolizing blood vessels
US5670558 *6 Jul 199523 Sep 1997Terumo Kabushiki KaishaMedical instruments that exhibit surface lubricity when wetted
US5711958 *11 Jul 199627 Jan 1998Life Medical Sciences, Inc.Methods for reducing or eliminating post-surgical adhesion formation
US5716981 *7 Jun 199510 Feb 1998Angiogenesis Technologies, Inc.Anti-angiogenic compositions and methods of use
US5721131 *28 Apr 199424 Feb 1998United States Of America As Represented By The Secretary Of The NavySurface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells
US5723219 *19 Dec 19953 Mar 1998Talison ResearchPlasma deposited film networks
US5735897 *2 Jan 19977 Apr 1998Scimed Life Systems, Inc.Intravascular stent pump
US5759205 *20 Jan 19952 Jun 1998Brown University Research FoundationNegatively charged polymeric electret implant
US5776184 *9 Oct 19967 Jul 1998Medtronic, Inc.Intravasoular stent and method
US5783657 *18 Oct 199621 Jul 1998Union Camp CorporationEster-terminated polyamides of polymerized fatty acids useful in formulating transparent gels in low polarity liquids
US5788979 *10 Feb 19974 Aug 1998Inflow Dynamics Inc.Biodegradable coating with inhibitory properties for application to biocompatible materials
US5800392 *8 May 19961 Sep 1998Emed CorporationMicroporous catheter
US5858746 *25 Jan 199512 Jan 1999Board Of Regents, The University Of Texas SystemGels for encapsulation of biological materials
US5865814 *6 Aug 19972 Feb 1999Medtronic, Inc.Blood contacting medical device and method
US5869127 *18 Jun 19979 Feb 1999Boston Scientific CorporationMethod of providing a substrate with a bio-active/biocompatible coating
US5873904 *24 Feb 199723 Feb 1999Cook IncorporatedSilver implantable medical device
US5876433 *29 May 19962 Mar 1999Ethicon, Inc.Stent and method of varying amounts of heparin coated thereon to control treatment
US5877224 *28 Jul 19952 Mar 1999Rutgers, The State University Of New JerseyPolymeric drug formulations
US5879713 *23 Jan 19979 Mar 1999Focal, Inc.Targeted delivery via biodegradable polymers
US5910564 *6 Dec 19968 Jun 1999Th. Goldschmidt AgPolyamino acid ester copolymers
US5914387 *28 Jan 199822 Jun 1999United States Surgical CorporationPolyesteramides with amino acid-derived groups alternating with alpha-hydroxyacid-derived groups and surgical articles made therefrom
US5919893 *28 Jan 19986 Jul 1999United States Surgical CorporationPolyesteramide, its preparation and surgical devices fabricated therefrom
US5925720 *18 Apr 199620 Jul 1999Kazunori KataokaHeterotelechelic block copolymers and process for producing the same
US5932299 *22 Apr 19973 Aug 1999Katoot; Mohammad W.Method for modifying the surface of an object
US5955509 *23 Apr 199721 Sep 1999Board Of Regents, The University Of Texas SystempH dependent polymer micelles
US5958385 *28 Sep 199528 Sep 1999Lvmh RecherchePolymers functionalized with amino acids or amino acid derivatives, method for synthesizing same, and use thereof as surfactants in cosmetic compositions, particularly nail varnishes
US6010530 *18 Feb 19984 Jan 2000Boston Scientific Technology, Inc.Self-expanding endoluminal prosthesis
US6011125 *25 Sep 19984 Jan 2000General Electric CompanyAmide modified polyesters
US6015541 *3 Nov 199718 Jan 2000Micro Therapeutics, Inc.Radioactive embolizing compositions
US6033582 *16 Jan 19987 Mar 2000Etex CorporationSurface modification of medical implants
US6034204 *7 Aug 19987 Mar 2000Basf AktiengesellschaftCondensation products of basic amino acids with copolymerizable compounds and a process for their production
US6042875 *2 Mar 199928 Mar 2000Schneider (Usa) Inc.Drug-releasing coatings for medical devices
US6051576 *29 Jan 199718 Apr 2000University Of Kentucky Research FoundationMeans to achieve sustained release of synergistic drugs by conjugation
US6051648 *13 Jan 199918 Apr 2000Cohesion Technologies, Inc.Crosslinked polymer compositions and methods for their use
US6054553 *12 Nov 199625 Apr 2000Bayer AgProcess for the preparation of polymers having recurring agents
US6080488 *24 Mar 199827 Jun 2000Schneider (Usa) Inc.Process for preparation of slippery, tenaciously adhering, hydrophilic polyurethane hydrogel coating, coated polymer and metal substrate materials, and coated medical devices
US6096070 *16 May 19961 Aug 2000Med Institute Inc.Coated implantable medical device
US6099562 *22 Dec 19978 Aug 2000Schneider (Usa) Inc.Drug coating with topcoat
US6110188 *9 Mar 199829 Aug 2000Corvascular, Inc.Anastomosis method
US6110483 *23 Jun 199729 Aug 2000Sts Biopolymers, Inc.Adherent, flexible hydrogel and medicated coatings
US6113629 *1 May 19985 Sep 2000Micrus CorporationHydrogel for the therapeutic treatment of aneurysms
US6120491 *7 Apr 199819 Sep 2000The State University RutgersBiodegradable, anionic polymers derived from the amino acid L-tyrosine
US6120536 *13 Jun 199619 Sep 2000Schneider (Usa) Inc.Medical devices with long term non-thrombogenic coatings
US6120788 *16 Oct 199819 Sep 2000Bioamide, Inc.Bioabsorbable triglycolic acid poly(ester-amide)s
US6120904 *24 May 199919 Sep 2000Schneider (Usa) Inc.Medical device coated with interpenetrating network of hydrogel polymers
US6121027 *15 Aug 199719 Sep 2000Surmodics, Inc.Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups
US6172167 *27 Jun 19979 Jan 2001Universiteit TwenteCopoly(ester-amides) and copoly(ester-urethanes)
US6177523 *14 Jul 199923 Jan 2001Cardiotech International, Inc.Functionalized polyurethanes
US6180632 *24 Nov 199830 Jan 2001Aventis Pharmaceuticals Products Inc.Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6203551 *4 Oct 199920 Mar 2001Advanced Cardiovascular Systems, Inc.Chamber for applying therapeutic substances to an implant device
US6211249 *13 Jan 19983 Apr 2001Life Medical Sciences, Inc.Polyester polyether block copolymers
US6214901 *15 Apr 199910 Apr 2001Surmodics, Inc.Bioactive agent release coating
US6240616 *15 Apr 19975 Jun 2001Advanced Cardiovascular Systems, Inc.Method of manufacturing a medicated porous metal prosthesis
US6245753 *27 Apr 199912 Jun 2001Mediplex Corporation, KoreaAmphiphilic polysaccharide derivatives
US6245760 *24 Nov 199812 Jun 2001Aventis Pharmaceuticals Products, IncQuinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6248129 *23 Oct 199819 Jun 2001Quanam Medical CorporationExpandable polymeric stent with memory and delivery apparatus and method
US6251136 *8 Dec 199926 Jun 2001Advanced Cardiovascular Systems, Inc.Method of layering a three-coated stent using pharmacological and polymeric agents
US6254632 *28 Sep 20003 Jul 2001Advanced Cardiovascular Systems, Inc.Implantable medical device having protruding surface structures for drug delivery and cover attachment
US6258121 *2 Jul 199910 Jul 2001Scimed Life Systems, Inc.Stent coating
US6258371 *3 Apr 199810 Jul 2001Medtronic IncMethod for making biocompatible medical article
US6262034 *25 Nov 199717 Jul 2001Neurotech S.A.Polymeric gene delivery system
US6270788 *4 Oct 19997 Aug 2001Medtronic IncImplantable medical device
US6277449 *30 Jun 199921 Aug 2001Omprakash S. KolluriMethod for sequentially depositing a three-dimensional network
US6283947 *13 Jul 19994 Sep 2001Advanced Cardiovascular Systems, Inc.Local drug delivery injection catheter
US6283949 *27 Dec 19994 Sep 2001Advanced Cardiovascular Systems, Inc.Refillable implantable drug delivery pump
US6284305 *18 May 20004 Sep 2001Schneider (Usa) Inc.Drug coating with topcoat
US6287628 *3 Sep 199911 Sep 2001Advanced Cardiovascular Systems, Inc.Porous prosthesis and a method of depositing substances into the pores
US6335029 *3 Dec 19981 Jan 2002Scimed Life Systems, Inc.Polymeric coatings for controlled delivery of active agents
US6344035 *20 Oct 20005 Feb 2002Surmodics, Inc.Bioactive agent release coating
US6346110 *3 Jan 200112 Feb 2002Advanced Cardiovascular Systems, Inc.Chamber for applying therapeutic substances to an implantable device
US6358556 *23 Jan 199819 Mar 2002Boston Scientific CorporationDrug release stent coating
US6379361 *16 Aug 199930 Apr 2002Charles L. Beck, Jr.Endosteal anchoring device for urging a ligament against a bone surface
US6419692 *3 Feb 199916 Jul 2002Scimed Life Systems, Inc.Surface protection method for stents and balloon catheters for drug delivery
US6451373 *4 Aug 200017 Sep 2002Advanced Cardiovascular Systems, Inc.Method of forming a therapeutic coating onto a surface of an implantable prosthesis
US6503538 *30 Aug 20007 Jan 2003Cornell Research Foundation, Inc.Elastomeric functional biodegradable copolyester amides and copolyester urethanes
US6503556 *28 Dec 20007 Jan 2003Advanced Cardiovascular Systems, Inc.Methods of forming a coating for a prosthesis
US6503954 *21 Jul 20007 Jan 2003Advanced Cardiovascular Systems, Inc.Biocompatible carrier containing actinomycin D and a method of forming the same
US6506437 *17 Oct 200014 Jan 2003Advanced Cardiovascular Systems, Inc.Methods of coating an implantable device having depots formed in a surface thereof
US6524347 *29 Sep 200025 Feb 2003Avantis Pharmaceuticals Inc.Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6527863 *29 Jun 20014 Mar 2003Advanced Cardiovascular Systems, Inc.Support device for a stent and a method of using the same to coat a stent
US6528526 *29 Sep 20004 Mar 2003Aventis Pharmaceuticals Inc.Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases
US6530950 *3 Aug 200011 Mar 2003Quanam Medical CorporationIntraluminal stent having coaxial polymer member
US6530951 *23 Oct 199711 Mar 2003Cook IncorporatedSilver implantable medical device
US6540776 *28 Dec 20001 Apr 2003Advanced Cardiovascular Systems, Inc.Sheath for a prosthesis and methods of forming the same
US6544223 *5 Jan 20018 Apr 2003Advanced Cardiovascular Systems, Inc.Balloon catheter for delivering therapeutic agents
US6544543 *27 Dec 20008 Apr 2003Advanced Cardiovascular Systems, Inc.Periodic constriction of vessels to treat ischemic tissue
US6565659 *28 Jun 200120 May 2003Advanced Cardiovascular Systems, Inc.Stent mounting assembly and a method of using the same to coat a stent
US6572644 *27 Jun 20013 Jun 2003Advanced Cardiovascular Systems, Inc.Stent mounting device and a method of using the same to coat a stent
US6585755 *29 Jun 20011 Jul 2003Advanced CardiovascularPolymeric stent suitable for imaging by MRI and fluoroscopy
US6585765 *29 Jun 20001 Jul 2003Advanced Cardiovascular Systems, Inc.Implantable device having substances impregnated therein and a method of impregnating the same
US6585926 *31 Aug 20001 Jul 2003Advanced Cardiovascular Systems, Inc.Method of manufacturing a porous balloon
US6605154 *31 May 200112 Aug 2003Advanced Cardiovascular Systems, Inc.Stent mounting device
US6616765 *10 Jan 20029 Sep 2003Advanced Cardiovascular Systems, Inc.Apparatus and method for depositing a coating onto a surface of a prosthesis
US6623448 *30 Mar 200123 Sep 2003Advanced Cardiovascular Systems, Inc.Steerable drug delivery device
US6625486 *11 Apr 200123 Sep 2003Advanced Cardiovascular Systems, Inc.Method and apparatus for intracellular delivery of an agent
US6673154 *28 Jun 20016 Jan 2004Advanced Cardiovascular Systems, Inc.Stent mounting device to coat a stent
US6673385 *28 Jun 20016 Jan 2004Advanced Cardiovascular Systems, Inc.Methods for polymeric coatings stents
US6689099 *27 Feb 200110 Feb 2004Advanced Cardiovascular Systems, Inc.Local drug delivery injection catheter
US6695920 *27 Jun 200124 Feb 2004Advanced Cardiovascular Systems, Inc.Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US6706013 *29 Jun 200116 Mar 2004Advanced Cardiovascular Systems, Inc.Variable length drug delivery catheter
US6709514 *28 Dec 200123 Mar 2004Advanced Cardiovascular Systems, Inc.Rotary coating apparatus for coating implantable medical devices
US6712845 *24 Apr 200130 Mar 2004Advanced Cardiovascular Systems, Inc.Coating for a stent and a method of forming the same
US6713119 *23 Dec 199930 Mar 2004Advanced Cardiovascular Systems, Inc.Biocompatible coating for a prosthesis and a method of forming the same
US6733768 *25 Jun 200211 May 2004Advanced Cardiovascular Systems, Inc.Composition for coating an implantable prosthesis
US6740040 *30 Jan 200125 May 2004Advanced Cardiovascular Systems, Inc.Ultrasound energy driven intraventricular catheter to treat ischemia
US6743462 *31 May 20011 Jun 2004Advanced Cardiovascular Systems, Inc.Apparatus and method for coating implantable devices
US6749626 *17 Nov 200015 Jun 2004Advanced Cardiovascular Systems, Inc.Actinomycin D for the treatment of vascular disease
US6753071 *27 Sep 200122 Jun 2004Advanced Cardiovascular Systems, Inc.Rate-reducing membrane for release of an agent
US6758859 *30 Oct 20006 Jul 2004Kenny L. DangIncreased drug-loading and reduced stress drug delivery device
US6759054 *28 Dec 20006 Jul 2004Advanced Cardiovascular Systems, Inc.Ethylene vinyl alcohol composition and coating
US6764505 *12 Apr 200120 Jul 2004Advanced Cardiovascular Systems, Inc.Variable surface area stent
US6780424 *30 Mar 200124 Aug 2004Charles David ClaudeControlled morphologies in polymer drug for release of drugs from polymer films
US20010007083 *21 Dec 20005 Jul 2001Roorda Wouter E.Device and active component for inhibiting formation of thrombus-inflammatory cell matrix
US20010014717 *28 Dec 200016 Aug 2001Hossainy Syed F.A.Coating for implantable devices and a method of forming the same
US20010018469 *28 Dec 200030 Aug 2001Yung-Ming ChenEthylene vinyl alcohol composition and coating
US20010020011 *23 Mar 20016 Sep 2001Edith MathiowitzPolymeric gene delivery system
US20020005206 *7 May 200117 Jan 2002Robert FaloticoAntiproliferative drug and delivery device
US20020007213 *7 May 200117 Jan 2002Robert FaloticoDrug/drug delivery systems for the prevention and treatment of vascular disease
US20020007214 *7 May 200117 Jan 2002Robert FaloticoDrug/drug delivery systems for the prevention and treatment of vascular disease
US20020007215 *7 May 200117 Jan 2002Robert FaloticoDrug/drug delivery systems for the prevention and treatment of vascular disease
US20020009604 *21 Dec 200024 Jan 2002Zamora Paul O.Plasma-deposited coatings, devices and methods
US20020016625 *7 May 20017 Feb 2002Robert FaloticoDrug/drug delivery systems for the prevention and treatment of vascular disease
US20020032414 *7 May 200114 Mar 2002Ragheb Anthony O.Coated implantable medical device
US20020032434 *21 Nov 200114 Mar 2002Chudzik Stephen J.Bioactive agent release coating
US20020071822 *27 Jul 200113 Jun 2002Uhrich Kathryn E.Therapeutic polyesters and polyamides
US20020077693 *19 Dec 200020 Jun 2002Barclay Bruce J.Covered, coiled drug delivery stent and method
US20020082679 *1 Nov 200127 Jun 2002Avantec Vascular CorporationDelivery or therapeutic capable agents
US20020087123 *2 Jan 20014 Jul 2002Hossainy Syed F.A.Adhesion of heparin-containing coatings to blood-contacting surfaces of medical devices
US20020091433 *17 Dec 200111 Jul 2002Ni DingDrug release coated stent
US20020094440 *25 Sep 200118 Jul 2002Llanos Gerard H.Coatings for medical devices
US20020111590 *25 Sep 200115 Aug 2002Davila Luis A.Medical devices, drug coatings and methods for maintaining the drug coatings thereon
US20020120326 *22 Dec 200029 Aug 2002Gene MichalEthylene-carboxyl copolymers as drug delivery matrices
US20020123801 *28 Dec 20005 Sep 2002Pacetti Stephen D.Diffusion barrier layer for implantable devices
US20030004141 *8 Mar 20022 Jan 2003Brown David L.Medical devices, compositions and methods for treating vulnerable plaque
US20030028243 *14 Aug 20026 Feb 2003Cook IncorporatedCoated implantable medical device
US20030028244 *14 Aug 20026 Feb 2003Cook IncorporatedCoated implantable medical device
US20030031780 *10 Oct 200213 Feb 2003Chudzik Stephen J.Bioactive agent release coating
US20030032767 *5 Feb 200113 Feb 2003Yasuhiro TadaHigh-strength polyester-amide fiber and process for producing the same
US20030036794 *19 Aug 200220 Feb 2003Cook IncorporatedCoated implantable medical device
US20030039689 *26 Apr 200227 Feb 2003Jianbing ChenPolymer-based, sustained release drug delivery system
US20030040712 *10 Oct 200227 Feb 2003Pinaki RaySubstance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway
US20030040790 *31 Jul 200227 Feb 2003Furst Joseph G.Stent coating
US20030059520 *27 Sep 200127 Mar 2003Yung-Ming ChenApparatus for regulating temperature of a composition and a method of coating implantable devices
US20030060877 *15 Apr 200227 Mar 2003Robert FaloticoCoated medical devices for the treatment of vascular disease
US20030065377 *30 Apr 20023 Apr 2003Davila Luis A.Coated medical devices
US20030072868 *25 Nov 200217 Apr 2003Sameer HarishMethods of forming a coating for a prosthesis
US20030073961 *28 Sep 200117 Apr 2003Happ Dorrie M.Medical device containing light-protected therapeutic agent and a method for fabricating thereof
US20030105518 *10 Jan 20035 Jun 2003Debashis DuttaBiodegradable drug delivery material for stent
US20030113439 *18 Nov 200219 Jun 2003Pacetti Stephen D.Support device for a stent and a method of using the same to coat a stent
US20030150380 *19 Feb 200314 Aug 2003Yoe Brandon J.Method and apparatus for coating an implant device
US20030157241 *5 Mar 200321 Aug 2003Hossainy Syed F.A.Method for coating an implantable device and system for performing the method
US20030158517 *11 Feb 200321 Aug 2003Lyudmila KokishBalloon catheter for delivering therapeutic agents
US20040018296 *23 Jun 200329 Jan 2004Daniel CastroMethod for depositing a coating onto a surface of a prosthesis
US20040029952 *1 Aug 200312 Feb 2004Yung-Ming ChenEthylene vinyl alcohol composition and coating
US20040047978 *12 Aug 200311 Mar 2004Hossainy Syed F.A.Composition for coating an implantable prosthesis
US20040047980 *8 Sep 200311 Mar 2004Pacetti Stephen D.Method of forming a diffusion barrier layer for implantable devices
US20040052858 *15 Sep 200318 Mar 2004Wu Steven Z.Microparticle coated medical device
US20040052859 *15 Sep 200318 Mar 2004Wu Steven Z.Microparticle coated medical device
US20040054104 *5 Sep 200218 Mar 2004Pacetti Stephen D.Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol)
US20040086542 *16 Dec 20026 May 2004Hossainy Syed F.A.Coating for implantable devices and a method of forming the same
US20040086550 *24 Oct 20036 May 2004Roorda Wouter E.Permeabilizing reagents to increase drug delivery and a method of local delivery
US20040096504 *12 Nov 200320 May 2004Gene MichalEthylene-carboxyl copolymers as drug delivery matrices
US20040098117 *22 Sep 200320 May 2004Hossainy Syed F.A.Composite stent with regioselective material and a method of forming the same
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US793168327 Jul 200726 Apr 2011Boston Scientific Scimed, Inc.Articles having ceramic coated surfaces
US79388552 Nov 200710 May 2011Boston Scientific Scimed, Inc.Deformable underlayer for stent
US794292611 Jul 200717 May 2011Boston Scientific Scimed, Inc.Endoprosthesis coating
US797691523 May 200712 Jul 2011Boston Scientific Scimed, Inc.Endoprosthesis with select ceramic morphology
US798115024 Sep 200719 Jul 2011Boston Scientific Scimed, Inc.Endoprosthesis with coatings
US798525230 Jul 200826 Jul 2011Boston Scientific Scimed, Inc.Bioerodible endoprosthesis
US79981929 May 200816 Aug 2011Boston Scientific Scimed, Inc.Endoprostheses
US800282113 Sep 200723 Aug 2011Boston Scientific Scimed, Inc.Bioerodible metallic ENDOPROSTHESES
US800282311 Jul 200723 Aug 2011Boston Scientific Scimed, Inc.Endoprosthesis coating
US80295542 Nov 20074 Oct 2011Boston Scientific Scimed, Inc.Stent with embedded material
US804815012 Apr 20061 Nov 2011Boston Scientific Scimed, Inc.Endoprosthesis having a fiber meshwork disposed thereon
US80527432 Aug 20078 Nov 2011Boston Scientific Scimed, Inc.Endoprosthesis with three-dimensional disintegration control
US805274413 Sep 20078 Nov 2011Boston Scientific Scimed, Inc.Medical devices and methods of making the same
US805274513 Sep 20078 Nov 2011Boston Scientific Scimed, Inc.Endoprosthesis
US805753414 Sep 200715 Nov 2011Boston Scientific Scimed, Inc.Bioerodible endoprostheses and methods of making the same
US806676311 May 201029 Nov 2011Boston Scientific Scimed, Inc.Drug-releasing stent with ceramic-containing layer
US80670545 Apr 200729 Nov 2011Boston Scientific Scimed, Inc.Stents with ceramic drug reservoir layer and methods of making and using the same
US807079727 Feb 20086 Dec 2011Boston Scientific Scimed, Inc.Medical device with a porous surface for delivery of a therapeutic agent
US80711564 Mar 20096 Dec 2011Boston Scientific Scimed, Inc.Endoprostheses
US808005527 Dec 200720 Dec 2011Boston Scientific Scimed, Inc.Bioerodible endoprostheses and methods of making the same
US80890291 Feb 20063 Jan 2012Boston Scientific Scimed, Inc.Bioabsorbable metal medical device and method of manufacture
US812868914 Sep 20076 Mar 2012Boston Scientific Scimed, Inc.Bioerodible endoprosthesis with biostable inorganic layers
US818762027 Mar 200629 May 2012Boston Scientific Scimed, Inc.Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents
US82166322 Nov 200710 Jul 2012Boston Scientific Scimed, Inc.Endoprosthesis coating
US822182230 Jul 200817 Jul 2012Boston Scientific Scimed, Inc.Medical device coating by laser cladding
US82319803 Dec 200931 Jul 2012Boston Scientific Scimed, Inc.Medical implants including iridium oxide
US823604610 Jun 20087 Aug 2012Boston Scientific Scimed, Inc.Bioerodible endoprosthesis
US82679922 Mar 201018 Sep 2012Boston Scientific Scimed, Inc.Self-buffering medical implants
US828793724 Apr 200916 Oct 2012Boston Scientific Scimed, Inc.Endoprosthese
US830364321 May 20106 Nov 2012Remon Medical Technologies Ltd.Method and device for electrochemical formation of therapeutic species in vivo
US835394910 Sep 200715 Jan 2013Boston Scientific Scimed, Inc.Medical devices with drug-eluting coating
US83828243 Oct 200826 Feb 2013Boston Scientific Scimed, Inc.Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides
US843114927 Feb 200830 Apr 2013Boston Scientific Scimed, Inc.Coated medical devices for abluminal drug delivery
US844960317 Jun 200928 May 2013Boston Scientific Scimed, Inc.Endoprosthesis coating
US857461525 May 20105 Nov 2013Boston Scientific Scimed, Inc.Medical devices having nanoporous coatings for controlled therapeutic agent delivery
US866873222 Mar 201111 Mar 2014Boston Scientific Scimed, Inc.Surface treated bioerodible metal endoprostheses
US871533921 Nov 20116 May 2014Boston Scientific Scimed, Inc.Bioerodible endoprostheses and methods of making the same
US8759454 *16 Apr 201324 Jun 2014Innovia LlcLow friction polymeric compositions as well as devices and device fabrication methods based thereon
US877134315 Jun 20078 Jul 2014Boston Scientific Scimed, Inc.Medical devices with selective titanium oxide coatings
US880872614 Sep 200719 Aug 2014Boston Scientific Scimed. Inc.Bioerodible endoprostheses and methods of making the same
US881527327 Jul 200726 Aug 2014Boston Scientific Scimed, Inc.Drug eluting medical devices having porous layers
US881527528 Jun 200626 Aug 2014Boston Scientific Scimed, Inc.Coatings for medical devices comprising a therapeutic agent and a metallic material
US88406605 Jan 200623 Sep 2014Boston Scientific Scimed, Inc.Bioerodible endoprostheses and methods of making the same
US89002926 Oct 20092 Dec 2014Boston Scientific Scimed, Inc.Coating for medical device having increased surface area
US892049117 Apr 200930 Dec 2014Boston Scientific Scimed, Inc.Medical devices having a coating of inorganic material
US893234623 Apr 200913 Jan 2015Boston Scientific Scimed, Inc.Medical devices having inorganic particle layers
US90288597 Jul 200612 May 2015Advanced Cardiovascular Systems, Inc.Phase-separated block copolymer coatings for implantable medical devices
US928440917 Jul 200815 Mar 2016Boston Scientific Scimed, Inc.Endoprosthesis having a non-fouling surface
US20130274423 *16 Apr 201317 Oct 2013Innovia LlcLow Friction Polymeric Compositions As Well As Devices And Device Fabrication Methods Based Thereon
Classifications
U.S. Classification424/486
International ClassificationA61K9/00
Cooperative ClassificationA61K9/0024
European ClassificationA61K9/00M5D