Polymer films for medical device coating

专利摘要:

公开号:AU2008256684A1
申请号:U2008256684
申请日:2008-05-23
公开日:2008-12-04
发明作者:James Mcclain；Douglas Taylor
申请人:MiCell Technologies Inc；
IPC主号:A61L27-04

专利说明:
WO 2008/148013 PCT/US2008/064732 POLYMER FILMS FOR MEDICAL DEVICE COATING RELATED APPLICATIONS [0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 60/940,365 filed May 25, 2007 and U.S. Provisional Patent Application Serial No. 60/979,375 filed October 11, 2007. The disclosure of these applications are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION [00021 Medical devices often must be shielded from interacting with body fluids in vivo. For example, for devices that are electrical in nature, for example, such as pacemakers and other "active" implants for sensing, delivery of therapeutics and/or active control of various bodily functions should be protected. [00031 One prevalent method used to provide this protection is to weld the device inside a titanium or other biocompatible metal "can." Another method to provide the shield necessary to protect a medical device from interaction with bodily fluids in vivo is polymer coating the device. Polymer coating such "active" implants has significant technical challenges and limitations which have made polymer coatings relatively unsuccessful as a means of sealing the devices. [00041 For example, one limitation of traditional coating processes in providing a seal is that traditional polymer coating processes (e.g. dip, spray, etc.) all require the use of a solvent-based system. Exposing the device to a solvent causes problems in the device. Furthermore, there are inherent challenges with effective drying of solvent-based polymer coatings. [00051 Solvent-less coating processes (e.g. vapor deposition, plasma deposition, dry powder coating, etc.) also have limitations in providing seals to active devices. Solvent-less coating processes all require very aggressive conditions that could damage the device - such as elevated temperatures to cure a dry powder coated device. [00061 Additionally, for most current coating technologies, solvent-based and solvent-less, it is often difficult to achieve coatings of uniform thicknesses and prevent the occurrence of defects (e.g. bare spots, webs, pools, clumps). As the size of the substrate decreases, and as the mechanical complexity increases, it grows increasingly difficult to uniformly coat all surfaces of a substrate. Supplemental steps, therefore, are sometimes necessary to assure proper coating, including, for example, multiple coating steps and/or drying between or after the coating steps (in solvent-based systems). [00071 Conventional polymer films likewise have limitations in providing a seal. Conventional polymer films are known to be quite ineffective barriers to the transport of gaseous materials. While this is especially true of small molecule gases, the problem extends to providing a barrier to water vapors and other gases that could deleteriously effect an electrical biomedical implant.
WO 2008/148013 PCT/US2008/064732 SUMMARY OF THE INVENTION [00081 A cost-effective, easy to apply polymer-based coatings and coating methods to seal a substrate, where the collection process on the substrate is efficient, the coating produced is conformal, substantially defect-free 5 and uniform, and the composition of the coating can be regulated and controlled is provided herein. The method and coatings provide a seal which is impermeable and/or imperveous to gas and/or fluid. The seal can be applied to a variety of substrates, including, but not limited to, implantable medical devices that are electrical in nature such as pacemakers and other "active" implants, which can shield the substrates from interacting with body fluids in vivo. 10 [00091 The present invention relates to coatings and methods for depositing a coating comprising a polymer and a impermeable dispersed solid onto a substrate. Provided herein are novel, easy to apply, polymer-based coatings and coating methods to seal and, thereby, shield, for example, medical devices that are electrical in nature such as pacemakers and other "active" implants from interacting with body fluids in vivo in a manner that disrupts the substrate's (e.g. active medical device's) intended functions and/or proper functioning, if any, or in a 15 manner that has unintended consequences within and/or to the patient. Provided herein are novel, easy to apply, polymer-based coatings and coating methods to seal, for example, implantable medical devices that are electrical in nature such as pacemakers and other "active" implants and, thereby, shield the body from degradation products, leachants, and extractables from the medical device. The coatings and methods provided herein result in a collection process on the substrate that is efficient, a conformal, substantially defect-free, and uniform 20 coating, and a regulatable and controllable coating composition. The coating structures and methods provided herein not only avoid the problems of polymer coatings (solvent-based, and solvent-less), but they also improve the barrier properties of polymer films for use as a seal upon, for example, biologically implanted devices. 100101 Provided herein is a method for electrostatic capture of polymer particles upon a substrate followed by sintering of these particles by exposure to compressed gasses. The coating methods used, including e-RESS, e 25 SEDS, and/or eDPC are free from elevated temperatures, solvent exposure, plasma environments, and other challenges associated with traditional polymer coating methods. [00111 In some embodiments, a coating comprising electrostatically captured polymer particles (generated by eRESS, eSEDS or eDPC) with either concurrent or sequential captured impermeable particles (by eDPC, eRESS, eSEDS) on a medical implant substrate. A method is also provided for electrostatically capturing polymer 30 particles (generated by eRESS, eSEDS or eDPC) with either concurrent or sequential capturing impermeable particles (by eDPC, eRESS, eSEDS) on a medical implant substrate. Following electrostatic capture of the impermeable particles and the polymer, the method comprises sintering the medical implant substrate with a compressed gas at conditions adequate to cause flow of the polymer particles into a continuous film on the substrate. 35 [0012] The polymers that could be used in the coatings or methods provided herein are all solution or thermally processible polymers (e.g. acrylates, olefins, fluoropolymers, urethanes, etc.). For example, a polymer (or polymers) could be used with known biocompatibility and high resistance to chemical degradation such as polymers of fluorinated olefins. The impermeable particles that could be used in this coating method includes all inorganic particles that can be obtained in the micron and/or sub-micron size range (for example, various 40 compositions of clay, metal-oxides, ceramics, etc.) 2 WO 2008/148013 PCT/US2008/064732 [0013] In one embodiment, a polymer coating is sufficient to provide the requisite sealing properties. In another embodiment, the coating would contain a polymer continuous phase with particles embedded therein. The existence and distribution of the particles cases an increase in the barrier properties of the film to small molecules and gases by blocking diffusion pathways. 5 [0014] In some embodiments, the surface of the particles is chemically modified to provide greater dispersion and incorporation into the polymer film. In some embodiments of the method for coating, the method comprises chemically modifying the surface of the particles to provide greater dispersion and incorporation into the polymer film. For example in the case of a highly polar particle (e.g. clay, SiO2, TiO2, etc.) in a highly non polar polymer (e.g. polymeric fluorinated olefins), the process comprises binding or bonding a non-polar 10 chemistry to the surface of the particle prior to incorporation into the powder-coating and sintering process. [0015] Also, provided herein are stacked polymer films with an intervening impermeable layer which could provide similar protection for sensitive devices in vivo without the difficulty associated with welding metal cans around the device. In some embodiments, polymers to be used in the processes and in the coatings provided herein are inherently hydrophobic, thereby greatly reducing the likelihood of penetration of biological fluids, 15 For example, fluoropolymers as a class yield high surface energy surfaces that meet this requirement. However, surfaces created from such polymers in some cases act as membranes through which water vapor transport can occur. Thus, in some embodiments, a second layer that can trap any water vapor that might permeate the fluoropolymer membrane is provided. In some embodiments, the method comprises depositing a hydrophilic polymer layer such as a silicon based polymer over the initial fluoropolymer layer. Silicon based polymers can 20 be designed to possess differing degrees of hydrophilicity and therefore trap any water vapor that might permeate the fluoropolymer layer membrane. In some embodiments, the silicon-based polymer is reduced to native silicon and metallized with titanium. In some embodiments, a third layer of fluoropolymer is deposited to encapsulate the silicon based polymer layer between the fluropolymer layers. In some embodiments, the coating comprises multiple alternating layers of fluoropolymers and silicon based polymers. In some embodiments, the 25 method comprises alternating multiple layers of the silicon based polymer and the fluropolymer. 100161 In some embodiments, the coating is designed to remain impermeable and/or impervious to gas and/or fluid for at least as long as the expected life span (e.g., period of time inside a subjects body) of the device and/or substrate it coats. [00171 One aspect of the invention provides methods for depositing a coating comprising a polymer and 30 impermeable dispersed solid on a substrate, comprising discharging at least one impermeable dispersed solid in dry powder form through a first orifice; discharging at least one polymer in dry powder form through a second orifice; depositing the polymer and/or impermeable dispersed solids onto said substrate, wherein an electrical potential is maintained between the substrate and the impermeable dispersed solid and/or polymer particles, thereby forming said coating; and sintering said coating under conditions that do not substantially affect the 35 substrate. In some embodiments, the impermeable dispersed solid is dispersed uniformly on all exposed surfaces of the substrate. In some embodiments, the impermeable dispersed solid is impermeable and/or impervious to gas. In some embodiments, the impermeable dispersed solid is impermeable and/or impervious to fluid. In some embodiments, the impermeable dispersed solid is impermeable and/or impervious to biological material. 3 WO 2008/148013 PCT/US2008/064732 100181 In some embodiments, the impermeable dispersed solid comprises nanoparticles, such as, for example, a polyurethane adhesive nanocomposite (organically modified montmorillonite and polyurethane). In some embodiments, the oxygen transmission rate across the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In some embodiments the water vapor permeation through the coating is at most about 1%, 5 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In referring to transmission rate or permeation, "about" refers to variations of .01% to .1%, or 1% to 5%. [0019] Although the size, resistivity and moisture content of the polymer and impermeable dispersed solid may vary widely based on the conditions used, desired particle sizes are typically in the range of 0.01 pm -2500 pm, and more preferably in the range of 0.01 gin - 100 pm, resistivity is typically in the range of from about 106A~m 10 to about 1024f9n and moisture content is less than 5% by weight. In one embodiment of the invention the molecular weight range of the polymer is from about 5,000 a.u. to about 100,000 a.u. [0020] In other embodiments, the first and second orifices are provided as one single orifice wherein the impermeable dispersed solid and polymer may be mixed together prior to discharging. In yet other embodiments the impermeable dispersed solid and polymer particles may be discharged simultaneously or in succession. In 15 another embodiment of the invention the method further comprises discharging a third dry powder comprising a second impermeable dispersed solid whereby a coating comprising at least two different impermeable dispersed solids is deposited on said substrate. In certain other embodiments of the invention the impermeable dispersed solid is prepared by milling, jet-milling, granulation, spray drying, crystallizing or fluidizing. [00211 In a further embodiment the impermeable dispersed solid and/or the polymer becomes electrostatically 20 charged prior to deposition, and the substrate may be electrically grounded. In a preferred embodiment, the substrate is electrostatically charged. In some embodiments the polymer and impermeable dispersed solid are discharged using a gas based propellant, which typically comprises carbon dioxide, nitrous oxide, hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressed air, argon, or volatile hydrocarbons with a vapor pressure greater than 750 Torr at 20oC, and is preferably carbon dioxide. 25 [0022] In one embodiment of the invention the impermeable dispersed solid comprises at least one drug. In another embodiment of the invention the ratio of impermeable dispersed solid to polymer is from about 1:1000 to about 3:10. In some embodiments, the amount of impermeable dispersed solid will depend on the particular dispersed solid being employed, the type of substrate, and the medical condition being treated, [00231 Yet another aspect of the invention provides methods for depositing a coating comprising a polymer 30 and a impermeable dispersed solid on a substrate, comprising discharging at least one impermeable dispersed solid in a therapeutically desirable morphology in dry powder form through a first orifice; forming a supercritical or near supercritical fluid mixture that includes at least one supercritical fluid solvent and at least one polymer and discharging said supercritical or near supercritical fluid solution through a second orifice under conditions sufficient to form solid particles of the polymer; depositing the polymer and/or impermeable dispersed solids 35 onto said substrate, wherein an electrical potential is maintained between the substrate and the impermeable dispersed solids and/or polymer particles, thereby forming said coating and sintering said coating under conditions that do not substantially disrupt the substrate's (e.g. active medical device's) intended functions and proper functioning, if any, or that have unintended consequences within and/or to the patient once implanted. 4 WO 2008/148013 PCT/US2008/064732 [0024] Each of the above methods may be carried out from about 0*C to about 80*C and from about 0.1 atmospheres to about 73 atmospheres, in either open or closed vessel. In some embodiments, the substrate is a biomedical implant which may be a. a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable 5 defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, 10 hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports. [00251 In some embodiments of the invention the thickness of said coating is from about 1 to about 100pm, 15 preferably about 10pm, and the variation in the thickness along said coating is within 0.5pm, within 0.25gm, within 0.1pm or within 10% of the total thickness of said coating, within 5% of the total thickness of said coating, or within 2.5% of the total thickness of said coating. In yet other embodiments, the impermeable dispersed solid is positioned at a selected distance from top of said coating. In further embodiments, the impermeable dispersed solid is positioned at about midway between the top of said coating and the substrate 20 surface. In other embodiments of the invention the variability in the amount of impermeable dispersed solid deposited on said substrate is 20% or less, 15% or less, 10% or less, 5% or less, for a batch of substrates coated at the same time. Preferably the variability is 5% or less. [0026] In yet other embodiments of the invention, the methods further comprise depositing a top layer on said coating wherein said top layer is a polymer film. In some embodiments, the polymer film has a thickness of 0.5 25 to 10 microns, and can be deposited by an eRESS or eSEDS, or a eDPC process. In yet other embodiments, the polymer film is formed by depositing a single polymer and for example by depositing substantially pure PBMA. [0027] The invention further relates to the use of a supercritical solution comprising a second fluid in its supercritical state. [0028] In some embodiments, the addition of a second fluid in its supercritical state is to act as a flammability 30 suppressor. In other embodiments, a second fluid is used, wherein said second fluid has critical parameters lower than the first fluid's critical parameters, and therefore lowers the critical properties of the mixture/solution enabling access to the mixture supercritical state. [00291 In some embodiments the supercritical solution comprises isobutylene. In other embodiments, the supercritical fluid comprises isobutylene and carbon dioxide as a second fluid. 35 [00301 Other embodiments of the invention provide a way to dissolve two polymers in a supercritical solvent. In some embodiments said two polymers are PEVA and PBMA. In other embodiments, a supercritical solution comprising two polymers is used to create a RESS spray of the polymers generating ~10 to 100 nm particles of each polymer. In further embodiments, PEVA and PBMA are dissolved in a supercritical solvent that further comprises CO 2 to act as a fire suppressor in the event of an ignition source causing a fire. 5 WO 2008/148013 PCT/US2008/064732 INCORPORATION BY REFERENCE [0031] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and 5 individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS 10032J The novel features of the invention are set forth with particularity in the appended Claims. A better 10 understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: 10033] Figure 1. Schematic Representation of the Coating and Sintering Process Apparatus. 10034] Figure 2. Detailed images of the Coating and Sintering Process Apparatus. 15 DETAILED DESCRIPTION OF THE INVENTION [0035] The present invention is explained in greater detail below. This description is not intended to be a 20 detailed catalog of all the different ways in which the invention may be implemented, or all the features that may be added to the instant invention. For example, features illustrated with respect to one embodiment may be incorporated into other embodiments, and features illustrated with respect to a particular embodiment may be deleted from that embodiment. In addition, numerous variations and additions to the various embodiments suggested herein will be apparent to those skilled in the art in light of the instant disclosure, which do not depart 25 from the instant invention. Hence, the following specification is intended to illustrate some particular embodiments of the invention, and not to exhaustively specify all permutations, combinations and variations thereof. 100361 Applicants specifically intend that all United States patent references cited herein be incorporated herein by reference in their entirety. 30 [00371 The present invention relates to coatings and methods for depositing a coating comprising a polymer and a impermeable dispersed solid onto a substrate. Provided herein are novel, easy to apply, polymer-based coatings and coating methods to seal and, thereby, shield, for example, implantable medical devices that are electrical in nature such as pacemakers and other "active" implants from interacting with body fluids in vivo in a manner that disrupts the medical device's intended functions and proper functioning, or in a manner that has 35 unintended consequences within and/or to the patient. Provided herein are novel, easy to apply, polymer-based coatings and coating methods to seal, for example, implantable medical devices that are electrical in nature such as pacemakers and other "active" implants and, thereby, shield the body from degradation products, leachants, extractables from the medical device. The coatings and methods provided herein result in a collection process on the substrate that is an efficient, conformal, substantially defect-free, and uniform coating, and a regulatable and 40 controllable coating composition. The coating structures and methods provided herein not only avoid the 6 WO 2008/148013 PCT/US2008/064732 problems of polymer coatings (solvent-based, and solvent-less), but they also improve the barrier properties of polymer films for use as a seal upon, for example, biologically implanted devices. 100381 Provided herein is a composite material coating containing polymer to provide increased barrier properties for gases such as water vapor, and method of creating such coating. 5 [00391 Provided herein is a composite material coating containing polymer plus a impermeable dispersed solid to provide increased barrier properties for gases such as water vapor, and method of creating such coating. [00401 Provided herein is the a method for electrostatic capture of polymer particles upon a substrate followed by sintering of these particles by exposure to compressed gasses. The coating methods used, including e-RESS, e-SEDS, and/or eDPC are free from elevated temperatures, solvent exposure, plasma environments, and other 10 challenges associated with traditional polymer coating methods. [00411 In some embodiments, a coating comprising electrostatically captured polymer particles (generated by eRESS, eSEDS or eDPC) alone or optionally with either concurrent or sequential captured impermeable particles (by eDPC, eRESS, eSEDS) on a medical implant substrate. A method is also provided for electrostatically capturing polymer particles (generated by eRESS, eSEDS or eDPC) alone or with either concurrent or sequential 15 capturing impermeable particles (by eDPC, eRESS, eSEDS) on a medical implant substrate. Following electrostatic capture of the polymer and optionally impermeable particles, the method comprises sintering the medical implant substrate with a compressed gas at conditions adequate to cause flow of the polymer particles into a continuous film on the substrate. [00421 The polymers that could be used in the coatings or methods provided herein are all solution or thermally 20 processible polymers (e.g. acrylates, olefins, fluoropolymers, urethanes, etc.). For example, a polymer (or polymers) could be used with known biocompatibility and high resistance to chemical degradation such as polymers of fluorinated olefins. The impermeable particles that could be used in this coating method includes all inorganic particles that can be obtained in the micron and/or sub-micron size range. For example various compositions of clay, metal-oxides, ceramics, etc. 25 [00431 The resulting film would contain a polymer continuous phase optionally with particles embedded therein. The existence and distribution of the particles causes an increase in the barrier properties of the film to small molecules and gases by blocking diffusion pathways. [00441 In some embodiments of the coating, the surface of the particles is chemically modified to provide greater dispersion and incorporation into the polymer film. In some embodiments of the method for coating, the 30 method comprises chemically modifying the surface of the particles to provide greater dispersion and incorporation into the polymer film. For example in the case of a highly polar particle (e.g. clay, SiO2, TiO2, etc.) in a highly non-polar polymer (e.g. polymeric fluorinated olefins), the process comprises binding or bonding a non-polar chemistry to the surface of the particle prior to incorporation into the powder-coating and sintering process. 35 [0045] Provided herein are stacked polymer films with an intervening impermeable layer which could provide similar protection for sensitive devices in vivo without the difficulty associated with welding metal cans around the device. In some embodiments, polymers to be used in the processes and in the coatings provided herein are inherently hydrophobic, thereby greatly reducing the likelihood of penetration of biological fluids. For example, fluoropolymers as a class yield high surface energy surfaces that meet this requirement. However, surfaces 40 created from such polymers in some cases act as membranes through which water vapor transport can occur. 7 WO 2008/148013 PCT/US2008/064732 Thus, in some embodiments, a second layer that can trap any water vapor that might permeate the fluoropolymer membrane is provided. In some embodiments, the method comprises depositing a hydrophilic polymer layer such as a silicon based polymer over the initial fluoropolymer layer. Silicon based polymers can be designed to possess differing degrees of hydrophilicity and therefore trap any water vapor that might permeate the 5 fluoropolymer layer membrane. In some embodiments, the silicon-based polymer is reduced to native silicon and metallized with titanium. [0046] In some embodiments, a highly absorbent material is used as the water-vapor trapping material. In some embodiments, the highly absorbent material comprises a hydrophilic polymer. In some embodiments, highly absorbent material comprises a superabsorbent polymer. 10 [00471 In some embodiments, a third layer of fluoropolymer is deposited to encapsulate the silicon based polymer layer between the fluropolymer layers. In some embodiments, the coating comprises multiple alternating layers of fluoropolymers and silicon based polymers. In some embodiments, the method comprises alternating multiple layers of the silicon based polymer and the fluropolymer. [0048] In some embodiments, the coating is designed to remain impermeable for at least as long as the 15 expected life span of the device and/or substrate it coats. [00491 One aspect of the invention provides methods for depositing a coating comprising a polymer and impermeable dispersed solid on a substrate, comprising discharging at least one impermeable dispersed solid in dry powder form through a first orifice; discharging at least one polymer in dry powder form through a second orifice; depositing the polymer and/or impermeable dispersed solids onto said substrate, wherein an electrical 20 potential is maintained between the substrate and the impermeable dispersed solid and/or polymer particles, thereby forming said coating; and sintering said coating under conditions that do not substantially affect the substrate. In some embodiments, the impermeable dispersed solid is dispersed uniformly on all exposed surfaces of the substrate. 10050] In some embodiments, the impermeable dispersed solid comprises a nanoparticle, such as, for example, 25 a polyurethane adhesive nanocomposite (organically modified montmorillonite and polyurethane). In some embodiments, the oxygen transmission rate across the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In some embodiments the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In referring to transmission rate or permeation, "about" refers to variations of .01% to .1%, or 1% to 5%. 30 [00511 In some embodiments, the impermeable dispersed solid comprises a nanoparticle that is impervious to small particle transport. In some embodiments, the nanoparticle comprises at least one of a ceramic and a metal. In some embodiments, the nanoparticle comprises clay. In some embodiments the nanoparticle comprises silica. In some embodiments, the nanoparticle comprises titanium oxide. In some embodiments, the nanoparticle does not include nickel. In some embodiments, the nanoparticle does not include copper. In some embodiments, the 35 small particle transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In some embodiments, the oxygen transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In some embodiments the water vapor permeation through the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. In referring to transmission rate or permeation, "about" refers to variations of .001% 40 to .01%, 0.01% to 0.1%, or 1% to 5%. 8 WO 2008/148013 PCT/US2008/064732 [0052] Although the size, resistivity and moisture content of the polymer and impermeable dispersed solid may vary widely based on the conditions used, desired particle sizes are typically in the range of 0.01 pm - 2500 im, and more preferably in the range of 0.01 pm - 100 pm, resistivity is typically in the range of from about 10692m to about 1024Qm and moisture content is less than 5% by weight. In one embodiment of the invention the 5 molecular weight range of the polymer is from about 5,000 a.u. to about 100,000 a.u. [0053] In other embodiments, the first and second orifices are provided as one single orifice wherein the impermeable dispersed solid and polymer may be mixed together prior to discharging. In yet other embodiments the impermeable dispersed solid and polymer particles may be discharged simultaneously or in succession. In another embodiment of the invention the method further comprises discharging a third dry powder comprising a 10 second impermeable dispersed solid whereby a coating comprising at least two different impermeable dispersed solids is deposited on said substrate. In certain other embodiments of the invention the impermeable dispersed solid is prepared by milling, jet-milling, granulation, spray drying, crystallizing or fluidizing. [00541 In a further embodiment the impermeable dispersed solid and/or the polymer becomes electrostatically charged prior to deposition, and the substrate may be electrically grounded. In a preferred embodiment, the 15 substrate is electrostatically charged. In some embodiments the polymer and impermeable dispersed solid are discharged using a gas based propellant, which typically comprises carbon dioxide, nitrous oxide, hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressed air, argon, or volatile hydrocarbons with a vapor pressure greater than 750 Torr at 20oC, and is preferably carbon dioxide. [0055J In one embodiment of the invention the impermeable dispersed solid comprises at least one drug. In 20 another embodiment of the invention the ratio of impermeable dispersed solid to polymer is from about 1:1000 to about 3:10. In some embodiments, the amount of impermeable dispersed solid will depend on the particular dispersed solid being employed, the type of substrate, and the medical condition being treated. [00561 Yet another aspect of the invention provides methods for depositing a coating comprising a polymer and a impermeable dispersed solid on a substrate, comprising discharging at least one a impermeable dispersed 25 solid in a therapeutically desirable morphology in dry powder form through a first orifice; forming a supercritical or near supercritical fluid mixture that includes at least one supercritical fluid solvent and at least one polymer and discharging said supercritical or near supercritical fluid solution through a second orifice under conditions sufficient to form solid particles of the polymer; depositing the polymer and/or impermeable dispersed solids onto said substrate, wherein an electrical potential is maintained between the substrate and the impermeable 30 dispersed solids and/or polymer particles, thereby forming said coating and sintering said coating under conditions that do not substantially disrupt the substrate's (e.g. implantable active medical device's) intended functions and proper functioning, if any, or that have unintended consequences within and/or to the patient once implanted. [00571 Each of the above methods may be carried out from about 09C to about 80*C and from about 0.1 35 atmospheres to about 73 atmospheres, in either open or closed vessel. In some embodiments, the substrate is a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic 40 implant, femoral pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor 9 WO 2008/148013 PCT/US2008/064732 hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic 5 device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.. [00581 In some embodiments of the invention the thickness of said coating is from about 1 to about 100pm, preferably about 10pm, and the variation in the thickness along said coating is within 0.5 m, within 0.25pm, within 0.1gm or within 10% of the total thickness of said coating, within 5% of the total thickness of said 10 coating, or within 2.5% of the total thickness of said coating. In yet other embodiments, the impermeable dispersed solid is positioned at a selected distance from top of said coating. In further embodiments, the impermeable dispersed solid is positioned at about midway between the top of said coating and the substrate surface. In other embodiments of the invention the variability in the amount of impermeable dispersed solid deposited on said substrate is 20% or less, 15% or less, 10% or less, 5% or less, for a batch of substrates coated 15 at the same time. Preferably the variability is 5% or less. [00591 In yet other embodiments of the invention, the methods further comprise depositing a top layer on said coating wherein said top layer is a polymer film. In some embodiments, the polymer film has a thickness of 0.5 to 10 microns, and can be deposited by an eRESS or eSEDS, or a eDPC process. In yet other embodiments, the polymer film is formed by depositing a single polymer and can be formed by depositing substantially pure 20 PBMA. [00601 The invention further relates to the use of a supercritical solution comprising a second fluid in its supercritical state. [00611 In some embodiments, the addition of a second fluid in its supercritical state is to act as a flammability suppressor. In other embodiments, a second fluid is used, wherein said second fluid has critical parameters lower 25 than the first fluid's critical parameters, and therefore lowers the critical properties of the mixture/solution enabling access to the mixture supercritical state. [0062] In some embodiments the supercritical solution comprises isobutylene. In other embodiments, the supercritical fluid comprises isobutylene and carbon dioxide as a second fluid. 10063] Other embodiments of the invention provide a way to dissolve two polymers in a supercritical solvent. 30 In some embodiments said two polymers are PEVA and PBMA. In other embodiments, a supercritical solution comprising two polymers is used to create a RESS spray of the polymers generating -10 to 100 nm particles of each polymer. In further embodiments, PEVA and PBMA are dissolved in a supercritical solvent that further comprises CO 2 to act as a fire suppressor in the event of an ignition source causing a fire. [0064] One aspect of the invention entails the deposition of the a impermeable dispersed solid as dry powders, 35 using electrostatic capture to attract the powder particles to the substrate. Dry powder spraying is well known in the art, and dry powder spraying coupled with electrostatic capture has been described, for example in US Patents 5,470,603 6,319,541 or 6,372,246. The deposition of the polymer can be performed in any number of standard procedures, as the morphology of the polymer, so long as it provides coatings possessing the desired properties (e.g. thickness, conformity, defect-free, uniformity), and are free from elevated temperatures, solvent 40 exposure, plasma environments, and other challenges associated with traditional polymer coating methods. 10 WO 2008/148013 PCT/US2008/064732 [00651 The second step of the coating process involves taking the substrates that have been coated with impermeable dispersed solids and polymers and subjecting them to a sintering process that takes place under conditions free from elevated temperatures, solvent exposure, plasma environments, and other challenges associated with traditional polymer coating methods. The sintering process as used in the current invention refers 5 to the process by which the co-deposited impermeable dispersed solid -polymer matrix become fused and adherent to the substrate by treatment of the coated substrate with a compressed gas, compressed liquid, or supercritical fluid that is a non-solvent for the polymers and the impermeable dispersed solid(s), but a plasticizing agent for the polymer. The sintering process takes place under conditions (e.g. mild temperatures), and using benign fluids (e.g. supercritical carbon dioxide) which will not affect the active substrate or its 10 subsequent function, if any. [00661 One aspect of the invention is the combination of two or more of the e-DPC, e-RESS and e-SEDS spraying techniques. [00671 A specific aspect of the invention involves the dry powder spraying of impermeable dispersed solid, in a preferred particle size, into the same capture vessel as a polymer that is also dry powder sprayed, whereby the 15 spraying of the impermeable dispersed solid and the polymer is sequential or simultaneous. [00681 In some embodiments, the invention involves the e-DPC spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eRESS spray process. In some embodiments, the invention involves the e-DPC spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eSEDS spray 20 process. In some embodiments, the invention involves the e-DPC spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eDPC spray process. 100691 In some embodiments, the invention involves the e-RESS spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eRESS spray 25 process. In some embodiments, the invention involves the e-RESS spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eSEDS spray process. In some embodiments, the invention involves the e-RESS spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eDPC spray process. 30 [00701 In some embodiments, the invention involves the e-SEDS spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eRESS spray process. In some embodiments, the invention involves the e-SEDS spraying of the impermeable dispersed solid, into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eSEDS spray process. In some embodiments, the invention involves the e-SEDS spraying of the impermeable dispersed solid, 35 into the same capture vessel as a polymer that is sequentially or simultaneously sprayed by the eDPC spray process. [00711 Any combination of the above processes is contemplated by this aspect of the invention. 11 WO 2008/148013 PCT/US2008/064732 [00721 In further aspects of the invention the substrates that have been coated with impermeable dispersed solid and polymers, as described in the above embodiments are then subjected to a sintering process. The sintering process takes place under conditions free from elevated temperatures, solvent exposure, plasma environments, and other challenges associated with traditional polymer coating methods, and refers to a process 5 by which the co-deposited impermeable dispersed solid-polymer matrix, becomes fused and adherent to the substrate. This is achieved by treating the coated substrate with a compressed gas, compressed liquid or supercritical fluid that is a non-solvent for the polymers, the impermeable dispersed solids, but a plasticizing agent for the polymer. The sintering process takes place under conditions (e.g. mild temperatures), and using benign fluids (e.g. supercritical carbon dioxide) which will not affect the active substrate or its subsequent 10 function, if any. Other sintering processes, which do not affect the active substrate or its subsequent function, if any may also be contemplated by the present invention. Definitions 100731 As used in the present specification, the following words and phrases are generally intended to have the 15 meanings as set forth below, except to the extent that the context in which they are used indicates otherwise. [00741 "Substrate" as used herein, refers to any surface upon which it is desirable to deposit a coating comprising a polymer or a mix of polymer with or without impermeable dispersed solid, or hydrophobic polymers and a water-vapor-trapping material, wherein the coating process does not substantially disrupt the substrate's (e.g. implantable active medical device's) intended functions and/or proper functioning, if any, or in a 20 manner that has unintended consequences within and/or to the patient. Biomedical implants are of particular interest for the present invention; however the present invention is not intended to be restricted to this class of substrates. Those of skill in the art will appreciate alternate substrates that could benefit from the coating process described herein, such as temporary implantable devices, diagnostic tests or kits. [00751 "Biomedical implant" as used herein refers to any implant for insertion into the body of a human or 25 animal subject, including but not limited to a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft, anastomotic device, perivascular 30 wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, 35 intraluminal devices, and vascular supports, etc. [0076J The implants may be formed from any suitable material, including but not limited to organic polymers (including stable or inert polymers and biodegradable polymers), metals, inorganic materials such as silicon, and composites thereof, including layered structures with a core of one material and one or more coatings of a different material. 12 WO 2008/148013 PCT/US2008/064732 [00771 Subjects into which biomedical implants of the invention may be applied or inserted include both human subjects (including male and female subjects and infant, juvenile, adolescent, adult and geriatric subjects) as well as animal subjects (including but not limited to dog, cat, horse, monkey, etc.) for veterinary purposes. [00781 In a preferred embodiment the biomedical implant is an implantable pacemaker, cardioverter or 5 defibrillator, or another active device or any implantable (permanent or temporary) device requiring sealing to prevent gas or fluid permeation. [0079] "Active" or "Active medical device" as used herein refers to medical devices that are electrical in nature, such as pacemakers and other medical devices for sensing, delivery of therapeutics and/or active control of various bodily functions. 10 [00801 "Medical device" as used herein can refer to biological implants as defined herein active or inactive. A medical device may be permanently implantable, temporarily implantable, entirely implantable (such as, for example, an implantable defibrillator), partially implantable (such as, for example, a sensing drainage catheter) and/or can refer to devices used on or in a patient during a diagnostic or therapeutic procedure, including during an invasive surgery or during a minimally invasive surgery. A medical device includes any instrument, 15 apparatus, appliance, material or other article, whether used alone or in combination, including any software necessary for its proper application intended by the manufacturer to be used for human beings for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease, alleviation of pain, diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap, investigation, replacement or modification of the anatomy or of a physiological process, control of conception, and which does not achieve its principal 20 intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means. For example, an insulin pump implanted in a diabetic person which dispenses insulin stored in the pump into the patient's blood based upon glucose levels sensed by the pump is a medical device (and is an active medical device and a biological implant). [00811 "Biological material" as used herein can refer a biological material in gas or fluid state including small 25 solid particles. 100821 "Defect" as used herein can refer to, but is not limited to: surface topology variability, such as a clump, a web, or a pool; a through-layer deficiency, such as a bare spot, a fracture, a crack, a pin hole, a thin spot, a blemish; or a under-layer defect, such as a bubble between layers, a bubble beneath a layer, matter trapped beneath a layer or between layers of coating which is not a part of the substrate or of the layer(s), such as dust, 30 liquid, gas, or particulate, An under-layer defect might affect the seal of a substrate device. For example, an under-layer water vapor bubble might act as a sink for diffusion of water vapor, making an active device more prone to interacting with the vapor and/or potentially with body fluids in vivo in a manner that disrupts the substrate's (e.g. active device's) intended functions and/or proper functioning, if any, or in a manner that has unintended consequences within and/or to the patient. Likewise, any other defect (through-layer, or surface 35 topology variability) which allows gas or fluids to interact with the substrate can potentially result in disruption of the substrate's (e.g. active device's) intended functions and/or proper functioning, if any, or in a manner that has unintended consequences within and/or to the patient (such as, for a non-limiting example, freeing leachables, and/or creating or releasing degradation products or extractables from the device and into the body of the patient). 13 WO 2008/148013 PCT/US2008/064732 [0083] "Conformal coating", "conformally coated", or "conformably coated" as used herein can refer to a protective covering that conforms to the configuration of the objects coated. A covering that is conformal covers susbtantially all surfaces with a uniform layer. For example, a coating layering process may confomally coat a device with a 10 micron coating (of a layer or of layers) plus or minus 10%, which results in a 10 micron plus or 5 minus 10% coating on every external surface of the device that is at least about 20 microns apart from another external surface of the device (external surfaces of the device that are closer may appear to have thicker coatings as the coatings on of the two nearby surfaces join). [00841 "Seal" or "Substantially sear' as used herein can refer to coating that substantially shields a substrate from interacting with materials (fluids, gases, solids), in a manner that disrupts the substrate's intended 10 functions and/or proper functioning, if any, or in a manner that has unintended consequences within and/or to the patient. As used herein, the term(s) can refer to coating that substantially shields transmission of degradation products, leachants, and extractables from the substrate past and/or through the coating. Seals on a substrate can be applied to electronic circuitry to act as protection for the circuitry against, for example, moisture, dust, chemicals, and/or temperature extremes. Similarly, seals can be applied to devices to act as protection against, 15 for example, moisture, dust, chemicals, leachants, extractable components (extractables) and/or degradation products, from passing from the device through the coating layer(s). A seal, therefore can be a one-way and/or two-way barrier to moisture, dust, chemicals, leachants, degradation products, and/or other material (fluid or gas), including biologic material. The one-way barrier can be a barrier in either direction, a barrier to allowing material to contact the substrate, or a barrier to allowing material to pass from the substrate through the coating 20 for example to the blood stream of a subject. For example, a medical device that is electrical in nature such as a pacemaker and/or another "active" implant body fluids in vivo can be substantially sealed by a coating and, thereby, substantially shielded from interacting with materials (fluids, gases, solids), in a manner that disrupts the substrate's intended functions and/or proper functioning, if any, or in a manner that has unintended consequences within and/or to the patient. Medical devices that are not electrical in nature (or not primarily 25 electrical in nature) may also be sealed as provided herein. "Substantially" where used herein with respect to sealing or seals, can mean at least about one of 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% 99.6%, 99.7%, 99.8%, 99.9%, 99.95%, 99.99%, and 99.995% sealed. "About" where used herein with respect to sealing or seals percentages, can mean variability of .1 to .5%, or 1-5%. "Substantially" where used herein with respect to sealing or seals, can also or alternatively mean a seal that passes a coating visual inspection, an adhesion test, a 30 chemical resistance test, and/or a coating fatigue test, device fatigue in an in vitro test, device fatigue in a simulated in vivo environment test, a resistance test in a simulated in vivo environment Examples of such tests include, but are not limited to, ASTM D6677, ASTM D3359, ASTM D4541, ASTM D2197, ASTM D2370, ASTM D5179, ASTM D4145, ASTM 4146, ASTM F1854-01. [00851 "Polymer" as used herein, refers to a series of repeating monomeric units that have been cross-linked or 35 polymerized. Any suitable polymer can be used to carry out the present invention. It is possible that the polymers of the invention may also comprise two, three, four or more different polymers. In some embodiments, of the invention only one polymer is used. In some preferred embodiments a combination of two polymers are used. Combinations of polymers can be in varying ratios, to provide coatings with differing properties. Those of skill in the art of polymer chemistry will be familiar with the different properties of polymeric compounds. Examples 40 of ploymers that may be used in the present invention include, but are not limited to polycarboxylic acids, 14 WO 2008/148013 PCT/US2008/064732 cellulosic polymers, , proteins, polypeptides, polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters, polyurethanes, polystyrenes, copolymers, silicones, polyorthoesters, polyanhydrides, copolymers of vinyl monomers, polycarbonates, polyethylenes, polypropylenes, polylactic acids, polyglycolic acids, polycaprolactones, 5 polyhydroxybutyrate valerates, polyacrylamides, polyethers, polyurethane dispersions, polyacrylates, acrylic latex dispersions, polyacrylic acid, mixtures and copolymers thereof. The polymers of the present invention may be natural or synthetic in origin, including gelatin, chitosan, dextrin, cyclodextrin, Poly(urethanes), Poly(siloxanes) or silicones, Poly(acrylates) such as poly(methyl methacrylate), poly(butyl methacrylate), and Poly(2-hydroxy ethyl methacrylate), Poly(vinyl alcohol) Poly(olefins) such as poly(ethylene), poly(isoprene), 10 halogenated polymers such as Poly(tetrafluoroethylene) - and derivatives and copolymers such as those commonly sold as Teflon@ products, Poly(vinylidine fluoride), Poly(vinyl acetate), Poly(vinyl pyrrolidone),. Poly(acrylic acid), Polyacrylamide, Poly(ethylene-co-vinyl acetate), Poly(ethylene glycol), Poly(propylene glycol), Poly(methacrylic acid); etc. Suitable polymers also include absorbable and/or resorbable polymers including the following, combinations, copolymers and derivatives of the following: Polylactides (PLA), 15 Polyglycolides (PGA), Poly(lactide-co-glycolides) (PLGA), Polyanhydrides, Polyorthoesters, Poly(N-(2 hydroxypropyl) methacrylamide), Poly(1-aspartamide), etc. [00861 "Water-vapor trapping material" as used herein includes, but is not limited to a hydrophilic polymer. "Water-vapor trapping material" as used herein includes, but is not limited to a highly absorbent material, which may comprises a superabsorbent polymer. Examples of water-vapor trapping materials include, but are not 20 limited to, acrylate polymers, generally formed from acrylic acid, methacrylic acid, acrylate, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, a dialkylaminoalkyl acrylate, a dialkylaminoalkyl methacrylate, a trialkylammonioalkyl acrylate, and/or a trialkylammonioalkyl methacrylate, and include the polymers or copolymers of acrylic acid, methacrylic acid, methyl methacrylate, ethyl methacrylate, 2 dimethylaminoethyl methacrylate, and trimethylammonioethyl methacrylate chloride. Examples of hydrophilic 25 polymers include, but is not limited to poly(N-vinyl lactams), poly(N-vinyl acrylamides), poly(N alkylacrylamides), substituted and unsubstituted acrylic and methacrylic acid polymers, polyvinyl alcohol (PVA), polyvinylamine, copolymers thereof and copolymers with other types of hydrophilic monomers (e.g. vinyl acetate), polysaccharides, crosslinked acrylate polymers and copolymers, carbomers, crosslinked acrylamide-sodium acrylate copolymers, gelatin, vegetable polysaccharides, such as alginates, pectins, 30 carrageenans, or xanthan, starch and starch derivatives, galactomannan and galactomannan derivatives. polyvinyl pyrrolidone (PVP), poly(N- vinyl caprolactam) (PVCap), poly(N- vinyl acetamides), polyacrylic acid, polymethacrylic acid, and copolymers and blends thereof. PVP and PVCap. Examples of superabsorbent polymers include hydrogels. Copolymers of any of the water-vapor trapping materials mentioned herein, and blends thereof may also be used. 35 [00871 "Hydrophobic polymer" as used herein can refer to any polymer resistant to wetting, or not readily wet, by water, i.e., having a lack of affinity for water. Examples of hydrophobic polymers include, by way of illustration only, polyolefins, such as polyethylene, poly(isobutene), poly(isoprene), poly(4-methyl- 1 -pentene), polypropylene, ethylene-propylene copolymers, ethylene-propylene-hexadiene copolymers, and ethylene-vinyl acetate copolymers; metallocene polyolefins, such as ethylene-butene copolymers and ethylene-octene 40 copolymers; styrene polymers, such as poly(styrene), poly(2-methylstyrene), and styrene-acrylonitrile 15 WO 2008/148013 PCT/US2008/064732 copolymers having less than about 20 mole-percent acrylonitrile; vinyl polymers, such as poly(vinyl butyrate), poly(vinyl decanoate), poly(vinyl dodecanoate), poly(vinyl bexadecanoate), poly(vinyl hexanoate), poly(vinyl octanoate), and poly(methacrylonitrile); acrylic polymers, such as poly(n-butyl acetate), and poly(ethyl acrylate); methacrylic polymers, such as poly(benzyl methacrylate), poly(n-butyl methacrylate), poly(isobutyl 5 methacrylate), poly(t-butyl methacrylate), poly(t-butylaminoethyl methacrylate), poly(do-decyl methacrylate), poly(ethyl methacrylate), poly(2-ethylhexyl methacrylate), poly(n-hexyl methacrylate), poly(phenyl methacrylate), poly(n-propyl methacrylate), and poly(octadecyl methacrylate); polyesters, such a poly(ethylene terephthalate) and poly(butylene terephthalate); and polyalkenes and polyalkynes, such as polybutylene and polyacetylene. Copolymers of any of the hydrophobic polymers mentioned herein, and blends thereof may also 10 be used. The hydrophobic polymer also may contain minor amounts of additives as is customary in the art. For example, the hydrophobic polymer may contain pigments, delustrants, antioxidants, antistatic agents, stabilizers, oxygen scavengers, and the like. In some embodiments, the hydrophobic polymer is a polymer having a bulk density of at least about 1.00 grams per cubic centimeter (g/cc). In some embodiments, the hydrophobic polymer is a polymer having a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc). In some 15 embodiments, the hydrophobic polymer is a polymer having a bulk density of one of at least about 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc). In referring to bulk density, "about" refers to variations of .001 to .005, or of 0.005 to 0.01 grams per cubic centimeter (g/cc). 20 [00881 "Polyolefim" as used herein can refer to a polymer prepared by the addition polymerization of one or more unsaturated monomers which contain only carbon and hydrogen atoms. Examples of such polyolefins include polyethylene, polypropylene, poly(l-butene), poly(2-butene), poly(I -pentene), poly(2-pentene), poly(3 methyl-l-pentene), poly(4-methyl-1-pentene), and the like. In addition, such term is meant to include blends of two or more polyolefins and random and block copolymers prepared from two or more different unsaturated 25 monomers. [0089] "Compressed fluid" as used herein refers to a fluid of appreciable density (e.g., >0.2 g/cc) that is a gas at standard temperature and pressure. " Supercritical fluid", "near-critical fluid", "near-supercritical fluid", "critical fluid", "densified fluid" or "densified gas" as used herein refers to a compressed fluid under conditions wherein the temperature is at least 80% of the critical temperature of the fluid and the pressure is at least 50% of 30 the critical pressure of the fluid. [0090] Examples of substances that demonstrate supercritical or near critical behavior suitable for the present invention include, but are not limited to carbon dioxide, isobutylene, ammonia, water, methanol, ethanol, ethane, propane, butane, pentane, dimethyl ether, xenon, sulfur hexafluoride, halogenated and partially halogenated materials such as chlorofluorocarbons, hydrochlorofluorocarbons, hydrofluorocarbons, perfluorocarbons (such 35 as perfluoromethane and perfuoropropane, chloroform, trichloro-fluoromethane, dichloro-difluoromethane, dichloro-tetrafluoroethane), 1,1,1,2,3,3-hexafluoopropane (R236ea) and mixtures thereof. 16 WO 2008/148013 PCT/US2008/064732 [00911 "Sintering" as used herein refers to the process by which the co-deposited impermeable dispersed solid polymer matrix, as described herein, or the hydrophobic polymer and water-vapor-trapping material becomes fused and adherent to the substrate by treatment of the coated substrate with a compressed gas, compressed liquid, or supercritical fluid that is a non-solvent for both the polymer and the impermeable dispersed solid or the 5 hydrophobic polymer and water-vapor-trapping material, but a plasticizing agent for the polymer(s). [0092] "Rapid Expansion of Supercritical Solutions" or "RESS" as used herein involves the dissolution of a polymer into a compressed fluid, typically supercritical CO 2 , followed by rapid expansion into a chamber at atmospheric pressure. The rapid expansion of the supercritical fluid solution through a small opening, with its accompanying decrease in density, reduces the dissolution capacity of the fluid and results in the nucleation and 10 growth of polymer particles. [00931 "Solution Enhanced Dispersion of Supercritical Solutions" or "SEDS" as used herein involves a spray process for the generation of polymer particles, which are formed when a compressed fluid (e.g. supercritical fluid, preferably supercritical CO 2 ) is used as a diluent to a vehicle in which a polymer dissolved, (one that can dissolve both the polymer and the compressed gas). The mixing of the compressed fluid diluent with the 15 polymer-containing solution may be achieved by encounter of a first stream containing the polymer solution and a second stream containing the diluent compressed fluid, for example, within one spray nozzle or by the use of multiple spray nozzles. The solvent in the polymer solution may be one compound or a mixture of two or more ingredients and may be or comprise an alcohol (including diols, trials, etc.), ether, amine, ketone, carbonate, or alkanes, or hydrocarbon (aliphatic or aromatic) or may be a mixture of compounds, such as mixtures of alkanes, 20 or mixtures of one or more alkanes in combination with additional compounds such as one or more alcohols. (e.g., from 0 or 0.1 to 5% of a Cj to C 15 alcohol, including diols, triols, etc.). See for example US Patent No. 6,669,785. The solvent may optionally contain a surfactant, as also described in (for example) US Patent No. 6,669,785. [00941 In one embodiment of the SEDS process, a first stream of fluid comprising a polymer dissolved in a 25 common solvent is co-sprayed with a second stream of compressed fluid. Polymer particles are produced as the second stream acts as a diluent that weakens the solvent in the polymer solution of the first stream. The now combined streams of fluid, along with the polymer particles, flow out of the nozzle assembly into a collection vessel. Control of particle size, particle size distribution, and morphology is achieved by tailoring the following process variables: temperature, pressure, solvent composition of the first stream, flow-rate of the first stream, 30 flow-rate of the second stream, composition of the second stream (where soluble additives may be added to the compressed gas), and conditions of the capture vessel. Typically the capture vessel contains a fluid phase that is at least five to ten times (5-10x) atmospheric pressure. [00951 "Electrostatically charged" or "electrical potential" or "electrostatic capture" as used herein refers to the collection of the spray-produced particles upon a substrate that has a different electrostatic potential than the 35 sprayed particles. Thus, the substrate is at an attractive electronic potential with respect to the particles exiting, which results in the capture of the particles upon the substrate. i.e. the substrate and particles are oppositely charged, and the particles transport through the fluid medium of the capture vessel onto the surface of the substrate is enhanced via electrostatic attraction. This may be achieved by charging the particles and grounding the substrate or conversely charging the substrate and grounding the particles, or by some other process, which 40 would be easily envisaged by one of skill in the art of electrostatic capture. 17 WO 2008/148013 PCT/US2008/064732 [00961 "Electrostatic Rapid Expansion of Supercritical Solutions" or "e-RESS" or "eRESS" as used herein refers to Electrostatic Capture as described herein combined with Rapid Expansion of Supercritical Solutions as described herein. [00971 "Electrostatic Solution Enhanced Dispersion of Supercritical Solutions" or "e-SEDS" or "eSEDS" as 5 used herein. refers to Electrostatic Capture as described herein combined with Solution Enhanced Dispersion of Supercritical Solutions as described herein. [0098] "Electrostatic Dry Powder Coating" or "e-DPC" or "eDPC" as used herein refers to Electrostatic Capture as described herein combined with Dry Powder Coating. e-DPC deposits material (including, for example, polymer or impermeable dispersed solid) on the device or other substrate as dry powder, using 10 electrostatic capture to attract the powder particles to the substrate. Dry powder spraying ("Dry Powder Coating" or "DPC" ) is well known in the art, and dry powder spraying coupled with electrostatic capture has been described, for example in US Patents: 5,470,603; 6,319,541; or 6,372,246. [00991 "Open vessel" as used herein refers to a vessel open to the outside atmosphere, and thus at substantially the same temperature and pressure as the outside atmosphere. 15 [001001 "Closed vessel" as used herein refers to a vessel sealed from the outside atmosphere, and thus may be at significantly different temperatures and pressures to the outside atmosphere. Examples [00101] The following examples are given to enable those skilled in the art to more clearly understand and to practice the present invention. They should not be considered as limiting the scope of the invention, but merely 20 as being illustrative and representative thereof. [00102] Example 1: [00103] A biocompatible fluoropolymer or other hydrophobic biocompatible polymer is dissolved in an appropriate supercritical solvent such as carbon dioxide. This solution is maintained in a syringe pump or other pressure vessel and transferred to a spraying vessel that is maintained above the compressed gas's critical 25 pressure and temperature as modified by the solute. The device or other substrate to be coated is held such that it can placed at an electrical potential relative to a nozzle through which the compressed gas solution is to be sprayed (10 kV, for example, with the device held at 5 kV and the nozzle held at -5kV). The electrical field between the device and the nozzle is designed to be homogenous and constant. The polymer solution is expanded through the restrictor nozzle by electrostatic rapid expansion of a supercritical solution (e-RESS), 30 thereby coating the device with a fine film controllable in both thickness and conformality. Subsequent processing in the gas in its uncompressed state further reduces the volume of the film increasing its conformality. A second layer is deposited consisting of a silicon based polymer in the same manner as the first polymer layer. Alternatively, this polymer could be deposited as a dry dispersed solid using e-DPC or from solution in a compressed gas solvent. This silicon based polymer is selected so that it traps any water vapor that permeates 35 the fluoropolymer layer. Finally, the polymer stack is completed by deposition of another layer of fluoropolymer using the e-RESS process and processed to reduce its volume (processing in the gas in its uncompressed state to further reduce the volume of the film and increase its conformality). 18 WO 2008/148013 PCT/US2008/064732 [001041 Example 2 [00105] A biocompatible fluoropolymer or other hydrophobic biocompatible polymer is dissolved in an appropriate supercritical solvent such as carbon dioxide. This solution is maintained in a syringe pump or other pressure vessel and transferred to a spraying vessel that is maintained above the compressed gas's critical 5 pressure and temperature as modified by the solute. The device or other substrate to be coated is held such that it can placed at an electrical potential relative to a nozzle through which the compressed gas solution is to be sprayed (10 kV, for example, with the device held at 5 kV and the nozzle held at -5kV). The electrical field between the device and the nozzle is designed to be homogenous and constant. The polymer solution is expanded through the restrictor nozzle by electrostatic rapid expansion of a supercritical solution (e-RESS), 10 thereby coating the device with a fine film controllable in both thickness and conformality. Subsequent processing in the gas in its uncompressed state further reduces the volume of the film increasing its conformality. A second layer of carbonaceous material is deposited by e-DPC. A quantity of carbonaceous material is loaded as a plug into a chamber. The quantity of material initially loaded is dependent upon the desired coating mass and is a function of the potential at which the device or other substrate is held and the backpressure placed on the 15 plug. A valve is rapidly opened through which the material expands creating an aerosolized cloud which coats the device or other substrate as a dry powder. This coating is immediately followed with a second fluoropolymer coating and undergoes the same volume reducing process as the initial layer (processing in the gas in its uncompressed state to further reduce the volume of the film and increase its conformality). 20 [001061 While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following Claims define the scope of the 25 invention and that methods and structures within the scope of these Claims and their equivalents be covered thereby. 19

权利要求:
Claims (262)
[1] 1. A method of preparing a coated substrate comprising:
[2] 2. providing a substrate;
[3] 3. depositing on said substrate at least one layer comprising a polymer, 5 4. wherein the layer substantially seals the substrate.
[4] 5. The method of Claim 1, wherein the layer is substantially impermeable to a gas.
[5] 6. The method of Claim 1, wherein the layer is substantially impermeable to a fluid.
[6] 7. The method of Claim 1-, wherein the layer is substantially impervious to a biological material.
[7] 8. The method of Claim 1, wherein the polymer is hydrophobic. 10 9. The method of Claim 1, wherein the polymer is at least one of a polyolefin, a metallocenc polyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne.
[8] 10. The method of Claim 1, wherein the polymer has a bulk density of at least about 1.00 grams per cubic centimeter (g/cc).
[9] 11. The method of Claim 1, wherein the polymer has a bulk density of greater than about 1.00 gram per cubic 15 centimeter (g/cc).
[10] 12. The method of Claim 1, wherein the polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc). 20 13. The method of Claims 1, further comprising:
[11] 14. depositing on said substrate at least one layer comprising an impermeable dispersed solid.
[12] 15. The method of Claim 1, wherein the layer provides a substantially conformal coating on the substrate.
[13] 16. The method of Claim 1, wherein the layer provides a coating that is substantially impermeable to leachants from the substrate. 25 17. The method of Claim 12, wherein the impermeable dispersed solid is impermeable to a gas.
[14] 18. The method of Claim 1, wherein the substrate is a medical device.
[15] 19. The method of Claim 14, wherein the medical device is an active medical device.
[16] 20. The method of Claim 1, further comprising depositing on said substrate one or more polymer layers.
[17] 21. The method of one of Claim 1, further comprising depositing on said substrate one or more impermeable 30 dispersed solid layers.
[18] 22. The method of Claim 1, comprising depositing 5, 10, 20, 50, or 100 layers of at least one of a polymer and an impermeable dispersed solid.
[19] 23. The method of Claim 10, comprising depositing said impermeable dispersed solid layer by an e-RESS, an e-SEDS, or an e-DPC process. 35 24. The method of Claim 1, comprising depositing said polymer layer by an e-RESS, an e-SEDS, or an e DPC process.
[20] 25. The method of Claim 1, wherein the polymer layer is substantially defect-free. 26, The method of Claim 1, comprising depositing a coating formed by the polymer layer and an impermeable dispersed solid layer in combination wherein the coating is substantially defect-free. 20 WO 2008/148013 PCT/US2008/064732
[21] 27. The method of Claim 10, wherein depositing said impermeable dispersed solid layer provides improved adherence of the impermeable dispersed solid to at least one of the substrate and the polymer layer.
[22] 28. The method of Claim 1, wherein depositing said polymer layer provides improved adherence of the polymer to the substrate. 5 29. A method of preparing a coated substrate comprising:
[23] 30. providing a substrate;
[24] 31. depositing on said substrate at least one layer comprising an impermeable dispersed solid and a polymer.
[25] 32. The method of Claim 25, wherein the layer substantially seals the substrate.
[26] 33. The method of Claim 25, wherein the layer is substantially impermeable to a gas. 10 34. The method of Claim 25, wherein the layer is substantially impermeable to a fluid.
[27] 35. The method of Claim 25, wherein the layer is substantially impervious to a biological material.
[28] 36. The method of Claim 25, wherein the polymer is hydrophobic.
[29] 37. The method of Claim 25, wherein the polymer is at least one of a polyolefin, a metallocene polyolefms, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne. 15 38. The method of Claim 25, wherein the polymer has a bulk density of at least about 1.00 grams per cubic centimeter (g/cc).
[30] 39. The method of Claim 25, wherein the polymer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc).
[31] 40. The method of Claim 25, wherein the polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 20 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.25, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
[32] 41. The method of Claim 25, wherein the layer provides a substantially conformal coating on the substrate.
[33] 42. The method of Claim 25, wherein the layer provides a coating that is substantially impermeable to 25 leachants from the substrate.
[34] 43. The method of Claim 25, wherein the impermeable dispersed solid is impermeable to a gas.
[35] 44. The method of Claim 25, wherein the substrate is a medical device.
[36] 45. The method of Claim 38, wherein the medical device is an active medical device.
[37] 46. The method of Claim 25, comprising depositing 5, 10, 20, 50, or 100 layers of at least one of a polymer 30 and a impermeable dispersed solid.
[38] 47. The method of Claim 25, comprising depositing said layer by an e-RESS, an e-SEDS, or an e-DPC process.
[39] 48. The method of Claim 25, wherein the layer is substantially defect-free.
[40] 49. The method of Claim 25, wherein depositing said layer provides improved adherence of the layer to the 35 substrate.
[41] 50. A method for depositing a coating comprising a polymer on a substrate, comprising the following steps:
[42] 51. discharging at least one polymer in dry powder form through a first orifice;
[43] 52. depositing the polymer onto said substrate, wherein an electrical potential is maintained between the substrate and the polymer particles, thereby forming said coating; and 21 WO 2008/148013 PCT/US2008/064732
[44] 53. sintering said coating under conditions that do not substantially disrupt the activity and/or function of the substrate,
[45] 54. wherein the coating substantially seals the substrate.
[46] 55. The method of Claim 44, further comprising: 5 56. discharging at least one impermeable dispersed solid in dry powder form through a second orifice.
[47] 57. The method of Claim 45, further comprising: depositing the gas impermeable dispersed solid onto said substrate, wherein an electrical potential is maintained between the substrate and the impermeable dispersed solid.
[48] 58. The method of Claim 45, wherein the impermeable dispersed solid and/or the polymer becomes 10 electrostatically charged prior to deposition on said substrate.
[49] 59. The method of Claim 45, wherein the substrate is electrostatically charged.
[50] 60. The method of Claim 45, wherein the substrate is electrically grounded, and the impermeable dispersed solid and/or the polymer particles are charged.
[51] 61. The method of Claim 45, wherein said polymer and said impermeable dispersed solid are discharged 15 using a gas based propellant.
[52] 62. The method of Claim 50, wherein said gas based propellant comprises at least one of the members selected from the group consisting of carbon dioxide, nitrous oxide, hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressed air, argon, and volatile hydrocarbons with a vapor pressure greater than 750 Torr at 20oC. 20 63. The method of Claim 51, wherein said gas based propellant comprises carbon dioxide.
[53] 64. The method of Claim 45, wherein the average particle size of said polymer and/or impermeable dispersed solid particles is from about 0.1 micron to about 100 microns.
[54] 65. The method of Claim 45, wherein the molecular weight range of said polymer is from about 5,000 a.u. to about 100,000 a.u. 25 66. The method of Claim 45, wherein the resistivity of said polymer and/or impermeable dispersed solid dry powders is from about 1060m to about 10241m.
[55] 67. The method of Claim 45, wherein the moisture content of said polymer and/or impermeable dispersed solid dry powders is less than 5% by weight.
[56] 68. The method of Claim 45, wherein said first and said second orifices are provided as one single orifice. 30 69. The method of Claim 57, wherein said impermeable dispersed solid and said polymer are mixed together prior to discharging.
[57] 70. The method of Claim 45, wherein said impermeable dispersed solid and said polymer particles are discharged simultaneously.
[58] 71. The method of Claim 45, wherein said impermeable dispersed solid and said polymer particles are 35 discharged in succession.
[59] 72. The method of Claim 45, carried out at a temperature from about OoC to about 80"C.
[60] 73. The method of one of Claims 1, 25, and 44, wherein the impermeable dispersed solid comprises a nanoparticle,
[61] 74. The method of Claim 62, wherein the nanoparticle is a polyurethane adhesive nanocomposite. 22 WO 2008/148013 PCT/US2008/064732
[62] 75. The method of Claim 62, wherein the nanoparticle comprises organically modified montmorillonite and polyurethane.
[63] 76. The method of one of Claims 1, 25, and 44, wherein the oxygen transmission rate across the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. 5 77. The method of one of Claims 1, 25, and 44, wherein the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[64] 78. The method of one of Claims 1, 25, and 44, wherein the small particle transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[65] 79. The method of Claim 44, carried out at a pressure from about 0.1 atmospheres to about 73 atmospheres. 10 80. The method of Claim 44, wherein said substrate is a biomedical implant.
[66] 81. The method of Claim 69, wherein said biomedical implant is selected from the group consisting of a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising 15 telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue 20 scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[67] 82. The method of Claim 44, wherein said sintering comprises treating said coated substrate with a compressed gas, compressed liquid, or supercritical fluid that is a non-solvent for both the polymer and 25 the impermeable dispersed solid, but a plasticizing agent for the polymer.
[68] 83. The method of Claim 71, wherein said compressed gas, compressed liquid, or supercritical fluid is carbon dioxide.
[69] 84. The method of any of Claims 1, 25, and 44, wherein at least one of the polymer and the impermeable dispersed solid is electrostatically deposited onto the substrate, wherein the polymer initially forms a 30 coating of individual polymer nanoparticles that subsequently coalesce with adjacent polymer nanoparticles to form a polymer film.
[70] 85. The method of Claim 73, wherein the polymer film comprises a microstructure.
[71] 86. The method of Claim 74, wherein the impermeable dispersed solid is are sequestered within said microstructure. 35 87. The method of Claim 44, wherein the coating is substantially impermeable to a gas.
[72] 88. The method of Claim 44, wherein the coating is substantially impermeable to a fluid.
[73] 89. The method of Claim 44, wherein the coating is substantially impervious to a biological material.
[74] 90. The method of Claim 44, wherein the polymer is hydrophobic.
[75] 91. The method of Claim 44, wherein the polymer is at least one of a polyolefin, a metallocene polyolefins, a 40 styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne. 23 WO 2008/148013 PCT/US2008/064732
[76] 92. The method of Claim 44, wherein the polymer has a bulk density of at least about 1.00 grams per cubic centimeter (g/cc).
[77] 93. The method of Claim 44, wherein the polymer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc). 5 94. The method of Claim 44, wherein the polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2,36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
[78] 95. A substrate comprising a coating deposited on said substrate according to any of Claims 1-83. 10 96. A device comprising:
[79] 97. a substrate and
[80] 98. a polymer layer disposed on the substrate
[81] 99. wherein the layer substantially seals the substrate.
[82] 100. The device of Claim 85, wherein said substrate is a medical device. 15 101. The device of Claim 86, wherein said medical device is selected from a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral 20 pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, 25 neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[83] 102. The device of Claim 85, wherein the polymer layer is substantially impermeable to a gas.
[84] 103. The device of Claim 85, wherein the polymer layer is substantially impermeable to a fluid.
[85] 104. The device of Claim 85, wherein the polymer layer is substantially impervious to a biological material. 30 105. . The device of Claim 85, wherein the polymer layer is hydrophobic.
[86] 106. The device of Claim 85, wherein the polymer layer comprises at least one of a polyolefin, a metallocene polyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne.
[87] 107. The device of Claim 85, wherein a polymer in the polymer layer has a bulk density of at least about 1.00 35 grams per cubic centimeter (g/cc).
[88] 108. The device of Claim 85, wherein a polymer in the polymer layer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc). 24 WO 2008/148013 PCT/US2008/064732
[89] 109. The device of Claim 85, wherein a polymer in the polymer layer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc). 5 110. The device of Claim 85, wherein the polymer layer provides a substantially conformal coating on the substrate.
[90] 111. The method of Claims 85, wherein the polymer layer provides a coating that is substantially impermeable to leachants from the substrate.
[91] 112. The device of Claim 85, comprising: at least one layer comprising an impermeable dispersed solid. 10 113. The device of Claim 98, wherein the polymer layer and the impermeable dispersed solid layer in combination provide a substantially conformal coating on the substrate,
[92] 114. The device of Claims 98, wherein the polymer layer and the impermeable dispersed solid layer in combination provide a coating that is substantially impermeable to leachants from the substrate.
[93] 115. The device of Claim 98, wherein the impermeable dispersed solid is impermeable to a gas. 15 116. The device of Claim 98, comprising 5, 10, 20, 50, or 100 layers of at least one of a polymer and an impermeable dispersed solid.
[94] 117. The device of Claim 98 , wherein the polymer layer is substantially defect-free.
[95] 118. The device of Claim 98, wherein a coating formed by the polymer layer and the impermeable dispersed solid layer in combination is substantially defect-free. 20 119. A device comprising:
[96] 120. a substrate and
[97] 121. a layer disposed on the substrate, said layer comprising a polymer and an impermeable dispersed solid
[98] 122. wherein the layer substantially seals the substrate.
[99] 123. The device of Claim 105, wherein said substrate is a medical device. 25 124. The device of Claim 105, wherein said medical device is selected from a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral 30 pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, 35 neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[100] 125. The device of Claim 105, wherein the layer is substantially impermeable to a gas.
[101] 126. The device of Claim 105, wherein the layer is substantially impermeable to a fluid.
[102] 127. The device of Claim 105, wherein the layer is substantially impervious to a biological material. 40 128. The device of Claim 105, wherein the layer is hydrophobic. 25 WO 2008/148013 PCT/US2008/064732
[103] 129. The device of Claim 105, wherein the polymer comprises at least one of a polyolefin, a metallocene polyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne.
[104] 130. The device of Claim 105, wherein a polymer has a bulk density of at least about 1.00 grams per cubic 5 centimeter (g/cc).
[105] 131. The device of Claim 105, wherein a polymer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc).
[106] 132. The device of Claim 105, wherein a polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 10 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
[107] 133. The device of Claim 105, wherein the layer provides a substantially conformal coating on the substrate.
[108] 134. The method of Claim 105, wherein the layer provides a coating that is substantially impermeable to leachants from the substrate. 15 135. The device of Claim 105, wherein the impermeable dispersed solid is impermeable to a gas.
[109] 136. The device of Claim 105, comprising 5, 10, 20, 50, or 100 layers of at least one of the polymer and the impermeable dispersed solid.
[110] 137. The device of Claim 105, wherein the layer is substantially defect-free.
[111] 138. A method of preparing a coated substrate comprising: 20 139. providing a substrate;
[112] 140. depositing on said substrate at least one layer comprising a water-vapor-trapping material, and
[113] 141. depositing on said substrate at least one layer comprising a hydrophobic polymer.
[114] 142. The method of Claim 121, wherein the hydrophobic polymer layer and the water-vapor-trapping material substantially seals the substrate. 25 143. The method of Claim 121, wherein the hydrophobic polymer comprises a fluoropolymer,
[115] 144. The method of Claim 121, wherein the water-vapor-trapping material comprises a silicon based polymer.
[116] 145. The method of Claim 124, wherein the silicon based polymer comprises native silicon and is metallized with titanium.
[117] 146. The method of Claim 121, comprising depositing at least a third layer of a hydrophobic polymer 30 encapsulate the water-vapor-trapping material between the hydrophobic polymer layers.
[118] 147. The method of Claim 126, wherein the hydrophobic polymer comprises a fluoropolymer.
[119] 148. The method of Claim 126, wherein the water-vapor-trapping material comprises a silicon based polymer.
[120] 149. The method of Claim 128, wherein the silicon based polymer comprises native silicon and is metallized with titanium. 35 150. The method of Claim 121, comprising depositing multiple alternating layers of a hydrophobic polymer and a water-vapor-trapping material.
[121] 151. The method of Claim 121, wherein the water-vapor-trapping material comprises a hydrophilic polymer.
[122] 152. The method of Claim 121, wherein the hydrophobic polymer is at least one of a polyolefin, a metallocene polyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a 40 polyalkyne. 26 WO 2008/148013 PCT/US2008/064732
[123] 153. The method of Claim 121, wherein the hydrophobic polymer has a bulk density of at least about 1.00 grams per cubic centimeter (g/cc).
[124] 154. The method of Claim 121, wherein the hydrophobic polymer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc). 5 155. The method of Claim 121, wherein the hydrophobic polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
[125] 156. The method of Claim 121, wherein the water-vapor-trapping material comprises a superabsorbent 10 polymer.
[126] 157. The method of Claim 121, wherein the hydrophobic polymer layer and the water-vapor-trapping later in combination provide a substantially conformal coating on the substrate.
[127] 158. The method of Claim 121, wherein the coated substrate is impervious to a biological material.
[128] 159. The method of Claim 121, wherein the hydrophobic polymer layer and the water-vapor-trapping later in 15 combination provide a coating that is substantially impermeable to leachants from the substrate..
[129] 160. The method of Claim 121, wherein the impermeable dispersed solid is impermeable to a gas.
[130] 161. The method of Claim 121, wherein the substrate is a medical device.
[131] 162. The method of Claim 141, wherein the medical device is an active medical device.
[132] 163. The method of Claim 121, further comprising depositing one or more water-vapor-trapping material 20 layers.
[133] 164. The method of Claim 121, further comprising depositing one or more hydrophobic polymer layers.
[134] 165. The method of Claim 121, comprising depositing 5, 10, 20, 50, or 100 layers of at least one of a water vapor-trapping material and a hydrophobic polymer.
[135] 166. The method of Claim 121, comprising depositing said hydrophobic polymer layer by an e-RESS, an e 25 SEDS, or an e-DPC process.
[136] 167. The method of Claim 121, comprising depositing said water-vapor-trapping material layer by an e-RESS, an e-SEDS, or an e-DPC process.
[137] 168. The method of Claim 121, wherein at least one of the hydrophobic polymer and the water-vapor-trapping material comprises a nanoparticle. 30 169. The method of Claim 121, wherein the nanoparticle is a polyurethane adhesive nanocomposite.
[138] 170. The method of Claim 149, wherein the nanoparticle comprises organically modified montmorillonite and polyurethane.
[139] 171. The method of Claim 121, wherein the oxygen transmission rate across the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. 35 172. The method of Claim 121, wherein the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[140] 173. The method of Claim 121, wherein the small particle transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[141] 174. The method of Claim 121, wherein the hydrophobic polymer layer and the water-vapor-trapping material 40 layer is substantially defect-free. 27 WO 2008/148013 PCT/US2008/064732
[142] 175. The method of Claim 121, wherein depositing said hydrophobic polymer layer provides improved adherence of the impermeable dispersed solid to the substrate.
[143] 176. The method of Claim 121, comprising depositing said water-vapor-trapping material layer provides improved adherence of the water-vapor-trapping material to at least one of the substrate and the 5 hydrophobic polymer.
[144] 177. A method of preparing a coated substrate comprising:
[145] 178. providing a substrate;
[146] 179. depositing on said substrate at least one layer comprising a hydrophobic polymer and a water-vapor trapping material. 10 180. The method of Claim 157, wherein the layer substantially seals the substrate.
[147] 181. The method of Claim 157, wherein the layer is substantially impermeable to a gas.
[148] 182. The method of Claim 157, wherein the layer is substantially impermeable to a fluid.
[149] 183. The method of Claim 157, wherein the layer is substantially impervious to a biological material.
[150] 184. The method of Claim 157, wherein the hydrophobic polymer comprises a fluoropolymer. 15 185. The method of Claim 157, wherein the water-vapor-trapping material comprises a silicon based polymer.
[151] 186. The method of Claim 163, wherein the silicon based polymer comprises native silicon and is metallized with titanium.
[152] 187. The method of Claim 157, comprising depositing at least a third layer of a hydrophobic polymer encapsulate the water-vapor-trapping material between the hydrophobic polymer layers. 20 188. The method of Claim 157, comprising depositing multiple alternating layers of a hydrophobic polymer and a water-vapor-trapping material.
[153] 189. The method of Claim 157, wherein the layer provides a substantially conformal coating on the substrate.
[154] 190. The method of Claim 157, wherein the layer provides a coating that is substantially impermeable to leachants from the substrate. 25 191. The method of Claim 157, wherein the substrate is a medical device.
[155] 192. The method of Claim 169, wherein the medical device is an active medical device.
[156] 193. The method of Claim 157, further comprising depositing one or more water-vapor-trapping material layers.
[157] 194. The method of Claim 157, further comprising depositing one or more hydrophobic polymer layers. 30 195. The method of Claim 157, comprising depositing 5, 10, 20, 50, or 100 layers of at least one of a water vapor-trapping material and a hydrophobic polymer.
[158] 196. The method of Claim 157, comprising depositing said layer by an e-RESS, an e-SEDS, or an e-DPC process.
[159] 197. The method of Claim 157, wherein at least one of the hydrophobic polymer and the water-vapor-trapping 35 material comprises a nanoparticle.
[160] 198. The method of Claim 175, wherein the nanoparticle is a polyurethane adhesive nanocomposite.
[161] 199. The method of Claim 175, wherein the nanoparticle comprises organically modified montmorillonite and polyurethane.
[162] 200. The method of Claim 157, wherein the oxygen transmission rate across the coating is at most about 1%, 40 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. 28 WO 2008/148013 PCT/US2008/064732 201, The method of Claim 157, wherein the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[163] 202. The method of Claim 157, wherein the small particle transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. 5 203. The method of Claim 157, wherein the layer is substantially defect-free.
[164] 204. A method for depositing a coating comprising a water-vapor-trapping material and hydrophobic polymer on a substrate, comprising the following steps:
[165] 205. discharging at least one water-vapor-trapping material in dry powder form through a second orifice;
[166] 206. discharging at least one hydrophobic polymer in dry powder form through a first orifice; 10 207. depositing the water-vapor-trapping material and/or hydrophobic polymer onto said substrate, wherein an electrical potential is maintained between the substrate and the hydrophobic polymer and/or water-vapor trapping material particles, thereby forming said coating; and
[167] 208. sintering said coating under conditions that do not substantially disrupt the activity and/or function of the substrate. 15 209. The method of Claim 182, wherein the hydrophobic polymer and/or the water-vapor-trapping material becomes electrostatically charged prior to deposition on said substrate.
[168] 210. The method of Claim 182, wherein the substrate is electrostatically charged.
[169] 211. The method of Claim 182, wherein the substrate is electrically grounded, and the hydrophobic polymer and/or the water-vapor-trapping material particles are charged. 20 212. The method of Claim 182, wherein said water-vapor-trapping material and said hydrophobic polymer are discharged using a gas based propellant.
[170] 213. The method of Claim 186, wherein said gas based propellant comprises at least one of the members selected from the group consisting of carbon dioxide, nitrous oxide, hydrofluorocarbons, chlorofluorocarbons, helium, nitrogen, compressed air, argon, and volatile hydrocarbons with a vapor 25 pressure greater than 750 Tor at 20oC.
[171] 214. The method of Claim 186, wherein said gas based propellant comprises carbon dioxide.
[172] 215. The method of Claim 182, wherein the average particle size of said water-vapor-trapping material and/or hydrophobic polymer particles is from about 0.1 micron to about 100 microns.
[173] 216. The method of Claim 182, wherein the molecular weight range of said water-vapor-trapping material is 30 from about 5,000 a.u. to about 100,000 a.u.
[174] 217. The method of Claim 182, wherein the resistivity of said water-vapor-trapping material and/or hydrophobic polymer dry powders is from about 106fm to about 1024Qm.
[175] 218. The method of Claim 182, wherein the moisture content of said water-vapor-trapping material and/or hydrophobic polymer dry powders is less than 5% by weight. 35 219. The method of Claim 188, wherein said first and said second orifices are provided as one single orifice.
[176] 220. The method of Claim 182, wherein said hydrophobic polymer and said water-vapor-trapping material are mixed together prior to discharging.
[177] 221. The method of Claim 182, wherein said hydrophobic polymer and said water-vapor-trapping material particles are discharged simultaneously. 29 WO 2008/148013 PCT/US2008/064732
[178] 222. The method of Claim 182, wherein said hydrophobic polymer and said water-vapor-trapping material particles are discharged in succession.
[179] 223. The method of Claim 182, carried out at a temperature from about 0"C to about 800C.
[180] 224. The method of Claim 182, carried out at a pressure from about 0.1 atmospheres to about 82 atmospheres. 5 225. The method of Claim 182, wherein said substrate is a biomedical implant.
[181] 226. The method of Claim 199, wherein said biomedical implant is selected from the group consisting of a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising 10 telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue 15 scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[182] 227. The method of Claim 178, wherein said sintering comprises treating said coated substrate with a compressed gas, compressed liquid, or supercritical fluid that is a non-solvent for both the water-vapor 20 trapping material and the hydrophobic polymer, but a plasticizing agent for the water-vapor-trapping material.
[183] 228. The method of Claim 201, wherein said compressed gas, compressed liquid, or supercritical fluid is carbon dioxide.
[184] 229. The method of Claim 178, wherein at least one of the hydrophobic polymer and the water-vapor-trapping 25 material comprises a nanoparticle.
[185] 230. The method of Claim 178, wherein the nanoparticle is a polyurethane adhesive nanocomposite.
[186] 231. The method of Claim 204, wherein the nanoparticle comprises organically modified montmorillonite and polyurethane.
[187] 232. The method of Claim 178, wherein the oxygen transmission rate across the coating is at most about 1%, 30 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[188] 233. The method of Claim 178, wherein the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[189] 234. The method of Claim 178, wherein the hydrophobic polymer comprises a fluoropolymer.
[190] 235. The method of Claim 178, wherein the water-vapor-trapping material comprises a silicon based polymer. 35 236. The method of Claim 178, comprising depositing at least a third layer of a hydrophobic polymer encapsulate the water-vapor-trapping material between the hydrophobic polymer layers.
[191] 237. The method of Claim 178, comprising depositing multiple alternating layers of a hydrophobic polymer and a water-vapor-trapping material.
[192] 238. The method of Claim 178, wherein the water-vapor-trapping material comprises a hydrophilic polymer. 40 239. The method of Claim 178 wherein the polymer is hydrophobic. 30 WO 2008/148013 PCT/US2008/064732
[193] 240. A substrate comprising a coating deposited on said substrate according to any of Claims 121-213.
[194] 241. A device comprising:
[195] 242. a substrate and
[196] 243. a water-vapor-trapping material layer, and 5 244. a hydrophobic polymer layer,
[197] 245. wherein the water-vapor-trapping material layer is disposed on the substrate,
[198] 246. wherein the hydrophobic layer is disposed on the water-vapor-trapping material layer, and
[199] 247. wherein at least one of the water-vapor-trapping material layer and the hydrophobic polymer layer substantially seals the substrate, 10 248. The device of Claim 215, wherein said substrate is an implantable device.
[200] 249. The device of Claim 216, wherein said implantable device is selected from a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising 15 electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shuntsfor hydrocephalus, dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, 20 prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[201] 250. A device comprising:
[202] 251. a substrate and 25 252. a layer disposed on the substrate, said layer comprising a polymer and an impermeable dispersed solid
[203] 253. wherein the layer substantially seals the substrate.
[204] 254. The device of Claim 218, wherein said substrate is a medical device.
[205] 255. The device of Claim 218, wherein the layer provides a substantially conformal coating on the substrate.
[206] 256. The device of Claim 218, wherein the layer is substantially defect-free. 30 257. A method of preparing a coated substrate comprising:
[207] 258. providing a substrate;
[208] 259. depositing on said substrate at least one layer comprising a nanoparticle; and
[209] 260. depositing on said substrate at least one layer comprising a polymer,
[210] 261. wherein the depositing of the nanoparticle and the polymer in combination substantially seals the substrate 35 262. The method of Claim 222, wherein the substrate is a medical device.
[211] 263. The method of Claim 222, further comprising depositing one or more polymer layers.
[212] 264. The method of Claim 222, further comprising depositing one or more layers of nanoparticles.
[213] 265. The method of Claim 222, comprising depositing 5, 10, 20, 50, or 100 layers of at least one of a polymer and a nanoparticle. 31 WO 2008/148013 PCT/US2008/064732
[214] 266. The method of Claim 222, comprising depositing said nanoparticle layer by an e-RESS, an e-SEDS, or an e-DPC process.
[215] 267. The method of Claim 222, comprising depositing said polymer layer by an e-RESS, an e-SEDS, or an e DPC process. 5 268. The method of Claim 222, comprising depositing said polymer layer in a substantially defect-free manner.
[216] 269. A method of preparing a conformally coated substrate impervious to a biological material comprising:
[217] 270. providing a substrate;
[218] 271. depositing on said substrate at least one layer comprising a nanoparticle and a polymer
[219] 272. wherein depositing the layer substantially seals the substrate 10 273. The method of Claim 230, wherein the substrate is a medical device.
[220] 274. The method of Claim 230, comprising depositing said layer by an e-RESS, an e-SEDS, or an e-DPC process.
[221] 275. The method of Claim 230, comprising depositing said layer in a substantially defect-free manner.
[222] 276. A method for depositing a coating comprising a polymer and a nanoparticle impervious to small particle 15 transport on a substrate, comprising the following steps:
[223] 277. discharging at least one nanoparticle in dry powder form through a first orifice;
[224] 278. discharging at least one polymer in dry powder form through a second orifice;
[225] 279. depositing the polymer and/or nanoparticle onto said substrate, wherein an electrical potential is maintained between the substrate and the nanoparticle and/or polymer particles, thereby forming said 20 coating; and
[226] 280. sintering said coating under conditions that do not substantially disrupt the activity and/or function of the substrate.
[227] 281. The method of Claim 230, wherein the nanoparticle and/or the polymer becomes electrostatically charged prior to deposition on said substrate. 25 282. The method of Claim 230, wherein the substrate is electrostatically charged.
[228] 283. The method of Claim 230, wherein the substrate is electrically grounded, and the nanoparticle and/or the polymer particles are charged.
[229] 284. The method of Claim 230, wherein said polymer and said nanoparticle are discharged using a gas based propellant. 30 285. The method of Claim 230, wherein the average particle size of said polymer particle and/or nanoparticle is from about 0.1 micron to about 100 microns.
[230] 286. The method of Claim 230, wherein the molecular weight range of said polymer is from about 5,000 a.u. to about 100,000 a.u.
[231] 287. The method of Claim 230, wherein the resistivity of said polymer and/or nanoparticle dry powders is from 35 about 106Dm to about 1024Qm.
[232] 288. The method of Claim 230, wherein the moisture content of said polymer and/or nanoparticle dry powders is less than 5% by weight.
[233] 289. The method of Claim 230, wherein said first and said second orifices are provided as one single orifice.
[234] 290. The method of Claim 239, wherein said nanoparticle and said polymer are mixed together prior to 40 discharging. 32 WO 2008/148013 PCT/US2008/064732
[235] 291. The method of Claim 230, wherein said nanoparticle and said polymer particles are discharged simultaneously.
[236] 292. The method of Claim 230, wherein said nanoparticle and said polymer particles are discharged in succession. 5 293. The method of Claim 230, carried out at a temperature from about 0*C to about 80*C.
[237] 294. The method of Claim 343, wherein the nanoparticle is a polyurethane adhesive nanocomposite.
[238] 295. The method of Claim 345, wherein the nanoparticle comprises organically modified montmorillonite and polyurethane,
[239] 296. The method of one of Claims 222, 230, and 234, wherein the oxygen transmission rate across the coating 10 is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[240] 297. The method of one of Claims 222, 230, and 234, wherein the water vapor permeation through the coating is at most about 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%.
[241] 298. The method of one of Claims 222, 230, and 234, wherein the small particle transmission rate across the coating is at most about 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or 70%. 15 299. The method of Claim 230, carried out at a pressure from about 0.1 atmospheres to about 73 atmospheres.
[242] 300. The method of Claim 230, wherein said substrate is a biomedical implant.
[243] 301. The method of Claim 230, wherein said sintering comprises treating said coated substrate with a compressed gas, compressed liquid, or supercritical fluid that is a non-solvent for both the polymer and the impermeable dispersed solid, but a plasticizing agent for the polymer. 20 302. The method of Claim 230, wherein said compressed gas, compressed liquid, or supercritical fluid is carbon dioxide.
[244] 303. The method of any of Claims 222, 230, and 234, wherein at least one of the polymer and the nanoparticle is electrostatically deposited onto the substrate, wherein the polymer initially forms a coating of individual polymer nanoparticles that subsequently coalesce with adjacent polymer nanoparticles to form a polymer 25 film.
[245] 304. The method of Claim 257, wherein the polymer film comprises a microstructure.
[246] 305. The method of Claim 257, wherein the impermeable dispersed solid is are sequestered within said microstructure.
[247] 306. A substrate comprising a coating deposited on said substrate according to any of Claims 222- 259. 30 307. A device comprising:
[248] 308. a substrate
[249] 309. a layer comprising at least one of a nanoparticle and a polymer disposed on the substrate,
[250] 310. wherein the layer substantially seals the substrate.
[251] 311. The device of Claim 261, wherein said substrate is a medical device. 35 312. The device of Claim 262, wherein said medical device is selected from a stent (e.g., vascular stents), electrode, catheter, lead, implantable pacemaker, implantable cardioverter, a housing for an implantable pacemaker, a housing for an implantable defibrillator, a housing for an implantable cardioverter, sensor, drug delivery device, therapy delivery device, device comprising telemetry capability, device comprising electrical impulses, diagnostic device, measurement device, joint, screw, rod, ophthalmic implant, femoral 40 pin, bone plate, graft, anastomotic device, perivascular wrap, suture, staple, shunts for hydrocephalus, 33 WO 2008/148013 PCT/US2008/064732 dialysis graft, colostomy bag attachment device, ear drainage tube, lead for pace makers and implantable cardioverters and defibrillators, vertebral disk, bone pin, suture anchor, hemostatic barrier, clamp, screws, plate, clip, vascular implant, tissue adhesive, sealant, tissue scaffolds, shunts, opthalmic implant, prosthetic, shunt, urologic implant, reproductive anatomy device, gastrologic device, neurologic lead, 5 neurologic device, various types of dressings (e.g., wound dressings), bone substitutes, intraluminal devices, and vascular supports.
[252] 313. The device of Claim 261, wherein the layer is substantially impermeable to a gas.
[253] 314. The device of Claim 261, wherein the layer is substantially impermeable to a fluid.
[254] 315. The device of Claim 261, wherein the layer is substantially impervious to a biological material. 10 316. The device of Claim 261, wherein the polymer is hydrophobic.
[255] 317. The device of Claim 261, wherein the polymer comprises at least one of a polyolefin, a metallocene polyolefins, a styrene polymers, a vinyl polymer, an acrylic polymers, a polyester, a polyalkene, and a polyalkyne.
[256] 318. The device of Claim 261, wherein the polymer has a bulk density of at least about 1.00 grams per cubic 15 centimeter (g/cc).
[257] 319. The device of Claim 261, wherein polymer has a bulk density of greater than about 1.00 gram per cubic centimeter (g/cc).
[258] 320. The device of Claim 261, wherein the polymer has a bulk density of at least about one of 1.01, 1.02, 1.03, 1.05, 1.06, 1.07, 1.08, 1.09, 2.00, 2.01, 2.02, 2.03, 2.04, 2.05, 2.06, 2.07, 2.08, 2.09, 2.10, 2.11, 2.12, 2.13, 20 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, 2.34, 2.35, 2.36, 2.37, 2.38, 2.39, 2.40 grams per cubic centimeter (g/cc).
[259] 321. The device of Claim 261, wherein the layer provides a substantially conformal coating on the substrate.
[260] 322. The device of Claim 261, wherein the layer provides a coating that is substantially impermeable to leachants from the substrate. 25 323. The device of Claim 261, wherein the layer provide a substantially conformal coating on the substrate.
[261] 324. The device of Claim 261, comprising 5, 10, 20, 50, or 100 layers of at least one of a polymer and an nanoparticle.
[262] 325. The device of Claim 261, wherein the layer is substantially defect-free. 34

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法律状态:
2012-10-11| FGA| Letters patent sealed or granted (standard patent)|

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2021-12-16| MK14| Patent ceased section 143(a) (annual fees not paid) or expired|

优先权:

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申请号 | 申请日 | 专利标题

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US94036507P| true| 2007-05-25|2007-05-25||

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US60/940,365||2007-05-25||

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US97937507P| true| 2007-10-11|2007-10-11||

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US60/979,375||2007-10-11||

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PCT/US2008/064732|WO2008148013A1|2007-05-25|2008-05-23|Polymer films for medical device coating|AU2012203203A| AU2012203203B2|2007-05-25|2012-05-30|Polymer films for medical device coating|