text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 19, 2008
|Filing date
|Sep 24, 2007
|Priority date
|Nov 9, 2006
|Also published as
|Publication number
|Torsten Scheuermann, Jan Weber, Yixin Xu
|Original Assignee
|Torsten Scheuermann, Jan Weber, Yixin Xu
|Export Citation
|BiBTeX, EndNote, RefMan
|Referenced by (28), Classifications (19), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims priority from U.S. Provisional Patent Application No. 60/857,849, filed Nov. 9, 2006 [Boston Scientific Docket No. 06-01579 with the Title "Medical Devices Having Nanoporous Coatings for Controlled Therapeutic Agent Delivery"], the entire contents of which is hereby incorporated by reference.
This invention relates to endoprostheses with coatings.
The body includes various passageways such as arteries, other blood vessels, and other body lumens. These passageways sometimes become occluded or weakened. For example, the passageways can be occluded by a tumor, restricted by plaque, or weakened by an aneurysm. When this occurs, the passageway can be reopened or reinforced with a medical endoprosthesis. An endoprosthesis is typically a tubular member that is placed in a lumen in the body. Examples of endoprostheses include stents, covered stents, and stent-grafts.
Endoprostheses can be delivered inside the body by a catheter that supports the endoprosthesis in a compacted or reduced-size form as the endoprosthesis is transported to a desired site. Upon reaching the site, the endoprosthesis is expanded, e.g., so that it can contact the walls of the lumen. Stent delivery is further discussed in Heath, U.S. Pat. No. 6,290,721, the entire contents of which is hereby incorporated by reference herein.
The expansion mechanism may include forcing the endoprosthesis to expand radially. For example, the expansion mechanism can include the catheter carrying a balloon, which carries a balloon-expandable endoprosthesis. The balloon can be inflated to deform and to fix the expanded endoprosthesis at a predetermined position in contact with the lumen wall. The balloon can then be deflated, and the catheter withdrawn from the lumen.
Passageways containing endoprostheses can become re-occluded. Re-occlusion of such passageways is known as restenosis. It has been observed that certain drugs can inhibit the onset of restenosis when the drug is contained in the endoprosthesis. It is sometimes desirable for an endoprosthesis-contained therapeutic agent, or drug to elute into the body fluid in a predetermined manner once the endoprosthesis is implanted.
In an aspect, the document features an endoprosthesis having a first coating including a polymer, and a second coating over the first coating formed of a porous ceramic or metal.
In another aspect, the document features a method of forming an endoprosthesis, including forming a polymer coating that has a drug on the endoprosthesis, and forming a layer of porous ceramic or metal over the drug-containing polymer coating.
Embodiments may include one or more of the following features. The polymer can include a drug. The polymer can have a drug content of about 8.8% by weight or more (e.g., 15% or more, 25% or more). The polymer can be a non-biodegradable polymer such as styrene-isobutylene-styrene (SIBS) or polybutylene succinate (PBS). The first coating can have a plurality of depressions. The second coating can be formed of a porous ceramic. The second coating can have pores with a pore diameter of about 1 nm to 20 nm. The ceramic can be an oxide. The ceramic can be iridium oxide (IROX), titanium oxide (TIOX), tantalum oxide, or niobium oxide. The ceramic can have a smooth globular morphology to enhance endothelial cell growing over the ceramic. The ceramic can have a porosity of about 80% or less. The second coating can have a thickness less than the thickness of the first coating. The thickness of the second coating can be about 10 to 500 nm. The thickness of the first coating is about 0.1 to about 10 micron (e.g., about 0.5 to about 3 micron). The first coating can contact a surface of an endoprosthesis body. The endoprosthesis body can be formed of a metal. The metal is stainless steel. The endoprosthesis body can be formed of a polymer. The polymer can be a biostable polymer. The polymer can be a bioerodible polymer. The second coating can be formed of porous metal. The porous metal can be copper, gold, ruthenium, titanium, tantalum, platinum, palladium, stainless steel or an alloy thereof.
Embodiments may also include one or more of the following features. The polymer coating can be formed by spraying a solution of a polymer and a drug to a surface of an endoprosthesis body. The endoprosthesis body can be a metal. The metal can be stainless steel. The endoprosthesis body can be a polymer. The drug can be introduced by coating, dipping, or spraying in a solvent. The polymer coating can be formed by introducing a polymer to the endoprosthesis by dipping, spraying, brushing, pressing, laminating, or pulsed laser deposition (PLD). The drug can be introduced by PLD. The layer can be formed by PLD. The layer can be formed by magnetron sputtering. The layer can be a metal, such as copper, gold, silver, ruthenium, titanium, tantalum, platinum, palladium, stainless steel or an alloy thereof. The layer can be ceramic. The layer can be IROX. The ceramic can have a smooth globular morphology to enhance endothelial cell growing over the ceramic. The method can further include forming depressions in the polymer coating by laser irradiation.
Embodiments may include one or more of the following advantages. Stents can be formed with coatings of a ceramic or metal and a polymer that have morphologies and/or compositions that enhance therapeutic performance. In particular, the ceramic or metal can be deposited over the polymer coating to form a porous coating or membrane that controls drug release rate from the polymer as well as reduces the likelihood of direct contact of polymer to the body tissue. The over coating or membrane can be formed of a ceramic, e.g. IROX, which can have therapeutic advantages such as reducing the likelihood of restenosis and enhancing endothelialization. The morphology of the ceramic coating can be controlled to tune the therapeutic properties and the porosity of the membrane to provide a desired drug release profile over an extended period. The over coating or membrane may also reduce polymer flaking or delamination by further fixing it to one side, e.g., the abluminal side of an endoprosthesis body due to integrity of the over coating. The over coating can also facilitate deployment from a delivery device during deployment by reducing friction between the stent and delivery device. The membrane can be formed by low temperature deposition process, such as PLD or sputtering, which reduces the likelihood of degradation of the underlying polymer and/or a drug in the polymer coating. The polymer coating can be selected to accommodate a large quantity of drug and at the same time be relatively thin. Likewise, the membrane can be relatively thin, so as not to substantially increase the overall thickness of the stent wall.
Still further aspects, features, embodiments, and advantages follow.
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In embodiments, the polymer coating 25 can be a drug eluting polymer ('DEP'), e.g., a biodegradable or non-biodegradable DEP. The coating 25 has a thickness Tp of about 100 nm to about 50 μm, e.g., about 200 nm to about 10 μm, or about 30 mm to about 2 μm, which is selected to control the total amount of the releasable drag once the stent is implanted. In embodiments, the drug content in the DEP is selected to be about 5 to about 50 weight percent (wt. %), e.g. about 8.8 to about 25 wt. %. In embodiments, compared to a DEP without coating 29, the polymer can be provided with higher loadings of drug since the ceramic coating 29 modulates the delivery of drug to the body.
In embodiments, the porous coating 29 is formed of a ceramic, such as iridium oxide ("IROX"). Certain ceramics, e.g. oxides, can reduce restenosis through the catalytic reduction of hydrogen peroxide and other precursors to smooth muscle cell proliferation. The oxides can also encourage endothelial growth to enhance endothelialization of the stent. When a stent is introduced into a biological environment (e.g., in vivo), one of the initial responses of the human body to the implantation of a stent, particularly into the blood vessels, is the activation of leukocytes, white blood cells which are one of the constituent elements of the circulating blood system. This activation causes an increase of reactive oxygen compound production. One of the species released in this process is hydrogen peroxide, H2O2, which is released by neutrophil granulocytes, which constitute one of the many types of leukocytes. The presence of H2O2 may increase proliferation of smooth muscle cells and compromise endothelial cell function, stimulating the expression of surface binding proteins which enhance the attachment of more inflammatory cells. A ceramic, such as IROX can catalytically reduce H2O2. The morphology of the ceramic can enhance the catalytic effect and reduce proliferation of smooth muscle cells. In a particular embodiment, IROX is selected to form the coating 29, which can have therapeutic benefits such as enhancing endothelialization. IROX and other ceramics are discussed further in Alt et al., U.S. Pat. No. 5,980,566 and U.S. Ser. No. 10/651,562 filed Aug. 29, 2003.
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An advantage of having coating 34 surrounding the stent strut as illustrated in
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In embodiments, the ceramic is provided over the polymeric coating by a technique that uses low temperature to reduce the likelihood of damaging the drug and/or the polymer, such as PLD. Referring to
The porosity of the ceramic can be controlled by selecting the morphology, crystallinity, thickness, and size of the clusters ablated and deposited. Higher crystallinity, more defined grain morphologies, and thinner coatings provide greater porosity. Coating thickness is controlled by controlling deposition time. Higher laser energies can provide larger cluster sizes.
In certain embodiments, if more than one targets, e.g., a polymer target and a ceramic target are needed for deposition, the composition of the deposited material is selected by controlling the exposure of the target materials to laser energy. For example, to deposit pure polymer or pure ceramic, only the polymer or ceramic material is exposed to laser energy. To deposit a composite layer of ceramic and polymer, both materials are exposed simultaneously or alternately exposed in rapid succession. The relative amount of polymer and ceramic is controlled by the laser energy and/or exposure time. In embodiments, the ceramic or polymer is deposited as small clusters, e.g., 100 nm or less, such as 1-10 nm, and preferably smaller than the gross morphological features of the layers. In embodiments, the clusters bond at contact points forming a continuous coating that is an amalgamation of the clusters. The molecular weight of the polymer can be controlled by selecting the laser wavelength and energy. In the ablation process, energy absorbed by the target can result in cleavage of covalent bonds in polymers, such that the chain lengths and molecular weight of the polymer in the target is reduced in the deposition material. The efficiency of the cleavage process can be enhanced by selecting a laser wavelength that the polymer absorbs strongly. In addition, at higher energies, the size of ablated clusters is increased, with less overall chain cleavage.
In particular embodiments, the laser energy is produced by an excimer laser operating in the ultraviolet, e.g. at a wavelength of about 248 nm. The laser energy is about 100-700 mJ, the fluence is in the range of about 10 to 50 mJ/cm2. The background pressure is in the range of about 1E-5 mbar to 1 mbar. The background gas includes oxygen. The substrate temperature is also controlled. The temperature of the substrate is between 0 to 150� C. during deposition. Substrate temperature can be controlled by directing an infrared beam onto the substrate during deposition using, e.g. a halogen source. The temperature is measured by mounting a heat sensor in the beam adjacent the substrate. The temperature can be varied to control the morphology of the ceramic and melting of the polymer. The selective sputtering of the ceramic or polymer is controlled by mounting the target material on a moving assembly that can alternately bring the materials into the path of the laser. Alternatively, a beam splitter and shutter can be used to alternatively or simultaneously expose multiple materials. PLD deposition services are available from Axyntec, Augsburg, Germany. Suitable ceramics include metal oxides and nitrides, such as of iridium, zirconium, titanium, hafnium, niobium, tantalum, ruthenium, platinum and aluminum. In embodiments, the thickness of the coatings is in the range of about 10 m to about 2 um, e.g. 100 nm to 500 nm. Pulsed laser deposition is also described in application U.S. Ser. No. 11/752,736, filed May 23, 2007 [Attorney Docket No. 10527-801001]. The target can be a pure metal, e.g. IR target or iridium oxide in the form of compressed powder. The polymer, e.g. including drug, can also be deposited by PLA. In embodiments, the polymer is SIBS and the drug is paclitaxal at e.g. 8.8%. The laser power is 100 to 250 mn and the pressure between about 0.04 mbar and 0.2 mbar.
In other embodiments, another physical vapor deposition ("PVD") process is selected such as magnetron sputtering e.g. an iridium target under an oxygen atmosphere or an IROX target. Sputtering deposition is described in application U.S. Ser. No. 11/752,772, filed May 23, 2007 [Attorney Docket No. 10527-805001]. In the case of a ceramic or a metal over coating, the porosity can be further controlled by laser ablating apertures into the layer with, e.g. a U.V. laser.
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The morphology of the ceramic is controlled by controlling the energy of the sputtered clusters on the stent substrate. Higher energies and higher temperatures result in defined grain, higher roughness surfaces. Higher energies are provided by increasing the temperature of the ceramic on the substrate, e.g. by heating the substrate or heating the ceramic with infrared radiation. In embodiments, defined grain morphologies are formed at temperatures of about 250� C. or greater. Globular morphologies are formed at lower temperatures, e.g. ambient temperatures without external factors. The heating enhances the formation of a more crystalline ceramic, which forms the grains. Intermediate morphologies are formed at intermediate values of these parameters. The composition of the ceramic can also be varied. For example, oxygen content can be increased by providing oxygen gas in the chamber.
The morphology of the surface of the ceramic is characterized by its visual appearance, its roughness, and/or the size and arrangement of particular morphological features such as local maxima. In embodiments, the surface is characterized by definable sub-micron sized grains. Referring particularly to
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The roughness of the surface is characterized by the average roughness, Sa, the root mean square roughness, Sq, and/or the developed interfacial area ratio, Sdr. The Sa and Sq parameters represent an overall measure of the texture of the surface. Sa and Sq are relatively insensitive in differentiating peaks, valleys and the spacing of the various texture features. Surfaces with different visual morphologies can have similar Sa and Sq values. For a surface type, the Sa and Sq parameters indicate significant deviations in the texture characteristics. Sdr is expressed as the percentage of additional surface area contributed by the texture as compared to an ideal plane the size of the measurement region. Sdr further differentiates surfaces of similar amplitudes and average roughness. Typically Sdr will increase with the spatial intricacy of the texture whether or not Sa changes.
In embodiments, the ceramic has a defined grain type morphology. The Sdr is about 30 or more, e.g. about 40 to 60. In addition or in the alternative, the morphology has an Sq of about 15 or more, e.g. about 20 to 30. In embodiments, the Sdr is about 100 or more and the Sq is about 15 or more. In other embodiments, the ceramic has a globular type surface morphology. The Sdr is about 20 or less, e.g. about 8 to 15. The Sq is about 15 or less, e.g. about less than 8 to 14. In still other embodiments, the ceramic has a morphology between the defined grain and the globular surface, and Sdr and Sq values between the ranges above, e.g. an Sdr of about 1 to 200 and/or an Sq of about 1 to 30. The Sa, Sq, and Sdr can be calculated from AFM data.
The morphology of the ceramic coating can exhibit high uniformity. The uniformity provides predictable, tuned therapeutic and mechanical performance of the ceramic. The uniformity of the morphology as characterized by Sa, Sq or Sdr and/or average peak spacing parameters can be within about +/−20% or less, e.g. +/−10% or less within a tam square. In a given stent region, the uniformity is within about +/−10%, e.g. about +/−1%. For example, in embodiments, the ceramic exhibits high uniformity over an entire surface region of stent, such as the entire abluminal or adluminal surface, or a portion of a surface region, such as the center 25% or 50% of the surface region. The uniformity is expressed as standard deviation. Uniformity in a region of a stent can be determined by determining the average in five randomly chosen 1 μm square regions and calculating the standard deviation. Uniformity of a morphology type in a region is determined by inspection of FESEM data at 50 kx.
The ceramics are also characterized by surface composition, composition as a function of depth, and crystallinity. In particular, the amounts of oxygen or nitride in the ceramic is selected for a desired catalytic effect on, e.g., the reduction of H2O2 in biological processes. The composition of metal oxide or nitride ceramics can be determined as a ratio of the oxide or nitride to the base metal. In particular embodiments, the ratio is about 2 to 1 or greater, e.g. about 3 to 1 or greater, indicating high oxygen content of the surface. In other embodiments, the ratio is about 1 to 1 or less, e.g. about 1 to 2 or less, indicating a relatively low oxygen composition. In particular embodiments, low oxygen content globular morphologies are formed to enhance endothelialization. In other embodiments, high oxygen content defined grain morphologies are formed, e.g., to enhance adhesion and catalytic reduction. Composition can be determined by x-ray photoelectron spectroscopy (XPS). Depth studies are conducted by XPS after FAB sputtering. The crystalline nature of the ceramic can be characterized by crystal shapes as viewed in FESEM images, or Miller indices as determined by x-ray diction. In embodiments, defined grain morphologies have a Miller index of <101>. Globular materials have blended amorphous and crystalline phases that vary with oxygen content. Higher oxygen content typically indicates greater crystallinity. Further discussion of ceramics and ceramic morphology and computation of roughness parameters is provided in U.S. Ser. No. 11/752,736, [Attorney Docket No. 10527-801001], filed May 23, 2007, U.S. Ser. No. 11/752,772, [Attorney Docket No. 10527-805001], filed May 23, 2007, and appendices.
In certain embodiments, referring back to
The kinetic energy (e.g., about 100 V to 50 keV) of the clusters partly controlled by the applied voltage on the substrate holder may induce clusters melting upon impact the substrate and may cause damage to the polymeric substrate due to local heating. In embodiments, a first collection of clusters are deposited with a kinetic energy, e.g., 0.1 keV, that is high enough for the clusters to adhere to or penetrate the polymer substrate but substantially causes no heat damage to the polymer and/or the drug incorporated in the polymer. A second collection of clusters with higher kinetic energy, e.g., 5 keV, can then be deposited on top of the first collection. In embodiments, the magnetron head can be moved within the aggregation zone. Reducing the distance from the magnetron head to the first aperture reduces the distance and time whereby condensation can occur so the average cluster size is reduced. In embodiments, several other gases (shown as "Gas Source 2") can be added into the source chamber. For example, introducing helium can lead to a reduction of the cluster size while introducing oxygen or nitrogen can lead to generation of ceramic clusters or nanoparticles by reactive sputtering and ceramic coating on the polymer substrate. Nanocluster or nanoparticle deposition services are available, e.g., from Mantis Deposition Ltd., England (http://www.mantisdeposition.com) and the relevant techniques are further disclosed by Weber et al., Provisional Application No. 60/857,849 [BSC Docket No. 06-01579], A. H. Kean et al., Mantis Deposition Ltd., NSTI Nano Tech 2006, Boston, May 7th-11th 2006, in Y. Qiang et al., Surface and Coating Technology, 100-101, 27-32 (1998) and in Kraft et al., Surface and Coating Technology, 158-159, 131-135 (2002).
In embodiments, the ceramic or metal is adhered only on the abluminal surface of the stent. This construction may be accomplished by, e.g. coating the stent before forming the fenestrations, as described in e.g., Weber, U.S. Pat. No. 6,517,888. In other embodiments, the ceramic or metal is adhered only on abluminal and cut-face surfaces of the stent. This construction may be accomplished by, e.g., coating a stent containing a mandrel, which shields the luminal surfaces. Masks can be used to shield portions of the stent. In embodiments, the stent metal can be stainless steel, chrome, nickel, cobalt, tantalum, superelastic alloys such as nitinol, cobalt chromium, MP35N, and other metals. Suitable stent materials and stent designs are described in Heath '721, supra. Other suitable ceramics include metal oxides and nitrides, such as of iridium, zirconium, titanium, hafnium, niobium, tantalum, ruthenium, platinum and aluminum. The ceramic can be crystalline, partly crystalline or amorphous. The ceramic can be formed entirely of inorganic materials or a blend of inorganic and organic material (e.g. a polymer). In other embodiments, the morphologies described herein can be formed of metal. As discussed above, different ceramic materials can be provided in different regions of a stent. For example, different materials may be provided on different stent surfaces. A rougher, defined grain material may be provided on the abluminal surface to, e.g. enhance porosity or adhesion to the polymer while a smooth globular material can be provided on the adluminal surface to enhance endothelialization. In yet some embodiments, a material of a defined grain morphology may be provided first on the stent surface to, e.g. enhance adhesion of the polymer while a smooth globular material can be provided on top of the polymer to enhance endothelialization.
The ceramic material can also be selected for compatibility with a particular polymer coating to, e.g. enhance adhesion. For example, for a hydrophilic polymer, the surface chemistry of the ceramic is made more hydrophilic by e.g., increasing the oxygen content, which increases polar oxygen moieties, such as OH groups. Suitable drug eluting polymers may be hydrophilic or hydrophobic. Suitable polymers include, for example, polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics such as polystyrene and copolymers thereof with other vinyl monomers such as isobutylene, isoprene and butadiene, for example, styrene-isobutylene-styrene (SIBS), styrene-isoprene-styrene (SIS) copolymers, styrene-butadiene-styrene (SBS) copolymers, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polybutylene succinate (PBS), and polybutylene suucinate adipate (PBSA), polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenerated polyalkylenes including polytetrafluoroethylene, natural and synthetic rubbers including polyisoprene, polybutadiene, polyisobutylene and copolymers thereof with other vinyl monomers such as styrene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers thereof as well as other biodegradable, bioabsorbable and biostable polymers and copolymers. Coatings from polymer dispersions such as polyurethane dispersions (BAYHDROL�, etc.) and acrylic latex dispersions are also within the scope of the present disclosure. The polymer may be a protein polymer, fibrin, collagen and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives of these polysaccharides, an extracellular matrix component, hyaluronic acid, or another biologic agent or a suitable mixture of any of these, for example. U.S. Pat. No. 5,091,205 describes medical devices coated with one or more polyiocyanates such that the devices become instantly lubricious when exposed to body fluids. In embodiments, a suitable polymer is polyacrylic acid, available as HYDROPLUS�. (Boston Scientific Corporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205, the disclosure of which is hereby incorporated herein by reference. Another polymer can be a copolymer of polylactic acid and polycaprolactone. The polymer can be biostable or biodegradable. Suitable polymers are discussed in U.S. Publication No. 2006/0038027.
In embodiments, the polymer is capable of absorbing a substantial amount of drug solution. In embodiments, when applied as a coating on a medical device, the dry polymer is typically on the order of from about 1 to about 50 microns thick, preferably about 1 to 10 microns thick, and more preferably about 2 to 5 microns. In embodiments, very thin polymer coatings, e.g., of about 0.2-0.3 microns and much thicker coatings, e.g., more than 10 microns, are also possible. In some embodiments, multiple layers of polymer coating can be provided onto a medical device. Such multiple layers are of the same or different polymer materials. Such multiple layers can contain different drugs in each layer, or some of the multiple layers may not contain any drugs. Suitable DEP coating are further disclosed in U.S. Pat. Nos. 5,605,696 and 5,447,724. In certain embodiments, the polymer can only act as a membrane to regulate drug release. For example, drug particles can first be applied to the stent, then a layer of polymer can be applied on top of the drugs and between the drugs and the ceramic coating to function a first drug release regulating layer while the ceramic coating functions as a second drug release regulating layer.
The terms "therapeutic agent", "pharmaceutically active agent", "pharmaceutically active material", "pharmaceutically active ingredient", "drug" and other related terms may be used interchangeably herein and include, but are not limited to, small organic molecules, peptides, oligopeptides, proteins, nucleic acids, oligonucleotides, genetic therapeutic agents, non-genetic therapeutic agents, vectors for delivery of genetic therapeutic agents, cells, and therapeutic agents identified as candidates for vascular treatment regimens, for example, as agents that reduce or inhibit restenosis. By small organic molecule is meant an organic molecule having 50 or fewer carbon atoms, and fewer than 100 non-hydrogen atoms in total.
Exemplary non-genetic therapeutic agents for use in conjunction with the present invention include: (a) anti-thrombotic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c) antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents such as lidocaine, bupivacaine and ropivacaine; (e) anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, hirudin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; (f) vascular cell growth promoters such as growth factors, transcriptional activators, and translational promotors; (g) vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; (h) protein kinase and tyrosine kinase inhibitors (e.g., tyrphostins, genistein, quinoxalines); (i) prostacyclin analogs; (j) cholesterol-lowering agents; (k) angiopoietins; (l) antimicrobial agents such as triclosan, cephalosporins, aminoglycosides and nitrofurantoin; (m) cytotoxic agents, cytostatic agents and cell proliferation affectors; (n) vasodilating agents; (o) agents that interfere with endogenous vasoactive mechanisms; p) inhibitors of leukocyte recruitment, such as monoclonal antibodies; (q) cytokines; (r) hormones; (s) inhibitors of HSP 90 protein (i.e., Heat Shock Protein, which is a molecular chaperone or housekeeping protein and is needed for the stability and function of other client proteins/signal transduction proteins responsible for growth and survival of cells) including geldanamycin, (t) alpha receptor antagonist (such as doxazosin, Tamsulosin) and beta receptor agonists (such as dobutamine, salmeterol), beta receptor antagonist (such as atenolol, metaprolol, butoxamine), angiotensin-II receptor antagonists (such as losartan, valsartan, irbesartan, candesartan and telmisartan), and antispasmodic drugs (such as oxybutynin chloride, flavoxate, tolterodine, hyoscyamine sulfate, diclomine), (u) bARKct inhibitors, (v) phospholamban inhibitors, (w) Serca 2 gene/protein, (x) immune response modifiers including aminoquizolines, for instance, imidazoquinolines such as resiquimod and imiquimod, and (y) human apolioproteins (e.g., AI, AII, AIII, AIV, AV, etc.).
Specific examples of non-genetic therapeutic agents include paclitaxel, (including particulate forms thereof, for instance, protein-bound paclitaxel particles such as albumin-bound paclitaxel nanoparticles, e.g., ABRAXANE), sirolimus, everolimus, tacrolimus, Epo D, dexamethasone, estadiol, halofuginone, cilostazole, geldanamycin, ABT-578 (Abbott Laboratories), trapidil, liprostin, Actinomcin D, Resten-NG, Ap-17, abciximab, clopidogrel, Ridogrel, beta-blockers, bARKct inhibitors, phospholamban inhibitors, Serca 2 gene/protein, imiquimod, human apolioproteins (e.g., AI-AV), growth factors (e.g., VEGF-2), as well a derivatives of the forgoing, among others.
Exemplary genetic therapeutic agents for use in conjunction with the present invention include anti-sense DNA and RNA as well as DNA coding for the various proteins (as well as the proteins themselves): (a) anti-sense RNA, (b) tRNA or rRNA to replace defective or deficient endogenous molecules, (c) angiogenic and other factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, endothelial mitogenic growth factors, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin-like growth factor, (d) cell cycle inhibitors including CD inhibitors, and (e) thymidine kinase ("TK") and other agents useful for interfering with cell proliferation. Also of interest is DNA encoding for the family of bone morphogenic proteins ("BMP's"), including BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively, or in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the "hedgehog" proteins, or the DNA's encoding them.
Vectors for delivery of genetic therapeutic agents include viral vectors such as adenoviruses, gutted adenoviruses, adeno-associated virus, retroviruses, alpha virus (Semliki Forest, Sindbis, etc.), lentiviruses, herpes simplex virus, replication competent viruses (e.g., ONYX-015) and hybrid vectors; and non-viral vectors such as artificial chromosomes and mini-chromosomes, plasmid DNA vectors (e.g., pCOR), cationic polymers (e.g., polyethyleneimine, polyethyleneimine (PEI)), graft copolymers (e.g., polyether-PEI and polyethylene oxide-PEI), neutral polymers PVP, SP1017 (SUPRATEK), lipids such as cationic lipids, liposomes, lipoplexes, nanoparticles, or microparticles, with and without targeting sequences such as the protein transduction domain (PTD).
Cells for use in conjunction with the present invention include cells of human origin (autologous or allogeneic), including whole bone marrow, bone marrow derived mono-nuclear cells, progenitor cells (e.g., endothelial progenitor cells), stem cells (e.g., mesenchymal, hematopoietic, neuronal), pluripotent stem cells, fibroblasts, myoblasts, satellite cells, pericytes, cardiomyocytes, skeletal myocytes or macrophage, or from an animal, bacterial or fungal source (xenogeneic), which can be genetically engineered, if desired, to deliver proteins of interest.
Numerous therapeutic agents, not necessarily exclusive of those listed above, have been identified as candidates for vascular treatment regimens, for example, as agents targeting restenosis. Such agents are useful for the practice of the present invention and include one or more of the following: (a) Ca-channel blockers including benzothiazapines such as diltiazem and clentiazem, dihydropyridines such as nifedipine, amlodipine and nicardapine, and phenylalkylamines such as verapamil, (b) serotonin pathway modulators including: 5-HT antagonists such as ketanserin and naftidrofuryl, as well as 5-HT uptake inhibitors such as fluoxetine, (c) cyclic nucleotide pathway agents including phosphodiesterase inhibitors such as cilostazole and dipyridamole, adenylate/Guanylate cyclase stimulants such as forskolin, as well as adenosine analogs, (d) catecholamine modulators including α-antagonists such as prazosin and bunazosine, β-antagonists such as propranolol and α/β-antagonists such as labetalol and carvedilol, (e) endothelin receptor antagonists, (f) nitric oxide donors/releasing molecules including organic nitrates/nitrites such as nitroglycerin, isosorbide dinitrate and amyl nitrite, inorganic nitroso compounds such as sodium nitroprusside, sydnonimines such as molsidomine and linsidomine, nonoates such as diazenium diolates and NO adducts of alkanediamines, S-nitroso compounds including low molecular weight compounds (e.g., S-nitroso derivatives of captopril, glutathione and N-acetyl penicillamine) and high molecular weight compounds (e.g., S-nitroso derivatives of proteins, peptides, oligosaccharides, polysaccharides, synthetic polymers/oligomers and natural polymers/oligomers), as well as C-nitroso-compounds, O-nitroso-compounds, N-nitroso-compounds and L-arginine, (g) ACE inhibitors such as cilazapril, fosinopril and enalapril, (h) ATII-receptor antagonists such as saralasin and losartin, (i) platelet adhesion inhibitors such as albumin and polyethylene oxide, (j) platelet aggregation inhibitors including cilostazole, aspirin and thienopyridine (ticlopidine, clopidogrel) and GP IIb/IIIa inhibitors such as abciximab, epitifibatide and tirofiban, (k) coagulation pathway modulators including heparinoids such as heparin, low molecular weight heparin, dextran sulfate and f-cyclodextrin tetradecasulfate, thrombin inhibitors such as hirudin, hirulog, PPACK(D-phe-L-propyl-L-arg-chloromethylketone) and argatroban, FXa inhibitors such as antistatin and TAP (tick anticoagulant peptide), Vitamin K inhibitors such as warfarin, as well as activated protein C, (l) cyclooxygenase pathway inhibitors such as aspirin, ibuprofen, flurbiprofen, indomethacin and sulfinpyrazone, (m) natural and synthetic corticosteroids such as dexamethasone, prednisolone, methprednisolone and hydrocortisone, (n) lipoxygenase pathway inhibitors such as nordihydroguairetic acid and caffeic acid, (o) leukotriene receptor antagonists, (p) antagonists of E- and P-selectins, (q) inhibitors of VCAM-1 and ICAM-1 interactions, (r) prostaglandins and analogs thereof including prostaglandins such as PGE1 and PGI2 and prostacyclin analogs such as ciprostene, epoprostenol, carbacyclin, iloprost and beraprost, (s) macrophage activation preventers including bisphosphonates, (t) HMG-CoA reductase inhibitors such as lovastatin, pravastatin, fluvastatin, simvastatin and cerivastatin, (u) fish oils and omega-3-fatty acids, (v) free-radical scavengers/antioxidants such as probucol, vitamins C and E, ebselen, trans-retinoic acid and SOD mimics, (w) agents affecting various growth factors including FGF pathway agents such as bFGF antibodies and chimeric fusion proteins, PDGF receptor antagonists such as trapidil, IGF pathway agents including somatostatin analogs such as angiopeptin and ocreotide, TGF-β pathway agents such as polyanionic agents (heparin, fucoidin), decorin, and TGF-β antibodies, EGF pathway agents such as EGF antibodies, receptor antagonists and chimeric fusion proteins, TNF-α pathway agents such as thalidomide and analogs thereof, Thromboxane A2 (TXA2) pathway modulators such as sulotroban, vapiprost, dazoxiben and ridogrel, as well as protein tyrosine kinase inhibitors such as tyrphostin, genistein and quinoxaline derivatives, (x) MMP pathway inhibitors such as marimastat, ilomastat and metastat, (y) cell motility inhibitors such as cytochalasin B, (z) antiproliferative/antineoplastic agents including antimetabolites such as purine analogs (e.g., 6-mercaptopurine or cladribine, which is a chlorinated purine nucleoside analog), pyrimidine analogs (e.g., cytarabine and 5-fluorouracil) and methotrexate, nitrogen mustards, alkyl sulfonates, ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin, macrolide antibiotics such as erythromycin), nitrosoureas, cisplatin, agents affecting microtubule dynamics (e.g., vinblastine, vincristine, colchicine, Epo D, paclitaxel and epothilone), caspase activators, proteasome inhibitors, angiogenesis inhibitors (e.g., endostatin, angiostatin and squalamine), rapamycin, cerivastatin, flavopiridol and suramin, (aa) matrix deposition/organization pathway inhibitors such as halofuginone or other quinazolinone derivatives and trailast (bb) endothelialization facilitators such as VEGF and RGD peptide, and (cc) blood rheology modulators such as pentoxifylline.
Further additional therapeutic agents include immunosuppressents such as sirolimus and antibiotics such as macrolide antibiotics, evorolimus, and Tacrolimus for the practice of the present invention are also disclosed in U.S. Pat. No. 5,733,925.
Where a therapeutic agent is included, a wide range of therapeutic agent loadings can be used in conjunction with the medical devices of the present invention, with the therapeutically effective amount being readily determined by those of ordinary skill in the art and ultimately depending, for example, upon the condition to be treated, the age, sex and condition of the patient, the nature of the therapeutic agent, the nature of the ceramic region(s), and/or the nature of the medical device, among other factors.
In a particular embodiment a 1% toluene solution of SIBS with 8.8 wt. % paclitaxel was sprayed onto a stainless steel stent with masks on its adluminal and cut-face surfaces until the thickness reached a desired value, e.g., 10 microns. The stent coated with DEP was then dried in air. The drug content of the dry DEP coating was about 8.8% by weight. Subsequently, the DEP-coated stent was mount in an Axplorer PLD system by Axyntec, Augsburg, Germany. An iridium (99.9 wt. %) target was ablated by a 248 nm laser of 10 ns pulse at an energy of 600 ml, base pressure of 0.8 mbar oxygen, and substrate temperature of 50 degrees of Celsius. The resultant IROX layer had a thickness of about 15 nm to 150 nm.
Referring to
In further embodiments, the polymeric coating may incorporate magnetic particles, e.g., nanoparticles. The embodiments may have one or more additional following advantages, including that the release profile of a therapeutic agent from an endoprosthesis can be controlled through non-invasive means, e.g., a magnetic field. The magnetic field can be used to selectively agitate the particles, to modify drug release from the polymeric coating. Use of magnetic particles is described further in U.S. Provisional Application No. 60/845,136, filed Sep. 15, 2006.
Any stent described herein can be dyed or rendered radiopaque by addition of, e.g., radiopaque materials such as barium sulfate, platinum or gold, or by coating with a radiopaque material. The stent can include (e.g., be manufactured from) metallic materials, e.g., biostable metallic materials such as stainless steel (e.g., 316L, BioDur� 108 (UNS S29108), and 304L stainless steel, and an alloy including stainless steel and 5-60% by weight of one or more radiopaque elements (e.g., Pt, Ir, Au, W) (PERSS�) as described in US-2003-0018380-A1, US-2002-0144757-A1, and US-2003-0077200-A1), Nitinol (a nickel-titanium alloy), cobalt alloys such as Elgiloy, L605 alloys, MP35N, titanium, titanium alloys (e.g., Ti-6Al-4V, Ti-50Ta, Ti-10Ir), platinum, platinum alloys, niobium, niobium alloys (e.g., Nb-1Zr) Co-28Cr-6Mo, tantalum, and tantalum alloys. Other examples of materials are described in commonly assigned U.S. application Ser. No. 10/672,891, filed Sep. 26, 2003; and U.S. application Ser. No. 11/035,316, filed Jan. 3, 2005. The stent can be formed of bioerodible metal such as magnesium, iron, calcium, aluminum, or their alloys. Other materials include elastic biocompatible metal such as a superelastic or pseudo-elastic metal alloy, as described, for example, in Schetsky, L. McDonald, "Shape Memory Alloys", Encyclopedia of Chemical Technology (3rd ed.), John Wiley & Sons, 1982, vol. 20. pp. 726-736; and commonly assigned U.S. application Ser. No. 10/346,487, filed Jan. 17, 2003.
The stents described herein can be configured for vascular, e.g. coronary and peripheral vasculature or non-vascular lumens. For example, they can be configured for use in the esophagus or the prostate. Other lumens include biliary lumens, hepatic lumens, pancreatic lumens, and urethral lumens.
The stent can be of a desired shape and size (e.g., coronary stents, aortic stents, peripheral vascular stents, gastrointestinal stents, urology stents, tracheal/bronchial stents, and neurology stents). Depending on the application, the stent can have a diameter of between, e.g., about 1 mm to about 46 mm. In certain embodiments, a coronary stent can have an expanded diameter of from about 2 mm to about 6 mm. In some embodiments, a peripheral stent can have an expanded diameter of from about 4 mm to about 24 mm. In certain embodiments, a gastrointestinal and/or urology stent can have an expanded diameter of from about 6 mm to about 30 mm. In some embodiments, a neurology stent can have an expanded diameter of from about 1 mm to about 12 mm. An abdominal aortic aneurysm (AAA) stent and a thoracic aortic aneurysm (TAA) stent can have a diameter from about 20 mm to about 46 mm. The stent can be balloon-expandable, self-expandable, or a combination of both (e.g., U.S. Pat. No. 6,290,721). Other medical devices, particularly implantable devices can be formed, such as catheters, guide wires, and filters, having implants and electrodes.
A number of embodiments have been described in the disclosure. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. For example, referring back to
All publications, patent applications, patents, and other references mentioned herein are incorporated by reference herein in their entirety.
Still other embodiments are in the following claims.
|Citing Patent
|Filing date
|Publication date
|Nov 28, 2007
|Nov 16, 2010
|Boston Scientific Scimed, Inc.
|Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment
|Jul 27, 2007
|Apr 26, 2011
|Boston Scientific Scimed, Inc.
|Articles having ceramic coated surfaces
|Nov 2, 2007
|May 10, 2011
|Boston Scientific Scimed, Inc.
|Deformable underlayer for stent
|Jul 11, 2007
|May 17, 2011
|Boston Scientific Scimed, Inc.
|Endoprosthesis coating
|Jul 23, 2008
|May 31, 2011
|Boston Scientific Scimed, Inc.
|Drug-eluting stent
|May 23, 2007
|Jul 12, 2011
|Boston Scientific Scimed, Inc.
|Endoprosthesis with select ceramic morphology
|Sep 29, 2006
|Aug 9, 2011
|Medtronic, Inc.
|Delivering a conduit into a heart wall to place a coronary vessel in communication with a heart chamber and removing tissue from the vessel or heart wall to facilitate such communication
|May 9, 2008
|Aug 16, 2011
|Boston Scientific Scimed, Inc.
|Mar 14, 2011
|May 29, 2012
|Boston Scientific Scimed, Inc.
|Drug eluting stent and method of making the same
|Dec 3, 2009
|Jul 31, 2012
|Boston Scientific Scimed, Inc.
|Medical implants including iridium oxide
|Mar 19, 2008
|Aug 28, 2012
|Boston Scientific Scimed, Inc.
|Drug eluting stent and method of making the same
|Feb 26, 2007
|Sep 25, 2012
|Medtronic Vascular, Inc.
|Drug coated stent with magnesium topcoat
|Feb 27, 2008
|Apr 30, 2013
|Boston Scientific Scimed, Inc.
|Coated medical devices for abluminal drug delivery
|Mar 18, 2011
|Sep 16, 2014
|Boston Scientific Scimed, Inc.
|Mar 18, 2011
|Nov 25, 2014
|Boston Scientific Scimed, Inc.
|Jan 22, 2013
|Apr 14, 2015
|Exogenesis Corporation
|Medical device for bone implant and method for producing such a device
|Jul 7, 2011
|Apr 28, 2015
|Biotronik Ag
|Abluminally coated drug-eluting stents having a form-fitting protective layer
|Feb 26, 2004
|Sep 1, 2005
|Colen Fredericus A.
|Medical devices
|Feb 26, 2007
|Aug 28, 2008
|Medtronic Vascular, Inc.
|Drug Coated Stent With Magnesium Topcoat
|Feb 11, 2010
|Exogenesis Corporation
|Drug delivery system and method of manufacturing thereof
|Feb 11, 2010
|Exogenesis Corporation
|Medical device for bone implant and method for producing such device
|Jul 7, 2011
|Boston Scientific Scimed, Inc.
|Drug Eluting Stent and Method of Making the Same
|Sep 29, 2011
|Boston Scientific Scimed, Inc.
|Jan 19, 2012
|Biotronik Ag
|Abluminally coated drug-eluting stents having a form-fitting protective layer
|Feb 14, 2012
|Jun 14, 2012
|Boston Scientific Scimed, Inc.
|Bioerodible endoprosthesis with biostable inorganic layers
|Jul 15, 2013
|Nov 14, 2013
|Hon Hai Precision Industry Co., Ltd.
|Porous metal article and about method for manufacturing same
|Jul 1, 2011
|Jan 18, 2012
|Biotronik AG
|Abluminally Coated Drug-Eluting Stents having a Form-Fitting Protective Layer
|Mar 18, 2011
|Oct 13, 2011
|Boston Scientific Scimed, Inc.
|U.S. Classification
|623/1.42, 427/2.25, 623/1.46, 604/523
|International Classification
|Cooperative Classification
|European Classification
|Mar 3, 2008
Owner name: BOSTON SCIENTIFIC SCIMED, INC., MINNESOTA
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Owner name: BOSTON SCIENTIFIC SCIMED, INC., MINNESOTA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SCHEUERMANN, TORSTEN;WEBER, JAN;XU, YIXIN;SIGNING DATES FROM 20071018 TO 20071019;REEL/FRAME:020591/0577
|Sep 27, 2011
|Certificate of correction
|Dec 6, 2011
|Certificate of correction
|Feb 27, 2015
|Maintenance fee reminder mailed


text:
Tuesday, August 22, 2006
Is a Federal Tax on Damages for Emotional Distress Unconstitutional?
Marty Lederman
The U.S. Court of Appeals for the District of Columbia Circuit today held that a federal statute, which imposes a tax on awards of compensatory damages for emotional distress and loss of reputation, is unconstitutional because such awards are not "income" within the meaning of the Sixteenth Amendment.
Section 9 is not the only part of the original text that restricts the tax power. Section 2 of Article I states ". . . direct Taxes shall be apportioned among the several States which may be included within this Union, according to their respective Numbers . . . ."
Your reading of the 16th Amendment as a clarification of the taxing power, and not restricted to income, is inconsistent with Supreme Court precedent on the issue. As the DC circuit states, the courts have interpreted the term "income" in the 16th Amendment, as explained in Eisner and Glenshaw Glass.
The critical distinction is that compensatory awards are not income, but instead an asset which the plaintiff already has. In contrast, noncompensatory awards, such as punitive damages are not the plaintiff's unless and until they are awarded. A tranfer of an asset may be taxed, but possession of the asset may not.
I was under the impression that prior to the Sixteenth, it was understood that the federal government did not have the power to levy income taxes at all. In that case the amendment would be giving the government an enumerated power. If I'm right it's a lot easier to rationalize the DC court's ruling.
I was under the impression that prior to the Sixteenth, it was understood that the federal government did not have the power to levy income taxes at all. In that case the amendment would be giving the government an enumerated power.
Congress has always had the power to levy taxes, including income taxes. Art. I, Sec. 8 specifically enumerates a general power to tax. The issue resolved by the 16A was that income taxes could be levied without apportionment as might otherwise be required under Art. I, Sec. 9.
Compensation for a tortious wrong is not income. If it were taxed, then you would not be made whole. Let's say someone negligently chops off your arm and then pays you a settlement that perfectly compensates you for the loss of your arm. There is no income. There is no gain. The money is just compensation for the loss of your arm. That money = your arm. Because the government cannot take a random piece of your arm, the government cannot tax your compensatory judgment. No level of American government has the right to just hack off a little piece of your arm.
Because the government cannot take a random piece of your arm, the government cannot tax your compensatory judgment.
The power to tax is plenary. Congress can tax anything it wants. The tax may be unwise, it may be subject to the direct/indirect restrictions, but the subjects of potential taxation are unlimited.
The power to tax is plenary. Congress can tax anything it wants. The tax may be unwise, it may be subject to the direct/indirect restrictions, but the subjects of potential taxation are unlimited.
Ummm, no. There are restrictions to the taxing power.
1)Article I, sections 2 and 9. As they stood at the beginning of the Constitution, any direct tax (and yes an income tax is a direct tax--see the definitions given by the IRS, see http://www.irs.gov/app/understandingTaxes/jsp/tools_glossary.jsp) could only be a poll tax. The 16th Amendment altered this status to allow income taxes. It does not allow any other direct taxes. To say that the taxing power is plenary renders either of these clauses a nullity.
2) Fifth Amendment Due Process and Takings Clause. A tax on possessions, rather than income, can and should be considered a taking. The estate and gift taxes are not contrary to this rule because there is no one from whom there is a taking. In the case of the estate tax, the taking can't be from the decedent, since he's dead and therefore has no rights. Further, there is no taking from an heir, because the tax is assessed prior to the heir's receiving any inheritance.
1. Congress can still enact any and all direct taxes. It's only the way it does so which is restricted.
2. Every tax is a "taking".
Your view contradicts 86 years of Supreme Court precedent.
Eisner: the taxing power extends to any gain derived from capital or labor. 252 U.S. 189 (1920).
Burk-Waggoner: Congress cannot make a thing income which it is not so in fact. 269 U.S. 110 (1925)
Do you have any support for your "breathtakingly expansive" (the DC Circuit Court's term) interpretation?
Again, is there an argument that does not render the 2 clauses of Article I (not to mention the 16th Amendment) nugatory?
As they stood at the beginning of the Constitution, any direct tax (and yes an income tax is a direct tax--see the definitions given by the IRS, see http://www.irs.gov/app/understandingTaxes/jsp/tools_glossary.jsp) could only be a poll tax. The 16th Amendment altered this status to allow income taxes. It does not allow any other direct taxes. To say that the taxing power is plenary renders either of these clauses a nullity.
The definition on the IRS website is wrong. A federal income tax on personal earnings has never been held to be a direct tax by any court in the history of the country. To the contrary, the Supreme Court in the 1880 Springer case upheld the validity of the Civil War era income tax by rejecting the argument that it was a direct tax and characterizing it instead as in the nature of an excise or a duty.
It is true that taxation of wages is generally not a direct tax. However, while taxation on some forms of income is not direct, to tax any and all forms of income, such as appreciation of capital, necessarily involves a direct tax.
In Murphy, the tax being levied is certainly a direct tax, since it taxes an amount which Murphy owned before the Court's judgment (which recognized an existing right rather than created a right). A direct tax can only be levied on income, and since the award was not income, but instead to make someone whole, it is unconstitutional.
A direct tax can only be levied on income, and since the award was not income, but instead to make someone whole, it is unconstitutional.
No, you're still confusing two different issues. A direct tax can be levied on ANYthing. When Congress does levy one, however, it has to do so within the restrictions of Art. I, Sec. 9.
The 16A modifies Sec. 9, not Sec. 8. It does not allow a new tax, it allows an old tax to be levied in a different way.
Burk-Waggoner: Congress cannot make a thing income which it is not so in fact. 269 U.S. 110 (1925)
This, again, has to do with the difference between Sec. 8 and Sec. 9, NOT the power of Congress to tax.
Do you have any support for your "breathtakingly expansive" (the DC Circuit Court's term) interpretation?
Federalist 34. Note this passage in particular:
"Constitutions of civil government are not to be framed upon a calculation of existing exigencies, but upon a combination of these with the probable exigencies of ages, according to the natural and tried course of human affairs. Nothing, therefore, can be more fallacious than to infer the extent of any power, proper to be lodged in the national government, from an estimate of its immediate necessities. There ought to be a CAPACITY to provide for future contingencies as they may happen; and as these are illimitable in their nature, it is impossible safely to limit that capacity. It is true, perhaps, that a computation might be made with sufficient accuracy to answer the purpose of the quantity of revenue requisite to discharge the subsisting engagements of the Union, and to maintain those establishments which, for some time to come, would suffice in time of peace. But would it be wise, or would it not rather be the extreme of folly, to stop at this point, and to leave the government intrusted with the care of the national defense in a state of absolute incapacity to provide for the protection of the community against future invasions of the public peace, by foreign war or domestic convulsions? If, on the contrary, we ought to exceed this point, where can we stop, short of an indefinite power of providing for emergencies as they may arise?"
Eisner: the taxing power extends to any gain derived from capital or labor. 252 U.S. 189 (1920).
That's a description, not a limit. Yes, it does include those things. It also includes other things. Property taxes, for example, or poll taxes. The power is plenary.
There are people who view our government as totally a creature of the Constitution, with such attributes, and only such attributes, as the Constitution grants it. Judging by that pesky "ink blot", the 10th amendment, the founders of this nation belonged to that school of thought.
Then there are those who have floating in the backs of their heads the vision of a Platonic ideal government, where all real world governments are only really "governments" in proportion as they approach that ideal. To such people, the fact that the Constitution may not have mentioned some power or attribute of government that their ideal possesses, is merely evidence that the Constitution is an incomplete description of our government.
The Platonic ideal government possesses plenary taxing power, in case you hadn't figured it out.
I hate to go all textualist on someone like Brett, especially since I'm not one in real life and I don't play one on TV, but here's the relevant text of Art. I, Sec. 8:
"The Congress shall have power to lay and collect taxes, duties, imposts and excises, to pay the debts and provide for the common defense and general welfare of the United States..."
If there's a limit on the kind of taxes Congress can levy, I don't think even Scalia's eyes can see it.
It does not allow a new tax, it allows an old tax to be levied in a different way.
So in what way are you claiming that such taxes could be levied before the 16th Amendment, and what new ways did the 16th Amendment allow?
And then we get to Article one, Section nine.
"No capitation, or other direct, Tax shall be laid, unless in Proportion to the Census or Enumeration herein before directed to be taken."
Oh, gee, I guess the power to tax wasn't plenary after all.
So in what way are you claiming that such taxes could be levied before the 16th Amendment, and what new ways did the 16th Amendment allow?
Before the 16A they had to be levied "in proportion to the Census" as required by Art. I, Sec. 9. After the 16A, that restriction no longer applied.
The point is, the Constitution is silent on the kind of tax which can be levied. It only restricted the manner in which it could be done.
Oh, gee, I guess the power to tax wasn't plenary after all.
The point I was making was that the power to tax is plenary with respect to the kind of taxes Congress can levy. I agree that it's not plenary with respect to the manner of levy. I thought that was clear from the context. If not, my bad.
The problem might have been that the government does not seem to have brought this up in their brief. I'm at least of the impression that courts don't generally take up arguments that were not brought up by at least one party.
There is also the question of whether this would be a direct tax or an indirect tax. I can see this as being seen as analogous to rent collected on property, which is considered to be a direct tax.
Before the 16A they had to be levied "in proportion to the Census" as required by Art. I, Sec. 9.
This however puts severe restrictions on how an income tax may be collected. Consider Justice Chase's illustrative example:
It appears to me that a tax on carriages cannot be laid by the rule of apportionment without very great inequality and injustice. For example, suppose two States equal in census to pay eighty thousand dollars each by a tax on carriages of eight dollars on every carriage; and in one State there are one hundred carriages, and in the other one thousand. The owners of carriages in one State would pay ten times the tax of owners in the other. A., in one State, would pay for his carriage eight dollars; but B., in the other State, would pay for his carriage eighty dollars.
Hylton v. U.S., 3 U.S. 171 (1796)
Now consider two states with equal population but unequal income. It is apparent that the two states could not have the same percentage of income taxed (to say nothing of the difficulties arising in determining which part of the tax is direct and which is indirect. This would look nothing like any income tax I know.
A previous commentator brought up Springer v. U.S. Here is a quote for you from Springer: "The power to levy the tax is a limited one, and if the limits prescribed by law are transcended, the levy is void." Also: "Was the tax here in question a direct tax? If it was, not having been laid according to the requirements of the Constitution, it must be admitted that the laws imposing it, and the proceedings taken under them by the assessor and collector for its imposition and collection, were all void."
After the 16A, that restriction no longer applied.
After the 16th Amendment, that restriction no longer applied to taxes on income. The restriction is still present for direct taxes on anything other than income.
After the 16th Amendment, that restriction no longer applied to taxes on income. The restriction is still present for direct taxes on anything other than income.
True, but then the issue would be whether the tax was a direct tax. Recall that in Springer and in one of the opinions in Hylton, it was stated that the only direct taxes under the Constitution were capitation taxes and taxes on land. The Pollock case expanded this to include taxes on the income from property, but the Pollock result was overturned by the 16th Amendment. So it's not necessarily the case that a tax on something other than income would be a direct tax.
The concept of whether a tax is direct or indirect certainly underwent some evolution. By the time of the 16th Amendment, the conception of a direct tax was broader than in Springer. But even at the time of Springer was a bit broader than what you state. A direct tax was not just a tax on land, but a tax on any income arising from land. This specifically included rents received. A tax on rents is certainly considered an income tax, but it was always considered a direct tax. I agree that not all income taxes are direct--such as a tax on wages, as was at issue in Springer.
I was thinking earlier that the uproar over Murphy reminded me a lot of the uproar over Lopez 11 years ago. In both cases an act thought to be within a plenary power of Congress was held to exceed that power. In both cases there have been apocolyptic predictions that this could be the first stage in a mass overturning of legislation. However, this did not follow from Lopez, although there were certainly many attempts to do so. I suspect that the same will be true after Murphy.
This however puts severe restrictions on how an income tax may be collected. Consider Justice Chase's illustrative example
Agreed -- if income taxes are direct, then there are real problems with trying to collect it. Ironically, Chase gave that example as a reason why the carriage tax should not be considered direct. His position was that the absurdity of the apportionment process was the very reason why it should not be considered a direct tax. The same reasoning could have been applied to the income tax, but Pollock disagreed.
After the 16th Amendment, that restriction no longer applied to taxes on income. The restriction is still present for direct taxes on anything other than income.
As the Supreme Court noted long ago, the "Congress cannot make a thing income which is not so in fact."...the term "incomes," as understood in 1913, clearly did not include damages received in compensation for a physical personal injury...
I agree! On both counts -- so let's make capital gains exempt from income tax too.
1) They aren't income in fact -- look at the national accounts, such as at www.bea.gov, and you will see capital gains are not included in income.
2) The Court in 1913, and the framers of the 16th, clearly did not consider capital gains to be income. In fact, the Court had held them not to be at least four times. E.g, in 1918 we have Lynch V. Turrish, 247 U.S. 221 striking down income tax on a capital gain realized on a corporate liquidation, approvingly quoting Gray v. Darlington in 1865...
'The mere fact that property has advanced in value between the date of its acquisition and sale does not authorize the imposition of a tax on the amount of the advance. Mere advance in value in no sense constitutes the gains, profits, or income specified by the statute. It constitutes and can be treated merely as increase of capital.'
I'm heading down to that District and filing for a tax refund right away.
What-if Congress is wrong to tax the status of one's mental-health via the existing IRC 61? If it is Congress's intent to tax the mental, but not the physical in injury-awards damages, at what cost do we retain our sanity without being taxed on it? If not Congress and the Courts, who is to intervene?
You need us if you have any of these tax problems: Back
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25/S 1025) is a bill in the United States Congress for changing Tax Solutions laws to replace the Internal Revenue Service (IRS) and all federal income taxes (including Alternative Minimum Tax), Past due tax returns, Past due tax returns, Past due returns, Past due taxes, Unpaid tax, Tax negotiation, Wage levy, Robert M. Adams, Bob Adams, Try to Be Happy, Search Engine Optimization
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Books by Balkinization Bloggers
Stephen M. Griffin, Broken Trust: Dysfunctional Government and Constitutional Reform (University Press of Kansas, 2015)
Frank Pasquale, The Black Box Society: The Secret Algorithms That Control Money and Information (Harvard University Press, 2015)
Bruce Ackerman, We the People, Volume 3: The Civil Rights Revolution (Harvard University Press, 2014)
Balkinization Symposium on We the People, Volume 3: The Civil Rights Revolution
Joseph Fishkin, Bottlenecks: A New Theory of Equal Opportunity (Oxford University Press, 2014)
Mark A. Graber, A New Introduction to American Constitutionalism (Oxford University Press, 2013)
John Mikhail, Elements of Moral Cognition: Rawls' Linguistic Analogy and the Cognitive Science of Moral and Legal Judgment (Cambridge University Press, 2013)
Gerard N. Magliocca, American Founding Son: John Bingham and the Invention of the Fourteenth Amendment (New York University Press, 2013)
Stephen M. Griffin, Long Wars and the Constitution (Harvard University Press, 2013)
Andrew Koppelman, The Tough Luck Constitution and the Assault on Health Care Reform (Oxford University Press, 2013)
James E. Fleming and Linda C. McClain, Ordered Liberty: Rights, Responsibilities, and Virtues (Harvard University Press, 2013)
Balkinization Symposium on Ordered Liberty: Rights, Responsibilities, and Virtues
Andrew Koppelman, Defending American Religious Neutrality (Harvard University Press, 2013)
Brian Z. Tamanaha, Failing Law Schools (University of Chicago Press, 2012)
Sanford Levinson, Framed: America's 51 Constitutions and the Crisis of Governance (Oxford University Press, 2012)
Linda C. McClain and Joanna L. Grossman, Gender Equality: Dimensions of Women's Equal Citizenship (Cambridge University Press, 2012)
Mary Dudziak, War Time: An Idea, Its History, Its Consequences (Oxford University Press, 2012)
Jack M. Balkin, Living Originalism (Harvard University Press, 2011)
Jason Mazzone, Copyfraud and Other Abuses of Intellectual Property Law (Stanford University Press, 2011)
Richard W. Garnett and Andrew Koppelman, First Amendment Stories, (Foundation Press 2011)
Jack M. Balkin, Constitutional Redemption: Political Faith in an Unjust World (Harvard University Press, 2011)
Gerard Magliocca, The Tragedy of William Jennings Bryan: Constitutional Law and the Politics of Backlash (Yale University Press, 2011)
Bernard Harcourt, The Illusion of Free Markets: Punishment and the Myth of Natural Order (Harvard University Press, 2010)
Bruce Ackerman, The Decline and Fall of the American Republic (Harvard University Press, 2010)
Balkinization Symposium on The Decline and Fall of the American Republic
Ian Ayres. Carrots and Sticks: Unlock the Power of Incentives to Get Things Done (Bantam Books, 2010)
Mark Tushnet, Why the Constitution Matters (Yale University Press 2010)
Ian Ayres and Barry Nalebuff: Lifecycle Investing: A New, Safe, and Audacious Way to Improve the Performance of Your Retirement Portfolio (Basic Books, 2010)
Jack M. Balkin, The Laws of Change: I Ching and the Philosophy of Life (2d Edition, Sybil Creek Press 2009)
Brian Z. Tamanaha, Beyond the Formalist-Realist Divide: The Role of Politics in Judging (Princeton University Press 2009)
Andrew Koppelman and Tobias Barrington Wolff, A Right to Discriminate?: How the Case of Boy Scouts of America v. James Dale Warped the Law of Free Association (Yale University Press 2009)
Jack M. Balkin and Reva B. Siegel, The Constitution in 2020 (Oxford University Press 2009)
Heather K. Gerken, The Democracy Index: Why Our Election System Is Failing and How to Fix It (Princeton University Press 2009)
Mary Dudziak, Exporting American Dreams: Thurgood Marshall's African Journey (Oxford University Press 2008)
David Luban, Legal Ethics and Human Dignity (Cambridge Univ. Press 2007)
Ian Ayres, Super Crunchers: Why Thinking-By-Numbers is the New Way to be Smart (Bantam 2007)
Jack M. Balkin, James Grimmelmann, Eddan Katz, Nimrod Kozlovski, Shlomit Wagman and Tal Zarsky, eds., Cybercrime: Digital Cops in a Networked Environment (N.Y.U. Press 2007)
Jack M. Balkin and Beth Simone Noveck, The State of Play: Law, Games, and Virtual Worlds (N.Y.U. Press 2006)
Andrew Koppelman, Same Sex, Different States: When Same-Sex Marriages Cross State Lines (Yale University Press 2006)
Brian Tamanaha, Law as a Means to an End (Cambridge University Press 2006)
Sanford Levinson, Our Undemocratic Constitution (Oxford University Press 2006)
Mark Graber, Dred Scott and the Problem of Constitutional Evil (Cambridge University Press 2006)
Jack M. Balkin, ed., What Roe v. Wade Should Have Said (N.Y.U. Press 2005)
Sanford Levinson, ed., Torture: A Collection (Oxford University Press 2004)
Balkin.com homepage
Cultural Software
The Information Society Project
Useful Links
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subset: commoncrawl


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One of the good things about dating again several decades after the prom is that we are clear — or clearer, at any rate — about what we can and cannot tolerate. His refusal to set foot inside a museum? No longer an issue! (The same goes for his mother's ridiculous fashion sense.) Ah, but his character quirks: Those just grow larger as the years roll on.
The five defects noted below can easily become deal-breakers. How many have you encountered in your own dating life? (Me, I'm 5 for 5!)
1. He suffers from selective hearing
During my first phone conversation with Rick, he mentioned he was taking a poetry course at the college where I teach nonfiction.
"I'll bring you some poems to read and critique when we meet," he said.
"Uh, better hold off on that," I responded. "I teach four courses, so I stopped reading my friends' and relatives' writing ages ago. I barely have time to read my students' work these days."
When I arrived at the restaurant, Rick sat at a table piled high with poetry — 200 pages of the stuff.
Did I throw them in his face? Did I "accidentally" drench them in water or ketchup? No, I did not. I merely (and calmly, I like to think) reminded him what I'd said on the phone.
"Just read the one on top," he pleaded.
I read the one on top. It was about his dog. His dead dog. I praised my date's dead-dog poem. Then I chugged my drink, told Rod McKuen I wasn't feeling well and hurried home.
Imagine what a turn-on it was, months later, to encounter this as the first line in my (eventual) husband's profile: "I am a good listener."
2. He is spoken for
I met a man on vacation. We clicked. He lived an hour away. He started visiting me, usually for half a weekend. Whenever I suggested returning the favor, he put me off. Finally I asked why.
"There's something in my house you might not like," he said.
"Termites?" I hazarded.
He laughed but said nothing.
"Another woman?" I asked next. Of course. He started to explain. "Don't bother," I told him. I may not have known exactly what I wanted in a relationship, but I knew a triangle wasn't it.
3. He doesn't understand kids
Many years ago, when my daughter was about 10 years old, I dated a calligrapher. He presented her with a set of calligraphy pens. Promising, right? She grabbed one and eagerly began drawing. The artist went berserk, shouting that she was "doing it all wrong." She flinched; I bridled. "Don't you dare talk to my daughter like that ever again," I told him.
He and I were wrong together for reasons I'd been able to ignore until then. But raising my daughter was the most important part of my life, and I realized I wanted to be with a man who had experienced parenting too. After that episode, I steered clear of partners who did not have children.
Next page: 2 more scenarios where you should break it off and never look back. »


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1 Like
The first rays of the sun already shine onto the famous Matterhorn. To reach the viewpoint at Gornergrat in time you can use the rack-and-pnion railway from Zermatt. A second option to see the sunrise is to sleep a night in the hotel just on top of Gornergrat.


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LEAST WANTED: A CENTURY OF AMERICAN MUG SHOTS Edited by Steven Kasher and Mark Michaelson (Steidl, $50)
If Satan had a scrapbook, it would look a lot like this. These bank robbers, fat mobsters, and kohl-eyed hookers�from the turn of the century through the �70s�make the Nick Nolte shot look like a Disney poster.
Here, we pick up where the book left off with the 19 most notorious celebrity mug shots from recent memory�Nolte included.


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121 Diamond Spring RoadDenville, NJ 07834
Bring a long sleeved, pre-washed, white or light colored shirt, and see what you can make using only Sharpies and rubbing alcohol! Other materials will be available as well to finish off your creations.
Boys and girls can practice their paper cutting skills as they create their own colorful ballet scene making ballerinas and other characters from the famous ballet.
If you're looking for something fun to do during your time off this week, we have just the winter wonderland craft for you!
Visit the children's room anytime between 5:30 and 8:30 PM and leave with a completed reindeer project that you can make here. No registration required.
Interested participants may come to the children's room anytime from 5:30-8 PM on Thursday, 12/13, to be shown how to make the craft.
Your colorful tissue paper turkeys will be the talk of your Thanksgiving table this year!
After reading this fun book by Mary Ann Hoberman, we'll make and eat our own no-bake mini birthday cakes! Please call Mr. Bryce at 973-627-6555 for a list of food to be used if your child has any food allergies.
Many windows in the late 1800s were covered with thick curtains. Those that were not, were often decorated with colorful paper window pictures. For this next session, we'll take a trip back in time and make our own window pictures, using a variety of colored paper.
Using seeds of varying colors, you can grow your own one of a kind pumpkin seed tree.
Find us on Facebook!
© 2011 Denville Public Library. All rights reserved.
121 Diamond Spring RoadDenville, NJ 07834973.627.6555


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Medicine Man is a company that uses its framework to express the cultural values of lacrosse to its members, and works within its system of values to promote the harmonious understanding of all lacrosse participants - past, present and future.
Medicine Man is a purposeful approach to lacrosse culture, meticulously crafted to reflect an organization whose core values revolves around the player, the game and the community. Each aspect of Medicine Man and the archetype it represents strives to promote the power of imagination, the culture of community, the lifestyle of talent and the self-expressive identity of play. Lacrosse Clothing by Medicine Man has become the extension of efforts to promote, develop and market lacrosse attune to the archetype of the Medicine Man.
Our Lacrosse Shorts and Our Lacrosse Shirts are designed with the specific purpose of nourishing our mission, so that Medicine Man is able to advocate and support the health and well-being of the game. Our mission since our founding in 2011 is simple, to use a portion of sales to provide physicial and educational resources to underprivileged children that desire to play lacrosse but have little to no opportunities to do so.
Our Lacrosse Clothing represents our passion for the game. We take great pride in our product, our designs and the customer experience.
Our Lacrosse clothing shirts are a unqiue blend of 60% Polyester and 40% Cotton materials that combine to create a superior lacrosse clothing shirt. Our Lacrosse clothing shirt uses polyester for its strong, lightweight, non shrinking and quick drying benefits while our cotton material provides a breathable, soft and durable benefit. The combination of fibers create a lacrosse clothing shirt that is resistant to shrinking, creasing, and streching but is light enough and strong enough to keep up with the demands of lacrosse player in intense activity. Medicine Man clothing shirts are unlike any other.
Our Lacrosse clothing shorts are 100% Polyester which means that bright colors will not fade or run in the washing machine and will dry quicker than any other short on the market. Our Lacrosse clothing shorts hold their form, size, color and quality after numerous washes, wears and intense athletic activity. Featuring two deep side pockets and a drawstring waist, Medicine Man Lacrosse shorts are the very best.
Receive flate rate shipping on all US orders for $5.95.
Receive a free drawstring bag with your purchase of Medicine Man Lacrosse.
Our company values the customer and the customer experience. We aim for 100 percent satisfaction.


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Fort Bragg klezmer bands
GigMasters has a number of talented Klezmer Bands that you can easily hire to play at your event – from traditional weddings to bar/bat mitzvahs. Search in the Fort Bragg, CA area for a listing of the bands nearest you. Book with the best, only on GigMasters!


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Perry Como Thanksgiving Special
TV Special
More in Television
TV Highlights
What's On This Week
A daily updated summary of the week in TV.
Program Overview
Genres: Music, Variety
Program Synopsis
A holiday program of music and song, hosted by Perry Como.
What's On Tonight
- Stephen Colbert, the Late Night Hope
- Maria on 'Sesame Street,' Sonia Manzano, Tells of Her Own Childhood
- The National Music Museum, an Unlikely Eden in South Dakota
- Noah Davis, 32, Artist and Founder of Underground Museum in Los Angeles, Dies
- Nikolaus Lehnhoff, German Opera Director, Dies at 76
- Review: 'Big Blue Live' Searches for Marine Life
- Wayne W. Dyer, Prolific Author of Self-Help Books, Dies at 75
- Blondell Cummings, Dancer of Life's Everyday Details, Dies at 70
- Michael Feinstein and the Club 54 Below Agree to a Partnership
- Review: Janet Jackson, on Unbreakable Tour, Shows Off Her Demure Side


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Monday, September 18, 2000
Johnson City, Tenn. -- East Tennessee State senior Chris Wisler (Dover, Del.) earned Golfweek Preseason All-America honors it was announced in the September 16, 2000 issue.
The two-time All-American, earned eight top-20 finishes last season including an individual title at the Bell South Intercollegiate. He tied for eighth at the 1999 NCAA Championships.
This summer Wisler won the Porter Cup and tied for 17th at the Sunnehanna Amateur. He finished second in this falls opening tournament, the Bank of Tennessee/The Ridges Intercollegiate (Sept. 9-10).
The other preseason All-Americans were: Bryce Molder (Georgia Tech), Luke Donald (Northwestern), Paul Casey (Arizona State), Lucas Glover (Clemson), Jeff Quinney (Arizona State), Andy Sanders (Houston), D.J. Trahan (Clemson), Ricky Barnes (Arizona) and Kyle Thompson (South Carolina).
Wisler and the Bucs return to action in the Tennessee Tournament of Champions from Sept. 18-19.
|Copyright ©2015 East Tennessee State Athletics. All Rights Reserved.


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Rangers Vs. Cardinals In World Series
Game 1 of the 2011 World Series is tonight on FOX. The St. Louis Cardinals have 10 World Series Championships with the last one in 2006, while the Rangers are still looking for their first.
The National League won the All-Star game back in July so they will have home field advantage for the World Series


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'Diamonds': Jonas Brothers, Sia Cover Rihanna's Hit — Which Version Wins? (POLL)
Rihanna's "Diamonds" is hot, hot, hot! The Billboard record-breaking single off Ri's new No. 1 album Unapologetic is stuck in everyone's heads these days, including some of the singer's pop peers.
The Jonas Brothers took the stage with a live, guitar-laden cover of RiRi's hit during


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Prepare for takeoff.
Climb into the cockpit of Urban Airship's powerful Mobile Relationship Management platform. Our comprehensive engagement tools fuel some of the world's most successful mobile apps and campaigns: powering push notifications, rich app pages, message centers, digital wallet programs, sophisticated audience targeting and mobile analytics.
Mobile is rapidly expanding your opportunities to drive brand awareness, engage and acquire new customers, and boost customer loyalty. Our mobile tools maximize your investments in this channel to increase the lifetime value of your app by driving deeper engagement, frequent use and value that builds long-term relationships.
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Give your app a voice.
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Location-based targeting makes mobile a radically new opportunity to deeply engage your audience with greater context and relevance than any other medium.
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Customer decisions can happen in a matter of minutes or even seconds, and only mobile is capable of reaching your audience at the moment of inspiration. That's why real-time mobile marketing automation for push messages is critical; it enables you to trigger messages when a customer enters your store or interacts with your app in a way that shows they're ready to take action.
Our intuitive platform helps marketers design and manage messaging programs that support their app's customer lifecycle. You can automatically send welcome messages to help onboard new app users, or setup re-engagement programs for customers who haven't opened your app lately.
It's not enough to send the right message to the right customers—be sure your message reaches customers when and where they're most receptive. With mobile messaging automation, we make it easy.
Mobile Analytics
Stay in the know.
Detailed engagement reports and audience trends help you evaluate the performance of each mobile messaging campaign. You can export this data to combine it with other marketing and analytics systems.
Leverage these insights to optimize your engagement efforts across platforms to drive results.
Digital Wallet
Coupons, loyalty programs and more.
Apple Passbook and Google Wallet offer new, dynamic ways to engage with your mobile audience. Urban Airship's Wallet Studio helps you create passes and cards for digital wallets within minutes through an intuitive drag-and-drop interface.
Deliver your wallet programs directly or use our robust API to distribute them at a large scale via your app, web pages, email and social media. Segment your audience to maximize relevance and response.
Best of all, Wallet Studio leverages the real-time nature of mobile. Update your customers' digital wallet items instantly when things change, such as when offer terms need updating, flight gates, event ticket times or venues change, and when new loyalty rewards are available.
Purpose built. Enterprise class.
Urban Airship's enterprise-class platform provides the performance, scalability and security the world's biggest brands demand. It powers billions of personalized and targeted messages each month, across every major mobile operating system and device.
Developers love our platform because it's so easy to integrate into their apps. Marketers love it because it's the most sophisticated mobile engagement suite in the world and is also the easiest to use.
It's always backed by our top-notch support team and professional services consultants, as well as an ecosystem of industry-leading partners.


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12-Bottle Silent Wine Refrigerator by Wine Enthusiast
Eco-friendly wine fridge keeps 12 bottles cool, without noise.
These premium 12-bottle wine refrigerators keep your bottles cool without making a peep. The secret is Peltier's thermoelectric cooling technology. This advanced cooling system has no moving parts and is CFC-free, meaning that you get silent, long-lasting, and environmentally safe refrigeration for your collection. Black with your choice of Stainless Steel- or Graphite-trimmed glass doors. Note: bottle capacity measured for standard 750ml Bordeaux-size bottles. Order yours today!
Before you choose a wine refrigerator, make sure it has these premium features:
Order your silent wine refrigerator from Brookstone today. Makes a great gift for wine enthusiasts.
12-Bottle Silent Wine Refrigerator by Wine Enthusiast
Reviewed by 2 customers
Sort by
- Attractive Design
- Durable
- Easy To Clean
- Easy to Use
Best Uses
- Home Bar
Comments about 12-Bottle Silent Wine Refrigerator by Wine Enthusiast:
This is very attractive and is perfect on the counter in a hallway next to my kitchen. It keeps my wine chilled at a consistent 54 degrees. Now I can keep several bottles of wine chilled without giving up space in my refrigerator! The inside is easy to clean and the see-through door in combination with the very cool looking led light allows me to look over my collection without opening the door. I store my wine glasses in a cabinet above the wine chiller so it is very convenient to grab a glass of wine in the evening. This wine refrigerator IS completely silent which is another great feature.
- Gift:
- No
- And SILENT
- Attractive Convenient
Best Uses
- Bar Rec Room
- Home Kitchen
Comments about 12-Bottle Silent Wine Refrigerator by Wine Enthusiast:
I've always wanted a dedicated home wine refrigerator, but I didn't want to remodel my kitchen. My Brookstone home wine refrigerator looks great on my counter top, and lets us keep many different kinds of wine at-the-ready for serving without wasting space in our food fridge. The silent operation is a nice touch. Cheers!
12-Bottle Silent Wine Refrigerator by Wine Enthusiast
Our innovative products will provide you and your family with years of enjoyment. And with the Brookstone Protection Plus service and replacement plans, you'll have the added peace of mind knowing that if the unexpected does happen, we will simply repair or replace your covered product. Our enhanced coverage goes above and beyond the manufacturer's warranty, saving you time and money.