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Publication numberUS20070191937 A1
Publication typeApplication
Application numberUS 11/784,882
Publication date16 Aug 2007
Filing date9 Apr 2007
Priority date27 Sep 2001
Also published asUS7223282, US20070191938
Publication number11784882, 784882, US 2007/0191937 A1, US 2007/191937 A1, US 20070191937 A1, US 20070191937A1, US 2007191937 A1, US 2007191937A1, US-A1-20070191937, US-A1-2007191937, US2007/0191937A1, US2007/191937A1, US20070191937 A1, US20070191937A1, US2007191937 A1, US2007191937A1
InventorsSyed Hossainy
Original AssigneeAdvanced Cardiovascular Systems, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Remote activation of an implantable device
US 20070191937 A1
Abstract
The invention is directed to an implantable device, such as a stent, for delivering a therapeutic substance. The device includes a reservoir containing a therapeutic substance and an energy converter to cause the release of the substance.
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Claims(14)
1. A method of delivering a therapeutic substance from a stent in a body vessel comprising:
inserting into a body vessel a stent comprising a first material containing a therapeutic substance and a second material capable of converting a first type of energy to a second type of energy; and
applying to the second material a first type of energy from an energy source external to the body vessel wherein the second material converts the first type of energy to the second type of energy and the second type of energy promotes the release of the therapeutic substance from the first material.
2. The method of claim 1, wherein the second material is selected from the group consisting of Au, Au-alloy, Au having a silica core, and ferromagnetic glass-ceramic.
3. The method of claim 1, wherein the second type of energy is thermal energy.
4. The method of claim 1, wherein the second material is disposed in depots positioned on the surface of the stent or the second material is connected to the surface of the stent.
5. The method of claim 1, wherein the stent further comprises a topcoat deposited over at least a portion of the first material.
6. The method of claim 1, wherein the second material comprises Au particles having a nanoparticle core.
7. The method of claim 1, wherein the stent further comprises a third material carried by the stent to convert a third type of energy received by the third material from an energy source positioned external to the body vessel to a fourth type of energy, wherein the fourth type of energy promotes release of the therapeutic substance from the first material.
8. The method of claim 7, wherein the first and third types of energy are electromagnetic energy, and wherein the electromagnetic energy of the first energy type has a different wavelength than the third energy type.
9. The method of claim 1, wherein the first type of energy is non-cytotoxic electromagnetic waves.
10. The method of claim 1, wherein the second material is capable of converting electromagnetic waves with wavelengths between 800 and 1200 nm into thermal energy.
11. The method of claim 1, wherein the first material is a temperature-sensitive hydrogel.
12. The method of claim 11, wherein the temperature-sensitive hydrogel is in thermal communication with the second material.
13. The method of claim 11, wherein the temperature-sensitive hydrogel is selected from the group consisting of N-isopropylacrylamide, polyoxyethylene-polyoxypropylene block copolymers, poly(acrylic acid) grafted pluronic copolymers, chitosan grafted pluronic copolymer, elastin mimetic polypeptides, and combinations and mixtures thereof.
14. The method of claim 1, wherein the energy source is external to the body of the patient.
Description
    CROSS REFERENCE
  • [0001]
    This is a divisional application of application Ser. No. 09/966,421 filed on Sep. 27, 2001.
  • BACKGROUND OF THE INVENTION
  • [0002]
    1. Field of the Invention
  • [0003]
    This invention relates generally to implantable devices, such as expandable intraluminal prosthesis. More particularly, this invention relates to a stent that delivers a therapeutic substance. Moreover, the present invention relates to a method of delivering a therapeutic substance with a stent.
  • [0004]
    2. Description of the Background
  • [0005]
    A variety of surgical procedures and medical devices are currently used to relieve intraluminal constrictions caused by disease or tissue trauma. An example of one such procedure is percutaneous transluminal coronary angioplasty (PTCA). PTCA is a catheter-based technique whereby a balloon catheter is inserted into a blocked or narrowed coronary lumen of the patient. Once the balloon is positioned at the blocked lumen or target site, the balloon is inflated causing the remodeling of the lumen. The catheter is then removed from the target site thereby allowing blood to freely flow through the lumen.
  • [0006]
    Although PTCA and related procedures aid in alleviating intraluminal constrictions, such constrictions or blockages reoccur in many cases. The cause of these recurring obstructions, termed restenosis, is due to the body's immune system responding to the trauma of the surgical procedure. As a result, the PTCA procedure may need to be repeated to repair the damaged lumen.
  • [0007]
    Stents or drug therapies, either alone or in combination with the PTCA procedure, are often used to avoid or mitigate the effects of restenosis at the surgical site. In general, stents are small, cylindrical devices whose structure serves to create or maintain an unobstructed opening within a lumen. The stents are typically made of, for example, stainless steel, Nitinol or other materials and are delivered to the target site via a balloon catheter. Although stents are effective in opening the stenotic lumen, the foreign material and structure of the stents themselves may exacerbate the occurrence of restenosis or thrombosis.
  • [0008]
    Drugs or therapeutic agents that limit migration and/or proliferation of vascular smooth muscle cells are used to significantly reduce the incidence of restenosis and thrombosis. Examples of various therapeutic agents commonly used include heparin, antithrombogenic agents, steroids, ibuprofen, antimicrobials, antibiotics, antiproliferatives, tissue plasma activator inhibitors, monoclonal antibodies, antiinflammatory substances, and antifibrosis agents.
  • [0009]
    Should the therapeutic agents be applied systemically to the patient, they are absorbed not only by the tissues at the target site, but by all areas of the body. As such, one drawback associated with the systemic application of drugs is that areas of the body not needing treatment are also affected. To provide a more site-specific treatment, stents are frequently used as a means of delivering the drugs exclusively to the target site. The drugs are included or incorporated in a tissue-compatible polymer, such as a silicone, polyurethane, polyester, hydrogel, hyaluronate, and various copolymers and blended mixtures thereof. By positioning the stent at the target site, the drugs can be applied directly to the area of the lumen requiring therapy.
  • [0010]
    The above-described device, for treatment of restenosis and thrombosis, offers many advantages to potential patients. However, such devices may be deficient in their current drug-delivery capabilities. In particular, restenosis does not necessarily develop at a constant rate. The polymer-coated device may have limited effectiveness because the therapeutic agents are released by passive diffusion, and therefore do not have a release pattern that corresponds to the pathological cascade of restenosis.
  • [0011]
    In view of the above, it is apparent that there is a need to provide a drug delivery device which can control the release of the therapeutic agents so that conditions such as restenosis, that develop at a variable rate, can be more effectively treated.
  • SUMMARY OF THE INVENTION
  • [0012]
    Herein is described an implantable device, such as as a stent, for delivering a therapeutic substance comprising a first material carried by the stent containing a therapeutic substance, and a second material carried by the stent to convert a first type of energy received by the second material from an energy source positioned external to the body vessel to a second type of energy, wherein the second type of energy promotes release of the therapeutic substance from the first material.
  • [0013]
    In an embodiment of the present invention, the second material can be, for example, Au, an Au-alloy, or ferrimagnetic glass-ceramic. In one variation, the second material can be Au particles with average diameters of, for example, from about 100-350 nm. In one embodiment, the second material can be capable of converting electromagnetic waves into thermal energy.
  • [0014]
    In one embodiment of the present invention, the first material is a temperature-sensitive hydrogel. The temperature-sensitive hydrogel can be N-isopropylacrylamide, polyoxyethylene-polyoxypropylene block copolymers, poly(acrylic acid) grafted pluronic copolymers, chitosan grafted pluronic copolymer, elastin mimetic polypeptides, and combinations and mixtures thereof.
  • [0015]
    Herein is also disclosed a method of delivering a therapeutic substance from a stent comprising inserting into a body vessel a stent comprising a first material containing a therapeutic substance and a second material capable of converting a first type of energy to a second type of energy, and applying to the second material a first type of energy from an energy source external to the body vessel wherein the second material converts the first type of energy to the second type of energy and the second type of energy promotes the release of the therapeutic substance from the first material.
  • [0016]
    Herein is also disclosed a stent for delivering thermal energy to a body vessel comprising a tubular body for implanting in a body vessel, and an energy converter carried by the tubular body to convert a first type of energy into thermal energy, wherein the energy converter is positioned to release the thermal energy to tissues adjacent to the tubular body and is responsive to an energy source remote from and not in direct physical contact with the energy converter.
  • [0017]
    Herein is also described a system for delivering a therapeutic substance comprising a device for implanting in the body, a reservoir carried by the device containing a therapeutic substance, an energy converter carried by the device to convert a first type of energy to a second type of energy to release the therapeutic substance from the reservoir, and an energy emitter for emitting the first type of energy to the energy converter.
  • BRIEF DESCRIPTION OF THE FIGURES
  • [0018]
    FIG. 1 is a side-view of a conventional stent in accordance with an embodiment of the present invention;
  • [0019]
    FIG. 2 is a diagram of an embodiment of the remote delivery system including a stent inserted into a body vessel;
  • [0020]
    FIG. 3 illustrates an enlarged view of a portion of a stent;
  • [0021]
    FIG. 4 illustrates a partial cross-section of a strut along the line 4-4 of FIG. 3;
  • [0022]
    FIG. 5 illustrates the partial cross-section of the strut in accordance with one embodiment of the invention;
  • [0023]
    FIG. 6 illustrates the partial cross-section of the strut in accordance with another embodiment of the invention;
  • [0024]
    FIG. 7 illustrates the partial cross-section of the strut in accordance with another embodiment of the invention;
  • [0025]
    FIG. 8 illustrates the partial cross-section of the strut in accordance with another embodiment of the invention; and
  • [0026]
    FIG. 9 graphically illustrates absorbance spectra of Au particles.
  • DETAILED DESCRIPTION
  • [0027]
    FIG. 1 illustrates an implantable prosthetic medical device. In the spirit of convenience and brevity, the medical device referenced in the text and figures of the present invention is a stent 10. However, it should be noted that other medical devices or prosthesis are also within the scope of the claimed invention. Suitable examples of other devices can include grafts (e.g., aortic grafts), stent-grafts, artificial heart valves, cerebrospinal fluid shunts, pacemaker electrodes, axius coronary shunts, and endocardial leads (e.g., FINELINE® and ENDOTAK®, available from Guidant Corporation).
  • [0028]
    As shown in FIGS. 1 and 2, stent 10 can have a tubular body structure 12, including a first end 14, a second end 16, and a mid-section 18. The structure of stent 10 should allow stent 10 to be inserted into and physically uphold an anatomical passageway by exerting a radially outward-extending force against the walls or inner lumen surface of the passageway. If desired, stent 10 can also expand the opening of the lumen to a diameter greater than its original diameter and, thereby, increase fluid flow through the lumen.
  • [0029]
    Stent 10 can include struts 22 that form a network structure. Struts 22 are radially expandable and interconnected by connecting elements 24 that are disposed between adjacent struts 22. Both struts 22 and connecting elements 24 have an outer (or lumen contacting) surface 26 and an inner surface 28, as shown in FIG. 2. In addition, a hollow bore 20 extends longitudinally through body structure 12 of stent 10.
  • [0030]
    Referring to FIG. 3, one or more depots (e.g., microdepots) or pores 30 can be formed on the surface of struts 22 and/or connecting elements 24. These depots 30 can act as reservoirs for various substances. In one embodiment of the present invention, as shown in FIG. 4, depots 30 that are formed on outer surface 26 carry an energy conversion material 32. Energy conversion material 32 can be any material that is capable of receiving a stimuli and converting such a stimuli to a form of energy. In one embodiment, for example, energy conversion material 32 is able to convert a first type of energy (e.g., electromagnetic, thermal, chemical) into a second type of energy (e.g., electromagnetic, thermal, chemical).
  • [0031]
    In one embodiment, gold (Au), in the form of particles, can be used as energy conversion material 32. The Au particles can be contained in depots 30 by various means, including but not limited to, by polymeric adhesives, or by sintering the Au particles in depots 30.
  • [0032]
    If the Au particles are exposed to electromagnetic waves, for example, the Au particles can convert the electromagnetic energy into thermal energy. The Au particles can have, for example, an average diameter from about 100-350 nm. The Au particles can have a silica nanoparticle core (e.g., 100-250 nm diameter) encapsulated by a thin (e.g., 1-100 nm) gold shell. By changing the relative thickness of the particle's core and shell, one can choose the peak absorbance to anywhere from about 600 nm to about 1400 nm. Au particles of this type can be capable of converting non-cytotoxic electromagnetic waves with wavelengths between 800 nm and 1200 nm into thermal energy. With the use of non-cytotoxic electromagnetic waves as the first energy type, the body tissues surrounding the body vessel do not readily absorb or refract the waves.
  • [0033]
    Since the Au particles are carried by depots 30 which are disposed on outer surface 26 as shown in FIG. 4, if inserted into a blood vessel, the stent can deliver heat to the tissues surrounding the blood vessel and cause heat shock protein generation. As a result, it is believed that restenosis in the blood vessel can be reduced.
  • [0034]
    One of ordinary skill in the art will understand that energy conversion materials 32 besides Au particles are within the scope of the invention. For instance, ferrimagnetic glass-ceramics can be used as energy conversion material 32. These ferrimagnetic glass-ceramics can convert magnetic field energy to thermal energy. A representative of this type of material is the ferrimagnetic glass-ceramics containing lithium ferrite and hematite crystallites in the system Al2O3—SiO2—P2O5. Also, one of ordinary skill in the art will understand that various parameters can be altered in order to control the thermal output of energy conversion material 32 such as core-shell ratio, the wavelength applied to the energy conversion material 32, the intensity of the radiation and the use of an insulating material.
  • [0035]
    As shown in FIG. 5, a carrier material 34 can coat at least a portion of outer surface 26 for release of a therapeutic substance in response to the stimuli. In one embodiment, carrier material 34 can be a temperature-sensitive hydrogel. “Hydrogel” is intended to include a cross-linked polymer, via covalent, ionic, or hydrogen bonding, to form a three-dimensional open lattice structure which is capable of entrapping water molecules to form a gel.
  • [0036]
    In another embodiment, as shown in FIG. 6, the hydrogel can be in the form of particles, microparticles, spheres, or ovoids. Particles, microparticles, spheres, or ovoids of the hydrogel can be formed by, for example, extrusion with a non-miscible substance such as oil, e.g., mineral oil or by agitation of the aqueous phase in contact with a non-miscible phase such as an oil phase to form small droplets. The macromer is then polymerized such as by exposure to light irradiation or to heat. Inclusion of a therapeutic substance mixed with the aqueous macromer solution results in the encapsulation of the therapeutic substance in the hydrogel. Energy conversion material 32 (e.g., Au particles) may also be encapsulated in the small droplets of the hydrogel.
  • [0037]
    For purposes of this invention, “temperature-sensitive hydrogel” means a hydrogel whose matrix constricts or collapses by exposing the hydrogel to a temperature greater than the hydrogel's lower critical solution temperature (LCST). The LCST (i.e., the temperature at which constriction occurs), should be above 37° C. (i.e., average human body temperature). One suitable example of a temperature-sensitive hydrogel is N-isopropylacrylamide (NIPAAm). One of ordinary skill in the art can also appreciate the implementation of other hydrogels in the polymeric coating of the present invention. Representative examples include polyoxyethylene-polyoxypropylene block copolymers (e.g., PLURONIC®, BASF Corporation, Parsippany, N.J.) such as those described in U.S. Pat. No. 4,188,373; poly(acrylic acid) or chitosan (a deacylated derivative of chitin) grafted pluronic copolymers, in which the grafted poly(acrylic acid) or chitosan improve the bio-adhesive properties of the hydrogel; and combinations and mixtures thereof, as well as elastin mimetic polypeptides, which are protein polymers based on the pentameric repeat -[(Val/Ile)-Pro-Gly-Xaa-Gly]5-, where Xaa is an amino acid and is Val in the first four repeat units and Ile or Lys for the last repeat. With Xaa of Ile in the last repeat unit and a pH of 7, the elastin-mimetic polypeptide has a transition temperature of approxiamately 37° C.
  • [0038]
    Referring to FIG. 2, energy conversion material 32 (e.g., Au particles) (not shown) can receive at least a portion of electromagnetic waves 42 emitted by an energy emitter 40 that is positioned external to body vessel 46 or completely external to the body of the patient. The Au particles are able to absorb electromagnetic waves 42 and convert the electromagnetic energy into thermal energy which is released into the environment adjacent to the Au particles. Should stent 10 be coated with a hydrogel containing a therapeutic substance, the thermal energy or stimuli can be used to promote the release of the therapeutic substance. For example, once the temperature surrounding the hydrogel exceeds the hydrogel's transition temperature, the hydrogel contracts. As the hydrogel contracts, it elutes the therapeutic substance by “squeezing” the substance out of the hydrogel's matrix. As shown in FIG. 2, therapeutic substance 36 is thereby locally delivered to body vessel 46. In order to reduce the amount of therapeutic substance 36 eluted into the aqueous environment before remote activation, it would be useful to pair an anionic hydrogel with a cationic therapeutic substance.
  • [0039]
    The therapeutic substance can be for inhibiting the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis. The active agent can also include any substance capable of exerting a therapeutic or prophylactic effect in the practice of the present invention. For example, the therapeutic substance can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site. Examples of substances include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I1, actinomycin X1, and actinomycin C1. The active agent can also fall under the genus of antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S.A., Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® from Pharmacia & Upjohn, Peapack, N.J.), and mitomycin (e.g., Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g., Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck & Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, rapamycin and dexamethasone. The foregoing substances are listed by way of example and are not meant to be limiting. Other therapeutic substances which are currently available or that may be developed in the future are equally applicable.
  • [0040]
    Referring to FIG. 6, in another embodiment, carrier material 34 (e.g., temperature-sensitive hydrogel), in the form of ovoids, encapsulates energy conversion material 32. Carrier material 34 further includes a therapeutic substance. As shown in FIG. 6, carrier material 34 is carried by depots 30, and is covered by a topcoat 50. In one embodiment, topcoat 50 is a hydrophilic polymer that inhibits the diffusion of the therapeutic substance from carrier material 34 until energy conversion material 32 is activated. A representative example of topcoat 50 is a blend of polyethylene glycol (PEG) and bishydroxyethoxypropylpolydimethylsiloxane (PDMS).
  • [0041]
    Referring to FIG. 7, in an alternative embodiment, carrier material 34, including energy conversion material 32 and a therapeutic substance, is suspended in topcoat 50. In one embodiment, topcoat 50 is a hydrophilic polymer that inhibits the diffusion of the therapeutic substance from carrier material 34 until energy conversion material 32 is activated.
  • [0042]
    Referring to FIG. 8, in a further embodiment, instead of being carried by depots 30, energy conversion material 32 (e.g., Au particles) can be attached directly to outer surface 26 of stent 10 over which carrier material 34 (e.g., a hydrogel coating) is deposited. Energy conversion material 32 can be in the form of particles randomly disbursed or evenly distributed on outer surface 26. Alternatively, the density of energy conversion material 32 could be greater at each end 14 and 16 of stent 10 compared to mid-section 18 of stent 10. One of ordinary skill in the art will understand that the location and configuration of energy conversion material 32, and its position relative to carrier material 34, may vary according to clinical purpose and usage requirements and the particular type of stent 10 used to carry the components.
  • [0043]
    Alternatively, two or more different types of energy conversion materials can be used. For example, depots 30 at ends 14, 16 of stent 10 can carry Au particles, whereas depots 30 at mid-section 18 carry an Au—Cu alloy. By providing stent 10 with different types of energy conversion material 32, there can be a non-uniform response to energy emitted so that the delivery of the therapeutic substance can differ either spatially, or temporally. For example, in the case of Au particles, particles with different core-shell ratios will have different peak absorbance profiles. Referring to FIG. 9, the absorbance spectra for particles A and B show that particle A has a different peak absorbance than particle B. By matching particle A with a carrier material that carries a different therapeutic substance than that matched with particle B, different therapeutic substances can be delivered at different wavelengths.
  • [0044]
    The present invention also includes a method of delivering a therapeutic substance from a stent in a body vessel. Again referring to FIG. 2, in one embodiment, stent 10 is inserted into body vessel 46 and then electromagnetic waves 42 are applied by using energy emitter 40 that is positioned external to body vessel 46. Stent 10 may comprise Au particles and a temperature-sensitive hydrogel that encapsulates a therapeutic substance. The Au particles are able to absorb the electromagnetic waves 42 and convert the electromagnetic energy into thermal energy which is transferred to the temperature-sensitive hydrogel. In one embodiment, the Au particles have an average diameter from about 100-350 nm. In another embodiment, the electromagnetic waves can have a wavelength of between 800 and 1200 nm. Once the environmental temperature surrounding the hydrogel reaches the hydrogel's transition temperature, the hydrogel contracts. As the hydrogel contracts, the hydrogel elutes the therapeutic substance by “squeezing” the therapeutic substance out of the hydrogel's matrix. As shown in FIG. 2, therapeutic substance 36 is locally delivered to body vessel 46.
  • EXAMPLES
  • [0045]
    The following prophetic examples are given by way of illustration.
  • Example 1
  • [0046]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles are mixed with a macromer solution and become suspended at a concentration of 30% w/w. The macromer solution contains 15% diacrylate end-capped pluronic diacrylate, 2.5% ethylene glycol dimethacrylate (EGDMA) (all monomer percentages are in molar), 0.5% benzolyl peroxide, 5% polyvinyl pyrrolidone (PVP), 7% ReoPro® (Eli Lilly and Company, Indianapolis, Ind.), and 70% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. The coating is activated by directing a 900-1200 nm wavelength light in the infrared region of the electromagnetic spectrum to the coating.
  • Example 2
  • [0047]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles are mixed with a macromer solution and become suspended at a concentration of 30% w/w. The macromer solution contains 10% diacrylate end-capped pluronic diacrylate, 5% N-isopropyl alcohol, 2.5% EGDMA, 0.5% benzolyl peroxide, 5% PVP, 5% ReoPro®, 5% TAXOL, and 67% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. The coating is activated by directing a 900-1200 nm wavelength light in the infrared region of the electromagnetic spectrum to the coating.
  • Example 3
  • [0048]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles are mixed with a macromer solution and become suspended at a concentration of 30% w/w. A 95:5 molar ratio of dimethyl aminoethylmethacrylate (DMAEMA) and acrylic acid (AAc) has an LCST of about 40° C. The macromer solution contains 10% DMAEMA, 0.5% AAc, 2.5% EGDMA, 0.5% benzolyl peroxide, 5% PVP, 5% ReoPro®, 5% R-7 conjugated heparin, and 71.5% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. The coating is activated by directing a 900-1200 nm wavelength light in the infrared region of the electromagnetic spectrum to the coating.
  • Example 4
  • [0049]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles with different sizes are mixed with a macromer solution and become suspended at a concentration of 30% w/w. The macromer solution contains 15% diacrylate end-capped temperature sensitive polymers with a LCST greater than 40° C., 2.5% EGDMA, 0.5% benzolyl peroxide, 5% PVP, 5% ReoPro®, 5% R-7 conjugated heparin, and 67% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. The coating is activated by directing a 900-1200 nm wavelength light in the infrared region of the electromagnetic spectrum to the coating.
  • Example 5
  • [0050]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles are mixed with a macromer solution and become suspended at a concentration of 30% w/w. A 93:7 molar ratio of DMAEMA and AAc has an LCST of about 42° C. The macromer solution contains 9.6% DMAEMA, 0.9% AAc 2.5% EGDMA, 0.5% benzolyl peroxide, 5% PVP, 5% ReoPro®, 5% R-7 conjugated heparin, and 71.5% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr.
  • Example 6
  • [0051]
    Stents are cleaned with isopropyl alcohol in combination with ultrasonication. Au particles (232 nm diameter silica core and 12 nm Au shell thickness) are mixed with a macromer solution and become suspended at a concentration of 30% w/w. A 95:5 molar ratio of NIPAAm and Acryl amide (AAm) has an LCST of about 40° C. The macromer solution contains 9.5% NIPAAm, 0.5% AAm, 2.5% EGDMA, 0.5% benzolyl peroxide, 5% PVP, 5% ReoPro®, 5% R-7 conjugated heparin, and 72% H2O. The Au suspension solution is applied as a coating to the surface of the stents with a wet weight of 1000 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr. Then the macromer solution (without Au particles) is applied to the surface of the stents by dip-coating with a wet weight of 800 μg. The coating is heated at 65° C. for 4 minutes to induce a cross-linking reaction. Following the cross-linking reaction, the coating is dried in a vacuum oven at 40° C. for 12 hr.
  • [0052]
    In another example an elastin-mimetic di-block copolypeptide is cross-linked by the same method as above. The LCST can be adjusted to a range of about 40-43° C. by adjusting the ratio of the hydrophobic and the hydrophilic block. An example of a hydrophobic block is [-Ile-Pro-Gly-Val-Gly-]. An example of a hydrophilic block is [-Val-Pro-Gly-Glu-Gly-]). Examples of cross-linking constituents include disuccinimydil glutarate and disuccinimydil suberate.
  • [0053]
    While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US4042519 *16 Feb 197316 Aug 1977Owens-Illinois, Inc.Ferrimagnetic glass-ceramics
US4188373 *18 Nov 197712 Feb 1980Cooper Laboratories, Inc.Clear, water-miscible, liquid pharmaceutical vehicles and compositions which gel at body temperature for drug delivery to mucous membranes
US4329383 *21 Jul 198011 May 1982Nippon Zeon Co., Ltd.Non-thrombogenic material comprising substrate which has been reacted with heparin
US4733665 *7 Nov 198529 Mar 1988Expandable Grafts PartnershipExpandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4800882 *13 Mar 198731 Jan 1989Cook IncorporatedEndovascular stent and delivery system
US4941870 *30 Dec 198817 Jul 1990Ube-Nitto Kasei Co., Ltd.Method for manufacturing a synthetic vascular prosthesis
US5112457 *23 Jul 199012 May 1992Case Western Reserve UniversityProcess for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5292516 *8 Nov 19918 Mar 1994Mediventures, Inc.Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
US5298260 *9 Jun 199229 Mar 1994Mediventures, Inc.Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality
US5300295 *13 Sep 19915 Apr 1994Mediventures, Inc.Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
US5304121 *22 Nov 199119 Apr 1994Boston Scientific CorporationDrug delivery system making use of a hydrogel polymer coating
US5306501 *8 Nov 199126 Apr 1994Mediventures, Inc.Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers
US5328471 *4 Aug 199312 Jul 1994Endoluminal Therapeutics, Inc.Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens
US5330768 *5 Jul 199119 Jul 1994Massachusetts Institute Of TechnologyControlled drug delivery using polymer/pluronic blends
US5380299 *30 Aug 199310 Jan 1995Med Institute, Inc.Thrombolytic treated intravascular medical device
US5417981 *28 Apr 199323 May 1995Terumo Kabushiki KaishaThermoplastic polymer composition and medical devices made of the same
US5605696 *30 Mar 199525 Feb 1997Advanced Cardiovascular Systems, Inc.Drug loaded polymeric material and method of manufacture
US5609629 *7 Jun 199511 Mar 1997Med Institute, Inc.Coated implantable medical device
US5624411 *7 Jun 199529 Apr 1997Medtronic, Inc.Intravascular stent and method
US5628730 *18 Jul 199413 May 1997Cortrak Medical, Inc.Phoretic balloon catheter with hydrogel coating
US5649977 *22 Sep 199422 Jul 1997Advanced Cardiovascular Systems, Inc.Metal reinforced polymer stent
US5658995 *27 Nov 199519 Aug 1997Rutgers, The State UniversityCopolymers of tyrosine-based polycarbonate and poly(alkylene oxide)
US5716981 *7 Jun 199510 Feb 1998Angiogenesis Technologies, Inc.Anti-angiogenic compositions and methods of use
US5735897 *2 Jan 19977 Apr 1998Scimed Life Systems, Inc.Intravascular stent pump
US5746998 *8 Aug 19965 May 1998The General Hospital CorporationTargeted co-polymers for radiographic imaging
US5776184 *9 Oct 19967 Jul 1998Medtronic, Inc.Intravasoular stent and method
US5788979 *10 Feb 19974 Aug 1998Inflow Dynamics Inc.Biodegradable coating with inhibitory properties for application to biocompatible materials
US5858746 *25 Jan 199512 Jan 1999Board Of Regents, The University Of Texas SystemGels for encapsulation of biological materials
US5865814 *6 Aug 19972 Feb 1999Medtronic, Inc.Blood contacting medical device and method
US5869127 *18 Jun 19979 Feb 1999Boston Scientific CorporationMethod of providing a substrate with a bio-active/biocompatible coating
US5873904 *24 Feb 199723 Feb 1999Cook IncorporatedSilver implantable medical device
US5876433 *29 May 19962 Mar 1999Ethicon, Inc.Stent and method of varying amounts of heparin coated thereon to control treatment
US5877224 *28 Jul 19952 Mar 1999Rutgers, The State University Of New JerseyPolymeric drug formulations
US5925720 *18 Apr 199620 Jul 1999Kazunori KataokaHeterotelechelic block copolymers and process for producing the same
US6010530 *18 Feb 19984 Jan 2000Boston Scientific Technology, Inc.Self-expanding endoluminal prosthesis
US6015541 *3 Nov 199718 Jan 2000Micro Therapeutics, Inc.Radioactive embolizing compositions
US6026316 *15 May 199715 Feb 2000Regents Of The University Of MinnesotaMethod and apparatus for use with MR imaging
US6033582 *16 Jan 19987 Mar 2000Etex CorporationSurface modification of medical implants
US6042875 *2 Mar 199928 Mar 2000Schneider (Usa) Inc.Drug-releasing coatings for medical devices
US6051576 *29 Jan 199718 Apr 2000University Of Kentucky Research FoundationMeans to achieve sustained release of synergistic drugs by conjugation
US6051648 *13 Jan 199918 Apr 2000Cohesion Technologies, Inc.Crosslinked polymer compositions and methods for their use
US6056993 *17 Apr 19982 May 2000Schneider (Usa) Inc.Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel
US6060451 *20 Mar 19959 May 2000The National Research Council Of CanadaThrombin inhibitors based on the amino acid sequence of hirudin
US6060518 *16 Aug 19969 May 2000Supratek Pharma Inc.Polymer compositions for chemotherapy and methods of treatment using the same
US6071944 *12 Nov 19976 Jun 2000Bowling Green State UniversityMethod of treatment of pigmented cancer cells utilizing photodynamic therapy
US6080488 *24 Mar 199827 Jun 2000Schneider (Usa) Inc.Process for preparation of slippery, tenaciously adhering, hydrophilic polyurethane hydrogel coating, coated polymer and metal substrate materials, and coated medical devices
US6096070 *16 May 19961 Aug 2000Med Institute Inc.Coated implantable medical device
US6099562 *22 Dec 19978 Aug 2000Schneider (Usa) Inc.Drug coating with topcoat
US6110188 *9 Mar 199829 Aug 2000Corvascular, Inc.Anastomosis method
US6110483 *23 Jun 199729 Aug 2000Sts Biopolymers, Inc.Adherent, flexible hydrogel and medicated coatings
US6187037 *11 Mar 199813 Feb 2001Stanley SatzMetal stent containing radioactivatable isotope and method of making same
US6200307 *22 May 199813 Mar 2001Illumenex CorporationTreatment of in-stent restenosis using cytotoxic radiation
US6201065 *26 Jul 199613 Mar 2001Focal, Inc.Multiblock biodegradable hydrogels for drug delivery and tissue treatment
US6203551 *4 Oct 199920 Mar 2001Advanced Cardiovascular Systems, Inc.Chamber for applying therapeutic substances to an implant device
US6231600 *26 May 199915 May 2001Scimed Life Systems, Inc.Stents with hybrid coating for medical devices
US6240616 *15 Apr 19975 Jun 2001Advanced Cardiovascular Systems, Inc.Method of manufacturing a medicated porous metal prosthesis
US6241719 *13 May 19995 Jun 2001Micro Therapeutics, Inc.Method for forming a radioactive stent
US6245753 *27 Apr 199912 Jun 2001Mediplex Corporation, KoreaAmphiphilic polysaccharide derivatives
US6251136 *8 Dec 199926 Jun 2001Advanced Cardiovascular Systems, Inc.Method of layering a three-coated stent using pharmacological and polymeric agents
US6254632 *28 Sep 20003 Jul 2001Advanced Cardiovascular Systems, Inc.Implantable medical device having protruding surface structures for drug delivery and cover attachment
US6258121 *2 Jul 199910 Jul 2001Scimed Life Systems, Inc.Stent coating
US6335029 *3 Dec 19981 Jan 2002Scimed Life Systems, Inc.Polymeric coatings for controlled delivery of active agents
US6346110 *3 Jan 200112 Feb 2002Advanced Cardiovascular Systems, Inc.Chamber for applying therapeutic substances to an implantable device
US6352683 *15 Jul 19975 Mar 2002Point Biomedical CorporationApparatus and method for the local delivery of drugs
US6358556 *23 Jan 199819 Mar 2002Boston Scientific CorporationDrug release stent coating
US6379380 *29 Aug 200030 Apr 2002Stanley SatzMetal stent containing radioactivatable isotope and method of making same
US6379381 *3 Sep 199930 Apr 2002Advanced Cardiovascular Systems, Inc.Porous prosthesis and a method of depositing substances into the pores
US6383217 *29 Aug 20007 May 2002Stanley SatzMetal stent containing radioactivatable isotope and method of making same
US6395326 *31 May 200028 May 2002Advanced Cardiovascular Systems, Inc.Apparatus and method for depositing a coating onto a surface of a prosthesis
US6419692 *3 Feb 199916 Jul 2002Scimed Life Systems, Inc.Surface protection method for stents and balloon catheters for drug delivery
US6503556 *28 Dec 20007 Jan 2003Advanced Cardiovascular Systems, Inc.Methods of forming a coating for a prosthesis
US6503954 *21 Jul 20007 Jan 2003Advanced Cardiovascular Systems, Inc.Biocompatible carrier containing actinomycin D and a method of forming the same
US6506437 *17 Oct 200014 Jan 2003Advanced Cardiovascular Systems, Inc.Methods of coating an implantable device having depots formed in a surface thereof
US6520957 *14 Nov 200018 Feb 2003Michael KasinkasTreatment of in-stent restenosis using cytotoxic radiation
US6527801 *13 Apr 20004 Mar 2003Advanced Cardiovascular Systems, Inc.Biodegradable drug delivery material for stent
US6527863 *29 Jun 20014 Mar 2003Advanced Cardiovascular Systems, Inc.Support device for a stent and a method of using the same to coat a stent
US6540776 *28 Dec 20001 Apr 2003Advanced Cardiovascular Systems, Inc.Sheath for a prosthesis and methods of forming the same
US6544223 *5 Jan 20018 Apr 2003Advanced Cardiovascular Systems, Inc.Balloon catheter for delivering therapeutic agents
US6544543 *27 Dec 20008 Apr 2003Advanced Cardiovascular Systems, Inc.Periodic constriction of vessels to treat ischemic tissue
US6544582 *5 Jan 20018 Apr 2003Advanced Cardiovascular Systems, Inc.Method and apparatus for coating an implantable device
US6555157 *25 Jul 200029 Apr 2003Advanced Cardiovascular Systems, Inc.Method for coating an implantable device and system for performing the method
US6558733 *26 Oct 20006 May 2003Advanced Cardiovascular Systems, Inc.Method for etching a micropatterned microdepot prosthesis
US6565659 *28 Jun 200120 May 2003Advanced Cardiovascular Systems, Inc.Stent mounting assembly and a method of using the same to coat a stent
US6572644 *27 Jun 20013 Jun 2003Advanced Cardiovascular Systems, Inc.Stent mounting device and a method of using the same to coat a stent
US6585765 *29 Jun 20001 Jul 2003Advanced Cardiovascular Systems, Inc.Implantable device having substances impregnated therein and a method of impregnating the same
US6585926 *31 Aug 20001 Jul 2003Advanced Cardiovascular Systems, Inc.Method of manufacturing a porous balloon
US6725081 *6 Jun 200120 Apr 2004Volcano Therapeutics, Inc.Intravascular radiation delivery device
US6736842 *24 Jul 200218 May 2004B. Braun Medical Inc.Thermo-mechanically expandable stent
US6758859 *30 Oct 20006 Jul 2004Kenny L. DangIncreased drug-loading and reduced stress drug delivery device
US6764507 *7 Sep 200120 Jul 2004Conor Medsystems, Inc.Expandable medical device with improved spatial distribution
US6887862 *31 May 20013 May 2005Miravant Systems, Inc.Method for improving treatment selectivity and efficacy using intravascular photodynamic therapy
US6899723 *13 Jul 200131 May 2005Light Sciences CorporationTranscutaneous photodynamic treatment of targeted cells
US20010018469 *28 Dec 200030 Aug 2001Yung-Ming ChenEthylene vinyl alcohol composition and coating
US20020077693 *19 Dec 200020 Jun 2002Barclay Bruce J.Covered, coiled drug delivery stent and method
US20020091433 *17 Dec 200111 Jul 2002Ni DingDrug release coated stent
US20020095197 *11 Jul 200118 Jul 2002Lardo Albert C.Application of photochemotherapy for the treatment of cardiac arrhythmias
US20030065377 *30 Apr 20023 Apr 2003Davila Luis A.Coated medical devices
US20030099712 *26 Nov 200129 May 2003Swaminathan JayaramanTherapeutic coating for an intravascular implant
US20050158363 *23 Apr 200321 Jul 2005Poly-Med Inc.Multifaceted endovascular stent coating for preventing restenosis
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US9072618 *13 Apr 20117 Jul 2015Biotronik AgBiocorrodable implant in which corrosion may be triggered or accelerated after implantation by means of an external stimulus
US20110276124 *13 Apr 201110 Nov 2011Biotronik AgBiocorrodable implant in which corrosion may be triggered or accelerated after implantation by means of an external stimulus
Classifications
U.S. Classification623/1.42
International ClassificationA61F2/06
Cooperative ClassificationA61F2/91, A61F2/915, A61F2002/91533, A61F2250/0001, A61F2002/91575, A61F2250/0068
European ClassificationA61F2/91, A61F2/915