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Publication numberUS20080091262 A1
Publication typeApplication
Application numberUS 11/582,706
Publication dateApr 17, 2008
Filing dateOct 17, 2006
Priority dateOct 17, 2006
Also published asUS8398706, US20110190875
Publication number11582706, 582706, US 2008/0091262 A1, US 2008/091262 A1, US 20080091262 A1, US 20080091262A1, US 2008091262 A1, US 2008091262A1, US-A1-20080091262, US-A1-2008091262, US2008/0091262A1, US2008/091262A1, US20080091262 A1, US20080091262A1, US2008091262 A1, US2008091262A1
InventorsDavid C. Gale, Bin Huang
Original AssigneeGale David C, Bin Huang
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Drug delivery after biodegradation of the stent scaffolding
US 20080091262 A1
Abstract
Disclosed herein is a stent comprising: a bioabsorbable polymeric scaffolding; and a coating comprising a bioabsorbable material on at least a portion of the scaffolding, wherein the degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating.
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Claims(32)
1. A stent comprising:
a bioabsorbable polymeric scaffolding; and
a coating comprising a bioabsorbable material on at least a portion of the scaffolding, wherein the degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating.
2. The stent according to claim 1, wherein the stent includes an anti-proliferative agent, an anti-inflammatory agent, or a mixture thereof.
3. The stent according to claim 2, wherein the anti-proliferative agent is selected from the group consisting of Everolimus, Rapamycin, and/or derivatives thereof.
4. The stent according to claim 2, wherein the anti-inflammatory agent is Clobetasol.
5. The stent according to claim 1, wherein the coating material comprises Everolimus and poly(D,L-lactide) of a 1:1 ratio, and the scaffolding comprises D,L-lactide and glycolide monomers of a 1:9 ratio.
6. A method treating a body lumen, the method comprising:
providing a stent comprising a scaffolding that degrades at a faster rate than a coating on the scaffolding; and
deploying the stent at a treatment area in a body lumen.
7. The method according to claim 6, wherein the stent includes an anti-proliferative agent, an anti-inflammatory agent, or a mixture thereof.
8. The method according to claim 6, wherein an anti-inflammatory agent is mixed or dispersed within the scaffolding.
9. The method according to claim 6, wherein an anti-inflammatory agent and the anti-proliferative agent is delivered from at least a portion of the coating.
10. The method according to claim 6, wherein an anti-inflammatory agent is delivered from the scaffolding and suppresses inflammation of the lumen during all or a majority of the degradation of the scaffolding.
11. The method according to claim 6, wherein the coating in the stent comprises Everolimus and poly(D,L-lactide) of a 1:1 ratio, and the scaffolding comprises D,L-lactide and glycolide monomers of a 1:9 ratio.
12. The method according to claim 6, wherein the stent includes Everolimus, Rapamycin, and/or derivatives thereof.
13. The method according to claim 6, wherein the stent includes Clobetasol.
14. The method according to claim 6, wherein upon deployment of the stent in the treatment area, the scaffolding substantially or completely degrades from the treatment area before the coating substantially or completely degrades.
15. The method according to claim 6, wherein the coating delivers a drug to the lumen during degradation of the scaffolding and after substantial or complete degradation of the scaffolding.
16. The method according to claim 6, wherein the coating becomes endothelialized in a wall of the lumen and delivers a drug after the scaffolding has substantially or completely degraded.
17. A method of treating a body lumen, the method comprising:
deploying a first stent at a treatment area, wherein the first stent includes a bioabsorbable polymeric scaffolding and a coating having a bioabsorbable material on at least a portion of the scaffolding, and wherein the degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating; and
deploying a second stent in at least a portion of the treatment area.
18. The method according to claim 17, wherein an anti-inflammatory agent is mixed or dispersed within the scaffolding.
19. The method according to claim 17, wherein an anti-inflammatory agent is delivered from at least a portion of the coating material of the first stent, wherein the coating material comprises an anti-proliferative agent.
20. The method according to claim 17, wherein an anti-inflammatory agent is delivered from the scaffolding of the first stent and suppresses inflammation of the body lumen during substantial or complete degradation of the scaffolding.
21. The method according to claim 17, wherein the stent includes an anti-proliferative agent.
22. The method according to claim 21, wherein the anti-proliferative agent in the first stent is Everolimus, Rapamycin, and/or derivatives thereof.
23. The method according to claim 17, wherein the first stent includes an anti-inflammatory agent.
24. The method according to claim 23, wherein the anti-inflammatory agent in the first stent is Clobetasol.
25. The method according to claim 17, wherein the coating material in the first stent comprises Everolimus and poly(D,L-lactide) of a 1:1 ratio, and the scaffolding comprises D,L-lactide and glycolide monomers of a 1:9 ratio.
26. The method according to claim 17, wherein the second stent is deployed when the scaffolding has substantially or completely degraded.
27. The method according to claim 17, wherein the coating material of the first stent is capable of at least partially eluting a drug when the second stent is deployed.
28. The method according to claim 17, wherein the first stent includes Everolimus, Rapamycin, and/or derivatives thereof.
29. The method according to claim 17, wherein the first stent includes Clobetasol.
30. The method according to claim 17, wherein upon deployment of the stent in the treatment area, the scaffolding substantially or completely degrades from the treatment area before the coating substantially or completely degrades.
31. The method according to claim 17, wherein the coating delivers a drug to the lumen during degradation of the scaffolding and after substantial or complete degradation of the scaffolding.
32. The method according to claim 17, wherein the coating becomes endothelialized in a wall of the lumen and delivers a drug after the scaffolding has substantially or completely degraded.
Description
    BACKGROUND OF THE INVENTION
  • [0001]
    1. Field of the Invention
  • [0002]
    This invention generally relates to a stent for treating a disorder with a drug over a period of time extending beyond biodegradation of the stent scaffolding.
  • [0003]
    2. Description of the Background
  • [0004]
    In particular, the invention relates to radially expandable endoprostheses that are adapted to be implanted in a bodily lumen. An “endoprosthesis” corresponds to an artificial device that is placed inside the body. A “lumen” refers to a cavity of a tubular organ such as a body lumen. A stent is an example of such an endoprosthesis. Stents are generally cylindrically shaped devices which function to hold open and sometimes expand a segment of a body lumen or other anatomical lumen such as urinary tracts and bile ducts. Stents are often used in the treatment of atherosclerotic stenosis in body lumens. “Stenosis” refers to a narrowing or constriction of the diameter of a bodily passage or orifice. In such treatments, stents reinforce body vessels and prevent restenosis following angioplasty. “Restenosis” refers to the reoccurrence of stenosis in a body lumen or heart valve after it has been subjected to angioplasty or valvuloplasty.
  • [0005]
    The treatment of a diseased site or lesion with a stent involves both delivery and deployment of the stent. “Delivery” refers to introducing and transporting the stent through a bodily lumen to the treatment area in a body lumen. “Deployment” corresponds to the expanding of the stent within the lumen at the treatment area. Delivery and deployment of a stent are accomplished by positioning the stent at one end of a catheter, inserting the end of the catheter through the skin into a bodily lumen, advancing the catheter in the bodily lumen to a desired treatment location, expanding the stent at the treatment location, and removing the catheter from the lumen. In the case of a balloon expandable stent, the stent is mounted about a balloon disposed on the catheter. Mounting the stent typically involves compressing or crimping the stent onto the balloon. The stent is then expanded by inflating the balloon. The balloon may then be deflated and the catheter withdrawn. In the case of a self-expanding stent, the stent may be secured to the catheter via a retractable sheath or a sock.
  • [0006]
    When the stent is in a desired bodily location, the sheath may be withdrawn allowing the stent to self-expand. This requires a sufficient degree of strength and rigidity or stiffness. In addition to having adequate radial strength, the stent should be longitudinally flexible to allow it to be maneuvered through a tortuous vascular path.
  • [0007]
    Thus, a stent is typically composed of scaffolding that includes a pattern or network of interconnecting structural elements or struts. The scaffolding can be formed of tubes, or sheets of material rolled into a cylindrical shape. The scaffolding is designed to allow the stent to be radially expandable. The pattern is generally designed to maintain the longitudinal flexibility and radial rigidity required of the stent. Longitudinal flexibility facilitates delivery of the stent and radial rigidity is needed to hold open a bodily lumen. A medicated stent may be fabricated by coating the surface of either a metallic or polymeric scaffolding with a polymeric carrier that includes a bioactive agent. The polymeric scaffolding may also serve as a carrier of bioactive agent.
  • [0008]
    In many treatment applications of stents, the presence of a stent in a body may be necessary for a limited period of time until its intended function of, for example, maintaining vascular patency and/or drug delivery is accomplished. Thus, stents are often fabricated from biodegradable, bioabsorbable, and/or bioerodable materials such that they completely erode only after the clinical need for them has ended. In addition, a stent should also be capable of satisfying the mechanical requirements discussed above during the desired treatment time.
  • [0009]
    A polymeric stent should be mechanically stable throughout the range of stress experienced during use. In addition to mechanical stability, a stent should have a sufficient rate of biodegradability or erosion as dictated by a treatment regimen. However, one of the major clinical challenges of bioabsorbable stents is adequately suppressing inflammatory responses triggered by the degradation of the stent. The embodiments of the invention address this and other concerns.
  • SUMMARY OF THE INVENTION
  • [0010]
    Disclosed herein is a stent comprising: a bioabsorbable polymeric scaffolding; and a coating comprising a bioabsorbable material on at least a portion of the scaffolding, wherein the degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating.
  • [0011]
    Also disclosed herein is a method treating a body lumen, the method comprising: providing a stent comprising a scaffolding that degrades at a faster rate than a coating on the scaffolding; and deploying the stent at a treatment area in a body lumen.
  • [0012]
    Further, disclosed herein is a method of treating a body lumen, the method comprising: deploying a first stent at a treatment area, wherein the first stent includes a bioabsorbable polymeric scaffolding and a coating having a bioabsorbable material on at least a portion of the scaffolding, and wherein the degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating; and deploying a second stent in at least a portion of the treatment area.
  • BRIEF DESCRIPTION OF THE FIGURES
  • [0013]
    FIG. 1 depicts a stent.
  • [0014]
    FIG. 2( a) depicts a cross-section of a stent implanted in a body lumen, the stent having a scaffolding and a coating.
  • [0015]
    FIG. 2( b) depicts the stent after endothelialization of the stent in the body lumen.
  • [0016]
    FIG. 2( c) depicts the stent after endothelialization of the stent and degradation of the scaffolding.
  • [0017]
    FIG. 3 depicts a second stent that is implanted at a treatment area of a first stent.
  • DETAILED DESCRIPTION
  • [0018]
    A common disorder associated with mechanical modification of a vessel, such as by a balloon or stenting is restenosis. A number of cellular mechanisms have been proposed that lead to restenosis of a vessel, such as inflammatory response to injury and foreign body presence.
  • [0019]
    Inflammation is a defensive, biological response to injury, infection, or an abrupt change in tissue homeostasis. In nature, inflammatory responses are designed to destroy, dilute and isolate injurious agents and then lead to recovery and repair of the affected tissue. Vascular inflammation is the first stage of the inflammatory response, developing after the initial contact with the stimulus and continuing sometimes for several days. The presence of a stimulatory agent in the blood or in the tissue triggers the body's response through endothelial cells. The endothelial cell layer is the innermost layer of larger vessels and the only cell layer of the smallest vessels, the capillaries.
  • [0020]
    Additionally, the presence of a biodegradable foreign body, such as a biodegradable stent in a vessel can lead to or aggravate an inflammatory response, thus leading to more aggressive restenosis. Biodegradation refers generally to changes in physical and chemical properties that occur (e.g., in a polymer) upon exposure to bodily fluids as in a vascular environment. The changes in properties may include a decrease in molecular weight, deterioration of mechanical properties, and decrease in mass due to erosion or absorption. The decrease in molecular weight may be caused by chemical reactions of bodily fluids with the polymer, for example, hydrolysis and/or metabolic processes. By-products of such degradation reactions can be responsible for inciting inflammation. For example, by-products of hydrolysis are produced when polymer molecules are cleaved into component parts by the addition of water. Various byproducts of degradation of biodegradable polymers are known to incite an inflammatory response. For example, lactic acid, a degradation by-product of poly(lactic acid) polymers, is known to cause an inflammatory response.
  • [0021]
    Furthermore, the release of by-products into the body from a biodegradable stent occurs continuously from the time of first exposure to bodily fluids to a time when the stent is either completely degraded and eliminated or removed from the body. It follows that throughout this time frame, the body is continuously exposed to inflammation-inciting by-products. Therefore, it is desirable for the stent to degrade rapidly once the need for support of the lumen has expired.
  • [0022]
    Described herein is a drug-delivery stent that allows delivery of drug even after the stent scaffolding has degraded. Thus, the stent scaffolding need not remain in the body lumen to deliver drug. The stent scaffolding may be made to degrade rapidly and completely or substantially completely disappear once the need for support of the lumen has expired. The drug-delivery stent described herein includes one or more drugs for treating a vascular disorder or a related disorder. The drugs, for example, can be a combination of at least one anti-proliferative agent, at least one anti-inflammatory agent, and optionally other types of bioactive agents.
  • [0023]
    A biodegradable stent and drug delivery can remain in the body for a duration of time at least until its intended function of, for example, maintaining vascular patency and drug delivery is accomplished. Biodegradable polymers are used to form the stent, such that the entire stent can be made to disappear after the process of degradation, erosion, or absorption. In some embodiments, very negligible traces of polymer or residue are left behind. The duration is typically in the range of 6-12, 6-18, or 6-24 months, for example. The time needed to maintain vascular patency can be shorter than the drug delivery time.
  • [0024]
    The term “stent” is intended to include, but is not limited to, self-expandable stents, balloon-expandable stents, stent-grafts, and grafts. The structure of the stent can be of virtually any design. A stent, for example, may include a pattern or network of interconnecting structural elements or struts. FIG. 1 depicts an example of a three-dimensional view of a stent 100. The stent may have any pattern that includes a number of interconnecting elements or struts 110. As shown in FIG. 1 the geometry or shape of stents vary throughout its structure. In some embodiments, a stent may be formed from a tube by laser cutting the pattern of struts into the tube. The stent may also be formed by laser cutting a polymeric sheet, rolling the pattern into the shape of the cylindrical stent, and providing a longitudinal weld to form the stent.
  • [0025]
    A stent 200 according to one embodiment of the invention includes a bioabsorbable polymeric scaffolding 210 and a coating material 220 on at least a portion of the scaffolding 210, as depicted in FIG. 2( a). Coating material 220 may include a drug and a bioabsorbable polymer. The degradation rate of at least a portion of scaffolding 210 is faster than the degradation rate of coating material 220. In one embodiment, the degradation rate of all or substantially all of scaffolding 210 is faster than the degradation rate of all or substantially all of coating material 220. Thus, the degradation time of all or substantially all scaffolding 210 is shorter than the degradation time of all or substantially all coating material 220. By providing a scaffolding 210 that has a faster degradation rate than its coating 220, the scaffolding 210 degrades first, while coating material 220 continues to deliver drug. In one embodiment, coating material 220 continues to deliver drug after scaffolding 210 has completely degraded. FIG. 2( b) depicts a cross-section of a stent implanted in body lumen 230. FIG. 2( b) depicts stent 200 after endothelialization of stent 200 in lumen wall 240. In one embodiment, all or substantially all of coating material 220 degrades faster than all or substantially all of scaffolding 210. In another embodiment, coating material 220 continues to elute drugs even after vascular patency has expired. The coating layer remains after there is no longer any stent vascular patency.
  • [0026]
    Turning now to FIG. 2( c), with continual reference to FIG. 2( b), coating material 220 remains lodged in lumen wall 240 after scaffolding 210 substantially degrades. Because coating material 220 can be made to deliver drug even after the disintegration of scaffolding 210, the invention enables stent 200 to release drug for an extended period of time throughout the life of stent 200 while scaffolding 210 degrades, and if desired, long after scaffolding 210 degrades. In one embodiment, stent 200 delivers drug for over 50% of the life of scaffolding 210. In another embodiment, stent 200 delivers drug for over 80% of the life of scaffolding 210. In yet another embodiment, stent 200 delivers drug for the entire life of scaffolding 210, or 100% of the life of scaffolding 210. Thus, after the entire scaffolding 210 has completely degraded, coating material 220 may be designed to continue to deliver drug, as depicted in FIG. 2( c).
  • [0027]
    In one embodiment, upon deployment of stent 200 in treatment area, scaffolding 210 substantially or completely degrades from treatment area before coating 220 substantially or completely degrades. In another embodiment, coating 220 delivers a drug to the lumen 240 during degradation of scaffolding 210 and after substantial or complete degradation of scaffolding 210. In yet another embodiment, coating 220 becomes endothelialized in a wall of lumen 240 and delivers a drug after scaffolding 210 has substantially or completely degraded.
  • [0028]
    In one embodiment, the stent includes an anti-proliferative agent that includes, but is not limited to, Everolimus, Rapamycin, and/or derivatives thereof. Everolimus is available under the trade name Certican™, Novartis Pharma AG, Germany. The anti-proliferative agent may be included within the coating material's polymer matrix and/or in the scaffolding's polymer matrix. In one embodiment, the anti-proliferative agent is intermixed or dispersed within the coating material's polymer matrix and/or intermixed or dispersed in the scaffolding's polymer matrix. In certain embodiments, the anti-proliferative agent is included in depots within the coating and/or the scaffolding.
  • [0029]
    The stent may also include an anti-inflammatory agent. Clobetasol is available under the trade name Temovate™, Glaxosmithkline, UK. The anti-inflammatory agent may be included within the coating material's polymer matrix and/or in the scaffolding's polymer matrix. In one embodiment, the anti-inflammatory agent is intermixed or dispersed within the coating material's polymer matrix and/or intermixed or dispersed within the scaffolding's polymer matrix. In certain embodiments, the anti-inflammatory agent is included in depots within the coating and/or the scaffolding.
  • [0030]
    The release of inflammation-inciting by-products into the body from a biodegradable device can occur continuously while the scaffolding is degrading within the body. An anti-inflammatory included within the scaffolding may allow for sustained release of the inflammatory agent throughout the scaffolding's degradation. The drug-delivery stent disclosed herein may include a sustained release of an anti-inflammatory agent from the scaffolding. After the scaffolding absorbs, the coating material remains in the lumen wall.
  • [0031]
    The underlying stent scaffolding is made from a polymeric material that degrades more rapidly than the polymer used to form the coating material. The polymer used to form the scaffolding is faster degrading than the coating material. Any biodegradable polymer may be used to the form the scaffolding and the coating material, as long as the polymer used to make all or substantially all the scaffolding degrades faster than the polymer used to make all or substantially all the coating material. In some embodiments, the scaffolding can be formed of a copolymer that includes two functional groups or units. One of the units tends to increase the degradation rate compared to a homopolymer including the other unit. Thus, glycolide has a faster degradation rate and is more hydrolytically active.
  • [0032]
    In one embodiment, the stent scaffolding is formed of poly(D,L-lactide-co-glycolide), where 10% of the copolymer is D,L-lactide and 90% of the copolymer is glycolide. In another embodiment, the stent scaffolding is formed of poly(L-lactide-co-glycolide), where 10% of the copolymer is D,L-lactide and 90% of the copolymer is glycolide. In this embodiment, any polymer that degrades at a slower rate than poly(D,L-lactide-co-glycolide) may be used to form the coating material. For example; PLLA can be used to form a coating material because PLLA is slower degrading than poly(D,L-lactide-co-glycolide). In another embodiment, the stent scaffolding is formed of poly(D,L-lactide-co-glycolide), where 5-45% of the copolymer is D,L-lactide and 55-95% of the copolymer is glycolide. In yet another embodiment, 1:1 Everolimus and poly(D,L-lactide) is used to form the coating material, which degrades at about 12 months and has the ability to deliver drug for 3 months. Thus, the drug will be delivered even after the scaffolding has degraded, or has been absorbed into the body, or no longer has vascular patency.
  • [0033]
    In one embodiment, the scaffolding is made to degrade rapidly, thereby reducing the risk of a negative reaction to the presence of a degrading stent. Certain embodiments provide for a rapidly degrading scaffolding, one that degrades within 6 months, within 3 months, or more narrowly within 2 months.
  • [0034]
    In one embodiment, the stent scaffolding may be fabricated to include an erodible metal, such as magnesium. Other material may also be used to fabricate the stent scaffolding, so long as all or substantially all of the scaffolding degrades at a faster rate than all or substantially all of the coating material. In one embodiment, the coating material includes Everolimus and poly(D,L-lactide) of a 1:1 ratio, and the scaffolding includes D,L-lactide and glycolide monomers of a 1:9 ratio, or poly(D,L-lactide-co-glycolide).
  • [0035]
    As described above, it is also possible to have a sustained release of an anti-inflammatory agent from the coating material. The anti-inflammatory agent may be included within the coating and is delivered from a surface of the coating. The coating material may be configured to sustain delivery of anti-inflammatory agent throughout the degradation of a stent scaffolding to counteract the inflammatory effect of the degradation of by-products.
  • [0036]
    In one embodiment, an anti-inflammatory agent is included in both the coating and the scaffolding. An anti-inflammatory agent may be delivered from the coating as well as the scaffolding to suppress inflammation of a body lumen during all or a majority of the degradation of the scaffolding.
  • [0037]
    In one embodiment, a first stent is deployed at a treatment area, and a second stent is deployed in at least a portion of the treatment area, or the treatment area is “re-stented”.
  • [0038]
    The first stent includes a bioabsorbable polymeric scaffolding and a coating having a bioabsorbable material on at least a portion of the scaffolding. The degradation rate of all or substantially all of the bioabsorbable polymer of the scaffolding is faster than the degradation rate of all or substantially all of the bioabsorbable material of the coating;
  • [0039]
    The second stent is deployed when the scaffolding of the first stent has at least partially degraded, has substantially degraded, or has completely degraded. Thus, embodiments disclosed herein may prove advantageous to methods for re-stenting a lumen. Certain embodiments provide for a rapidly degrading scaffolding, that degrades within 6 months, within 3 months, or more narrowly within 2 months. Re-stenting is facilitated by rapid degradation of the first stent's scaffolding, enabling a second stent to be implanted in the stented area or treatment area within only a few months after the first stent has been implanted. When the second stent is deployed in the treatment area, the functional lumen diameter is not reduced as is the case when a second stent is deployed at an treatment area of a first stent that has only partially degraded. In the latter case, the reduced functional diameter causes the blood flow to fall significantly and possibly congest the lumen.
  • [0040]
    Depicted in FIG. 3 is a second stent 300 that has been implanted in the same treatment area 310 as a first stent 320. In some embodiments, second stent 300 is implanted in lumen 330 after endothelialization of first stent 320. In some embodiments, second stent 300 is implanted in lumen 330 after a scaffolding (not depicted) of a first stent 320 is at least partially degraded, substantially degraded, or more narrowly, completely degraded in lumen 330. In some embodiments, second stent 300 is deployed in treatment area 310 when scaffolding (not pictured) of the first stent is greater than 50% degraded, greater than 75% degraded, and more narrowly, greater than 95% degraded as known of those skilled in the art.
  • [0041]
    In one embodiment, second stent 300 may be implanted in treatment area 310 after all or substantially all of scaffolding of first stent 320 has is degraded, such that only a coating material 340 of first stent 320 remains in the lumen. In certain embodiments, coating material 320 of first stent 340 continues to deliver drug when second stent 300 is implanted.
  • [0042]
    As discussed above, a drug(s) may be included in the coating or scaffolding of the first stent. Thus, when the second stent is implanted, the first stent may deliver drug from at least a portion of the coating material of the first stent while the second stent is implanted. For example, an anti-inflammatory agent may be included within the coating material of the first stent, such that when the scaffolding of the second stent is implanted, the anti-inflammatory agent continues to deliver drug to prevent inflammation. As mentioned above, the anti-inflammatory agent that is delivered from the coating material of the first stent may also effectively suppress inflammation of a lumen during all or a majority of the degradation of the scaffolding of the first stent.
  • [0043]
    In a further embodiment, an anti-inflammatory drug and/or an anti-proliferative drug is included in the coating and/or the scaffolding of the stent and is designed to have release parameters for drugs included. The second stent may have a biostable or biodegradable scaffolding made from a metal, polymer, or combination thereof. The second stent may or may not include a coating or a drug.
  • [0044]
    The drug mixed or dispersed within a biodegradable scaffolding may be delivered into a lumen at substantially the same, a faster rate, or a slower rate as the scaffolding degrades. In one embodiment, the drug may be incorporated within the scaffolding during fabrication of the stent according to the general skill in the art. For example, an anti-inflammatory agent may be incorporated in the scaffolding, and configured to be delivered through the coating material to treat inflamed portions of lumens.
  • [0045]
    Moreover, the properties of the coating, such as thickness and porosity, may influence the rate of release of the drug(s) from the stent. Some embodiments may include controlling the release rate of the drug by modifying the properties of the coating.
  • [0046]
    In one embodiment, the stent includes a scaffolding and depots having drug. As used herein, the coating described above includes depots. In one embodiment, one or more drugs may be contained within at least one depot or cavity on at least a portion of a surface of the scaffolding. The drug in the depot may be pure or substantially pure drug. Alternatively, the drug in the depot may be mixed or dispersed in a polymer matrix, which degrades at a faster rate than the scaffolding. Thus, the scaffolding may degrade first, while the drug/polymer mixture within the depots continues to deliver drug long after the scaffolding has degraded. Numerous embodiments of a stent with depots configured to hold a drug are possible. Depots may be placed at one or more arbitrary locations on a stent. The greater inflammation may arise from a larger concentration of degradation products closer to the center of the stent than the ends of the stent. Thus, the center of the lesion may require more anti-inflammatory agent than the ends of the lesion. Alternatively, the ends of the lesion may be more inflamed due to mechanical stresses causing irritation or injury to the ends of the lesion. Thus, a stent may include depots or more depots in regions of a stent adjacent portions of a lesion having more inflammation.
  • [0047]
    The anti-proliferative agent can be a natural proteineous agent such as a cytotoxin or a synthetic molecule. Preferably, the active agents 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), all taxoids such as taxols, docetaxel, and paclitaxel, paclitaxel derivatives, all olimus drugs such as macrolide antibiotics, rapamycin, Everolimus, structural derivatives and functional analogues of rapamycin, structural derivatives and functional analogues of Everolimus, FKBP-12 mediated mTOR inhibitors, biolimus, perfenidone, prodrugs thereof, co-drugs thereof, and combinations thereof. Representative rapamycin derivatives include 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, or 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578 manufactured by Abbot Laboratories, Abbot Park, Ill.), prodrugs thereof, co-drugs thereof, and combinations thereof.
  • [0048]
    Any drugs having anti-inflammatory effects can be used in the present invention. The anti-inflammatory drug can be a steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, or a combination thereof. In some embodiments, anti-inflammatory drugs include, but are not limited to, alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anirolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelains, broperamole, budesonide, carprofen, cicloprofen, cintazone, cliprofen, Clobetasol propionate, clobetasone butyrate, clopirac, cloticasone propionate, cormethasone acetate, cortodoxone, deflazacort, desonide, desoximetasone, dexamethasone dipropionate, diclofenac potassium, diclofenac sodium, diflorasone diacetate, diflumidone sodium, diflunisal, difluprednate, diftalone, dimethyl sulfoxide, drocinonide, endrysone, enlimomab, enolicam sodium, epirizole, etodolac, etofenamate, felbinac, fenamole, fenbufen, fenclofenac, fenclorac, fendosal, fenpipalone, fentiazac, flazalone, fluazacort, flufenamic acid, flumizole, flunisolide acetate, flunixin, flunixin meglumine, fluocortin butyl, fluorometholone acetate, fluquazone, flurbiprofen, fluretofen, fluticasone propionate, fuiraprofen, furobufen, halcinonide, halobetasol propionate, halopredone acetate, ibufenac, ibuprofen, ibuprofen aluminum, ibuprofen piconol, ilonidap, indomethacin, indomethacin sodium, indoprofen, indoxole, intrazole, isoflupredone acetate, isoxepac, isoxicam, ketoprofen, lofemizole hydrochloride, lomoxicam, loteprednol etabonate, meclofenamate sodium, meclofenamic acid, meclorisone dibutyrate, mefenamic acid, mesalamine, meseclazone, methylprednisolone suleptanate, momiflumate, nabumetone, naproxen, naproxen sodium, naproxol, nimazone, olsalazine sodium, orgotein, orpanoxin, oxaprozin, oxyphenbutazone, paranyline hydrochloride, pentosan polysulfate sodium, phenbutazone sodium glycerate, pirfenidone, piroxicam, piroxicam cinnamate, piroxicam olamine, pirprofen, prednazate, prifelone, prodolic acid, proquazone, proxazole, proxazole citrate, rimexolone, romazarit, salcolex, salnacedin, salsalate, sanguinarium chloride, seclazone, sermetacin, sudoxicam, sulindac, suprofen, talmetacin, talniflumate, talosalate, tebufelone, tenidap, tenidap sodium, tenoxicam, tesicam, tesimide, tetrydamine, tiopinac, tixocortol pivalate, tolmetin, tolmetin sodium, triclonide, triflumidate, zidometacin, zomepirac sodium, aspirin (acetylsalicylic acid), salicylic acid, corticosteroids, glucocorticoids, tacrolimus, pimecorlimus, prodrugs thereof, co-drugs thereof, and combinations thereof.
  • [0049]
    The relative amount of the anti-proliferative agent and/or anti-inflammatory agent in the stent can be determined by the lumen to be treated. For example, where Everolimus is used as the anti-proliferative agent and Clobetasol is used as the anti-inflammatory agent, the relative amount of Everolimus and Clobetasol can be varied for different types of lesions, that is, the relative amount of Everolimus can be higher for more proliferative lesions, and on the other hand, the relative amount of Clobetasol can be higher for more inflammatory lesions.
  • [0050]
    In some embodiments, other agents can be used in combination with the anti-proliferative agent and the anti-inflammatory agents. These bioactive agents can be any agent which is a therapeutic, prophylactic, or diagnostic agent. These agents can also have anti-proliferative and/or anti-inflammmatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombonic, antimitotic, antibiotic, antiallergic, antioxidant as well as cystostatic agents. Examples of suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities. Nucleic acid sequences include genes, antisense molecules which bind to complementary DNA to inhibit transcription, and ribozymes. Some other examples of other bioactive agents include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides and ribozymes and retroviral vectors for use in gene therapy. Examples of antineoplastics and/or antimitotics include 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, thrombin inhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.), 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), nitric oxide or nitric oxide donors, super oxide dismutases, super oxide dismutase mimetic, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), estradiol, anticancer agents, dietary supplements such as various vitamins, and a combination thereof. Examples of such cytostatic substance 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.). An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, and genetically engineered epithelial cells. The foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
  • [0051]
    Representative examples of polymers that may be used to fabricate the scaffolding, the coating, or to provide a drug delivery particle with the anti-proliferative drug and/or anti-inflammatory drug include, but are not limited to, poly(N-acetylglucosamine) (Chitin), Chitosan, poly(3-hydroxyvalerate), poly(lactide-co-glycolide), poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide), poly(L-lactide-co-D,L-lactide), poly(caprolactone), poly(L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone), poly(glycolide-co-caprolactone), poly(trimethylene carbonate), polyester amide, poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers other than polyacrylates, vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidene halides (such as polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon 66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides, polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, and carboxymethyl cellulose. Additional representative examples of polymers that may be especially well suited for use in fabricating embodiments of stents disclosed herein include ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL), poly(butyl methacrylate), poly(vinylidene fluoride-co-hexafluoropropene) (e.g., SOLEF 21508, available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (otherwise known as KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate copolymers, poly(vinyl acetate), styrene-isobutylene-styrene triblock copolymers, and polyethylene glycol.
  • [0052]
    The coating material described herein can be formed by spray coating or any other coating process available in the art. Generally, the coating material involves dissolving or suspending the coating material, or one or more components thereof, in a solvent or solvent mixture to form a solution, suspension, or dispersion of the coating material or one or more components thereof, applying the solution or suspension to an implantable stent, and removing the solvent or solvent mixture to form a coating or a layer of coating. As used herein, the term “solvent” refers to a liquid substance or coating material that is compatible with the polymer and is capable of dissolving or suspending the polymeric coating material or one or more components thereof at a desired concentration.
  • [0053]
    In some embodiments, the coating can include a primer layer and/or topcoat layers or sub-layers. The primer layer will be beneath the drug/therapeutic substance layer and the topcoat layer above it. Both the primer layer and the topcoat layer can be without any drugs/therapeutic substances. In some embodiments, some drug may incidentally migrate into the primer layer or region. The topcoat layer reduces the rate of release of the drug and/or provides for bio-beneficial properties.
  • [0054]
    Although embodiments disclosed herein are focused on stents, the embodiments may be applied to any implantable medical device that has a coating and a substrate.
  • [0055]
    The stent or drug-delivery system disclosed herein can be used to treat or prevent a disorder including but not limited to thrombosis, high cholesterol, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, restenosis and progression of atherosclerosis in patient subsets including type I diabetics, type II diabetics, metabolic syndrome and syndrome X, vulnerable lesions including those with thin-capped fibroatheromatous lesions, systemic infections including gingivitis, hellobacteria, and cytomegalovirus, and combinations thereof.
  • [0056]
    A stent having the above-described coating material is useful for a variety of medical procedures, including, by way of example, treatment of obstructions caused by tumors in bile ducts, esophagus, trachea/bronchi and other biological passageways. A stent having the above-described coating material is particularly useful for treating occluded regions of body lumens caused by abnormal or inappropriate migration and proliferation of smooth muscle cells, thrombosis, and restenosis. Stents may be placed in a wide array of body lumens, both arteries and veins. Representative examples of sites include the iliac, renal, and coronary arteries.
  • [0057]
    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.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US4321711 *Oct 12, 1979Mar 30, 1982Sumitomo Electric Industries, Ltd.Vascular prosthesis
US4633873 *Apr 26, 1984Jan 6, 1987American Cyanamid CompanySurgical repair mesh
US4656083 *Mar 11, 1985Apr 7, 1987Washington Research FoundationPlasma gas discharge treatment for improving the biocompatibility of biomaterials
US4718907 *Jun 20, 1985Jan 12, 1988Atrium Medical CorporationVascular prosthesis having fluorinated coating with varying F/C ratio
US4722335 *Oct 20, 1986Feb 2, 1988Vilasi Joseph AExpandable endotracheal tube
US4723549 *Sep 18, 1986Feb 9, 1988Wholey Mark HMethod and apparatus for dilating blood vessels
US4732152 *Dec 5, 1985Mar 22, 1988Medinvent S.A.Device for implantation and a method of implantation in a vessel using such device
US4733665 *Nov 7, 1985Mar 29, 1988Expandable Grafts PartnershipExpandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4739762 *Nov 3, 1986Apr 26, 1988Expandable Grafts PartnershipExpandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4740207 *Sep 10, 1986Apr 26, 1988Kreamer Jeffry WIntralumenal graft
US4800882 *Mar 13, 1987Jan 31, 1989Cook IncorporatedEndovascular stent and delivery system
US4816339 *Apr 28, 1987Mar 28, 1989Baxter International Inc.Multi-layered poly(tetrafluoroethylene)/elastomer materials useful for in vivo implantation
US4818559 *Jul 29, 1986Apr 4, 1989Sumitomo Chemical Company, LimitedMethod for producing endosseous implants
US4902289 *Aug 9, 1988Feb 20, 1990Massachusetts Institute Of TechnologyMultilayer bioreplaceable blood vessel prosthesis
US4994298 *Apr 18, 1990Feb 19, 1991Biogold Inc.Method of making a biocompatible prosthesis
US5084065 *Jul 10, 1989Jan 28, 1992Corvita CorporationReinforced graft assembly
US5085629 *Sep 27, 1989Feb 4, 1992Medical Engineering CorporationBiodegradable stent
US5100429 *Oct 20, 1989Mar 31, 1992C. R. Bard, Inc.Endovascular stent and delivery system
US5104410 *Oct 22, 1990Apr 14, 1992Intermedics Orthopedics, IncSurgical implant having multiple layers of sintered porous coating and method
US5108417 *Sep 14, 1990Apr 28, 1992Interface Biomedical Laboratories Corp.Anti-turbulent, anti-thrombogenic intravascular stent
US5108755 *Apr 27, 1989Apr 28, 1992Sri InternationalBiodegradable composites for internal medical use
US5192311 *Aug 13, 1990Mar 9, 1993Angeion CorporationMedical implant and method of making
US5197977 *Apr 30, 1992Mar 30, 1993Meadox Medicals, Inc.Drug delivery collagen-impregnated synthetic vascular graft
US5279594 *May 23, 1990Jan 18, 1994Jackson Richard RIntubation devices with local anesthetic effect for medical use
US5282860 *Oct 8, 1992Feb 1, 1994Olympus Optical Co., Ltd.Stent tube for medical use
US5289831 *Apr 21, 1992Mar 1, 1994Vance Products IncorporatedSurface-treated stent, catheter, cannula, and the like
US5290271 *Jul 29, 1993Mar 1, 1994Jernberg Gary RSurgical implant and method for controlled release of chemotherapeutic agents
US5306286 *Feb 1, 1991Apr 26, 1994Duke UniversityAbsorbable stent
US5306294 *Aug 5, 1992Apr 26, 1994Ultrasonic Sensing And Monitoring Systems, Inc.Stent construction of rolled configuration
US5383925 *Sep 14, 1992Jan 24, 1995Meadox Medicals, Inc.Three-dimensional braided soft tissue prosthesis
US5385580 *Sep 21, 1992Jan 31, 1995Meadox Medicals, Inc.Self-supporting woven vascular graft
US5389106 *Oct 29, 1993Feb 14, 1995Numed, Inc.Impermeable expandable intravascular stent
US5399666 *Apr 21, 1994Mar 21, 1995E. I. Du Pont De Nemours And CompanyEasily degradable star-block copolymers
US5502158 *Sep 22, 1992Mar 26, 1996Ecopol, LlcDegradable polymer composition
US5591199 *Jun 7, 1995Jan 7, 1997Porter; Christopher H.Curable fiber composite stent and delivery system
US5591607 *Jun 6, 1995Jan 7, 1997Lynx Therapeutics, Inc.Oligonucleotide N3→P5' phosphoramidates: triplex DNA formation
US5593403 *Sep 14, 1994Jan 14, 1997Scimed Life Systems Inc.Method for modifying a stent in an implanted site
US5593434 *Jun 7, 1995Jan 14, 1997Advanced Cardiovascular Systems, Inc.Stent capable of attachment within a body lumen
US5599301 *Nov 22, 1993Feb 4, 1997Advanced Cardiovascular Systems, Inc.Motor control system for an automatic catheter inflation system
US5599922 *Mar 18, 1994Feb 4, 1997Lynx Therapeutics, Inc.Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
US5605696 *Mar 30, 1995Feb 25, 1997Advanced Cardiovascular Systems, Inc.Drug loaded polymeric material and method of manufacture
US5607442 *Nov 13, 1995Mar 4, 1997Isostent, Inc.Stent with improved radiopacity and appearance characteristics
US5607467 *Jun 23, 1993Mar 4, 1997Froix; MichaelExpandable polymeric stent with memory and delivery apparatus and method
US5618299 *Aug 8, 1995Apr 8, 1997Advanced Cardiovascular Systems, Inc.Ratcheting stent
US5707385 *Nov 16, 1994Jan 13, 1998Advanced Cardiovascular Systems, Inc.Drug loaded elastic membrane and method for delivery
US5711763 *Jun 30, 1995Jan 27, 1998Tdk CorporationComposite biological implant of a ceramic material in a metal substrate
US5716981 *Jun 7, 1995Feb 10, 1998Angiogenesis Technologies, Inc.Anti-angiogenic compositions and methods of use
US5725549 *Sep 12, 1996Mar 10, 1998Advanced Cardiovascular Systems, Inc.Coiled stent with locking ends
US5726297 *Jun 5, 1995Mar 10, 1998Lynx Therapeutics, Inc.Oligodeoxyribonucleotide N3' P5' phosphoramidates
US5728751 *Nov 25, 1996Mar 17, 1998Meadox Medicals, Inc.Bonding bio-active materials to substrate surfaces
US5733326 *May 28, 1996Mar 31, 1998Cordis CorporationComposite material endoprosthesis
US5733330 *Jan 13, 1997Mar 31, 1998Advanced Cardiovascular Systems, Inc.Balloon-expandable, crush-resistant locking stent
US5733564 *Apr 12, 1994Mar 31, 1998Leiras OyMethod of treating endo-osteal materials with a bisphosphonate solution
US5733925 *Oct 28, 1996Mar 31, 1998Neorx CorporationTherapeutic inhibitor of vascular smooth muscle cells
US5741881 *Nov 25, 1996Apr 21, 1998Meadox Medicals, Inc.Process for preparing covalently bound-heparin containing polyurethane-peo-heparin coating compositions
US5855612 *May 10, 1996Jan 5, 1999Ohta Inc.Biocompatible titanium implant
US5855618 *Sep 13, 1996Jan 5, 1999Meadox Medicals, Inc.Polyurethanes grafted with polyethylene oxide chains containing covalently bonded heparin
US5858746 *Jan 25, 1995Jan 12, 1999Board Of Regents, The University Of Texas SystemGels for encapsulation of biological materials
US5865814 *Aug 6, 1997Feb 2, 1999Medtronic, Inc.Blood contacting medical device and method
US5868781 *Oct 22, 1996Feb 9, 1999Scimed Life Systems, Inc.Locking stent
US5873904 *Feb 24, 1997Feb 23, 1999Cook IncorporatedSilver implantable medical device
US5874101 *Apr 14, 1997Feb 23, 1999Usbiomaterials Corp.Bioactive-gel compositions and methods
US5874109 *Sep 4, 1997Feb 23, 1999The Trustees Of The University Of PennsylvaniaIncorporation of biological molecules into bioactive glasses
US5874165 *May 27, 1997Feb 23, 1999Gore Enterprise Holdings, Inc.Materials and method for the immobilization of bioactive species onto polymeric subtrates
US5876743 *Sep 22, 1997Mar 2, 1999Den-Mat CorporationBiocompatible adhesion in tissue repair
US5877263 *Nov 25, 1996Mar 2, 1999Meadox Medicals, Inc.Process for preparing polymer coatings grafted with polyethylene oxide chains containing covalently bonded bio-active agents
US5879713 *Jan 23, 1997Mar 9, 1999Focal, Inc.Targeted delivery via biodegradable polymers
US5888533 *Nov 21, 1997Mar 30, 1999Atrix Laboratories, Inc.Non-polymeric sustained release delivery system
US5891192 *May 22, 1997Apr 6, 1999The Regents Of The University Of CaliforniaIon-implanted protein-coated intralumenal implants
US6010445 *Nov 12, 1997Jan 4, 2000Implant Sciences CorporationRadioactive medical device and process
US6015541 *Nov 3, 1997Jan 18, 2000Micro Therapeutics, Inc.Radioactive embolizing compositions
US6042875 *Mar 2, 1999Mar 28, 2000Schneider (Usa) Inc.Drug-releasing coatings for medical devices
US6169170 *Sep 3, 1997Jan 2, 2001Lynx Therapeutics, Inc.Oligonucleotide N3′→N5′Phosphoramidate Duplexes
US6171609 *Oct 23, 1995Jan 9, 2001Neorx CorporationTherapeutic inhibitor of vascular smooth muscle cells
US6174330 *Aug 1, 1997Jan 16, 2001Schneider (Usa) IncBioabsorbable marker having radiopaque constituents
US6177523 *Jul 14, 1999Jan 23, 2001Cardiotech International, Inc.Functionalized polyurethanes
US6183505 *Mar 11, 1999Feb 6, 2001Medtronic Ave, Inc.Method of stent retention to a delivery catheter balloon-braided retainers
US6187045 *Feb 10, 1999Feb 13, 2001Thomas K. FehringEnhanced biocompatible implants and alloys
US6511748 *Jan 6, 1999Jan 28, 2003Aderans Research Institute, Inc.Bioabsorbable fibers and reinforced composites produced therefrom
US6517888 *Nov 28, 2000Feb 11, 2003Scimed Life Systems, Inc.Method for manufacturing a medical device having a coated portion by laser ablation
US6527801 *Apr 13, 2000Mar 4, 2003Advanced Cardiovascular Systems, Inc.Biodegradable drug delivery material for stent
US6537589 *Jul 25, 2000Mar 25, 2003Kyung Won Medical Co., Ltd.Calcium phosphate artificial bone as osteoconductive and biodegradable bone substitute material
US6676697 *Mar 17, 1998Jan 13, 2004Medinol Ltd.Stent with variable features to optimize support and method of making such stent
US6679980 *Jun 13, 2001Jan 20, 2004Advanced Cardiovascular Systems, Inc.Apparatus for electropolishing a stent
US6689375 *Oct 14, 2002Feb 10, 2004Coripharm Medizinprodukte Gmbh & Co. KgResorbable bone implant material and method for producing the same
US6695920 *Jun 27, 2001Feb 24, 2004Advanced Cardiovascular Systems, Inc.Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US6706273 *Aug 14, 2000Mar 16, 2004Ivoclar Vivadent AgComposition for implantation into the human and animal body
US6709379 *Nov 2, 1999Mar 23, 2004Alcove Surfaces GmbhImplant with cavities containing therapeutic agents
US6846323 *May 15, 2003Jan 25, 2005Advanced Cardiovascular Systems, Inc.Intravascular stent
US7335314 *Aug 4, 2004Feb 26, 2008Advanced Cardiovascular Systems Inc.Method of making an implantable medical device
US20020002399 *May 8, 2001Jan 3, 2002Huxel Shawn ThayerRemovable stent for body lumens
US20020004060 *Jul 17, 1998Jan 10, 2002Bernd HeubleinMetallic implant which is degradable in vivo
US20020004101 *Aug 30, 2001Jan 10, 2002Schneider (Usa) Inc.Drug coating with topcoat
US20030033001 *Apr 27, 2001Feb 13, 2003Keiji IgakiStent holding member and stent feeding system
US20030039689 *Apr 26, 2002Feb 27, 2003Jianbing ChenPolymer-based, sustained release drug delivery system
US20040030380 *Mar 5, 2003Feb 12, 2004Sun Biomedical, Ltd.Drug-delivery endovascular stent and method for treating restenosis
US20040039441 *May 20, 2003Feb 26, 2004Rowland Stephen MaxwellDrug eluting implantable medical device
US20050033412 *Aug 4, 2004Feb 10, 2005Wu Steven Z.Method of making an implantable medical device
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US8137396 *May 19, 2010Mar 20, 2012480 Biomedical, IncMedical implant
US8398706Mar 19, 2013Advanced Cardiovascular Systems, Inc.Drug delivery after biodegradation of the stent scaffolding
US8469968Jul 18, 2011Jun 25, 2013Abbott Cardiovascular Systems Inc.Methods of treatment with drug delivery after biodegradation of the stent scaffolding
US8540765Feb 9, 2012Sep 24, 2013480 Biomedical, Inc.Medical implant
US8661630May 21, 2008Mar 4, 2014Abbott Cardiovascular Systems Inc.Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer
US8840678 *Feb 10, 2012Sep 23, 2014Abbott Cardiovascular Systems Inc.Drug-eluting bioabsorbable renal artery stent for renal cancer and inflammatory disorders
US8888840 *Apr 16, 2013Nov 18, 2014Boston Scientific Scimed, Inc.Drug eluting medical implant
US8992601Feb 13, 2013Mar 31, 2015480 Biomedical, Inc.Medical implants
US9090745Nov 15, 2013Jul 28, 2015Abbott Cardiovascular Systems Inc.Biodegradable triblock copolymers for implantable devices
US9155638 *May 10, 2013Oct 13, 2015480 Biomedical, Inc.Drug eluting medical implant
US9278016Feb 22, 2011Mar 8, 2016480 Biomedical, Inc.Medical implant
US9309347Oct 5, 2011Apr 12, 2016Biomedical, Inc.Bioresorbable thermoset polyester/urethane elastomers
US20090110713 *Oct 31, 2007Apr 30, 2009Florencia LimBiodegradable polymeric materials providing controlled release of hydrophobic drugs from implantable devices
US20090291111 *May 21, 2008Nov 26, 2009Florencia LimCoating comprising an amorphous primer layer and a semi-crystalline reservoir layer
US20100070013 *Mar 18, 2010Medtronic Vascular, Inc.Medical Device With Microsphere Drug Delivery System
US20100298952 *May 19, 2010Nov 25, 2010Arsenal MedicalMedical implant
US20110190875 *Aug 4, 2011Advanced Cardiovascular Systems, Inc.Drug Delivery After Biodegradation Of The Stent Scaffolding
US20110238162 *Sep 29, 2011Arsenal MedicalMedical implant
US20130138219 *Nov 21, 2012May 30, 2013Cook Medical Technologies LlcBiodegradable stents having one or more coverings
US20140242144 *Apr 30, 2014Aug 28, 2014Abbott Cardiovascular Systems Inc.Drug eluting scaffold for kidney-related disease
WO2015160501A1Mar 31, 2015Oct 22, 2015Auburn UniversityParticulate vaccine formulations for inducing innate and adaptive immunity
Classifications
U.S. Classification623/1.38, 623/1.42
International ClassificationA61F2/82
Cooperative ClassificationA61L2300/416, A61L31/148, A61L2300/41, A61L31/10, A61L31/16
European ClassificationA61L31/10, A61L31/16, A61L31/14K
Legal Events
DateCodeEventDescription
Jan 16, 2007ASAssignment
Owner name: ADVANCED CARDIOVASCULAR SYSTEMS, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GALE, DAVID C.;HUANG, BIN;REEL/FRAME:018805/0969
Effective date: 20070108