Patent Application
20100256772
The present invention relates to implantable medical devices. More particularly, the invention relates to stents, including plastic tubular stents adapted for use in the biliary tract.
Stents are frequently used to enlarge, dilate, or maintain the patency of narrowed body lumens. Non-expandable tubular stents are typically made from plastics and contain a lumen extending throughout.
Implantation of biliary stent structures provides treatment for various conditions, such as obstructive jaundice. Biliary stenting treatment approaches can be used to provide short-term treatment of conditions such as biliary fistulae or giant common duct stones. Biliary stents may be implanted to treat chronic conditions such as postoperative biliary stricture, primary sclerosing cholangitis, and chronic pancreatitis.
A biliary stent can be made in the form of a polymer tube that can be advanced on a delivery catheter through an endoscope and into the bile duct where it is deployed. The tubular stent is selected to be sufficiently strong to resist collapse to maintain an open lumen through which digestive liquids can flow into the digestive tract. Among the desirable features of such a stent is that it be longitudinally flexible to be advanced along a path that may include sharp bends. It is also desirable that the stent maintain its intended position within the bile duct without migrating from that position.
As bodily fluid travels through the lumen of the stent, cumulative matter within the bodily fluid adheres to the inner surface of the stent. Cumulative matter is material traversing the stent that if undisturbed, would otherwise accumulate on the passageway surfaces to reduce the diameter of the flow path there through, reduce the stent's patency, and could eventually clog the stent. Cumulative matter includes, but is not limited to biofilm, bacterial growth, and sludge deposition. A biliary stent can become occluded within a bile duct, as cumulative material, such as an encrustation of amorphous biological material and bacteria, and/or sludge, accumulates on the surface of the stent gradually obstructing the lumen of the stent. Biliary sludge is an amorphous substance often containing crystals of calcium bilirubinate and calcium palimitate, along with significant quantities of various proteins and bacteria. Sludge can deposit rapidly upon implantation in the presence of bacteria. For example, bacteria can adhere to plastic stent surfaces through pili or through production of a mucopolysaccharide coating. Bacterial adhesion to the surface of a stent lumen surface can lead to occlusion of the stent lumen as the bacteria multiply within a glycocalyx matrix of the sludge to form a biofilm over the sludge within the lumen of an implanted drainage stent. The biofilm can provide a physical barrier protecting encased bacteria from antibiotics. With time, an implanted biliary stent lumen can become blocked, thereby restricting or blocking bile flow through the biliary stent. As a result, a patient can develop symptoms of recurrent biliary obstruction due to restricted or blocked bile flow through an implanted biliary stent, which can be complicated by cholangitis and sepsis.
Often such conditions are treated by antibiotics and/or endoscopic replacement of an obstructed biliary stent. Typically, biliary stents need replacing every three months. Replacement procedures cause medical risk and financial strain to the patient.
There exists a need in the art for an implantable medical device that prevents or reduces the biofilm and sludge deposition process inside the lumen of implantable drainage stents, such as biliary stents, at little cost and with minimal patient and medical personnel intervention. There is a need for a stent that resists clogging by using a non-invasive, mechanical means that does not require the use of electricity or expensive equipment.
In a first aspect, a system for maintaining the patency of a plastic tubular stent is provided. The system includes a plastic tubular stent having a lumen and one or more magnetically reactive objects; wherein the one or more magnetically reactive objects are movably disposed within the lumen; and an actuation device, separate from the plastic tubular stent, wherein the actuation device repels or attracts the one or more magnetically reactive objects disposed within the lumen of the plastic tubular stent.
In a second aspect, a system for maintaining the patency of a plastic tubular stent is provided. The system includes a plastic tubular stent having a first portion, a second portion, a lumen extending throughout the first portion and second portion, and a magnetically reactive object moveably disposed within the lumen; wherein the lumen is configured to retain the magnetically reactive object within the plastic tubular stent; and wherein the magnetically reactive object of the plastic tubular stent is configured to at least partially dislodge cumulative matter, deposited within the plastic tubular stent, when an actuation device is passed near the plastic tubular stent.
In a third aspect, a method for preventing the occlusion of a plastic tubular stent is provided. The method includes providing a plastic tubular stent having a lumen containing one or more magnetically reactive objects movably disposed therein; providing an actuation device, separate from the plastic tubular stent, for actuating the one or more magnetically reactive objects of the plastic tubular stent; and implanting the plastic tubular stent into a bodily lumen of a patient.
The embodiments will be further described in connection with the attached drawing figures. It is intended that the drawings included as a part of this specification be illustrative of the embodiments and should in no way be considered as a limitation on the scope of the invention.
The exemplary embodiments disclosed herein provide a system and method for maintaining the patency of a stent, such as a plastic tubular biliary stent, using a magnet and a magnetically reactive object to at least partially inhibit long-term adherence of cumulative matter to the interior of the stent so that the amount of time the stent can reside within a patient before needing to be replaced is extended. The present invention is not limited to any particular type of stent; it is contemplated that stents dwelling in locations other than the biliary can also benefit from the inventive concepts disclosed herein. Furthermore, the present invention is not limited for use within any particular part of the body or for use with humans.
A more detailed description of the embodiments will now be given with reference to
Contained within stent 10a is one or more magnetically reactive objects 13 that are free to move about lumen 14 and will likely inherently move about lumen 14 as the patient moves, although such inherent movement is not required. First portion 11 and second portion 12 of stent 10a are tapered to act as a magnetically reactive object securing mechanisms to maintain the one or more magnetically reactive objects 13 therein. Magnetically reactive object 13 should be sufficiently sized and shaped such that it does not completely obstruct fluid flow and such that it is able to move about lumen 14 without causing stent 10a to become dislodged from its dwelling place. The shape of magnetically reactive object 13 is not limited to having a spherical-shape; other shapes are contemplated including, but not limited to, a cube, pyramid, and box. Additionally, magnetically reactive object 13 may have additional materials or coatings attached thereto to aid in the removal of cumulative matter. Magnetically reactive object 13 may further comprise lumen 41 that permits fluid to pass there through.
Using actuation device 10b which is separate from stent 10a and located outside of patient, one actuates magnetically reactive object 13 within stent 10a by manually manipulating magnetically reactive object 13 using external forces that repel or attract magnetically reactive object 13. It is contemplated that magnetically reactive object and/or any portion of actuation device may be made from a magnetic material (such as a rare earth magnet) or a metallic material that is attracted to or repelled by a magnetic material. Additionally, it is contemplated that if both made from a magnetic material, actuation device and magnetically reactive object may have a polarity that is the same or different such that they will relatively attract or repel each other.
Actuation device 10b depicted in
As depicted in
As is readily apparent, patient 18 may be able to perform the method for removing cumulative matter attached to the stent by using actuation device 10b, such as a glove, without the costly assistance of a medical professional or expensive equipment. Because no electronics or invasive equipment are used, the risk to patient health is minimized. Additionally, because actuation caused by manual manipulation of magnetically reactive object is used, rather than gravity, patients who live a sedentary lifestyle, are bed-bound, or who are otherwise less mobile, are able to benefit from that which is disclosed herein. It is contemplated that patient 18 (or anyone else) can perform the cleaning procedure one, two, or more times daily to help maintain the patency of the stent for a period longer than what a typical stent (such as a plastic biliary stent) would experience.
Although glove 10b is depicted with a plurality of magnets 17 on the fingers and palm, glove 10b is not limited to having a plurality of magnets. Rather, it is contemplated that glove 10b may only have one magnet.
Additionally, although actuation device is depicted as a glove, the actuation device is not limited to a glove. Rather, it further contemplates any hand-held actuation device such that magnetically reactive objects are attracted to or repelled from actuation device, including but not limited to, a cloth member, mitt, mitten, wand, strap, housing, or any other device that may be temporarily attached and/or disposed at least partially about a hand, including a magnet alone. Additionally, it is contemplated that actuation device may have one or more magnets or metallic material that may be of differing sizes, dimensions, strengths, and polarities. Likewise, different actuation devices may have one or more magnets or metallic material having different sizes, dimensions, strengths, and polarities, such that if one actuation device does not achieve the desired results, a different actuation device may be used.
Walls 15 may be formed from any suitable biocompatible and biostable material. Walls 15 are preferably resiliently compliant enough to readily conform to the curvature of the duct in which it is to be placed, while having sufficient “hoop” strength to retain its form within the duct. Walls 15 are preferably made from a medium density biocompatible polyethylene, although other materials are contemplated, including but not limited to polyurethane, polytetrafluoroethylene (PTFE), stainless steel, and Nitinol. In one aspect, walls 15 are formed from a polyolefin such as a metallocene catalyzed polyethylene, polypropylene, polybutylene or copolymers thereof. Other suitable materials for walls 15 include polyurethane (such as a material commercially available from Dow Corning under the tradename PELLETHANE); a silicone rubber (such as a material commercially available from Dow Corning under the tradename SILASTIC); a polyetheretherketone (such as a material commercially available from Victrex under the tradename PEEK); vinyl aromatic polymers such as polystyrene; vinyl aromatic copolymers such as styrene-isobutylene copolymers and butadiene-styrene copolymers; ethylenic copolymers such as ethylene vinyl acetate (EVA), ethylene-methacrylic acid and ethylene-acrylic acid copolymers where some of the acid groups have been neutralized with either zinc or sodium ions (commonly known as ionomers); polyacetals; chloropolymers such as polyvinylchloride (PVC); polyesters such as polyethyleneterephthalate (PET); polyester-ethers; polyamides such as nylon 6 and nylon 6, 6; polyamide ethers; polyethers; elastomers such as elastomeric polyurethanes and polyurethane copolymers; silicones; polycarbonates; and mixtures and block or random copolymers of any of the foregoing.
The surface of walls 15 may be coated with a polymer. Walls 15 are illustrated as having a polymer coating on both its outer surface 19 and its inner surface 101. Magnetically reactive object 13 can also have a polymer coating on its outer surface 102. The polymer coating on outer surface 19, 102 and inner surface 101 can be a biocompatible polymer, including but not limited to PTFE. Polymer coating can also comprise a hydrophilic polymer selected from the group comprising polyacrylate, copolymers comprising acrylic acid, polymethacrylate, polyacrylamide, poly(vinyl alcohol), poly(ethylene oxide), poly(ethylene imine), carboxymethylcellulose, methylcellulose, poly(acrylamide sulphonic acid), polyacrylonitrile, poly(vinyl pyrrolidone), agar, dextran, dextrin, carrageenan, xanthan, and guar. The hydrophilic polymers can also include ionizable groups such as acid groups, e.g., carboxylic, sulphonic or nitric groups. The hydrophilic polymers may be cross-linked through a suitable cross-binding compound. The cross-binder actually-used depends on the polymer system: if the polymer system is polymerized as a free radical polymerization, a preferred cross-binder comprises two or three unsaturated double bonds.
The polymer coating on inner surface 101 and outer surface 19, 102 can also be loaded with a variety of bioactive agents. The bioactive agent preferably includes one or more antimicrobial agents. The term “antimicrobial agent” refers to a bioactive agent effective in the inhibition of, prevention of or protection against microorganisms such as bacteria, microbes, fungi, viruses, spores, yeasts, molds and others generally associated with infections such as those contracted from the use of the medical articles described herein. The antimicrobial agents include antibiotic agents and antifungal agents.
Antibiotic agents may include cephalosporins, clindamycin, chloramphenicol, carbapenems, penicillins, monobactams, quinolones, tetracycline, macrolides, sulfa antibiotics, trimethoprim, fusidic acid and aminoglycosides. Antifungal agents may include amphotericin B, azoles, flucytosine, cilofungin and nikkomycin Z. Specific non-limiting examples of suitable antibiotic agents include: ciprofloxacin, doxycycline, amoxicillin, metronidazole, norfloxacin (optionally in combination with ursodeoxycholic acid), ciftazidime, and cefoxitin. Other suitable antibiotic agents include rifampin, minocycline, novobiocin and combinations thereof discussed in U.S. Pat. No. 5,217,493 (Raad et al.), which is incorporated herein by reference in its entirety. Rifampin is a semisynthetic derivative of rifamycin B, a macrocyclic antibiotic compound produced by the mold Streptomyces mediterranic. Rifampin is believed to inhibit bacterial DNA-dependent RNA polymerase activity and is bactericidal in nature. Rifampin is available in the United States from Merrill Dow Pharmaceuticals, Cincinnati, Ohio. Minocycline is a semisynthetic antibiotic derived from tetracycline. It is primarily bacteriostatic and is believed to exert an antimicrobial effect by inhibiting protein synthesis. Minocycline is commercially available as the hydrochloride salt which occurs as a yellow, crystalline powder and is soluble in water and slightly soluble in alcohol. Minocycline is available from Lederle Laboratories Division, American Cyanamid Company, Pearl River, N.Y. Novobiocin is an antibiotic obtained from cultures of Streptomyces niveus or S. spheroides. Novobiocin is usually bacteriostatic in action and is believed to interfere with bacterial cell wall synthesis and inhibit bacterial protein and nucleic acid synthesis. Novobiocin also appears to affect stability of the cell membrane by complexing with magnesium. Novobiocin is available from The Upjohn Company, Kalamazoo, Mich.
The polymer coating is preferably capable of releasing the bioactive agent into the body at a predetermined time and at a predetermined rate. Such polymeric coatings include drug-eluting matrix materials described in U.S. Pat. Nos. 5,380,299, 6,530,951, 6,774,278 and U.S. patent application Ser. Nos. 10/218,305, 10/223,415, 10/410,587, 10/000,659, and 10/618,977 all of which are incorporated in their entirety herein by reference.
Alternatively, different polymer coatings can be coated on outer surface 19, 102 and inner surface 101. For example, the polymer coating on outer surface 19 can include any polymer coating commonly known to those skilled in the art to help reduce tissue irritation incurred as a result of stent 10a being in contact with a passageway of the patient for a prolonged period of time. The polymer coating on inner surface 101 and outer surface 102 can also include any coating commonly known to those skilled in the art to further help prevent clogging of stent 10a.
Alternatively, inner surface 101 and outer surface 19, 102 of stent 10a can be composed from a biodegradable polymer that gradually bioerodes with time. Biodegradable polymers may include rigid dissolvable polymers such as poly(lactid acid), poly(glycolic acid), and poly-epsilon-capro-lactone, or combinations thereof. Other rigid dissolvable polymers will be apparent to those of ordinary skill in the art. Suitable biodegradable polymers may be selected from the group consisting of: a hydrogel, an elastin-like peptide, a polyhydroxyalkanoates (PHA), polyhydroxybutyrate compounds, and co-polymers and mixtures thereof. The biodegradable material can be selected and varied based on various design criteria. The biodegradable material preferably comprises one or more hydrolyzable chemical bonds, such as an ester, a desired degree of crosslinking, a degradation mechanism with minimal heterogeneous degradation, and nontoxic monomers. The biodegradable material is preferably a polyhydroxyalkanoate compound, a hydrogel, poly(glycerol-sebacate) or an elastin-like peptide. Desirably, the biodegradable material comprises a poly-a-hydroxy acid, such as polylactic acid (PLA). PLA can be a mixture of enantiomers typically referred to as poly-D, L-lactic acid. Alternatively, the biodegradable material is poly-L(+)-lactic acid (PLLA) or poly-D(-)-lactic acid (PDLA), which differ from each other in their rate of biodegradation. PLLA is semicrystalline. In contrast, PDLA is amorphous, which can promote the homogeneous dispersion of an active species. Unless otherwise specified, recitation of “PLA” herein refers to a biodegradable polymer selected from the group consisting of: PLA, PLLA and PDLA.
Stent 10a may also comprise a drug-releasing which may be formed by any suitable process conventionally used to shape polymeric materials such as thermoplastic and elastomeric materials. Shaping processes can include, but not limited to, extrusion including coextrusion, molding, calendaring, casting and solvent coating. Preferred shaping processes include extrusion and coextrusion processes. For example, a biodegradable coating polymer mixed with a drug may be applied to inner surface 101 of stent 10a by applying a solvent solution or liquid dispersion of a biodegradable polymer onto a surface of walls 15 followed by removing the solvent or liquid dispersing agent, e.g., by evaporation. Such a solution or dispersion of the biodegradable polymer may be applied by contacting a surface of the support member with the solution or dispersion by, for example, dipping or spraying. For example, the biodegradable coating may be applied by spraying a solution of a biodegradable polymer onto walls 15 within lumen 14 of stent 10a. Alternatively, a coated stent 10a can be formed by applying a polymer to the exterior surface of a biodegradable coating to form a multilayer medical device. For example, a solution of a biostable polymer can be applied to the external surface of a tube of the biodegradable coating and dried in place to form stent 10a.
Alternatively, each of the multiple layers may be solvent cast. The second layer is cast from a solvent that does not dissolve the already-cast layer. For example, a polyurethane used to form stent 10a may be dissolved in dimethylformamide, while PLA used to form a biodegradable coating may be dissolved in dichloromethane. Where the second solvent does not dissolve the support member polymer, the second solution may be spread on the first layer once dry, and the solvent evaporated off. The resulting multi-layers have a strong bond between the layers.
Biodeposition-reducing bioactive agents can be selected to withstand the extrusion temperature. In a first aspect, a bioactive agent may be included within, or mixed with, the polymer prior to extrusion. Extrusion of the film allows inclusion of a drug or agent that can withstand the extrusion temperatures. For example, the antimicrobial agents described in U.S. patent application US2005/0008763A1 are compatible with this manufacturing technique, which is incorporated herein by reference in its entirety. The bioactive agent preferably does not materially interfere with the physical or chemical properties of the biodegradable material in which it is included. The bioactive agent and the biodegradable material may be preformed using any of the conventional devices known in the art for such purposes. Where thermoplastic materials are employed, a polymer melt may be formed by heating the various agents, which can then be mixed to form a homogenous mixture. A common way of doing so is to apply mechanical shear to a mixture of the matrix polymer and additives. Devices in which the biodegradable material and the bioactive(s) may be mixed in this fashion include, but are not limited to, devices such as a single screw extruder, a twin screw extruder, a banbury mixer, a high-speed mixer, and a ross kettle.
In a second aspect, the biodegradable coating is adhered to stent 10a without a bioactive agent, and the bioactive agent may be subsequently absorbed into the biodegradable coating after the formation of the device. For example, the biodegradable coating can be contacted with a solution of the bioactive agent within the drainage lumen 16 of stent 10a. The effective concentration of the bioactive agent within the solution can range from about 1 to 10 μg/ml for minocycline, preferably about 2 μg/ml; 1 to 10 μg/ml for rifampin, preferably about 2 μg/ml; and 1 to 10 μg/ml for novobiocin, preferably about 2 μg/ml. The solution is preferably composed of sterile water or sterile normal saline solutions.
Magnetically reactive object may also include projections to provide additional contact with stent wall. For example, magnetically reactive object 50 depicted in
Using imaging device, medical personnel are able to observe the actuation of magnetically reactive object 13 relative to stent 80 to determine if actuation of magnetically reactive object 13 is sufficient to restore the patency of the stent. For example, if magnetically reactive object 13 is unable to move about within stent 80, it may mean that stent 80 is sufficient clogged so as to prevent the movement of magnetically reactive object 13. Accordingly, the medical professional may continue actuating magnetically reactive object 13 until a sufficient flow-path is created. Alternatively, the medical professional can use a different actuation device having different properties, including but not limited to, a stronger or weaker magnet, to create a stronger or weaker reaction between the actuation device and magnetically reactive object 13. Once actuation device is able to move magnetically reactive object 13 sufficiently about stent 80, it can be believed that stent 80 is sufficiently free from cumulative matter so as to not significantly occlude stent 80. Additionally, by using actuation devices having different properties, including but not limited to, a stronger magnet or weaker magnet, the medical professional is able to actuate magnetically reactive object 13 amongst different planes and accordingly have magnetically reactive object 13 contact the near and far walls 15 of stent 80.
The foregoing description and drawings are provided for illustrative purposes only and are not intended to limit the scope of the invention described herein or with regard to the details of its construction and manner of operation. It will be evident to one skilled in the art that modifications and variations may be made without departing from the spirit and scope of the invention. Changes in form and in the proportion of parts, as well as the substitution of equivalence, are contemplated as circumstances may suggest and render expedience; although specific terms have been employed, they are intended in a generic and descriptive sense only and not for the purpose of limiting the scope of the invention set forth in the following claims.
The present patent document claims the benefit of the filing date under 35 U.S.C. §119(e) of Provisional U.S. patent application Ser. No. 61/166,109, filed Apr. 2, 2009, which is hereby incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61166109 | Apr 2009 | US |
