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USOO7694683B2

(12) United States Patent (10) Patent No.: US 7,694,683 B2 Callister et al. (45) Date of Patent: Apr. 13, 2010

(54) METHODS AND DEVICES FOR OCCLUDING (56) References Cited BODY LUMENS AND/OR FOR DELIVERING U.S. PATENT DOCUMENTS THERAPEUTICAGENTS 3,334,629 A 8, 1967 Cohn ...... 606, 194 (75) Inventors: Jeffrey P. Callister, Redwood City, CA 3,687,129 A * 8/1972 Nuwayser ...... 606, 191 (US); William S. Tremulis, Redwood 3,865,108 A * 2/1975 Hartop ...... 424/430 City, CA (US) 3,991,760 A * 1 1/1976 Drobish et al...... 128,832 4,279.252 A 7/1981 Martin (73) Assignee: Conceptus, Inc., Mountain View, CA 4,579, 110 A * 4, 1986 Hamou ...... 128,831 (US) 5,024,671 A 6, 1991 Tu et al...... 623, 142 ( c ) Notice: Subject tO any disclaimer, the term of this 5,152.777 A * 10, 1992 Goldberg et al...... 606,200 atent is extended or adjusted under 35 5,256,146 A * 10/1993 Ensminger et al...... 606/198 p S.C. 154(b) by Oda 5,433,218 A * 7/1995 Wildemeersch ...... 128,833 .S.C. 154(b) by 0 days. 5,601,600 A 2, 1997 Ton ...... 606, 198 5,634.942 A * 6/1997 Chevillon et al...... 606/200 (21) Appl. No.: 10/880,355 5,704.910 A 1/1998 Humes ...... 604/5O2 5,792,154 A * 8/1998 Doan et al...... 606,151 (22) Filed: Jun. 28, 2004 5,935,137 A 8/1999 Saadat et al. O O 5,979,446 A * 1 1/1999 Loy ...... 128,830 (65) Prior Publication Data 5,980,554 A * 1 1/1999 Lenker et al...... 606, 198 US 2005/OO45183 A1 Mar. 3, 2005 6,099,562 A * 8/2000 Ding et al...... 623, 146 6,432,116 Bl 8, 2002 Callister et al. Related U.S. Application Data 6,517,559 B1 2/2003 O’Connell 6,526,979 B1* 3/2003 Nikolchev et al...... 128,831 (63) Continuation-in-part of application No. 08/770,123, filed on Dec. 18, 1996, now Pat. No. 7,073,504. (60) Provisional application No. 60/483,587, filed on Jun. * cited by examiner 27, 2003. Primary Examiner Julian WWoo (74) Attorney, Agent, or Firm Blakely, Sokoloff, Taylor & (51) Int. Cl. Zafman llp A6 IF 6/06 (2006.01) A6B I7/08 (2006.01) (57) ABSTRACT (52) U.S. Cl...... 128/831: 128/832: 606/157 (58) Field of Classification Search ...... 606/157, Devices, systems and methods for occluding the lumens of 606/158, 213, 191, 193, 194, 198, 200; 424/422, anatomical passageways and/or for delivering drugs or other 424/423, 430, 433; 623/1.46, 1.39, 1.4, 1.42: Substances to the bodies of human or animal Subjects. 128/832, 830, 831, 833, 842,843; 604/502 See application file for complete search history. 26 Claims, 13 Drawing Sheets

U.S. Patent Apr. 13, 2010 Sheet 1 of 13 US 7.694,683 B2 -10 CS

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U.S. Patent Apr. 13, 2010 Sheet 13 of 13 US 7.694,683 B2

US 7,694,683 B2 1. 2 METHODS AND DEVICES FOR OCCLUDING SUMMARY OF THE INVENTION BODY LUMENS AND/OR FOR DELVERING THERAPEUTICAGENTS The present invention provides devices that may be implanted into a body lumens (e.g., fallopian tube, Vas defer RELATED APPLICATIONS ens, bronchus, blood vessel or other anatomical passageway or lumen) of a human or veterinary Subject to occlude that This patent application claims priority to U.S. Provisional body lumen and/or to deliver a Substance (e.g., a drug, a Patent Application No. 60/483,587 filed on Jun. 27, 2003, the protein, cells, a biological material, a chemical Substance, a entirety of which is expressly incorporated herein by refer gene therapy preparations, etc.) for at least a period of time ence. Additionally, this application is a continuation-in-part 10 following implantation of the device. of co-pending U.S. patent application Ser. No. 08/770,123 In accordance with the invention there is provided an (Callister et al.) filed on Dec. 18, 1996 and published on Jan. implantable occlusion and/or substance delivery device of the 31, 2002 as U.S. patent application 2002/0013589A1, the foregoing character that comprises; a) an expandable intralu entirety of which is expressly incorporated herein by refer minal member which is i) disposable in a first configuration CCC. 15 wherein it is sufficiently compact to be advanced into the body lumen and ii) Subsequently expandable to a second FIELD OF THE INVENTION configuration wherein the intraluminal member becomes This invention relates generally to medical devices, meth implanted within the body lumen; and... b) a quantity of a ods and systems and more particularly to medical devices and Substance disposed on or in the device Such that the Substance more particularly to devices that are implanted within body will be delivered from the intraluminal member into some lumens (e.g., fallopian tubes, vas deferens, bronchi, blood target tissue for at least Some period of time following vessels, etc.) to occlude that body lumen and/or to deliver implantation of the intraluminal member within the body therapeutic Substance(s) for local or systemic therapeutic lumen. In some embodiments, the intraluminal member may effect. include a mesh material or other matrix designed to facilitate 25 cellular or tissue ingrowth Such that cells or tissue that ingrow BACKGROUND OF THE INVENTION into the device will effect occlusion of the body lumen in which the device is implanted. The present invention addi There exist various situations in which it is desirable to tionally includes systems wherein the implantable occlusion implant embolic or occlusive devices within lumens or ana and/or substance delivery device is used in combination with tomical passageways within the bodies of human or animal 30 a delivery catheter and/or guidewire and/or endoscopic Subjects. In at least Some of those situations, it is additionally device. desirable to deliver a substance (e.g., a drug, a protein, cells, Further in accordance with the invention, there are pro a biological material, a chemical Substance, a gene therapy vided methods for sterilization or contraception wherein a preparations, etc.) for at least an initial period of time follow lumen occluding and/or substance delivering device of the ing implantation of the embolic or occlusive device. 35 foregoing character is implanted in a fallopian tube of a For example, it has been known to implant occlusive female subject or the vas deferens of a male subject. In such devices into the fallopian tubes of females or the vas deferens applications, the Substance disposed on or in the device may of males for contraceptive purposes. Examples of implant comprise a contraceptive or spermicidal agent that will be able occlusive devices useable for Such purposes are delivered by the device in a concentration and form that is described in U.S. Pat. No. 6,096,052 (Callister et al.) entitled 40 effective to cause a contraceptive effect in the subject, at least Occluding Device and Method of Use and U.S. Pat. No. during a period of required for the implanted device to effect 6.432,116 (Callister et al.) entitled Occluding Device and complete occlusion of the fallopian tube or vas deferens. Still Method of Use, the entireties of both such United States further in accordance with the invention, there are provided Patents being expressly incorporated herein by reference. methods for treating disorders or injuries of the lung by Some of these devices have been constructed and/or 45 implantation of a lumen occluding and/or substance deliver implanted in a manner to facilitate tissue ingrowth Subsequent ing device of the foregoing character within a bronchus, bron to implantation of the device Such that, after Such tissue chiole or other anatomical passageway within the lung. In ingrowth has occurred, the ingrown tissue alone or in combi Such applications, the device may occlude a bronchus to stop nation with the implanted device will provide complete the flow of inspired air to a portion of the lung (e.g., a lobe or occlusion of the lumen of the fallopian tube or vas deferens. 50 portion of a lobe) that is diseased or injured. In Such applica Thus, during the period between implantation of the device tions, the Substance disposed on or in the device may com and completion of the lumen-occluding tissue ingrowth, the prise an agent that causes a therapeutic effect in the lung Such lumen of the fallopian tube or vas deferens may remain at as an antimicrobial agent, mucolytic agent, bronchodilator, least partially open. Thus, it may be desirable to provide antiinflamatory, expectorant, antineoplastic agent, chemo alternative contraceptive means to prevent unwanted preg 55 therapeutic agent, immunomodulator, etc. nancy during the period between implantation of the device Still further in accordance with the invention, there are and completion of the lumen-occluding tissue ingrowth. provided varied and universal methods for treating disorders The above incorporated U.S. patent application Ser. No. or injuries of human or animal Subjects by implanting a 08/770,123 (Callister et al.) described various embodiments device of the foregoing character in a body lumen (e.g., a of lumen occluding devices that may be used to occlude the 60 man-made lumen or a natural passageway within the body lumen of a fallopian tube or vas deferens, some of which may such as a blood vessel, lymphatic duct, duct of the biliary tree, deliver a drug, such as a contraceptive agent. etc.) so as to cause occlusion of that body lumen and to release There remains a need in the art for the development of new a therapeutically or diagnostically effective amount of a Sub implantable lumen occluding devices that are capable of stance for at least some period of time following implantation delivering a Substance (e.g., a drug, a protein, cells, a biologi 65 of the device. cal material, a chemical Substance, a gene therapy prepara Further aspects, elements and embodiments of the inven tions, etc.). tion will become apparent to those of skill in the art upon US 7,694,683 B2 3 4 reading and consideration of the detailed description set forth FIG. 6C is an enlarged view of a portion of the device of herebelow and the accompanying drawings to which it refers. FIG. 6 illustrating yet another way in which the device may be constructed to deliver a Substance following its implantation BRIEF DESCRIPTION OF THE DRAWINGS within the body of a patient. FIG. 7 is a side view of alumen occluding/substance deliv FIG. 1A is a side view of one embodiment of a lumen ery device according to the present invention, disposed in a occluding and/or Substance delivery device according to the collapsed configuration and having a Substance delivery res present invention, disposed in a collapsed configuration. ervoir thereon. FIG.1B is a side view of the device of FIG. 1A, disposed in FIG. 7A is a side view of the device of FIG. 7 disposed in an expanded configuration. 10 an expanded configuration. FIG. 1C is a side view of the device of FIGS. 1A and 1B, FIG. 7B is an enlarged perspective view of the substance disposed in an expanded configuration and having an optional delivery reservoir of the device of FIGS. 7 and 7A. Substance delivery and/or ingrowth Supporting matrix FIG. 8 is a perspective view of another embodiment of a thereon. lumen occluding/substance delivery device according to the FIG. 2A is an exploded perspective view of one embodi 15 present invention having an optional visualization member ment of system of the present invention comprising a lumen thereon. FIG. 8A is an enlarged view of a portion of the device of occluding/substance delivery device as shown in FIGS. 1A FIG 8. and 1B, in combination with a delivery cannula and a pusher FIG.9 is a sectional showing of the uterus and left fallopian device. tube of a human patient having a hysteroscope and a delivery FIG. 2B is a perspective view of the system of FIG. 2A system according to the present invention inserted into the left wherein the pusher has been used to expel the lumen occlud fallopian tube. ing/substance delivery device out of the distal end of the FIG. 9A is an enlarged view of the distal end of the hyst delivery catheter. eroscope and adjacent portion of segment 9A of FIG. 9. FIG. 3A is a partial longitudinal sectional view of another 25 showing advancement of the delivery catheter out of a work embodiment of system of the present invention designed for ing channel of the hysteroscope. over-the-wire delivery of the implantable device. FIG. 10 is a schematic showing of the trachea and lungs of FIG. 3B is a showing of the system of FIG. 3A with the a human patient wherein a lumen occluding/substance deliv guidewire protruding from the distal end of the delivery cath ery device of the present invention implanted in a bronchus of eter. 30 the patient’s left lung. FIG. 4 is a sectional showing of the uterus and left fallopian FIG. 10A is an enlarged sectional view of a bronchus of the tube of a human patient having the over-the-wire system of left lung shown in FIG. 10 having a lumen occluding/sub FIGS. 3A and 3B inserted into the left fallopian tube. stance delivery device of the present invention implanted FIGS. 4A-4C show three steps in a procedure wherein the therein. system shown in FIG. 4 is used to implanta lumen occluding/ 35 FIG. 11 is a view of the lungs of a patient into which an substance delivery device in the patient’s left fallopian tube. occlusive delivery device of the invention has been inserted. FIG. 5 is an enlarged perspective view of a lumen occlud FIG. 11A is an expanded, partially cut-away view of the ing/substance delivery device of the present invention having portion of FIG. 11 indicated by the dashed circle. an optional Substance delivery and/or ingrowth supporting FIG. 11B is a cut-away view of a portion of a patient’s lung matrix thereon. 40 showing the delivery catheter and the occlusive device in FIG. 5A is an enlarged, cut away view of a portion of the place. Substance delivery and/or ingrowth Supporting matrix of the device of FIG. 5 illustrating one way in which the substance DETAILED DESCRIPTION delivery and/or ingrowth Supporting matrix may be con 45 In particular, the present invention relates to devices, meth structed to deliver a Substance following its implantation ods and systems for the occlusion of various passageways of within the body of a patient. the body including the delivery of therapeutic substances by FIG. 5B is an enlarged, cut away view of a portion of the placement of drugs or drug secreting material on or within Substance delivery and/or ingrowth Supporting matrix of the Such devices. In the various aspects of occluding body pas device of FIG. 5 illustrating another way in which the sub 50 sageways, one object of this invention that is particularly stance delivery and/or ingrowth Supporting matrix may be useful is for the occlusion of the fallopian tubes to effect constructed to deliver a Substance following its implantation permanent contraception. Although the occlusion of the fal within the body of a patient. lopian tubes will be discussed in detail, it can be appreciated FIG. 6 is an enlarged perspective view of a lumen occlud that the devices, methods and systems described herein can ing/substance delivery device of the present invention having 55 easily be adapted to occlude the vas in the male patient, an optional Substance delivery and/or ingrowth supporting arteries or veins in the nidus of an arterial-venous malforma matrix thereon and wherein portions of the device are con tion, patent ductus arteriosis in infants, as well as feeding structed to carry out controlled delivery of a substance fol arteries to cancerous tumors, among other passageways. The lowing its implantation within the body of a patient. invention also provides means for delivering vessel Support FIG. 6A is an enlarged view of a portion of the device of 60 ing devices Such as coronary stents or venous or arterial FIG. 6 illustrating one way in which the device may be con embolic filters, to the desired location through a steerable structed to deliver a Substance following its implantation system. Although any of these procedures may benefit from within the body of a patient. the inventions described herein, one particularly useful and FIG. 6B is an enlarged view of a portion of the device of immediate benefit for these devices, methods and systems is FIG. 6 illustrating another way in which the device may be 65 in the delivery of occlusion devices to the fallopian tubes for constructed to deliver a Substance following its implantation contraceptive purposes. At least Some of these objectives will within the body of a patient. be met by the novel inventions, devices, methods and systems US 7,694,683 B2 5 6 described hereinbelow. This invention in some embodiment body lumen is avoided. Also, by back-loading the device into also provides for delivery of therapeutic substances to desired the distal end of the delivery catheter, it need not be pushed locations and in advantageous manners through the entire length of the catheter. Thus the distal end Those skilled in the art will recognize that various combi portion of the delivery cannula 20 may be reinforced, perhaps nations, modifications, and equivalents of the inventions with slippery substance that makes movement of the device described herein can be used without departing from the Smooth and convenient, and may be reinforced, perhaps with Scope of these inventions. stainless steel wire or the like which would be undesirable for The present invention provides devices, methods and sys flexibility if the entire length of the catheter had to be so tems for the occlusion of various body passageways. It also reinforced. In those cases, the “pusher does not expel the includes catheter systems for the delivery of embolic devices 10 device forward and push it longitudinally thorough the body as well as vascular stents, especially Small diameterstents as lumen, but rather stabilizes it as the catheter is withdrawn may be desirable in the coronary or cerebral vasculature. from over it. Nonetheless, with that understanding, the term Typically these devices are delivered either by direct place “pusher wire' will be used in this patent to describe that ment or by using “over-the-wire' (OTW) designs or tech device. niques. Although OTW designs allow for steerability of the 15 In the particular embodiment of the device 10 shown in the guide wires and delivery catheters, the devices typically must drawings, a plurality of first leg segments 15 emanate from a have in inner diameter larger than the removable guide wire central apex 16. Each first leg segment 15 is joined at an angle with which it is used. The diameter of the guide wire, how with a second leg segment 12, thereby forming a plurality of ever, may be too large, even it its Smallest functional diameter, secondary apices 14, as shown. When the device 10 is to allow for a small enough collapsed profile to transverse expanded or allowed to expand within a body lumen, the through the target passageway. The alternative means of using second leg segments 12 will contact and exert a constant a pushing device proximal to the collapsed device allows for outward force on the wall of the body lumen in which the the device to have a very small collapsed profile since no device 10 is positioned thereby maintaining in a Substantially guide wire needs to pass through it, however Such systems stationary position within that body lumen. Sometimes at may have reduced steerability of the system through the body 25 least one of the second leg segments 12 may be formed of lumens, particularly distal to the collapsed device. For these thin, relatively rigid material and/or may comprise a projec reasons and others it would be desirable to have a small tion (e.g., a hook, barb, etc.) that will lodge in the lumen wall diameter system that still allows for steerability of the guide to secure the device 10 in place. wire while advancing through the body passageways. It will be appreciated that, although the device 10 may Referring now to the examples of the invention shown in 30 comprise a single unit as shown in the figures, the invention the drawings, in accordance with one aspect of this invention, includes systems or embodiments wherein a plurality of these there is provided an expandable lumen occluding and/or sub single unit devices 10 are aligned or positioned adjacent to stance delivery device 10 that is delivered through a suitable each other to form a multi-unit occluding system or structure delivery cannula 20 (e.g., a rigid or flexible tube or catheter within a body lumen. In Such embodiments, the aligned or such as a microcatheter or hypotube). As shown in FIGS. 2A 35 adjacently positioned single unit devices 10 may optionally and 2B, the device 10 may be placed in its collapsed configu be joined or connected to one another to form a unitary ration and inserted into the lumen of a delivery cannula 20. structure. In this regard, it will be appreciated that two or more The delivery cannula 20 comprises a wall 24 that devices a of the devices 10 (separate or conjoined) may be loaded into lumen that extends through the cannula 20. A hub 26 may be the lumen of the delivery cannula 20 an expelled from the formed on the proximal end of the delivery cannula 20. After 40 distal end 25 of the delivery cannula 20 by the pusher 22. the device 10 has been advanced into the lumen of the can Alternatively, a plurality of the devices 10 may be loaded into nula, the cannula wall 24 will constrain the device 10 in a and expelled from the delivery cannula 20, one at a time, relatively collapsed configuration while the device 10 thereby implanting a plurality of the devices 10 in series remains inside lumen. In this example, a pusher device 22 within a body lumen. comprising an elongate rod 28 and pusher head 30, is useable 45 In some embodiments, the configuration of the device may to facilitate expulsion or release of the device 10 from the be modified from that shown in the figures to a generally delivery cannula 20. Upon exiting the delivery cannula 20, the tubular shape that is expandable and collapsible, as with a device 10 resumes its expanded or remembered configuration stent. Devices of this general nature are described in U.S. Pat. by the release of a radially expansive force. Alternatively, the No. 6,096,052 (Callister et al.) and U.S. Pat. No. 6,432,116 device 10 may expand or assume a larger diameter as a result 50 (Callister et al.), the complete disclosures of which are incor of shape memory (e.g., becoming larger in diameteras a result porated herein as if set forth in full. of temperature change) or other shape altering properties or The device 10 may be configured, constructed or contain instrumentalities. materials that Support or facilitate tissue ingrowth. As used Although the pusher 28 with bulbous pusher head 30 may, herein, the term tissue ingrowth includes but is not limited to in some embodiments, comprise a “pusher wire', it will be 55 cell mulitiplication and/or or growth resulting in tissue for understood that the device 10 may be end-loaded into the mation into, onto, or Surrounding a particular region and/or cannula 20 in the compressed configuration with the pusher into, onto or Surrounding an obstructive device. This may be 28 in place immediately proximal to the device. When the epithelization, Scar formation, or other cell growth or multi delivery catheter 20 is placed in the desired location in the plication. For example, the leg portions 12, 15 and/or matrix body, for example in the fallopian tube, then the cannula 20 60 18 may incorporate materials that promote epithelialization, may then be withdrawn in the proximal direction while the endothelialization, granulation or other proliferative or tissue pusher 28 is held stationary in the longitudinal direction. This growth response within the body to create a more effective has the effect of laying down the expanding occlusive device occlusion of the passageway or to result in a more secure without actually pushing it forward in the potentially fragile attachment of the occlusion device to the walls of the body body lumen Such as a fallopian tube or tubule in the lung. In 65 lumen. For instance, polyester fibers may be attached to the this way any injury to the body structure that would otherwise device 10 such that tissue ingrowth into and around the device occur by pushing the expanded device forward through the will form a plug and thereby occlude the lumen in which the US 7,694,683 B2 7 8 device is implanted. In some embodiments, a Volitionally wall of the body lumen. Thereafter, the delivery cannula 20, deployable wall abrading projection (e.g., a flare or projec pusher 28a and guidewire 32 may be removed, leaving the tion) may be provided on the distal portion of the cannula 20 device 10 implanted within the body lumen. and/or on the device 10 to abrade or denude the epithelial FIGS. 4-4C show a specific procedure in which the OTW layer of the fallopian tube FT or other body lumen in which the device 10 is implanted, thereby enhancing the tissue system shown in FIGS. 3A-3C is used to implant a lumen ingrowth response. Such volitionally deployable wall abrad occluding and/or substance delivery device 10 within a fallo ing projection could both be deployed when entering the body pian tube. Initially, the guidewire 32 is advanced through the lumen and/or when deploying the device 10. uterus UT and into the fallopian tube FT. The delivery cath Additionally, as described in detail herebelow, substances 10 eter 20 (with the collapsed device 10 and pusher 28a posi Such as therapeutic agents, drugs, (e.g., contraceptive hor tioned therein) is advanced over the guidewire 32, as seen in mones, spermicidal agents, spermatogenesis inhibitors, anti FIG. 4A. Thereafter, as shown in FIG. 4B, the pusher 28a is microbials, antibiotics, antifungals, chemotherapeutic advanced over the guidewire 32 such that the enlarged distal agents, biologics, etc.) or biological factors (VEG?, FGF, etc.) end 30a of the pusher 28a pushes the device 10 out of the may be incorporated on or within the device in order to bring 15 distal end 25 of the delivery cannula 20. Upon exiting the about Some desired effect (e.g., to accelerate tissue ingrowth, distal end 25 of the delivery cannula 20, the device 10 self prevent/treat infection, cause drug-induced contraception for expands to its expanded configuration whereby the second leg at least a sufficient period of time to allow the implanted segments 12 of the device 10 are urged against the wall of the lumen occluding device to become fully functional, treat a fallopian tube FT, thereby holding the device 10 in a fixed disease or disorder in the adjacent tissue, etc). When the position, as shown in FIG. 4C. The delivery cannula 20, implantable device of this invention is used to block the pusher 28a and guidewire 32 are then withdrawn through the lumen of a fallopian tube, was deferens or other body lumen uterus UT and removed, leaving the device 10 implanted for the purpose of deterring pregnancy, the lumen blocking within the fallopian tube FT. Following implantation, tissue efficacy of the device (and thus its reliability as a contracep will ingrow into the device 10 to cause complete occlusion of tive measure) may not become maximized for several weeks 25 the fallopian tube FT. At least during the period of time during or months after the initial implantation of the device 10 as which Such tissue ingrowth is occurring, the device 10 may Such amount of time may be required for the implanted device elute a Substance (e.g., a contraceptive or spermicidal Sub 10 to become fully epithelialized or for other tissue ingrowth stance) in an amount that causes a desired therapeutic effect to become complete. In Such instances, a quantity of a con (e.g., contraception or spermicide) in the patient. Optionally, traceptive agent and/or spermicidal agent may be incorpo 30 the device 10 may include a matrix 18, as described above, to rated on or in the device so as to provide for drug-induced facilitate the desired tissue ingrowth and/or to deliver the contraception for a period of time that is at least sufficient to desired substance. allow the lumen blocking efficacy of the device to become If more than one device 10 is to be implanted within the maximized. Examples of specific Substances (e.g., drugs, subject’s body, there is no need to remove the delivery can therapeutic agents, biological factors, etc.) that may be incor 35 nula 20 to deliver the additional devices. For instance, if porated into or onto the device 10 of this invention or any devices 10 are to be implanted in both fallopian tubes FT, the other lumen occluding device are described herebelow. delivery catheter 20 may initially contain two devices 10, one FIGS. 3A-3B show a system for OTW delivery of the for each fallopian tube FT. In such an instance, the physician lumen occluding and/or substance delivery device 10. This may insert the delivery catheter 20 through the uterus of the system generally comprises the lumen occluding and/or Sub 40 patient, and deliver one device to the first of two fallopian stance delivery device 10, a delivery cannula 20 as described tubes FT, and, after delivery of the first device 10, the physi above and a modified pusher device 28a that has a guidewire cian may then insert the delivery catheter 20 into the other lumen extending longitudinally therethrough Such that a fallopian tube 20 and deploy the second device 10 into the guidewire 32 may pass through the lumen of the pusher other fallopian tube FT without having to withdraw the deliv device 28a, through the lumen occluding and/or Substance 45 ery cannula 20 from the uterus UT. This has the advantage of delivery device 10 and through the lumen of the delivery speeding the overall procedure time since there is no need to cannula 20, as shown in FIG. 3A. Alternatively, and not remove and replace a delivery cannula 20 for each fallopian shown in the figures, the pusher head 30a may have a groove tube FT. Additionally, overall costs for the procedure are therein through which the guidewire 32 may slide so that it reduced since only one delivery cannula 20 and one pusher will be located longitudinally side-by side with the pusher 50 28a are used to place two devices 10. Alternatively, the 29a. Optionally, the guidewire 32 may have a distal portion 34 present invention also allows for the lumen occluding and/or that is more flexible than the proximal portion of the substance delivery device 10 to be advanced through the guidewire and/or is otherwise deflectable, flexible or steer entire length of the delivery cannula 20. In such an instance, able. In operation, the guidewire 32 may be advanced into a the delivery cannula 20 is advanced to the location where the desired body lumen (e.g., a fallopian tube) into which it is 55 device 10 is to be placed. The guide wire 32 may aid in desired to implant the lumen occluding and/or Substance positioning the delivery cannula 20. Following acceptable delivery device 10. Thereafter, the delivery cannula 20 having placement of the delivery cannula 20, the guide wire 32 may the device 10 and pusher 28a within its lumen may be be removed from the delivery cannula 20 and the first occlu advanced over the previously inserted guidwire to a location sion device 10 may then be placed in a collapsed configura where the distal end of the delivery cannula 20 is adjacent to 60 tion and loaded into the lumen of the cannlua 20 through its the location where it is desired to implant the device 10. proximal end. After the device 10 has been located within Thereafter, the pusher 28a may be advanced over the lumen of the delivery cannula 20, a standard pusher 38 (see guidewire 32 such that the enlarged distal end 30a of the FIGS. 2A and 2B) may be used to advance the device 10 pusher 28a will expel the lumen occluding and/or Substance through the length of the delivery cannula 20 and out of its delivery device 10 out of the distal end of the delivery cannula 65 distal end 25. The device 10 will then expand and become 20. The device 10 will then self expand within the body lumen implanted within the lumen of the fallopian tube FT in the Such that the second leg segments 12 of the device engage the manner described hereabove. US 7,694,683 B2 10 In accordance with yet another aspect of this invention, it distal end of the hysteroscope 64. Thus, the physician may will be appreciated that the enlarged pusher head 30 or 30a advance the cannula 20 until he or she sees a specific colored could actually be mounted on the guidewire 32 at a location Zone or other length marking 72 which indicates that the proximal to the device 10 such that, as the guidewire 32 is cannula 20 has been advanced to the desired depth or location advanced in the distal direction (or as the cannula 20 is with within the fallopian tube FT. length marking(s) 72 may be drawn in the proximal direction) the pusher head 30 or 30a formed at locations on the delivery cannula 20 to indicate to will push the device 10 along with it. the physician through the hysteroscope 64 that the distal end One major advantage to the type of system shown in FIGS. of the delivery cannula 20 has reached a desired implantation 4A-4B is that the entire system may be steerable, since the site distal to the fallopian tube ostium OS, typically within the distal portion 34 of the guide wire 32 may be constructed to be 10 intramural portion IMP of the fallopian tube FT or within the torqued or steered through the body passageways to its utero-tubal UTJ. In some cases the device 10 may be desired location. A small hole may be formed in the central implanted elsewhere in the fallopian tube FT, such as in the apex 16 of the device 10 and the guidewire 32 may pass isthmic region of the fallopian tube FT, distal to the isthmic through that hole. Thus, such torquing the guide wire 32 may region, or even in or near the ampulla region of the fallopian have no significant effect on the device 10 since even in its 15 tube. In some embodiments, three separate markings 72 (e.g., collapsed state within the delivery cannula 20 there is still a 3 different colored Zones or visible markings such as ruler small hole through the device 10 through which the guide type hash marks) the physician to selectively advance the wire 32 passes. delivery cannula 20 to one of several identified implantation The distal portion 34 of the guide wire 32 may be flexible sites (e.g., in the isthmus, between or spanning the transition and may incorporate a conventional spring tip or, alterna between the isthmus and ampulla and in the ampulla. An tively, it may be made of or incorporate a plastic or Teflon alternative to visual means of determining the position or coating to prevent any Snagging of any attached fibers on the depth of insertion of the delivery cannula 20 is the use of occlusion device. Additionally, the device 10 may be posi ultrasound, electronic or image based guidance. In embodi tioned on a reduced diameter segment of the guidewire 32 and ments where ultrasound is used to determine the position of Such reduced diameter segment may belonger than the device 25 the delivery cannula 20, one or more echogenic marker(s) 10. This will permit a limited amount of axial movement of may be placed on the tip of or elsewhere on the delivery the guide wire 32, either proximally or distally, to further aid cannula 20 and/or on the implantable device 10 within the in the bendability and/or steerability of the system. Delivery delivery cannula 20 to facilitate ultrasonic imaging and cannula 20 may thus be able to provide either more or less proper placement of the device 10 under ultrasonic guidance. Support for the guide wire Support, depending on the circum 30 Optionally, a physical barrier may be located on the delivery stances and the tortuosity of the vasculature or passageway cannula 20 to prevent over-insertion. being navigated. In such embodiments wherein the guide Another means of placement for the device is under fluo wire 32 is axially moveable over a limited range but not roscopic guidance. In this case, one or more radiopaque completely removeable may allow the use of a steerable guide marker(s) may be located on the tip of or elsewhere on the wire 32 having a relatively large diameter distal portion in 35 delivery cannula 20 and/or on the implantable device 10 combination with a low profile delivery cannula 20 (e.g., a within the delivery cannula 20 to facilitate positioning of the delivery cannula 20 that has a diameter that is the same as or delivery cannula 20 and/or device 10 under fluoroscopy. even smaller than the diameter of the distal portion of the The lumen occluding and/or substance delivery device 10 guide wire 32). It will be appreciated by those of skill in the art may deliver (e.g., elute) Substance(s) (e.g., drugs, therapeutic that the device 10 may be self-expanding, or it may be pres 40 agents, biologics, proteins, spermicides, biological factors, Sure expanded (e.g., plastically deformable) through the use cell preparations, friendly microbes, etc.) for Some period of of a balloon catheter or the like. In some self-expanding time following implantation into the body. In this regard, the embodiments, the device 10 may assume its expanded con device 10 may be of the configuration and structure shown in figuration as a result oftemperature shape memory or release the figures and described hereabove, may be configured as a of compression, or any other appropriate means. As the 45 drug eluting Substance Such as fibers contained in a tubular device 10 assumes its expanded configuration as shown in structure, or may be of any other Suitable configuration or FIG. 4C, it may expand across the body lumen in which it is structure. The rate and/or amount of substance delivered from positioned and assume a configuration wherein any guidewire the implanted device may be designed or controlled, in accor passage hole or opening formed in the device 10 will be large dance with known drug delivery technology, to both control enough to allow the guidewire 32 to be retracted through the 50 dosage (e.g. concentration in the uterus, fallopian tube, lung, expanded device 10 and back into the lumen of the delivery tumor or other tissue, organ or anatomical structure), the cannula 20 for withdrawal, leaving the device 10 in place. location of delivery (e.g. systemic, local, topical, directed FIGS.9 and 9A show an example of a procedure wherein a downstream in a feeding artery, etc.) and the time period over hysteroscope 64 is used to view and/or facilitate implantation which the drug or other substance would be eluded or other of a lumen occluding and/or substance delivery device 10. 55 wise delivered by the implanted device. Also, in some The hysteroscope 64 comprises an elongate, flexible device aspects, the delivery of a substance from the device 10 may be having a lumen or working channel 70, a light emission lens responsive to a physical condition or presence/flow of a body orport 68 and an image receiving lens orport 66. Initially, the fluid in the patient, such as a substance that is eluted by the hysteroscope 64 is advanced through the uterus UT and into device 10 and/or carried from the device 10 to another loca the proximal fallopian tube FT, as shown. The delivery can 60 tion as a result of the presence of certain conditions, such as nula 20 is then advanced through the working channel 70 of different times in the menstrual cycle, or different blood the hysteroscope 64. The physician may view, through the chemistry conditions during the diurnal cycle, or different hysteroscope 64, the advancement of the delivery cannula 20 conditions as a result of physical or medical conditions such out of the distal end of the hysteroscope 64. Length indicating as the presence of certain biological factors, the blood pres colored Zone(s) and/or markings 72 may be provided at spe 65 sure presented, the blood flow encountered, or the like. cific locations on the delivery cannula 20 to indicate the The substance that is to be eluted or delivered from the length delivery cannula 20 that has been advanced from the implanted intraluminal device may be placed on or in the US 7,694,683 B2 11 12 device 10 in various ways, examples of which are shown in purpose of contraception, the reservoir member 47 may be FIGS. 5A-7B. For example, the device 10 or some portion removed and/or replaced at a later date via a hysteroscope 64 thereofmay be consist of or comprise a hollow member (e.g., and a suitable removal device Such as a gripping device or a tube or hollow fiber) having alumen or inner cavity wherein forceps that may be passable through a working channel 70 of the Substance is contained and the Substance may then elute the scope 64. Alternatively, the reservoir member 47 may be from that hollow member by diffusion through a wall or refillable, for example by a syringe. portion of the hollow member, by seepage or transport out of FIG. 6B shows an example wherein a portion 48 of a leg an aperture or opening formed in the hollow member, or by member 12 is hollow and contains the drug or Substance and any other suitable means. FIG. 5 shows an example of the wherein a semipermiable window 50 is formed of material device 10 wherein a substance delivering matrix 18 is dis 10 through which the drug or other substance will diffuse such posed on the device 10. This matrix 18 acts not only acts as a that therapeutically effective dose of the drug or substance matrix (e.g., scaffold, form or Support structure) for tissue will be delivered to the subject over a desired period of time. ingrowth but also is coated with, impregnated with or con FIG. 6C shows an example wherein a portion 44 of a leg tains a Substance, Such that the Substance will elute from or member 12 is hollow and contains the drug or Substance and otherwise be delivered from the matrix 18 following implan 15 wherein a plurality of small holes 46 are formed in that tation of the device 10. FIG. 5A shows an example wherein portion of the leg 12 such that the drug or other substance will the matrix 18 or a portion thereof is formed of a hollow seep or otherwise flow out of the holes and a therapeutically member 18a (e.g., a hollow fiber) that has a lumen38 wherein effective dose of the drug or substance will be delivered to the the substance is initially contained and a wall 36 through subject over a desired period of time. which the substance will diffuse or otherwise pass, thereby Additionally or alternatively, the Substance may comprise resulting in a release or elution of the Substance from the or may be contained in particles (e.g., granules, beads, hollow member 18a. FIG. 5B shows another example vesicles, blisters, bubbles, capsules, lyposomes, microcap wherein the matrix 18 or a portion thereof is formed of a Sules, etc.) that are disposed on (e.g., adhered or affixed to) hollow member 18B that has a wall 40 and a lumen of inner some portion of the device 10 such that the substance will be cavity that opens through an opening 42 formed in one end or 25 released is from the particles after the device 10 has been elsewhere in the wall 40 of the hollow member 18b such that implanted. substance contained in the lumen or inner cavity of the hollow FIGS. 7-7B show another example, wherein a substance member 18b will pass out of the opening 42, thereby resulting delivering implant 52. Such as a pellet or capsule, is separate in a release or elution of the substance from the hollow mem from or may be attached to and/or associated with the lumen ber 18a. Each hollow member 18a, 18b may be extruded or 30 occluding and/or substance delivery device 10. otherwise formed such that its inner diameter, wall thickness For example, in embodiments where the device 10 is and/or outlet opening size controls the rate at which the drug implanted in a fallopian tube FT for contraceptive purposes, a or other substance will be eluted from or delivered by the contraceptive drug delivering implant 52 may be implanted device 10. The amount of or depth to which the drug or other proximally to, within, or distally to the device 10. The matrix substance is loaded into each hollow member 18a, 18bcould 35 of the pellet, in some embodiments, may be biodegradable control the dispersal of the drug over time (i.e. more drug in (e.g., formed of polylactic acid, polyglycolic acid, etc.) Such the hollow fiber will provide for a longer period of time over that after a desired or predetermined period of time, the pellet which the drug will be delivered). It will be appreciated that, would dissolve and be gone. Methods for making Substance additionally or alternatively, the hollow members 18a, 18b delivering pellets or implants are previously known in the art shown in FIGS 5A and SB could be used to form all or 40 including those described in U.S. Pat. Nos. 3,625,214: 3,991, portions of the leg members 12 and/or 15 such that substance 750; 5,855,915 and 6,306,914, the entireties of which are will elute from or be delivered by the leg members 12 and/or expressly incorporated herein by reference. 15 in addition to or as an alternative to elution or delivery of It is to be appreciated that the drug or other Substance may substance from the matrix 18. be incorporated into any portion or element of the device 10 FIGS. 6-6C show other examples wherein all or portion(s) 45 in any suitable way. For example, the drug or Substance may of the leg member(s) 12 and/or 15 are constructed to contain be mixed into a material (e.g., a plastic) that flows, dissolves, and deliver a drug or other Substance. In some embodiments, melts, oozes or otherwise passes out of the device 10 follow all or portion(s) of the leg members 12 and/or 15 may be ing implantation. In Such embodiments, the molecules of the hollow, cellular, permeable or cavernous such that they may drug or substance may be sized so as to migrate or pass contain a drug or other substance (see FIGS. 6B and 6C) or 50 between polymer chains of the plastic Such that the drug or one or more reservoir members may be attached to the device substance will leach or pass out of the plastic over a desired 10 to contain the drug or other substance (see FIG. 6A). The time period. In certain embodiments, the drug or Substance drug or other Substance may then diffuse, leak, transport or may makeup or beincorporated into a coating that is extruded otherwise pass out of the reservoir through semipermiable or applied over all or a portion of the material located in or on membrane(s) or openings. 55 the device, Such that the drug or Substance will elute or pass For example, as shown in FIG. 6A, a semipermiable reser out of the coating at a desired rate or over a desired time voir member 47 which contains the drug or other substance period. In certain embodiments the drug or Substance may may be attached to the end of one or more leg(s) 12 such that make up or may be incorporated in a coating that is applied to the drug or substance will diffuse through the wall of the all or a portion of the device 10 (e.g., the leg members 12 reservoir member 47 thereby delivering a therapeutically 60 and/or 15 may be formed of a material such as self expanding effective dose of the drug or substance to the subject over a nickel-titanium alloy or other metal and may be coated with a desired period of time. The reservoir member 47 may or may coating that consists of or contains the drug or Substance) not be removable from the implanted device 10 and, in some such that the drug or substance will elute or pass out of that embodiments, the reservoir member 47 may be replaceable coating at a desired rate or over a desired time period. In by another full reservoir member 47 in situ while the device 65 certain embodiments, one or more holes, indentations or 10 remains in place. For example, in applications where the other texture may be drilled or otherwise formed in the leg device 10 is implanted within a fallopian tube FT for the members 12 and/or 15 or the optional matrix 18 or other US 7,694,683 B2 13 14 portion(s) of the device 10 and the desired drug or substance effective contraceptive or spermicidal agent may be used, in may be placed in the hole(s), indentation(s) or other texture amounts that result in the desired therapeutic effect of avoid such that the drug or substance will elute or pass out of the ing pregnancy. hole(s), indentation(s) or other texture over a desired time Specific examples of contraceptive agents that may be used period. The diameter(s) and/or depth(s) of the hole(s), inden include: the contraceptive contained in the Norplant tation(s) or other texture may be selected to control the rate system (e.g., a synthetic progestin, namely, and time over which the drug or substance will elute or having the molecular formula (d (-)-13-beta-ethyl-17-alpha otherwise pass from the device. In certain embodiments the ethinyl-17-beta-hydroxygon-4-en-3-one) and a molecular Substance may be responsive to the physiological conditions weight of 312.45 and/or various other contraceptive hormone 10 preparations including but not limited to medroxyprogester and thereby control the delivery of the substance in response one acetate, enanthate, , levonorg to those conditions. For example, where the Substance is estrel, levonorgestrel (as progestogen), ethinyl (as released for contraceptive purposes within the fallopian ), (as progestogen), levonorgestrel incom tubes, the release of the substance may be controlled to some bination with ethinyl estradiol, , extent by the menstrual cycle of the patient. Certain well 15 norgestrel in combination with ethinyl estradiol, quinacrine, known biochemical conditions prevail within the uterus and etc. Quinacrine is not a hormone. Rather, quinacrine is an fallopian tubes at the time and shortly after the release of the agent which may be used to cause chemical, non-Surgical egg from the ovaries (referred to hereas ovulation). A pellet of femalesterilization. When a quinacrine hydrocholoride pellet spermicidal Substance or other similar contraceptive Sub is inserted directly into the uterus, the guinacrine liquefies and stance may be coated with a substance that is soluble in flows into the fallopian tubes, causing permanent scarring. response to the biochemical conditions that prevail at the time Although recorded failure rates and persistent side effects of ovulation, but relatively insoluble in the biochemical con related to quinacrine sterilization have been low, controversy ditions that prevail in the uterus and fallopian tubes at other has developed around quinacrine's long-term safety, efficacy, times. This would result in the release of the substance pri and link to upper genital tract infections. However, direct marily at the time of ovulation, and thus resultina long lasting 25 placement of quinacrine into the fallopian tube in combina contraceptive pellet that enhances contraception at precisely tion with or as part of alumen blocking implantable device of the time when it will be effective. Another example of the this invention may permit the use or relatively low levels of release of the Substance in response to physiological condi quinacrine which would facilitate a local effect within the tions would be where a greater amount of Substance is fallopian tube without untoward systemic toxicity. released in response to increased blood flow, as in a chemo 30 In applications where the device 10 is implanted within a therapeutic agent located in a feeding artery to a tumor. As the fallopian tube FT to cause contraception, the device 10 may blood flow decreases, smaller amounts of the chemotherapeu deliver a contraceptive agent in an amount that a) causes an tic Substance is released, resulting in decreased systemic effect on the uterine tissue (e.g., endometrium) Such that eggs effects as the blood flow to the tumor is cut off. Responses to will not become implanted within the uterus UT and/or b) blood pressure, diurnal cycles, and the like can also be engi 35 causes cessation of ovulation. Typically, the dose of contra neered in accordance with this invention. ceptive Substance delivered to cause cessation of ovulation is As shown in FIGS. 8 and 8A, the invention also provides an higher than the dose delivered to cause non-implantation of implantable lumen occluding and/or Substance delivering eggs in the endometrium. For example, the device 10 may device 54 that further comprises a flag or marker 60 that deliver from about 10 micrograms to about 70 micrograms of unravels or extends out of the fallopian tube and into the 40 levonorgestrel (d (-)-13-beta-ethyl-17-alpha-ethinyl-17 uterus for visual confirmation to indicate which fallopian tube beta-hydroxygon-4-en-3-one). Dosages of levonorgestrel has a device 54 in it. In this particular non-limiting example, within the lower portion of this dosage range (e.g., from about the device 54 comprises a mesh body 56 that is designed to 10 micrograms per day to about 30 micrograms per day) may facilitate tissue ingrowth and occlude of a fallopian tube or be used to cause non-implantation of eggs in the endometrium other body lumen in which it is implanted. An arm 58 extends 45 while dosages within the higher portion of that dosage range from the body 56 and the marker 60 is attached to the arm 58, (e.g., from about 30 micrograms per day to about 70 micro as shown. Optionally, this flag or marker 60 and/or the body grams per day) may be used to cause cessation of ovulation. 56 of the device 54 can contain a Substance (e.g., contracep The dosages may vary however and this invention is not tive drug, antifungal, antibiotic, agent for treatment of STD limited to any specific dosage or any specific agent. Indeed, Such as pelvic inflammatory disease, spermicidal agent, etc.) 50 the optimal dosage of a particular contraceptive agent to be as described above. Also, optionally, this flag or marker 60 delivered from the device 10 may depend on various factors, may be dissolvable or biodegradable and/or retrievable and Such as the age of the patient, the specific location at which the removable at a later date, such through an endoscope or device 10 is implanted in the fallopian tube FT, whether hysteroscope as described above. In embodiments, where the devices 10 are implanted on only one or both fallopian tubes flag or marker 60 or any other component of the device is 55 FT, etc. removable from the body, that component may contain Sub Specific examples of specific spermicidal agents that may stance(s). Such as copper, that are desirable for only for short be used include but are not limited to nonoxynol-9, octox term implantation. ynol-9, menfegol, benzalkonium chloride and N-docasanol. The substance eluting implantable devices 10, 54 of the Also, in any application where infection or microbial infes present invention may be useable in various applications. For 60 tation is a concern, the device may elute or deliver antimicro example, as described above, inapplications where the device bial agent(s) (e.g., microbicidal agents, antibiotics, antiviral 10, 54 is implanted in a fallopian tube FT or elsewhere in the agent(s), anti paracyte agent(s), etc.) Specific examples of female genitourinary tract for the purpose of blocking egg antimicrobial agents that may be eluted or delivered from the migration or implantation, the device 10,54 may additionally implanted device include but are not limited to: Acyclovir; elute or deliver a female contraceptive agent or spermicidal 65 Amantadine; Aminoglycosides (e.g., Amikacin, Gentamicin agent to deter pregnancy, at least for some initial period of and Tobramycin); Amoxicillin: Amoxicillin/Clavulanate: time following implantation of the intraluminal device. Any Amphotericin B; Ampicillin; Ampicillin/sulbactam; Atova US 7,694,683 B2 15 16 quone; Azithromycin; Cefazolin; Cefepime; Cefotaxime; interferon, bacillus calmette-guerin (BCG), monoclonal anti Cefotetan: Cefpodoxime; Ceftazidime; Ceftizoxime; Ceftri bodies, interluken 2, granulocyte colony stimulating factor axone; Cefuroxime; Cephalexin; Chloramphenicol; Clotri (GCSF), etc.), PGDF receptor antagonists, herceptin, aspara mazole; Ciprofloxacin; Clarithromycin; Clindamycin; Dap ginase, buSulphan, carboplatin, cisplatin, carmustine, sone; Dicloxacillin; Doxycycline; Erythromycin; cchlorambucil, cytarabine, dacarbazine, etoposide, flucarba Fluconazole; Foscarnet; Ganciclovir, Gatifloxacin; Imi Zine, flurouracil, gemcitabine, hydroxyurea, ifosphamide, penem/Cilastatin: Isoniazid, Itraconazole--(SporanoXCR); irinotecan, lomustine, melphalan, mercaptopurine, methotr ; Metronidazole; Nafcillin; Nafcillin; Nystatin: exate, thioguanine, thiotepa, tomudex, topotecan, treosulfan, Penicillin: Penicillin G. Pentamidine; Piperacillin/Tazobac vinblastine, Vincristine, mitoaZitrone, oxaliplatin, procarba tam; Rifampin; Quinupristin-Dalfopristin; Ticarcillin/clavu 10 Zine, Streptocin, taxol, taxotere, analogs/congeners and lanate; Trimethoprim/Sulfamethoxazole; Valacyclovir; Van derivatives of Such compounds as well as other antitumor comycin; Mafenide; Silver Sulfadiazine; Mupirocin: agents not listed here. Nystatin: Triamcinolone/Nystatin: Clotrimazole/Betametha In some embodiments the lumen occluding and/or Sub sone; Clotrimazole; Ketoconazole; Butoconazole; Micona stance delivering device 10, 54 may be used for antitumor Zole; Tioconazole, detergent-like chemicals that disrupt or 15 applications. In the example shown in FIGS. 10 and 10A, a disable microbes (e.g., nonoxynol-9, octoxynol-9, benzalko tumor Thas a peduncle P through which and artery A and vein nium chloride, menfegol, and N-docasanol); chemicals that Vrun. Alumen occluding and/or Substance delivering device block microbial attachment to target cells and/or inhibits 10 of the present invention is implanted in the artery A to entry of infectious pathogens (e.g., Sulphated and Sulponated occlude the artery A thereby cutting of blood flow to the polymers such as PC-515 (carrageenan), Pro-2000, and Dex tumor and/or to deliver an antineoplastic or antitumor Sub trin 2 Sulphate); antiretroviral agents (e.g., PMPA gel) that stance to the tumor T. In some of these applications, the prevent HIV or other retroviruses from replicating in the implanted device 10 may continue to allow some flow of cells; genetically engineered or naturally occurring antibod blood or other body fluid through the body lumen in which it ies that combat pathogens such as anti-viral antibodies is positioned and into the tumor for at least an initial period of genetically engineered from plants known as “Plantibodies.” 25 time following implantation of the device (e.g., until tissue agents which change the condition of the tissue to make it ingrowth into the device 10 closes off the lumen of the blood hostile to the pathogen (such as Substances which alter vagi vessel or other body lumen). In this way, the antitumor sub nal pH (e.g., Buffer Gel and Acid form) or bacteria which stance eluted or delivered by the device 10 will be carried into cause the production of hydrogen peroxide within the vagina the tumor T for some desired period of time following (e.g., lactobacillus). 30 implantation. Thereafter, cellular ingrowth into the device 10 Also, in some applications, a Substance eluting implantable causes a progressive and complete occlusion of the artery A device may be placed in a body lumen (e.g., blood vessel, after the desired dose of antitumor substance has been deliv bronchus, hepatic duct, common bile duct, pancreatic duct, ered to the tumor T. This blockage of blood flow to the tumor etc.) near a tumor and the device may deliver one or more T may further serve to inhibit or kill some or all of any anti-tumor agents to treat the tumor. Specific examples of 35 remaining tumor cells that have not been killed by the anti anti-tumor agents that may be used in this invention include tumor drug. The release of the drug may be controlled based but are not limited to: alkylating agents or other agents which on the rate of blood flow through the feeding vessel. As the directly kill cancer cells by attacking their DNA (e.g., cyclo artery A occludes overtime, less total amount of the drug will phosphamide, isophosphamide), nitrosoureas or other agents be released into the bloodstream and thus there will be less which kill cancer cells by inhibiting changes necessary for 40 systemic effects of the chemotherapeutic agent which will cellular DNA repair (e.g., carmustine (BCNU) and lomustine generally result in less dramatic side effects. On the other (CCNU)), antimetabolites and other agents that block cancer hand, the concentration of the antitumor Substance will gen cell growth by interfering with certain cell functions, usually erally be slightly more concentrated in the blood based on the DNA synthesis (e.g., 6 mercaptopurine and 5-fluorouracil reduced flow, resulting in a more concentrated but more local (5FU), Antitumor antibiotics and other compounds that act by 45 ized therapeutic effect on the tumor T. binding or intercalating DNA and preventing RNA synthesis In yet another example of an application of this invention (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin, shown in FIGS. 11-11B, the implantable intraluminal device mitomycin-C and bleomycin)Plant (vinca) alkaloids and 10 is implanted into a lung L to block air flow to a portion of other anti-tumor agents derived from plants (e.g., Vincristine the lung L. As seen in FIG. 11, the trachea T is bifurcated into and vinblastine), , hormone inhibitors, hor 50 right and left mainstem bronchi MB. Each mainstem bron mone receptor antagonists and other agents which affect the chus MB then branches into a number of secondary bronchi growth of hormone-responsive cancers (e.g., , her SB. In the particular non-limiting example shown, the device ceptin, aromatase ingibitors such as aminoglutethamide and 10 is implanted into a secondary bronchus SB that leads into formestane, trriazole inhibitors such as and anastra the lower lobe of the left lung L. Following implantation, the Zole, steroidal inhibitors such as ), antiangiogenic 55 device 10 may cause instant or progressive full occlusion of proteins, Small molecules, gene therapies and/or other agents the secondary bronchus SB, so as to prevent air from entering that inhibit angiogenesis or vascularization of tumors (e.g., the diseased lobe or region of lung parenchyma that receives meth-1, meth-2, (Thalomid), bevacizumab air through that secondary bronchus SB. Such leakage or (Avastin), squalamine, endostatin, angiostatin, Angiozyme, disease may result from, for example, a ruptured emphyse AE-941 (Neovastat), CC-5013 (Revimid), medi-522 (Vi 60 matous bleb, traumatic lung puncture or iatrogenic lung rup taxin), 2-methoxyestradiol (2ME2, Panzem), carboxyami ture. In other cases the device 10 may be constructed so as not dotriazole (CAI), combretastatin A4 prodrug (CA4P), to substantially block airflow through the bronchus and pos SU6668, SU11248, BMS-275291, COL-3, EMD 121974, sibly even to perform a scaffolding or stenting function which IMC-1C11, IM862, TNP-470, celecoxib (Celebrex), rofe holds the lumen of the bronchus open. In either type of device, coxib (Vioxx), interferon alpha, interleukin-12 (IL-12) or any 65 a drug or substance may be eluted or delivered by the device of the compounds identified in Science Vol. 289, Pages 1197– into the adjacent pulmonary tissue. For example, in cases 1201 (Aug. 17, 2000)), biological response modifiers (e.g., where the device has been implanted to close off flow to a US 7,694,683 B2 17 18 punctured area of the lung, the device may elute an antibiotic 2. A device for implantation within a body lumen of a or other agent (e.g., a bronchodilator, mucolytic agent, expec human or veterinary subject, said device comprising: torant, etc.) to locally deter or treat any infection or other an intraluminal member having at least three radially condition present or developing in the lung tissue. In cases expandable legs, each of said legs including first and where the device 10 is implanted in a bronchus to treat second segments joined at an apex, said second segment emphysema or chronic obstructive pulmonary disease, the being in a radially-expandable, spaced-apart relation device may elute a therapeutic agent that is effective to treat ship from said first segment such that an acute angle is that underlying condition or its symptoms. formed between said first and second joined segments in Some examples of drugs that may be eluted from the device the expanded configuration, at least one of said legs for the purpose of treating such lung diseases include but are 10 including a cavity therewithin in the expanded configu not limited to: antimicrobial substances (examples of which ration and a plurality of openings comprising semi-per are listed hereabove); corticosteroids such as beclomethasone meable membranes on the surface of said at least one leg, (Vanceril. Beclovent), triamcinolone (Azmacort), flunisolide the intraluminal member structured to be implantable in (Aerobid), fluticasone (Flovent), budesonide (Pulmicort), a body lumen having a wall and configured to facilitate dexamethasone, prednisone, prednisolone, methylpredniso 15 tissue or cellular ingrowth from the lumen wall into the lone (Medrol, SoluMedrol, DepoMedrol), methylpredniso intraluminal member to cause occlusion of the body lone (Depo-Medrol), hydrocortisone (SoluCortef), methyl lumen; and prednisolone (SoluMedrol); Mediator-release inhibitors or a quantity of therapeutic substance initially contained cromones such as, cromolyn sodium (Intal), nedocromil within the cavity of the at least one leg such that the Sodium (Tilade); anti-leukotriene drugs such as leukotriene therapeutic substance will be delivered from said cavity receptor antagonists (e.g., Zafirlukast (Accolate)), leukot through the semi-permeable membranes of the at least riene-synthesis inhibitors (e.g., zileuton (Zyflo)) and other one leg to a target tissue for at least some period of time anti-leukotrienes (e.g., montelukast (Singulair)), mucolytic following implantation of the intraluminal member agents and expectorants (e.g., guifenisn); bronchodilator within the body lumen. drugs such as beta-adrenergic agonists (e.g., epinephrine (Pri 25 3. A device for implantation within a body lumen of a matene), isoproterenol (Isuprel), isoetharine (Bronkosol), human or veterinary subject, said device comprising: metaproterenol (Alupent, Metaprel), albuterol (Proventil, an intraluminal member comprising at least three radially Ventolin), terbutaline (Bricanyl, Brethine), bitolterol (Tor expandable legs, each of said legs including first and nalate), pirbuterol (Maxair), salmeterol (Serevent), Methyl second segments joined at an apex, said second segment Xanthines (e.g., caffeine, theophylline, aminophylline and 30 being in a radially-expandable, spaced-apart relation OXtriphylline (Choledyl)) and anticholinergics (e.g., atropine, ship from said first segment such that an acute angle is ipratropium bromide (Atrovent). formed between said first and second joined segments in It will be appreciated by those skilled in the art that various the expanded configuration; at least one leg comprising modifications, additions, deletions, combinations and semi-permeable membranes disposed within openings changes may be made to the examples described hereabove 35 of said at least one leg, said at least one leg having a and shown in the drawings, without departing from the lumen containing a quantity of therapeutic substance intended spirit and scope of this invention. All such reason therewithin, the intraluminal member being implantable able modifications, additions, deletions, combinations and in a body lumen having a wall and configured to facili changes are included in this disclosure. tate tissue or cellular ingrowth from said body lumen 40 wall onto the intraluminal member to cause occlusion of What is claimed is: the body lumen, 1. A device for implantation within a body lumen of a wherein said quantity of therapeutic substance diffuses human or Veterinary subject, said device comprising: through said semi-permeable membranes to a targettis an intraluminal member having at least three radially-ex Sue for a period of time following implantation of the pandable legs, each of said legs including first and sec 45 intraluminal member within the body lumen. ond segments joined at an apex, said second segment 4. A device according to claim 1, 2 or 3 wherein the device being in a radially-expandable, spaced-apart relation is implantable in a body lumen comprising a fallopian tube or ship from said first segment such that an acute angle is other lumen of the female reproductive tract and is effective to formed between said first and second joined segments in occlude that lumen following implantation. the expanded configuration, at least one of said legs 50 5. A device according to claim 4 wherein the therapeutic including a lumen therewithin in the expanded configu Substance delivered by the device comprises a contraceptive. ration and openings on the surface of said legs, said 6. A device according to claim 5 wherein the contraceptive openings comprising semi-permeable membranes, said device substance is selected from the group consisting of: intraluminal member including a fibrous matrix dis Synthetic progestins, levonorgestrel, medroxyprogester posed within the confines of the radially expandable 55 one acetate, norethisterone enanthate, progestogen, legs, the intraluminal member being implantable in a levonorgestrel, levonorgestrel (as progestogen), ethinyl body lumen having a wall, the fibrous matrix structured estradiol (as estrogen), norgestrel (as progestogen). to promote tissue or cellular ingrowth from the lumen levonorgestrel in combination with ethinyl estradiol, wall into the fibrous matrix disposed in the intraluminal norethisterone enanthate, norgestrel in combination member, said tissue or cellular ingrowth causing occlu 60 with ethinyl estradiol and quinacrine. sion of the body lumen; and 7. A device according to claim 4 wherein the therapeutic a quantity of therapeutic substance contained within said at Substance delivered by the device comprises a spermicidal least one leg lumen such that the therapeutic substance agent. will be delivered from the lumen of said leg through the 8. A device according to claim 7 wherein the spermicidal semi-permeable membrane to a target tissue for a period 65 agent is selected from the group consisting of nonoxynol-9, of time following implantation of the intraluminal mem octoxynol-9, menfegol, benzalkonium chloride and ber within the body lumen. N-docasanol. US 7,694,683 B2 19 20 9. A device according to claim 4 wherein the therapeutic each of said legs including a lumen therewithin and com substance delivered by the device comprises an antimicrobial prising at least one semi-permeable membrane on a Sur agent. face thereof, and 10. A device according to claim 9 wherein the antimicro a quantity of contraceptive Substance which diffuses from bial agent is selected form the group consisting of acyclovir, 5 the lumen of said hollow fiber membranes in sufficient an aminoglycoside, gentamicin, tobramycin, amoxicillin, amount to cause a pharmacologic contraceptive effect in amoxicillin+clavulanate, amphotericin B, amplicillin, ampi the patient for a period of time following implantation of cillin/Sulbactam, atovaquone, azithromycin, cefazolin, the occluding member within the reproductive passage cefepime, cefotaxime, cefotetan, cefpodoxime, cefiazidime, way to enhance contraception. ceflizOXime, ceftriaxone, ceftiroXime, cephalexin, chloram 10 15. A system according to claim 14 wherein the occluding phenicol, clotrimazole, ciprofloxacin, clarithromycin, clinda member further comprises means for securing the occluding mycin, dapsone, dicloxacillin, doxycycline, erythromycin, member to the wall of the reproductive passageway. fluconazole, foScarnet, ganciclovir, gatifloxacin, imipenem, 16. A system according to claim 15 wherein the means for cilastatin, imipenem+cilastatin, isoniazid, itraconazole, keto securing the occluding member to the wall of the reproductive conazole, metronidazole, nafcillin, nafcillin, nystatin, peni 15 passageway comprises a mechanical Securing apparatus. cillin, penicillin G, pentamidine, piperacillin, taZobactam, piperacillin+taZobactam; rifampin, quinupristin, dalfopris 17. A system for causing contraception in a human or tin, quinupristin--dalfopristin, ticarcillin, clavulanate, ticar animal Subject, said system comprising: cillin+clavulanate, trimethoprim, Sulfamethoxazole, trime an expandable occluding member implantable in a repro thoprim-i-Sulfamethoxazole, Valacyclovir, Vancomycin, ductive passageway of the Subject, the reproductive pas mafenide, silver Sulfadiazine, mupirocin, nystatin, triamcino sageway having a wall, the expandable occluding mem lone, nystatin, triamcinolone--nyStatin, clotrimazole+be ber configured to facilitate tissue or cellular ingrowth tamethasone, butoconazole, miconazole, tioconazole, a from said passageway wall into the expandable occlud detergent-like Substances that disrupt or disable microbes, ing member said occluding member being a) disposable nonoxynol-9, octoxynol-9, benzalkonium chloride, menfe 25 in a first configuration wherein it is sufficiently compact gol, N-docasanol, a chemical that blocks microbial attach to allow the occluding member to be advanced into the ment to target cells and/or inhibits entry of infectious patho reproductive passageway and b) Subsequently expand gens into cells, Sulphated and Sulponated polymers, able to a second configuration wherein the occluding carrageenan, Pro-2000, dextrin 2 sulphate, antiretroviral member engages the wall of the reproductive passage agents, PMPA gel, genetically engineered or naturally occur 30 way, said expandable occluding member including at ring antibodies that combat pathogens, agents which change least three radially expandable plurality of legs, each of the condition of the tissue to make it hostile to the pathogen, said legs including first and second segments joined at an Substances which alter vaginal pH, buffer gel, acidform, apex, said second segment being in a radially-expand microbes that cause the production of hydrogen peroxide able, spaced-apart relationship from said first segment 35 Such that an acute angle is formed between said first and within the vagina, and lactobacillus. secondjoined segments in the expanded second configu 11. A device according to claims 1, 2 or 3, wherein the device is implanted in a lumen of the vas deferens or other ration, at least one of said legs including a cavity there lumen of the male reproductive tract and is effective to within in the expanded second configuration and a plu occlude that lumen following implantation. rality of semi-permeable windows on a surface thereof; 40 and 12. A device according to claim 11 wherein the therapeutic a quantity of contraceptive Substance which is delivered substance delivered by the device comprises a spermicidal from said cavity through said semi-permeable windows agent. in Sufficient amount to cause a pharmacologic contra 13. A device according to claim 12 wherein the spermicidal ceptive effect in the patient for a period of time following agent is selected from the group consisting of nonoxynol-9, 45 implantation of the occluding member within the repro octoxynol-9, menfegol, benzalkonium chloride and ductive passageway, wherein the occluding member fur N-docasanol. ther comprises means for securing the occluding mem 14. A system for causing contraception in a human or ber to the wall of the reproductive passageway and animal Subject, said system comprising: wherein the means for securing the occluding memberto an expandable occluding member implantable in a repro 50 the wall of a reproductive passageway comprises an ductive passageway of the Subject, the reproductive pas adhesive. sageway having a wall, the expandable occluding mem 18. A system according to claim 14 or 17 wherein the ber configured to facilitate tissue or cellular ingrowth Substance comprises a hormone. from the wall of the passageway into the expandable 19. A system according to claim 18 wherein the substance occluding member, said occluding member beinga) dis 55 comprises a progestin. posable in a first configuration wherein it is sufficiently 20. A system according to claim 18 wherein the substance compact to allow the occluding member to be advanced comprises a synthetic progestin. into the reproductive passageway and b) Subsequently expandable to a second configuration wherein the 21. A system according to claim 14 or 17 wherein the occluding member engages the wall of the reproductive 60 Substance comprises levonorgestrel. passageway, said occluding member having at least 22. A system according to claim 14 or 17 wherein the three radially-expandable legs, each of said legs includ substance comprises (d(-)-13-beta-ethyl-17-alpha-ethinyl ing first and second segments joined at an apex, said 17-beta-hydroxygon-4-en-3-one). second segment being in a radially-expandable, spaced 23. A system according to claim 14 or 17 wherein the apart relationship from said first segment, wherein an 65 substance comprises (d(-)-13-beta-ethyl-17-alpha-ethinyl acute angle is formed between said first and second 17-beta-hydroxygon-4-en-3-one) having a molecular weight joined segments in the expanded second configuration; of 312.45. US 7,694,683 B2 21 22 24. A system according to claim 14 or 17 wherein the 26. A system according to claim 25 wherein the occlusion occluding member is sized and configured to be implanted of the reproductive passageway is reversible by removing at within the lumen of a fallopian tube. least a portion of the occluding member and any tissue that has grown into the occluding member or that portion of the 25. A system according to claim 14 or 17 wherein the 5 occluding member. occluding member causes a reversible occlusion of the repro ductive passageway. k . . . .