# Patent

## Title
Systems and methods for treatment of perforator veins for venous insufficiency

## Abstract

Systems and methods for the treatment of perforator veins for venous insufficiency are described. The systems can include a catheter assembly comprising a proximal hub, a spin lock on the proximal hub, a elongate body overmolded to the proximal hub, and a distal end, the catheter, the elongate body configured to be placed within a perforator vein; an extension tubing having a proximal female hub, a distal male hub, and an elongate body therebetween, the distal male hub having a spin lock thereon, the distal male hub configured to be attached to the proximal hub of the catheter assembly; a syringe filled with a volume of media including cyanoacrylate; and an injector configured to automatically dispense a bolus of the media sufficient to coapt the perforator vein from the syringe upon actuation of a control on the injector. Methods are also disclosed.

## Background
This application claims the benefit of U.S. Provisional Application No. 61/925,478, which was filed on Jan. 9, 2014 and is entitled, “SYSTEMS AND METHODS FOR TREATMENT OF PERFORATOR VEINS FOR VENOUS INSUFFICIENCY,” the entire content of which is incorporated herein by reference.


BACKGROUND OF THE INVENTION
Healthy leg veins contain valves that allow blood to move in one direction from the lower limbs toward the heart. These valves open when blood is flowing toward the heart, and close to prevent venous reflux, or the backward flow of blood. When veins weaken and become enlarged, their valves cannot close properly, which leads to venous reflux and impaired drainage of venous blood from the legs. Venous reflux is most common in the superficial veins. The largest superficial vein is the great saphenous vein (GSV), which runs from the top of the foot to the groin, where it terminates at the saphenofemoral junction. There are veins which lead from the superficial veins (great and small saphenous veins, (GSV, SSV, respectively) and “perforate” the fascia and join with a deep vein. Like the GSV and SSV, these perforator veins can become diseased and experience reflux. This could compound the general symptoms of venous reflux, creating additional venous hypertension throughout the region where the perforator is located. These sites are often associated with skin degradation leading to venous stasis ulcers.
Factors that contribute to venous reflux disease include female gender, heredity, obesity, lack of physical activity, multiple pregnancies, age, past history of blood clots in the legs and professions that involve long periods of standing. According to population studies, the prevalence of visible tortuous varicose veins, a common indicator of venous reflux disease, is up to 15% for adult men and 25% for adult women. A clinical registry of over 1,000 patients shows that the average age of patients treated for venous reflux is 48 and over 75% of the patients are women.
Venous reflux can be classified as either asymptomatic or symptomatic, depending on the degree of severity. Symptomatic venous reflux disease is a more advanced stage of the disease and can have a profound impact on the patient's quality of life. People with symptomatic venous reflux disease may seek treatment due to a combination of symptoms and signs, which may include leg pain and swelling, painful varicose veins, skin changes such as discoloration, inflammation and open skin ulcers in the lower legs.
A primary goal of treating symptomatic venous reflux is to eliminate the reflux at its source, such as, for example, the great saphenous vein. If a diseased vein is either closed or removed, blood can automatically reroute into other veins without any negative consequences to the patient. The perforator veins of the leg can, however, still be the source of symptoms despite GSV or SSV occlusion. The most common perforating veins that account for the condition are found in the medial aspect of the lower leg. These were traditionally termed the Cockett's (lower leg), Boyd's (knee region), Dodd's and Hunterian (thigh) perforators. New naming conventions assign names of given perforating veins of the leg as to their location; e.g., tibial, paratibial, patellar, etc. as described further below.
Current non-invasive methods for treatment of reflux in the perforating veins include thermal ablative techniques such as, e.g., radiofrequency (RF) and laser ablation. Sclerotherapy, including foam sclerotherapy, is used as well. Radiofrequency and laser ablation often require tumescent anesthesia which produces both bruising and pain along the treatment zone for several days post-procedure. Both can have side effects such as burns and nerve damage, each of which can result in paresthesia or hypoesthesia. Radiofrequency and laser ablation also can require expensive radiofrequency devices and/or laser boxes in addition to expensive single use disposable components. In addition, these methods are often challenging to perform. The perforating veins typically are tortuous and short in length (e.g., between about 2 and about 7 cm), making the steps of needle access, positioning a laser fiber or RF catheter and injecting tumescent anesthesia technically difficult. And while foam sclerotherapy is relatively non-invasive, it is known to have a high rate of recurrence and potentially undesirable side effects. All of the methods generally require that the patient wear compression stockings for a period of about 1 to about 4 weeks post-procedure.
For those treatments that involve careful placement of a catheter at a particular intravenous treatment site, a reliable means for visualizing the instruments is needed. Ultrasound is a common method for device visualization in the medical device industry. Ultrasound works by emitting sound waves and analyzing the waves that are reflected and returned to the ultrasound sensing device. Despite its popularity, ultrasound visualization often provides inadequate resolution for careful intravenous placement of a catheter for the treatment of venous reflux disease, and improved echogenic catheters and methods of use are needed.
SUMMARY OF THE INVENTION
Systems and methods for the treatment of perforator veins for venous insufficiency are described. In some embodiments, the systems can include a catheter assembly comprising a proximal hub, a spin lock on the proximal hub, an elongate body overmolded to the proximal hub, and a distal end. The catheter, the elongate body configured to be placed within a perforator vein through a needle; an extension tubing having a proximal female hub, a distal male hub, and an elongate body therebetween, the distal male hub having a spin lock thereon, the distal male hub configured to be attached to the proximal hub of the catheter assembly; a syringe filled with a volume of media comprising cyanoacrylate; and an injector configured to automatically dispense a bolus of the media sufficient to coapt and embolize the perforator vein from the syringe upon actuation of a control on the injector.
Also disclosed herein are methods of treating venous insufficiency. In some examples, the methods comprise advancing an access needle percutaneously into a perforator vein in a patient under ultrasound guidance; advancing a portion of a catheter assembly through the access needle and into the perforator vein; injecting a volume of media comprising cyanoacrylate through the catheter assembly into the perforator vein such that the media does not substantially flow into adjacent superficial or deep veins, the volume of media being sufficient to coapt and/or embolize the perforator vein; withdrawing the needle and catheter from the perforator vein; and applying external pressure sufficient to coapt the perforator vein. In some examples, the methods may further comprise identifying a perforator vein in a patient having venous insufficiency.
In some embodiments, disclosed herein is a system for treating venous insufficiency, the system comprising a catheter assembly comprising a proximal hub having a spin lock, an elongate body operably connected to the proximal hub, and a distal end, the catheter assembly having an elongate body configured to be placed within a perforator vein; an extension tubing having a proximal female hub, a distal male hub, and an elongate body therebetween, the distal male hub having a spin lock thereon, the distal male hub configured to be attached to the proximal hub of the catheter assembly; a volume of media comprising cyanoacrylate; and an injector configured to automatically dispense a bolus of the media upon actuation of a control on the injector.



BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1-11 schematically illustrate a method for occluding a vein, such as the great saphenous vein, using a vein-occluding substance and an imaging tool, according to some embodiments of the invention.
FIGS. 12-16 schematically illustrate a method for occluding a vein, such as the great saphenous vein, according to other embodiments of the invention.
FIGS. 17-21E schematically illustrate methods for occluding a vein, such as the great saphenous vein, according to other embodiments of the invention.
FIGS. 22A-22D illustrate embodiments of an echogenic catheter with embedded microlumens.
FIG. 23 illustrates an echogenic catheter with microwells.
FIG. 24 illustrates an echogenic catheter with enclosed gas pockets.
FIGS. 25-35 illustrate various views and components of a vein-occluding dispensing system according to some embodiments of the invention.
FIGS. 36 and 37 schematically illustrate an example glue gun and adapter assembly.
FIG. 38 schematically illustrates a front view of a glue gun, according to some embodiments of the invention.
FIG. 39 schematically illustrates an example perforator vein and adjacent veins.
FIGS. 40A-40I schematically illustrate features of a catheter assembly configured to be inserted into a perforator vein, according to some embodiments of the invention.
FIGS. 41A-41L schematically illustrate features of extension tubing connectable to a catheter assembly configured to be inserted into a perforator vein, according to some embodiments of the invention.
FIGS. 42A-45G schematically illustrate steps of a method for treating a perforator vein in a patient with venous reflux in a perforator vein, according to some embodiments of the invention.



DETAILED DESCRIPTION
Disclosed herein are systems, methods and devices for the minimally invasive treatment of varicose veins and other medical conditions. When used herein with respect to the device, proximal can refer to toward the access insertion site into a blood vessel, while distal refers to away from the access insertion site and in the direction of the patient. In the treatment as applied to the great saphenous vein, proximal may mean cephalad, or towards the head, while distal refers to the caudal direction. In some embodiments an occlusive device is deployed to block the saphenous vein just distal to the Superficial Femoral Vein Junction (SFJ) to coapt the vein walls together encouraging adherence of the walls. This technique may be used with a drug such as sclerosing solution or a device like medical adhesive. In some embodiments, complete vein closure is the desired clinical result of all treatments to mitigate the effects of venous hypertension caused by retrograde venous flow. The occlusion device and medical adhesive can be delivered through a catheter utilizing a “single stick” method. This approach is designed to produce less pain and fewer skin injections than used in current treatment approaches, as well as to mitigate or eliminate the need for patients to wear uncomfortable compression stockings after treatment since the desired outcome of occlusion/embolization is one of relatively immediate relief.
Vein-Collapsing Methods
Methods to treat venous insufficiency are now described, in which the vein is compressed at least partially along the treatment zone. Doing so can better ensure that the vein is partially or fully collapsed as opposed to merely occluded, depending on the desired clinical result. Not to be limited by theory, collapsing the vein may place two or more luminal surfaces of endothelial cells into opposing contact with each other, stimulating fibrous tissue proliferation and resulting in improved long-term closure of the vein with a lower risk of recanalization and vein re-opening. In some embodiments, a deployment catheter is percutaneously introduced into a vein at an access site, and transluminally distally advanced across a treatment zone within a vein. External compression is applied to collapse the vein distal of the deployment catheter after it is positioned at the proximal target within the vein. After a bolus of plug forming media is expressed from the distal end of the catheter, the occlusion at the end of the catheter forces the vein-occluding substance to flow retrograde (proximally) toward the catheter insertion point into the vein and reduce the distal flow force and mixing with any blood that may be remaining within the vessel. The compression with the ultrasound transducer and the practitioners hand and the mere presence of the introducer/catheter, in some cases, generally creates a nearly blood-free zone. This method also allows the vein-occluding media to replace any existing blood “trapped” between the catheter and the occluded vein and forms an occlusive plug within the vein while minimizing mixing with the blood. This reduction in mixing can be advantageous in certain embodiments because it can increase the bonding strength between the vein-occluding media and the vein wall. External compression distally to the treatment zone optionally may be removed, or may remain throughout all or a portion of the procedure. External compression can also occur around the area of the vein where the plug forming media is expressed in order to collapse the vein as noted above. The catheter is thereafter proximally retracted towards the access site while dispensing a vein occluding substance, either continuously or via discrete boluses spaced apart from the initial bolus at regular or irregular intervals across the treatment zone. External compression can continue proximally where the vein occluding substance is being dispensed in order to ensure collapse of the vein as noted above. The catheter is thereafter withdrawn, and the access site closed using conventional techniques. The method is described in greater detail below.
The vein closure system can enter the vein such as the great saphenous or small saphenous vein, perforating vein or other vessel using fluoroscopy, ultrasound, or other guidance means. A micro-catheter system can be placed over a wire for introduction of an outer catheter or introduction sheath into the vein. In some embodiments, the vein is entered as distal as possible or as clinically relevant in the abnormal vein. In some embodiments, the closure method comprises advancement of an introducing sheath and/or dilator over a guide wire to the saphenofemoral junction below the superior epigastric vein, which in some embodiments, can be approximately 1.5 centimeters (cm) to 2.5 cm from the sapheno-femoral junction. Following placement of the sheath to this level and optional verification with ultrasound, an inner catheter is introduced through the sheath and is luer-locked or otherwise secured to the sheath to maintain a fixed position with the tip extending approximately 5 cm from the end of the sheath.
In accordance with FIG. 1, the occlusion method comprises providing an injector such as a glue gun 300 that assists in injecting a vein-occluding substance to occlude vessel 400. In some embodiments, the distal end 302 of the glue gun 300 includes a syringe that is operably connected to an inner catheter 204 by a luer lock 602. A sheath or outer catheter 202 surrounds the inner catheter 204, and assists in providing access to a target site within the vessel 400 interior. In some embodiments, the outer catheter 202 is introduced first followed by the inner catheter 204, while in other embodiments, the outer catheter 202 and inner catheter 204 are introduced simultaneously. As shown in FIG. 1, the outer catheter 202 and inner catheter 204 are introduced near the proximal end 402 of the vessel 400 and are directed towards the distal end 401 of the vessel, where the vein-occluding substance will be released. In one embodiment, at the site of release of the vein-occluding substance, the inner catheter 204 will extend beyond the distal end of the outer catheter 202, such as by between about 3 cm and 7 cm, to prevent any vein-occluding substance from contacting the outer catheter 202.
As shown in FIG. 1, an imaging tool such as an ultrasound transducer 630 can also be provided that could be multifunctional, including guiding one or more catheters, serving as a compression element, and/or identifying areas in the interior of the vessel that may need further occlusion or closure. In some embodiments, the ultrasound transducer 630 can be placed into contact with an external surface of a patient's skin prior to placing the outer catheter 202 and/or inner catheter 204 through the vessel 400. The ultrasound transducer 630 can assist in generating images to help guide one or more catheters to a site where a vein-occluding substance will be introduced. In some embodiments, the ultrasound transducer 630 can also serve as a compression element prior to, during or after introducing a vein-occluding substance to assist in closure of the vessel 400. By serving as a compression element, the ultrasound transducer can help to flatten and/or reduce the size of the vessel 400. In some embodiments, the ultrasound transducer 630 can include a Doppler flow detection capability, and help to identify areas in the interior of the vessel 400 that may need further closure or occlusion and thus, further application of a vein-occluding substance.
When the inner catheter is in position and verified with ultrasound to be in the appropriate position below the sapheno-femoral junction, compression at the sapheno-femoral junction is performed and small amounts of vein occluding substances, including liquid adhesives such as glues including cyanoacrylates, or any substances described elsewhere herein or known in the art, are injected into the vein. The vein can then be collapsed using compression, such as external compression to assist in coapting the vein and adhering the internal walls of the vein to the vein-occluding substance in a solid, permanent bond. In some embodiments, an additional compression device can be provided in addition to the ultrasound transducer or probe (either proximally or distally) to assist in collapsing the vein. In some embodiments, the compression device can be a sequential compression device configured to apply compressive pressure from a compressor against the patient's limb through a flexible pressurized sleeve. The compression can be configured to deliver uniform compression along its length, distal-to-proximal compression in a peristaltic wave or other modes depending on the desired clinical result. In some embodiments, the compressive device could be configured to deliver a pressure of at least about 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, or more millimeter of mercury (mmHg), or between about 30-150 or 50-100 mmHg in some embodiments. In some embodiments, an external device delivering energy to create a controlled vasospasm of the vein is used. The energy could be, for example, electrical stimulation, cryotherapy, infrared, visible, or UV light, microwave, RF energy, ultrasound energy, magnetic energy, thermal energy, or a combination of the energy sources.
In accordance with FIG. 2, the tip of the inner catheter 204 is placed at a site adjacent to the blocked or distal end 401 of the vessel 400 with a minimum distance between them. Once the outer catheter 202 and inner catheter 204 are in place, the glue gun 300 can inject a vein-occluding substance 502 that is released from the inner catheter 204. In some embodiments, the inner catheter 204 can release at least 1, 2, 3, 4, 5, 7, 10, 12, 15, 20, or more boluses of vein-occluding media along a treatment site within a vein. For example, in some embodiments, a single continuous flow of vein-occluding media can be introduced across a treatment site, while in other embodiments, multiple spaced-apart boluses of vein-occluding media can be introduced at regular or irregular intervals across a treatment site. In some embodiments, the treatment site can be a total length of between about 2 cm and 80 cm, between about 2 cm and 50 cm, or between about 5 cm and 40 cm in some embodiments. Along the treatment site, one or more boluses of vein-occluding media can be introduced at spaced-apart intervals, such as between every approximately 1 cm and 7 cm, more preferably between every approximately 3 cm and 5 cm. The intervals need not be evenly spaced. Each bolus of media can occlude and treat at least a portion of the treatment site. In some embodiments, a single bolus of media can occlude and treat a length of the vein that is between about 0.5 cm to 5 cm, such that at least about 0.5 cm, 1 cm, 2 cm, 3 cm, 4 cm, or 5 cm of the vein can be treated. In other embodiments, the length of the treatment site within the vein will be greater than 5 cm by a single bolus of media. Providing one or more boluses of vein-occluding media, particularly in selected intervals, as described herein advantageously provides a treatment that can be performed with greater control and ease over conventional vein-occluding processes and which can be tailored to specific patients (e.g., having different lengths of treatment zones).
In some embodiments, each bolus of media can have a volume of between about 0.01 to 3 cubic centimeters (cc or cm3) of a vein-occluding substance (e.g., cyanoacrylate compound), such as between about 0.01 cc to 1 cc of a vein-occluding substance. The rate of injection can be controlled manually, or by a mechanical and/or electronic controller configured to release a pre-determined volume of vein-occluding substance at a specified flow rate. While in some embodiments the injection rate can be relatively constant throughout the procedure in some embodiments, in other embodiments, the injection rate can be variable, releasing periodic boluses of vein-occluding substance at specified time and/or distance intervals. In some embodiments, the injection rate is between about 0.002 cc per second (cc/sec) and 6 cc/sec, such as between about 0.02 cc/sec and 0.2 cc/sec. Controlling the volume and flow rate of the bolus of media to levels described herein advantageously prevents unnecessary overflow or undertreatment of the media within the vein. In some embodiments, an injector is provided that is configured to precisely deliver a predetermined volume of media, such as between about 0.05 milliliters (mL) and 0.5 mL, or between about 0.1 mL and 0.2 mL, into the vein when a physician actuates a control, such as a button, switch, dial, or foot pedal, for example. In some embodiments, the injector includes a safety feature, such as an electronic lockout that prevents unintended multiple bolus injections of glue within a specified period of time, such as, for example, requires that bolus injections be spaced apart by at least about 0.5, 1, 2, 3, 4, 5 seconds, or more.
In accordance with FIG. 3, once the vein-occluding substance 502 is injected out of the tip of the inner catheter 204, the vein-occluding substance 502 flows against the distal end of the proximal side of the occluded vessel 400 and then reverses flow proximally traveling along the outside of the catheter track while displacing the blood content along the target area of the vessel 400. Then, the outer catheter 202 and inner catheter 204 can be pulled back or withdrawn to target a different site along the vessel 400. For example, the outer catheter 202 and inner catheter 204 can be moved in a direction towards the proximal end 402 of the vessel 400 prior to injecting additional vein-occluding substance 502 into the vessel 400.
In accordance with FIG. 4, an optional compression element, e.g., an operator's hand 640, a sequential compression device, or the ultrasound transducer 630 can be used to apply pressure on the external surface of the patient's body and compress the interior walls of the vessel 400. The optional compression element can be used to compress portions of the vessel prior to, during or after the introduction of the vein-occluding substance. When the compression element compresses portions of the vessel during or after the introduction of the vein-occluding substance, the vessel is compressed against the vein-occluding substance 502, as shown in FIG. 4. This compression assists in occlusion as well as collapse of the vessel. In some embodiments, as additional portions of the vessel are treated with the vein-occluding substance, the target regions can be compressed immediately following, or no more than about 5 minutes, 4 minutes, 3 minutes, 2 minutes, 1 minute, 30 seconds, 15 seconds, or less following injection of the vein-occluding substance in some embodiments.
FIGS. 5 and 6 illustrate the ultrasound transducer 630 guided or moved from a first location to a second location following injection of the vein-occluding substance 502 at the first site. Once the vein-occluding substance 502 is injected to a targeted site and preferably, once the vein is completely occluded and/or collapsed at that site, the ultrasound transducer 630 can be moved to a second location, e.g., a location closer towards the proximal end 402 of the vessel 400, to assist in collapse of the vessel 400 at a different site. In some embodiments, by moving the ultrasound transducer 630 along the length of the vessel 400 in a proximal direction, the ultrasound transducer can serve as a compression element that provides a compression that follows the length of the vessel 400 in a proximal direction to better ensure collapse of the vessel. In some embodiments, the ultrasound transducer or other external compression element can be moved a distance between the first location to a second location spaced apart between about 0.5 cm to 5 cm with respect to the first location. In other embodiments, the ultrasound transducer can be moved a distance between the first location to a second location that is between 3% and 50%, such as between 3% and 20% of the total length of the treatment site. Guiding the ultrasound transducer over a discrete distance advantageously helps to ensure that portions of the treatment site are effectively occluded before guiding the ultrasound transducer over different portions of the treatment site. After moving the ultrasound transducer 630, the glue gun 300 can inject a vein-occluding substance 502 at the different site of the vessel 400, as shown in FIG. 6. As shown in FIG. 7, in some examples, after glue gun 300 injects the vein occluding substance 502 at the different site of the vessel 400, outer catheter 202 and inner catheter 204 can again be pulled back or withdrawn to target a different site along the vessel 400.
Once the vein-occluding substance 502 is injected into the second site of the vessel 400, a compression element e.g., the hand 640, can once again be used to assist in collapse of the portion of the vessel 400, as shown in FIG. 8. After achieving partial or complete closure of a portion of the vessel 400, the ultrasound transducer 630 can once again be guided or moved along the vessel 400 to different locations to assist in closure or occlusion of the vessel 400, providing a moveable compression element in some instances. With the assistance of the ultrasound transducer 630 and/or additional compression element as described above, which can move along the length of the vessel 400 and serve as a compression element and/or image generator, it is possible to collapse the vessel 400 along the entire treatment length. As shown in FIG. 9, the ultrasound transducer 630 is guided to the second location along the vein 400 to assist in collapse of the vessel 400 at the different location.
The application of the ultrasound probe and/or additional compression device can be repeated at multiple locations along the great saphenous vein, small saphenous vein, perforator vein, varicosity or branch vein as shown in FIGS. 10 and 11, until the vein is partially or entirely coapted and closed in a flattened state. The inner catheter 204 can then be removed, and an adhesive bandage or other dressing can be placed over the entrance site. In some embodiments, the ultrasound probe can generate images that confirm the closure/embolization or coaptation of the vein. Once the vein is closed partially or completely, the injector is removed from the access site, and the procedure then is completed. In one embodiment, only a small amount of local anesthesia at the entrance site is used. No tumescent anesthesia is required. No general or conscious sedation is required as the procedure produces no significant heat or other types of damage to surrounding tissues, whose by-product symptomatology can include pain to the subject being treated.
While the methods above have been described with the intention of occluding the great saphenous vein, a wide variety of other veins, arteries, lymphatics, or other body lumens, natural or artificial can be occluded as well using systems and devices as disclosed herein. Furthermore, a variety of conditions can be treated with the systems, devices, and methods disclosed herein, for example, venous insufficiency/varicose veins of the upper and/or lower extremities, esophageal varices, gastric varices, hemorrhoidal varices, venous lakes, Klippel-Trenaunay syndrome, telangiectasias, aneurysms, arterio-venous malformations, embolization of tumors or bleeding vessels, lymphedema, vascular and non-vascular fistulas, closure of fallopian tubes for sterilization, etc.
In some embodiments, the vein-occluding substance can be injected into the vein using an automated process in order to minimize undesired over-injection or under-injection of the vein-occluding substance, injection at undesired intervals or injection of undesired bolus sizes. For example, the outer catheter member of the catheter can be made easily compressible (e.g., with a thin wall). The column strength needed for catheter placement can thus be supplied predominantly with the inner tube. Once the inner catheter has been withdrawn from the vein, the remaining outer catheter is filled with the vein-occluding substance. The proximal end of the outer catheter just distally of the luer lock, manifold, or other coupling to the vein-occluding substance injector can carry a compression element such as a clamp, parallel rollers, or a slideable compression element with the catheter extending transversely between two portions of the slideable compression element. Actuating the compression element will radially compress the outer catheter. An operator can then hold the clamp in place while the catheter is pulled proximally toward the access site through the clamp. The clamp thus slides, rolls, or otherwise moves along the limb or target anatomy, while the catheter is compressed to precisely compress the volume of the catheter as a function of the distance the catheter is withdrawn proximally from the vein.
FIGS. 12-16 schematically illustrate a method for occluding a vein, such as the great saphenous vein, according to one embodiment of the invention. Ultrasonographic vein mapping, contrast venography, or other technique, for example, can be used prior to the occlusion procedure to better visualize a patient's particular vascular anatomy in some embodiments. The entry site is prepped and draped in a sterile fashion, and local anesthesia such as lidocaine can be provided, although may not be required. First, the vascular system, such as a superficial vein in the foot, ankle, calf, or thigh, for example, great saphenous, small saphenous vein, perforating vein, superficial varicosity a dorsal digital vein, intercapitular vein, common digital vein, dorsal venous arch, medial marginal vein, lateral marginal vein, plantar cutaneous venous arch, or a vein of the plantar cutaneous venous network is cannulated, such as percutaneously or alternatively through a cut-down procedure. Any of these veins can also be occluded using the systems and methods described herein. Imaging such as ultrasound or fluoroscopy, for example, can be used for access assistance. A guidewire (not shown) can then be inserted into the vessel. A sheath or introducer, such as a needle, can also be placed to facilitate catheter entry into the appropriate vein. Next, a delivery catheter 200, including inner catheter member and outer catheter member, as well as housing an occlusion device such as described above can be inserted into the vessel as shown in FIG. 12 via, for example, the Seldinger technique over a guidewire. The catheter 200 is then advanced distally from the access site into the venous system to a desired location, such as within the great saphenous vein (or small saphenous vein or accessory saphenous vein) directly in to a perforating vein as shown in FIG. 13. The inner catheter can then be actuated relative to the outer catheter or needle to deploy an occlusion device 100 to its expanded configuration within the desired location within the vein 400. The occlusion device can in some embodiments include components as described, for example, in U.S. Provisional Application No. 61/154,322, filed on Feb. 20, 2009, and herein incorporated by reference in its entirety, including (but not limited to) those having tissue anchors or bars or other features for engaging vessel walls. In some embodiments, the occlusion device can include components as described with respect to FIGS. 36-44. FIG. 14 illustrates the inner catheter being advanced in preparation to deploy an occlusion/embolization device 100. Once desired placement is confirmed, the detachment mechanism such as a suture (not shown) is then actuated to release the occlusion device 100 within the vessel. Deployed anchors on the frame portion of the occlusion device 100, can prevent migration of the occlusion device 100 from the desired location within the vein 400. Next, the inner catheter can be withdrawn, as illustrated in FIG. 15.
After withdrawal of the inner catheter or dilator, a vein-occluding substance such as described above can be injected through the outer catheter into the vein 400 proximal to the deployed occlusion device. As illustrated in FIG. 16, the outer catheter can then be withdrawn while the vein-occluding substance continues to be injected, in order to occlude the vein in a proximal direction to the access site relative to the occlusion device. The outer catheter can then be fully withdrawn, and an external compression stocking applied, completing the procedure. Percutaneous closure methods can also be utilized in some embodiments. In some embodiments, about 0.01 cc to 1 cc of vein-occluding substance, e.g., a cyanoacrylate compound, can be injected over a distance of about 0.5 cm to 5 cm of vein, such as at least about 0.5 cm, 1 cm, 2 cm, 3 cm, 4 cm, or 5 cm of vein to be treated. The injection rate can be relatively constant throughout the procedure in some embodiments, or variable, releasing periodic boluses of vein-occluding substance at specified time and/or distance intervals. Withdrawal through the vein to be treated can take place, for example, over a period of about 30 seconds to 5 minutes in some embodiments, or about equal to, or less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 minute, 45 seconds, or 30 seconds in some embodiments.
A method of occluding a vein utilizing a vein-occluding substance as an occluding member according to some embodiments will now be described in further detail. First, a catheter can be deployed to a desired location in a tubular structure such as a vein as illustrated and described in connection with FIGS. 12 and 13 above. The vein 400 can then optionally be compressed, either before or after placing the catheter, such as by, for example, external manual compression of the leg or with a tourniquet or other type of compression device at a distal location as shown schematically with arrows in FIG. 17. Next, a vein-occluding substance can be injected at a first location within the vein 400 to serve as an occluder 500, as shown in FIG. 18, to prevent embolization more distally. External compression prior to and at a location just distal to the injection site can advantageously help to prevent migration of the formed in situ occluder 500 prior to polymerization or other fixation process. Compression can also prevent unwanted embolization distally into more central veins, as well as induce retrograde flow of the vein-occluding substance proximally when the vein-occluding substance, upon distal ejection from the catheter, contacts the vein at the point that is collapsed from compression, forcing the vein-occluding substance to flow proximally. In some embodiments, the distance from the exit port on the catheter where the vein-occluding substance is ejected to the area of the vein that is collapsed from compression is no more than about 3 cm, 2.5 cm, 2 cm, 1.5 cm, 1 cm, 0.75 cm, 0.5 cm, 0.25 cm, or less.
The vein-occluding substance serving as an occluder 500 can be, for example, a larger-volume bolus of a vein-occluding substance compared to a volume of vein-occluding substance injected more proximally over a specified period of time and/or length of vein, of which specific ranges are described above. The initial bolus can be at least about 0.1 cc, 0.25 cc, 0.5 cc, 0.75 cc, 1 cc, 1.5 cc, or more in some embodiments, or between about 0.05 mL and about 0.9 mL, between about 0.05 mL and about 0.5 mL, or between about 0.1 mL and about 0.2 mL in other embodiments The initial bolus can be at least about 10%, 25%, 50%, 75%, 100%, 150%, 200%, or more greater than a volume of vein-occluding substance injected more proximally over a similar length of vein.
In addition to, or instead of a large bolus volume of vein-occluding substance as described above, a second vein-occluding substance with different properties than a first vein-occluding substance used to treat the vein more proximally can also be used as an occluder. The second vein occluding substance is deployed first, to form the distal vein block. The first vein occluding substance is then dispensed along the length of the treatment site as the catheter is proximally retracted.
The second vein-occluding substance can be, for example, a glue or other occlusive medium that expands to a greater volume, hardens more rapidly, and/or has a shorter polymerization time relative to the first vein-occluding substance. In some embodiments, the second vein-occluding substance can be partially or completely bioresorbable. If multiple different vein-occluding substances are used, the catheter can be configured to have two or more lumens to accommodate delivery of the different vein-occluding substances. Alternatively the first and second occluding substances can be deployed sequentially via a common lumen.
When the vein-occluding substance serving as a distal occluder hardens such that a plug 500 is formed to completely prevent blood flow distally as shown in FIG. 19, the catheter 200 can be withdrawn and the same or a different vein-occluding substance 502 as described above can be injected along the length of the vein segment to be treated to occlude the rest of the vein 400 to be treated while the catheter is withdrawn partially, and fully proximally as shown in FIGS. 20 and 21, respectively. As illustrated in FIG. 21, in some embodiments, 2, 3, 4, or more veins (that may be in some cases a branch of the first vein) can be treated during the procedure using a single puncture, or with 2, 3, 4, or more punctures.
Thus, in accordance with one implementation of the present invention, a deployment catheter 200 is percutaneously introduced into a vein at an access site, and translumenally distally advanced across a treatment zone within a vein. External compression, such as manual compression, is applied to collapse the vein distally of the deployment catheter and create a first occlusion. A bolus of plug forming media (e.g., the vein occluding media described above) is expressed from the distal end of the catheter against a proximal side of the first occlusion, to form an occlusive plug 500 within the vein. External compression optionally may be removed, or may remain throughout the procedure. The catheter 200 is thereafter proximally retracted while dispensing a vein occluding substance 502 across the treatment zone, either continuously as a long stream, or intermittently at spaced apart intervals, where a second occlusion in the vein can be created, spaced apart from the first occlusion, and then a second bolus of media is introduced against the proximal side of the second occlusion External compression may be applied proximally, anywhere along the length of the vein, to ensure complete filling of the vein with the vein occluding substance 502. In some embodiments, a second, third, or more boluses of plug-forming media are progressively released into the vein more proximally at desired intervals, and external compression can be applied just distal to the point in which the catheter releases the plug forming media as described above. The catheter 200 is thereafter withdrawn, and the access site closed using conventional techniques.
FIG. 21A illustrates a vein 400 that is compressed distally at point 440 to create a first occlusion, such as with external compression. Also shown is catheter 200 with distal end 201. After the creation of an occlusion 440 in a vein, a first volume V1 within the vein 400 can be defined between the distal end 201 of the catheter 200 and the occlusion 440, as illustrated in FIG. 21B. Media having a second volume V2, such as in a bolus, can then be injected from the distal end 201 of the catheter 200 into the vein 400. In some embodiments, the second volume V2 (of the media injected) is at least about 100%, 105%, 110%, 120%, 125%, 130%, 140%, 150%, 175%, 200%, 250%, or more of the first volume V1 (of the vein in between the occlusion and the distal end of the catheter), such that a proximally advancing meniscus of media V2 passes proximally past the distal end 201 of the catheter 200, as illustrated in FIG. 21C. The catheter 200 is then withdrawn proximally, as illustrated in FIG. 21D, and a second more proximal occlusion 440′ can be created, such as via external compression. Media can then be injected to create a volume of media V2′ greater than the volume within the vein 400 between the distal end 201 of the catheter 200 and the occlusion 440′, as illustrated in FIG. 21E. The process can then be repeated for a total of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times depending on the desired clinical result.
In some embodiments, an occlusion in a vein can be created as described herein. A deployment catheter having a distal opening and side wall is provided. The distal end of the deployment catheter can be positioned within the vein at the desired location. Media can then be introduced through the distal opening in a volume sufficient to advance proximally around the catheter between the sidewall of the catheter and the wall of the vein. In some embodiments, the volume sufficient to advance proximally around the catheter between the sidewall of the catheter and the wall of the vein is at least about 0.05 mL, 0.1 mL, 0.2 mL, 0.3 mL, 0.5 mL, 0.7 mL, 0.8 mL, 1 mL, 1.5 mL, 2 mL, 3 mL, or more.
The distal plug 500 may be formed by a bolus of the same material as used for the vein occluding substance 502. Alternatively, the distal plug 500 may be formed from a material that polymerizes more rapidly than vein occluding substance 502, or solidifies through a mechanism other than polymerization to form an occlusive plug. Plug 500 may alternatively be formed by a self-expanding preformed material, such as a foam or woven or non-woven fiber based material, which may be displaced distally from the catheter such as by distally advancing a push wire, or utilizing the pressure of vein occluding substance 502. The self-expanding foam or other plug material 500 may be a bioabsorbable material, so that no long term implant is left behind in the body.
Proximal retraction of the deployment catheter 200 may be accomplished in either a steady, continuous fashion, or in an intermittent, stepped manner. Similarly, extrusion of vein occluding substance 502 may be accomplished in a continuous manner as the catheter 200 is proximally retracted. Alternatively, vein occluding substance 502 may be dispensed in a plurality of bolus ejections along the length of the treatment zone, spaced apart by a predetermined or clinically determined distance. Spacing between adjacent injected volumes of vein occluding substance 502 may be at least about 0.5 cm, at least about 1 cm, at least about 2 cm, and, in some implementations, at least about 4 cm. This procedure minimizes the total volume of injected vein occluding substance 502, while providing a plurality of distinct bonding points along the length of the treatment zone.
Also disclosed herein is a method of obliterating a hollow structure, such as a vein, including the steps of reducing an interior cross-sectional area of the hollow structure near the obliterating site by applying a pressure to an exterior of the hollow structure; and placing a catheter in the hollow structure and advancing it to the obliterating site, where the obliterating site is next to the reduced cross-sectional area. A medical adhesive can then be injected at the obliterating site. The interior cross-sectional area of the medical adhesive at the obliterating site can then be reduced by compressing an exterior of the hollow structure to form an occlusion in the hollow structure. Compression can be achieved, for example, via an imaging probe such as an ultrasound transducer, manual pressure, or a harness. The medical adhesive can then solidify, forming an occlusion in the hollow structure. The method can also include the step of identifying an obliterating site prior to reducing an interior cross-sectional area of the hollow structure. In some embodiments, the catheter is removed from the obliterating site before compression.
With any of the methods and devices described herein, a wide variety of vein-occluding substances can be used. In some embodiments, the substance can include an adhesive such as cyanoacrylate, e.g., 2-octyl cyanoacrylate, and/or a sclerosing agent such as hypertonic saline, sodium tetradecyl sulfate, chromated glycerol, tetracycline, talc, bleomycin, or polydocanol. In some embodiments, a cyanoacrylate can be an aliphatic 2-cyanoacrylate ester such as an alkyl, cycloalkyl, alkenyl or alkoxyalkyl 2-cyanoacrylate ester. The alkyl group may have from 1 to 16 carbon atoms in some embodiments, and can be a C1-C8 alkyl ester or a C1-C4 alkyl ester. Some possible esters include the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, cyclohexyl, heptyl, octyl, 2-methoxyethyl and 2-ethoxyethyl esters of cyanoacrylic acid. Other adhesives that can be used include a biological glue such as a bovine serum albumin-gluteraldehyde combination (e.g., BIOGLUE, Cryolife, Atlanta, Ga.), PVA, Biogard, collagen, fibrinogen, fibronectin, vitronectin, laminin, thrombin, gelatin, mixtures thereof, or other biocompatible adhesives. In some embodiments, a foam generated from, for example, one or more of the above components can be used to enhance ablation and closure of the vein. The viscosity and air bubble mixture can also be controlled while taking into account the desired clinical result.
In one embodiment, the chosen adhesive will not produce a significant thermal effect or significant local tissue abnormal effect, but rather produces an initial vessel co-aption/adhesion which will withstand physiological venous pressures within the immediate post-procedure period. Since the adhesive will not produce a significant thermal reaction, no tumescent anesthesia is needed. In some embodiments, the chosen adhesive induces an inflammatory reaction which scars. The inflammatory reaction can be followed by permanent closure of the abnormal greater or less saphenous vein. In some embodiments, the chosen adhesive is hardened after the first few moments (e.g., seconds or minutes) of application and therefore, compression stockings may not be required. With the chosen adhesive, there can be minimal or no danger to surrounding nerves or tissue. While the amount of chosen adhesive delivered to a target site in a vessel will vary depending on the size of the vessel itself, in some embodiments, the amount of adhesive or other vein-occluding substance delivered in a single injection can be between about 0.05 mL and about 0.9 mL, between about 0.05 mL and about 0.5 mL, or between about 0.1 mL and about 0.2 mL in other embodiments. In some embodiments, the amount delivered in a single injection could be more than about 0.4 mL, 0.6 mL, 0.8 mL, 0.9 mL, 1 mL, or more. In some embodiments, the amount delivered in a single injection could be less than about 0.8 mL, 0.6 mL, 0.4 mL, 0.3 mL, 0.2 mL, 0.1 mL, 0.05 mL, or less.
In some embodiments, the cyanoacrylate preparation will contain any additives necessary to impart the desired properties to the preparation as viscosity, color, X-ray opacity, etc. Certain examples of additives such as thickening agents and polymerization inhibitors are discussed further below.
In some embodiments, the chosen adhesive can also be mixed with a thickening agent, including various cyanoacrylate polymers, cyanoacrylate oligomers and biocompatible polymers. The biocompatible polymers can include, for example, polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolide (PGA) polycaprolactone (PCL), poly-DL-lactide (PDLLA), polyglycolide including D and L glutamate (PLDGA), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), nylon, polyethylene (PE), polypropylene (PP), or polyether ether ketone (PEEK), and in some embodiments, the biocompatible polymers are soluble in a cyanoacrylate monomer. In some embodiments, the thickening agent can comprise glucose, sugar, starch or hydrogel. In some embodiments, the thickening agent can also comprise various particulates, ranging in size between about 0.001 microns to 100 microns. The particulates can be provided in dry solid form and can disperse throughout a liquid adhesive to thicken the adhesive prior to use. In some embodiments, the particulate comprises any of the biocompatible polymers above, such as PLA, PLLA, PGA, PCL, PDLLA, PLDGA, PMMA, PET, nylon, PE, PP, CAB and PEEK, while in other embodiments, the particulate comprises a silica material with or without an acrylic polymer. The thickening agent can assist in providing a suitable viscosity for the adhesive as it flows through the catheter to a target site.
In some embodiments, the chosen adhesive can also be mixed with one or more polymerization inhibitors, which could be, for example, an anionic or a free-radical polymerization inhibitor. Anionic polymerization inhibitors can include soluble acidic gases such as sulfur dioxide, or a biocompatible acid including, but not limited to, acetic acid, sulfuric acid, sulfonic acid, hydrochloric acid, phosphoric acid, carboxylic acid, nitric acid, or combinations thereof. In some embodiments, the acid can be from about 0.01% to about 10% by weight, such as between about 0.01% and 1% by weight. Free-radical polymerization inhibitors include hydroquinone, t-butyl catechol, hydroxyanisole, butylated hydroxyanisole and butylated hydroxytoluene. The addition of one or more polymerization inhibitors such as a biocompatible acid helps to change the curing rate of the adhesive to prevent the adhesive from sticking prematurely to the catheter and prevent premature curing of the adhesive prior to binding to the vein wall. In some embodiments, the acid helps to delay the curing and/or polymerization of the adhesive to prevent the glue from sticking to sections of the catheter.
One skilled in the art will appreciate that multiple compositions of adhesive mixtures can be used in accordance with the embodiments described herein. In one embodiment, a composition of adhesive comprises from about 0.01 to about 50.0 weight percent of cyanoacrylate polymer, from about 0.01 to about 50.0 weight percent of a thickening agent selected from the group consisting of cyanoacrylate polymer, cyanoacrylate oligomer and biocompatible polymers, and from about 0.01 to about 10.0 weight percent of a biocompatible acid.
In some embodiments, the adhesive can also include a therapeutic agent such as an anti-inflammatory agent, an anti-infective agent, an anesthetic, a pro-inflammatory agent, a cell proliferative agent, or combinations thereof.
In some embodiments, the medical adhesives, such as the cyanoacrylate adhesives, can have select properties. In some embodiments, the medical adhesives can have a setting time of between about 5 to 60 seconds. The medical adhesives can also have a viscosity of between about 40 to 3000 cp. In some embodiments, the viscosity could be at least about 500 cp, at least about 1,000 cp, at least about 1,500 cp, at least about 2,000 cp, at least about 2,500 cp, or more. In some embodiments, the viscosity could be no more than about 2,000 cp, no more than about 1,500 cp, no more than about 1,000 cp, no more than about 500 cp, no more than about 300 cp, or less. One skilled in the art will appreciate that the type of adhesive is not limited to these particular characteristics, and that other adhesives having different properties may also be applicable.
Additional Embodiments Related to the Vein Closure System
In additional embodiments, a vein closure system is described that does not require capital purchases for a radiofrequency device or laser box. Simple and non-invasive methods of using the vein closure system are provided, and in some embodiments, the methods do not require application of a tumescent anesthesia or wearing compression stockings. The acceptance by and demand from patients of the vein closure system described herein will be much higher over existing devices and techniques.
In some embodiments, the closure system comprises at least two major components. One is a vein closure device which precisely delivers an adhesive to the abnormal saphenous vein under ultrasound guidance. The other component is a unique intravascular adhesive which allows for co-aptation and closure of the abnormal saphenous vein in a flattened, closed position. In other embodiments, the closure system comprises three major components. The first is a vein closure device which precisely delivers an adhesive to the abnormal saphenous vein under ultrasound guidance. The second is a unique intravascular adhesive which allows for co-aptation and closure of the saphenous vein just distal to the Superficial Femoral Vein Junction, such as within about 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, or less in a flattened, closed position. The third is a solution that can have adhesive and/or sclerosing properties which allows for co-aptation and closure of the rest of the saphenous vein to alter the vein such that blood flow is prevented therein.
The Vein Closure Device
In some embodiments, the vein closure device which delivers the vein-occluding substance, e.g., an embolic adhesive, comprises three components. The first component is an outer catheter or introducer sheath that allows for placement under precise ultrasound guidance into the saphenous vein from as low a position as possible in the greater saphenous vein or lesser saphenous vein. The vein closure device is also configured for precise distal tip placement into the vein to be occluded. In some embodiments, the sheath is available in multiple size ranges and includes an inner diameter (ID) of 3 French (fr) to 7 fr and a length from about 25 cm to 100 cm depending on the placement site. In some embodiments, the sheath is echogenic under ultrasound observation and therefore can be precisely placed below the sapheno-femoral junction. The sheath can have multiple graduations, as well as measurement markings that indicate increments along the sheath, such as 0.2, 1, 2, or 5 cm increments. The graduations and markings assist in providing precise, monitored pull-back motions along the saphenous vein. In some embodiments, a dilator is positioned within the introducer sheath to aid in positioning the device at the treatment site. The dilator may have comparatively greater stiffness than the introducer sheath. Upon advancement to the desired treatment site, the dilator may be removed, followed by advancement of the introduction or inner catheter through the introducer sheath. In some embodiments, the dilator is echogenic under ultrasound observation which may aid in precise placement below the sapheno-femoral junction.
The second portion of the vein closure system is an introduction or inner catheter for the vein-occluding substance or adhesive. The inner catheter can be multiple sizes, such as from 3 fr-7 fr and include lengths of between about 25 cm to 100 cm to match the introduction sheath size ranges. In some embodiments, the inner catheter can be longer than the introduction sheath to allow the inner catheter to extend from a distal end of the introduction sheath. In one embodiment, both the inner catheter and the introducer sheath are made of materials such as polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), perfluoroalkoxy alkane (PFA), fluorinated ethylene propylene (FEP), or similar polymeric materials that will provide for negligible (if any) adhesion to the vein-occluding substance. In some embodiments, the inner catheter has an echogenic tip that assists in advancement through the introducer sheath. The inner catheter can be attached to the introducer sheath, such as by luer lock or other locking mechanism. The inner catheter protrudes from the introduction sheath at its distal end approximately 0.5-10 cm. and is visible under ultrasound due to its echogenic tip. The inner catheter is used for precise delivery of a vein-occluding substance into the vein for co-apting and occluding the vein into a flattened configuration. In some embodiments, the outer catheter and/or inner catheter can be coupled to or extend from a syringe designed to dispense a vein-occluding substance.
Also disclosed herein is a medical device that can include one, two, or more echogenic characteristics for enhanced visualization. For example, one or more of the outer catheter, the dilator, and the inner catheter may be echogenic in certain embodiments, providing for improved visualization under ultrasound. Since sound waves are reflected at junctions of differentiated density, the greater the density difference, the brighter the junction appears on an ultrasound visualization monitor. Since ultrasound waves do not pass easily through gases and are mostly reflected, the presence of gas in the path of ultrasound waves provides for improved visualization. In certain embodiments, to provide a high degree of visualization, the introducer sheath, dilator, and/or the catheter may include a high degree of density differentiation by using gas, such as air. This reflection of ultrasound waves provides a means to visualize the location and allow ease of placement of devices within soft tissue.
Most ultrasound visualization of medical devices involves using metals (such as platinum marker bands or metal wire woven extrusions) or the addition of powders (such as barium sulfate) to extrusions to create density differences between the device and the surrounding tissues. Using a gas, rather than a metal or powder, to create the density differences provides several distinct advantages in certain situations. First, gas can be orders of magnitude less expensive than other ultrasound visualization materials of the same given volume. Even relatively inexpensive metals, such as stainless steel, cannot compete with the low cost of a gas, such as air. Second, gas does not need to be processed into a particular shape; it takes the form of whatever void it is filling. Hence it is more pliable and retains much less embodied energy. This improves the ease of manufacture as well as the final flexibility of the catheter. Third, the density disparity between the gas and the object holding and/or the surrounding tissue is typically greater than that of other visualization methods, thereby allowing the device to reflect more ultrasound waves and providing a clearer or brighter image. Improved ultrasound imaging may facilitate more accurate placement of the device to the desired treatment spot, such as within the greater saphenous vein or other vessels as described herein. Ultrasound can also be advantageous in not carrying the radiation concerns inherent in, for example, fluoroscopy. This gas/solid boundary can be created in any number of ways. Some non-limiting examples follow.
In one embodiment, microlumens containing trapped gas may be formed within the sidewall of the catheter. With reference to FIGS. 22A-22D, catheter 600 includes a catheter wall 602, defining a main or central inner lumen 604, and open proximal and distal ends, or a proximal end with at least one side port for accessing the central inner lumen 604. In certain embodiments, a dilator or a second inner catheter (not shown) may pass through the inner lumen 604 of first (outer) catheter 600. In other embodiments, adhesive may flow through the inner lumen 604 of catheter 600. Within the catheter wall 602 are one or more microlumens 606 which run partially or completely along the length of catheter 600. These microlumens 606 may contain air or any other trapped gas to improve ultrasound visibility. The microlumens 606 may be sealed at the distal tip during the tipping process, and the proximal end may be sealed, such as with adhesive when affixing a luer lock or other connector thereto. In other words, the microlumens could have closed proximal as well as distal ends. Alternatively, only the distal ends may be sealed. The proximal ends may then be left open to atmospheric conditions. In other embodiments, gas may be delivered to the proximal end, whereby the gas is allowed to flow distally from the proximal end, down through the microlumens, and back out the proximal end again. Any other mechanism which permits air to be trapped within the microlumens may be employed. For instance, instead of physical sealing, the microlumens may be tapered at the distal and proximal ends such that the opening is small enough to prevent the entry of fluids due to surface tension. As such, in some embodiments the microlumens could be hermetically sealed, or alternatively having openings of a diameter to allow a gas therethrough, but that is insufficient to permit the entry of a liquid. In alternative embodiments, the catheter may include more than one inner lumen. For example, a configuration in which two separate lumens are arranged within the catheter would permit the delivery of two separate components to the delivery site, where mixing would only occur after each of the components is dispensed from the catheter.
Embedding the microlumens 606 within the catheter wall 602 ensures that they do not interfere with the operation of the catheter or hinder its intravascular mobility. Any raised edge or protruding portion on the outer surface of catheter 600 could potentially increase the likelihood of the catheter being caught or even causing injury to the vasculature during advancement to the treatment site, or during retraction therefrom. Similarly, any protrusion into the inner lumen 604 would potentially inhibit the flow of adhesive or the passage of an inner catheter therethrough. Since embedding the microlumens 606 within the wall 602 maintains both a smooth outer surface and a smooth inner surface, these potential problems may advantageously be avoided.
In certain embodiments, the catheter 600 may include one microlumen 606. Other embodiments may include two, three, four, five, six, or more microlumens embedded within the catheter wall 602. According to some embodiments, the microlumens may run parallel or substantially parallel to the main inner lumen 604 and/or the catheter sidewall 602. In other embodiments, the microlumens may be oriented in another configuration. For instance, the microlumens may spiral helically around the catheter 600, or may form a zig-zag pattern along its length. Other configurations are also possible.
As shown in FIG. 22A, in certain embodiments a plurality of microlumens 606 may be arranged such that they are equally spaced radially within the catheter wall 602. In other embodiments, the microlumens may be arranged in irregularly, or in clusters, as shown in FIG. 22B. The catheter may be formed of any desired material. For instance, the catheter may be formed from a plastic such as PTFE, stainless steel, or other material.
The use of a gas/solid boundary may also be combined with other techniques for improving ultrasound visibility. For instance, as shown in FIG. 22C, a wire 608 that could be made of a metal may be located within each gas-filled microlumen 606. The cross-sectional diameter of the microlumens may vary. For example, in various embodiments, the diameter of the microlumens may be about or less than 50 micrometers (μm), 100 μm, 150 μm, 200 μm, 250 μm, or more. In some embodiments, the diameter of the microlumens may be about or more than about 250 μm, 200 μm, 150 μm, 100 μm, 50 μm, or less. In certain embodiments, each microlumen 606 includes a thin metal wire 608 located within it, the wire 608 having an outer diameter that about or no more than about 90%, 80%, 70%, 60%, 50%, or less of the diameter of the microlumen. In other embodiments, some but not all of the microlumens 606 include metal wires 608 located within. The metal wires 608 may be placed within previously existing microlumens 606, or alternatively the catheter tubing may be extruded directly over the metal wires 608 to enclose them within the microlumens. The metal wire 608 may extend along the entire length of the microlumen 606. Alternatively, the metal wire 608 may only extend along a portion of the microlumen 606.
In some embodiments, the length of the metal wire 608 varies from one microlumen to the next. For instance, a first microlumen may contain a metal wire 608 of a first length. A second microlumen may contain a metal wire 608 of a second length longer than the first length. A third microlumen may contain another metal wire 608 that is longer than the second, and so forth. In certain embodiments, the lengths of the metal wires may be offset from one another by a uniform amount. For instance, a one metal wire may extend the full length of the catheter, while the next metal wire terminates 1 cm short of the distal tip. Another metal wire may terminate 2 cm short of the distal tip, and so forth. The arrangement of several metal wires of subsequently shorter lengths may advantageously provide a means for determining more precisely the location of the catheter within the body. This configuration may aid in determining the position of the catheter within the body.
With reference to FIG. 22D, at least a portion of the catheter sidewall 602 may include first see-through (e.g., transparent or translucent) sections 609 and second opaque sections 608 (in the lower cross-section A-A of the view of catheter 600 in the upper part of FIG. 22D). Providing see-through sections 609 may allow the physician to view fluid within the lumen 604. A series of indicia, e.g., laser markings 611 may be disposed at one, two, or more locations along the axial length of the catheter. The opaque section 608 can provide improved visibility of the markings 611. In various embodiments, the opaque sections 608 can comprise, for example titanium dioxide or a material having a desired color. The laser markings 611 can be spaced apart at regular or irregular intervals permitting the user to judge distances. In some embodiments, the laser markings 611 can be spaced at regular intervals, for example every 3 cm, every 5 cm, or more which can be advantageous in determining locations to release a bolus of a substance within a body lumen. In various embodiments, the laser markings 611 can be spaced irregularly. For example, in the illustrated embodiment, the distal-most laser marking 611 is positioned 3 cm from the distal tip 613, and the second laser marking 611 is positioned 85 cm from the distal tip 613, which can be advantageous positioning, for example, at an appropriate starting location for a procedure to coapt a vein such as the saphenous vein.
With continuing reference to FIG. 22D, the catheter 600 may be outfitted with an atraumatic distal tip 613, which includes an opening of the lumen 604. As described above, in various embodiments some or all of the microlumens 606 may also be open at the distal tip 613. In other embodiments, some or all of the microlumens 606 may be sealed at the distal tip 613. The catheter 600 also includes a strain relief 615, which is adjacent to the proximal hub 617. The hub 617 comprises one or more input ports which can include spin locks. In some embodiments, the spin lock can be a Luer lock consistent with ISO prescribed dimensions, for example as described in ISO 594-1 (First Edition 1986 Jun. 15) and ISO 594-2 (Second Edition 1998 Sep. 1), both of which are hereby incorporated by reference in their entireties. Various other configurations for the hub 617 are possible. For example, the input port could be on the proximal end of the hub 617 as shown coaxial with the longitudinal axis of the catheter. In some embodiments, one or more input ports could be longitudinally offset from the longitudinal axis of the catheter, such as at an angle to the sidewall of the hub.
In another embodiment, a gas/solid boundary may be provided via small holes in a direction either normal or oblique to the longitudinal axis of the catheter. The apertures form microwells that are large enough to hold gas within, but small enough to prevent fluids from entering the hole due to surface tension. As such, a meniscus 612 naturally forms at the boundary of gas and liquid at the surface of the microwell 610. The gas trapped within each microwell provides for increased ultrasound visibility. In exemplary embodiments, the microwells are configured such that gas is retained therein when the catheter is submerged within whole blood. For example, the microwells may be dimensioned so that surface tensions between about 30×10−3 Newtons per meter (N/m) and 80×10−3 N/m, or about 50×10−3 N/m and 64×10−3 N/m prevent liquids from entering the microwells. With reference to FIG. 23, microwells 610 are drilled into the surface of catheter 600. The microwells may be formed by mechanical drilling, laser drilling, chemical etching, or any other means. The microwells may extend partially through the catheter wall 602. In other embodiments, the microwells may extend completely through the catheter wall 602. The microwells 610 may have a cross-section that is circular, elliptical, rectangular, irregular, or any other shape, so long as the surface tension prohibits any, or substantially any liquid, whether bodily fluids or adhesives, from entering the microwell 610. In some embodiments, the cross-sectional area of the microwells may range from 1 μm2 to 1 mm2, from 50 μm2 to 750 μm2, or from 100 μm2 to 500 μm2. In certain embodiments, the cross-sectional area of the microwells may be 1 μm2, 5 μm2, 10 μm2, 25 μm2, 50 μm2, 100 μm2, 500 μm2 or more. In other embodiments, the cross-sectional area of the microwells may be 500 μm2, 100 μm2, 50 μm2, 25 μm2, 10 μm2, 1 μm2, or less.
The microwells 610 may be arranged radially in a regular pattern. For instance, the microwells 610 may be spaced equally radially around the catheter 600. Alternatively, the microwells 610 may be arranged in clusters or irregularly radially around the catheter 600. In addition to the radial orientation, the longitudinal spacing of the microwells may be varied. For instance, the microwells may be oriented in groups arranged circumferentially and spaced apart longitudinally by equal distances. In this configuration, each ring of microwells surrounds the catheter at a given location, and is spaced apart from the longitudinally adjacent ring of microwells by a particular distance. In certain embodiments, the longitudinal distance between adjacent rings of microwells may vary to provide location identification.
In some embodiments, the microwells may have identical sizes. In other embodiments, the cross-sectional dimensions may vary, as may the depth.
In still another embodiment, a gas/solid boundary may be formed via enclosed gas pockets, whether random or otherwise, within the wall of the catheter 600. For instance, as shown in FIG. 24, the catheter may be manufactured with closed cell expanded PTFE (ePTFE), which will contain pockets of air 612 within it, the air pockets being isolated and spaced apart from the central lumen of the catheter. Alternatively, open cell ePTFE may be used in conjunction with an enclosing sheath. Methods of manufacturing ePTFE are well known in the art. Due to its natural resistance to adhesion, ePTFE may facilitate the unimpeded flow of adhesive material through the lumen to the treatment site. The use of enclosed air pockets is not limited to ePTFE, however, but rather any suitable expanded plastic or other material that contains enclosed pockets of air may be used, such as an open or closed cell material, including a sponge material. Additionally, in some embodiments differing materials are used as an outer sheath. One way of accomplishing this would be through the manufacture of closed cell ePTFE or open cell ePTFE with an enclosing sheath.
The enclosed gas pockets may be formed within any suitable material within the catheter. For instance, in some embodiments, a polymer containing gas-filled microspheres may be used to manufacture the catheter. In other embodiments, gas or foaming agents may be injected into a polymer, such as polyurethane, to form a polymeric layer with enclosed gas pockets. Chemical foaming agents that could be added to the plastics material include azodicarbonamides, dinitrosopentamethylene-tetramine, benzenephonohydrazine, 4,4 oxybis(benzenephonohydrazine), NN1dimethyl-NN.sup.1dinitrosoterephthalamide, azobisisobutyronitrile, sodium bicarbonate, terephthalazide or trihydrazinatrazine. Another way of forming the gas pockets would be by incorporating a liquid into the plastics melt which volatizes during the melt process. Alternatively, solid powdered dry ice (carbon dioxide) could be incorporated into the melt so that the particles of dry ice become gas pockets during the forming process. It could be possible to use other solids which undergo sublimation in this way. The gas pockets could be formed directly as a result of chemical reaction during polymerization and or alternatively during cross-linking. The gas pockets could be formed mechanically by whipping the plastics in a liquid form, such as in the manner used to form latex foam. Alternatively, small particles of a soluble material could be added to the plastics melt and subsequently dissolved away.
A protective sheath may surround a polymer with enclosed gas pockets to define the catheter, or in other embodiments no such sheath is required.
The gas pockets in some embodiments extend in a continuous or discontinuous region along the length of the device. The gas pockets may have a dimension, such as a width of between about 0.1 μm to 300 μm, between 1 μm and 50 μm, or between 5 μm and 10 μm. In some embodiments, the width of the gas pockets are 0.1 μm, 5 μm, 10 μm, 50 μm, 300 μm, or more. In other embodiments, the width of the gas pockets are 300 μm, 50 μm, 10 μm, 5 μm, 0.1 μm, or less. In certain embodiments, the enclosed gas pockets are distributed uniformly along the length of the device. In other embodiments, the enclosed gas pockets may be patterned, irregularly distributed, or otherwise within the device.
In each of these aforementioned non-limiting examples, the inclusion of gas regions within the catheter provides for multiple gas/solid boundary regions. As discussed above, each of these boundaries allows for improved ultrasound visibility. With greater visibility and heightened resolution, the location of the catheter within the body may be accurately determined. In particular, the use of such an echogenic catheter may advantageously facilitate precise placement below the sapheno-femoral junction for use in the treatment of venous reflux, such as for injection of an adhesive composition at one, two, or more locations within the vein for example.
Glue Gun and Adapter
The third portion of the vein closure system is the glue gun or other adhesive introducing device that attaches to the inner catheter. In some embodiments, the adhesive introducing device is a manual liquid dispenser gun that can dispense an adhesive into a vessel with control and accuracy. One such dispenser gun is disclosed in U.S. Pat. No. 6,260,737 to Gruendeman et al., which is incorporated by reference herein in its entirety. Other embodiments of the glue gun are discussed in more detail below.
Additional embodiments are provided that are directed to a vein-occluding substance dispenser adapter, such as a glue gun, and associated components. In some embodiments, a glue gun is provided that is mateably attachable to a dispensing catheter or syringe by an adapter. The adapter can advantageously convert, for example, a conventional industrial glue gun for medical use, such as described herein while being properly sterilized as well.
FIGS. 25-35 illustrate a glue gun system configured to assist in the dispensation of a vein-occluding substance, according to some embodiments of the invention. FIG. 25 illustrates a side view of a glue gun and adapter system including an adapter 1, a glue gun 2, and a plunger 3 according to one embodiment. The adapter 1 includes an adapter lock end 4 with collars or flanges 25 that allow the adapter 1 to be fixed to the glue gun 2 via a holding segment 33. The adapter 1 further includes a syringe lock end 5 that allows the adapter 1 to be fixed to a syringe 36.
The glue gun 2 includes a handle 31 and a pull trigger 12. The pull trigger 12 is used in connection with internal mechanisms of the glue gun 2 (shown in FIGS. 36 and 37 and described further below) and the plunger 3 to provide controlled dispensation of a vein-occluding substance through syringe 36.
The plunger 3 comprises a solid rail-like segment that extends from outside the body of the glue gun 2 and through the internal body of the glue gun 2. The plunger 3 includes teeth that work in conjunction with a spring pawl mechanism (shown in FIG. 37) to lock the position of the plunger 3 and provide controlled dispensation of glue. The distal end of the plunger 3 makes contact with the proximal end of the syringe 36 such that the plunger 3 is capable of pushing the syringe to dispense a vein-occluding substance such as an adhesive.
FIG. 26 illustrates a perspective view of the adapter 1 in FIG. 25. The adapter 1 includes an adapter lock end 4, a syringe lock end 5, a holding slot 6 and a hollow body 7.
The adapter lock end 4 includes one or more collars or flanges 25 that are receivable into a holding segment of the dispenser gun upon rotation. The adapter lock end 4 is configured such that upon rotation of the adapter 1, the flanges 25 are received in and secured in the holding segment 33. In addition, the adapter lock end 4 includes an opening or slot (shown in FIG. 28) through which the distal end of the plunger 3 can be inserted.
The syringe lock end 5 includes a holding slot 6 for receiving a syringe 36 and an opening 41 through which the plunger 3 can pass. As shown in FIG. 26, the holding slot 6 is shaped like a barrel-wing. To secure a syringe to the syringe lock end 5, a proximal end of a syringe can be introduced into the holding slot 6. In some embodiments, the proximal end of the syringe can be barrel-wing shaped such that when the syringe is introduced to the syringe lock end 5, the syringe comes into contact with walls 34 of the holding slot 6. The syringe can then be rotated so that it is securely received in the holding slot 6. One skilled in the art will appreciate that the holding slot 6 and the proximal end of the syringe need not be shaped similarly. Nor is it necessary for the holding slot 6 to be barrel-wing shaped; any shape is suitable so long as it can receive a syringe end prior to rotating and securing of the syringe.
The hollow body 7 of the adapter 1 is designed to receive the syringe plunger 3 as it moves transversely substantially along a longitudinal axis of the hollow body 7 during injection. In some embodiments, the length of the hollow body 7 of the adapter is between 2 and 5 inches. The hollow body can be circular, elliptical or any other shape suitable for receiving the plunger 3. The diameter of the hollow body 7 can be, in some embodiments, between 0.5 and 1.1 inches.
FIG. 27 illustrates a front perspective view of the adapter 1 in FIG. 25, including the opening 41 through which the plunger 3 can be received. Also shown are walls 34 of the syringe lock end 5. The walls 34 are shaped such that upon initial entry of a syringe into the syringe lock end 5, surfaces of the syringe 36 are placed into contact with the walls 34. Upon rotation of the syringe 36, the syringe 36 can be locked into place in the holding slots 6.
FIG. 28 illustrates a rear perspective view of the adapter 1 in FIG. 25, including the adapter lock end 4 and flanges 25 receivable in the holding segment 33 of dispenser gun 2. Also illustrated is hole or opening 9 through which the plunger 3 can pass during the injection of vein-occluding substance.
FIG. 29 illustrates a cross-sectional view of the adapter 1 and its hollow body 7. From this view, it is possible to see the adapter 1 as having at least two separate diameters, an inner diameter (formed at the openings to the hollow body 7) and an outer diameter (formed in the hollow body 7 itself). In some embodiments, the inner diameter is between 0.5 and 0.9 inches, while the outer diameter is between 0.7 and 1.1 inches.
FIG. 30 illustrates a side view of a glue gun system including an adapter 1, a glue gun 2, and a plunger 3 according to another embodiment. The system includes an adapter lock end 4 and a syringe lock end 5 having a syringe 36 attached thereto. In contrast to the system in FIG. 25, the glue gun system in FIG. 30 does not include an adapter lock end 4 having an exposed collar or flange that is placed in a holding segment of the gun 2. Instead, the adapter lock end 4 includes a flange 25 (shown in FIG. 32) that mates with the glue gun 2 and remains unexposed upon final assembly.
FIG. 31 illustrates a side view of the glue gun and adapter system of FIG. 30 including the adapter 1, the glue gun 2, the plunger 3, and in addition, a delivery catheter 200. In some embodiments, the delivery catheter 200 includes an outer catheter surrounding an inner catheter. The delivery catheter 200 extends from the distal tip of the syringe 36 and is designed to provide access to a target site within a vessel interior.
FIG. 32 illustrates a perspective view of the adapter 1 in FIG. 30 having an adapter lock end 4, a syringe lock end 5, a hollow body 7 and a fit-in notch 8 located near the adapter lock end 4. The fit-in notch 8 is capable of receiving a mateable collar or flange located on the glue gun 2 that will lock the adapter 1 to the glue gun 2 upon rotation of the adapter.
FIG. 33 illustrates a front perspective view of the adapter 1 of FIG. 30, including the syringe lock end 5. An opening 41 located on the syringe lock end 5 is also shown. The opening 41, which is configured to receive a dispenser plunger 3, is T-shaped in some embodiments, although single slit, “I”, arcuate, or other shaped openings are also possible. The advantage of the T-shaped opening 41 is that it can provide better guidance for a dispenser plunger 3 that is received through the syringe lock end 5, as the T-shaped opening provides specific paths along the “T” shape for the plunger 3 to move. The T shape can also add strength to the plunger 3, such as in the longitudinal direction, for more efficient dispensing. The T shape also could add stability to the plunger 3 in the transverse direction to increase its buckling strength so that it will be less likely to buckle during the dispensing of high viscosity materials.
FIG. 34 illustrates a rear perspective view of the adapter 1 of FIG. 30, including the adapter lock end 4. The adapter lock end 4 includes its own T-shaped opening 9, similar to the T-shaped opening 41 in the syringe lock end 41, through which dispenser plunger 3 can pass.
FIG. 35 illustrates a cross-sectional view of the adapter 1 of FIG. 30 and its hollow body 7. The adapter 1 includes a central lumen 7 with open proximal and/or distal ends and designed to allow the syringe plunger 3 to move through during the injection process. The adapter 1 also can optionally include one, two, or more side lumens 10 defined between walls 70 and 72, which can provide the adapter 1 with a reduced weight, which can be beneficial in some circumstances. In some embodiments, the side lumens 10 define a closed free space volume that is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more of the entire enclosed volume between walls 70, 72. By providing an adapter with reduced weight, this allows for improved handling, reduced weight, and cost efficiencies for manufacturing purposes. In other embodiments, the adapter 1 can include regions besides or in addition to the second hollow space 10 that are removed or cut-out of the adapter 1 to provide additional weight reduction.
FIG. 36 illustrates an adapter 1 and glue gun 2 prior to assembly. In some embodiments, the glue gun 2 includes extensions 66 that enclose an open space 67 for receiving the adapter lock end 4 of the adapter 1. While the adapter lock end 4 is placed in the open space 67, the extensions 66 of the glue gun 2 enclose the fit-in notch 8 of the adapter 1, thereby forming a secure connection between the adapter 1 and glue gun 2, as shown in FIG. 37.
FIG. 37 illustrates the adapter 1 and glue gun 2 of FIG. 36 following assembly. Included in the assembly within the hollow body 17 of the glue gun are plunger 3 with teeth 16, stopper 11, spring mechanism 15 including spring pin 13 and spring pawl 14, plunger release button 18, floating gripper 19, plunger pocket 20 and spring stop 21.
As shown in FIG. 37, the assembly includes a glue gun 2 having a trigger 12 for controlling the dispensation of glue from the gun. The trigger 12 of the glue gun is integrated with the gun body by a spring pin 13, which is part of a spring mechanism 15. The spring mechanism 15 also includes a spring pawl 14 designed to interact with teeth 16 of the plunger 3 to precisely lock the position of the plunger. Movement of the spring pawl 14 is controlled by the trigger 12. Upon pressing or clicking of the trigger, the spring pawl 14 is adjusted to allow one or more teeth 16 of the plunger 3 to move forward through the adapter 1 and press against a syringe (not shown) to dispense a glue or adhesive. To prevent the rearward movement of the plunger 3 after clicking the trigger, a floating gripper 19 is provided that engages with the plunger 3 to stop rearward movement by frictional force. Plunger pocket 20 can allow movement (both forward and backward) of floating gripper 19 in the pocket. During the forward movement of the plunger 3, the floating gripper 19 moves with the plunger 3 (because of the friction between them) assisted by the plunger pocket 20. After the trigger is released and the plunger 3 (with the floating gripper 19) moves backward, the plunger pocket 20 sets the limit for the movement of the plunger 3. The plunger release button 18 allows the disengagement between the plunger 3 and the spring pawl 14. Pushing the plunger release button 18 will move the spring pawl 14 downward and release the plunger 3 from the spring pawl 14. Then the plunger 3 will be free to move in either backward or forward directions.
To limit the effect of the spring mechanism 15 and restrict the forward displacement of the plunger teeth 16, the spring mechanism 15 is accompanied by a stopper 11. The stopper 11 serves as a physical barrier to the movement of the spring mechanism, thereby providing for greater control over dispensation of the glue or adhesive.
FIG. 38 is a front view of the glue gun 2 that illustrates the gun hollow body 17. Among the mechanisms within the gun hollow body 17 includes the plunger 3, which is displaced within the hollow body by the pull of the gun trigger.
The embodiments of the glue gun system described in FIGS. 25-38 are designed to deliver precise amounts of adhesive or similar vein-occluding substance and can be used with the methods described above. By providing greater control over the dispensation of vein-occluding substance, such as by using a spring mechanism 15 including spring pawl 14 and stopper 11, the glue gun system can deliver the vein-occluding substance continuously or in discrete injectable quantities, such as 0.1 ml to 1.0 ml per injection, thereby advantageously reducing the risk of overflow and back-clogging of the delivery system. The amount of vein-occluding substance used can depend on the size of the vein, the compression pressure, and surrounding environment. The glue gun will allow for exact increments of adhesive to be extruded or discharged from a catheter. This will allow a vein to be sealed shut at multiple sites along its length.
Perforator Vein Therapy
Perforator veins, sometimes referred to as ‘perforators,’ perforate the deep fascia of muscles, to connect the superficial veins to the deep veins where they drain. FIG. 39 illustrates schematically a perforator vein 700 connecting a superficial vein 702 to a deep vein 704, and the skin surface 703 for reference. Perforator veins typically each have about one, two, or three bicuspid one-way valves 701 that prevent blood flowing back (reflux), from deep to superficial veins in muscular systole. The one-way blood flow through the perforators is also maintained by an oblique course of the perforators through the muscle and aponeurosis. Perforator veins exist along the length of the leg, in greater number in the calf (below the knee) than in the thigh (above the knee). Some perforator veins are named after the physician who first described them: Dodd's perforator at the inferior 1⁄3 of the thigh; Boyd's perforator at the knee level; and Cockett's perforators at the inferior 2⁄3 of the leg (usually there are three: superior medium and inferior Cockett perforators). Other perforator veins carry the name of the deep vein where they drain, such as the medial gastrocnemius perforator, draining into the gastrocnemius vein; and fibular perforators, usually two, one superior near the lateral aspect of the knee and one inferior at the lateral aspect of the ankle Peroneal perforator veins, also referred to as ‘lateral calf perforators,’ are found 5-7 cm (Bassi's veins) and 12-14 cm from the lateral ankle. The peroneal perforators connect the lesser saphenous veins with peroneal veins.
Perforator veins can also be classified by their topography. The perforators of the foot (venae perforantes pedis) are divided into dorsal foot perforators, with their equivalent term intercapitular veins, medial foot perforators, lateral foot perforators, and plantar foot perforators, according to their location. The ankle perforators (venae perforantis tarsalis) are designated in medial ankle perforators, anterior ankle perforators, and lateral ankle perforators, according to their topography. The perforators of the leg (venae perforantes cruris) are divided in four main groups. The perforators of the medial leg are designated as paratibial and posterior tibial. Paratibial perforators connect the main trunk or tributaries of the great saphenous vein with the posterior tibial veins and course close to the medial surface of the tibia. These correspond to the so-called Sherman perforator veins (at the lower and mid leg) and Boyd perforator veins (at the upper leg). Posterior tibial perforators (Cockett perforators—upper, middle, and lower) connect the posterior accessory great saphenous vein with the posterior tibial veins. These correspond to the so-called Cockett perforator veins. The anterior leg perforators pierce the anterior tibial compartment and connect the anterior tributaries of the great saphenous vein to the anterior tibial veins. The lateral leg perforators connect veins of the lateral venous plexus with the fibular veins. The perforators of the posterior leg are divided into medial gastrocnemius perforators (in the medial calf), lateral gastrocnemius perforators (in the lateral calf), intergemellar perforators (connecting the small saphenous vein with the calf veins, also called “mid-calf perforator of May”), para-Achillean perforators (connecting the small saphenous vein with the fibular veins; also called “perforator of Bassi”). The perforators of the knee (venae perforantes genus) are designated as medial knee perforators, suprapatellar perforators, lateral knee perforators, infrapatellar perforators, popliteal fossa perforators, according to their location. The perforators of the thigh (venae perforantes femoris) are grouped on the basis of their topography. On the medial thigh are the perforators of the femoral canal (Dodd) and the inguinal perforators, which connect the GSV (or its tributaries) with the femoral vein at the groin. The anterior thigh perforators pierce the quadriceps femoris. The lateral thigh perforators pierce the lateral muscles of the thigh. On the posterior thigh, perforators are designated as posteromedial thigh perforators (those piercing the adductor muscles), sciatic perforators (lying along the midline of the posterior thigh), posterolateral thigh perforators (those piercing the biceps femoris and semitendinosus muscles, also called “perforator of Hach”), and pudendal perforators. The perforators of the gluteal muscles (venae perforantes glutealis) are divided in superior, mid, and lower perforators. Any number or combination of the aforementioned perforator veins can be treating using systems and methods as disclosed herein.
Incompetent perforator veins can result in significant morbidity, above and beyond pathology of other lower extremity veins, such as the great or small saphenous veins. When the valves of perforator veins become incompetent, they can cause or exacerbate venous insufficiency. The resulting perforator vein reflux can cause a rapid deterioration in an existing varicose vein disease state and be responsible for the development of venous ulcers. It has been reported that patients with recurrent varicose veins may have a higher prevalence and a greater quantitative number of incompetent perforators compared with patients with primary varicose vein disease. When they are incompetent, perforator veins can reach diameters of 5 mm or more and can have large volume flow, feeding an array of varicose veins above the fascial layer of the muscle. The gaiter areas of the leg are the areas where skin changes and venous stasis ulcers are likely to occur, and are also where prominent perforator veins may likely be found. Perforator vein incompetence in these gaiter areas have been shown to increase ambulatory venous pressures above 100 mm Hg or more (venous hypertension), a phenomenon which has also been referred to “ankle blow-out” syndrome in the gaiter areas. The combination of incompetent perforator veins and resultant venous hypertension over time causes damage to capillaries in the skin and subcutaneous capillaries, allowing protein-rich fluid and red blood cells to escape into the subcutaneous tissue around the ankle. As such, the subcutaneous tissue becomes fibrotic and skin pigmentation results from hemosiderin deposition.
A primary goal of treating symptomatic venous reflux is to eliminate the reflux at its source, such as, for example, the great saphenous vein. If a diseased vein is either closed or removed, blood can automatically reroute into other veins without any negative consequences to the patient. The perforator veins of the leg can, however, still be the source of symptoms despite great or small saphenous vein occlusion. Because of anatomic and physiologic differences, treatment protocols for incompetent perforator veins can be different from that of, for example, the great or small saphenous vein, including systems and methods that are disclosed herein.
Disclosed are embodiments of a catheter system for the treatment of incompetent perforator veins. The system can include a perforator catheter assembly, an extension tubing, and media for occluding and/or coapting the perforator vein (e.g., a single component medical grade cyanoacrylate as described elsewhere herein). FIG. 40A illustrates a perforator catheter assembly 800, including a proximal end 810 having a proximal hub 802, a distal end 808, and an elongate tubular body 806. The proximal hub 802 can be operably connected or attached, such as overmolded in some embodiments onto the elongate body 806 of the catheter 800. In some embodiments, the proximal hub 802 can be integrally formed with the elongate body 806. The catheter assembly 800 can include a spin lock 804 thereon, such as on a distal part of the proximal hub 802. The proximal end 810 can also include a central lumen 812 from the proximal end 810 to the distal end 808 for withdrawal of blood and/or infusion of a media, such as a cyanoacrylate media, into the perforator vein. The catheter assembly 800 and the hub 802 can be made of any appropriate material, such as polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE) for the catheter assembly 802 and high density polyurethane (HDPE) for the hub, for example.
FIG. 40B is a cross-sectional view through line A-A of FIG. 40A, illustrating the proximal end 810 of the catheter 800, and the central lumen 812, which may have a first proximal diameter, a transition tapered diameter, and a second distal diameter that is less than that of the proximal diameter as illustrated. In some embodiments, the catheter can have a length of between about 3 inches and about 6 inches, or between about 4 inches and about 5 inches, such as about 4.3 inches for example. In some embodiments, the catheter body 806 can have an outer diameter of between about 0.02 inches and about 0.03 inches, such as about 0.024 inches, and an inner diameter of between about 0.01 inches and about 0.02 inches, such as about 0.014 inches.
FIG. 40C illustrates a perspective view of the hub 802 which can be overmolded as described, without the elongate catheter body present. FIG. 40D illustrates a cross-sectional view of the spin lock 804 having a threaded sidewall 837. FIG. 40E illustrates a cross-sectional view through the proximal hub 802 having a luer lock, and illustrating section 814 in which the hub 802 can be overmolded onto the catheter extrusion 806. FIG. 40F illustrates an end view of the proximal end 843 of the hub 802, while FIG. 40G illustrates an end view of the distal end 841 of the hub 802.
FIG. 40H illustrates a distal portion of the catheter assembly 800, illustrating the catheter body 806 gradually tapering at transition point 807 from a first, proximal larger diameter to a second, distal smaller diameter at the distal tip 808. The distal tip 808 and/or other regions of the catheter assembly 800 may include echogenic features such as microlumens for example, as illustrated, for example, in FIG. 22A-24 above and the accompanying text.
FIG. 40I illustrates a proximal portion of the catheter body 806 including proximal end 811, which may optionally be flared and which can advantageously interface with the overmolded hub (not shown).
FIG. 41A illustrates an embodiment of an extension tubing 820, the distal end of which can be configured to reversibly mate with the proximal end of the catheter assembly (not shown). The extension tubing 820 can include a proximal hub 822, an elongate tubular body 824, a distal hub 826, and a spin lock 828 proximate the distal hub 826. Also shown is the central lumen 829 which can, for example, extend throughout the length of the extension tubing 820. FIG. 41B is a cross-section through line A-A of FIG. 41A, illustrating the distal end 827 of the extension tubing 820 in which the distal hub 826 can be overmolded or otherwise attached to the tubular body 824, having an optional flared end 825. FIG. 41C is a cross-section through line B-B of FIG. 41B, illustrating the proximal end 823 of extension tubing 820, in which the proximal hub 822 can be overmolded or otherwise attached to the tubular body 824, having flared end 825. In some embodiments, the extension tubing can have an axial length of between about 12 inches and 18 inches, or about 16 inches, or about 15.7 inches. FIG. 41D illustrates schematically a flared end 825 (e.g., proximal end or distal end) of the tubular body 824 segment of the extension tubing, which can advantageously interface with the overmolded hub (not shown). In some embodiments, the elongate body 824 of the extension tubing 820 can have an outer diameter of between about 0.05 inches and about 0.10 inches, such as about 0.072 inches, and an inner diameter of between about 0.02 inches and about 0.05 inches, such as about 0.037 inches.
FIG. 41E illustrates a perspective view of a distal (e.g., male) hub 826 with a spin lock 828 thereon. The distal hub 826 can be configured to be reversibly connected to the proximal end of the catheter assembly, as previously described, and have a luer lock configuration. In some embodiments, the distal hub 826 of the extension tubing 820 can be the same or similar in configuration to that of the proximal hub 802 of the catheter assembly previously described. FIG. 41F illustrates a cross-section of spin lock 828 including threaded sidewall 829. FIG. 41G illustrates a cross-section of the distal hub 826 and section 831 that can be overmolded or otherwise attached to the tubular body 826 of the extension tubing 820 (not shown). FIG. 41H illustrates an end view of the proximal end 861 of the distal hub 826, while FIG. 41I illustrates an end view of the distal end 863 of the distal hub 826.
FIG. 41J illustrates a cross-section of proximal (e.g., female) hub 822, illustrating section 867 that can be overmolded or otherwise attached to the tubular body 826 of the extension tubing 820 (not shown). FIG. 41K illustrates an end view of the proximal end 873 of the proximal hub 822, which can be connected, such as via a luer connection to an injector, such as a syringe operably attached to a dispenser gun (not shown). FIG. 41L illustrates an end view of the distal end 873 of the proximal hub 822 which can be, e.g., overmolded to the tubular body 826 of the extension tubing as previously described.
Methods of treating a perforator vein will now be described, according to some embodiments of the invention. The patient is prepped using sterile technique, and local and/or topical anesthetic can be applied to the patient to the patient's skin and/or subcutaneous tissue. A needle can be advanced, e.g., percutaneously, toward a perforator vein of interest. The needle can cannulate the desired perforator vein or other vessel, using ultrasound or other imaging or visualization methods. Access can be confirmed, for example, by the appearance of venous blood return into the needle (for a perforator or other vein), and visualization of the needle location, such as under ultrasound. After cannulation of the perforator vein (not shown) is confirmed, the needle can be detached from the syringe and held in place. In some embodiments, a guidewire is optionally threaded through the needle to maintain positioning, the needle is removed, and a dilator and/or sheath positioned in the perforator vein. In some embodiments the needle is left in place in the perforator and a small diameter catheter is inserted into the needle enabling direct injection of a media such as cyanoacrylate.
FIG. 42A schematically illustrates a syringe 900 reversibly connected to a needle 902 (e.g., a 14 gauge needle), and drawing up an amount of media, such as a vein-coapting media (e.g., a sterile single-component medical grade cyanoacrylate media 904 as described elsewhere herein). As shown schematically in FIG. 42B, the syringe plunger can be depressed slightly to eliminate air, and the syringe 900 detached from the needle 902 and removed, as shown in FIGS. 43A and 43B. In some embodiments, the syringe 900 can be pre-filled with media by the manufacturer. The distal end of the syringe 900 filled with media can then be attached to the proximal hub 822 of the extension tubing 820, e.g., via luer fittings. The distal hub 826 of the extension tubing 820 can be attached to the proximal hub 802 of the catheter assembly 800.
As illustrated schematically in FIG. 44A, the proximal end of the syringe 900 filled with media can be inserted into slot 909 at the distal end 911 of the syringe receiver 907 portion of the dispenser gun 908, which can include features of dispenser guns as described and illustrated in connection with FIGS. 25-38. In some embodiments, the dispenser gun is configured to allow the release of, for example, about 0.01 cc to about 0.10 cc, or about 0.05 cc of media per actuation.
As shown in FIG. 44B and the associated detail view of FIG. 44C, the syringe 900 can be rotated to an appropriate position, such as by, for example, 45, 60, or 90 degrees, to secure the flanges 905 of the syringe 900 within the partially circumferential slot 909 of the distal end 911 of the syringe receiver 907 portion of the dispenser gun 908, as previously described in connection with FIGS. 25-38.
As illustrated schematically in FIG. 45A, the dispenser gun 908, media-filled syringe 900, extension tubing 820, and catheter assembly 800 may all be connected together in that order, and the extension tubing 820 and catheter assembly 800 primed with media by actuating the control, e.g., trigger 920 of the dispenser gun 908 prior to connection to the perforator vein access needle (not shown). As illustrated in FIG. 45B, if excess media extends out the distal end 808 of the catheter assembly 800 after priming, it can be wiped off using any appropriate material and/or technique, such as via gauze 930, for example. In addition, the syringe plunger can be withdrawn proximally if over-priming occurs such that excess media no longer extends out the distal end 808 of the catheter assembly 800. In some embodiments, the dispenser control can be configured with a first actuation setting such that a volume of media is released sufficient to coapt the perforator vein and a second setting such that a relatively greater volume of media is released sufficient to prime the extension tubing and the catheter assembly. FIG. 45C illustrates the distal end 808 and tubular body 806 of the catheter assembly 800 inserted through the access needle, and secured in place via the spin lock 804. Also illustrated is ultrasound transducer 930, which may optionally be used to aid in visualizing the methods as described herein. As shown in FIG. 45D, the dispenser gun 908 is actuated such as by depressing the trigger 920, allowing media, such as a single bolus of between about 0.01 cc and about 0.10 cc, or about 0.05 cc of media to flow from the media-filled syringe 900 (or other volumes as described elsewhere herein), distally through the extension tubing 820 and catheter assembly 800 into the perforator vein, such as at or in the vicinity of the proximal end, midpoint, or distal end of the perforator vein, or in the vicinity or at the location of a perforator vein valve. In some embodiments, the media does not flow substantially, or does not flow at all into the adjacent superficial or deep veins of which the perforator vein of interest connects. As shown in FIGS. 45E and 45F, the needle and catheter assembly can then be removed, and pressure applied (such as manual pressure for example) for a desired time period, e.g., about 1-5 minutes, or about 3 minutes. FIG. 45G illustrates that ultrasound 930 or another imaging modality can be used to confirm occlusion of the perforator vein. The process can then be repeated for any desired number of perforator veins or other veins during the same or a follow-up procedure, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times.
It is contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments disclosed above may be made and still fall within one or more of the inventions. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an embodiment can be used in all other embodiments set forth herein. Accordingly, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed inventions. Thus, it is intended that the scope of the present inventions herein disclosed should not be limited by the particular disclosed embodiments described above. Moreover, while the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “inserting a catheter assembly into a perforator vein” include “instructing the inserting of a catheter assembly into a perforator vein.” The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “approximately”, “about”, and “substantially” as used herein include the recited numbers, and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount.

## Claims

1. A method of treating a vein, the method comprising:
advancing an access needle percutaneously into a perforator vein in a patient under ultrasound guidance;
advancing a portion of a catheter assembly through the access needle and into the perforator vein;
injecting a volume of media comprising cyanoacrylate through the catheter assembly into the perforator vein such that the media substantially does not flow into adjacent superficial or deep veins, the volume of media being sufficient to coapt the perforator vein;
withdrawing the needle and catheter from the perforator vein; and applying external pressure sufficient to coapt the perforator vein.

2. The method of claim 1, further comprising confirming coaptation of the perforator vein under ultrasound guidance.

3. The method of claim 1, wherein the catheter assembly is operably connected at a proximal end to an extension tubing, wherein the extension tubing is operably connected at a proximal end to a media-filled syringe.

4. The method of claim 3, wherein the media-filled syringe is operably connected to an injector configured to automatically dispense a bolus of about 0.05 cubic centimeters (cc) of the media from the syringe upon actuation of a control on the injector.

5. The method of claim 1, wherein the volume of media is between about 0.01 cubic centimeters (cc) and about 0.10 cc.

6. The method of claim 1, wherein the volume of media is about 0.05 cubic centimeters (cc).

7. The method of claim 1, wherein the catheter assembly is operably connected at a proximal end to an extension tubing, the method further comprising priming the extension tubing and catheter assembly with the media prior to the injecting step.