Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
  • A61B17/00234—Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
  • A61B8/12—Diagnosis using ultrasonic, sonic or infrasonic waves in body cavities or body tracts, e.g. by using catheters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
  • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
  • A61B18/14—Probes or electrodes therefor
  • A61B18/1492—Probes or electrodes therefor having a flexible, catheter-like structure, e.g. for heart ablation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
  • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
  • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
  • A61B18/24—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
  • A61B17/11—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis
  • A61B2017/1139—Side-to-side connections, e.g. shunt or X-connections
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
  • A61B17/34—Trocars; Puncturing needles
  • A61B2017/348—Means for supporting the trocar against the body or retaining the trocar inside the body
  • A61B2017/3482—Means for supporting the trocar against the body or retaining the trocar inside the body inside
  • A61B2017/3484—Anchoring means, e.g. spreading-out umbrella-like structure
  • A61B2017/3486—Balloon
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
  • A61F2/02—Prostheses implantable into the body
  • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
  • A61F2002/043—Bronchi

Definitions

• the methods and devices create channels in lung tissue and maintain the patency of these surgically created channels in tissue. Maintaining the patency of the channels allows air to pass directly out of the lung tissue which facilitates the exchange of oxygen ultimately into the blood and/or decompresses hyper-inflated lungs.
• COPD chronic obstructive pulmonary disease
• COPD chronic obstructive pulmonary disease
• ALA estimated that COPD was the fourth-ranking cause of death in the U.S.
• the ALA estimates that about 14 million and 2 million Americans suffer from emphysema and chronic bronchitis respectively.
• Those inflicted with COPD face disabilities due to the limited pulmonary functions. Usually, individuals afflicted by COPD also face loss in muscle strength and an inability to perform common daily activities. Often, those patients desiring treatment for COPD seek a physician at a point where the disease is advanced.
• the primary function of the lungs is to permit the exchange of two gasses by removing carbon dioxide from arterial blood and replacing it with oxygen.
• the lungs provide a blood gas interface.
• the oxygen and carbon dioxide move between the gas (air) and blood by diffusion. This diffusion is possible since the blood is delivered to one side of the blood-gas interface via small blood vessels (capillaries).
• the capillaries are wrapped around numerous air sacs called alveoli which function as the blood-gas interface.
• a typical human lung contains about 300 million alveoli.
• the air is brought to the other side of this blood-gas interface by a natural respiratory airway, hereafter referred to as a natural airway or airway, consisting of branching tubes which become narrower, shorter, and more numerous as they penetrate deeper into the lung.
• a natural respiratory airway hereafter referred to as a natural airway or airway
• branching tubes which become narrower, shorter, and more numerous as they penetrate deeper into the lung.
• the airway begins with the trachea which branches into the left and right bronchi which divide into lobar, then segmental bronchi.
• the branching continues down to the terminal bronchioles which lead to the alveoli. Plates of cartilage may be found as part of the walls throughout most of the airway from the trachea to the bronchi. The cartilage plates become less prevalent as the airways branch.
• the bronchi and bronchioles may be distinguished as the bronchi lie proximal to the last plate of cartilage found along the airway, while the bronchiole lies distal to the last plate of cartilage.
• the bronchioles are the smallest airways that do not contain alveoli.
• the function of the bronchi and bronchioles is to provide conducting airways that lead air to and from the gas-blood interface. However, these conducting airways do not take part in gas exchange because they do not contain alveoli. Rather, the gas exchange takes place in the alveoli which are found in the distal most end of the airways.
• the mechanics of breathing include the lungs, the rib cage, the diaphragm and abdominal wall.
• inspiratory muscles contract increasing the volume of the chest cavity.
• the pleural pressure the pressure within the chest cavity, becomes sub- atmospheric. Consequently, air flows into the lungs and the lungs expand.
• the inspiratory muscles relax and the lungs begin to recoil and reduce in size.
• the lungs recoil because they contain elastic fibers that allow for expansion, as the lungs inflate, and relaxation, as the lungs deflate, with each breath. This characteristic is called elastic recoil.
• the recoil of the lungs causes alveolar pressure to exceed atmospheric pressure causing air to flow out of the lungs and deflate the lungs. 'If the lungs' ability to recoil is damaged, the lungs cannot contract and reduce in size from their inflated state. As a result, the lungs cannot evacuate all of the inspired air.
• the lung's elastic fibers also assist in keeping small airways open during the exhalation cycle. This effect is also known as "tethering" of the airways. Tethering is desirable since small airways do not contain cartilage that would otherwise provide structural rigidity for these airways. Without tethering, and in the absence of structural rigidity, the small airways collapse during exhalation and prevent air from exiting thereby trapping air within the lung.
• Emphysema is characterized by irreversible biochemical destruction of the alveolar walls that contain the elastic fibers, called elastin, described above. The destruction of the alveolar walls results in a dual problem of reduction of elastic recoil and the loss of tethering of the airways.
• Chronic bronchitis is characterized by excessive mucus production in the bronchial tree. Usually there is a general increase in bulk (hypertrophy) of the large bronchi and chronic inflammatory changes in the small airways. Excessive amounts of mucus are found in the airways and semisolid plugs of this mucus may occlude some small bronchi. Also, the small airways are usually narrowed and show inflammatory changes.
• bronchodilator drugs relax and widen the air passages thereby reducing the residual volume and increasing gas flow permitting more oxygen to enter the lungs.
• bronchodilator drugs are only effective for a short period of time and require repeated application.
• the bronchodilator drugs are only effective in a certain percentage of the population of those diagnosed with COPD.
• patients suffering from COPD are given supplemental oxygen to assist in breathing.
• the oxygen is only partially functional and does not eliminate the effects of the COPD.
• Lung volume reduction surgery is a procedure which removes portions of the lung that are over-inflated.
• the portion of the lung that remains has relatively better elastic recoil, providing reduced airway obstruction.
• the reduced lung volume also improves the efficiency of the respiratory muscles.
• lung reduction surgery is an extremely traumatic procedure which involves opening the chest and thoracic cavity to remove a portion of the lung. As such, the procedure involves an extended recovery period. Hence, the long term benefits of this surgery are still being evaluated.
• lung reduction surgery is sought in those cases of emphysema where only a portion of the lung is emphysematous as opposed to the case where the entire lung is emphysematous.
• the lung is only partially emphysematous, removal of a portion of emphysematous lung which was compressing healthier portions of the lung allows the healthier portions to expand, increasing the overall efficiency of the lung.
• the entire lung is emphysematous, however, removal of a portion of the lung removes gas exchanging alveolar surfaces, reducing the overall efficiency of the lung. Lung volume reduction surgery is thus not a practical solution for treatment of emphysema where the entire lung is diseased.
• Drug eluting coronary-type stents are not known to overcome the above mentioned events because these stents are often substantially cylindrical (or otherwise have a shape that conforms to the shape of a tubular blood vessel). Hence, they may slide and eject from surgically created openings in an airway wall leading to rapid closure of any channel. Additionally, the design and structure of the coronary- type stents reflect the fact that these stents operate in an environment that contains different tissues when compared to the airways not to mention an environment where there is a constant flow of blood against the stent. Moreover, the design of coronary stents also acknowledges the need to avoid partial re-stenosis of the vessel after stent placement.
• implants suited for placement in the coronary are often designed to account for factors that may be insignificant when considering a device for the airways.
• experiments in animal models found that placement of a paclitaxel drug eluting vascular stent into the opening did not yield positive results in maintaining the patency of the opening.
• the shortcomings were both in the physical structure of the stent along with the failure to control the healing cascade caused by creation of the channel.
• An understanding of the distinctions between the healing response in the coronary versus the airways may explain this outcome.
• the healing response in both the coronary and the lungs may be divided into approximately four stages as measured relative to the time of the injury: 1) acute phase; 2) sub-chronic phase; 3) chronic phase; and 4) late phase.
• the healing process begins in the acute phase with thrombus and acute inflammation.
• the sub-chronic phase there is an organization of the thrombus, an acute/chronic inflammation and early neointima hyperplasia.
• chronic phase there is a proliferation of smooth muscle cells along with chronic inflammation and adventitial thickening.
• the healing response in the airway begins with a fibrinous clot, edema hemorrhage, and fibrin deposition, hi the sub-chronic phase there is re-epithelialization, mucosal hypertrophy, squamous metaplasia, fibroplasias and fibrosus.
• the chronic phase while the epithelium is intact and there is less mucosal hypertrophy, there is still fibroplasia and fibrosis.
• the respiratory epithelium is intact and there is evidence of a scar.
• the invention includes methods and devices for treating a lung suspected of having chronic obstructive pulmonary disease through the creation of collateral channels.
• the invention also includes extending the duration during which these channels remain open (e.g., maintaining patency.)
• the invention includes a method comprising selecting a treatment site in an airway of the lung, creating a hole in an airway wall of the airway; and expanding the hole in the airway wall.
• Selecting the treatment site may include visual inspection of the site or inspection for the presence or absence of a blood vessel underneath the surface of the airway wall.
• Selection of the site may be performed or aided by non-invasive imaging.
• imaging may include x-ray, ultrasound, Doppler, acoustic, MRI, PET, and computed tomography (CT) scans.
• CT computed tomography
• a substance may be administered into the lungs to assist in the selection of the treatment site.
• the substance may comprise a hyperpolarized gas, a thermochromatic dye, a regular dye, and/or a contrast agent.
• Variations of the invention include the use of a less-traumatic holemaker for creation of the channel (note that a channel includes a hole that is created and subsequently expanded.)
• the less traumatic holemaker may include a piercing member (e.g., a needle, a cannula, a blade, a tube, a rod or other similar structure).
• the less traumatic holemaker may also include devices which minimize the collateral damage to tissue (e.g., low temperature RF devices, pulsating RF, low temperature laser, ultrasound, high pressure water, etc.) [0027]
• the devices and methods prevent closure of the channel such that air may flow through the channel and into the airway.
• Such channels may be made by a variety of methods as discussed in the patents incorporated by reference above.
• the channel may be made via a surgical incision, a needle, a rotary coring device, etc.
• the channel may be made by an energy based device, e.g., RF device, laser, etc.
• an energy based device e.g., RF device, laser, etc.
• use of low temperature devices, e.g., mechanical devices to create the channel result in less trauma to surrounding tissue and thereby minimize the healing response of the tissue. Accordingly, such modes of creating the channel often result in less occlusion of the channel.
• the method includes expanding the hole by inserting a conduit into the hole. Furthermore, the method may comprise partially expanding the hole by deploying the conduit in the hole, and then fully expanding the hole by expanding the conduit within the hole.
• Preventing closure may be performed using various approaches including, but not limited to, biochemical, electrical, thermal, irradiation, or mechanical approaches (or any combination thereof).
• the method may also include delivering a bio-active composition, as described herein, to maintain patency of the channel or conduit.
• the bio-active composition may be delivered to the airway wall prior to creation of the channel, subsequent to creation of the channel, and/or after insertion and deployment of the conduit.
• the bio-active composition may also be delivered through a drug eluting process, either through a composition placed on the conduit, or via delivery of a separate eluting substance.
• Biochemical approaches include delivery of medicines that inhibit closure of the surgically created channel. The medicines may be delivered locally or systematically.
• a delivery catheter includes a dispense lumen that sends a drug to the target site.
• bioactive substances may be delivered to the channel tissue using various delivery vehicles such as a conduit.
• the bioactive substance may be disposed on an exterior surface of the conduit such that it interacts with the channel tissue when the conduit is placed at the injury site.
• bioactive substances may be delivered to the channel tissue before or after the conduit is positioned in the channel.
• the bioactive agent may also be delivered to the target site alone. That is, a medicine may be sent to the surgically created channel as the sole mechanism for maintaining the patency of the channel.
• systematic delivery of medicines may be carried out through digestion, injection, inhalation, etc.
• Systematic delivery of medicines may be provided alone or in combination with other techniques described herein.
• a patient having undergone the procedures described herein may be prescribed steroids and/or COX-2 inhibitors in an attempt to prolong the effects of the treatment.
• any of the conduits discussed herein may also include at least one visualization feature disposed on a portion of the tissue barrier.
• the visualization feature may be a stripe circumferentially disposed about at least a portion of the center section.
• the visualization feature serves to aid in placement or deployment of the conduit in a target site.
• Another conduit for maintaining the patency of a channel created in tissue comprises a radially expandable center section and extension members as described above.
• a bioactive substance is disposed on at least a portion of a surface of the conduit.
• the conduit when the conduit is radially expanded it has an overall length and an inner diameter such that a ratio of the overall length to the inner diameter ranges from 1/6 to 2/1.
• the conduit may also be provided such that this ratio ranges from 1/4 to 1/1 and perhaps, 1/4 to 1/2.
• a tissue barrier may be disposed on at least a portion of the exterior surface corresponding to the center section.
• the tissue barrier may be comprised of various materials including but not limited to polymers and elastomers.
• An example of a material which may be used for the tissue barrier is silicone. Additional matrixes of biodegradable polymer and medicines may be associated with the tissue barrier such that controlled doses of medicines are delivered to the tissue opening.
• the invention includes a hole-making catheter for creating and dilating an opening within tissue, the catheter comprising an elongate shaft having a proximal portion and a distal portion, and at least one lumen extending through the proximal end; a balloon having an interior in fluid communication with the lumen, the balloon located on the distal portion of the elongate shaft, the balloon having an uninflated state and an inflated state; a piercing member located at the distal portion of the elongate shaft, the piercing member being extendable and retractable within the elongate shaft; and a depth limiter stop located on the exterior of the distal portion of the elongate shaft, proximal to the balloon and larger in working diameter than the uninflated balloon, which limits the maximum penetration of the catheter into tissue.
• the piercing member may include a body portion having a lumen extending therethrough.
• the lumen of the piercing member may be in fluid communication with a central lumen of the elongate shaft.
• an obturator is used within the device, where the obturator is slidably located within the lumen of the elongate body and piercing member.
• the elongate body and/or piercing member may have multiple lumens. For example, they may be constructed from multi-lumen tubing. In some variations, the piercing member is retractable within the elongate shaft.
• the balloon member may consist of a distensible balloon or a non- distendsible balloon.
• the working diameter may closely match the outer diameter of the piercing member.
• the invention may also include an implant located about the balloon of the device. In use, the piercing member would create a channel within the tissue, the device is then further advanced until the implant is located within the channel.
• Implants for the present invention include, but are not limited to, a stent, conduit, grommet, valve, graft, anchor, etc.
• the elongate shaft may be comprised of a flexible material.
• the elongate shaft may be sufficiently flexible to pass through a fully articulated bronchoscope.
• the piercing member of the current invention may also be used to deliver bio-active agents to the site of the collateral channel. As described herein, such agents may increase the duration of patency of the channels and/or implants.
• the invention includes a balloon catheter for deploying a device within an opening in tissue, the balloon catheter comprising an elongate shaft having a proximal portion, a distal portion, a proximal end, a distal end; and at least one lumen extending through the proximal end, a balloon having an interior in fluid communication with the lumen, the balloon located on the distal end portion of the elongate shaft, a guide member extending distally from the distal end of the elongate shaft, the guide member comprising a rounded surface at an end opposite to the elongate shaft, where the guide member has sufficient column strength to penetrate the opening in tissue, the guide member further comprising at least one resistance surface a such that when the body enters the opening, the resistance surface exerts resistance against tissue upon removal of the guide member from the opening.
• the resistance surface may have an increased diameter greater to provide resistance upon removal from tissue. It may alternatively, or in combination, comprise a rough surface to provide added friction upon removal of the device.
• the guide member may be tapered, rounded, partially-spherical, elliptical, prolate, cone-shaped, triangular, or any similar shape. It is contemplated that there may be more than one resistance surface on the guide body. Moreover, the guide body may have a wavy/variable diameter shape providing several resistance surfaces on the areas of increased diameter.
• the device may also be used with an implant that may be located about the balloon where upon expansion of the balloon, the implant deploys.
• the implant may be selected from a stent, conduit, grommet, valve, graft, and anchor.
• the balloon catheter may further comprise a dilating member located distally of the balloon.
• the dilating member may be is located on the distal portion of the shaft between the distal end and the balloon and may comprise a tapered section, a second balloon, or other similar structure.
• the dilating member may be retractable within the elongate shaft.
• the device may also include a needle assembly moveably located in the instrument lumen, where the needle assembly is advanceable through a hole- making lumen and out of the opening in the rounded surface.
• the balloon catheter may be constructed to be sufficient flexibility to advance through a fully articulated bronchoscope.
• the balloon catheter may also be configured to deliver bio-active substances (e.g., drugs, medicines, compounds, etc.) to the tissue, either via the elongate tube or the guide member.
• the device may be adapted to provide suction to clear the target site.
• Figures 1A-1C illustrate various states of the natural airways and the blood-gas interface.
• Figure ID illustrates a schematic of a lung demonstrating a principle of the invention described herein.
• Figure 2A illustrates a side view of a conduit in an undeployed state.
• Figure 2B illustrates a side view of the conduit of Figure 2 A shown in a deployed shape.
• Figure 2C illustrates a front view of the conduit shown in Figure 2B.
• Figure 2D is a cylindrical projection of the undeployed conduit shown in Figure 2A.
• Figure 2E illustrates a side view of another variation of a conduit in an undeployed shape.
• Figure 2F illustrates a side view of the conduit of figure 2E in a deployed state.
• Figure 2G is a cylindrical projection of the undeployed conduit shown in Figure 2E.
• Figure 3 A illustrates a side view of a conduit having a tissue barrier in a deployed state.
• Figure 3B illustrates a side view of a conduit having a tissue barrier.
• Figure 3C is a front view of the conduit shown in Figure 3B.
• Figure 3D illustrates a conduit positioned in a channel created in a tissue wall.
• Figure 3E is a cross sectional view of the conduit shown in Figure 3B taken along line 3E-3E.
• Figures 3F-3G depict another conduit including a membrane that supports a bioactive substance; the bioactive substance may be coated on the membrane.
• Figures 4A-4C a variation of selecting a site, creating a channel at the site using a less traumatic hole-maker, and expanding the channel.
• Figures 4D-4K illustrate variations of piercing members for creating collateral channels.
• Figures 5A-5C illustrate a method for deploying a conduit.
• Figures 5D-5E illustrate a method for deploying a conduit within another implant.
• Figures 6A-6B illustrate a method for deploying a conduit at an angle.
• Figures 7A-7B illustrate placement of a conduit within a channel by using a guide member.
• Figures 8A-8F illustrate additional variations of guide bodies for use with catheters of the present invention.
• Figures 9A-9B illustrate additional features for use with guide bodies of the present invention.
• methods and devices are described that serve to maintain collateral openings or channels through an airway wall so that air is able to pass directly out of the lung tissue and into the airways. This facilitates exchange of oxygen into the blood and decompresses hyper inflated lungs.
• channel it is meant to include, but not be limited to, any opening, hole, slit, channel or passage created in the tissue wall (e.g., airway wall).
• the channel may be created in tissue having a discrete wall thickness and the channel may extend all the way through the wall.
• a channel may extend through lung tissue which does not have well defined boundaries such as, for example, parenchymal tissue.
• the channels may be maintained by preventing or inhibiting tissue from growing into or otherwise blocking the channel.
• Chemical, electrical, light, mechanical, or a combination of any two or more of these approaches may be performed to maintain the channel openings.
• the channel walls may be treated with a bioactive agent which inhibits tissue growth.
• the bioactive agent may be delivered locally or systematically.
• the channels may be treated with rf energy, heat, electrical energy, or radiation to inhibit tissue overgrowth. These treatments may be performed once, periodically, or in response to the severity of the channel blockage.
• the tissue blockage may be periodically removed with a laser or another tissue-removal tool.
• mechanical devices and instruments may be deployed in the channel to prevent tissue growth from blocking the channel.
• FIGS 1A-1C are simplified illustrations of various states of a natural airway and a blood gas interface found at a distal end of those airways.
• Figure 1 A shows a natural airway 100 which eventually branches to a blood gas interface 102.
• the airway comprises an internal layer of epithelial pseudostratified columnar or cuboidal cells.
• Mucous secreting goblet cells are also found in this layer and cilia maybe present on the free surface of the epithelial lining of the upper respiratory airways. Supporting the epithelium is a loose fibrous, glandular, vascular lamina basement including mobile fibroblasts. Deep in this connective tissue layer is supportive cartilage for the bronchi and smooth muscle for the bronchi and bronchioles.
• Figure IB illustrates an airway 100 and blood gas interface 102 in an individual having COPD.
• the obstructions 104 impair the passage of gas between the airways 100 and the interface 102.
• Figure 1C illustrates a portion of an emphysematous lung where the blood gas interface 102 expands due to the loss of the interface walls 106 which have deteriorated due to a bio-chemical breakdown of the walls 106. Also depicted is a constriction 108 of the airway 100. It is generally understood that there is usually a combination of the phenomena depicted in Figures lA-lC. Often, the states of the lung depicted in Figures IB and 1C may be found in the same lung.
• Figure ID illustrates airflow in a lung 118 when conduits 200 are placed in collateral channels 112.
• collateral channels 112 located in an airway wall
• the invention is not limited to the number of collateral channels which may be created, it is to be understood that 1 or 2 channels may be placed per lobe of the lung and perhaps, 2-12 channels per individual patient.
• the invention includes the creation of any number of collateral channels in the lung. This number may vary on a case by case basis.
• Figure ID depicts a mechanical approach to maintaining channels in the airway walls, the channel openings may be maintained using a variety of approaches or combinations of approaches.
• the conduits described herein generally include a center section 208 and at least one extension member (or finger) 202 extending from each end of the center section.
• the extension members are capable of deflecting or outwardly bending to secure the conduit in an opening created in an airway wall thereby maintaining the patency of the opening.
• the extension members may deflect such that opposing extension members may form a V, U or other type of shape when viewed from the side.
• the conduits shown in Figures 2A-2G include a center- control segment 235, 256 which restricts or limits radial expansion of the center section.
• the center-control segments are adapted to straighten as the center section is radially expanded. Once the center-control segments become straight or nearly straight, radial expansion of the conduit is prevented. In this manner, the radial expansion of the conduit maybe self controlled.
• conduits discussed herein are not limited to those shown in the figures. Instead, conduits of various configurations may be used as described herein. Such conduits are described in the following patent applications 09/908,177 filed 7/18/01; PCT/US03/12323 filed 4/21/03; 09/947,144 filed 9/4/01; 10/235,240 filed 9/4/02; and 10/458,085 filed 6/9/03 the entirety of each of which is hereby incorporated by reference.
• the conduits described herein may have various states (configurations or profiles) including but not limited to (1.) an undeployed state and (2.) a deployed state.
• the undeployed state is the configuration of the conduit when it is not secured in an opening in an airway wall and, in particular, when its extension members (or fingers) are not outwardly deflected to engage the airway wall.
• Figure 2A is a side view of a conduit 200 in an undeployed state. As shown in this figure, extension members 202A, 202B extend straight from the ends 210, 212 respectively of center section 208. The extension members shown in this example are parallel. However, the invention is not so limited and the extension members need not be parallel.
• the deployed state is the configuration of the conduit when it is secured in a channel created in an airway wall and, in particular, when its extension members are outwardly bent to engage the airway wall such that the conduit is fixed in the opening.
• An example of a conduit in its deployed configuration is shown in
• Figure 2B is a side view of a conduit in its deployed state
• Figure 2C shows a front view of the conduit of Figure 2B.
• the conduit includes a center section 208 having a short passageway.
• This center section may be a tubular-shaped open-frame
• the center section may be a sheet of material.
• the axial length of the center section or passageway may be relatively short, i Figures 2A-2D, the passageway's length is about equal to the width of a wire segment or rib.
• the center section serves as a bridge or junction for the extension members and it is not required to be long.
• the axial length of the passageway may therefore be less than 1 mm and even approach 0 mm.
• the length of the center section is less than twice the square root of a cross sectional area of the center section.
• the center section may also have passageways which have lengths greater than 1 mm.
• the overall length (L) of the conduit may be distinguished from the length of the center section because the overall length includes the lengths of the extension members.
• the overall length (L) is dependent on which state the conduit is in.
• the overall length of the conduit will typically be shorter when it is in a deployed state as shown in Figure 2B than when it is in an undeployed state as shown in Figure 2A.
• the overall length (L) for a deployed conduit may be less than 6 mm and perhaps, between 1 and 20 mm.
• Figure 2C shows a front view of the conduit 200 shown in figure 2B.
• Figure 2C shows the passageway having a hexagonal (or circular) cross section.
• the cross-section is not so limited.
• the cross section may be circular, oval, rectangular, elliptical, or any other multi-faceted or curved shape.
• the inner diameter (Di) of the center section, when deployed, may range from 1 to 10 mm and perhaps, from 2 to 5 mm.
• the cross-sectional area of the passageway, when deployed may be between 0.2 mm 2 to 300 mm 2 and perhaps between 3 mm 2 and 20 mm 2 .
• the diameter of the center section when deployed, thus may be significantly larger than the passageway's axial length (e.g., a 3 mm diameter and an axial length of less than 1 mm).
• This ratio of the center section length to diameter (DI) may range from about 0:10 to 10:1, 0.1:6 to 2:1 and perhaps from 1:2 to 1:1.
• the diameter of the center section, when deployed, may also be nearly equal to the overall length (L) of the conduit 200.
• This overall length (L) to diameter (DI) ratio may range from 1:10 to 10:1, 1:6 to 2:1, and perhaps from 1:4 to 1:1.
• the invention is not limited to any particular dimensions or ratio unless so indicated in the appended claims.
• the conduit should have a center section such that it can maintain the patency of a collateral channel in an airway wall.
• the dimensions of the center section may be chosen based on the tissue dimensions.
• the length of the center section may likewise be long or identical to the channel's length.
• extension members 202A, 202B which, when the conduit is deployed, form angles Al, A2 with a central axis of the passageway.
• opposing extension members may have a V, U, or other shape.
• the extension members 202A, 202B may thus outwardly rotate until they sandwich tissue (not shown) between opposing extension members.
• the angles Al, A2 may vary and may range from, for example, 30 to 150 degrees, 45 to 135 degrees and perhaps from 30 to 90 degrees.
• Opposing extension members may thus form angles Al and A2 of less than 90 degrees when the conduit is deployed in a channel.
• angles Al and A2 may range from 30 to 60 degrees when the conduit is deployed.
• the conduits of the present invention are effective and may maintain a surgically created opening despite not substantially sandwiching tissue between opposing extension members as described above. Additionally, it is not necessary for the conduits of the present invention to prevent air from flowing along the exterior of the conduit. That is, air may move into (and through) spaces between the exterior of the conduit and the interior wall of the tissue channel. Thus, fluidly sealing the edges of the conduit to prevent side flow or leakage around the conduit is not crucial for the conduits to be effective.
• the conduits of the present invention are not so limited and may reduce or eliminate side flow by, for example, increasing the angles Al and A2 and adding sealant around the exterior of the conduit. [00100] Moreover, the angle Al may be different than angle A2.
• the conduit may include proximal extension members which are parallel (or not parallel) to the distal extension members. Additionally, the angle corresponding to each proximal extension member may be different or identical to that of another proximal extension member. Likewise, the angle corresponding to each distal extension member may be different or identical to that of another distal iextension member. [00101]
• the extension members may have a length between 1 and 20 mm and perhaps, between 2 and 6 mm. Also, with reference to Figure 2C, the outer diameter (D 2 ) of a circle formed by the free ends of the extension members may range from 2 to 20 and perhaps, 3 to 10 mm. However, the invention is not limited to the dimensions disclosed above.
• the length of the distal extension members may be different than the length of the proximal extension members.
• the length of the distal extension members may be, for example, longer than that of the proximal extension members.
• the lengths of each proximal extension member may be different or identical to that of the other proximal extension members.
• the lengths of each distal extension member may be different or identical to that of the other distal extension members.
• the number of extension members on each end of the center section may also vary.
• the number of extension members on each end may range from 2-10 and perhaps, 3-6.
• the number of proximal extension members may differ from the number of distal extension members for a particular conduit.
• the extension members may be symmetrical or non-symmetrical about the center section.
• the proximal and distal extension members may also be arranged in an in-line pattern or an alternating pattern.
• the extension members or the center section may also contain barbs or other similar configurations to increase adhesion between the conduit and the tissue.
• the extension members may also have openings to permit tissue ingrowth for improved retention.
• the shape ofthe extension members may also vary.
• the extension members 202A, 202B comprise wire segments or ribs that define openings or spaces between the members.
• the invention is not so limited and the extension members may have other shapes.
• the extension members may, for example, be solid or they may be filled.
• the conduit is constructed to have a delivery state.
• the delivery state is the configuration ofthe conduit when it is being delivered through a working channel of a bronchoscope, endoscope, airway or other delivery tool.
• the maximum outer diameter ofthe conduit in its delivery state must therefore be such that it may fit within the delivery tool, instrument, or airway.
• the conduit is radially expandable such that it may be delivered in a smaller working channel of a scope while maximizing the diameter to which the conduit may expand upon deployment. For example, sizing a conduit for insertion into a bronchoscope having a 2 mm or larger working channel may be desirable. Upon deployment, the conduit may be expanded to have an increased internal diameter (e.g., 3 mm.) However, the invention is not limited to such dimensions. It is contemplated that the conduits 200 may have center sections that are expanded into a larger profile from a reduced profile, or, the center sections may be restrained in a reduced profile, and upon release ofthe restraint, return to an expanded profile.
• the conduit need not have a smaller delivery state.
• a maximum diameter ofthe first or deployed profile will be sufficiently small such that the conduit may be placed and advanced within an airway or a working channel of a bronchoscope or endoscope.
• the deployed shape may be identical to the shape ofthe conduit when the conduit is at rest or when it is completely unrestrained.
• the conduit may be partially expanded in its proximal region in the delivery state, as shown in figure X.
• the partially expanded portion would still me sized small enough to fit within the working channel ofthe bronchoscope, but would be significantly larger (e.g., 0.5 - 2 mm) larger that the distal portion ofthe conduit.
• This partial expansion allows for easy placement ofthe conduit by providing a physical stop for the conduit within the airway wall. After the conduit is placed the entire conduit can be expanded to its intended expanded shape.
• the partial expansion state can also be achieved by partially inflating the proximal section ofthe conduit with a separate balloon on the delivery device. Another possible method is to design the conduit to preferentially expand the proximal section before the distal section, thereby partially expanding the conduit to create the size differential, placing the stent inside the airway wall with the aid ofthe stop, and then fully expanding the conduit.
• the conduit 200 shown in Figures 2A-2D also includes diametric- control segments, tethers, or leashes 235 to control and limit the expansion ofthe center section 208 when deployed.
• This center-control segment 235 typically is shaped such that when the conduit radially expands, the center-control segment bends until it is substantially straight or no longer slack.
• Such a center-control segment 235 may be circular or annular shaped. However, its shape may vary widely and it may have, for example, an arcuate, semi-circular, V, or other type of shape which limits the expansion ofthe conduit.
• one end ofthe center-control segment is attached or joined to the center section at one location (e.g., a first rib) and the other end ofthe center- control segment is connected to the center section at a second location (e.g., a rib adjacent or opposite to the first rib).
• the center-control segments may have other constructs.
• the center-control segments may connect adjacent or non-adjacent center section members.
• each center-control segment may connect one or more ribs together.
• the center-control segments may further be doubled up or reinforced with ancillary control segments to provide added control over the expansion ofthe center section.
• the ancillary control segments may be different or identical to the primary control segments.
• Figure 2B illustrates the conduit 200 in its deployed configuration.
• the center-control segments 235 may bend or otherwise deform until they maximize their length (i.e., become substantially straight) such as the center- control segments 235 shown in Figure 2B.
• the invention is not so limited and other types of center-control segments may be employed.
• control segments 252 may also be used to join and limit the expansion ofthe extension members 254 or the control segments may be placed elsewhere on the conduit to limit movement of certain features to a maximum dimension.
• the shape of the deployed conduit may be controlled.
• the conduit shown in Figures 2E-2G the conduit includes both center-control segments 256 and distal control segments 252.
• the center-control segments are arcuate shaped and join adjacent rib sections ofthe center section and the distal-control segments are arcuate and join adjacent distal extension members.
• Figure 2F illustrates the conduit in a deployed configuration and shows the various control members straightening as the extension members and center section deploy.
• proximal extension members are not restricted by a control member and consequently may be deflected to a greater degree than the distal extension members. Accordingly, a conduit having control members connecting, for example, regions ofthe center section and having additional control segments connecting extension members, may precisely limit the maximum profile of a conduit when it is deployed. This is desirable where overexpansion ofthe conduit is hazardous.
• This also serves to control the deployed shape ofthe conduit by, for instance, forcing angle Al to differ from angle A2.
• Using control segments in this manner can provide for cone-shaped conduits if the various types of control-segments ' have different lengths. For example, providing longer proximal-control segments than distal-control segments can make angle Al larger than angle A2.
• cylindrical-shaped conduits may be provided if the center-control segments and the extension-control segments are sized similarly such that angle Al equals angle A2. Again, the control segments straighten as the conduit expands and the conduit is thus prevented from expanding past a predetermined amount.
• the control segments may be added or mounted to the center section or alternatively, they may be integral with the center section. That is, the control segments may be part ofthe conduit rather than separately joined to the conduit with adhesives or welding, for example.
• the control segments may also be mounted exteriorly or interiorly to the members to be linked. Additionally, sections ofthe conduit may be removed to allow areas ofthe conduit to deform more readily. These weakened areas provide another approach to control the final shape ofthe deployed conduit. Details for creating and utilizing weakened sections to control the final shape ofthe deployed conduit may be found in U.S. Pat. No. 09/947,144 filed on September 4, 2001.
• the conduit described herein may be manufactured by a variety of manufacturing processes including but not limited to laser cutting, chemical etching, punching, stamping, etc.
• the conduit may be formed from a tube that is slit to form extension members and a center section between the members.
• One variation ofthe conduit may be constructed from a metal tube, such as stainless steel, 316L stainless steel, titanium, titanium alloy, nitinol, MP35N (a nickel-cobalt- chromium-molybdenum alloy), etc.
• the conduit may be formed from a rigid or elastomeric material that is formable into the configurations described herein.
• the conduit may be formed from a cylinder with the passageway being formed through the conduit.
• the conduit may also be formed from a sheet of material in which a specific pattern is cut. The cut sheet may then be rolled and formed into a tube.
• the materials used for the conduit can be those described above as well as a polymeric material, a biostable or implantable material, a material with rigid properties, a material with elastomeric properties, or a combination thereof. If the conduit is a polymeric elastic tube (e.g. a thermoplastic elastomer), the conduit may be extruded and cut to size, injection molded, or otherwise formed.
• the conduits described herein may be comprised of a shape memory alloy, a super-elastic alloy (e.g., a NiTi alloy), a shape memory polymer, or a shape memory composite material.
• the conduit may be constructed to have a natural self-assuming deployed configuration, but is restrained in a pre- deployed configuration. As such, removal ofthe restraints (e.g., a sheath) causes the conduit to assume the deployed configuration.
• a conduit of this type could be, but is not limited to being, comprised from an elastic polymeric material, or shape memory material such as a shape memory alloy. It is also contemplated that the conduit could comprise a shape memory alloy such that, upon reaching a particular temperature (e.g., 98.5 °F), it assumes a deployed configuration.
• the conduit described herein may be formed of a plastically deformable material such that the conduit is expanded and plastically deforms into a deployed configuration.
• the conduit may be expanded into its expanded state by a variety of devices such as, for example, a balloon catheter.
• the conduit's surface may be modified to affect tissue growth or adhesion.
• an implant may comprise a smooth surface finish in the range of 0.1 micrometer to 0.01 micrometer. Such a finish may serve to prevent the conduit from being ejected or occluded by tissue overgrowth.
• the surface may be roughened or porous.
• the conduit may also comprise various coatings and tissue barriers as discussed below.
• FIG 3A illustrates another variation of a conduit 200 having a tissue barrier 240.
• the tissue barrier 240 prevents tissue ingrowth from occluding the collateral channel or passage ofthe conduit 200.
• the tissue barrier 240 may coaxially cover the center section from one end to the other or it may only cover one or more regions ofthe conduit 200.
• the tissue barrier may completely or partially cover the conduit so long as the ends are at least partially open. Moreover, the tissue barrier may only be placed on the center section ofthe conduit.
• the tissue barrier 240 may be located about an exterior ofthe conduit's surface, about an interior ofthe conduit's surface, or the tissue barrier 240 may be located within openings in the wall ofthe conduit's surface.
• the center section 208 itself may provide an effective barrier to tissue ingrowth.
• the tissue barrier should not cover or block the entrance and exit ofthe passageway such that air is prevented from passing through the conduit's passageway. However, in some constructs, the tissue barrier may partially block the entrance or exit ofthe passageway so long as air may continue to pass through the conduit's passageway.
• the tissue barrier may be formed from a material, mesh, sleeve, or coating that is a polymer or an elastomer such as, for example, silicone, fluorosilicone, polyurethane, PET, PTFE, or expanded PTFE. Other biocompatible materials will work, such as a thin foil of metal, etc.
• the coatings may be applied, for example, by either dip coating, molding, spin-coating, transfer molding or liquid injection molding.
• the tissue barrier may be a tube of a material and the tube is placed either over and/or within the conduit. The tissue barrier may then be bonded, crimped, heated, melted, shrink fitted or fused to the conduit. The tissue barrier may also be tied to the conduit with a filament of, for example, a suture material.
• Still other techniques for attaching the tissue barrier include: solvent swelling applications and extrusion processes; wrapping a sheet of material about the conduit, or placing a tube ofthe material about the conduit and securing the tube to the conduit.
• the tissue barrier may be secured on the interior ofthe conduit by positioning a sheet or tube of material on the inside ofthe center section and securing the material therein.
• the tissue barrier may also be formed of a fine mesh with a porosity or treatment such that tissue may not penetrate the pores.
• a ChronoFlexTM DACRON® or TEFLON® mesh having a pore size of 100-300 microns may be saturated with collagen or another biocompatible substance.
• This construct may form a suitable tissue barrier.
• the mesh may be coaxially attached to a frame such as the open frame structures disclosed above. Still other suitable frames include a continuous spiral metallic or polymeric element.
• FIGS 3B and 3C respectively illustrate a side view and a front view of another conduit 300 having a partial tissue barrier coating.
• the conduit 300 includes a center section 310, a plurality of extension members 320, and a partial tissue barrier 330.
• the conduit 300 is thus different than that shown in Figure 3A in that the center section is longer and that the tissue barrier 330 only partially covers the extension members 320.
• the center section 310 shown in figures 3B-3C is cylindrical or tubular-shaped.
• the overall (or three dimensional) shape ofthe center section when deployed, is not limited to the shape shown here. Rather, it may have various shapes such as, for example, rectangular, tubular, conical, hour-glass, hemi-toroidal, etc.
• the tissue barrier 330 covers only a first region 350 of the extension members and leaves a second region 340 ofthe extension members uncovered.
• the second or free region 340 ofthe extension members 320 is shown as being open- framed.
• the second region of the extension members may be solid and it may include indentations, grooves, and recesses for tissue ingrowth.
• the extension members may include small holes for tissue ingrowth.
• the second region ofthe extension members may have a dense array of small holes.
• the conduits described herein may include at least one region or surface which is susceptible to tissue ingrowth or is otherwise adherent to the tissue. Accordingly, tissue ingrowth at the second region 340 ofthe extension members is facilitated while tissue growth into the passageway 325 is thwarted. [00126] As shown in Figure 3D, tissue growth 360 into the uncovered region
• Free region 340 of the extension members may also include tissue growth substances such as epithelial growth factors or agents to encourage tissue ingrowth. Accordingly, conduit 300 may be configured to engage the tissue wall 370 as well as to allow tissue to grow into predetermined regions ofthe conduit.
• the conduit shown in Figure 3 A also includes a visualization ring or marker 242.
• the marker 242 is visually apparent during a procedure. The marker is observed as the conduit is placed in a collateral channel and, when the marker is even with the opening ofthe channel, the conduit may be deployed. In this manner, the visualization feature facilitates alignment and deployment ofthe conduits into collateral channels.
• the visualization ring or mark may be a biocompatible polymer and have a color such as white. Also, the visualization feature may protrude from the center section or it may be an indentation(s).
• the visualization mark may also be a ring, groove or any other physical feature on the conduit. Moreover, the visualization feature may be continuous or comprise discrete segments (e.g., dots or line segments).
• the visualization feature may be made using a number of techniques.
• the mark is a ring formed of silicone and is white.
• the polymeric ring may be spun onto the tissue barrier.
• a clear silicone barrier may be coated onto the conduit such that it coaxially covers the extension members and the center section as shown in Figure 3 A.
• a thin ring of white material such as a metal oxide suspended in clear silicone may be spun onto the silicone coating.
• another coating of clear silicone may be applied to coat the white layer.
• the conduit thus may include upwards of 1-3 layers including a tissue barrier, a visualization mark layer, and a clear outer covering.
• the shape ofthe visualization mark is not limited to a thin ring.
• the visualization mark may be large, for example, and cover an entire half of the conduit as shown in Figure 3B.
• the visualization mark may, for example, be a white coating disposed on the proximal or distal half of the conduit.
• the visualization mark thus may extend from an end ofthe extension members to the center section ofthe conduit.
• the physician may observe when one-half of the conduit extends into the channel. This allows the physician to properly actuate or deploy the conduit to secure the conduit in the tissue wall.
• the visualization member is made visually apparent for use with, for example, an endoscope.
• the visualization feature may also be made of other vision-enhancing materials such as radio-opaque metals used in x- ray detection.
• other elements ofthe conduit can include visualization features such as but not limited to the extension members, tissue barrier, control segments, etc.
• incorporation of a bioactive, as discussed herein, or other substance into the coating caused a coloration effect in the composition layer (e.g., the polymer turns white). This coloration obscures the support member structure in the layer making it difficult to identify the edges and center ofthe support member or implant.
• placement ofthe implant may depend upon positioning the center ofthe implant within the opening in tissue. If the support member structure is identifiable, then one is able to visually identify the center ofthe implant. When the composition colors obscures the support member or renders the implant otherwise opaque, it may become difficult to properly place the device. This may be especially true when the composition layer extends continuously over the support member. [00133] Additionally, the coloration may render the visualization mark difficult to identify especially under direct visualization (e.g., using a scope) In some cases it was undesirable to simply add additional substances on or in the composition layer for marking because such substances could possibly interfere with the implant's ability to deliver the substance as desired.
• a variation ofthe invention includes a delivery device for delivering an expandable implant (such as those described herein and in the cases referenced herein), where the delivery device includes an expandable member having an expandable implant located about the expandable member.
• the implant and the expandable member are of different visually identifiable colors or shades such that they distinction is easy to identify under endoscopic or bronchoscopic viewing.
• a balloon catheter has a colored sleeve 306 located about the balloon.
• the sleeve 306 comprises a visually identifiable color where selection ofthe colors should ease identification ofthe implant an endoscopic visualization system (e.g., blue or a similar color that is not naturally occurring within the body.)
• the implant is placed about the sleeve 306 where the proximal and distal areas ofthe implant would be identifiable by the difference in color.
• the sleeve 306 may be fashioned from any expandable material, such as a polymer.
• the sleeve 306 may also provide an elastic force to return the balloon to a reduced profile after expansion ofthe balloon.
• Such a system allows for identification without affecting the properties ofthe implant.
• variations ofthe invention include coloring the balloon itself, or other expandable member, a color that meets the above criteria.
• the visualization mark may comprise providing a contrast between the implant and a delivery catheter. In one example the implant is appears mostly white and while mounted on a contrasting color inflation balloon. In this example the implant would be placed over a blue deflated balloon catheter.
• the proximal and distal areas ofthe implant would be flanked by the deflated blue balloon, thus giving the appearance of a distinct distal and proximal end ofthe implant. This would allow a physician to place the implant properly by using the blue flanks as a guide for placing the central white portion in the tissue wall. Similarly, a colored flexible sheath covering the balloon would also suffice. [00137] It is noted that while the visualization features described above are suitable for use with the implants described herein, the inventive features are not limited as such. The features may be incorporated into any system where placement of an implant under direct visualization requires clear identification of he implant regardless of whether the implant is opaque or colored.
• the bio-active substance or combination of bioactive substances is selected to assists in modifying the healing response as a result ofthe trauma to the lung tissue resulting from creation ofthe collateral channel.
• lung tissue is intended to include the tissue lining the airway, the tissue beneath the lining, and the tissue within the lung but exterior to the airway (e.g., lung parenchyma.)
• the purpose of modifying the healing response is to further extend the patency ofthe channel or implant to increase the duration which trapped gasses may exit through the implant into the airways.
• antiproliferative agent is intended to include those bioactive substances that directly modify the healing response described herein.
• the bioactive substances are intended to interact with the tissue ofthe surgically created channels and in particular, lung tissue. These substances may interact with the tissue in a number of ways. They may, for example, 1.) accelerate cell proliferation or wound healing to epithelialize or scar the walls ofthe surgically- created channel to maintain its patent shape or 2.) the substances may inhibit or halt tissue growth when a channel is surgically created through an airway wall such that occlusion ofthe channel due to tissue overgrowth is prevented.
• bioactive agents may'inhibit wound healing such that the injury site (e.g., the channel or opening) does not heal leaving the injury site open and/or inhibit infection (e.g., reduce bacteria) such that excessive wound healing does not occur which may lead to excessive tissue growth at the channel thereby blocking the passageway.
• infection e.g., reduce bacteria
• bioactive substances may be used alone or in combination with the devices described herein.
• bioactive substances include, but are not limited to, antimetabolites, antithrobotics, anticoagulants, antiplatelet agents, thorombolytics, antiproliferatives, antinflammatories, agents that inhibit hyperplasia and in particular restenosis, smooth muscle cell inhibitors, growth factors, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters and drugs that may enhance the formation of healthy neointimal tissue, including endothelial cell regeneration.
• the positive action may come from inhibiting particular cells (e.g., smooth muscle cells) or tissue formation (e.g., fibromuscular tissue) while encouraging different cell migration (e.g., endothelium, epithelium) and tissue formation (neointimal tissue).
• bioactive agents include but are not limited to analgesics, anticonvulsives, anti-infectives (e.g., antibiotics, antimicrobials), antineoplastics, H2 antagonists (Histamine 2 antagonists), steroids, non-steroidal anti-inflammatories, hormones, immunomodulators, mast cell stabilizers, nucleoside analogues, respiratory agents, antihypertensives, antihistamines, ACE inhibitors, cell growth factors, nerve growth factors, anti-angiogenic agents or angiogenesis inhibitors (e.g., endostatins or angiostatins), tissue irritants (e.g., a compound comprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g., a compound that can cause cell death), various metals (silver, aluminum, zinc, platinum, arsenic, etc.), epithelial growth factors or a combination of any ofthe agents disclosed herein.
• analgesics e
• agents include pyrolitic carbon, titanium-nitride-oxide, taxanes, fibrinogen, collagen, thrombin, phosphorylcholine, heparin, rapamycin, radioactive 188Re and 32P, silver nitrate, dactinomycin, sirolimus, everolimus, Abt- 578, tacrolimus, camptothecin, etoposide, vincristine, mitomycin, fluorouracil, or cell adhesion peptides.
• Taxanes include, for example, paclitaxel, 10-deacetyltaxol, 7- epi- 10-deacetyltaxol, 7-xylosyl- 10-deacetyltaxol, 7-epi-taxol, cephalomannine, baccatin III, baccatin V, 10-deacetylbaccatin III, 7-epi-10-deacetylbaccatin LTLdocetaxel.
• bioactive materials having other functions can also be successfully delivered in accordance with the present invention.
• an antiproliferative agent such as methotrexate will inhibit over-proliferation of smooth muscle cells and thus inhibit restenosis.
• the antiproliferative is desirably supplied for this purpose until the tissue has properly healed.
• localized delivery of an antiproliferative agent is also useful for the treatment of a variety of malignant conditions characterized by highly vascular growth, hi such cases, an implant such as a implant could be placed in the surgically created channel to provide a means of delivering a relatively high dose ofthe antiproliferative agent directly to the target area.
• a vasodilator such as a calcium channel blocker or a nitrate may also be delivered to the target site.
• the agent may further be a curative, a pre-operative debulker reducing the size ofthe growth, or a palliative which eases the symptoms of the disease.
• tamoxifen citrate, Taxol ® or derivatives thereof Proscar ® , Hytrin ® , or Eulexin ® may be applied to the target site as described herein.
• Variations ofthe invention may also include fibrino lyrics such as tPA, streptokinase, or urokinase, etc. Such fibrinolytics prevent or reduce the accumulation of fibrin within the opening.
• Accumulation of fibrin in the opening may result from inflammation ofthe tissue.
• the fibrin may form a structure which makes it easier for tissue to grow into the opening using the fibrin structure as a framework.
• Use of fibrinolytics, either topically, locally, or on the implant, serves to remove or hinder the network of fibrin from forming within the opening (or implant) and therefore aids in modifying the healing response.
• the poisonous and toxic compounds In the event that poisonous and toxic compounds are delivered, they should be controlled so that inadvertent death of tissue does not occur.
• the poisonous agent should be delivered locally or only be effective locally.
• One method for delivering the bioactive agent locally is to associate the bioactive agent with an implant.
• the implants described herein may include a bioactive substance or medicine deposited onto the interior, the exterior, or both the interior and exterior surfaces ofthe implant. The bioactive substance may remain on the implant so that it does not leach. Cells that grow into the surgically created channel contact the poison and die.
• the bioactive agent may be configured to gradually elute as discussed below.
• the implant When used in the lungs, the implant modifies the healing response of the lung tissue (e.g., at the site of newly created hole/channel) for a sufficient time until the healing response ofthe lung tissue subsides or reduces such that the hole/channel becomes a persistent air path.
• the implant and bioactive substance will modify the healing response for a sufficient time until the healing response is reduced and, from a visual observation, the body treats the opening essentially as a natural airway passage rather than as an injury to the airway wall.
• the implant provides a steady release rate of bio-active substance as well as has a sufficient amount of available bio-active substance to modify the healing response ofthe lung tissue.
• lung tissue is intended to include the tissue lining the airway, the tissue beneath the lining, and the tissue within the lung but exterior to the airway (e.g., lung parenchyma.) Such a delivery profile allows for a concentration gradient of drug to build in these tissues adjacent to the delivery site ofthe implant.
• the concentration gradient affects the healing response ofthe lung tissue so that the implant does not become occluded as a result ofthe healing response. Because the implant is often placed in the airway wall it is exposed to the healing process ofthe multiple tissues. Providing a sufficient amount of bio-active substance allows for the formation of a concentration ofthe bioactive substance across these various tissues. In one variation ofthe invention it is believed that the fluids from these tissues enter into the composition layer ofthe device. The fluids then combine with the bio-active substances and migrate out of the composition layer to settle into the lung tissue. A concentration gradient forms when the drug 'saturates' local tissue and migrates beyond the saturated tissues.
• the healing response may be affected or suppressed during the critical time immediately after the wounding caused by creation ofthe collateral channel when the healing response is greatest.
• the solubility parameter ofthe polymer must be matched with the bio-active substance to provide an acceptable slow elution rate from the polymer.
• the polymer itself must be selected to have the proper attributes, such as a proper diffusion coefficient (to slow fluid entering and departing from the implant), and proper mechanical expansion properties (to allow for the significant expansion ofthe polymer to accommodate fo ⁇ nation ofthe grommet shape.)
• the solubility parameter is defined as the square root ofthe cohesive energy ofthe molecules in a compound.
• the level of control that a polymer has over the elution of a drug is the difference between the solubility parameters ofthe polymer and the solubility parameter ofthe drug.
• a polymer with a high internal density could be selected to be less permeable to a complex molecule such as paclitaxel.
• Using a polymer with high internal density also accommodated the significant expansion required ofthe polymer to form the structure necessary to grommet about the airway wall. An example ofthe polymer selection is found below.
• paclitaxel is a taxane that is regarded as a microtubule stabilizer.
• the benefits of a microtubule stabilizing substance for use in vascular drug eluting stents is discussed, for example, in U.S. Patent No. 5,616,608 to Kinsella et al. This type of drug operates to enhance microtubule polymerization which inhibits cell replication by stabilizing microtubules in spindles which block cell division.
• the implant for use in the present invention may use microtubule stabilizing substances such as taxanes (e.g., paclitaxel) as well as those microtubule destabilizing substances that are believed to promote microtubule disassembly in preventing cell replication.
• destabilizing substances include, but are not limited to vincristine, vinblastine, podophylotoxin, estramustine, noscapine, griseofu ⁇ vin, dicoumarol, a vinca alkaloid, and a combination thereof.
• the exterior surface ofthe implant may be treated via etching processes or with electrical charge to encourage binding ofthe bioactive substances to the implant.
• the exterior surface may also be roughened to enhance binding ofthe medicine to the surface as discussed in U.S. Patent Application Publication No. 2002/0098278. See also U.S. Patent Application Publication Nos. 2002/0071902, 2002/0127327 and U.S. Patent No. 5,824,048 which discuss various techniques for coating medical implants.
• the implant may comprise a frame or body with a bioactive matrix disposed or otherwise associated therewith, the invention is not so limited, i one variation, the support member is formed from a polymer and the composition is joined to the polymeric support member. Alternatively, the bioactive substances may be placed directly onto the polymeric support member.
• Adverse reactions include, but are not limited to, granulation, swelling, and mucus overproduction. These substance may also be inhaled, injected, orally applied, topically applied, or carried by the implant. These substances may include anti-inflammatory, infection-fighting substances, steroids, mucalytics, enzymes, and wound healing-accelerating substances. Examples of these substances include but are not limited to, acetylcysteine, albuterol sulfate, ipratropium bromide, dornase alfa, and corticosteroids.
• FIG. 4A-4C illustrates creation ofthe collateral channel and selecting a treatment site in the airway 100.
• a single device may be used to select the site and create the channel.
• another variation ofthe invention includes using such a device to deploy the conduit at the target site.
• the invention also contemplates using separate devices to perform each step or a combination of steps.
• a device 602 is advanced, for example, via a bronchoscope 404, into the airway 100.
• the device 602 may be a Doppler ultrasound device, a thermal device, an imaging device, etc.
• Figure 4B illustrates another variation of selecting a site for a channel.
• a piercing member e.g., a blade affixed to a shaft, a needle, cannula, sharpened tube or rod, etc., is advanced into the airway wall.
• the surgeon may inspect the area for blood to determine whether the device punctured a blood vessel. After the opening is created the surgeon may also remove collect a biopsy of material behind the airway wall. If the opening is large enough as created by a balloon, as described herein, the surgeon may use forceps to visually obtain the sample. This may preferable to a blind method of obtaining biopsies, considering that the risk of bleeding may be reduced because the area has been scanned for blood vessels.
• the piercing member 604 may have a lumen and may be open at a distal end or closed. In those cases where the piercing member 604 is hollow and has an opening at or near the distal end, the surgeon may aspirate the site using the piercing member 604 to determine whether a blood vessel is present and/or penetrated.
• flashback catheters contain chambers which will fill with blood upon the penetration of a vessel by the distal tip ofthe catheter.
• the piercing member may be incorporated to have a flashback chamber to detect the presence of blood flow from a penetrated vessel. Using these approaches, a target site may not be selected until after a hole is made in the airway 100 wall.
• a piercing member may be of a diameter which results in closure ofthe puncture site upon removal ofthe piercing member.
• the piercing member may be of a sufficient size or construction that the hole remains open upon removal ofthe piercing member.
• the piercing member or another device may be used to mark the site ofthe opening (e.g., via ink, dye, physical marker, via application of electrical energy, etc.)
• the invention includes use of both a detecting device as described above in combination with a piercing member. For example, the site may be inspected by the detecting device prior to insertion of a piercing member.
• the piercing member lumen may also be used to deliver therapeutic fluids to the lungs.
• the physician may apply epinephrine or saline the lungs.
• the physician may use the piercing member to apply epinephrine to the airway wall prior to creation of the channel, to prevent bleeding. This may be done by injecting directly into the airway wall at or about the site of passage creation; singly or in a surrounding pattern of multiple applications.
• the physician may also use the piercing member lumen to apply any ofthe bioactive agents discussed herein, before or after passage creation.
• a piercing member may be selected to have a length that will sufficiently pass through the airway wall, while being small enough that it will also pass through a fully articulated bronchoscope.
• the piercing member may have sections of varying stiffness where a distal portion, (that is sufficient stiff to penetrate the tissue) may be of a length such that it is able to advance through a fully articulated bronchoscope.
• the piercing member may comprised of a sharpened cannula which has a length from between 2mm to 30mm. The diameter may range between 16 Ga to 25 Ga or larger.
• the cannula may be affixed to a catheter having a relatively flexible proximal portion. In any case, the length ofthe piecing member 604 may vary as needed.
• the piercing member is not limited to a cannula, it may be of solid construction, such as a sharpened rod or wire. Additionally the piercing member may be adapted with an elongate member, such as a wire, rod, or tube, which extends throughout the device.
• the purpose ofthe elongate member is to provide column strength to the piercing member and necessary bending resistance to the catheter, because it has been found that the device must have high column strength to effectively pierce the airway wall, otherwise the device will deflect and not create a passageway.
• the elongate member may be utilized to expose and retract the piercing member within the catheter, as the elongate member may extend throughout the device to a user interface.
• the elongate member and piercing member may also be constructed from one piece of material, thereby making them one part.
• the elongate member may be a separate part welded, bonded, mechanically attached, or a combination thereof, to the piercing member.
• the current invention is not limited to any particular length ofthe piercing member.
• the piercing member may be comprised of a resilient polymer, a polymer with a reinforced structure (e.g., a braid, coil, etc.), a super-elastic alloy, a metallic material with sufficient resilience, etc, such that it may navigate through a fully articulated bronchoscope yet return to its original profile upon exiting the working channel ofthe scope.
• the piercing member ofthe device may be retractable within a lumen of an elongate shaft so as to prevent damage to the bronchoscope or to tissue as the device advances to the target site. Additionally the piercing member may be retracted after the initial piercing ofthe airway wall, and blunt trauma may be used to further push the remaining portion ofthe catheter into the airway wall. This technique may help avoid additional bleeding and pneumothoraxes from an exposed piercing member.
• the catheter may be advanced to tortuous locations, therefore the device may incorporate low friction materials to make it easier to reach the treatment site. The materials may be selected from a group of low friction polymers, for example PTFE.
• Low friction materials may also be applied as a coating onto the pierced member or elongate member, for example PTFE or titanium nitride. Reducing the contact surface area between the members may also help to reduce friction. Adding or removing material from the surfaces of members is one way to reduce contact surface area. For example attaching a closed coiled spring around the piercing member or elongate member, effectively reduces the surface area contacted between the elongate member and lumen because only the peaks ofthe coils contact the lumen. [00166] In additional variations ofthe invention, as shown in Fig. 4C, a balloon catheter may be configured with a piercing member 604.
• the balloon 614 advances into the opening created by the piercing member (in which case the piercing member either retracts into the catheter or advances with the catheter.)
• the balloon 614 would then deploy to dilate the opening for ease of later inserting a conduit.
• a conduit may be located on the balloon itself and deployed on inflation of the balloon. Examples of variations of such a balloon catheter may be found below.
• the needle may be affixed to a tapered introducer type device which is able to dilate the opening.
• the piercing member 604 may also be used to deliver bioactive substances (as described herein) to the site ofthe opening.
• the piercing member 604 may deliver the bioactive substance during creation ofthe opening (e.g., see Fig. 4B) or after dilation ofthe opening (see e.g., Fig. 4C).
• the piercing member 604 may be have a multi- lumen cross-section with different lumens being reserved, for example, for inflating the balloon, aspirating the site for blood, drug delivery, and suction of mucous/fluids at the site.
• an obturator (not shown) may be used to fill a lumen during advancement ofthe piercing member into tissue so that the lumen does not become blocked with tissue or other debris.
• the obturator may be a guide- wire, polymeric column of material, etc.
• Fig. 4D illustrates a variation of a balloon catheter 606 having a piercing member 604.
• the balloon catheter 606 comprises two lumens 608, 610.
• One lumen 608 is fluidly coupled to the interior ofthe balloon 614 while the second lumen 610 extends through the piercing member 604.
• the device 606 may be configured to have any number of lumens as required.
• the piercing member 604 may either be fixedly attached to the distal end ofthe balloon catheter 606. Alternatively, the piercing member 604 may be retractable into the balloon catheter 606 so that it does not cause damage to lung parenchyma when the catheter 606 is inserted into the airway 100 wall.
• the balloon catheter 606 may have a tapered section 612 between the piercing member 604 and the balloon 614 to assist in insertion ofthe balloon 614 into the opening 112.
• Figure 4E illustrates an additional variation of a piercing member 604 according the present invention.
• the piercing member 604 may have a number of ports 616 (e.g., openings, holes, etc.).
• the ports 616 may allow for either aspiration of blood or delivery of bio-active substances as described herein.
• the piercing members 604 shown herein are configured with a beveled tip, it is contemplated that the tip may be any type of tip sufficient to penetrate the airway wall.
• the tip may be non-beveled with sharpened edges, the tip may be a trocar tipped needle, or any other available needle tip configuration.
• the piercing member 604 of Figure 4E is also shown with an obturator placed therein. In this configuration, the obturator 618 blocks the lumen of the piercing member 604 at the distal end. Moreover, as shown, a portion ofthe obturator 618 may be sized such that it is smaller than a lumen ofthe piercing member 604 to allow for delivery of substances or aspiration through the ports 616.
• Figure 4F illustrates yet another variation of a balloon catheter 606 having a piercing member 604.
• the piercing member 604 is capable of being retracted into the catheter 606..
• the ability to retract the piercing member 604 into the catheter 606 reduces the possibility ofthe piercing member 604 causing damage to any lung tissue that is behind the airway wall.
• this variation combines the channel-making step with the conduit deployment step.
• the catheter 606 may have a conduit 202 placed over the balloon 614. Such a variation may create the opening or channel and then deploy the conduit 200 with a single device.
• Figure 4G illustrates another variation of a balloon catheter 606 where the piercing member 604 is slidably located within the catheter 606.
• the catheter 606 contains an outer and inner sheaths 620, 622 which define two lumens.
• the lumen defined by the inner sheath 622 extends to the distal end ofthe catheter 606 and may be used to deliver bioactive substances, for suction, or for irrigation.
• variations ofthe invention include a piercing member which is affixed to the catheter.
• the piercing member could have a flexible body that extends through the catheter to a proximal hub which is able to be coupled to a vacuum source, a source of medication, etc.
• either the piercing member and/or balloon catheter may be "pre-loaded" with a bioactive substance.
• the piercing member 604 may be of a sufficient size or construction that the hole remains open upon removal ofthe piercing member. Once variation of this as shown in Figure 4H, where the device has a conical tip 658 with a lumen extending through out. A piercing member 604 is extendable past the distal tip to pierce the airway wall, after the initial opening is made, the rest ofthe device can be driven into the airway wall, gradually expanding the hole to a desirable diameter which allows the conduit to be subsequently placed. [00174] The makeup of airway tissue may require a considerable amount of force to create a channel with the piercing device.
• Nondistensible balloons are generally made up of relatively inelastic materials consisting of PET, nylons, polyurethanes, polyolefins, PVC, and other crosslinked polymers.
• the makeup of airway tissue may be very tough and resist radial expansions. Therefore it will be generally easier to expand the channel in the airway wall using high pressure nondistensible balloons (> 6 atm), which generally inflate in a uniform shape.
• Nondistensible balloons will occupy a greater mass than distensible balloons because they in an inelastic predetermined form. Too much balloon mass will have too large of a working diameter, which in turn will hinder entry into a channel. Working diameter is the smallest effective diameter opening the uninflated nondistensible balloon can be inserted into. Therefore it is desirable to have the uninflated nondistensible balloon to have a working diameter close to the diameter of the piercing device 604.
• a device of insufficient sharpness will "tent" the airway wall 450. Tenting occurs when a device is placed against an airway wall with significant force but with no puncturing ofthe airway wall. The airway wall will deflect and become displaced until the device is withdrawn. If the tissue becomes tented there remains a significant amount of potential energy placed by the device onto the airway wall.
• a depth limiting feature 654 may overcome this problem.
• Variations ofthe invention include a depth limiting feature that may prevent inadvertent advancement ofthe device when creating the channel.
• a depth limiting feature may prevent inadvertent advancement ofthe device when creating the channel.
• One example of this may be a circular tube 654 placed over the device and set at a fixed distance (e.g. 10 mm) from the distal tip ofthe piercing member, proximal to the balloon, as shown in Figure 4J. If the device does tent and plunge into the airway wall the front face ofthe tube may halt the plunging effect by acting as a barrier.
• Another example would be a secondary balloon, proximal to the channel expansion balloon, placed in a similar position to the circular tube as described above.
• Another example would be a folding basket formed from the outer lumen ofthe device, or constructed from wire.
• variations ofthe invention may include a distal collar 650 on the distal portion ofthe piercing member 604 to precisely limit the maximum extension and retraction ofthe piercing member 604.
• the distal collar 650 would be attached to the piercing member and travel between two set collar stops 652 which are attached to the lumen 656 the piercing member travels in.
• This feature has multiple benefits; first, it has the safety setting a maximum distance for the piercing member to extend, around 2-3 mm has been found to be sufficient in most cases. Thus, the maximum penetration ofthe piercing member 604 is limited which may prevent unintentional damage to the lung tissue.
• the collar 650 protects the bronchoscope by preventing deflection of the distal tip. Deflection can take place when there is a significant amount of gap between the inner sheath 622 and the distal tip ofthe piercing member in the retracted mode.
• the lumen 656 can deflect while the stiffer piercing member will not, and thus the piercing member may pierce through the deflected lumen 656 and subsequently into the bronchoscope.
• a small gap e.g. ⁇ 1mm
• the collar 650 also allows the piercing member to be reliably extended. It was found that when a similar feature was placed at the proximal section ofthe device the piercing member could not reliably be extended to a set distance beyond the distal tip. This is because when in a torturous configuration the outer sheath 620 ofthe device may have a tendency to stretch or compress. As a result the tubing may stretch to such a degree that when the piercing member is fully extended it still may not fully extend past the distal tip ofthe lumen 656. By locating the collar 650 in the distal portion ofthe lumen 656 (e.g. less than 2 inches from the distal tip) the stretching or compression is minimized or eliminated.
• Figures 5A-5C illustrate a way to deploy a conduit in a channel.
• a delivery device 400 is loaded with a conduit 200.
• An access scope-type device 404 e.g., an endoscope, a bronchoscope, or other device
• a guide wire 402 may be used to place the delivery device 400 into the collateral channel 112.
• the guide wire 402 may be a conventional guide- wire or it may simply be comprised of a super-elastic material.
• the use of a guide wire is optional as the invention contemplates placement ofthe conduit 200 using only the delivery device
• Figure 5 A also illustrates articulation (or bending) ofthe deliver device 400 to access the collateral channel 112.
• the invention also contemplates articulation ofthe access device 404.
• the access device 404 may be articulated such that the delivery device 400 may advance straight into the collateral channel 112. Accordingly, the delivery device 400 may exit straight from the access device 404 or it may be articulated into the opening.
• Figure 5B illustrates deployment ofthe conduit 200.
• balloon member 406 is shown in an expanded state resulting in (1) the conduit's center section being radially expanded and (2) the conduit's extension members being outwardly deflected such that opposing extension members sandwich portions ofthe tissue wall 422.
• Diametric-control members 424 are also shown in this figure. The diametric or center-control segments limit the center section's radial expansion. In this manner, conduit 200 is securely placed in the channel to maintain a passageway through the airway wall 422.
• Figure 5C illustrates the deployed conduit 200 once the delivery device 400 is removed from the site. It should be noted that dilation ofthe collateral channel or opening 112 may be performed by mere insertion ofthe conduit 200 and/or delivery device 400.
• conduits deployment of conduits is not limited to that shown in Figures 5A-5C, instead, other means may be used to deploy the conduit.
• spring-loaded or shape memory features may be actuated by mechanical or thermal release and unlocking methods.
• mechanical wedges, lever- type devices, scissors-jack devices, open chest surgical placement and other techniques may be used to deploy the conduit.
• the conduit 200 may be comprised of an elastic or super-elastic material which is restrained in a reduced profile for deployment and expands to its deployed state upon mechanical actuator or release.
• a conduit 201 may be deployed within a second structure such as a second conduit or stent.
• a second structure such as a second conduit or stent.
• Such an approach may be used to increase retention ofthe conduits within the channel as well as prevent closing ofthe channel.
• an initial conduit 200 or stent may be deployed within the channel 112.
• This first conduit or stent may have certain properties that make it more acceptable to implantation within the body without generating an aggressive tissue healing response.
• the stent may be a drug eluting stent, or the conduit may be constructed from a bio-compatible metal without any additional tissue barrier.
• a first conduit 200 (or stent) is placed within the channel 112.
• Figure 5D illustrates a second conduit 201 advanced towards the first conduit 200.
• Figure 5E illustrates the second conduit 201 deployed within the first conduit 200.
• the second conduit 201 may have additional properties that permit the channel to remain patent.
• the second conduit 201 my have a tissue barrier as discussed above, or other construction that generates an aggressive healing response within the lung. Therefore, the first conduit 200, being more conducive to implantation, will serve to anchor both conduits 200, 201 as the tissue either does not grow, or it grows around the outer conduit 200.
• the second conduit for example, may have a tissue barrier placed thereon.
• the tissue barrier ofthe second conduit 201 will prevent tissue from growing through the stent structure.
• the structure of a conduit within a conduit may be incorporated into a single composite structure.
• the conduit 200 is deployed with the distal side towards the parenchymal tissue 460 while the proximal side remains adjacent or in the airway 450.
• the conduit may be deployed with either side towards the parenchymal tissue.
• Figures 6A-6B illustrate another example of deploying a conduit 500 in a channel 510 (or opening) created in a tissue wall 520.
• a delivery tool 530 carrying a deployable conduit 500 is inserted into the channel 510.
• the delivery tool 530 is extended straight from an access catheter 540 such that the delivery tool forms an angle b with the tissue wall 520.
• the tissue wall of airway 522 is shown as being thin and well defined, the present invention may be utilized to maintain the patency of channels and openings which have less well defined boundaries.
• the delivery tool is further manipulated until the conduit is properly positioned which is determined by, for example, observing the position of a visualization mark 552 on the conduit relative to the opening ofthe channel 510.
• Figure 6B illustrates enlarging and securing the conduit in the channel using an expandable member or balloon 560.
• the balloon 560 may be radially expanded using fluid (gas or liquid) pressure to deploy the conduit 500.
• the balloon may have a cylindrical shape (or another shape such as an hourglass shape) when expanded to 1.) expand the center section and 2.) deflect the proximal and distal sections ofthe conduit such that the conduit is secured to the tissue wall 520.
• the tissue wall 520 may distort or bend to some degree but when the delivery tool is removed, the elasticity ofthe tissue tends to return the tissue wall to its initial shape. Accordingly, the conduits disclosed herein may be deployed either perpendicular to (or non-perpendicular to ) the tissue wall.
• Figure 7A illustrates another variation of deploying a conduit 200 into an opening 112.
• the channel 112 prior to deployment ofthe conduit 200, may have a diameter or size that may require an additional dilation or expansion ofthe channel 112 for proper deployment ofthe conduit 200.
• the channel 112 may be created by a piercing member, as described above, where the channel 112 nearly closes upon removal ofthe piercing member.
• the devices and method described herein are not limited to channels 112 of any particular size. The channels may in fact be larger than a diameter ofthe conduit 200 in its un-deployed state.
• the surgeon may advance a balloon catheter 630 containing a conduit 200 towards the site ofthe opening 112.
• the variation ofthe balloon catheter 630 depicted in the figure also includes a guide body 632.
• the guide body 632 may serve various functions to assist in locating the opening 112 and placing the conduit 200.
• the guide body 632 may have a rounded front surface. This allows probing ofthe catheter 630 against the airway 100 wall to more easily locate the opening 112. The rounded surface ofthe guide body 632 will not drag on the airway tissue.
• the guide body 632 provides an additional function of temporarily anchoring the device 630 within the opening 112.
• the ability to temporarily anchor the device 630 into the opening 112 may be desirable due to the natural tidal motion ofthe lung during breathing.
• the increased surface area ofthe guide body 632 requires increased resistance upon remove the guide body 632 from the opening 112. Such a feature lessens the occurrence of unintended removal ofthe device from the site as the lung tissue moves.
• a portion ofthe guide body 632 serves as a resistance surface to provide the temporary anchoring function. Additional variations ofthe guide body 632 are shown below.
• FIGS 8A-8F illustrate additional variations of guide bodies 632 for use with the present invention.
• the guide body 632 is located on the distal end ofthe balloon catheter 630.
• the guide body 632 will have a front surface 634 that is preferably smooth such that it can easily be moved over the airway wall.
• the guide body 632 Proximal to the front surface 634, the guide body 632 will have at least one resistance surface 636 which is defined as an area that causes increased resistance upon removal of he guide body 634 from the airway wall.
• the resistance surface 636 will be adjacent to an area of reduced diameter 638 to which allows the guide body 632 to nest within the opening 112 in the airway wall.
• the guide body 632 may have any number of shapes as shown in the figures.
• Figure 8F illustrates another variation of a guide body 632 having a resistance surface 636 which comprises an area of increased surface roughness such that the surface will drag upon the airway wall or tissue surrounding the channel 112.
• the balloon catheters 630 ofthe present invention may include a dilating member between the guide body 632 and balloon 614.
• the dilating member comprises a tapered section.
• the invention is not limited as such.
• the dilating member may comprise a second inflatable balloon, or other expanding device.
• the dilating members may also be retractable within the elongate shaft.
• Figures 9A and 9B depict cross sections of examples of a balloon catheter 630 having a guide body 632 that includes a lumen 642 which terminates at a surface ofthe guide body 632.
• the lumen 642 may be used for suction, irrigation, or deliver bio-active substances, etc.
• the catheter 630 may also have an additional lumens 646, 646, 648 as shown, for inflation ofthe balloon 614 and for additional suction 644, and for communication with the guide body lumen 642.
• the lumen may also be used to advance a piercing member 604 to the airway wall to create the channel 112.
• any ofthe balloons described herein may be distensible balloons (e.g., they assume a predetermined shape upon expansion) or elastic balloons (e.g., simply expand). Use of a distensible balloon permits control in dilating the opening 112 or placement ofthe conduit.
• EXAMPLE - Implant Implants comprising stainless steel mesh frame fully encapsulated with a composition comprising silicone (as described below) and paclitaxel were implanted in several canine models. Visual observation indicated that, on average, the passage through the implants ofthe present invention remained unobstructed and were associated with significantly reduced fibrotic and inflammatory responses, in canine models, at a considerably higher rate than an implant without any drug adjunct or coronary drug eluting stents (as shown in Figure 12). [00202] The composition comprised approximately a 9% paclitaxel to silicone ratio with approximately 400 micrograms of paclitaxel per implant. Measurements found that approximately 30% ofthe paclitaxel released after 60 days, hi general, for implants with the paclitaxel silicone composition, observations of chronic inflammation, epithelial metaplasia and fibrosis were all very mild.
• paclitaxel as the bioactive substance, polymers with solubility parameters between 5 - 25 (MPa) ⁇ l/2 were believed to provide sufficient elution rates.
• the polymer used in the example device has good diffusivity for lipophilic drug (such as paclitaxel) because the side methyl group on the silicone may be substituted with more lipophilic hydrocarbon molecules containing vinyl group or groups in addition polymerization by platinum catalyst.
• composition for the example may be as follow: polymer part: polydimethylsiloxane, vinyldimethyl terminated, any viscosity; and/or polydimethylsiloxane, vinylmonomethyl terminated, any viscosity.
• the cross-linker part polydimethylsiloxane, any viscosity; and or polymonomethylsiloxane, any viscosity.
• Platinum catalyst part and/or cross-linker part platinum; and/or platinum- divinyltetramethyldisiloxane complex in xylene, 2-3% Pt; and/or platinum- divinyltetramethyldisiloxane complex in vinyl terminated polydimethylsiloxane, 2- 3% Pt; and/or platinum- divinyltetramethyldisiloxane complex in vinyl terminated polydimethylsiloxane, ⁇ 1% Pt; platinum-Cyclovinylmethylsiloxane complex, 2-3% Pt in cyclic vinyl methyl siloxane. [00205] These components may be combined in different ratios to make the polymer.
• the hydrocarbon side chain off the silicone back bone makes this polymer system unique and may result in a "zero-order"-like release profile.
• the amount of vinyl siloxane cross- linker may determine the rate ofthe drug release and diffusivity ofthe polymer to the drug.
• polydimethylsiloxanes such as: trimethylsiloxy terminated polydimethylsiloxane in various viscosities, (48-96%) dimethyl (4-52%) diphenylsiloxane copolymer in various viscosities, dimethylsiloxane-ethylene oxide copolymer, dimethyl diphenylsiloxane copolymer, polymethylhydrosiloxane, trimethylsilyl terminated at various viscosities, (30-55%) methyldro- (45-70%) dimethylsiloxane copolymer at various viscosities, polymethylphenylsiloxane, polydimethylsiloxane silanol terminated at various viscosities, polydimethylsiloxane aminopropyldimethyl terminated at various viscosities.
• paclitaxel a release profile was found to be acceptable with a polymer system consisting of polydimethylsiloxane vinyl terminated at various viscosity and a range of platinum-mono, di, tri and/or tetramethyldisiloxane complex.

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• 2004
  • 2004-07-19 WO PCT/US2004/023304 patent/WO2005006963A2/en active Application Filing
  • 2004-07-19 WO PCT/US2004/023305 patent/WO2005006964A2/en active Application Filing
  • 2004-07-19 EP EP04778682A patent/EP1648283A4/de not_active Withdrawn
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