[go: up one dir, main page]

WO2024182596A2 - Tube endoluminal à ballonnet avec système d'administration de médicament - Google Patents

Tube endoluminal à ballonnet avec système d'administration de médicament Download PDF

Info

Publication number
WO2024182596A2
WO2024182596A2 PCT/US2024/017843 US2024017843W WO2024182596A2 WO 2024182596 A2 WO2024182596 A2 WO 2024182596A2 US 2024017843 W US2024017843 W US 2024017843W WO 2024182596 A2 WO2024182596 A2 WO 2024182596A2
Authority
WO
WIPO (PCT)
Prior art keywords
balloon
ett
tube
perforations
lumen
Prior art date
Application number
PCT/US2024/017843
Other languages
English (en)
Other versions
WO2024182596A3 (fr
Inventor
Ihab Kamel
Original Assignee
Temple University-Of The Commonwealth System Of Higher Education
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Temple University-Of The Commonwealth System Of Higher Education filed Critical Temple University-Of The Commonwealth System Of Higher Education
Publication of WO2024182596A2 publication Critical patent/WO2024182596A2/fr
Publication of WO2024182596A3 publication Critical patent/WO2024182596A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1011—Multiple balloon catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0068—Static characteristics of the catheter tip, e.g. shape, atraumatic tip, curved tip or tip structure
    • A61M25/007—Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes

Definitions

  • the ETT is used to intubate the respiratory channel (i.e., the trachea) of a patient to deliver air, oxygen, and/or anesthetic gases during general anesthesia and mechanical ventilation.
  • the ETT is a standard component of general anesthesia administered worldwide on a daily basis.
  • the ETT is used to ventilate patients after they stop breathing following the induction of anesthesia and until emergence. Further, the ETT is used to provide respiratory support for critically ill patients in the intensive care unit.
  • the ETT has an air-inflated cuff that exerts circumferential pressure against the tracheal mucous membrane (lining tissue) and tracheal structure to create an air-tight, fluid-tight seal.
  • This air-tight, fluid-tight seal is to prevent anesthetics and respiratory gas leaks out of the lungs and prevent secretions from entering into the airway during ventilation.
  • the tracheal mucosa is highly innervated and protected by resilient reflexes rendering it highly sensitive to tactile stimulation.
  • the circumferential pressure resulting from the ETT cuff inflation causes intense stimulation that leads to significant short and long-term adverse consequences.
  • the primary cause of the short-term consequences is the stimulus caused by the endotracheal tube pressure that often exceeds the stimulus from the surgical procedure and leads to major adverse physiologic consequences.
  • the intense stimulation caused by the inflated endotracheal tube cuff leads to local respiratory and broad Attorney Docket No.: 206017-0214-00WO systemic responses.
  • Local respiratory responses are mediated by reflexes and include closure of the small airways, coughing, retching, and straining.
  • Broad systemic body responses are primarily due to stimulation of the sympathetic nervous system with the resulting tachycardia (increased heart rate), hypertension (increased blood pressure), release of stress response mediators such as epinephrine and norepinephrine, and systemic vasoconstrictors with a resultant reduced blood flow in most tissues.
  • the systemic effects of the ETT stimulation can be appreciated as early as 15 second after intubation while the local effects are usually immediate.
  • the long-term complications of the endotracheal tube are often seen in critically ill patients intubated for prolonged periods of time (days to weeks) due to continued stimulation and compression of the tracheal mucosa with the resultant pathologic morphological and anatomical changes that constitute the body’s and tracheal tissue reaction to the continuous ETT cuff pressure.
  • compression of the inaccessible area of the tracheal mucosa by the inflated cuff prevents proper ventilation and draining of this area leading to colonization of pathogens and infection.
  • the short-term adverse physiologic consequences caused by the intense stimulation of the ETT cuff have numerous clinical implications that can adversely impact patient safety and clinical outcomes.
  • the first adverse consequence of this intense stimulation of the tracheal mucosa is bronchospasm (constriction of the airways, making it very difficult to ventilate the patient and it can be life-threatening if not promptly treated).
  • This complication is exaggerated in patients under light or inadequate anesthesia, smokers, as well as patients with asthma and chronic obstructive pulmonary disease (COPD) who already have sensitive airways even in the absence of the stimulus of the ETT.
  • COPD chronic obstructive pulmonary disease
  • anesthesiologists increase the anesthetic depth to overcome the stimulus through the inhibition of the tracheal and bronchial reflexes that will be triggered by the ETT cuff pressure in addition to administering bronchodilators like albuterol.
  • Emergence reactions include violent and combative emergence, coughing, retching, stimulation of the sympathetic nervous system, and bucking.
  • Emergence reactions can lead to serious deleterious consequences that include increased intracranial pressure, increase intraocular pressure, acute increase in heart rate (tachycardia), increase in the blood pressure (hypertension), myocardial ischemia and infarction( increased stress on the heart leading to oxygen supply demand mismatch especially in patients with coronary artery disease), excessive stress on critical surgical repair sutures and anastomosis due to straining, premature extubation by the anesthesiologist to mitigate the emergence reactions, inadvertent premature extubation by the patient due to violent emergence, aspiration pneumonitis (due to vomiting, straining, and early extubation by the anesthesiologist to control violent emergence), and physical injury for the patient and perioperative staff.
  • the patient wakes up after a significant delay to emergence and extubation while the emergence reactions still ensues because at this point the patient is lightly sedated while being stimulated by the inflated ETT cuff.
  • the major factor behind the ineffectiveness of current approaches is that they don’t treat the stimulus of the tube at the local level (treating the cause) but rather focus on masking the symptoms by providing sedation and analgesia using systemic intravenous drugs that affect the entire nervous system at the level of the brain and the spinal cord.
  • lidocaine LTA 360 an FDA approved device that allows the injection of lidocaine using an introducer with an atomizer spraying lidocaine in multiple angles (360 degrees’ distribution pattern) to anesthetize the tracheal mucosa immediately before intubation. This device is valuable to prevent the response related to the tube during intubation and shortly afterwards.
  • Lidocaine LTA 360 is usually ineffective because the duration of most surgical procedures outlasts the effective duration of this single preintubation topical lidocaine application device.
  • the LTA device is used primarily to mitigate the stimulus of the ETT during intubation.
  • the LTA 360 does not result in effective saturation of the tracheal mucosa with the sprayed medication at the target area (the ETT cuff abutting the tracheal mucosa) for two reasons.
  • the first reason is that the portion of the sprayed liquid lidocaine that is not immediately absorbed by mucosa during application will trickle distally (further down the bronchial tree) away from the target area.
  • the blind lidocaine injection process is independent from the endotracheal tube placement which may lead to suboptimal local anesthetic distribution to the target tracheal mucosal area determined by final placement of the ETT tube.
  • the third adverse consequence is the hemodynamic change associated with the administration of higher doses of anesthetics to overcome the physiological effects of the ETT cuff stimulation while these higher doses are not necessarily needed for the stimulation caused by the procedure.
  • the administration of higher doses of anesthetics to mitigate the major adverse physiological responses of the ETT can lead to hypotension and tachycardia in patients with heart disease, cerebral aneurysm, vascular disease, renal disease, and pulmonary disease increasing the risk of perioperative adverse outcomes in this high-risk patient population.
  • the fourth adverse consequence is the hemodynamic change associated with the administration of the lower doses of anesthetics that are inadequate to overcome the ETT stimulation.
  • the administration of lower dose of anesthesia may be due to patient frailty, profound hypotension, significant cardiovascular disease, and shock. In this case the patient may experience cough and increased heart rate response to the ETT cuff stimulation while experiencing critically low blood pressure levels precluding safe administration of high levels of anesthetics.
  • Intraoperative administration of opioids has been linked to prolonged postoperative opioid use, a contributing factor to the opioid pandemic.
  • the ability to provide regional anesthesia to the tracheal mucosa to mitigate the adverse physiologic consequences of the endotracheal tube cuff inflation can have an opioid sparing effect in the perioperative period.
  • a sixth and long-term adverse consequence associated with the stimulation caused by the ETT is tracheal stenosis. Tracheal stenosis is the result of prolonged endotracheal intubation in critically ill patients in intensive care unit.
  • Tracheal stenosis is a significant source of morbidity and mortality for patients as it leads to shortness of breath, limitation of physical activity, inability to lie supine, hypoxia, worsening of cardiac pulmonary disease, and multiple surgical interventions.
  • tracheal stenosis for causes other than intubation (such as idiopathic stenosis) is usually performed to avoid the progression to severe stenosis.
  • Treatment usually includes intralesional injection of steroids (directly into the narrow tracheal area) and/or laser excision.
  • steroids directly into the narrow tracheal area
  • laser excision The ability to apply steroids topically to the narrow tracheal area while avoiding direct injection of steroid in the trachea may assist in early treatment of patient with tracheal stenosis while minimizing local and systemic complications associated direct needle injections.
  • a seventh long-term adverse consequence associated with prolonged endotracheal intubation and continuous endotracheal cuff inflation is pulmonary infection.
  • Infection can be caused by the lack of ventilation and proper drainage of the area of tracheal mucosa continually compressed by the ETT cuff leading to pathogen colonization and multiplication. This can be a contributing factor to tracheal stenosis and pulmonary infections such as pneumonia. Infiltrating the target tracheal mucosa area continually compressed by the ETT cuff with antibiotics can reduce colonization of pathogens and mitigate infectious complications.
  • the present invention relates to an endoluminal medication delivery device comprising an elongated tube having proximal and distal ends with a lumen therethrough, a plurality of balloons positioned on the outer surface of the elongated tube, the plurality of balloons comprising a first balloon connected to one or more conduits extending proximally along the elongated tube, wherein the first balloon is configurable between at least first and second configurations as a fluid moves in and out of the balloon and a second balloon at least partially surrounding the first balloon and connected to one or more conduits extending proximally along the elongated tube, wherein the second balloon comprises an impermeable proximal portion, and at least one permeable portion.
  • the one or more conduits of the second balloon comprise any of: an even number of tubes, symmetrical positioning, symmetrical configuration, collapsible material, impermeable material, equal length, equal run, or equal flow.
  • each balloon of the plurality of balloons at least partially surrounds the elongated tube and is formed in one or more shapes selected from: sphere, hemisphere, cylinder, half-cylinder, ellipsoid, flower, petals, star, burst, crescent, oval, polygon, cone, prism, ellipsoid, flower shape, concentric ellipsoids, concentric spheres, or any combination thereof.
  • the plurality of balloons are configured or positioned in one or more patterns along the elongated tube selected from: linear, non- linear, asymmetric, zig-zag, circular, spiral, or any combination thereof.
  • the at least one permeable portion comprises a plurality of perforations that are patterned or configured in one or more configurations selected from: horizontal pattern, vertical pattern, x-pattern, v-pattern, z-pattern, zig-zag pattern, spiral, or gradient pattern.
  • the first balloon is completely disposed within the second balloon.
  • the plurality of perforations are positioned circumferentially on the second balloon and patterned in 1 to 15 lines and comprising at least one central line. In some embodiments, the plurality of perforations are circumferentially limited to 10 – 75% of the at least one central line. In some embodiments, each perforation of the plurality of perforations have similar diameter or different diameters. In some embodiments, the at least one permeable portion comprises at least one porous membrane. In some embodiments, the impermeable proximal portion of the second balloon is a circumferentially impermeable surrounding the elongated tube.
  • the device further comprises an impermeable distal portion on the second balloon that is circumferentially impermeable surrounding the elongated tube.
  • each balloon of the plurality of balloons comprises one or more internal chambers.
  • the plurality of balloons comprises repeating pairs of first and second balloons positioned along the length of the elongated tube.
  • the device further comprises one or more medication delivery devices positioned within or in fluid connection with the one or more conduits of the second balloon.
  • an external reservoir is fluidly connected to the one or more conduits of the second balloon and configured to allow the introduction of a fluid or solution to the second balloon.
  • the fluid used to inflate the first balloon is a gas, solution, or a liquid.
  • the elongated tube is sized and shaped in the form of a tube selected from: an endotracheal tube, an endobronchial tube, a tracheostomy tube, a laryngeal mask airway, an oral airway, a nasal airway, a nasogastric tube, a feeding tube, interventional vascular catheter, compression inflatable balloon, a dilating device, indwelling catheter, an endoscope, topicalization device, or a drainage catheter.
  • the present invention provides a method of providing access to a bodily passage comprising the steps of providing an endoluminal medication delivery device comprising an elongated tube having proximal and distal ends with a lumen therethrough, a plurality of balloons positioned on the outer surface of the elongated tube, the plurality of balloons comprising a first balloon connected to one or more conduits extending proximally along the elongated tube, wherein the first balloon is configurable between at least first and second configurations as a first fluid moves in and out of the balloon, and a second balloon at least partially surrounding the first balloon and connected to one or more conduits extending proximally along the elongated tube, wherein the second balloon comprises an impermeable proximal portion, and at least one permeable portion, wherein the one or more conduit of the second balloon is fluidly connected to an external reservoir, introducing the endoluminal medication delivery device into the bodily passage, configuring the first balloon to the second configuration thereby sealing the bodily passage,
  • the bodily passage is an airway.
  • the bodily passage is gastrointestinal tract lumen, blood vessel lumen, bodily pouch, external auditory canal, urinary system lumen, intracranial passage, bodily space, bodily passage, and bodily endocrine ducts.
  • the second fluid comprises at least one therapeutic agent selected from lidocaine, steroid, antibiotics, or vasoactive drug.
  • the external source is one selected from a pump, a manually operated syringe, or a programmable syringe.
  • FIG.1 depicts an exemplary endoluminal medication delivery device of the present invention.
  • FIG.2 depicts five cross-sections (A, B, C, D, E) in the endoluminal medication delivery device 100 that will represent the cross-sections depicted in FIGS.3- 6.
  • FIG.3A through FIG.3E depict five cross-sections of device 100 where lumen 116 and lumen 122 are embedded in the inner curvature of body 107 of device 100.
  • the 5 cross-sections A, B, C, D, E correspond to those depicted in Fig.2.
  • FIG.4A through FIG.4E depict five cr4oss-sections of device 100 where lumen 116 is embedded in the inner curvature of body 107 of device 100 and lumen 122 is externally attached to the inner curvature of body 107 of device 100.
  • the 5 cross- sections A, B, C, D, E correspond to those depicted in Fig.2.
  • FIG.5A through FIG.5E depict five cross-sections of device 100 where lumen 116 is embedded in the inner curvature of body 107 of device 100 and lumen 122 is embedded in the outer curvature of body 107 of device 100.
  • the 5 cross-sections A, B, C, D, E correspond to those depicted in Fig 2.
  • An alternative but similar design would be reversing the positions of lumen 116 and lumen 122 in the inner and outer curvatures of body 107 of device 100.
  • FIG.6A through FIG.6G depict various designs of opening 119 at the cross-sectional plane B depicted in FIG.2.
  • FIG.7 depicts the second balloon body of an exemplary endoluminal medication delivery device of the present invention having five middle circumferential lines of perforations.
  • FIG.8A through FIG.8C depict examples of various locations of perforations 124 in the second balloon body 118.
  • FIG.8A depicts the location of perforations 124 in the middle 1/3 of the second balloon body.
  • FIG.8B depicts the Attorney Docket No.: 206017-0214-00WO location of perforations 124 in the middle 1 ⁇ 2 of the second balloon body.
  • FIG.8C depicts the location of perforations 124 in the distal 1 ⁇ 2 of the second balloon body.
  • FIG.9A through FIG.9S depict various configurations of perforations 124 within a given location in the second balloon body 118.
  • FIG.9A depicts a gradual increase in the size of the perforations 124 with the small perforations located proximally and larger perforations located distally.
  • FIG.9B depicts a smaller number of perforations 124 located proximally and a larger number of perforations 124 located distally.
  • FIG.9C depicts longitudinal columns of the perforations.
  • FIG.9D depicts smaller size perforations 124 located in the hemisphere of the second balloon body on the same side of opening 119 while larger perforations 124 are located in the hemisphere opposite to opening 119.
  • FIG.9E depicts smaller number of perforations 124 located in the hemisphere of the second balloon body on the same side of opening 119 while larger number of perforations 124 are located in hemisphere opposite to opening 119.
  • FIG.9F depicts perforations 124 located at a relatively more distal position in the hemisphere of the second balloon body on the same side of opening 119 while perforations 124 on the hemisphere opposite to opening 119 are located relatively more proximal.
  • FIG.9G depicts the perforations 124 configured in circumferential “V” shaped patterns.
  • FIG.9H depicts perforations 124 configured in circumferential “X” shaped patterns as one layer of large sized “X” shapes or multiple horizontal circumferential layers of small size “X” shaped perforations.
  • FIG.9I depicts perforations 124 configured in multiple circumferential “Z” shaped patterns.
  • FIG.9J depicts perforations 124 configured in multiple horizontal layers of zig-zag patterns.
  • FIG.9K depicts perforations 124 widely spaced on the horizontal axis (horizontal distance between each perforation may range from 2-10 mm) while vertically aligned.
  • FIG.9L depicts perforations 124 widely spaced on the horizontal axis (horizontal distance between each perforation may range from 2-10 mm) while vertically alternating.
  • FIG.9M depicts the medication delivery area of the second cuff being a membrane.
  • FIGs.9N and 9O depicts the truss-cuff design of the medication delivery second cuff in which the medication delivery tube 122 and opening 119 continue as an even numbered network of symmetrically opposing impermeable delivery tubes of equal lengths that open into a circumferential collapsible perforated band shaped second cuff that surrounds the middle and/or distal portion of the first cuff.
  • FIG.9N depicts the longitudinal view of the truss-cuff design for the second medication delivery cuff using 2 symmetrically opposing equal-length impermeable delivery tubes ending in the perforated/permeable medication delivery cuff.
  • FIG.9O depicts the top apical view of the truss-cuff design for the second medication delivery cuff using 4 symmetrically opposing equal-length impermeable medication delivery tubes ending in the perforated/permeable medication delivery cuff.
  • FIG.9P depicts the cross-section of the medication delivery system in a hemi-cuff design consisting of 4 separate cuffs (2 inflating first cuffs and 2 medication delivery second cuffs.
  • FIG.9Q depicts the cross- section of the Quad-cuff design consisting of 8 separate cuffs (4 inflating first cuffs and 4 medication delivery second cuffs).
  • FIG.9R depicts a longitudinal view of an endotracheal tube with variable sets of medication delivery system of the invention.
  • a distal medication delivery system consisting of full-cuff design to seal the trachea and provide medication delivery to the tracheal mucosa.
  • a second and separate proximal medication delivery system (MD 2) utilizing a hemi-cuff design along the length of the endotracheal tube.
  • the separate hemi-cuffs of the second medication delivery system (MD2) are located at various sites along the length of the ETT.
  • FIG.9S Depicts a longitudinal view of an endotracheal tube with variable sets of medication delivery system of the invention.
  • a distal medication delivery system consisting of truss-cuff design with 2 delivery tubes to seal the trachea and provide medication delivery to the tracheal mucosa.
  • a second and separate proximal medication delivery system (MD 2) utilizing a hemi-cuff design along the length of the endotracheal tube.
  • the separate hemi-cuffs of the second medication delivery system (MD2) are located at various sites along the length of the ETT.
  • FIG.10 depicts the location of perforations or permeable membrane 124 on various second balloon designs.
  • FIG.11 is a flowchart depicting an exemplary method of providing access and delivering medication to a bodily passage.
  • FIG.12A and FIG.12B depict an exemplary endotracheal tube (ETT).
  • FIG.12A depicts an ETT with a first balloon body inflated using a syringe with a manometer.
  • FIG.12B depicts a magnified view of the digital reading of the manometer depicted in FIG.12A.
  • FIG.13A through FIG.13B depict an exemplary ETT positioned within a cylindrical tube with a diameter similar to the average diameter of the adult human trachea.
  • FIG.13A depicts an exemplary ETT with a first balloon body inflated using a syringe with a manometer positioned within the cylindrical tube.
  • FIG.13B depicts a magnified view of the digital reading of the manometer and the inflated first balloon body depicted in FIG.13A. The digital reading indicated represents an average pressure derived from peer-reviewed reports of ETT cuff pressures during clinical use.
  • FIG.14A and FIG.14B depict addition of an absorbent paper towel to the distal end of an exemplary ETT.
  • FIG.14A depicts an exemplary ETT having a paper towel wrapped around the distal half of the second balloon.
  • FIG.14B depicts an exemplary ETT within the cylindrical tube having a paper towel wrapped around the distal half of the second balloon with a first balloon body inflated using a syringe with a digital manometer.
  • FIG.15 depicts an exemplary ETT device having a second balloon body wherein the second balloon body comprises plurality of perforations distributed uniformly throughout its entire surface area (alternative design).
  • FIG.16 depicts movement and delivery pattern of injected dye within an exemplary ETT device having a first balloon body inflated to 42 cmH2O and a second balloon body wherein the second balloon body comprises plurality of perforations distributed uniformly throughout its entire surface area (alternative design).
  • FIG.17A through FIG.17D depict distribution of the injected dye in a model simulating clinical application.
  • First balloon body is inserted in a cylindrical tube and inflated to 42 cmH 2 O.
  • FIG.17A depicts an exemplary ETT device having a second balloon body with plurality of perforations distributed uniformly throughout its entire surface area positioned within a cylindrical tube.
  • FIG.17B depicts the distribution of the dye from the first low-pressure pores first encountered by the injected dye without any delivery of the dye to the compressed area between the ETT and the cylindrical tube.
  • FIG.17C depicts a magnified view of FIG.17B showing the dye accumulation and failure of delivery of the dye to the target area.
  • FIG.17D depicts an upper view of the cross-section of the lower end of the cylindrical tube demonstrating the accumulated dye.
  • FIG.18A through FIG.18D depicts movement and delivery pattern of injected dye within an exemplary ETT device having a second balloon body with plurality of perforations distributed uniformly throughout its entire surface area in the presence of a highly absorbent lining positioned within a cylindrical tube.
  • FIG.18A depicts a top view of the exemplary ETT device before dye injection (baseline).
  • FIG.18B depicts the ETT device after dye injection (2 ml).
  • FIG.18C depicts a top view of the exemplary ETT device after dye injection and the inability of the dye to reach the middle part of ETT cuff which is the target high-pressure area.
  • FIG.18D depicts a magnified top view of the exemplary ETT device after dye injection.
  • FIG.19A through FIG.19D depict movement and delivery pattern of injected dye within an exemplary ETT device of the present invention having a second balloon body with plurality of perforations positioned in three middle circumferential lines. The first balloon body is inflated to 42 cmH2O.
  • FIG.19A depicts a top view of an exemplary ETT device of the present invention before dye injection (baseline).
  • FIG.19B depicts a top view of an exemplary ETT device of the present invention after injection of the dye (2 ml).
  • FIG.19C depicts another top view of an exemplary ETT after injection of the dye to provide a 360-degree view of the ETT device.
  • FIG.19D depicts another top view of an exemplary ETT after injection of the dye to provide a 360-degree view of the ETT device.
  • FIG.20A and FIG.20B depict movement and delivery pattern of injected dye within an exemplary ETT device of the present invention having a second balloon body with plurality of perforations positioned in three middle circumferential lines, wherein the exemplary ETT is positioned within a cylindrical tube simulating clinical application with the first balloon chamber inflated to 42 cmH 2 O.
  • FIG.20A depicts a top view of an exemplary ETT device of the present invention before dye injection Attorney Docket No.: 206017-0214-00WO (baseline).
  • FIG.20B depicts a magnified top view of an exemplary ETT device of the present invention after dye injection and depicts the circumferential delivery of the dye to the target high-pressure point.
  • FIG.21A and FIG.21B depict an exemplary ETT device of the present invention with the first balloon chamber inflated to 42 cmH2O after dye injection wherein the circumferential spread of the dye around the center of the second balloon body at the high-pressure area of the balloon-cylinder interface is depicted.
  • FIG.21A depicts a top view of an exemplary ETT device of the present invention after dye injection.
  • FIG.21B depicts a magnified top view of an exemplary ETT device of the present invention after dye injection.
  • the distribution pattern depicted in FIG.21A and FIG.21B indicated the optimal and desired distribution pattern for maximal efficacy and minimal side effects.
  • FIG.22A depicts a perspective view of an exemplary ETT device of the present invention after dye injection.
  • FIG.22B depicts a perspective view of an exemplary ETT device of the present invention after dye injection wherein a small dose of dye is accumulated beyond the high-pressure point.
  • FIG.23A through FIG.23D depict movement and delivery pattern of an exemplary ETT device of the present invention with the first balloon chamber inflated to 42 cmH2O inside the cylindrical tube in the presence of a highly absorbent lining to demonstrating the diffusion pattern and to confirm delivery of the medication to and beyond the middle high-pressure point (target area).
  • FIG.23A depicts a top view of an exemplary ETT device of the present invention before injection of the dye (baseline).
  • FIG.23B depicts a top view of an exemplary ETT device of the present invention after injection of the dye (2 ml).
  • FIG.23C depicts a top view of an exemplary ETT device of the present invention after injection of the dye.
  • FIG.23D depicts a magnified top view of an exemplary ETT device of the present invention after injection of the dye.
  • FIGS.23B- 23D demonstrate a diffusion pattern that indicates the ability of the present invention to deliver the dye to and beyond the middle high-pressure point of the ETT second cuff Attorney Docket No.: 206017-0214-00WO while avoiding loss of dye in the low-pressure area proximal to ETT compressed area (target area) as indicated by the dashed blue arrow.
  • Attorney Docket No.: 206017-0214-00WO The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal amenable to the systems, devices, and methods described herein.
  • the patient, subject or individual may be a mammal, and in some instances, a human.
  • cuff and “balloon”, and the like are used interchangeably herein, and refer to any inflatable portions, regions or members on catheter or tube devices or related methods described herein.
  • the cuff or balloon may be any inflatable portion or member found on any related medical device or system such as an endoluminal medication delivery system.
  • fluid as used herein may refer to any substance capable of flowing freely and having no fixed shape.
  • the fluid may be any fluid including, but not limited to, gases, liquids, solutions, compositions, agents, drugs, therapeutics, medications, or any combination thereof. Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format.
  • range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.
  • the present invention provides an endoluminal medication delivery device configured to allow precise and controlled circumferential medication delivery to the interface between the device and the compressed surrounding tissue lining the lumen (e.g., mucosa/mucous membrane).
  • the endoluminal medication delivery device may be used as one including but not limited to an endotracheal tube (ETT), an endobronchial tube, tracheostomy tube, a laryngeal mask airway, an oral Attorney Docket No.: 206017-0214-00WO airway, a nasal airway, a nasogastric tube, airway topicalization device, feeding tube, a dilating device, an endoscope, a drainage catheter, and etc.
  • the endoluminal medication delivery device of the present invention may be used with cuffed endoluminal catheters/tubes.
  • endoluminal device may be a solid tube, stylet, or a boogie.
  • the endoluminal cuffed catheters/tubes aim is to deliver medications, fluids, air, medical gases, or provide access into a lumen within the human body through the patent lumen of the catheter/tube.
  • endoluminal catheters/tubes use inflatable circumferential cuffs usually filled with air (most common) or saline (less common).
  • the device of the present invention provides a medication delivery system through a second perforated circumferential cuff (balloon) that overlaps the main air-inflated sealing cuff to reach the tissue surface under compression by the main inflated cuff, an area that is otherwise impossible to reach and medicate using currently available devices and practices.
  • the second cuff is specifically designed to serve as an access port operating at and utilizing the high-pressure created by inflated first cuff and surrounding lumen interface.
  • the invention offers a unique and specific design to deliver a liquid or viscous medication to the target area.
  • the endoluminal medication delivery device of the present invention may be added to uncuffed endoluminal devices that require the injection of a medication to the surrounding endoluminal tissues or mucosa.
  • the first cuff can be inflated to enable delivery of the medication to the surrounding lumen surface from the perforated second cuff under the pressure created by the inflated first cuff, then the first cuff can be deflated after medication delivery to maintain the uncuffed configuration within the lumen.
  • FIG.1 an exemplary endoluminal medication delivery device 100 is shown.
  • Device 100 comprises a proximal end 102, a distal end 104, a tube 106, a first balloon 108 and a second balloon 110.
  • Tube 106 is within the body (outer wall) 107 of device 100.
  • body (outer wall) 107 may be oval or circular in cross-section with variable diameter and length defining the shape and capacity of tube 106. In some embodiments, body 107 may have variable length, design, and angles. The space between the inner walls of body 107, the proximal end 102, and distal end 104 define the boundaries of tube 106. Attorney Docket No.: 206017-0214-00WO Tube 106 is positioned between proximal end 102 and distal end 104. In some embodiments, tube 106 may be used to accommodate a guidewire or a stylet for introduction of device 100 into the subject’s body cavity.
  • tube 106 may have any suitable diameter and length known to one skilled in the art based on various considerations, including the desired bodily passage within which the medical device is intended to be used. In some embodiments, tube 106 may have an internal diameter ranging between 2 - 14 mm. In some embodiments, tube 106 may have an internal diameter ranging between 5 - 36 mm. In some embodiments, tube 106 may have a length ranging between 20 - 450 mm. In some embodiments, tube 106 may have a length ranging between 80 - 1200 mm. In some embodiments, tube 106 may be made with any suitable material known to one skilled in the art based on various considerations, including the desired flexibility, shape (curvature and angle), and rigidity of tube 106.
  • tube 106 may be straight. In some embodiments, tube 106 may be curved to fit the anatomical curvature of the airway with radius of approximately 140 mm (Magill curve).
  • Example materials considered suitable to form tube 106 may include, but are not limited to, biocompatible materials, materials that can be made biocompatible, metals such as stainless steel, titanium, nickel-titanium alloys (e.g., Nitinol), polymers, polyvinyl chloride (PVC), rubber, nylon, polyethylene, polyurethane, polytetrafluoroethylene (PTFE), ePTFE, silicone, coiled materials, braided materials, and any other material considered suitable for a particular application.
  • metals such as stainless steel, titanium, nickel-titanium alloys (e.g., Nitinol), polymers, polyvinyl chloride (PVC), rubber, nylon, polyethylene, polyurethane, polytetrafluoroethylene (PTFE), ePTFE, silicone, coiled materials, braided
  • tube 106 may have a tip 105 positioned at distal end 104.
  • tip 105 may have any diameter known to one skilled in the art.
  • tip 105 may have a diameter smaller than the diameter of tube 106.
  • tip 105 may have the same diameter as of the diameter of tube 106.
  • tip 105 may have any shapes known to one skilled in the art including but not limited to pointed, beveled, etc.
  • tube 106 may be configured to attach to any device known to one skilled in the art at proximal end 102.
  • tube 106 may be connected to any device through any method including but not limited to a luer lock connection, a smooth push-in adaptor, and etc.
  • the proximal end Attorney Docket No.: 206017-0214-00WO 102 is attached using an adaptor to the breathing circuit and respiratory gases delivery system, while the distal end is inserted in the patient’s trachea through vocal cords.
  • first balloon 108 is externally attached to tube 106 anywhere between proximal end 102 and distal end 104. In some embodiments, first balloon 108 may be positioned closer to distal end 104.
  • First balloon 108 comprises a first balloon body 112 having a proximal end 117 and a distal end 109 and a first opening 111.
  • First balloon body 112 and the portion of the exterior surface of tube 106 define a first balloon chamber 114.
  • First opening 111 is fluidly connected to an external source through an inflation conduit or lumen 116 and is adapted to receive a medium therethrough such that first balloon 108 can be moved between a first, deflated configuration and second, inflated configuration.
  • any medium known to one skilled in the art including but not limited to air, saline, etc. may be used to inflate first balloon 108.
  • first opening 111 may have any diameter known to one skilled in the art.
  • first opening 111 may have a diameter ranging between 0.2 - 3 mm. In some embodiments, first opening 111 may have a diameter ranging between 0.5 - 10 mm. In some embodiments, first opening 111 may be positioned anywhere on first balloon body 112. In some embodiments, first opening 111 may be positioned near proximal end 117 of first balloon body 112. Inflation lumen 116 may have any diameter known to one skilled in the art. In some embodiments, inflation lumen 116 may have a diameter ranging between 0.2 - 3 mm. In some embodiments, inflation lumen 116 may have diameter ranging from 0.5 -10 mm. In some embodiments, inflation lumen 116 may have any length known to one skilled in the art.
  • inflation lumen 116 may have a length ranging between 10 - 36 cm. In some embodiments, lumen 116 may have a length between 20 - 110 cm. In some embodiments, inflation lumen 116 may further comprise a valve positioned anywhere on its length configured to provide a mechanism for preventing medium from escaping during use. In some embodiments, the valve may be any valve known to one skilled in the art including but not limited to a spring-loaded back-check valve. In some embodiments, spring-loaded back-check valve 126 may be positioned at the proximal end of lumen 116. In some embodiments, a pilot balloon 128 is connecting lumen 116 to spring-loaded back-check valve 126.
  • opening 111 and lumen 116 may be embedded in the body 107 of device 100. In some embodiments, opening 111 and lumen 116 may be attached on the outer surface of body 107 of device 100. In some embodiments, lumen 116 may be positioned inside tube 106 attached to the inner surface of body 107 such as laser ETT with metal body 107. In some embodiments opening 111 may be smaller in diameter than lumen 116. In some embodiments, the external source may be configured to introduce any medium into first balloon chamber 114 to inflate first balloon 108.
  • the external source is configured to introduce medium into first balloon chamber 114 to adjust the pressure within first balloon chamber 114 between approximately 10 – 120 cmH2O. In some embodiments, the external source is configured to achieve an average pressure of 42 cmH2O within first balloon chamber 114. In some embodiments, the external source is configured to achieve a pressure ranging between 20-30 cmH2O within first balloon chamber 114. In some embodiments, the external source is configured to adjust the pressure within first balloon chamber 114 to more than 120 cmH 2 O. In some embodiments, the external source may be configured to apply vacuum pressure to remove any medium within first balloon chamber 114 and to deflate first balloon 108.
  • the external source may be any device known to one skilled in the art configured to allow inflation and deflation of first balloon 108 including but not limited to manually operated inflation devices, syringes, electromechanical inflation devices, pumps, etc.
  • First balloon 108 may be made of any suitable material known to one skilled in the art.
  • first balloon 108 may be made from biocompatible materials, materials that can be made biocompatible, flexible materials, substantially flexible materials, polymers, PVC, nylon, polyethylene, polyurethane, and any other material considered suitable for a particular application.
  • first balloon 108 may comprise any suitable type of balloon, such as a compliant or non- compliant balloon, low-pressure or high-pressure balloon, high-volume or low-volume.
  • first balloon 108 may be conical (tapered), cylindrical, globular, asymmetric, or spheroid.
  • Attorney Docket No.: 206017-0214-00WO First balloon 108 is disposed within second balloon 110.
  • Second balloon 110 comprises a second balloon body 118 having a proximal end 126, a distal end 128 and an opening 119.
  • opening 119 may be positioned closer to proximal end 126.
  • opening 119 may have any diameter known to one skilled in the art.
  • opening 119 may have a diameter ranging between 0.2 - 3 mm.
  • opening 119 may have a diameter ranging between 0.5 - 10 mm.
  • opening 119 and conduit or lumen 122 may be embedded in the body 107 of device 100. In some embodiments, opening 119 and lumen 122 may be attached on the outer surface of body 107 of device 100. In some embodiments, lumen 122 may be positioned inside tube 106 attached to the inner surface of body 107 such as laser ETT with metal body 107. Second inflation conduit or lumen 122 may have any diameter known to one skilled in the art. In some embodiments, second inflation lumen 122 may have a diameter ranging between 0.2 - 3 mm. In some embodiments, second inflation lumen 122 may have a diameter ranging between 0.5-10 mm. In some embodiments, second lumen 122 may have any length known to one skilled in the art.
  • second lumen 122 may have a length ranging between 10 - 36 cm. In some embodiments, second inflation lumen 122 may have a length between 20 - 110 cm. In some embodiments, second lumen 122 may further comprise a valve positioned anywhere on its length configured to provide a mechanism for preventing fluid from escaping during use. In some embodiments, the valve may be any valve known to one skilled in the art including but not limited to a spring-loaded back-check valve. In some embodiments, spring-loaded back-check valve 127 may be positioned at the proximal end of lumen 122. In some embodiments, a pilot balloon 129 is connecting lumen 122 to spring-loaded back-check valve 127.
  • valve 127 may be in continuity with a programmable infusion delivery device. In some embodiments, valve 127 is fluidly connected with a programmable infusion delivery device.
  • second balloon 110 may be made from biocompatible materials, materials that can be made biocompatible, flexible materials, substantially flexible materials, polymers, PVC, nylon, polyethylene, polyurethane, and any other material considered suitable for a particular application.
  • Attorney Docket No.: 206017-0214-00WO second balloon 110 may comprise any suitable type of balloon, such as a compliant or non-compliant balloon, low-pressure or high-pressure balloon.
  • the second balloon 110 may be conical (tapered), cylindrical, globular, spheroid, asymmetrical.
  • second balloon 110 is at least partially formed in the shape of a cuff, or comprises a cuff shape or design.
  • the first and second balloon are at least partially formed in the shape of one or more shapes, the one or more shapes selected from: sphere, hemisphere, cylinder, half-cylinder, ellipsoid, flower, petals, star, burst, crescent, oval, polygon, cone, prism, ellipsoid, flower shape, concentric ellipsoids, concentric spheres, or any combination thereof.
  • the first and second balloon each comprise a plurality of chambers (or a plurality of portions), each chamber or portion securely attached to and extending outward radially from the elongated tube, wherein each chamber of the second balloon at least partially encloses a respective chamber of the first balloon.
  • the first balloon is completely disposed within the plurality of chambers of the second balloon.
  • the plurality of second chambers at least partially covers a single circumferential first balloon.
  • the plurality of chambers of the second balloon may be disposed on the middle 1/3, middle 1 ⁇ 2 or upper (distal) 1 ⁇ 2 of the plurality of chambers of the first balloon body.
  • each chamber or portion may be asymmetrically positioned along the length of the elongated tube.
  • the endoluminal medication delivery device comprises a plurality of first and second balloons, positioned at any location along the elongated tube.
  • the plurality of first and second balloons may be positioned on one side of the elongated tube.
  • the plurality of first and second balloons may be positioned on both sides of the elongated tube.
  • the plurality of first and second balloons circumferentially surrounds the elongated tube.
  • the plurality of first and second balloons may be configured in any suitable pattern along the elongated tube selected from: linear, non- linear, zig-zag, spiral, circular, or any combination thereof.
  • second balloon 110 body is made of or manufactured from the same material as first balloon 108.
  • second balloon 110 body is made of or manufactured from a different material from that of the first balloon 108.
  • the outer surface of second balloon 110 is at least partially porous or comprises one or more porous or perforated regions.
  • the outer surface of second ballon 110 comprises at least one membrane.
  • second balloon 110 shape is the same as the first balloon 108 shape.
  • second balloon 110 shape is different from that of the first balloon 108 shape.
  • the second balloon 110 size is minimally larger than the size of the first balloon 108.
  • the second balloon 110 size is significantly larger than the size of the first balloon 108.
  • the gap between the body of the second balloon 118 and the first balloon body 112 at full inflation of the first balloon measures between 0.2- 5 mm.
  • second balloon body 118, the portion of the outer surface of body 107 of tube 106 disposed within second balloon 110, and the portion of the exterior surface of first balloon 108 is disposed within second balloon 110 and defines a second balloon chamber 120 that is adapted to receive a fluid or gel through opening 119.
  • Opening 119 is fluidly connected to an external source through a second lumen 122.
  • the fluid may be any fluid known to one skilled in the art including but not limited to solutions, compositions, agents, drugs, therapeutics, therapeutic medications, or any combination thereof.
  • the fluid may comprise one or more local anesthetic medications such as lidocaine to provide regional anesthesia to the tracheal mucosa surrounding the inflated endotracheal tube cuff to prevent emergency reactions during anesthesia and reduce the higher anesthetic requirements resulting for the ETT first cuff stimulation.
  • local anesthetic medications such as lidocaine to provide regional anesthesia to the tracheal mucosa surrounding the inflated endotracheal tube cuff to prevent emergency reactions during anesthesia and reduce the higher anesthetic requirements resulting for the ETT first cuff stimulation.
  • Examples of medications that may be administered may include any medication or therapeutic agent which would be desirably applied locally to a specific, internal tissue site which is accessible by the catheter.
  • medications or therapeutic agents include but is not limited to anti-thrombogenic agents or other agents for suppressing stenosis or late restenosis such as heparin, streptokinase, urokinase, tissue plasminogen activator, anti- thromboxane B 2 agents, anti-B-thromboglobulin, prostaglandin E, aspirin, dipyridimol, Attorney Docket No.: 206017-0214-00WO anti-thromboxane A2 agents, murine monoclonal antibody 7E3, triazolopyrimidine, ciprostene, hirudin, ticlopidine, nicorandil, steroids and the like.
  • anti-thrombogenic agents or other agents for suppressing stenosis or late restenosis such as heparin, streptokinase, urokinase, tissue plasminogen activator, anti- thromboxane B 2 agents, anti-B-thromboglobulin, prostaglandin E
  • Anti-platelet derived growth factor may be used as a therapeutic agent to suppress subintimal fibromuscular hyperplasia at an arterial stenosis site, or any other inhibitor of cell growth at the stenosis site may be used.
  • the therapeutic agent also may comprise a vasodilator to counteract vasospasm, for example an antispasmodic agent such as papaverine.
  • the therapeutic agents may be vasoactive agents generally such as calcium antagonists, or alpha and beta adrenergic agonists or antagonists.
  • the therapeutic agent may include a biological adhesive such as medical grade cyanoacrylate adhesive or fibrin glue, for example to adhere an occluding flap of tissue in a coronary artery to the wall, or for a similar purpose.
  • an anti-thrombogenic agent may be applied to its internal tissue site for preferably long-term suppression of thrombogenic activity.
  • the therapeutic agent in accordance with this invention may be an anti- neoplastic agent such as 5-fluorouracil or any known anti-neoplastic agent, preferably mixed with a controlled release carrier for the agent, for the application of a persistent, controlled release anti-neoplastic agent.
  • the therapeutic agent may be an antibiotic for the purpose of minimizing pathogen colonization in a localized tissue site.
  • the therapeutic agent may comprise steroids for the purpose of suppressing inflammation, stenosis, or for other reasons in a localized tissue site.
  • the therapeutic agent may constitute any desired mixture of individual pharmaceuticals of the like, for the application of combinations of active agents. Additionally, glucocorticosteroids or omega-3 fatty acids may be applied, particularly to stenosis sites to obtain clinical benefit thereby. Any of the above medications may include controlled release agents to prolong the persistence of the medication.
  • vasoconstrictors may be applied to an endoluminal area of profuse bleeding after applying compression by first balloon 108 and injecting the vasoconstrictor (including but not limited to epinephrine, norepinephrine, vasopressin etc.) through second balloon 110 to the target area to control bleeding.
  • any other medication may be injected into a vascular bodily lumen (such Attorney Docket No.: 206017-0214-00WO as the trachea) to provide rapid systemic absorption in case of lack of vascular access, unavailability of extremities, lack of access to extremities, or failure of intraosseous and interosseous access.
  • the external source or reservoir may be configured to introduce any fluid, solution, composition, drug, medium or the like into second balloon chamber 120.
  • the external source may be any device known to one skilled in the art configured to allow introduction of fluid or medium into second balloon chamber 120 including but not limited to manually operated syringes, programmable syringes, pumps, medication delivery devices, etc.
  • drug delivery opening 119 opens directly into the second balloon chamber 120 and provides access to the balloon through a second inflation lumen 122, pilot balloon 129, and back-check valve 127.
  • the main purpose of opening 119 is to deliver the medication into the second balloon chamber 120.
  • the design of the drug delivery opening may be a factor determining the pattern of medication distribution within the proximal non-perforated impermeable end of the second balloon body 118 in certain applications.
  • position of opening 119 is proximal in the second balloon body 118.
  • opening 119 may have the same diameter of inflation lumen 122 while cross-section of opening 119 may be flat, beveled towards the surface of the second cuff body118, or beveled towards outer surface of body 107 of device 100 between the body balloon 118 and the body of balloon 112 as depicted in FIGs.6A-6C.
  • the cross-section diameter of the tip of opening 119 may be smaller than diameter of lumen 122 as depicted in FIG.6D.
  • the tip of lumen 122 extending between the body balloon 118 and the body of balloon 112 may be sealed with the most distal aspect of lumen 122 exhibiting 2 side perforations for medication delivery into chamber 120 as depicted in FIG.6E.
  • the tip of lumen 119 may bifurcate into 2 branches within the proximal non-perforated impermeable end of the second balloon with two equilateral medication delivery tips on both sides (180 degrees between both tips) with both medication delivery tips at end of the “Y” shaped bifurcation as depicted in FIG.6F.
  • the tip of lumen 119 may be sealed with lumen 122 extending between the body balloon 118 and the body of balloon 112 and fixed around the entire circumference of the body 107 of device 100 forming a circular loop, exhibiting multiple circumferential medication release perforations facing distally as depicted in FIG.6G.
  • second balloon 110 comprises a truss-cuff design wherein second lumen 122 and opening 119 extend into a parallel network of symmetrically opposing, impermeable and equal length delivery tubes that open into a circumferential, collapsible and perforated band shaped cuff that surrounds the middle and/or distal portion of the first balloon (FIG.9N and FIG.9O).
  • the delivery tubes are compressible and/or collapsible.
  • the second balloon comprises an even number of delivery tubes. In some embodiments, the second balloon comprises between about 2-12 delivery tubes.
  • any disclosed device e.g., device 100 or method comprises a plurality of delivery tubes extending through the second lumen and fluidly connected to the at least one permeable portion.
  • the plurality of delivery tubes comprise any of: an even number of tubes, symmetrical positioning, symmetrical configuration, collapsible material, impermeable material, equal length, equal run, or equal flow, equal flowrate.
  • second balloon 110 comprises hemispherical or hemicylindrical second cuffs (hemi-cuff design) (FIG.9P).
  • This hemi-cuff (half) second cuff design applies the same concept of impermeable proximal portion and permeable middle and/or distal potion with both portions existing in separate identical hemi second balloon chambers with two separate medication delivery tubes 122 and two openings 119 for each chamber.
  • the two hemispherical or hemicylindrical second cuffs may cover the entire circumference of the endoluminal delivery device with each hemi-second cuff covering about 180-degrees of the 360-degree circumference.
  • the 2 hemispherical or hemicylindrical cuffs my cover a portion of the circumference of the endoluminal device ranging between about 60-degrees and 160- degrees leaving part of the outer wall of the endoluminal device uncovered with the cuffs.
  • the hemi-second cuff design may be used with a single first inflating cuff.
  • the hemi-second cuff design may comprise two hemi-first inflating cuff design, making a system of 2 separate hemi-second cuff medication delivery chambers with 2 medication delivery tubes 122 and 2 openings 119 and 2 first inflating hemi-cuffs with 2 inflation tubes 116 and opening 111.
  • the first and second cuffs of the hemi-second cuff design may be elongated.
  • the first and second cuffs of the hemi-second cuff design can cover an extended length of the outer surface the endoluminal device.
  • the first and second cuffs of the hemi-second cuff design may cover a variable portion of the length of the outer surface of the endoluminal device.
  • the first and second cuffs of the hemi-second cuff design can be of shapes other than spherical or cylindrical to better conform to bodily cavity or passage including, but not limited to, elongated, irregular, asymmetrical, symmetrical, curved, tapered, double-balloon shaped.
  • the first and second cuffs on each side of the hemi-second cuff design may have the same shape.
  • the first and second medication delivery cuffs on each side of the hemi-cuff design may have different shapes. In some embodiments, the first and second medication delivery cuffs on each side of the hemi-second cuff design may be symmetrical. In some embodiments, the first and second medication delivery cuffs on each side of the hemi-second cuff design may be asymmetrical. In some embodiments, the first and second medication delivery cuffs on each side of the hemi-second cuff design may be made from the same material. In some embodiments, the first and second medication delivery cuffs on each side of the hemi-second cuff design may be made from different material.
  • second balloon 110 comprises 4 separate hemispherical or hemicylindrical medication delivery cuffs (quad-cuff design) that circumferentially surrounds the endoluminal device with each cuff covering 45-degree to 90-degress of the circumference (FIG.9Q).
  • This quad-second cuff design applies the same concept of impermeable proximal portion and permeable middle and/or distal Attorney Docket No.: 206017-0214-00WO potion with both portions existing in separate quad-second balloon chambers with four separate medication delivery tubes 122 and four openings 119 for each chamber.
  • each of the 4 second medication delivery cuffs has a separate medication delivery tubing 122 and opening 119.
  • the quad-second cuff design may be used with a single first inflating cuff.
  • the quad-second cuff design may comprise quad first inflating cuff design, making a system of 4 separate second cuff medication delivery chambers with 4 medication delivery tubes 122 and 4 openings 119 and 4 first inflating cuffs with 4 inflation tubes 116 and opening 111.
  • the first and second cuffs of the quad-second cuff design may be elongated.
  • the first and second cuffs of the quad-second cuff design may cover an extended length of the outer surface the endoluminal device.
  • the first and second cuffs of the quad-second cuff design can cover a variable portion of the length of the outer surface the endoluminal device.
  • the first and second cuffs of the quad-second cuff design can be of shapes other than spherical or cylindrical to better conform to bodily cavity or passage, including, but not limited to, elongated, irregular, asymmetrical, symmetrical, curved, tapered, double-balloon shaped...etc.
  • the first and second cuffs of the quad-second cuff design may have the same shape. In some embodiments, the first and second cuffs of the quad-cuff design may have different shapes.
  • the first and second cuffs of the quad-second cuff design may be symmetrical. In some embodiments, the first and second cuffs of the quad-second cuff design may be asymmetrical. In some embodiments, the first and second cuffs may be made from the same material. In some embodiments, the first and second cuffs may be made from different materials. In some embodiments, the endoluminal tube may further comprise a plurality of medication delivery cuffs to achieve medication delivery at variable locations along the length of the endoluminal device during clinical application.
  • a distal medication delivery system can be added which consists of: full- cuff design (FIG.9R) or truss-cuff design (FIG.9S) at the distal end of the endotracheal tube positioned in the trachea to provide a continuous seal of the trachea (first cuff) and deliver medications on demand to the tracheal mucosa (second cuff).
  • first cuff full- cuff design
  • second cuff truss-cuff design
  • a quad-cuff design may be utilized along the length of the ETT in the areas abutting the patient’s hypopharynx, base of the tongue, tongue, pharyngeal wall, and palate (FIG.9R and FIG.9S).
  • the second proximal medication delivery system can be used to inject medications (such as local anesthetics) to minimize the stimulation caused by the pressure of the ETT on the surrounding structures and alleviating the gag reflex.
  • medications such as local anesthetics
  • the use of the second proximal medication delivery system entails the following steps: inflating the first cuff/s, injecting the medication through the second cuff/s, deflating the first cuff/s.
  • a third balloon can be secured to the outer surface of the elongated lumen in any position along the elongated lumen.
  • the third balloon comprises a third balloon chamber in fluid connection with a third lumen.
  • the third balloon chamber is configurable between a first, deflated configuration and a second, inflated configuration as a fluid moves into and out of the third balloon chamber.
  • a fourth balloon is secured to the outer surface of the elongated lumen and positioned around the third balloon such that the third balloon is at least partially disposed within the fourth balloon.
  • the fourth balloon comprises a fourth balloon chamber in fluid connection with a fourth lumen.
  • the fourth balloon comprises a fourth balloon body having an impermeable proximal end, and at least one permeable portion in the fourth balloon body fluidly connecting to the fourth balloon chamber.
  • the fourth balloon comprises a truss-cuff design.
  • the fourth balloon comprises a hemi-cuff design. In some embodiments, the fourth balloon comprises a quad-cuff design. In some embodiments, a fifth balloon is secured to the outer surface of the elongated lumen in any position along the elongated lumen. In some embodiments, the fifth balloon comprises a fifth balloon chamber in fluid connection with a fifth lumen. In some embodiments, the fifth balloon chamber is configurable between a first, deflated configuration and a second, inflated configuration as a fluid moves into and out of the fifth balloon chamber. In some embodiments, a sixth balloon is secured to the outer surface of the elongated lumen and positioned around the fifth balloon such that the fifth balloon is at least partially disposed within the sixth balloon.
  • the sixth balloon comprises a sixth Attorney Docket No.: 206017-0214-00WO balloon chamber in fluid connection with a sixth lumen.
  • the sixth balloon comprises a sixth balloon body having an impermeable proximal end, and at least one permeable portion in the sixth balloon body fluidly connecting to the sixth balloon chamber.
  • the sixth balloon comprises a truss-cuff design.
  • the sixth balloon comprises a hemi-cuff design.
  • the sixth balloon comprises a quad-cuff design.
  • second balloon body 118 comprises plurality of perforations 124 extending through second balloon body 118, providing access to second balloon chamber 120 and positioned circumferentially in at least one central line around second balloon body 118.
  • second balloon body 118 may comprise three circumferential central lines of perforations 124.
  • second balloon body 118 may comprise 1 - 15 circumferential central lines of perforations 124 (FIG.7). The number of circumferential lines depends on the shape, size of the ETT second balloon and the size of the perforations. The perforations must only be present on the second balloon surface abutting the tracheal mucosa or part of that surface.
  • perforations 124 are present on second, fourth and sixth balloon surfaces with the second, fourth, and sixth balloons overlapping the first, third and fifth underlying balloons respectively.
  • plurality of perforations 124 may be vertically alternating between the horizontal rows.
  • plurality of perforations 124 may be vertically aligned between the horizontal rows.
  • plurality of perforations 124 may be positioned in the middle third of second balloon body 118 (FIG.8A).
  • plurality of perforations 124 may be positioned in the middle half of second balloon body 118 (FIG.8B).
  • plurality of perforations 124 may be positioned in the upper (distal) half of second balloon body 118 (FIG.8C).
  • the second balloon surface that abuts the surrounding lumen may comprise at least one membrane (FIG.9M).
  • the membrane can be made from or formed of the same material as the second cuff or can be of a different material and structure.
  • the second cuff medication delivery system can be reduced to a truss-cuff design consisting of a truss delivery tubes design.
  • the truss delivery tubes design comprises even numbered, equal-length, symmetrically positioned, impermeable Attorney Docket No.: 206017-0214-00WO collapsible delivery tubes emerging from the medication delivery tube 122 and opening 119.
  • the delivery tubes in the truss design open into a band-shaped perforated second cuff that circumferentially surrounds the middle and/or distal portion of the first cuff.
  • plurality of perforations 124 is limited to a fraction of the external circumference of second balloon 110 (10% to 75%) for specific, directional, and targeted medication delivery to limited aspect of the lumen.
  • the vertical distance between each two lines may be ranging between about 0.5 - 5 mm.
  • the vertical spaces between horizontal lines of perforations 124 may be equal.
  • the vertical spaces between the horizontal lines of perforations 124 may be larger between the proximal perforations and smaller between distal perforations.
  • horizontal spaces between vertical longitudinal lines of perforations 124 may be equal.
  • horizontal spaces between vertical lines of perforation 124 may be larger between the proximal end of these vertical lines and smaller in the middle and distal ends of the vertical lines.
  • the horizontal or vertical distance between perforations on each line may range between 1 - 15 mm.
  • plurality of perforations 124 may have any shape known to one skilled in the art including but not limited to circular, oval, etc. In some embodiments, plurality of perforations 124 may have any diameter ranging between approximately 0.1 - 0.8 mm. In some embodiments, plurality of perforations 124 may have any diameter gauge ranging between approximately 34 – 23 Gauge. In some embodiments, plurality of perforations 124 may have any diameter gauge ranging between approximately 32 – 28 Gauge for low viscosity liquids.
  • the diameter of plurality of perforations 124 may be uniform throughout the centrally located horizontal layers. In some embodiments, the diameter of plurality of perforations 124 may vary throughout each layer. In some embodiments, plurality of perforations 124 having larger diameters may be positioned centrally and/or distally towards distal end 128 of the middle 1/3 or the middle 1 ⁇ 2 or upper 1 ⁇ 2 of the second balloon body 118 while plurality of Attorney Docket No.: 206017-0214-00WO perforations 124 having smaller diameters are positioned towards proximal end 126 of the middle 1/3 or middle 1 ⁇ 2 or upper 1 ⁇ 2 of second balloon body 118 to augment the pressure buildup within second balloon 108 for maximal central circumferential delivery of the medication to the high pressure contact area between the second balloon body 118 abutting the tracheal mucosa.
  • a larger number of similar size plurality of perforations 124 may be positioned centrally and/or distally towards distal end 128 of the middle 1/3 or the middle 1 ⁇ 2 or upper 1 ⁇ 2 of the second balloon body 118 while lesser number of similar size plurality of perforations 124 are positioned towards proximal end 126 of the middle 1/3 or middle 1 ⁇ 2 or upper 1 ⁇ 2 of second balloon body 118 to augment the pressure build within second balloon 108 for maximal central circumferential delivery of the medication to the high pressure contact area between the second balloon body 118 abutting the tracheal mucosa.
  • lesser number of similar size of plurality of perforations 124 may be positioned vertically on the longitudinal axis of the balloon body on the same side of the fluid delivery port 119, while a larger number of similar size of the plurality of perforations 124 are positioned vertically on the longitudinal axis of the balloon body opposing the medication delivery port 119 between proximal and distal ends of the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 to allow for circumferential and vertical pressure build up between both sides ( the medication release side containing port 119 and the opposite side) in addition to augmenting the pressure build within second balloon 108 for maximal central circumferential delivery of the medication to the high-pressure contact area between the second balloon body 118 and the tracheal mucosa.
  • smaller size plurality of perforations 124 may be positioned vertically on the longitudinal axis of the balloon body on the same side of the fluid delivery port 119, while larger size of plurality of perforations 124 are positioned vertically on the longitudinal axis of the balloon body opposing the medication delivery port 119 positioned between the proximal and distal ends of the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 to allow for vertical pressure build up between both sides (the medication release side containing port 119 and the opposite Attorney Docket No.: 206017-0214-00WO side) in addition to augmenting the pressure build within second balloon 108 for maximal central circumferential delivery of the medication to the high-pressure contact area between the second balloon body 118 and the tracheal mucosa.
  • allocation of plurality of perforations 124 of the same size may be positioned at a vertically higher position on the longitudinal axis of the second balloon body on the same side of the fluid delivery port 119, while perforations 124 of the same size are positioned vertically lower on the longitudinal axis of the second balloon body opposing the medication delivery port 119 positioned between the proximal and distal ends of the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 to allow for vertical pressure build up between both sides (the medication release side containing port 119 and the opposite side) in addition to augmenting the pressure build within second balloon 108 for maximal central circumferential delivery of the medication to the high pressure contact area between the second balloon body 118 and the tracheal mucosa.
  • various combinations of size, pattern, and position of perforations aforementioned may be used to optimize vertical and circumferential distribution of medication within the second balloon.
  • no perforations are positioned at proximal end 126 and distal end 128 of second balloon body 118.
  • no perforations are positioned at proximal end 126.
  • plurality of perforations 124 may have varying diameters based on different applications and physical structure of the injected material.
  • the configuration and size of the plurality of perforations may vary depending on the type of medication, application type, level of pressure in system, and rigidity of the surrounding lumen.
  • a large second balloon contact surface area with the surrounding lumen, and considerable compression pressure to the second balloon similar size Attorney Docket No.: 206017-0214-00WO plurality of perforations 124 can be configured circumferentially as depicted in Figs, 7, 8A-C.
  • variable size perforations can be used with the smaller perforations 124 placed proximally and larger perforations 124 placed distally as depicted in FIG.9A.
  • same size perforations 124 can be used with lesser number of perforations 124 placed proximally and larger number of perforations 124 placed distally as depicted in FIG.9B.
  • same size perforations 124 can be vertically aligned as depicted in FIG.9C.
  • smaller size perforations 124 are located in the hemisphere of the second balloon body on the same side of opening 119 while larger perforations 124 are located in the hemisphere opposite to opening 119 as depicted in FIG.9D.
  • a smaller number of perforations 124 are located in the hemisphere of the second balloon body on the same side of opening 119 while larger number of perforations 124 are located in hemisphere opposite to opening 119 as depicted in FIG.9E.
  • perforations 124 are Attorney Docket No.: 206017-0214-00WO located at a relatively more distal position in the hemisphere of the second balloon body on the same side of opening 119 while perforations 124 on the hemisphere opposite to opening 119 are located relatively more proximal as depicted in FIG.9F.
  • plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to circumferential “V” shaped pattern (FIG. 9G).
  • plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to a single large or multiple small circumferential “X” shaped pattern (FIG.9H). In some embodiments, plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to “Z” shaped pattern (FIG.9I).
  • plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to horizontal layers of zig-zag patterns (FIG.9J). In some embodiments, plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to perforations widely spaced on horizontal axis while vertically aligned (FIG.9K).
  • plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body 118 that include but are not limited to perforations widely spaced on a horizontal axis while vertically alternating (FIG.9L). In some embodiments, plurality of perforations 124 can have variable configurations within the middle 1/3 or middle 1 ⁇ 2 or upper(distal) 1 ⁇ 2 of second balloon body that include but are not limited to a gradient pattern or a spiral pattern. In one exemplary embodiment, injected materials with viscus and gel-like forms, require larger diameter perforations than materials with liquid form.
  • the medication delivery area of the second cuff is a membrane as depicted in FIG.9M. Attorney Docket No.: 206017-0214-00WO Depending on the application and the characteristics of the surrounding tissues and the material injected into the second balloon, membrane molecular structure and design may vary.
  • the membrane can be natural, synthetic, biological or non- biological. In some embodiments, the membrane may be dense, semipermeable, or permeable.
  • the membrane may be neutral or charged, homogeneous or heterogeneous.
  • the membrane may apply microscopic and/or macroscopic conceptual structural design characteristics.
  • the membrane may apply one or more of the following microscopic conceptual structural design characteristics and membrane processes types: dense, porous, microporous, symmetric (both sides are structurally similar; having the same molecular and design structure), asymmetric (both sides are structurally different; having different molecular and design structure), isotropic (uniform pore size and porosity), anisotropic (variable pore size and porosity), temperature regulated membrane permeability (the molecular structure and porosity changes at different temperature allowing molecules to cross), temperature regulated diffusion of the injected material, pressure regulated membrane permeability (the molecular structure and porosity changes at different pressures allowing molecules to cross), bioreactive membrane, and nanostructured membranes.
  • the membrane may apply macroscopic conceptual structure design characteristics and configurations such as hollow fiber, laminar flow sheet, plate and frame, ceramic and polymeric sheets, tubular, and spiral wound.
  • the membrane may include one or more of the following principles and technologies of molecular transfer: pressure-drive membrane technology, passive diffusion principles, active transport, microfiltration, ultrafiltration, osmosis, reverse osmosis, nanofiltration, and membrane bioreactors.
  • the membrane technology, design, and material can be based on any of the following parameters to facilitate and regulate diffusion: molecular weight (mass), molecular size, polarity, ionization, biosynthesis, charge number, chemical gradient, electrical gradients, concentration gradient, pressure gradient, osmolality, pressure regulated diffusion, and temperature regulated diffusion.
  • the membrane may include various flow geometries (operation modes) such as cross-flow filtration and dead-end filtration.
  • second balloon chamber 120 acts as an immediate variable high-pressure delivery conduit and not as a reservoir for the injected fluid.
  • the system allows the delivery of medication to the target area while the endotracheal tube first balloon 112 is continually and fully inflated maintaining the seal and full functionality of the endoluminal device.
  • Forces determining the pattern of distribution of the injected medication within the second balloon chamber are the presence of most or all of the non-perforated impermeable surface area of body of the second balloon in the proximal and/or proximal and distal area that is not abutting the surrounding lumen (Key factor), the presence of perforations 124 only on the second balloon surface abutting (in direct contact with) the surrounding lumen (key factor), continued normal and/or augmented temporary inflation of the first balloon(key factor), the degree of circumferential pressure exerted by the surrounding lumen on both balloons (key factor), the ratio of the surface area of the impermeable non-perforated proximal balloon body to the perforated middle and/or distal perforations 124, relationship between the viscosity of the injected medication and the size of perforations 124
  • the presence of an unperforated impermeable proximal portion is responsible for circumferential and vertical pressure build up within the second balloon chamber 120 by avoiding the loss of the injected medication through proximal and/or proximal and distal perforations that are not abutting the mucosa.
  • Second balloon chamber 120 capacity should be kept to a minimum in high-pressure applications with considerable luminal structural support such as the endotracheal tube.
  • the second balloon body 110 should have the same shape of the first balloon 108 body.
  • the capacity of the second balloon chamber 120 at full inflation of the first balloon body 108 should be kept to a minimum to the extent permitted by manufacturing methodology and logistics.
  • the capacity (volume) of the second balloon chamber 120 and inflation lumen 122 during inflation of the first balloon body at a certain compression pressure measured directly thought back-check valve 126 of the first balloon body within a specific lumen is considered the dead space of the second balloon and of the medication injected at this specific pressure for this lumen.
  • the manufacturer should measure the balloon dead space at various clinically relevant inflation pressures to help the operator determine the ratio of dead space medication waste with precision when applicable or clinically relevant.
  • sufficient pressure buildup and circumferential distribution must be achieved within the second balloon chamber 120 to develop a high-pressure point at plurality of perforations 124 of second balloon 110 abutting the mucosa (in case of an ETT).
  • the pressure inside the first balloon can be temporarily increased by injecting more air into it before injecting the medication into the second balloon, with the extra air injected being withdrawn from the first balloon immediately after medication delivery to bring the first balloon back to its original pressure.
  • the fluid distributes within second balloon chamber 120 starting with circumferential distribution in the non-porous non-permeable proximal end 126. After the drug in the lower unperforated proximal end of second balloon chamber 120 is circumferentially distributed, pressure builds up in this section (end) of second balloon chamber 120.
  • any additional injected fluid is then delivered in the middle high-pressure zone achieving adequate pressure to overcome the compressive forces induced by first balloon body 112 and the surrounding tissue (e.g., tracheal mucosa interface in case of an ETT).
  • first balloon body 112 and the surrounding tissue e.g., tracheal mucosa interface in case of an ETT.
  • second balloon chamber 120 After reaching the middle high-compression portion of second balloon chamber 120 with at Attorney Docket No.: 206017-0214-00WO least one line of perforations 124, it is immediately expelled out of plurality of perforations 124 by virtue of existing high-compression pressure into the surrounding tissue (highly absorbent compressed tracheal mucosa in case of an ETT).
  • This configuration allows for delivery of fluid under pressure from second balloon chamber 120 and directly into the mucosa with minimal waste of the administered fluid.
  • This configuration does not cause any excessive pressure to expel the medication out of the perforations as it uses the existing high-pressure generated by the first inflated balloon 112 to expel the medication from the perforations 124 of the second balloon 118. Further, this configuration provides adequate distancing between plurality of perforations 124 and opening 119. This adequate distancing allows for adequate circumferential pressure build-up and even circumferential distribution of the injected fluid within second balloon chamber 120 before it reaches plurality of perforations 124 compressed by the surrounding tissue (e.g., tracheal mucosa and rigid external tracheal structure).
  • tissue e.g., tracheal mucosa and rigid external tracheal structure
  • this configuration prevents the leak of the injected fluid at the low-pressure proximal end 126 of second balloon body 118 (path of least resistance for the fluid) that is not compressed by the surrounding tissue (e.g. tracheal mucosa).
  • This configuration allows this system to function as intended irrespective of gravitation forces, pressure variability in the first cuff, and independent of patient positing, type of ventilation, orientation of the ETT, repositioning of the ETT during surgery or during intubation in the intensive care unit, or other variables existing outside this delivery system.
  • opening 119 and second lumen 122 may be positioned on the inner concave edge or outer convex edge of the ETT or can be embedded in the concave inner or convex outer curvatures of the ETT. In the case of outer placement of lumen 122 on the outer surface of ETT, placement on the inner convex surface is preferred to avoid injury to the vocal cord during periods of prolonged intubation.
  • the free non-attached portion of the lumen 122 should start proximally as customary in ETT design to avoid trauma and injury to the vocal cords.
  • Lumen 122 should be attached to the ETT tube or embedded in the tube in the ETT portion going through the vocal cords and into the trachea.
  • Lumen 122 can be Attorney Docket No.: 206017-0214-00WO embedded in the inner curvature or outer curvature of body 107 of the endoluminal device 100.
  • lumen 122 may be positioned inside tube 106 attached to the inner surface of body 107 such as laser ETT with metal body 107.
  • high-pressure within the first and second balloons may be required for optimal delivery of the medication into the surrounding lumen, therefore inflation pressure in the first balloon chamber 114 may be temporarily increased by injection more air (or saline) through lumen 116 before delivery of the medication into the second balloon through lumen 122, while removing excessive air (or saline) after the injection of the medication and returning to the original normal first balloon inflation pressure.
  • device 100 may be used during general anesthesia.
  • device 100 may be used in the intensive care unit.
  • device 100 may be used in tracheostomy tubes.
  • device 100 may be used for urological, gastroenterological, neurological, critical care, and vascular procedures.
  • device 100 enables flexible application of any medium including but not limited to any medicine known to one skilled in the art at any time throughout any procedure regardless of the duration of surgery.
  • device 100 is configured to allow application of any medication (e.g., local anesthetic) where it is exactly needed, in small doses that can be repeated and thereby minimizing systemic absorption. The dose absorbed systemically is minimal and well- below the threshold of systemic toxicity even with repeated applications and thereby minimizes any drug side effects.
  • any medication e.g., local anesthetic
  • device 100 is configured to allow for drug titration, appropriate and exact timing of drug delivery and sustained delivery for long duration and thereby allows for a reduced dose of intravenous and inhalational anesthetics and unnecessary deeper levels of anesthesia needed to overcome the stimulating effect of the endotracheal tube.
  • device 100 may be used as a port for delivering medications emergently and electively. Examples of emergent applications include but is not limited to medical emergencies, lack of intravenous access as in trauma patients, or Attorney Docket No.: 206017-0214-00WO resuscitation in the field by paramedics.
  • examples of elective applications include but is not limited to delivering medications such as lidocaine, steroids, vasoactive drugs, and antibiotics at the ETT-mucosa interface for patients with prolonged intubation times.
  • device 100 may be used in any patient regardless of age and hemodynamic stability as it involves delivering the medication to the effect site without considerable systemic exposure.
  • device 100 may be placed and function anywhere in the body including but not limited to a low-pressure position (intestines) or a high- pressure position (endotracheal intubation) as the design involves a circumferential pressure build up and distribution mechanism.
  • device 100 is configured to have high patient safety profile because a specific amount of medication may be injected to the target area and after a specific time a second dose may be safely administered again with minimal systemic effects.
  • an aspect of the invention is a separate device comprising an annular or ring-shaped elastic structure comprising one or more permeable portions. It should be appreciated that this structure may be formed separately from other devices, or formed as one unit, and may be used with any medical device with inflatable portions for accurately dispensing fluid (e.g., medication or lubricant) to a portion surrounding the inflatable member or balloon of the medical device.
  • the present innovation allows standardizing the dispensing of fluids in bodily passages with many different devices. Aspects of the invention include applying the device separately to, or using the device with, any medical device.
  • the ring structure comprises a hollow portion forming a lumen inside the ring, with one or more conduits extending out of the structure fluidly connected to the lumen and one or more permeable portions.
  • the ring structure and/or one or more conduits comprise one or more inflatable sections.
  • the one or more conduits comprise a plurality of channels extending therethrough.
  • a portion of the channels are Attorney Docket No.: 206017-0214-00WO connected at their distal end to one or more inflatable members positioned inside the lumen of the ring, wherein inflating the portion of the channels allows fluid to flow freely through the other portion of channels to the one or more permeable portions.
  • any conduit, lumen, tube or structure disclosed herein may be appropriately terminated with any connector known by one of ordinary level of skill in the art. This includes, but is not limited to, tube connectors, locking connectors, Luer locks, syringe connectors, surgical connectors, medical connectors, and the like.
  • the present invention provides a method configured to allow precise, immediate, repeated, and controlled circumferential endoluminal medication delivery to any bodily passage known to one skilled in the art.
  • the method of the present invention may be used in a low-pressure position within a soft non-rigid lumen (intestines) or a high-pressure position within a well-supported lumen structure (endotracheal intubation).
  • the method of the present invention may provide access to an airway, such as the trachea.
  • the method of the present invention allows medication delivery to the interface between an endotracheal tube and the compressed surrounding tissue lining the lumen (e.g., Mucosa/mucous membrane).
  • the method of the present invention may be used during general anesthesia. In some embodiments, the method of the present invention may be used in the intensive care unit. In some embodiments, the method of the present invention may be used for urological, gastroenterological, neurosurgical, critical care, and vascular procedures. In embodiment, the method of the present invention may be used in humans. In some embodiments, the method of the present invention may be used in all animal species. In some embodiments, the method of the present invention is configured to have a high patient safety profile because a specific amount of medication may be injected to the target area and after a specific time a second dose may be safely administered again.
  • the method is configured to allow application of any medication where it is exactly needed and in small doses that can be repeated with minimal systemic absorption.
  • the dose absorbed systemically is minimal and well-below Attorney Docket No.: 206017-0214-00WO the threshold of systemic toxicity even with repeated applications and thereby minimizes any drug side effects.
  • FIG.11 an exemplary method 200 of providing access and delivering medication to a bodily passage is depicted.
  • Method 200 begins with step 202, wherein an endoluminal medication delivery device comprising an elongated lumen having an outer surface, a proximal end, and a distal end; a first balloon secured to the outer surface of the elongated lumen, wherein the first balloon comprises a balloon chamber in fluid connection with an inflation lumen; and a second balloon secured to the outer surface of the elongated lumen and positioned around the first balloon such that the first balloon is at least partially disposed within the second balloon, wherein the second balloon comprises a second balloon body having an impermeable proximal end, and at least one permeable portion in the second balloon body fluidly connecting to a second balloon chamber, and wherein the second balloon chamber is fluidly connected to an external reservoir or source through a second lumen, is provided.
  • the endoluminal medication delivery device is introduced into the bodily passage.
  • the first balloon is inflated with a medium through the first inflation lumen, such that the inflated first balloon seals the bodily passage.
  • any medium known to one skilled in the art including but not limited to a gas, viscous solution, or liquid may be used to inflate the first balloon.
  • medium may be saline.
  • medium may be air, saline, gas or oxygen.
  • a fluid is introduced to the second balloon chamber through the second lumen and results in an increase in circumferential pressure within the proximal impermeable cavity of the balloon leading to immediate circumferential delivery and distribution of the fluid under high-pressure of the inflated first balloon to the middle and distal portions within the balloon cavity.
  • the fluid exits to a compressed area between the second balloon body and the bodily passage through the plurality of perforations.
  • the fluid diffuses into the compressed area by virtue of existing compression and is readily absorbed by the surrounding lumen.
  • the fluid injected into the body cavity through the second balloon perforations while the first balloon is continually inflated at normal pressure without interruption in functionality or safety profile of the endoluminal device.
  • any fluid known to one skilled in the art may be introduced to the balloon chamber including but not limited to medications, etc.
  • EXPERIMENTAL EXAMPLES The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified.
  • Second medication delivery ETT cuffs (second balloon) were designed using ETT cuffs for 8.5 mm ID tubes (Shiley TM Lo-Pro oral/nasal tracheal tube cuffed, Coviden, Mansfield, MA. Ref 86054). The cuffs were cut from the ETT, perforated in the desired pattern using insulin syringe tip (item #12). 3. Clear plastic elastic rubber bands (10 mm diameter) 4. Commercially available clear silicone. 5.
  • Second ETT cuff medication delivery tubing (second inflation lumen): the ETT cuff inflating tubing was separated from the 8.5 mm ID ETT (Shiley TM Lo-Pro oral/nasal tracheal tube cuffed, Coviden, Mansfield, MA. Ref 86054) 6. A- 30 ml plastic B-D syringe (20 mm internal diameter) used to simulate the human trachea (Becton-Dickinson, Franklin Lakes, NJ). 7.
  • B-D 10 cc syringe for air inflation of the main ETT cuff) (Becton- Dickinson, Franklin Lakes, NJ). 10. B-D 5 cc syringe (for medication solution injection in the second medication delivery cuff) (Becton-Dickinson, Franklin Lakes, NJ). 11. McCormick® Culinary Blue Food Color (simulating the medication injected in the second ETT cuff). (McCormick & Company, Baltimore, Maryland) 12. Insulin Vanish Point 29 G (0.33 MM) 1 ML syringe. The 29 G needle was used to perforate the second cuff creating a medication delivery surface.
  • the ETT was labelled indicating the pattern of perforation of the second balloon body placed on the 6.5 mm ETT. This step was performed because the plurality of perorations are not visible to naked eye even under simple lens magnification.
  • the ETT with a second balloon body that is perforated over the entire surface area of the second balloon body was marked at the ETT proximal end using the unique identifier “I.........I” using a permanent marker.
  • the endotracheal tube assembly of the present invention was marked by 3 circumferential dotted line at the center of the second balloon body using a permanent market in addition to marking it at the ETT proximal end using the unique identifier “__...__”. 3.
  • the second inflation lumen (#5) was inserted between the first balloon body of the 6.5 mm ETT (#1) and the second balloon (#2) body having plurality of perforations.
  • the tip of the second lumen was inserted between the proximal ends of both first and second balloon body. 4.
  • the second inflation lumen (#5) extending beyond the proximal end of the second balloon body having plurality of perforations was positioned at the inner concave curvature of the ETT (#1). 5.
  • the second inflation lumen (#5) and the second balloon (#2) were secured using multiple clear elastic rubber bands (#3) at proximal and distal ends of the second balloon body using multiple silicone layers on both proximal and distal ends for Attorney Docket No.: 206017-0214-00WO proper sealing.
  • the goal of the first experiment was to establish and test a simulated experimental platform to be used in the second and third experiments (Examples 3 and 4 respectively).
  • the goal of the second experiment was to test the functionality of an alternative design other than invention.
  • the goal of the third experiment was to test the functionality of the invention.
  • Each of the three of experiments included 3 independent methods to derive conclusions. These methods are described in detail in the experiments and referred to as Method 1, 2 and 3.
  • This pressure is essential for the functionality of the device as it represents the actual condition Attorney Docket No.: 206017-0214-00WO of medication application through the endotracheal tube.
  • This pressure is the function of interaction between the inflated first balloon body and inner tracheal lining mucosa supported by the outer rigid tracheal structure.
  • the ETT balloon pressure provides a seal that protects the patient’s lungs from secretions entering and maintains a closed-circuit system for delivery of anesthetic and respiratory gases (to provide anesthesia and support life).
  • Endotracheal Diameter in Humans The average internal diameter of the trachea is 15-25 mm.
  • tracheal mucosa is an inner mucous membrane lining the rigid cylindrical tracheal structure created by the cartilaginous rings.
  • the tracheal mucous membrane is a delicate layer of tissue that is in direct contact with the endotracheal tube cuff and the target tissue for the injected medication delivery.
  • the tracheal mucous membrane is normally compressed between the rigid external structure of the trachea and pressure generated by the inflated first balloon body of the ETT.
  • absorbent white paper towel was used to simulate the absorption of the injected medication by the tracheal mucosa to evaluate the delivery and distribution pattern of the injected medication.
  • the white paper towel is highly absorbent compared to the tracheal mucosa which will lead to movement of injected material across the paper towel fabric regardless of the point of origin, thus leading to inaccurate conclusion.
  • the paper towel simulating the tracheal mucosa was not applied over the entire first balloon body of the ETT. Instead, the paper towel was applied over the target medication delivery area (middle and distal aspect of the second balloon) to be conclusive of the distribution being observed.
  • Method 1 Referring now to FIG.12A and FIG.12B, the pattern of the injected medication distribution and delivery outside the human body while maintaining average clinically used inflation pressure of 42 cmH 2 O was tested. The goal of this experiment was to observe the distribution of the medication outside the body (in vitro) while the first balloon body of the endotracheal tube is inflated to clinically relevant pressures.
  • this experiment demonstrates the ability to inflate the first balloon body of the ETT to a pressure of 42 cmH 2 O and the ability to maintain this pressure as needed. While this setup does not parallel the conditions of the injecting the medication inside the body (in vivo), it establishes baseline functionality with the original configuration of the ETT design before allowing the distortion of the shape to conform to the tracheal cylindrical structure. A design that fails to deliver the injected medication as intended using this method is highly unlikely (essentially impossible) to deliver medications under clinical circumstances. Also, a design that fails to deliver the injected medication as intended using this method in the absence of second balloon compression by the surrounding lumen, is inherently flawed to an extent that it is unlikely to be improved or modified.
  • FIG.12A reflects the ability to inflate the first balloon chamber of the ETT to achieve an inflation pressure of 42 cmH 2 O.
  • the blue tack reversible putty–like adhesive was used to secure the plunger.
  • FIG.12B depicts a magnification of the digital reading and inflated ETT balloon as depicted in FIG.12A.
  • Method 2 Referring now to FIG.13A and FIG.13B, the 6.5 mm ETT used, was inserted into a 30 ml syringe, and then inflated. The first balloon body was inflated to achieve an intraballoon inflation pressure of 42 cmH 2 O. This experiment simulates actual clinical application with endotracheal tube inside the patient’s trachea.
  • FIG.13A demonstrates the ability to inflate the first balloon body of the endotracheal tube inside a 30-ml syringe to achieve an inflation pressure of 42 cmH 2 O.
  • FIG.13B depicts a magnification of the digital manometer reading the inflated first balloon body inside the plastic cylinder from FIG.13A.
  • Method 3 Referring now to FIG.14A and FIG.14B, an absorbent paper towel lining was added to the distal end of the ETT to test for medication diffusion.
  • the paper towel has a lateral diffusion capacity that matches or exceeds that of tracheal mucosa. However, pattern and surface area of the dye diffusion in the paper towel indicates the direction, position, and extent of medication delivery to the distal one-half of the tube.
  • the challenge to medication delivery is the high-pressure middle zone of the ETT balloon created by compression against the trachea. Placing the paper towel in the distal (one- half) end of the ETT allows to test for the delivery of the medication at and beyond the middle high-pressure point of the ETT balloon (target medication delivery area).
  • FIG.14A depicts wrapping the distal end of the endotracheal tube with paper towel.
  • FIG.14B reflects the ability to inflate the first balloon body of the endotracheal tube inside a 30-ml syringe to achieve an inflation pressure of 42 cmH 2 O while wrapping the distal end of the ETT with paper towel.
  • the blue-tack reusable adhesive was used to prevent movement of the manometer syringe plunger to maintain the pressure within the first balloon chamber at 42 cmH 2 O throughout the inflation period.
  • This experiment established a platform to investigate the distribution of injected medication within the second balloon body while maintaining variables simulating intraoperative clinical conditions (e.g., under normal inflation pressure, physical contact, compression, and deformation of the ETT by the tracheal structure).
  • Example 3 Experiment 2: “Investigating an alternative design”
  • the functionality and efficacy of an ETT with a second balloon body having plurality of perforations distributed uniformly throughout the entire surface area of the second balloon body was investigated (alternative design) (FIG.15).
  • Method 1 First, the medication movement and delivery pattern were investigated with the alternative design ETT, wherein the first balloon body was inflated to 42 cmH2O outside the body. Referring now to FIG.16, distribution of the injected dye (2 ml) from the pores located at proximal end (arrow) of the of the second balloon body is shown.
  • Method 2 Next, the medication movement and delivery pattern were investigated with the alternative design ETT, wherein the first balloon body was inflated to 42 cmH2O inside the plastic cylinder simulating the human trachea.
  • ETT alternative design
  • FIG.17A through FIG.17D distribution of the injected blue dye (2 ml) in a model simulating clinical application is shown.
  • FIG.17A depicts the setup prior to starting the experiment with the ETT inserted inside the cylindrical plastic tube while the first balloon chamber is inflated to a pressure of 42 cmH 2 O.
  • FIG.17B demonstrates the distribution of the dye at proximal end of the second balloon body as all the dye was expelled from the first low- pressure perforations encountered without any delivery of the dye to the compressed area of the balloon (target area). This led to the accumulation of the injected dye at the bottom of the cylindrical tube in an area of no contact (least resistance) between the second balloon body and the cylindrical tube. This confirms the finding as above (FIG.16) that failure of this design to build pressure in the second balloon body and deliver the medication beyond the low-pressure initial point to the target area.
  • FIG.17C is a magnified view of FIG.17B for better visualization of the dye accumulation and failure of delivery of the dye to the target area.
  • FIG.17D is an upper view of the cross section of the lower end of the tube placed in reverse (proximal end) after dye injection (2 ml is shown). This is demonstrating the accumulated dye around the tube due to inability to overcome the high-pressure mid-cuff area and inability to reach to the target area.
  • Method 3 Attorney Docket No.: 206017-0214-00WO
  • the medication movement and delivery pattern were investigated with the alternative design ETT, wherein the first balloon body was inflated to 42 cmH2O inside the plastic cylinder simulating the human trachea in the presence of a highly absorbent lining to demonstrating lateral diffusion pattern and to confirm delivery of the medication to and beyond the middle high-pressure point (target area).
  • FIG.18A through FIG.18D the arrow indicates the placement of the absorbent paper towel edge at the middle section of the high-pressure area of the ETT balloon (target area).
  • FIG.18A depicts the setup before injection of the dye (baseline).
  • FIG.18B depicts the setup after injection of the dye (2 ml). This experiment demonstrates failure of the dye to diffuse and reach the high-pressure zone as indicated by the lack of absorption in the paper towel compared to baseline (FIG.18A). Instead, the dye escaped from the perforations positioned at the proximal end of the second balloon body in the low- pressure zone and was spilled as indicated by the solid arrows in FIG.18C and FIG.18D.
  • Example 4 Experiment 3: “Investigating the present invention design”
  • Method 1 Attorney Docket No.: 206017-0214-00WO
  • FIG.19A depicts the ETT with 3 middle circumferential lines of perforations indicated by the permanent block dots before injection of the dye.
  • FIG.19B depicts the ETT after injection of the dye (2 ml).
  • the arrow points to the remaining drops from the diffusion of the dye through the central pores (target area).
  • Most of the dye fell on the absorbent paper towel below due to the slippery smooth surface of the ETT in an inflated state.
  • the distribution was observed in real-time while the dye was injected and leaking through the pores. This experiment indicated the ability of this device to deliver the medication to target location with minimal or no waste.
  • FIG.19C depicts the ETT after injection of the dye (2 ml) from a different angle of the ETT to provide a 360-dgreee view.
  • FIG.19D depicts the ETT after injection of the dye (2 ml) from different angle to provide a 360-degree view of the ETT.
  • the drops at both proximal end and the distal end of the second balloon body were not leaking from the edges of the tube as there are no perforations at the edges but they are the result of accumulation of the dye that leaked from the central pores and accumulated at the lower point by gravity and due to the slippery surface of the second balloon body and the lack of absorptive surface.
  • Method 2 Next, the medication movement and delivery pattern were investigated with the device of the present invention, wherein the first balloon body was inflated to 42 cmH2O inside a plastic cylindrical tube simulating intraoperative clinical application inside the patient’s body.
  • FIG.20A depicts the ETT with 3 middle circumferential lines of perforations indicated by the permanent block dots before injection of the dye.
  • the first balloon chamber was inflated to 42 cmH 2 O using air.
  • the blue-tack reusable adhesive was used to prevent movement of the manometer syringe plunger to maintain the pressure within the first balloon body at 42 cmH 2 O throughout the inflation period.
  • FIG.20B depicts the ETT after injection of the dye (2 ml) and demonstrates a clearly delineated central circumferential distribution pattern of the dye around the center of the Attorney Docket No.: 206017-0214-00WO second balloon body, at the compressed area between the ETT and circular tubing. This is the target area for medication delivery inside the human trachea for maximal efficacy and safety.
  • FIG.21A depicts the ETT after injection of the dye (2 ml) with the experiment tube rotated to provide a view at a different angle providing a 360-degree view.
  • FIG.21A and FIG.21B demonstrate a clearly delineated circumferential spread of the dye around the center of the second balloon body at the high pressure point of the ETT-tube interface. This is the target area for medication delivery inside the human trachea for maximal efficacy and safety.
  • FIG.21B depicts a magnified view of FIG.21A. The pattern observed here under magnification is exactly the pattern required for effective and safe administration of the medication to the target area.
  • FIG.22A and FIG.22B depict the ETT after injection of the dye (2 ml) with the experiment tube rotated to provide a view at a different angle providing a 360- degree view.
  • FIG.22A demonstrates a clearly delineated circumferential spread of the dye around the center of the second balloon body at the high-pressure area of the ETT- tube interface. This is the target area for medication delivery inside the human trachea for maximal efficacy and safety.
  • FIG.22B depicts accumulation of a small dose of dye beyond the high pressure point after injection of the dye (2 ml). This indicates the ability of the invention to overcome the high-pressure point at the central portion of the second balloon body.
  • Method 3 Last, the medication movement and delivery pattern were investigated with the device of the present invention, wherein the first balloon body was inflated to 42 cmH 2 O inside a plastic cylindrical tube simulating intraoperative clinical application inside the patient’s body in the presence of a highly absorbent lining to demonstrating lateral diffusion pattern and to confirm delivery of the medication to and beyond the Attorney Docket No.: 206017-0214-00WO middle high-pressure point (target area).
  • FIG.23A depicts the ETT device with 3 middle circumferential lines of perforations before injection of the dye.
  • An absorbent white paper towel was wrapped around distal half of the second balloon body (baseline).
  • the first balloon body was inflated to 42 cmH2O using air.
  • the blue-tack reusable adhesive was used to prevent movement of the manometer syringe plunger to maintain the pressure within the first balloon chamber at 42 cmH 2 O throughout the inflation period.
  • FIG.23B depicts the ETT device after injection of the dye (2 ml).
  • FIG.23C depicts the ETT device with 3 middle circumferential lines of perforations after injection of the dye.
  • the device of the present invention is capable of delivering medication to the high-pressure target area of compression between the ETT balloons and the tracheal mucosa with minimal waste of the medication. As it was shown in Example 3, the alternative design failed to deliver the medication to the target area with most the medication being wasted away from the target area.
  • the device of the present invention is superior in functionality and efficacy compared to alternative ETT design with medication delivery systems.
  • the disclosures of each and every patent, patent application, and publication cited herein are hereby each incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by Attorney Docket No.: 206017-0214-00WO others skilled in the art without departing from the true spirit and scope of the invention.
  • the appended claims are intended to be construed to include all such embodiments and equivalent variations.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

La présente invention concerne un dispositif et un procédé d'administration de médicament par voie endoluminale, configurés pour permettre une administration de médicament circonférentielle immédiate, répétée, précise et contrôlée au niveau de l'interface entre le dispositif et le tissu environnant comprimé tapissant la lumière (par exemple, une muqueuse/membrane muqueuse).
PCT/US2024/017843 2023-03-01 2024-02-29 Tube endoluminal à ballonnet avec système d'administration de médicament WO2024182596A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363487632P 2023-03-01 2023-03-01
US63/487,632 2023-03-01

Publications (2)

Publication Number Publication Date
WO2024182596A2 true WO2024182596A2 (fr) 2024-09-06
WO2024182596A3 WO2024182596A3 (fr) 2024-10-10

Family

ID=92590462

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/017843 WO2024182596A2 (fr) 2023-03-01 2024-02-29 Tube endoluminal à ballonnet avec système d'administration de médicament

Country Status (1)

Country Link
WO (1) WO2024182596A2 (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4994033A (en) * 1989-05-25 1991-02-19 Schneider (Usa) Inc. Intravascular drug delivery dilatation catheter
US5049132A (en) * 1990-01-08 1991-09-17 Cordis Corporation Balloon catheter for delivering therapeutic agents
US8827953B2 (en) * 2013-01-15 2014-09-09 Krishna Rocha-Singh Apparatus and method for delivering intraluminal therapy

Also Published As

Publication number Publication date
WO2024182596A3 (fr) 2024-10-10

Similar Documents

Publication Publication Date Title
US6706013B1 (en) Variable length drug delivery catheter
CA2090765C (fr) Tube medico-chirurgical dote d'un mecanisme ameliore d'administration de liquides ou de gaz
US8425455B2 (en) Bronchial catheter and method of use
US7942848B2 (en) Medical apparatus for distributing a predetermined amount of foreign substance to a predetermined area in living body
Soares et al. The effects of tracheal tube cuffs filled with air, saline or alkalinised lidocaine on haemodynamic changes and laryngotracheal morbidity in children: a randomised, controlled trial
US20130047992A1 (en) Endotracheal tube comprising corrugated cuff
AU2013344546B2 (en) Nasal pulsatile oxygenation and ventilation airway apparatus
CN217908578U (zh) 一种给药球囊导管
AU2013344546A1 (en) Nasal pulsatile oxygenation and ventilation airway apparatus
WO2014129552A1 (fr) Moyen de libération contrôlée de fluide, et endoscope et instrument chirurgical endoscopique le comprenant
US20170266406A1 (en) Nasal air jet insufflator
KR20200118469A (ko) 기도 확장 장치 및 관련된 전개 방법
RU2739347C1 (ru) Эндотрахеальная трубка (варианты)
WO2024182596A2 (fr) Tube endoluminal à ballonnet avec système d'administration de médicament
EP1974766A1 (fr) Ballonnet multicouche
JP2018527131A5 (fr)
CN217041057U (zh) 一种给药球囊导管
CN113926058A (zh) 一种药物释放球囊扩张导管
JP6341532B2 (ja) 生体管留置チューブ
CN117224823A (zh) 喉气管狭窄扩张管及含有其的产品和系统
Singh et al. Tracheostomy from Insertion to de cannulation
CN209033428U (zh) 可行气道表面麻醉的插管型喉罩
CN207101604U (zh) 一种可送药的单腔支气管导管
Shimamura et al. Endoscopic laser coagulation through an optical laser balloon
JP3406343B2 (ja) 医療用チューブおよびその製法