Noninvasive transient atomization delivery system

Abstract

A noninvasive transient atomization delivery system includes an atomization catheter and a catheter stabilizer and enables a user to visualize and securely position the distal end of an atomizing nozzle into the oropharynx above vocal cords of a respiratory distress syndrome (RDS) neonate at risk of nasal continuous positive airway pressure (nCPAP) failure. The associated therapeutic system may be used to load medicinal fluids such as Perfluorooctylbromide (PFOB) into a syringe attached to the catheter with atomizing nozzle. The medicinal fluid is pushed through the tubing of the catheter and out the distal end of the atomizing nozzle by controlled external driving pressure. The therapeutic dose is delivered as a precise transiently atomized mist above the vocal cords of a spontaneously breathing patient and inhaled into the lungs via inspiration. The atomization delivery system prevents the need of invasive intervention such as intubation in preterm infants suffering from RDS.

Description

PATENT APPLICATION FILED UNDER THE PATENT COOPERATION TREATYFORNON1NVAS1VE TRANSIENT ATOMIZATION DELIVERY SYSTEMINVENTORSWilliam Fox, M.D.Kaitlin CapuanoDoug BoydDaniel Malleske, M.D.Scott DanhofNONINVASIVE TRANSIENT ATOMIZATION DELIVERY SYSTEMTECHNICAL FIELD

[0001] This disclosure describes a noninvasive transient atomization delivery system and method for delivering medicinal fluid (including but not limited to gene therapy or other therapeutic agents) noninvasively into a patient’s airway and to pulmonary tissues in atomized form without penetrating the vocal cords. This noninvasive transient atomization delivery7system also may be utilized in any luminal passage (e.g., gastrointestinal track) for medicinal fluid delivery or suction in mammals.BACKGROUND

[0002] Preterm birth is associated with several adverse outcomes the severity7of which mostly depends on the infant’s gestational age and birth weight. The mortality7rate in this population is 10-20%. with respiratory distress syndrome (RDS) as a primary cause of death in the first few weeks of life.

[0003] Approximately 460,000 infants were bom prematurely in the United States in 2017, and an estimated 166,000 of them developed RDS that can lead to significant respiratory morbidity related treatment and re-hospitalizations, and frequently death as a result. Infants bom prematurely during 24-29 weeks of gestational age experience a very high incidence of RDS. RDS is treated by neonatologists and pediatricians, most often in neonatal intensive care units (NICUs) and special care nurseries. The treatment regimen depends on disease severity7and persistence of RDS.

[0004] The first line of defense for an infant presenting clinical signs of respiratory distress is to deliver supplemental oxygen by nasal continuous positive airway pressure (nCPAP) or nasal intermittent mandatory ventilation (nIMV) as an attempt to keep the alveoli open in the lungs. If the infant continues to deteriorate, the patient will be intubated, mechanically ventilated, and receive exogenous lung surfactant within the first 1-2 hours to survive. However, the intubation and mechanical ventilation of these infants can induce airway trauma and / or other long-term complications, such as bronchopulmonary7dysplasia (BPD).

[0005] Despite surfactant being the gold standard for RDS, the incidence rate of chronic lung diseases such as BPD has not changed, and surfactant faces many limitations. As a result, medical practitioners see a significant unmet need for a non-invasive treatment that could potentially alleviate the need for intubation in infants, thereby decreasing the incidence of intubation-related complications.SUMMARY

[0006] Various examples are now described to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. The Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.

[0007] The present disclosure relates to examples of noninvasive airway devices for delivering medicinal fluids to the respiratory system, including but not limited to perfluorocarbons, aqueous medications, gene therapies, cell therapies, and gene editing technologies suspended in fluid. Sample configurations of the noninvasive airw ay devices include a medicinal fluid delivery catheter having a proximal end that connects to a source of a medicinal fluid and a distal end that delivers the medicinal fluid to the patient’s airway and pulmonary tissues. The distal end may have an angle (e.g., 30°) relative to tubing of the medicinal fluid delivery’ catheter whereby the distal end of the medicinal fluid delivery’ catheter is aimed at the vocal cords of the patient when inserted in the patient’s airway. This noninvasive airway device also may include an oropharyngeal stylus having a curved end that is designed to follow' the natural curvatures of the orophary nx, has at least one passage to accept the distal end of the medicinal fluid delivery’ catheter and that is positionable w ithin the oropharynx of a patient to secure and facilitate placement of the distal end of the medicinal fluid delivery catheter over the vocal cords. The source of the medicinal fluid may include one or more syringes that are connected to the medicinal fluid delivery catheter via a luer-lock. For example, the medicinal fluid may include Perfluorooctylbromide (PFOB) that is delivered by the medicinal fluid delivery catheter into an oropharyngeal region above the vocal cords of the patient.

[0008] In example configurations of the noninvasive airway device, the medicinal fluid delivery’ catheter may be an atomization catheter that atomizes the medicinal fluid for delivery' to the patient’s airway. The noninvasive airway medicinal fluid deliverydevice may further include a camera (e.g., a fiber optic nasopharyngeal camera) and optional light held in place by the stylus and positioned slightly above the distal end of the atomization catheter so as to provide a visual image for proper placement of the atomization catheter and administration of the medicinal fluid to the patient. In sampleconfigurations, the atomization catheter and / or the camera may be affixed to the stylus during manufacture. The stylus may have vertical channels adapted to accept the atomization catheter and the camera and optional light. The channels of the stylus may allow the atomization catheter and / or camera to be removed and replaced without removing the stylus from the patient’s oropharyngeal cavity during use. The distal end of the atomization catheter also may include means for aiming the camera and optional light so that the vocal cords of the patient remain within a field of view of the camera while illuminated and in a direction of a plume from the distal end of the atomization catheter during a procedure. By maintaining visualization of the vocal cords throughout the procedure, delivery of the medicinal fluid to the vocal cords may be maintained through realignment of the camera (and optional light) and atomization catheter with the vocal cords, as needed.

[0009] Sample configurations of the noninvasive airway device may further include concomitant use of nasal continuous positive airway pressure device including dual nasal prongs that are inserted into one or both nares of the patient’s nose to position distal tips of the dual nasal prongs in a nasopharynx of the patient and that are attached to a Y-shaped adapter that connects directly to a ventilator circuit. This may be used for positive pressure administration.

[0010] Other sample configurations of the noninvasive airway device also may be adapted to provide suction through the catheter and / or via a Y-shaped adapter that connects directly to a suction device. With the aid of a camera, the catheter may provide micro-suction to clear portions of the airway for any secretions, blood, or emesis visualized by the camera.

[0011] Sample configurations of the noninvasive airway device may further include an atomization catheter sheath tube adapted to accept the atomization catheter for insertion, removal and axial positioning relative to the stylus.

[0012] In sample configurations of the noninvasive airway device, the curve of the stylus may allow a user to depress a tongue of the patient and restrain an epiglottis of the patient when the atomization catheter sheath tube is inserted into an airway of the patient.

[0013] The present disclosure also relates to a method of delivering a medicinal fluid to a patient. The method includes connecting the noninvasive airway device to one or more syringes containing a medicinal fluid for delivery' to the patient. If the userdetermines that the vocal cords should be desensitized before the procedure, one of the syringes may include a predetermined dose of lidocaine that is infused by the atomization delivery' device into the airway of the patient. The infusion may be made by a catheter inserted into the noninvasive airway device that is separate from the atomization catheter or the infusion may be made via the atomization catheter. The lidocaine is dispersed across at least one of a mucosal surface of the pharynx of the patient or the vocal cords of the patient while a nasal continuous positive airway pressure is administered to the patient. If not already inserted for the lidocaine delivery, the atomization catheter is then inserted into a sheath tube and the atomization catheter is extended until an atomizing tip of the atomization catheter is a predetermined distance (e.g., approximately 1-2 cm) above the vocal cords of the patient for a treatment. A target dose of the medicinal fluid is provided to the atomization catheter by a syringe and delivered via the atomization catheter to the vocal cords of the patient. The medicinal fluid may include a perfluorocarbon, an aqueous medication, and / or at least one of a gene therapy, a cell therapy, or a gene editing technology suspended in fluid.

[0014] Sample implementations of the method may further include monitoring delivery of the medicinal fluid to the vocal cords of the patient using a video monitoring device such as a video laryngoscope or a disposable fiber optic cable that provides the image to a digital imaging system or medical image viewing application to ensure that the medicinal fluid is atomizing and clearing the vocal cords and that the patient continues spontaneous breathing. The video monitoring device also may be used to locate the vocal cords of the patient and to ensure that the vocal cords are open before delivering the medicinal fluid to the vocal cords.

[0015] Inserting the atomization catheter may further include inserting the stylus to an appropriate depth and rotational orientation relative to the vocal cords before inserting the atomization catheter into the stylus until the atomizing tip of the atomization catheter is at the predetermined distance above the vocal cords of the patient. The angle of the atomizing tip also may be adjusted toward the vocal cords of the patient.

[0016] The explanations provided for each of the above-mentioned aspects and its implementation apply equally to the other aspects and the corresponding implementations. Also, any one of the foregoing examples may be combined with any one or more of the other foregoing examples to create a new configuration within the scope of the present disclosure.DETAILED DESCRIPTION OF THE DRAWINGS

[0017] The foregoing and other beneficial features and advantages of the subject matter described herein will become apparent from the following detailed description in connection with the attached figures, of which:

[0018] FIG. 1 illustrates noninvasive delivery of a transiently atomized medicinal fluid to the vocal cords of a neonate in a sample configuration.

[0019] FIG. 2 illustrates a distal end of a noninvasive transient atomization delivery system in a sample configuration.

[0020] FIGS. 3A-3D illustrate an end perspective view of the noninvasive transient atomization delivery device with tubing, a side perspective view of the curved delivery' sty lus, a side view of the curved delivery7stylus, and a top view of the curved delivery7stylus, respectively, in a sample configuration.

[0021] FIG. 4 illustrates a nasal continuous positive airyvay pressure (nCPAP) device in a sample configuration.

[0022] FIG. 5 is a plot of a compliance curve for cohorts treated yvith 5 ml / kg of Perfluorooctylbromide (PFOB), 10 ml / kg of PFOB, and a randomized control in each group for a sample study of the sample configuration of the delivery device.

[0023] FIG. 6 illustrates placement of the nCPAP device and noninvasive transient atomization delivery device for delivery of PFOB to lungs of a lamb in a sample configuration.

[0024] FIGS. 7A-7C are plots of baseline compliance, final compliance, and increase in compliance, respectively, upon application of a subtherapeutic dose of PFOB to lambs in a sample configuration.

[0025] FIG. 8 illustrates the noninvasive transient atomization delivery device with an endoscope attached according to a sample configuration.

[0026] FIGS. 9A-9C illustrate the placement of a suction catheter and endoscope in the channels of the stylus.DETAILED DESCRIPTION OF ILLUSTRATIVE CONFIGURATIONS

[0027] The following description relates to methods and devices for delivering transiently atomized medicinal fluids to the respiratory system, including but not limited to perfluorocarbons, traditional aqueous medications, gene therapies, cell therapies, and gene editing technologies suspended in fluid. Atomization of a medicinal fluid in a transient fashion will lead to less upper airyvay (trachea, upper airyvay generations 2-3)fluid bolus-based obstruction, thus supporting safer medicinal fluid delivery to the lungs. For example, the medicinal fluids may include Perfluorooctylbromide (PFOB), which is an inert fluorocarbon delivered to the respiratory' system of a neonatal patient for multiple acute life threatening neonatal respiratory conditions such as Respiratory Distress Syndrome (RDS). The physical and chemical properties of PFOB, such as antiinflammatory, radiopaque, and surfactant-like properties, make PFOB a promising ventilation medium for multiple respiratory' indications. The targeted RDS indication uses transiently atomized PFOB as an acute non-invasive treatment option to reduce frequency and severity of neonates requiring invasive intubation and mechanical ventilation. The delivery device described herein also may be used to deliver other transiently atomized medicinal fluids besides PFOB to a patient, including non-neonatal patients or animal models.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0029] An “individual,” “patient,” “subject,” “neonate,” or “animal” as used interchangeably herein, can be a human (e.g., neonate) or non-human animal. Nonlimiting examples of non-human animal subjects including non-human primates, dogs, cats, mice, rats, guinea pigs, rabbits, pigs, fowl, horses, cows, goats, sheep, and cetaceans.

[0030] The term “coupled,” as used herein, refers to the connection of a device component to another device component by any means known in the art. The ty pe of coupling used to connect two or more device components can depend on the scale and operability of the device. For example, and not by way of limitation, coupling of two or more components of a device disclosed herein can include one or more joints, valves, fittings, couplings, transfer lines, or sealing elements.

[0031] With years of historical data supporting the benefits of PFOB as a therapeutic medicinal fluid for RDS and its unmet clinical need, a noninvasive deliverymethod has been developed to leverage the therapeutic benefits of partial liquid ventilation (PLV) without intubation. A noninvasive delivery device also has been developed that noninvasively delivers a rescue dose of PFOB (either 2.5cc / kg, 5cc / kg, or lOcc / kg) as a plume of transiently atomized particles into the oropharyngeal region 2-3 mm above the vocal cords allowing the fine mist to be inhaled into the lungs of a neonate patient at risk of or diagnosed with RDS receiving only nCPAP or other support. As will be appreciated by those skilled in the art, the methods and devices used herein also maybe used to deliver transiently atomized particles of other medicinal fluids into the oropharyngeal region above the vocal cords of a patient.

[0032] FIG. 1 illustrates noninvasive delivery of a transiently atomized medicinal fluid such as PFOB to the vocal cords 110 of a neonate 100 in a sample configuration. As illustrated, the neonate 100 may receive nasal CPAP 120 or nIMV simultaneously with application of the noninvasive transient atomization delivery system 130 into the airway 135. One or more syringes 140 infuse a medicinal fluid (e.g., PFOB) into a medicinal fluid delivery catheter such as an atomization catheter 150 that has been inserted into an atomization catheter sheath tube 145 for spraying of a PFOB plume 160 out of the atomization catheter tip 170 at a therapeutic position 2-3 mm above the vocal cords 110. The optimal position for PFOB delivery7was determined to be approximately 1 cm above the glottis with a plume generating flow of 20 to 30 ml / min. The noninvasive transient atomization delivery system 130 may also include a camera 180 (e.g., a fiber optic nasopharyngeal camera) and optional light that may be used to guide the noninvasive transient atomization delivery system 130 during placement. The camera 180 also may be used to observe the dispersal of the medicinal fluid into the patient’s airway. An aiming adjustment 190 enables the user to aim the camera 180 (and optional light) and the atomization catheter tip 170 so that the vocal cords 110 remain within the field of view 195 of the camera 180 and to keep the PFOB plume 160 aimed towards the vocal cords 110 during a procedure.

[0033] FIG. 2 better illustrates the distal end 200 of the noninvasive transient atomization delivery system 130 in a sample configuration. As illustrated, the distal end 200 includes multiple (e.g., 2-3) lumens 210 that accept the atomization catheter sheath tube 145 including the atomization catheter 150 having atomization catheter tip 170 as well as other devices such as a catheter for lidocaine delivery, a camera, and the like. For example, the camera 180 (and optional light) may be inserted into one of the other distal openings 220 of the distal end 200. As illustrated, the distal end 200 may be angled at approximately 25°-30° relative to the catheter 150 so that the noninvasive transient atomization delivery system 130 may aim the atomization catheter tip 170 towards the vocal cords 110 of the patient 100 in accordance with the anatomy of the patient's airway when inserted into a treatment position within the patient’s airway. A distal end with a 90° angled distal end 200 was found to be the easiest to position.

[0034] FIG. 3A illustrates an end perspective view of the noninvasive transient atomization delivery system 130 including catheter tubing 150, luer lock 300, and a curved assembly stylus 310. FIG. 3B shows a side perspective view of the curved assembly stylus 310. while FIG. 3C shows a side view of the curved assembly stylus 310 and FIG. 3D shows a top view of the curved assembly stylus 310. The stylus 310 assist with positioning of the noninvasive transient atomization delivery system 130 in the oropharynx and contains channels for an endoscope and a suction catheter. As illustrated, the noninvasive transient atomization delivery system 130 includes a luer lock 300 for connecting the atomization catheter 150 to a syringe (not shown). The distal end 200 of the noninvasive transient atomization delivery system 130 may be placed in a curved assembly sty lus 310 having a curved distal end 320 and vertical channels 330 that run on each side of the noninvasive transient atomization delivery system 130. In sample configurations, the camera 180 and the atomization catheter 150 may be affixed to the stylus 310 during manufacture. The vertical channels 330 of the stylus 310 also may allow the atomization catheter 150 and camera 180 to be removed and replaced without removing the stylus 310 from the patient’s oropharyngeal cavity' during use.

[0035] Ancillary components of the noninvasive delivery device 130 include one or more syringes 140 and a nasal CPAP 120. A syringe 140 may comprise a 10 mL syringe with a Luer-Lok™ tip, and the nasal CPAP 120 may include custom dual nasal prongs 400 (FIG. 4) made from 3.0 French or 3.5 French un-cuffed endotracheal tubes attached to a custom-made “Y” adapter 410 that connects directly to a ventilator circuit (not shown) or suction device (not shown) via connector 420. During use, the nasal prongs 400 are inserted into each nare of the nose to a depth of 7 to 8 cm to position the distal tips in the nasophary nx.

[0036] An example noninvasive transient atomization delivery' device 130 is light in weight, portable, requires minimum set up, does not pass the vocal cords 110, and enables quick instillation. In sample configurations, a noninvasive single use disposable atomization delivery device 130 delivers medicinal fluids such as PFOB into the oropharyngeal region above the vocal cords 110. A sample configuration of the noninvasive single use disposable atomization delivery device 130 includes one or more syringes 140. atomization catheter 150, fiber-optic camera 180 with light source, and the curved assembly stylus 310 made of biocompatible materials. As shown in FIGS. 3A-3D, the assembly stylus 310 has a slim durable design with a curved distal end 320 andvertical channels 330 that run on each side. The slim design ensures that the noninvasive single use disposable atomization delivery' device 130 will not obstruct the air flow into the lungs. The curved distal end 320 of the noninvasive single use disposable atomization delivery device 130 allows it to bypass the oral cavity and to follow the natural curvatures of the oropharynx for positioning in the oropharyngeal region. Also, the vertical channels 330 provide the location of where the fiber-optic camera 180 with light source and the atomization catheter 150 are incorporated into the overall design.

[0037] During use, a syringe 140 is filled with a medicinal fluid (e.g.. PFOB) and connected to the luer lock adapter 300 at the proximal end of the atomization catheter 150. The atomization catheter 150 has the luer lock adapter 300 at the proximal end and the atomizing nozzle 170 at the distal end. A force generated from plunging the fluid out of the syringe 140 and through the atomization catheter 150 propels the fluid out of the atomizing nozzle 170 as a plume 160 of fine mist.

[0038] The fiber-optic camera 180 with light source is positioned slightly above the distal end of the atomization catheter 150. The camera 180 with light source provides a visual image for proper placement of the noninvasive single use disposable atomization delivery device 130 and administration of fluids for an optimal therapeutic delivery’.

[0039] The noninvasive single use disposable atomization delivery device 130 includes the following features to facilitate placement and medicinal fluid delivery:The rigid positioning device 310 that allows a user to push down the patient’s tongue and restrain the epiglottis in a manner similar to a laryngoscope.- The camera 180 with light source provides visualization of positioning and the medicinal fluid delivery process.The atomization catheter sheath tube 145 allows for insertion, removal and axial positioning of the atomization catheter 150 relative to the positioning device 310.- A 30-degree angle at the distal end of the positioning device 310 enables proper positioning of the atomization catheter 150 relative to the vocal cords 110.

[0040] The key elements of a sample noninvasive transient atomization delivery device 130 thus include components from an atomization catheter 150 (e.g., a MADgic® Laryngo-Tracheal Mucosal Atomization Device available from Teleflex) and a camera 180 from a video lary ngoscope (e.g., a Peak Medical video lary ngoscope). In a sampleconfiguration, the atomization catheter 150 is used to administer medication across the entire upper airway and beyond the vocal cords 110. The atomization catheter 150 is not prefilled, so the clinician may select the type of medication and exact dosing desired. A malleable atomization catheter 150 enables precise, targeted delivery that is specific to the patient’s anatomy. The atomization catheter 150 so configured provides a consistent, transiently atomized spray 160 (e.g., 30-100 microns in diameter) for direct coverage of the pharynx and vocal cords 110 of the patient. Such a particle size demonstrates the ability of the noninvasive transient atomization delivery device 130 to deliver the medicinal fluid rapidly through the patient's airway and to effectively distribute the medicinal fluid evenly throughout the lungs. It will be appreciated that some medicinal fluids, such as PFOB, just need to get across the vocal cords 110 to “wick” to the relevant part of the lungs to convey the pharmacology. The narrow; long atomization catheter 150 easily reaches the vocal cords 110 to allow the medicinal fluid to get across the vocal cords 110 while adapting to any luer-lock syringe.

[0041] In a pilot feasibility study, the cohorts tested doses of 2.5ml / kg, 5ml / kg, and lOml / kg with a randomized control in each group to determine if the animal model aligned with the full Dose Range Finding (DRF) study. X-rays of the animals indicated an even medicinal fluid distribution post medicinal fluid exposure, reflecting an effective non-invasive medicinal fluid delivery method. In a full DRF study, the cohorts included 2.5 ml / kg, 5 ml / kg and 10 ml / kg with a randomized control in each group. As illustrated in FIG. 5, the noninvasive transient atomization delivery device 130 provides an increased tidal volume to the patient for higher doses of PFOB.

[0042] A full DRF study measured the dose dependent effects on the following: Pulmonary gas exchange measured by arterial blood gases;Pulmonary mechanics by compliance measurements via ventilator and plethysmography bands;- Pulmonary distribution captured by x-ray; and Anti-inflammatory effects measuring inflammatory cytokines.As represented in the comparison of the baseline compliance in FIG. 7A and final compliance in FIG. 7B of pilot and DRF data, the end of study compliance increased 3-4 times from the baseline compliance measurement, as shown in FIG. 7C.Method of Operation

[0043] 1. At least 20 minutes prior to medicinal fluid (e g., PFOB) administration, place sealed medicinal fluid vials into a water bath at 37° - 40 C.

[0044] 2. Prepare the noninvasive transient atomization delivery device 130 by connecting a fluid transfer line and connectors to the atomization catheter 150, and fill one or more syringes 140 with a predetermined dose of lidocaine if desensitization of the vocal cords 110 is desired.

[0045] 3. When desired, deliver the lidocaine by infusing a 0.5 ml volume of a solution of 10% lidocaine using a catheter (not shown) that is separate from the atomization catheter 150 being used to deliver the medicinal fluid to disperse the lidocaine across the mucosal surface of the nasopharynx. An additional 0.5ml of lidocaine may be sprayed directly on the vocal cords 110 using the atomization catheter 150 and visualized with a standard laryngoscope.

[0046] 4. Administer the nasal CPAP 120.

[0047] 5. Prepare the patient 100 for medicinal fluid deliver}' in a prone position.

[0048] 6. Fill a syringe 140 with a predetermined dose of the medicinal fluid(from the 40° C bath) and connect the syringe 140 to the fluid transfer line.

[0049] 7. Insert the atomization catheter 150 into the sheath tube 145 and extend until the atomizing tip 170 is 1-2 cm above the vocal cords 110.

[0050] 8. Deliver a target dose of the medicinal fluid at a predetermined dosage of at least 10 mL / min, and monitor delivery via use of a video monitoring device such as a video laryngoscope to ensure that the medicinal fluid is atomizing and clearing the vocal cords 1 10 and that the patient continues spontaneous breathing. Deliver}' should be paused if the liquid medicinal fluid accumulates above the vocal cords 110.Delivery may be resumed after the liquid above the vocal cords 1 f 0 is inhaled.

[0051] 9. Prepare the patient 100 for dosing in a supine position.

[0052] 10. Repeat the lidocaine delivery as described in step 3 above, as needed.

[0053] 11. Repeat steps 8, 9, and 10 (if needed).Device Workflow

[0054] 1. Identify a patient fOO that is clinically declared at risk of RDS.

[0055] 2. Prepare the noninvasive transient atomization delivery device 130 by unpackaging the noninvasive transient atomization delivery device 130 and connecting the fluid lines.

[0056] 3. Warm the syringe(s) 140 filled with the medicinal fluid to be delivered (e g., PFOB);

[0057] 4. Fill the syringe(s) 140 with the medicinal fluid.

[0058] 5. Insert the custom positioning device 310 and position with the appropriate depth and rotational orientation to position the noninvasive transient atomization delivery device 130 for the desired treatment. For example, a single disposable noninvasive transient atomization delivery device 130 may be noninvasively inserted into the oral airway from a patient interface and a visualization device such as camera 180 with light source may be used for depth and rotation orientation to the desired treatment position. Placement at the patient interface is similar to a standard feeding tube placement. The device’s outer sheath 145 and patient interface placement will prevent the movement of the noninvasive transient atomization delivery device 130 in the oropharynx. Once the noninvasive transient atomization delivery device 130 is properly placed and secured, an esophageal tube (not shown) may be inserted into a lumen 210 of the noninvasive transient atomization delivery device 130 to prevent the medicinal fluid from getting into the patient’s stomach. The atomization catheter 150 is removed from the overall system before and after medicinal fluid administration. When the atomization catheter 150 is inserted, the angle of the atomization nozzle 170 is adjusted toward the vocal cords 1 10.

[0059] 6. The patient 100 is oriented as needed.

[0060] 7. A syringe 140 is filled with lidocaine, as desired to desensitize the vocal cords, and attached to the atomization catheter 150 for delivery of a dose to the vocal cords 110.

[0061] 8. A medicinal fluid filled syringe 140 is attached to the atomization catheter 150.

[0062] 9. The syringe plunger is pressed to deliver the medicinal fluid dose and dose deliver}’ is monitored using a camera / video screen. Delivery is paused if medicinal fluid liquid accumulates above the vocal cords 110.

[0063] 10. After the dosing session, the noninvasive transient atomization delivery’ device 130 is removed from the patient 100.

[0064] For additional dosing exposures, the noninvasive transient atomization delivery device 130 is inserted and steps 2-3 and 6-10 are repeated, if needed.Testing

[0065] In the case of testing of the delivery device on a lamb model as the patient, the setup is as follows. Each lamb is placed on nCPAP, an esophageal balloon is placed in the esophagus to prevent accumulation of the medicinal fluid in the gastrointestinal tract, and an atomization catheter 150 is placed in the posterior pharynx as illustrated in FIG. 6. The medicinal fluid is transiently atomized above the vocal cords 110 for gravitational delivery into the lungs of the spontaneously breathing animal.

[0066] The charts in FIG. 7 show preliminary evidence of increased compliance with the subtherapeutic dose. The noninvasive delivery device 130 effectively administered the medicinal fluid to the targeted therapeutic area without adverse events such as pneumothorax. X-rays of the lambs showed the non-invasive method was successful in delivering a subtherapeutic dose of the medicinal fluid to the targeted area of the lungs. Results showed a 3-to-4-fold improvement of compliance in the subtherapeutic and intermediate therapeutic doses from baseline to end of study compared to the control.

[0067] The noninvasive transient atomization delivery device 130 is considered to be noninvasive as it does not breach the vocal cords 110 of the patient 100. As noted above, the noninvasive transient atomization delivery device 130 is made up of two components, including an atomization catheter 150 (e g., MADgic) and a camera 180 from a video laryngoscope (e.g.. Peak Medical). In a sample configuration, both components are integrated into a 20 cm plastic sheath tube 145 allowing the user to depress the tongue and restrain the epiglottis in a manner like a lary ngoscope. The distal end of the noninvasive transient atomization delivery device 130 is angled at 30° to achieve the proper positioning of the atomization catheter 150. The laryngoscope camera 180 is used as a visual aid to locate the vocal cords 110 and to ensure that the vocal cords 110 are open before delivering the medicinal fluid to targeted area. A lOmL Luer-Lok syringe 140 with the medicinal fluid may be connected to the input end of the atomization catheter 150 to inject the medicinal fluid at a force to create a transiently atomized plume 160 of the medicinal fluid.

[0068] For use with a human subject, the sheath 145 has a curved, rigid hook shape that mimics the typical airway of a neonate. Two channels 330 are provided alongthe sides of the sheath 145 that house the atomization catheter 150 and the camera 180. As shown in FIG. 8, an endoscope 800 or fiber optic cable may be utilized to assist in visualization of the targeted area. In sample configurations, the atomization catheter 150 and disposable fiberoptic camera 180 with light source may be pre-installed with the curved assembly 310 to create an all-in-one, disposable product.

[0069] The advantages of the transient atomization approach of PFOB described herein, are not limited to, but include:There is no strict time limitation to PFOB administration after birth, unlike surfactant.PFOB is an inert molecule that will not degrade in the body unlike surfactant. A noninvasive transient atomization delivery system 130 reduces the need for invasive interventions such as intubation and mechanical ventilation and reduces the complications associated with invasive interventions that can lead to chronic lung disease.The noninvasive transient atomization delivery system 130 is not limited to PFOB therapy but can be used for other respiratory therapies.

[0070] It is believed that the noninvasive transient atomization delivery device 130 described herein will reduce the rate of intubation within the neonatal patient population by 20% and prevent the long-term complications associated with intubation and conventional mechanical ventilation (CMV), which can induce airway trauma and long-term complications such a chronic lung diseases.

[0071] The catheter-accepting channel in the noninvasive transient atomization delivery device 130 is not limited to a medicinal fluid delivery catheter. For example, FIGS. 9A-9C illustrate the placement of a micro-suction catheter 910 (e.g., standard 8 French, thumb controlled, straight suction catheter) and endoscope 920 in the channels of the stylus 900. As illustrated in FIGS. 9A-9C, an open channel (e.g., channel 180 of the noninvasive transient atomization deliver}' system 130 of FIG. 2) can accept a microsuction catheter 910 and, with the aid of a fiberoptic camera of the endoscope 920, the user can visualize the airway for any secretions, blood, or emesis and use the microsuction catheter 910 to clear the airway prior to intubation. This eliminates the need for multiple pieces of equipment of various sizes and limits special maneuvers to effectively clear the airway. The channel 180 may be connected to a Y -shaped adapter to connect the micro-suction catheter 910 directly to a suction device (not shown).

[0072] It will be appreciated by those skilled in the art that the noninvasive transient atomization delivery device described herein has a number of unique aspects and advantages over existing devices. For example, the noninvasive transient atomization delivery device described herein provides integrated videoscopic visualization and airway suction capabilities in a single device allowing for a simplified approach to intubation. The noninvasive transient atomization delivery device itself also fulfills the purpose of a laryngoscope tongue blade and also allows for simultaneous airway clearance (suction) and visualization during the intubation attempt, reducing or eliminating the need for separate airway suction and intubation procedures. The noninvasive transient atomization delivery device described herein also serves as an adjunct to intubation by providing a simplified approach to intubation, combining lary ngoscopy and airway clearance (suction) in one device. The noninvasive transient atomization delivery device described herein further enables airway’ assessments that are independent of intubation. Such assessments allow for unsedated evaluation of the upper airway during spontaneous breathing, including but not limited to assessment of vocal cord movement, pharyngomalacia, laryngomalacia, vocal cord or supraglottic lesions, etc.

[0073] It will be further understood by those skilled in the art that this disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the above description or illustrated in the drawings. The configurations herein are capable of other configurations, and capable of being practiced or carried out in various ways. Also, it will be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0074] Although the presently disclosed subject matter and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the presently disclosed subject matter as defined by the appended claims. Moreover, the scope of the presently disclosed subject matter is not intended to be limited to the particular configurations described in the specification. Accordingly, the appended claims are intended to include within their scope such modifications. Various references are cited herein, the contents of which are hereby incorporated by reference in their entireties.

Claims

WHAT TS CLAIMED:

1. A noninvasive airway device, comprising: a catheter having a proximal end that connects to a source of a medicinal fluid or a suction device and a distal end that delivers the medicinal fluid or suction to a patient’s airway, wherein the distal end is secured at an angle relative to tubing of the catheter to direct the distal end towards vocal cords of a patient when inserted in the patient's airway; and an oropharyngeal stylus having a curved end that follows natural curvatures of a patient’s oropharynx, has at least one passage adapted to accept the distal end of the catheter, and that is positionable within the patient’s oropharynx to secure and direct the distal end of the catheter over the vocal cords of the patient.

2. The delivery device of claim 1, wherein the catheter comprises an atomization catheter that atomizes the medicinal fluid for delivery to the patient’s airway.

3. The delivery device of claim 2. further comprising a camera held in place by the stylus and positioned slightly above the distal end of the atomization catheter so as to provide a visual image for proper placement of the atomization catheter and administration of the medicinal fluid to the patient.

4. The delivery device of claim 3. wherein the atomization catheter and camera are affixed to the stylus during manufacture.

5. The delivery' device of claim 3. wherein the sty lus has vertical channels adapted to accept the atomization catheter and the camera.

6. The delivery device of claim 5, wherein the channels are adapted to allow at least one of the atomization catheter or camera to be removed and replaced w ithout removing the stylus from the patient’s airway during use.

7. The delivery device of claim 3, wherein the distal end of the atomization catheter comprise means for aiming the camera and a distal atomization tip so that thevocal cords of the patient remain within a field of view of the camera and in a direction of a plume from the distal atomization tip during a procedure.

8. The delivery device of claim 1. wherein the source of the medicinal fluid comprises a syringe that is connected to the catheter via a luer-lock.

9. The deliver^' device of claim 1, further comprising a nasal continuous positive airway pressure device including dual nasal prongs that are inserted into each nare of the patient’s nose to position distal tips of the dual nasal prongs in a nasopharynx of the patient and that are attached to a Y -shaped adapter that connects directly to a ventilator circuit.

10. The delivery device of claim 1. further comprising dual nasal prongs that are inserted into each nare of the patient’s nose to position distal tips of the dual nasal prongs in a nasopharynx of the patient and that are attached to a Y -shaped adapter that connects directly to the suction device.

11. The delivery device of claim 1, wherein the medicinal fluid comprises at least one of a perfluorocarbon, an aqueous medication, or at least one of a gene therapy, a cell therapy, or a gene editing technology suspended in fluid that is delivered by the catheter into an oropharyngeal region above the vocal cords of the patient.

12. The delivery device of claim 3, further comprising an atomization catheter sheath tube adapted to accept the atomization catheter for insertion, removal and axial positioning relative to the stylus.

13. The delivery device of claim 12, wherein the atomization catheter is integrated into the atomization catheter sheath tube so as to allow a user to depress a tongue of the patient and restrain an epiglottis of the patient when the atomization catheter sheath tube is inserted into an airway of the patient.

14. The delivery device of claim 1, wherein the angle of the distal end relative to the tubing of the catheter is approximately 30°.

15. A method of delivering a medicinal fluid or suction to an airway of a patient, comprising: connecting the noninvasive airway device of claim 1 to a syringe having a predetermined dose of a medicinal fluid; inserting an atomization catheter into a sheath tube of the noninvasive transient atomization delivery7device of claim 1 and extending the atomization catheter until an atomizing tip of the atomization catheter is a predetermined distance above vocal cords of the patient for a treatment; and delivering a target dose of the medicinal fluid via the atomization catheter to the vocal cords of the patient.

16. The method of claim 15, further comprising monitoring delivery7of the medicinal fluid to the vocal cords of the patient using a video monitoring device to ensure that medicinal fluid is atomizing and clearing the vocal cords and that the patient continues spontaneous breathing.

17. The method of claim 16, further comprising using the video monitoring device to locate the vocal cords of the patient and to ensure that the vocal cords are open before delivering the medicinal fluid to the vocal cords.

18. The method of claim 15, wherein inserting the atomization catheter further comprises inserting the stylus to an appropriate depth and rotational orientation relative to the vocal cords before inserting the atomization catheter into the stylus until the atomizing tip of the atomization catheter is at the predetermined distance above the vocal cords of the patient.

19. The method of claim 18, further comprising adjusting an angle of the atomizing tip toward the vocal cords of the patient.

20. The method of claim 15, further comprising: connecting the noninvasive airway7device of claim 1 to a syringe having a predetermined dose of lidocaine; andinfusing a volume of lidocaine via a catheter inserted into the noninvasive airway device that is separate from the atomization catheter, whereby the lidocaine is dispersed across at least one of a mucosal surface of a nasopharynx of the patient or the vocal cords of the patient prior to delivery of the medicinal fluid.

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