NASAL CANNULA FOR DISTRIBUTION OF THERAPEUTIC GAS TO A PATIENT

专利摘要:
cannula to minimize dose dilution during nitric oxide delivery. the present invention, in general, relates to, among other things, systems, devices, materials and methods that can improve the efficiency and/or accuracy of the treatment with nitric oxide through, for example, the reduction of the dilution of nitric oxide (in ) inhaled. as described in this document, dilution of in may occur due to several factors. to reduce the dilution of an intended dose of no, various exemplary nasal cannulas, pneumatic configurations, production methods and methods of use, etc., are disclosed.
公开号:BR112015013095B1
申请号:R112015013095-0
申请日:2013-12-04
公开日:2021-08-17
发明作者:Craig Flanagan；Simon Freed；John Klaus；Thomas Kohlmann；Martin D. Meglasson；Manesh Naidu；Parag Shah
申请人:Mallinckrodt Hospital Products IP Limited；
IPC主号:

专利说明:

TECHNICAL FIELD
[0001] The present invention generally relates to improving the accuracy and/or precision of nitric oxide therapy, reducing the dilution of inhaled nitric oxide and/or ensuring mixing within the patient's nose. FUNDAMENTALS
[0002] Nitric oxide gas (NO), when inhaled, dilates blood vessels in the lungs, improving blood oxygenation and reducing pulmonary hypertension. Because of this, some provide nitric oxide as a therapeutic gas in the inspiratory respiratory gases for patients with pulmonary hypertension.
[0003] Typically, inhaled NO is delivered in a carrier gas from a high pressure source (eg a pressurized cylinder) to the patient at or near ambient pressure via a breathing tube for anesthesia patients or dependents/subjects a UTI respirator or a nasal cannula for patients to breathe spontaneously. Delivering an accurate and consistent dose to the patient through a nasal cannula can be particularly challenging when the flow rate is pulsatile, for example, because dose dilution can occur.
[0004] In this regard, there is a need for new methods and apparatus to avoid dosage dilution within the delivery channel of a nitric oxide delivery device, as well as manufacturing methods of these devices. ABSTRACT
[0005] Aspects of the present invention relate to improved nasal cannulas that minimize retrograde flow and/or permeation of oxygen, air, and/or other gases during NO therapy allowing delivery of NO to one or both nostrils. Such cannulas can reduce the dose dilution provided by using cannula materials and/or coatings that limit oxygen diffusion through the cannula walls and/or use cannula configurations that avoid mixing of O2 and NO co-delivered and/or reduce the retrograde flow through the end of the patient's cannula.
[0006] Aspects of the present invention also relate to methods of minimizing the dose dilution of NO. Other aspects of the present invention relate to methods of treatment using these nasal cannulas and/or methods of administration. Other aspects of the present invention relate to methods of manufacturing multi-lumen cannulas and their nasal adapters.
[0007] In exemplary embodiments, a nasal cannula of the present invention may be for delivering at least one therapeutic gas to a patient in need thereof. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The nasal cannula may also include a nasal cannula adapter. The first lumen may be capable of delivering a first therapeutic gas to a patient in respective need, the second lumen may be capable of transmitting a pressure change to a pressure change sensor and/or breathing sensor, the third lumen may be capable of delivering a second therapeutic gas to the patient, and/or the cannula nose adapter may include separate patient flow paths to the first lumen, the second lumen, and the third lumen. At least one therapeutic gas can be nitric oxide.
[0008] In exemplary embodiments, a nasal cannula of the present invention can be used to deliver therapeutic gas to a patient. The nasal cannula can include a first lumen, a second lumen and/or a third lumen. The first lumen can be a first therapeutic gas lumen for delivering a first therapeutic gas to a patient, the trapped lumen can be a trigger lumen, and the third lumen can be a second therapeutic gas lumen for delivering a second gas therapeutic for the patient. In addition, a cannula nose adapter can allow separate flow paths for the patient to the first therapeutic gas lumen, the trigger lumen and/or the second therapeutic gas lumen.
[0009] In exemplary embodiments, the nasal cannula can reduce the dilution of one or more of the first and second therapeutic gases delivered to the patient and/or can be configured to be placed in fluid communication with at least one system to deliver the first or second therapeutic gas to the patient. The nasal cannula can inhibit the mixture of nitric oxide and oxygen and/or the nasal cannula can reduce the delivery of nitrogen dioxide to the patient.
[0010] In exemplary embodiments, one or more of the first and second therapeutic gases for the patient for the treatment of pulmonary hypertension. In exemplary modalities, the nasal cannula can deliver therapeutic gases first or second to the patient for the treatment of pulmonary hypertension, pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), pulmonary hypertension such as pulmonary arterial hypertension (PAH), pulmonary hypertension secondary to idiopathic pulmonary fibrosis (IPF), and/or pulmonary hypertension secondary to sarcoidosis. The first therapeutic gas and the second therapeutic gas can be different gases or the same gas. In exemplary embodiments, the first therapeutic gas can be nitric oxide and the second therapeutic gas can be oxygen and/or the first therapeutic gas lumen for the delivery of nitric oxide can be smaller than the second therapeutic gas lumen for the delivery of oxygen and/or the triggering lumen. In exemplary embodiments, the first therapeutic gas lumen can be for nitric oxide delivery and/or can be six to eight feet long with an internal diameter of 0.01 inches to 0.10 inches. In exemplary hyodalities, the trigger lumen can be six to eight feet long with an internal diameter of 0.05 inches to 0.20 inches.
[0011] In exemplary embodiments, the first therapeutic gas may be nitric oxide and/or the cannula nosepiece may include a nitric oxide flow path that may have an inner diameter that may be less than the inner diameter of the gas lumen therapeutic first. In exemplary embodiments, the first therapeutic gas can be nitric oxide and/or the cannula nosepiece can include a nitric oxide flow path having a volume that can be less than about 10% of a minimum pulse volume of the nitric oxide. The cannula may include a wall material with a low oxygen transmission rate that may be between

In exemplary embodiments, the cannula may further include a fourth lumen which may be another first therapeutic gas lumen to deliver the first therapeutic gas to the patient. In addition, the first lumen can deliver the first therapeutic gas to one nostril of the patient and the fourth lumen can deliver the first therapeutic gas to another nostril of the patient. In exemplary embodiments, the cannula can include at least one check valve in fluid communication with the therapeutic gas lumen first, a cannula wrench, an oxygen-absorbing material, or a flexible support bridge that cushions the patient's nasal septum. .
[0013] In exemplary embodiments, a nasal cannula of the present invention can be used to deliver therapeutic gas to a patient. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The first lumen can be a first therapeutic gas lumen for delivering a first therapeutic gas to a patient, the second lumen can be a trigger lumen and/or the third lumen can be a second therapeutic gas lumen for delivering a second therapeutic gas for the patient. The first therapeutic gas lumen, trigger lumen, and the second therapeutic gas lumen can aggregate in a cannula nose adapter. The cannula nose adapter may allow separate flow paths for the patient to the first therapeutic gas lumen, the trigger lumen and/or the second therapeutic gas lumen. The first therapeutic gas lumen can have an inside diameter that can be smaller than the inside diameter of the second therapeutic gas lumen and an inside diameter of the triggering lumen and/or the first therapeutic gas lumen can have an inside diameter that can be larger than an inside diameter of the flow path to the therapeutic gas lumen first in the nasal cannula nosepiece.
[0014] In exemplary embodiments, the nasal cannula can reduce the dilution of the first and/or second therapeutic gases delivered to the patient and/or can be configured to be placed in fluid communication with at least one system for delivering the first or second therapeutic gas to the patient. The nasal cannula can inhibit the mixture of nitric oxide and oxygen and/or the nasal cannula can reduce the delivery of nitrogen dioxide to the patient.
[0015] In exemplary embodiments, one or more of the first and second therapeutic gases for the patient for the treatment of pulmonary hypertension. In exemplary modalities, the nasal cannula can deliver therapeutic gases first or second to the patient for the treatment of pulmonary hypertension, pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), pulmonary hypertension such as pulmonary arterial hypertension (PAH), pulmonary hypertension secondary to idiopathic pulmonary fibrosis (IPF), and/or pulmonary hypertension secondary to sarcoidosis. In exemplary embodiments, the first lumen of therapeutic gas can be for nitric oxide delivery and can be six to eight feet long with an internal diameter of 0.01 inches to 0.10 nnlαriadαc Cl li'irnan rlacαnradaqnta ππdp <!Pr Hα coic ar» itr> nΔc rlo ^VIVyVIMMW. V-Z IMI III ll WVI I VMM VMI I IV f^VW VVI MV WIV V• VHV f-z K/ <4 length with an internal diameter of 0.05 inches to 0.20 inches.
[0016] In exemplary embodiments, the first therapeutic gas can be nitric oxide and/or the cannula nosepiece can include a nitric oxide flow path with a volume that can be less than about 10% of a minimum pulse volume of the nitric oxide pulse. The cannula may include a wall material with a low oxygen transmission rate which may be between 0.001
and 10
In exemplary embodiments, the cannula can include at least one check valve in fluid communication with the therapeutic gas lumen first, a cannula wrench, an oxygen-absorbing material, or a flexible support bridge that cushions the patient's nasal septum. .
[0017] In exemplary embodiments, a nasal cannula of the present invention can be used to deliver therapeutic gas to a patient. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The first lumen can be a first therapeutic gas lumen for delivering nitric oxide gas to a patient, the second lumen can be a trigger lumen and the third lumen can be a second therapeutic gas lumen for delivering one or more between oxygen gas and air gas for the patient. The first therapeutic gas lumen, the trigger lumen, and/or the second therapeutic gas lumen may aggregate into a cannula nosepiece, the cannula nosepiece may allow separate flow paths for the patient to the therapeutic gas lumen first, the trigger lumen and/or therapeutic gas lumen second. The flow path to the therapeutic gas lumen first for delivery of nitric oxide to the patient may have a volume in the cannula nosepiece that may be less than about 10% of a minimum pulse volume of the nitric oxide pulse. The first therapeutic gas lumen can have an inside diameter that can be smaller than the inside diameter of the second therapeutic gas lumen and an inside diameter of the triggering lumen and/or the first therapeutic gas lumen can have an inside diameter that can be larger than an inside diameter of the flow path to the therapeutic gas lumen first in the nasal cannula nosepiece.
[0018] In exemplary embodiments, a method for treating pulmonary hypertension may include administering nitric oxide gas to a patient in need thereof, wherein the nitric oxide may be administered through a nasal cannula, wherein the cannula nasal can include a first lumen, a second lumen, and a third lumen. In exemplary modalities, nitric oxide is for the treatment of pulmonary hypertension. In exemplary modalities, the nasal cannula can deliver nitric oxide to the patient for the treatment of pulmonary hypertension, pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), pulmonary hypertension such as pulmonary arterial hypertension (PAH), pulmonary hypertension secondary to idiopathic pulmonary fibrosis (IPF), and/or pulmonary hypertension secondary to sarcoidosis.
[0019] Exemplary modalities, nitric oxide can be pulsed early in inspiration and/or delivered in the first half of inspiration. In exemplary modalities, nitric oxide can be administered by pulsed inhalation to spontaneously breathing patients, nitric oxide can be administered at the beginning of inspiration, the dose of nitric oxide can be about 0.010 mg/kg/hr, and/or dose can be delivered at the beginning of inspiration at a pulse width of less than 260 milliseconds. In exemplary embodiments, the method can further include administering oxygen to the patient.
[0020] In exemplary embodiments, a nitric oxide administration method of the present invention can be used for the treatment of pulmonary hypertension. The method can include administering nitric oxide gas to a patient, wherein the nitric oxide can be administered through a nasal cannula. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The first lumen can be a therapeutic gas first lumen for delivering nitric oxide gas to a patient, the second lumen can be a trigger lumen and the third lumen can be a therapeutic gas second lumen for delivering oxygen gas to the patient. In addition, a cannula nose adapter can allow separate flow paths for the patient to the first therapeutic gas lumen, the trigger lumen and/or the second therapeutic gas lumen. The second lumen can be for detecting the onset of inspiration and/or a change in pressure.
[0021] In exemplary embodiments, the nasal cannula can reduce the dilution of one or more of the first and second therapeutic gases delivered to the patient and/or can be configured to be placed in fluid communication with at least one system to deliver the first or second therapeutic gas to the patient. The first lumen of therapeutic gas for delivery of nitric oxide may be smaller than both the second lumen of therapeutic gas for oxygen delivery and the triggering lumen. The first lumen of therapeutic gas can have an inside diameter dimension that can be selected to be substantially reduced to reduce nitric oxide dilution, reducing NO transit time through the cannula, and is also substantially large enough not to cause back pressure significantly and substantially not distorting nitric oxide pulses and/or the triggering lumen can have an inside diameter dimension that can be selected to be substantially small while also being substantially large enough to reduce delay and distortion of pressure signals. The cannula nosepiece may include a nitric oxide flow path which may have an inner diameter which may be less than the inner diameter dimension of the first therapeutic gas lumen.
[0022] In exemplary embodiments, the cannula can include at least one check valve in fluid communication with the therapeutic gas lumen first, a cannula wrench, an oxygen-absorbing material, or a flexible support bridge that cushions the septum. the patient's nasal cavity. The cannula may include a wall material with a low (cc)(miQ oxygen transmission rate that may be between 0.001)
and
In exemplary embodiments, the cannula may further include a fourth lumen which may be another first therapeutic gas lumen to deliver the first therapeutic gas to the patient. In addition, the first lumen can deliver the first therapeutic gas to one nostril of the patient and the fourth lumen can deliver the first therapeutic gas to another nostril of the patient. BRIEF DESCRIPTION OF THE FIGURES
[0023] The characteristics and advantages of various embodiments of the present invention will be more fully understood with reference to the following detailed description when taken in conjunction with the accompanying figures, in which:
[0024] FIG. 1 shows an exemplary nasal cannula in accordance with exemplary embodiments of the present invention;
[0025] FIG. 2A shows exemplary flow directionality of NO gas during delivery to patients, in accordance with exemplary embodiments of the present invention;
[0026] FIG 2B shows an exemplary retrograde flow path, in accordance with exemplary embodiments of the present invention;
[0027] FIGS. 3A and 3B show an exemplary mono-lumen cannula in accordance with exemplary embodiments of the present invention;
[0028] FIGS. 4 and 5A show an exemplary dual lumen cannula and/or exemplary pneumatic pathways for NO, oxygen, and trigger lumens in accordance with exemplary embodiments of the present invention;
[0029] FIG. 5B shows an exemplary nose adapter of an exemplary dual-lumen cannula and/or pneumatic pathways, in accordance with exemplary embodiments of the present invention;
[0030] FIGS. 6A and 6B show an exemplary dual lumen cannula and/or exemplary pneumatic pathways for NO, oxygen, and trigger lumens in a tri-lumen cannula, in accordance with exemplary embodiments of the present invention;
[0031] FIGS. 6C and 7 show exemplary nasal adapters of a tri-lumen cannula and/or pneumatic pathways, in accordance with exemplary embodiments of the present invention;
[0032] FIGS. 8A and 8B show exemplary pneumatic pathways for NO, oxygen, and triggering lumens in a quad-lumen cannula, in accordance with exemplary embodiments of the present invention;
[0033] FIGS. 8C and 8D show exemplary nasal adapters of a quad-lumen cannula and/or pneumatic pathways, in accordance with exemplary embodiments of the present invention;
[0034] FIG. 9A shows an exemplary duckbill check valve in accordance with exemplary embodiments of the present invention;
[0035] FIGS. 9B and 9C show exemplary umbrella and/or hinge check valves in accordance with exemplary embodiments of the present invention;
[0036] FIG. 10 shows an exemplary nasal cannula with an umbrella or hinge valve for delivering NO, in accordance with exemplary embodiments of the present invention;
[0037] FIGS. 11A and 11B show exemplary valves incorporated in the NO delivery line, in accordance with exemplary embodiments of the present invention;
[0038] FIG. 12 shows exemplary flow from one blocked nostril to the patient's other nostril, in accordance with exemplary embodiments of the present invention;
[0039] FIG. 13 shows the injection of NO into a stream of ambient air in each nostril, in accordance with exemplary embodiments of the present invention;
[0040] FIGS. 14A-14B show exemplary configurations of dual-channel delivery systems, in accordance with exemplary embodiments of the present invention;
[0041] FIG. 15 shows exemplary device components for exemplary embodiments of a dual-channel delivery system, in accordance with exemplary embodiments of the present invention;
[0042] FIG. 16 shows an exemplary nasal cannula with a tri-lumen nasal adapter, in accordance with exemplary embodiments of the present invention;
[0043] FIG. 17 shows an exemplary tri-lumen nosepiece prior to assembly, in accordance with exemplary embodiments of the present invention;
[0044] FIG. 18 shows an exemplary nose projection of the assembled molded tri-lumen nasal adapter in accordance with exemplary embodiments of the present invention;
[0045] FIGS. 19A-19B show a perspective and two-dimensional representation of an exemplary nasal projection with a proximal NO lumen and within a trigger lumen, in accordance with exemplary embodiments of the present invention;
[0046] FIG. 20 shows an exemplary nasal cannula in accordance with exemplary embodiments of the present invention;
[0047] FIG. 21A shows an exemplary double "D" shaped paratube, in accordance with exemplary embodiments of the present invention;
[0048] FIGS. 21B and 21C show exemplary lumens with geometric protrusions and/or inserts, in accordance with exemplary embodiments of the present invention;
[0049] FIGS. 22A-22E are views of exemplary nasal cannula device connecting pieces, in accordance with exemplary embodiments of the present invention;
[0050] FIG. 23 shows an exemplary oxygen connecting piece, in accordance with exemplary embodiments of the present invention;
[0051] FIG. 24 shows an exemplary reducer and/or additional line support, in accordance with exemplary embodiments of the present invention;
[0052] FIGS. 25A-C show several views of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0053] FIG. 25D shows an upper right front perspective view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0054] FIG. 25E shows a bottom view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0055] FIG. 25F shows a top view of an exemplary cannula nose adapter, in accordance with exemplary embodiments of the present invention;
[0056] FIG. 25G shows a first side view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0057] FIG. 25H shows second side view of an adapter of the present invention;
[0058] FIG. 25I shows a front view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0059] FIG. 25J shows a rear view of an exemplary cannula nose adapter, in accordance with exemplary embodiments of the present invention;
[0060] FIG. 25K shows an upper right front perspective view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0061] FIG. 25L shows a bottom view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0062] FIG. 25M shows a top view of an exemplary cannula nose adapter, in accordance with exemplary embodiments of the present invention;
[0063] FIG. 25N shows a first side view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0064] FIG. 250 shows a second side view of an exemplary cannula nose adapter, in accordance with exemplary embodiments of the present invention;
[0065] FIG. 25P shows a front view of an exemplary cannula nose adapter, in accordance with exemplary embodiments of the present invention;
[0066] FIG. 25Q shows a rear view of an exemplary cannula nosepiece, in accordance with exemplary embodiments of the present invention;
[0067] FIGS. 26A-26D show cross-sectional views of several exemplary cannula nosepiece nostrils, in accordance with exemplary embodiments of the present invention;
[0068] FIG. 27 shows exemplary positioning elements, in accordance with exemplary embodiments of the present invention;
[0069] FIG. 28 shows an exemplary NO delivery device with a key entry and a nasal cannula with a positioning element, in accordance with exemplary embodiments of the present invention;
[0070] FIG. 29 illustratively depicts exemplary retrograde flows during inspiratory breathing along with pulsed delivery, in accordance with exemplary embodiments of the present invention;
[0071] FIG. 30 illustratively depicts exemplary retrograde flows during inspiratory and expiratory breathing, in accordance with exemplary embodiments of the present invention;
[0072] FIG. 31 illustratively depicts exemplary retrograde flows for various exemplary cannula configurations, in accordance with exemplary embodiments of the present invention;
[0073] FIGS. 32A-32C show exemplary cannula configurations for tests 1-3 of FIG. 31, in accordance with exemplary embodiments of the present invention;
[0074] FIG. 33A shows an upper right front view in perspective of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0075] FIG. 33B shows a front view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0076] FIG. 33C shows a rear view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0077] FIG. 33D shows a first side view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0078] FIG. 33E shows a second side view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0079] FIG. 33F shows a top view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0080] FIG. 33G shows a bottom view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0081] FIG. 34A shows a left rear view in perspective of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0082] FIG. 34B shows an upper right front view in perspective of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0083] FIG. 34C shows a top view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0084] FIG. 34D shows a bottom view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0085] FIG. 34E shows a front view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0086] FIG. 34F shows a rear view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
[0087] FIG. 34G shows a first side view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention; and
[0088] FIG. 34H shows a second side view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention. DETAILED DESCRIPTION
[0089] The present invention generally relates, among other things, to systems, devices, materials and methods that can improve the accuracy and/or precision of nitric oxide therapy, for example, reduce the dilution of inhaled therapeutic gases such as nitric oxide (NO) and/or limit the mixing of therapeutic inhaled gases prior to delivery to the patient's nose. As described in this document, dilution of NO can occur due to a number of factors not limited to but such as mixing of NO with oxygen and/or air. To reduce the dilution of an intended dose of NO, various specimens of nasal cannulas, pneumatic configurations, manufacturing methods and methods of use etc. are disclosed. For example, the various examples of nasal cannulas, pneumatic configurations, manufacturing methods and usage methods etc. of the present invention can reduce the mixing of NO with oxygen and/or air (eg before being delivered to the patient's nose etc.) thus reducing the dilution of the intended doses of NO.
[0090] Due to the unique nature of NO delivery, many factors need to be considered to ensure accurate and accurate delivery of NO doses to the patient. In contrast to the administration of other gases, such as oxygen (02), NO dosage can be particularly susceptible to dilution because, among other things, the dose volume can be less than 1 ml (for example, a substantially small dose that can be lost to the environment) and/or NO may be reactive with 02 present in ambient air and/or 02 co-administered producing nitrogen dioxide (NO2). In addition, timing of NO delivery can also be more critical (eg for effectiveness) than timing of other gases (eg 02 delivery), so there is a need to reduce NO dilution and certify Be sure that the onset of the patient's breathing can be accurately determined as soon as possible and/or to ensure that the NO dose waveform does not significantly distort as it travels through the nasal cannula of the NO delivery device to the patient. In addition, patient comfort may need to be factored into the design of the nasal cannula, for example, because the nasal cannula can be used for extended periods of time.
[0091] Various cannulas, systems and methods of the present invention may use, modify and/or be affiliated with various systems for delivering pharmaceutical gas to a patient and/or for delivering a pulse of pharmaceutical gas to a patient. For example, various cannulas, systems and methods of the present invention can use, modify and/or be affiliated with at least the therapeutic gas delivery systems depicted illustratively in Figs. 33A-34H. The various cannulas, systems and methods of the present disclosure may use, modify and/or be affiliated with the teachings of US Patent No. 7,523,752 entitled "System and Method of Administering a Pharmaceutical Gas To a Patient", the contents of which are incorporated. addendum by reference in its entirety.
[0092] Referring to FIG. 1, typically, using a delivery system of 100, NO can be delivered to a patient through a nasal cannula 101. Nasal cannula 101 can receive NO at relatively low volumetric percent concentrations in a carrier gas of, for example, a therapeutic gas delivery device (eg NO) 103 and/or nasal cannula 101 may receive oxygen and/or ambient air (sometimes referred to simply as oxygen, 02, etc.) from an oxygen/ambient air source 105 A commonly used carrier gas is nitrogen because nitrogen is non-reactive with NO, but other inert carrier gases such as helium can be used.
[0093] Delivery of the NO/N2 gas mixture (sometimes referred to simply as nitric oxide, NO, etc.) to the patient generally requires that the NO gas travel from a high-pressure NO source (eg, a pressurized cylinder , pressurized cylinder affiliated with NO 103 delivery device, etc.) to the patient at or near ambient pressure, eg via a delivery tube to anesthesia patients and/or ICU respirator subjects/dependents through a nasal cannula for spontaneously breathing patients. It will be understood that various techniques and/or embodiments of the invention disclosed herein can be used for a delivery tube and/or a nasal cannula, as well as other devices such as nasal pillows and/or nasal masks, to name a few. To make it easier, sometimes only one cannula is shown and/or described. This is for ease only and is in no way intended to be a limitation.
[0094] The transit described above the NO, ideally, will be devoid of contact with other gases, such as ambient air, oxygen, carbon dioxide, etc., until the gas enters the patient's upper respiratory tract. However, in practice this may not be easily achieved. By way of example, oxygen and/or ambient air may enter the 100 delivery system at a variety of points such as, but not limited to: • During transit time within delivery device 103 (eg due to diffusion of oxygen through pneumatic interfaces, such as elastomeric O-rings in the inner pneumatics of the delivery device, etc.); cannula, nose adapter, connectors, reducer, connection joints etc.); • During the malation/exhalation cycle when a driving pressure gradient can reverse the flow in the NO supply lumen of the nasal cannula producing mixing within the nasal cannula 101 with ambient air and/or exhaled gas; • During the inhalation/exhalation cycle. exhalation when NO and air/02 mix in one of the patient's nostrils; • During connection from the high pressure source (eg a pressurized cylinder etc.) to the delivery device (eg as a cylinder replacement can trap small amounts of gas in the delivery pneumatics etc.); and• During high pressure NO source manufacturing cylinder filling operation in which a substantially pure mixture of NO and carrier gas may be sought but may not be easily achieved.
[0095] Dilution of NO during pulsed NO therapy can be problematic as only a substantially small volume of NO can be delivered to the patient. For example, gas containing NO can be administered in pulses that can be less than one (1) milliliter (ml). With substantially small pulse volumes, even small volumes of retrograde flow and/or diffuse gases can be significant, for example because the small dose of NO can be easily diluted. Of course, larger volumes of NO can also be diluted. MINIMIZATION OF NO/O2 CONTACT DUE TO THE DIFFUSION OF 02: MINIMIZATION OF NO TRANSIT TIME
[0096] One or more embodiments of the present invention relate to nasal cannulas that address NO/O2 contact sources (e.g., one or more of the above NO/O2 contact sources) and thus dilution (e.g. , by mixing NO with 02 etc.) of the intended dose of NO minimizing contact time of NO with 02, by minimizing the transit time through the cannula, minimizing the oxygen transit through the cannula walls, and/or minimizing the amount of 02 to contact NO. Referring to Fig. 1, addressing at least dilution of the intended doses of NO, described in more detail below, oxygen transit can be minimized through any wall of cannula lumens 101 such as, but not limited to, cannula walls , walls associated with a trigger lumen 104, NO lumen 106, O2/air lumen 108, and/or any combination and/or additional separation thereof, to name a few. Furthermore, by addressing at least dilution of the intended doses of NO, oxygen transit can be minimized through the entire cannula wall 101, such as, but not limited to, cannula walls associated with a cannula nose adapter 102, a limb position 110, reducer 112, connection piece 114, oxygen connection piece 116, and/or any combination and/or additional separation thereof, to name a few. Small ID NO Lumen
[0097] In one or more embodiments, cannulas can be provided that include a smaller inner diameter (ID) lumen/delivery tube for NO, for example, to reduce the dilution of the intended doses of NO. This smaller DI tube can reduce the transit time of NO molecules through the cannula. This, in turn, can reduce the time available for mixing with oxygen, which can diffuse through the cannula walls and oxidize the internal NO to NO2.
[0098] By way of example, to reduce the dilution of the intended doses of NO by minimizing transit time of NO through the cannula, the ID for the delivery tube/lumen for NO can be approximately 0.01 inches to about 0.10 inches and/ or about 0.03 inches to about 0.08 inches. In exemplary embodiments, the Dl of delivery tube/lumen for NO can be selected to ensure reduced transit time of NO (eg, reducing NO dilution, etc.) while not resulting in significant back pressure and/or shape distortion. NO pulse and/or NO waveform distortion (discussed in more detail below). To reduce transit time as well as not significantly cause back pressure and/or distortion, the DI for the NO delivery tube/lumen can be substantially less than about 0.03 inches, eg for a cannula with a length of about from 6 feet to 8 feet. For shorter lengths a smaller Dl can be used and/or for longer lengths a larger Dl can be used as resistance and/or distortion may be a function of tube length and tube Dl.
[0099] In exemplary embodiments, the Dl of shorter tubes/lumens for NO delivery (e.g., cannula nostrils, shorter nasal cannulas, etc.) may have a substantially smaller tube ID than for tubes/ delivery lumens for NO, which can also have a substantially small DI as described above, without significant back pressure and/or NO pulse shape and/or the occurrence of pulse waveform distortion.
[00100] In exemplary embodiments, the potential for NO exposure time to 02 can be minimized using other techniques such as, but not limited to, increasing the rate of delivery of NO through the NO lumen. The velocity of NO through the NO lumen can be increased, for example, by increasing the pressure gradient within the system and/or reducing the tube diameter. Although the NO velocity can be increased to reduce the NO exposure time by 02, it may be necessary for the velocity to be minimized so that the pulse shape is not substantially distorted, the patient does not feel discomfort, and/or slip into count any competing metrics.
[00101] It will be understood that any of the above teachings (e.g. small DI for delivery tube lumen for NO etc.) may be combined with any of the other pneumatic configurations, cannula configurations, teachings and/or modalities herein described. For example, the above teachings (eg small ID for tube/lumen delivery for NO, etc.) can be used with the below described mono-lumen cannulas, double lumen cannulas, tri-lumen cannulas, quad-lumen, and/or any other teachings and/or modalities described herein. Materials to limit oxygen diffusion and/or remove 02 and/or N02
[00102] Currently, many use polyvinyl chloride (PVC) and/or silicone as a common material for constructing nasal cannulas; however, oxygen can diffuse through the lumen walls of these nasal cannulas. To minimize oxygen contact occurring due to oxygen diffusion, permeation, and/or transmission through cannula walls, cannula wall materials can be selected that minimize oxygen diffusion rate, permeability rate, and/or transmission rate of oxygen (OTR). In exemplary embodiments, the cannula wall can include a material with a low oxygen diffusion coefficient, permeability rating, and/or oxygen transmission rate (OTR). By way of example, the cannula wall may include a material that may have an oxygen transmission rate (OTR) of about 0.001 to 10, for example, using the following units:
where: "cc" refers to the cubic centimeters (ml) of oxygen that passes through a square of material; "mil" refers to 1 mil (0.001" thick) of the square of material; "ATM" refers to number of ambient pressure atmospheres; "24 hours" refers to the allowable duration for oxygen flow; and "100 in2" refers to the square surface area of the material.
[00103] sometimes, when describing oxygen diffusion, permeation and/or transmission through cannula walls and/or cannula materials, reference can only be made to at least one of the diffusion rates, diffusion coefficients, rates of permeability, permeability ratings and/or OTR. It will be understood that reference to any of the above terms, where applicable, may be used with and/or replaced by any of the above and related terms. To make it easier, sometimes only one or a few of the terms above are described. This is for ease only and is in no way intended to be a limitation.
[00104] In exemplary embodiments, cannula materials (eg, cannula tubing material, cannula nose adapter, etc.) can be adjusted and/or varied to address O2 permeation along with patient comfort.
[00105] In exemplary embodiments, cannulas can be constructed using polyurethane or similar soft material. In exemplary embodiments, the polyurethane or similar soft material can include an additive to increase oxygen diffusion resistance and/or tube coaxially located over at least some of the NO delivery cannulas filled with a gas providing oxygen diffusion resistance. Cannulas can be constructed by coaxially coating a tube and/or co-extruding two or more materials (eg to form the tube etc.). Of course, other construction methods and/or techniques are within the scope of the disclosure.
[00106] Examples of at least some materials that can be used for construction and/or that may have desired oxygen permeating properties include, but are not limited to, polymers such as polyvinylidene chloride (PVDC), ethylene vinyl alcohol ( EVOH), polyamide (PA), polyvinylidene difluoride (PVDF), fluorinated polyurethane, Nylon 6, Nylon 12 and/or similar materials, to name a few. In addition, PVC can be used as the cannula material with one or more materials and/or additives, such as oxygen resistant polymers, incorporated to reduce oxygen permeation, diffusion coefficient and the like. Oxygen resistant polymers can be incorporated with polyurethane, PVC, and/or other cannula materials, for example, through co-extrusion. By way of example, such extrusion can be achieved with co-extrusion molds and/or using other known techniques.
[00107] Pipe/lumen barriers to oxygen ingress can take one of a variety of potential forms such as, but not limited to: • Homogeneous and/or single-material extrusions that can use at least one material with permeation characteristics of low oxygen; • Co-extrusions of two or more polymers, one or more of the polymers with low oxygen permeation characteristics; • Surface coatings/surface treatment on materials/pipe with such coatings may have low oxygen permeation characteristics; • Mixtures; and• Eliminators/absorbers/cleansers.
[00108] Single-material and/or homogeneous extrusions with low oxygen permeability: In exemplary embodiments, materials such as polyvinylidine chloride (PVDC.tradename Saran ®), ethylene vinyl alcohol (EVOH), Nylon 6, Nylon 12 , and/or any single and/or homogeneous material extrusions with low oxygen permeability can be used for the cannula material. Other materials are envisioned with such properties and the use of compatible low oxygen permeation extrusion material is within the scope of the present invention.
[00109] Co-extrusions of Two or More Polymers: In exemplary embodiments, tube-in-tube configurations and/or multiple sandwich layers can be constructed using co-extrusions of two or more polymers. For example, two or more polymers, with at least one having low oxygen permeation properties, can be co-extruded (for example, using common co-extrusion methods known in the art) to construct a tube-in-tube configuration. or several layers of sandwich. The low oxygen permeation layer can include the polymers disclosed herein (for example, those listed in the previous section) and/or other polymers with similar characteristics. Since these polymers may or may not co-extrude well with other polymers, extrusion of an intermediate polymer or so-called co-extrusion adhesive may be necessary. Exemplary co-extruded polymers may include, but are not limited to, PVC/EVOH/PVDC, PVC/EVOH/PFDF, Fluoride Polyurethane/EVOH/PVDC and Fluoride Polyurethane/EVOH/PVDF, PVC/PVDC, Polyurethane/PVDC, PVC/Nylon 6, PVC/Nylon 12, PVC/PVDC/Nylon 6, PVC/PVDC/Nylon 12, Polyurethane/PVDC/Nylon 6, Polyurethane/PVDC/Nylon12, co-extrusion adhesive polymers, any combination and/or separation thereof, or any other material that can be used with co-extrusions of two or more polymers.
[00110] In exemplary embodiments, co-extrusions can be layered in a specific order, for example, to reduce oxygen permeation and/or diffusion and/or for construction purposes. For example, if an adhesive used (eg at the junction of cannula components, etc.) bonds PVC to PVC, then the outer layer of a co-extrusion exposed to such an adhesive may be PVC. In addition, additional polymers (eg, which may have reduced properties when in contact with water vapor) such as, but not limited to, EVOH can be squeezed into hydrophobic and/or water resistant exterior or interior extrusion layers to minimize the contact of the internal compound with water vapor.
[00111] Surface coatings/surface treatment on tubes: In exemplary embodiments, surface coatings (eg surface treatments, surface coatings etc.) for low oxygen permeation can be applied to nasal cannula construction. Such coatings may include but are not limited to vacuum-deposited silicon dioxide (silica) and/or aluminum (eg, aluminum oxides, etc.) coatings heated above their sublimation temperature which may be deposited in thin layers of some microns (or less) thick. For example, silica coatings can be from about 0.001 microns to about 10 microns and/or about 0.01 microns to about 1 microns, and/or about 0.04 microns.
[00112] In exemplary embodiments, silica coatings can be deposited onto plastic in layers that can be substantially thin enough that the plastic's flexibility cannot be materially affected. It will be understood that any reasonable technique may be used for disposal of such materials. For example, low cost deposition can be achieved using chemical vapor deposition treatment. Of course other deposition methods for these coatings can also be used other methods such as, but not limited to E-beam and thermal evaporation, DC Magnetron Cathodic Spraying, Plasma Assisted Reactive Cathodic Spraying, any combination and/or further separation respective, and/or any technique capable of deposition.
[00113] In exemplary embodiments, other coatings such as, but not limited to, thermosetting epoxy-amine coatings, epoxy-amine coatings, etc. may be used. Coatings can be applied and/or supplied using techniques described in this document and/or known techniques.
[00114] Blends: In exemplary embodiments, materials can be blended to obtain the beneficial properties of one or the other materials and/or used as the cannula material. In exemplary embodiments, Nylon 6 and EVOH, which can adhere to each other in co-extrusions without the need for a co-extrusion adhesive, can be used as a blended cannula material. Other blends may include, but are not limited to, Nylon 6 with amorphous nylon and Nylon 6 with HDPE. Of course, other mixtures can be used.
[00115] In exemplary embodiments, a posterior material may be overlaid with an anterior material. By way of example, when two materials are not compatible with co-extrusion due to different melting temperatures, one polymer may be extruded first and the second polymer may be heated and coated with the first in a secondary operation.
[00116] Eliminators/absorbers: In exemplary embodiments, the eliminators can be coated onto the interior of the lumen (for example, by cooking the liquid in a liquid suspension of the eliminator inside the lumen, condensing the eliminator outside the interior of the lumen by processes by evaporation, by absorption/adsorption to the interior surface of the lumen using a liquid source or source of gaseous scavenger, by chemically bonding the scavenger to the inside surface of the cannula etc.) and/or the scavenger can be packaged within the connector device and/ or nosepiece, for example, as a plug (eg a plug with at least one hole to allow gas to flow through it, etc.) for scavenging oxygen and/or nitrogen dioxide. Such scavengers can include, but are not limited to, alumina compounds such as activated alumina, ascorbic acid and/or any other scavenger compound. Potential disadvantages of such an approach include the finite life expectancy of the disposal material. This inconvenience can be overcome by taking into account the duration of use of the cannula in the project. At least one additional potential disadvantage may be that some plug configuration for transiting gas through an eliminator may distort the gas waveform. Because of this, described plugs can be designed to minimize such waveform distortion. Either method can be used to coat the interior of the lumen. For example, a liquid that is concentrated with a scavenger (eg ascorbic acid) can be passed through the tube and then dried in such a way that it can then be deposited on the inner wall of the tube.
[00117] In exemplary embodiments, activated alumina can be used in the cannula, for example, as a coating within the lumen, as a plug-in, and/or used in any other way, for example, to capture carbon dioxide. nitrogen. With a thin layer of alumina coated on the inside of the lumen, the effect can not only be a reduction in the oxygen permeation rate, but it can also be successful in capturing nitrogen dioxide. Activated alumina and/or other scavengers can also be made in the form of a plug fitted to the tube, for example, in an area close to the patient's nostrils. The plug can be designed to minimize pressure drop and/or maintain the nitric oxide pulse waveform. The high surface area of activated alumina can effectively pull nitrogen dioxide out of the gas mixture. Furthermore, the eraser can also be located on the device, for example on the device connector. In this way, the eliminator can be part of the cannula and/or can be removable (eg such that it can be removed when changing the cannula) and/or the design life of the eliminator can be combined with the anticipated use duration and /or real cannula.
[00118] It will be understood that the invention is not limited to activated alumina and that any material with a high surface area, substantial nitrogen dioxide scrubbing capacity, adequate pore sizes, sufficient physical strength so that the shape can be maintained, and/or that cannot generate dusts and/or other materials that may spill or sβ dissociate from the cannula, may act in the capacity of the scrubbing material. It is further understood that internal filtration can be used to contain loss of compounds to prevent aspiration into the respiratory system. Examples of scrubbing materials include, but are not limited to, zeolites, silica-alumina, activated carbon/carbon and adsorbents which may have solid base sites on the surface. To make things easier, activated alumina is sometimes described as a scrubbing material. This is for ease only and is in no way intended to be a limitation.
[00119] In exemplary embodiments, a reducing agent can be coated on the surface of the scrubbing material, for example, to increase its ability to capture and/or reduce nitrogen dioxide into nitric oxide. Such reducing agents include, but are not limited to ascorbic acid.
[00120] In exemplary embodiments, additives can be added to the polymer to change permeation/barrier properties, such as, but not limited to, oxidizable plastic (eg, PET or polyamide), nanoclays, any combination and additional separation thereof, and/or any other additives. Additives can work to scavenge oxygen and/or provide a barrier to penetration into the polymer matrix, both of which can result in reduced oxygen permeating through the material. Oxidizable plastics (eg PET or polyamide) can react with oxygen that may be permeating through the polymer matrix. Oxygen that may be permeating through the membrane may react with the oxidizable plastic before passing through the cannula and/or reacting with NO. Nanoclays (eg, which tend to have a plaque like morphology) can provide a barrier to permeation, for example, when properly dispersed within the polymer matrix. When dispersed, diffusion may be required to occur around the plates, which can result in a tortuous path through the polymer, effectively reducing pθrmθαbilidαdθ dβ yα3.
[00121] It will be understood that any of the above teachings (e.g. materials etc.) may be combined with any of the other pneumatic configurations, cannula configurations, teachings and/or modalities described herein. For example, the above teachings (e.g. materials, etc.) can be used with the below-described mono-lumen cannulas, dual lumen cannulas, tri-lumen cannulas, quad-lumen cannulas, and/or any other teachings. and/or modalities described herein. RETROGRADE FLOW SETTINGS
[00122] Referring to FIGS. 2A-2B, surprisingly it has been found that another source of dilution can be caused by a phenomenon (eg retrograde flow, cross flow etc.) in which ambient air and/or exhaled gas flows into the nasal cannula (eg , on or near the cannula nose adapter 200). This gas flow within the nasal cannula may be between two cannula nostrils (eg 202/203 cannula nostrils) displacing nitric oxide resident gas and/or pushing nitric oxide gas out of the cannula such that the nitric oxide is displaced. and/or pushed out cannot be delivered to the patient and/or may mix with the flow of gas and/or other gases, thus not diluting the intended dose of NO. Retrograde flow, moreover, may depend on factors such as but not limited to the pressure difference between the nostrils during both inhalation and exhalation. The pressure difference between the nostrils may vary depending on factors such as but not limited to the person's breathing pattern, occlusions and/or partial occlusions in the person's nostrils (for example, as shown in FIG. 12), placement of the nasal nostrils and the degree of imbalance between nasal flow during breathing, to name a few. Accordingly, one or more embodiments of the present invention pertain to nasal cannulas that can minimize retrograde flow and/or dilution resulting from retrograde flow in the nasal cannula.
[00123] As shown in Figure 2A, during normal pulsed delivery, NO flows out of both nostrils 202/203 of the cannula nose adapter 200. However, during at least the static phase between pulses, retrograde flow can occur. For example, during the static phase, exhaled or ambient air may flow in a circular motion and/or reverse flow through one cannula nostril 202 and out of the other cannula nostril 203 as indicated in FIG. 2B. This retrograde flow can result in dilution and/or fading of NO in the nasal nostrils and/or flow path, which can cause a delay and/or reduction of the delivered dose. In addition, this retrograde flow can result in the oxygen in the air and/or exhaled gas flow mixing with the NO to a greater degree and/or reacting with nitric oxide in the nasal cannula, which can cause the formation of diluting NO2 the concentration of NO. Thus, to reduce retrograde flow (eg, which can result in the formation of NO2 which dilutes NO doses and which can act as a known respiratory irritant, etc.), the potential nitric oxide mix volume with the expired gas and /or ambient gas can be minimized.
[00124] Noting the foregoing, the amount of dilution resulting from retrograde flow may be dependent on the volume of the lumen associated with NO delivery (for example, the NO lumen; combined NO lumen and trigger; NO lumen, trigger, and the 02/air combined; etc.) in the nasal cannula adapter (eg the flow path) where retrograde flow can occur. The segment where retrograde flow can occur can have any shape. For ease, this segment where the retrograde flow occurs is sometimes described as being U-shaped and the like. This is for ease only and is in no way intended to be a limitation.
[00125] In exemplary embodiments, optimized Dl dimensions (eg, Dl size, D! shape, etc.) of the lumen associated with NO delivery (eg, the NO lumen; NO lumen combined with trigger; lumen NO combined with trigger and 02/air; etc.) in the nosepiece (eg the flow path) can be selected to reduce the volume of the U-shaped region, thus minimizing the potential volumetric shift associated with the retrograde flow and/or dilution resulting from the retrograde flow. Furthermore, in exemplary embodiments, such ideal DI dimensions may vary depending on the volume of NO gas delivered. By way of example, a nitric oxide delivery device can deliver pulses of NO-containing gas with a minimum dose volume of 0.35 ml. In order to ensure volumetric dosing accuracy, it may be preferable that no more than a small percentage (eg 10%, 5%, 20%, etc.) of the dose can be lost due to retrograde flow.
[00126] One or more embodiments of the present invention limits the internal volume of this "U" shape to be no more than a small percentage (e.g. 10%, 5%, 20%, etc.) of the minimum dose volume (eg, 0.035 ml for a pulse of 0.35 ml of therapeutic gas) to ensure that if NO loss occurs it is an acceptable amount of NO loss due to retrograde flow (eg loss to the environment during the exhalation). Following the above example, for a 10% minimum dose volume of 0.035 ml, the lumen ID in the "U" segment may be no more than 0.046 inches given a 0.63 inch projection spacing and a projection length 0.315 inches. Therefore, a lumen ID significantly greater than 0.046 inches may not be beneficial in maintaining dose volume accuracy for minimum dose volumes of 0.35 ml.
[00127] It will be understood that the mathematics of this construction can be modified by variations in systems such as, but not limited to systems with appropriately larger or smaller volumes of minimum dose, systems with different projection lengths, and/or systems with different projection spacing, to name a few. Those skilled in the art can perform the calculations necessary to determine the DI required to deliver a desired volume in the "U" shaped segment so that it does not exceed 10% of the dose volume. In addition, depending on the accuracy required for dosing, the internal volume of the "U" or other volume available for crossflow can be, but is not limited to, less than 50%, 45%, 40%, 35%, 30 %, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2% or 1% of dose volume, to name a few.
[00128] For example, if the "U" shape consists of two nostrils and a bottom panel, the maximum dimensions such that the "U" volume does not exceed 20% of the minimum dose volume can be calculated using the following formula , where background refers to the length of the lumen inside the nosepiece and/or which forms the base of the "U" shape: Minimum dose volume> „ 5[27t(projection diameter/^)"* * ( projection length) + n(background diameter/2)2 * (background length)]
[00129] Thus, if the minimum dose is known, the dimensions of the "U" section of the cannula can be calculated. For dosing accuracies other than 20%, the volume ratio factor of 5 can be changed in accordance with the volume ratio factor equal to [100 / (% dose accuracy)].
[00130] In exemplary embodiments, during expiration and/or before inhalation (eg felt and/or sensed by the delivery device, etc.) the U-shaped volume in the nosepiece can be purged with a pulse of NO substantially equal to the U-volume. This can cause the U-volume to be substantially filled with NO (eg after exhalation). In addition, this NO filling the U-volume can be delivered to the patient during the next inhalation, for example, ensuring early delivery of the NO to the patient to provide optimal clinical efficacy (eg, discussed below).
[00131] In exemplary modalities, retrograde flow can be reduced by reducing at least the ID of the NO delivery lumen within the nasal projection (eg, NO flow path) so that the resistance to flow through the NO lumen in the projection nasal can be increased. Observing this configuration, under the same differential pressure, the flow within the lumen of NO from the nasal projections can be reduced compared to projections with a larger lumen. This can result in cross-flow reduction at least under these conditions, for example, because the smaller DI lumen of NO can produce resistance to gas flow that can be inversely proportional to the fourth power of the lumen radius by Poiseuille's law.
[00132] In exemplary embodiments, retrograde flows can be reduced by the use of check valves and/or check valves, for example, as discussed in more detail below.
[00133] Sometimes the NO lumen described in this document can be described as being optimized for a minimum pulse volume of 0.35 ml and/or allowed 10% dose error resulting in an allowable U-shaped volume in the lumen of NO (eg 0.035 ml). In exemplary modalities, changes in this minimum pulse volume and/or optimal pulse volume range can affect at least the size of the NO lumen. For example, the minimum pulse volume should be smaller due to, for example, high concentrations of nitric oxide being used, the inner diameter of the NO lumen and/or "U" volume can be reduced to ensure the 10% target of error. For example, the NO lumen and/or "U" volume can be reduced by taking into account various metrics for optimization, such as, but not limited to, pulse shape. Furthermore, for example, if the minimum pulse volume is increased due, for example, to the use of low concentration nitric oxide, then the inner diameter of the NO lumen and/or "U" volume can be increased. For example, the NO lumen and/or "U" volume can be increased taking into account various metrics for optimization, such as, but not limited to, pulse shape. It will be understood that if the NO lumen and/or "U" volume is too large (eg, about 0.1 ml to about 0.5 ml) then small volume pulses may not be able to be delivered accurately, delivery may be delayed, dilution may occur, and/or other problems may occur due to the unique nature of NO delivery. MINIMIZING DELAY AND/OR DISTORTION
[00134] For nitric oxide delivery systems (for example, which can pulse nitric oxide gas to patients) to have optimal clinical efficacy it may be necessary to deliver a nitric oxide flow or pulse to the patient as early as possible in the inspiratory phase and /or with a desired flow waveform (eg pulse shape). Observing this, pneumatic delays can be and/or should be minimized, because, for example, patient pressure signals can be used as an indication of the patient's inspiratory effort and/or the beginning of the patient's inspiration. Also, distortion of flow or pulse waveforms can be and/or should be minimized because, for example, waveform and/or timing can be linked to clinical efficacy. Accordingly, one or more embodiments of the present invention relate nasal cannula configurations that minimize delay and/or distortion of pressure signals, for example, when in transit through the patient's cannula back to the device and/or that minimize flux waveform distortion.
[00135] In exemplary modalities, the associated cannula lumen with trigger (for example, the trigger lumen; combined NO and trigger lumen; combined NO, trigger and 02/air lumen; etc.) can be configured to minimize the delay and/or distortion of pressure signals when in transit through the cannula. To minimize delay and/or distortion of pressure signals when in transit through the cannula, the cross section of the trigger affiliated lumen may be selected to reduce the delay and/or distortion and/or the cross section size can be increased and /or maximized to reduce delay and/or distortion.
[00136] In exemplary embodiments, the NO delivery affiliated cannula lumen (for example, the NO lumen; combined NO and trigger lumen; combined NO, trigger and 02/air lumen; etc.) can be configured to minimize stream waveform distortion. To minimize distortion of flux waveforms, the cross-section of the lumen affiliated with NO delivery can be increased and/or maximized and/or the cross-sectional shape can be selected to reduce delay and/or distortion. Furthermore, in exemplary modalities, to minimize the distortion of flux waveforms the associated lumen to NO delivery can be done with reduced compliance, that is, with greater rigidity. For example, to minimize distortion of flux waveforms the lumen affiliated with NO delivery can be made of a substantially rigid material. Material stiffness can be selected to reduce compliance while still taking into account at least patient comfort. COMPETITING METRICS
[00137] In at least some embodiments the cannula can be configured so that a lumen can be to deliver NO and be to be actuated (eg, mono-lumen cannulas, dual lumen cannulas, etc.). These configurations may require optimizing the lumen for both NO delivery and triggering to have minimal NO dose dilution, as well as allowing the trigger signal to propagate to the device without attenuation substantially over the spectral band of human breathing (eg, 0-4 Hz). This can be quite difficult as these can be competing metrics for optimization. For example, to deliver a pulse and/or flow of NO earlier in the inspiratory phase, reduce pneumatic delays, reduce waveform distortion of the flow, reduce delay and/or distortion of pressure signals, reduce mixing volume of NO and/or NO oxidation in the nosepiece and/or resolve any other desired property (eg for a combined NO/triggering lumen) various competing lumen ID metrics can be optimized such as, but not limited to:a . Reduce formation of NO2-> Reduce DI from lumen;b. Maintain volumetric NO dosing accuracy -> Reduce lumen Dl;c. Reduce NO flow distortion - > increase lumen Dl; ed. Minimize trigger signal attenuation or delay -> increase Lumen Dl.
[00138] In exemplary embodiments, cannulas of the present invention that have matched NO/trigger lumen configurations may require compromise of the ideal geometry (e.g., shape, size, etc.) of the NO/trigger lumen to, for example, deliver NO pulses and/or flows earlier in the inspiratory phase, reduce pneumatic delays, reduce flow waveform distortion, reduce delay and/or distortion of pressure signals, reduce NO mixing volume in the adapter nasal, and/or NO oxidation in the nose adapter. Such compromise may be necessary for cannulas of the present invention that have a combined NO/trigger lumen (e.g., mono-lumen cannulas, dual-lumen cannulas, etc.). However, cannula configurations of the present invention that have at least three lumens (e.g., tri-lumen cannula, quad-lumen cannula, etc.), as discussed below, can allow dedicated lumens to deliver NO and trigger signal and can, at least in some cases, allow a dedicated 02/air delivery lumen. As such, for cannulas of the present invention with dedicated lumens for NO delivery and triggering (eg, tri-lumen cannulas, quad-lumen cannulas, etc.) the optimized NO lumen may be smaller than the already improved trigger lumen that it may be beneficial to have a larger trigger lumen to ensure at least minimal signal attenuation while it may be beneficial to have a smaller NO lumen to reduce at least NO dilution. As such, cannulas of the present invention having combined NO/trigger lumens (e.g., mono-lumen, dual-lumen cannulas, etc.) and cannulas of the present invention with dedicated lumens for NO delivery and dedicated trigger lumens (e.g., trilumen cannulas, quad-lumen cannulas, etc.) can have different geometries when optimized.
[00139] By way of example, in addition to ensuring volumetric dosing accuracy (for example, described above with regard to minimizing dilution resulting from retrograde flow), Dl of the combined NO/trigger lumens can be designed to reduce and /or not produce undue gas flow distortion and/or delay in signal propagation, for example, from the patient to the device (for example, described above in relation to minimizing the delay and/or distortion of pressure signals). Such distortion and/or delay can occur as pneumatic tubes can behave like first order pneumatic low-pass filters and attenuate higher frequency signal components. Modification of the inside diameters can change the bandpass characteristics of the filtering effect. However, as noted above, the inner diameter (eg at the U) can be set to a given maximum ID based on the accuracy of delivering the required dose of the system.
[00140] In light of at least the foregoing, in exemplary embodiments, to minimize the effects of the potentially attenuated frequency pressure signal: (1) the diameter upstream (near device) of the combined NO/trigger lumen of cannulae The present invention can be adjusted to increase (e.g., optimize) the bandpass characteristics of the cannula and/or (2) trigger onset of cHucya vipuiow viMv pvi CÃOIipiv, pciv uiopuoiiivu uc ciiucyα) μuuc ici the triggering strategy of typical threshold pressure (eg the pressure signal may be attenuated and/or delayed by the pneumatic filtering effect of the cannula construct) and therefore it may be advantageous to supplement/replace this threshold pressure trigger with a trigger based strategy falling pressure based on a falling pressure pattern indicative of patient effort. Such a triggering strategy based on pressure drop in the presence of significant signal attenuation may be more agile (eg, faster) to the patient's effort. It will be understood that to minimize the effects of the potentially attenuated/delayed pressure signal, the diameter downstream of the combined NO/trigger lumen of the cannulas of the present invention can be adjusted to increase (e.g., optimize) the bandpass characteristics of the cannula; however, this can produce an undesirable side effect of the size of the cannula nosepiece being increased, which in turn can make the cannula less comfortable for the patient.
[00141] In exemplary embodiments, the diameter upstream of the combined NO/trigger lumen can be adjusted to widen the bandpass characteristics of the cannula to ensure that unnecessary compressible volume may be unavailable upstream of the nosepiece restriction (by example, DI restriction of 0.046 inches, etc.). This can reduce the compressible volume in the cannula and/or effectively increase the cannula's bandpass characteristics.
[00142] In exemplary modalities, triggering dose delivery (eg, by the delivery device) may be based on a sloped pressure pattern indicative of patient efforts and/or the drop may be reduced in magnitude by the characteristics of the tube. filtering, however, the drop may still be present for triggering algorithmic decisions (eg, the delivery device). In exemplary modalities, triggering methodologies could be based not on pressure limits, rather triggering methodologies could be based on pressure drop trends which can also be employed to improve overall timely dose delivery to the patient. It will be understood that a triggering implementation may be optional. MONO-LUMEN CANNULA
[00143] Referring to FIG. 3A, in exemplary embodiments, the nasal cannula can have at least one lumen (i.e., a 300 monolumen cannula) that can produce nitric oxide in the same lumen used to deliver oxygen and/or trigger a 303 delivery device. Using the 300 mono-lumen cannula, in a single lumen, oxygen and/or 305 ambient air flow can be delivered to a patient with doses of NO 307 pulsed intermittently in the flow. This same lumen can also be used to trigger. Using this technique, retrograde flow can be substantially reduced, for example, because O2 and/or air can effectively clean the cannula nosepiece after each NO pulse and or because the single lumen can be a closed system in the device when closing of valve and therefore the flow in the cannula lumen can be avoided. However, using this technique, oxygen and/or air 305 can be in contact with NO 307 within the cannula 300 lumen and react (eg, forming NO2) thereby diluting the intended dose of NO.
[00144] In exemplary embodiments, a carrier gas can be used to buffer (e.g., isolate) the NO from O2 and/or a carrier gas can be used to increase the effective volume of the delivered dose, e.g., to reduce time transit of NO in the cannula. This buffer gas can be diffused in the NO dose and/or surround the NO dose (eg, spatially before and after).
[00145] Referring to FIG. 3B, in exemplary embodiments, to reduce the dilution of NO 307 with oxygen and/or air 305 within the NO/O2 lumen, a 309 buffering agent can be delivered between NO 307 and oxygen 305. By way of example, first oxygen can be delivered through the NO/O2 lumen, then a buffering agent (eg an inert gas, nitrogen gas, etc.) can be delivered, then NO can be delivered, then another buffering agent can be delivered, and then oxygen can be delivered. The buffering agent can reduce the interaction between NO and oxygen, thus reducing the dilution of NO, for example caused by the formation of NO2.
[00146] In exemplary embodiments, when using a buffer gas to transport NO within the cannula, the amount of contact between NO and O2 and the contact time can be minimized without substantially distorting the shape of the NO pulse dose. In exemplary embodiments, the buffer gas can be substantially devoid of O2 such that it can act as a stopper for any entrained O2 and/or can increase the volume of gas delivered, thereby decreasing the NO dose time to the cannula. In exemplary embodiments, the buffer gas can include oxygen, however, the diameter of the cannula lumen can be small enough that the cross section of the NO dose exposed to O2 can be minimized and/or the diameter can be large or large. sufficient to ensure that the pulse shape of the dose cannot be substantially distorted.
[00147] In exemplary embodiments, a buffer gas can be supplied by using the remaining O2 exhaust gas mixture after an oxygen concentrating system has removed the O2 from the air.
[00148] It will be understood that the disclosed plug can be used with any multi-lumen cannula (e.g., double lumen cannula, tri-lumen cannula, quad-lumen cannula, etc.) where NO and O2 can be delivered in the same lumen. For example, a dual lumen cannula cannot have a trigger lumen and combined NO/O2 lumen where NO can be pulsed intermittently at 02 with a buffer separating the MH and DQ
[00149] In exemplary embodiments, the internal diameter of the monolumen (eg NO/O2 combined lumen, NO/O2/trigger combined lumen, etc.) can be configured to be substantially small, eg to reduce mixing of waste gas. As discussed above, lumens that include different functions (eg NO delivery, trigger, 02 delivery, etc.) can have competing metrics for optimization. For optimization, the mono-lumen cross-sectional dimensions may require a compromise between at least some of these competing metrics. For example, because the mono-lumen has a combined NO/trigger and/or NO/O2/trigger lumen, the optimal geometry (eg, shape, size, etc.) of the mono-lumen may require compromise between at least some competing metrics to, for example, deliver NO pulses and/or flows early in the inspiratory phase, reduce pneumatic delays, reduce flow waveform distortion, reduce delay and/or distortion of pressure signals, reduce the volume of NO mix in the nosepiece, and/or NO oxidation in the nosepiece. Considering at least competing metrics for optimization, in at least some modalities the mono-lumen inner diameter (eg NO/O2 combined lumen, NO/O2 combined lumen/trigger, etc.) may be less of about 0.07 inches. DOUBLE LUMEN CANNULA
[00150] Referring to FIG. 4, in exemplary embodiments, the nasal cannula can have at least two lumens (i.e., a double-lumen 400 cannula) that can produce nitric oxide in a separate lumen (e.g., NO 404 lumen) than at least one lumen 406 that can deliver oxygen (eg, oxygen/air supply 405) and/or that can trigger the delivery device (eg, delivery device 403). The NO lumen can carry therapeutic gas comprising NO from the NO delivery device 403 to the patient (e.g., nasal cannula adapter 402). The two lumens can be aggregated into a single cannula nosepiece (eg, 402 cannula nosepiece) that can have separate flow paths for each lumen.
[00151] In exemplary embodiments, the lumen (e.g., the double lumen cannula) carrying the gas containing nitric oxide may have a substantially small internal diameter that may be smaller than the other lumens (e.g., the trigger lumen, lumen of oxygen, etc.). In at least these embodiments, having a substantially small internal diameter for the NO-carrying lumen, the cannula can reduce dilution with at least the following mechanisms: (i) minimizing the mixing of oxygen and NO due to a reduction in retrograde flow in the lumen carrying NO of small Dl due to smaller Dl; (ii) minimizing the mass volume of gas mixing because the gas volume of NO per unit length can be reduced by having a small DI carrying NO lumen; and/or (iii) the lumen carrying small DI NO can produce a narrow jet of gas flow that can effectively minimize O2/NO mixing during NO delivery and/or can minimize O2/NO mixing during NO delivery up to much farther into the nasal cavity. Similar mechanisms to reduce dilution can be accomplished by reducing the DI lumen for NO delivery used in other multi-lumen cannulas described herein (eg, tri-lumen cannulas, quad-lumen cannulas, etc.).
[00152] In exemplary embodiments, the small lumen diameter can be minimized such that it can be as small as reasonably possible without producing confounding upstream effects on the flow delivery mechanics of the device. For example, in one or more embodiments, the NO lumen can have an ID in the range of about 0.01 inches to about 0.10 inches and/or about 0.03 inches to about 0.08 inches. Also, in one or more modalities, the oxygen lumen and/or trigger lumen (eg, dedicated trigger lumen, etc.) can have a Dl in the range of approximately 0.05 inches to about 0.20 inches and /or about 0.08 inches.
[00153] Referring to FIGS. 5A-5B, in exemplary embodiments, a dual lumen cannula can have a first lumen 502 for oxygen delivery and a second lumen 504 for NO delivery and transmit the pressure signal to the trigger sensor of the delivery device 505. In this configuration, first lumen 502 can carry oxygen from an oxygen conservator/concentrator 507 to the nose adapter 506 of the cannula. The 504 second lumen can deliver NO from the nitric oxide delivery device to the patient and/or can deliver the triggering signal based on the patient's pressure to trigger the nitric oxide delivery device's sensor. Both lumens can be constructed to connect (eg T-shape) to both nostrils, 508/510, and therefore be in unobstructed fluid communication with both nostrils 508/510.
[00154] The prime lumen for oxygen transport can be constructed with a lumen inner diameter geometry consistent with industry standards. For example, nasal cannulas with a calculated oxygen delivery capacity of 6 LPM may have an oxygen lumen inner diameter of approximately 0.08 inches near or in the nosepiece. Thus, in one or more embodiments, the oxygen lumen can have an internal diameter in the range of about 0.05 inches to about 0.20 inches and/or about 0.08 inches.
[00155] The second lumen to load NO and trigger can be constructed based on the compromise of concurrent metrics (eg as discussed above). For example, because the second lumen combines NO charging and triggering, the ideal geometry (eg shape, size, etc.) of the second lumen may require compromise between at least some competing metrics to, for example, deliver pulses and/or NO flows early in the inspiratory phase, reduce pneumatic delays, reduce flow waveform distortion, reduce delay and/or distortion of pressure signals, reduce NO mixing volume in the nosepiece, and/or oxidation of NO in the nosepiece. Considering at least competing metrics for optimization, in at least some embodiments the combined NO lumen/dual-lumen cannula trigger geometry may be in the range of about 0.08 inches. In exemplary embodiments, the inside diameter of the second lumen can be dictated by considerations of volumetric metering accuracy, the second lumen can have an ID in the range of approximately 0.01 inches to about 0.10 inches, and/or the second lumen can have a Dl in the range of approximately 0.01 inches to about 0.06 inches with upstream piping that can be adjusted to optimize (eg widen, etc.) the system's bandpass performance.
[00156] In exemplary embodiments, a dual-lumen cannula may have a first lumen for NO delivery and a second lumen for O2 delivery and transmit the pressure signal to the trigger sensor of the delivery device. In this configuration the NO lumen can be substantially small (eg similar in size to the NO lumen described below in a tri-lumen cannula) and/or the combined trigger and O2 lumen can have an internal diameter in the range of about 0.07 inches to 0.14 inches and/or 0.03 to about 0.08 inches on the nosepiece. In exemplary embodiments, a dual-lumen cannula can have a first lumen for delivering NO and O2 and a second lumen for transmitting the pressure signal to the trigger sensor of the delivery device. In this configuration, the first lumen for NO and O2 delivery can use similar techniques for delivering NO and O2 into the lumen thereof, for example, as described herein with reference to a mono-lumen cannula. TRI-LUMEN CANNULA
[00157] Referring to FIGS. 6A-7, in exemplary embodiments, the nasal cannula can have at least three lumens (ie, a 600 tri-lumen cannula): a lumen that can deliver nitric oxide into one lumen (eg, NO 604 lumen), for example, from a delivery device (e.g., delivery device 603); another lumen that may be for triggering (e.g., trigger lumen 606), e.g., the delivery device (e.g., delivery device 603); and another lumen that can deliver 02 into a lumen (eg, 02 608 lumen), eg, from an air/02 source (eg, conservator and/or 605 concentrator). The three lumens can be aggregated into a single cannula nosepiece (eg, cannula nosepiece 602) that can have separate flow paths to each lumen and/or at least one lumen.
The NO lumen can be a dedicated lumen that can transport therapeutic gas composed of NO from the NO delivery device 603 to the patient (eg through nostrils 610/612 in the cannula nose adapter 602). The oxygen lumen can be a dedicated lumen that can transport an oxygen-enriched gas (eg, such as oxygen-enriched air, substantially pure oxygen, etc.) from an oxygen source to the patient (eg, through the nostrils 610/612 on the cannula nose adapter 602). The oxygen source can be an oxygen pulsation device (eg as an oxygen conservator) and/or a constant flow oxygen device (eg as an oxygen concentrator) and/or it can be a port on the NO delivery device that delivers oxygen enriched gas. The trigger lumen can be a dedicated lumen that allows the propagation of trigger signals from the patient to the NO 603 delivery device.
[00159] In exemplary embodiments, the nasal cannula can connect the oxygen lumen to an oxygen source (eg, an oxygen pulsation device, an oxygen conservator, a constant flow oxygen device, an oxygen concentrator, etc. .) and/or the nasal cannula may not connect the oxygen lumen to an oxygen source (eg for patients not receiving supplemental oxygen). For patients who are not receiving supplemental oxygen, the oxygen lumen can be removed and/or it can be partially removed. For example, the oxygen lumen can be partially preserved to support the oxygen side of the cannula that surrounds the patient's head, while the portion of the lumen provides the connection to an oxygen source (eg, an oxygen coil outside the reducer ) can be removed. Removal and/or partial lumen removal of oxygen can be done in the same way for other multi-lumen cannulas described herein (eg, dual lumen cannulas, quad-lumen cannulas, etc.).
[00160] Referring to FIGS. 6C and 7, an exemplary cannula may include three lumens in the nosepiece (e.g., nose bridge fitting, etc.) and/or the tire paths and/or lumens may be separated by dividers and/or diaphragms that may be inside the nosepiece and/or cannula nostrils. NO delivery can pass through the nosepiece through a lower gas resistance source to larger resistance holes that can be included in the cannula nostrils. In exemplary embodiments, each lumen may be separated by a diaphragm partition within the cannula nosepiece and/or within the cannula nostrils to prevent mixing of fluid flows in the separate lumens.
[00161] The three lumens can be extruded through a single mold, producing a multi-lumen tube, can be extruded into a single multi-cavity extrusion, can be extruded separately and placed together in a tube arrangement disclosed herein, and/or using any other reasonable technique. Similar techniques can be used for other multi-lumen cannulas described herein (eg, dual-lumen cannulas, quad-lumen cannulas, etc.).
[00162] Referring to FIG. 7, in exemplary modalities, the NO 604 delivery tube/lumen may decrease in internal diameter (ID) at least once when only just before and/or just after entering the nasal cannula 602 nasal adapter. or more modalities, pneumatic resistance may be greater in one of the nasal cannula nostrils than in the tubing carrying NO from the NO delivery device to the nasal cannula adapter. In exemplary modalities, the smaller DI tube of the dedicated NO delivery lumen can allow advantages such as, but not limited to: • Short gas transit times; (eg reduce according to Knudsen diffusion, which states that the rate of diffusion is proportional to the average free path length of the gas molecule which can be reduced with smaller Dl);• Increased gas resistance to flow (by example, tube with smaller Dl produces resistance to gas flow which can be inversely proportional to the fourth power of the tube's radius by Poiseuille's law); and• Reduced volume in the T-loop of the NO delivery lumen.
[00163] The foregoing can reduce the retrograde flow potential, reduce the retrograde flow volume, and/or reduce the duration of contact and/or contact between NO and other gases, including oxygen in the cannula, to name a few. This in turn may reduce NO dilution and/or increase the accuracy of the NO dose delivered. Accordingly, in exemplary embodiments, the DI of the NO lumen can be approximately 0.01 inches to about 0.10 inches and/or approximately 0.07 inches.
[00164] The Dl of the NO lumen can decrease from a maximum Dl to a minimum Dl, for example, to at least reduce cross-flow and/or increase patient comfort. In exemplary embodiments, the ratio of the minimum Dl to the maximum Dl of the NO lumen can be, but is not limited to, 1:1, 1: 1.2, 1: 1.3, 1: 1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:7, 1:8, 1:9, and/or 1:10, to name a few . Similar ratios of minimum Dl to maximum NO lumen Dl can be used for other multi-lumen cannulas (eg, dual lumen, tri-lumen, quad-lumen cannula, etc.) described herein that may have dedicated lumens for NO delivery and/or combined NO delivery lumens and triggers.
The ID of the triggering lumen may be comparatively much larger than the ID of the NO lumen. The ID of the triggering lumen can be substantially larger such that trigger pressure drop on inhalation can be transmitted through this cannula lumen with the least possible loss of signal magnitude and/or phase delay to the NO delivery device that in turn can use this pressure signal to deliver pulsed NO. Therefore, in exemplary embodiments, the trigger lumen DI can be approximately 0.05 inches to about 0.20 inches and/or approximately 0.08 inches. In exemplary embodiments, the ratio of the DI of the NO lumen to the DI of the trigger lumen can be, but is not limited to, 1:1, 1: 1.2, 1: 1.3, 1: 1.5, 1:2, 1: 2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:12, 1:15, 1:20, 1:25, and/or 1:30, to name a few.
[00166] The oxygen lumen can also be larger than the NO lumen, for example, to minimize oxygen flow resistance and/or reduce the velocity of gas flow in the nostrils, which can serve to interfere with the signal of triggering pressure due to gas flow effects (eg as from Bernoulli's principle) and/or reducing high frequency resonance (eg auditory range) with high-speed oxygen transit to reduce " noise" associated with oxygen delivery. Accordingly, in exemplary embodiments, the ID of the oxygen lumen can be approximately 0.05 inches to about 0.20 inches and/or approximately 0.08 inches. In exemplary embodiments, the ratio of the DI of the NO lumen to the DI of the oxygen lumen can be, but is not limited to, 1:1, 1: 1.2, 1: 1.3, 1: 1.5, 1:2, 1: 2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:7, 1:8, 1:9, 1: 10, 1:12, 1:15, 1:20, 1:25, and/or 1:30, to name a few. QUAR-LUMEN CANNULA
[00167] Referring to FIGS. 8A-8D, in exemplary embodiments, the nasal cannula can have at least four lumens (ie, an 800 quad-lumen cannula): two lumens that can deliver nitric oxide into one lumen (eg, NO lumen 804A and 804B ), for example, from a delivery device (eg, delivery device 803); another lumen that may be for triggering (e.g., trigger lumen 806), e.g., the delivery device (e.g., delivery device 803); and another lumen that can deliver 02 into a lumen (eg 02 808 lumen), eg from an air/02 source (eg conservator and/or concentrator 805). The four lumens can be aggregated into a single cannula nosepiece (eg, 802 cannula nosepiece) that can have separate flow paths to each lumen and/or at least one lumen.
[00168] In exemplary modalities, such as the pneumatic configurations discussed above, this configuration can separate the pneumatic paths of NO, oxygen, and trigger. Furthermore, in exemplary embodiments, the NO flow delivery paths to each nostril can be kept separate and distinct and/or have its own pneumatic delivery source in the NO delivery device.
[00169] Referring to FIG. 8D, an exemplary quad-lumen cannula having the above configuration can be constructed into the cannula nosepiece in which the quad-lumen cannula can fuse with the cannula lumen in a single umbilical cord between the cannula nosepiece and the device, for example, as can be done in the same way with the tri-lumen cannula. Similar to the tri-lumen cannula (e.g., as described at least referring to FIG. 7, the 804A and 804B NO delivery tube/lumen may decrease in internal diameter (ID) at least once when only just before and /or just after the tube enters the nasal cannula 802. In this sense, in one or more modalities, the pneumatic resistance may be greater in one of the nasal cannula nostrils than in the tubing carrying the NO from the NO delivery device for the cannula nose adapter.
[00170] In exemplary embodiments, the dimensions of the trigger lumen 806, oxygen lumen 808, NO lumens 804A and 804B may be similar to respective lumens in the tri-lumen cannula and/or the geometry of these lumens may provide similar benefits as the described above with respect to the tri-lumen cannula.
[00171] In addition to the above benefits, the quad-lumen cannula configuration can, among other things, prevent the movement of gas through the connected (eg T) delivery loop of the NO supply line during exhalation. This can reduce NO/oxygen contact and/or substantially reduce or eliminate cross-flow. In at least some cases, use of the quad-lumen cannula may require dedicated pneumatic circuits for each NO lumen.
[00172] In exemplary embodiments, the quad-lumen cannula configuration can include two trigger lumens (eg, a two to each nostril) as well as an NO delivery lumen and an O2 delivery lumen. are within the scope of the invention. CHECK VALVES AND VALVES
[00173] In one or more embodiments, a nasal cannula (e.g., single-lumen cannula, multi-lumen cannula, any of the nasal cannulas disclosed herein, etc.) may include one or more check valves that can be located , and/or be in fluid communication with the nitric oxide delivery line. Furthermore, in exemplary embodiments, one or more check valves located in and/or in fluid communication with the nitric oxide supply line can be combined with any of the multi-lumen configurations described. Check valves can be used to, among other things, prevent retrograde movement of gas into the NO supply lumen during inhalation/exhalation. Check valves can be any low opening pressure check valve that can be placed at some point in and/or fluidly communicating with the NO delivery path. Such check valves may include, but are not limited to, duckbill valves, umbrella valves, or any other valve.
[00174] Referring to FIG. 9A, exemplary duckbill valve 902 and/or referring to figs. 9B-9C, exemplary umbrella valves 904 are illustrated that can be used in accordance with nasal cannulas of the present invention. These check valves can be miniature check valves, for example, such that they can be sized to fit the NO delivery lumen and/or be in fluid communication with the NO delivery lumen and/or can be constructed out of the lumen itself by appropriately molding and/or cutting off the lumen outlet during the molding and/or manufacturing process.
[00175] Referring to FIG. 10, in one or more embodiments, the NO delivery cannula and/or the lumen can have a small barrel and/or umbrella check valve 1000 that can be located in the nasal adapter of cannula 1002 and/or that I could allow NO pulses to be delivered to the general nose/mouth area during device NO pulse. This configuration may allow NO to also flow into and/or both nostrils upon inhalation and/or may restrict retrograde flow in the lumen of NO (eg during exhalation). The O2 and/or trigger lumen can be combined or kept separate from the NO lumen, for example, to reduce any adverse signal-to-noise ratio impact on trigger lumen performance due to oxygen flow. This configuration with the flapper valve can prevent retrograde oxygen flow in the NO delivery path, thus reducing the potential for dose dilution. A diaphragm and/or other barrier can separate the NO delivery line from the 02/trigger line on the cannula nosepiece, for example, to prevent mixing.
[00176] In one or more modalities, the nasal cannula can incorporate an impermeable or semi-permeable membrane that can be fixed or mobile and/or can be actively or passively moved when necessary. In addition, the membrane can separate the NO-containing gas or material from the O2 containing gas or material, for example, until the NO needs to be delivered to the patient. This membrane can reduce the contact time, surface area, and/or diffusion rate between the NO and O2 containing gases. This can reduce the formation of NO2, which can dilute the intended delivery concentration of NO.
[00177] Referring to FIG. 11A, in one or more embodiments of the invention, a normally closed valve 1100 (e.g., a duckbill valve, flap valve, pressure valve, etc.) substantially at or near the end of the NO-containing cannula , NO lumen, and/or cannula nosepiece can prevent air from contacting the NO-containing gas inside the cannula, for example, until valve opening can be triggered (eg, a drop in pressure caused by inhalation by the patient or positive pressure caused by the delivery device as it attempts to deliver the NO-containing gas to the patient). When valve opening is triggered, NO can then be delivered to the patient.
[00178] In one or more embodiments, a system may be used and/or provided to expel gas or other material containing NO that comes in contact with 02 containing gas or material that may have otherwise formed NO2 in this mixture. The system can then allow the other part of the gas containing NO or material that has minimal or no NO2 to be delivered to the patient.
[00179] Referring to FIG. 11B, in one or more embodiments of the invention, the nasal system and/or cannulas may include and/or be in fluid communication with an electromechanical valve system 1104 which may actuate, for example, to pump a fixed or adjustable amount of the mixture of gases that may contain NO2 through a separate orifice than the cannula opening to the patient. The system can then trigger to pump the NO containing gas or material to the patient.
[00180] It will be understood that any of the above teachings (for example, check valves, check valve configurations, membranes, valves, electromechanical valve systems, etc.) may be combined with any of the other pneumatic configurations, configurations of cannula, teachings and/or modalities described herein. For example, the above teachings (e.g., check valve configurations, etc.) can be used with the mono-lumen or multi-lumen cannulas described herein and/or any other teachings and/or embodiments described herein. MINIMIZING NO/O2 CONTACT DURING CONNECTION TO THE SOURCE
[00181] One or more embodiments of the present invention relate to nasal cannulas and/or systems that reduce NO/O2 contact during connection of the high pressure source (e.g., a pressurized cylinder, etc.) to the delivery device (eg one or more of the above sources of oxygen/NO contact) and thus dilution of the intended dose of NO using a three-way valve. For example, nasal cannulas and/or systems of the present invention include a valve of three-way with a port to the room that can be configured so that the three-way valve opens to the room at the time of pipe connection to remove (eg blow out) oxygen. PROPORTIONAL NOZZLE DELIVERY
[00182] Referring to FIGS. 12-13, one or more embodiments of the present invention relate to nasal cannulas and/or systems that address the problem of drug loss (e.g., to the environment) when delivering a gaseous drug (e.g., in the form of of pulsed nitric oxide etc.) through a nasal cannula due to at least one partially closed nasal passage (eg as shown in FIG. 12). As an example of a problem, if one side of the nose (eg, nose 1201) is occluded (eg, occlusion 1203) and drug is being delivered to both sides of the nose through a 1200 cannula/delivery system that does not discriminate how much of the drug goes into each nostril (eg 1205 nostrils), so there may be drug loss due to the obstructed nostril. In addition, there may be other undesirable consequences, such as the reaction of unused gas therapy with other materials and/or compounds that may come into contact with the gas.
[00183] This inadequate dosing can be a particular problem when delivering drug therapy in limited set amounts, such as when pulsed (for example, when delivered synchronous to the patient's breathing pattern and rhythm) through a single egress lumen s the delivery device, which in turn can then be split at some point downstream before reaching the patient. Furthermore, this can be a particular problem because, when pulsing the drug dose through a single lumen which is then split, the dose can be equally or substantially equally split into two streams without regard to obstruction in the nose downstream of the split. Thus, a significant part (eg, up to half) of the dose may not be delivered to the patient and/or may remain in the vicinity of blocked or obstructed nostrils.
[00184] One or more embodiments of the present invention pertain to nasal cannulas and/or systems that solve or minimize the above problem, for example, providing approximately proportional delivery of therapy to each nostril with delivery being proportional to air flow and gas in the nostrils and/or inversely proportional to the resistance in the nostrils. This can be achieved by using the driving force of the patient's breathing, which can be generally and more or less proportional to the air/gas flow rate in each of the nostrils, to proportionally divide and/or pull the therapy gas to the nose the patient and subsequently to the patient's lungs. This system can deliver the dose to a patient in order to ensure that the projected, defined, or adequate dose can be delivered proportional to the airflow in each nostril (or inversely proportional to the resistance of each nostril) such that total or partial blockage (whether permanent or transient) of one or both nostrils does not affect the amount of medication delivered to the patient.
[00185] For example, the cannula/lumen can be designed to deliver a desired amount of therapeutic gas, such that the delivered dose can be injected and/or delivered in an inspiratory airflow, driven by the patient's breathing, with such separating flow, downstream of the drug delivery point, proportional to the amount of air that goes into each nostril or simply delivered to one nostril if flow from the other nostril is below a predetermined threshold such that the drug delivered can also be divided proportional and/or approximately proportional or directed to one or the other nostril in an all-or-nothing configuration based on the upper flow nostril for said gas flow. Airflow in a stream to the patient can be achieved with an ambient airflow path (eg through a simple hole in the cannula nose) to each nostril such that this flow path crosses the delivery point/ area/volume of the drug before moving to the point of separation leading to each nostril.
[00186] In exemplary embodiments, exemplary cannula/lumen configurations can allow delivery of NO to each nostril by injecting NO into an ambient air stream to each nostril (eg, as shown in FIG. 13) and/or configurations can allow beneficial transverse flow between the two nostrils that can be designed and/or used to help guide NO to the unobstructed nostril (eg, as shown in FIG. 12). The delivery cannula/lumen can be designed to ensure therapeutic gas cannot be dragged or transmitted out of the airflow path to the patient. The delivery cannula/lumen and inspiratory airflow path to the patient can be designed to ensure that drug delivery to the airflow cannot be hampered or accelerated by the creation of back pressure or lower partial pressure or other flow patterns drugs at the point of injection of the drug into the ambient air stream. The delivery cannula/lumen, inspiratory airflow path, airflow split across the nostrils, and individual nostril lumen pieces can be designed to ensure that there can be adequate airflow versus other air sources or oxygen to the patient, such that the drug can be drawn and carried into the nostrils proportional or substantially proportional to the air flow in the nostrils. INDEPENDENT DELIVERY TO NARINA
[00187] One or more embodiments of the present invention relate to nasal cannulas and/or systems that address the problem of underdosing due to a partially or completely blocked nostril motor in each nostril and adjusting the amount of drug delivered to each nostril. This can be done using valves, baffles, flaps, or any other device to ensure proportional and/or substantially proportional dosing in each nostril.
[00188] At least addressing the above, dual-channel systems (eg, which can work with multi-lumen cannulas like quad-lumen cannulas) can utilize at least two independent flow channels: one for each nostril. In exemplary modalities, these independent flow channels can have drug flows tailored to the inspiratory draw of each nostril, for example, configuring the flow channels to provide flow proportional to the draw of each nostril with total flow from both nostrils adding to proper dose and/or configuring the flow channels to deliver to the working one (eg high-flow nostril draw) if the obstructed nostril draw-flow falls below a pre-set threshold.
[00189] Referring to FIGS. 14A-14B, in order to implement a dual channel system, it may be necessary to have two independent flow delivery channels coupled by a single (global) controller module module (eg a control module associated with a delivery device, etc.). Each of these delivery channels may require a pressure and/or flow signal from the particular nostril of interest, as well as the ability to deliver gas to the nostril. By way of example, as illustrated in FIG. 14A, cannula 1400 may have separate 1402 sensing lumens and 1404 delivery lumens for each nostril (e.g., a dual-lumen cannula, tri-lumen cannula, quad-lumen cannula, etc.). As another example, as illustrated in FIG. 14B, cannula 1410 may have combined sensing and delivery lumens 1412 for each nostril where the trigger or breath detection signal can be determined and/or detected and drugs delivered through the same lumen of the cannula (e.g., a lumen cannula single, double lumen cannula, etc.) as illustrated in FIG. 14B.
[00190] Referring to FIG. 15, in exemplary embodiments, pneumatic systems 1500 (eg, the delivery device) for the cannula may need to be implemented to support previous lumen configurations (eg, as described above) and/or may require configurations having (1 ) a 1502 pressure sensor and/or 1504 integral flow sensors that can monitor each channel independently or in pneumatic isolation and/or (2) flow delivery mechanism(s) that can software controlled solenoid valves (on-off type ) and/or software controlled proportional solenoid valves 1506. Configurations using a pressure and/or flow sensor may include a dedicated pressure and/or flow sensor for each delivery channel and/or a pressure interrupted by valve and/or sensors that can switch between delivery channels and/or determine and/or detect pressure and/or flow readings for each channel in isolation. Pressure and/or flow can be measured (eg using 1502 pressure sensors, 1504 integral flow sensors, etc.) independently and/or differentially using one or more sensors. In addition, one or more valves may actuate (eg, independently, in tandem, proportionately, etc.) to deliver the proper amount of therapeutic gases.
[00191] In exemplary embodiments, the pneumatic channels can be controlled by a controller and/or a built-in (global) controller module that can be capable of independent control of both channels, for example, to ensure correct overall dosing. This controller can receive input from the flow or pressure sensor(s) (eg two separate pressure sensors, a single pressure sensor that can take two pressure measurements in isolation, etc.) and can control both solenoid valves to achieve the adcCjuαdO dosing regime. MANUFACTURING OF MULTI-LUMEN NASAL CANNULA
[00192] As described above, the individual lumen of a multi-lumen cannula can be manufactured separately and then affixed to the other (eg paratube arrangement, etc.) and/or the multiple lumens can be extruded through a single mold , producing a multi-lumen tube.
According to one or more embodiments, the multi-lumen nosepiece of the multi-lumen cannulas described herein can be manufactured using molding techniques. For example, the cannula can be manufactured to have a triple lumen cannula nose adapter for separate oxygen, nitric oxide, and trigger lumens.
[00194] Referring to FIG. 16, in one or more embodiments, the 1602 nosepiece for a tri-lumen cannula may include three lumens, two lumens with internal diameters of about 0.08 inches (e.g., for a 1608 oxygen lumen and/or trigger lumen 1066) and a lumen with a smaller inner diameter of about 0.045 inches (eg for 1604 nitric oxide lumen). This configuration may not be readily molded by typical injection molding techniques, for example, since the small lumen may require an injector pin (about 0.045 inch outside diameter) that may be too small to be robust (or be able to withstand large numbers of shattered parts without bending) in a molding tool designed to last through many uses.
[00195] Referring to FIG. 17, to manufacture the multi-lumen cannula nosepiece, a mold can be used which can have at least two halves (eg, 1701 and 1702) in urethane, PVC, silicone, or other low durometer elastomer with large lumen trim. 1704 and 1705) (eg oxygen lumen, trigger lumen, etc.) being defined by larger core/injector pins (about 0.08 inches outside diameter) and with small halved lumen indentations (eg, 1706 and 1708) defining the contour of the small lumen (eg, NO lumen). These two halves can be folded and glued together, preferably with a gluing technique that does not produce residue or flash such as RF soldering and/or solvent gluing, to form a nosepiece whole.
[00196] In exemplary embodiments, to bypass the injector pin limitation with the small DI lumen being defined by indentations in the halves, the two halves can be molded flat in one step, for example, with a belt (eg belt 1709 ) holding the halves together and providing rough alignment during the folding and binding process. Molded halves may, in some cases, include integral holes and cylindrical mating guides or other complementary members (eg guide 1710 and guide plate 1712) so that the halves can be correctly aligned when folded together. The belt may also be optional, for example if appropriate complementary indexing members on the two halves ensure that the two parts forming the outer wall of the NO lumen can be properly aligned. The mounted nosepiece can allow three lumen inputs and can be connected (eg t) to each lumen input inside the appropriate nosepiece. Of course, the nosepiece can be constructed using any reasonable technique. By way of example, a nosepiece with a substantially small NO lumen can also be constructed using liquid silicone rubber injection molding (eg a low pressure molding technique where a more robust mold tool can be achieved ), and/or using a low pressure molding technique. In addition, a nosepiece with a substantially small NO lumen can be constructed using micromoulding techniques known in the art which can be used for high resolution production of small parts, including parts with small mold pins. By way of example, a nosepiece with a substantially small NO lumen can be constructed using micro-molding techniques known in the art.
[00197] Referring to FIG. 18 is a perspective view of the nostril (e.g., nostril 1716) of the multi-lumen cannula nasal adapter of FIG. 17 is pictured after the two halves have been assembled.
[00198] The Dl of the lumen can be adjusted as described above. For example, the ID of the oxygen lumen can range from about 0.05 inches to about 0.20 inches, the ID of the trigger lumen can range from about 0.05 inches to about 0.20 inches, and the ID of the NO lumen can range from about 0.01 inches to about 0.10 inches. In one or more embodiments, the Oxygen lumen and trigger lumen IDs can both be in the range of approximately 0.07 inches to about 0.09 inches and/or about 0.08 inches and the NO lumen ID it can be in the range of approximately 0.035 inches to about 0.055 inches and/or approximately 0.045 inches.
[00199] Referring to FIG. 19A-19B, within and/or before nostril 1900 the small lumen of NO 1902 may exit proximal to and/or within the larger triggering lumen 1904, for example, so that any triggering larger lumen tip blockage (for which it may not there is a purge capability) can be blown out/expelled by the NO pulse function. The geometry can be designed to ensure that all, and/or substantially all, NO in the triggering larger lumen can reach the respiratory system during inspiration and/or not be left behind so that it can be swept out during expiration. EXEMPLARY NASAL CANNULA
[00200] Referring to FIG. 20, in accordance with exemplary modalities, a 2001 nasal cannula is shown that includes three separate lumens for oxygen delivery, NO delivery, and for respiration triggering. The nasal cannula may include a 2002 nose adapter to interface with the patient's nose. The 2003 NO lumen and 2004 trigger lumen can carry NO to the patient and transmit the pressure signal, respectively. NO 2003 lumen and 2004 trigger lumen can both be tubes (eg D-shaped tubes), such that their combined tubes appear as a single 2003/2004 "paratube" tube. Paratubo 2003/2004 can connect to NO delivery device per nasal cannula connection piece 2014. Nasal cannula 2001 may also include positioning member 2010, reducer 2012, and/or oxygen connection piece 2016 discussed in more detail below.
[00201] Referring to FIG. 21 A, the "paratube" can be formed by two tubes (eg two D-shaped tubes). By way of example, the D-shaped tubes can be extruded separately and/or joined in a later operation, eg sticking (eg adhesive, glue, etc.) and/or bonding (eg heating, melting , etc.) to form a single paratube that may appear to be a single tube. In addition, the flat interface between the tube halves can be changed to have a tongue and groove type configuration allowing easy alignment of the tubes relative to each other for a subsequent gluing operation. As another example, D-shaped tubes can be extruded in a single operation and then split at the ends (eg using a splicer). Furthermore, the D-shaped tube extrusions can be of the same material and/or different materials. For example, the NO D-shape pipe can be constructed of oxygen resistant materials and/or the other D-shape pipe can be constructed of PVC and/or other materials used for the construction of the pipe. Paratubo 2003/2004 can be connected to the NO delivery device by the 2014 nasal cannula connection piece.
[00202] Referring to FIGS. 21B and 21C, in modalities gvgrnplorθc Q rjjôrno+rQ intθrnQ HQC f|jbθS (pOT θXθ!Tip!θ lÚmOO dθ NO 2003 triggering lumen 2004, oxygen lumen 2008, combined lumens etc.) and/or paratube may include geometrical protrusions. eg bulges, ribs, etc.) and/or inserts (eg guides etc) to prevent complete occlusion of the tube, eg due to bending of the tube and/or compression of the tube. These geometric protrusions can be spaced radially in such a way that they can be symmetrically and/or asymmetrically located within the tube and/or paratube.
[00203] Referring to FIGS. 20 and 22A-22E, 2014 nasal cannula connection piece can be constructed to ensure fluid communication between the patient and the device. The connecting piece can be plugged into the device and/or can be designed in such a way that unidirectional connection may be required (eg such that it cannot be installed backwards). Furthermore, the connecting piece may include additional features such as, but not limited to, a color and/or differentially reflective stamped area that can be used with IR detection sensors to confirm the insertion and/or the part. The connection may include a strain relief member 2202 (for example, as shown in figs. 22C-22E), which may be an integral part of the connection piece to prevent twisting of the tubing, for example, as the tube exits the connector. Of course, other techniques can be used to ensure the detection/sensing intersection. Nasal Cannula Connecting Piece 2014 may include ribs and/or substantially soft exteriors to aid in at least manipulation and removal of elements; strain reliefs, for example, which can serve to prevent kinking. 2014 nasal cannula connection piece can be constructed to ensure that the connector seats in the socket can be detected or seen by the user; to name a few.
[00204] Referring to FIGS. 20 and 23, in exemplary embodiments, Oxygen Connection Piece 2016 may allow connection to external oxygen delivery devices such as, but not limited to, oxygen conservators and/or concentrators. 2016 Oxygen Connection Piece can be designed with industry standard dimensions, for example, to ensure ease of use and/or connection to oxygen delivery devices. Additionally, Oxygen Lumen 2008 can connect to an oxygen conservator or other oxygen delivery device per Oxygen Connection Piece 2016.
[00205] Referring to FIGS. 20 and 24, the 2003 NO lumen, 2004 trigger lumen and 2008 oxygen lumen each may have a smaller inner and/or outer diameter per cannula nose adapter 2002 than the related 2014 and 2016 connection pieces. a 2012 reducer can be used to connect portions of the nasal cannula lumens that have different dimensions and/or transverse profiles. In addition, reducer 2012 can also be used to terminate the oxygen lumen, for example, when no oxygen tail is provided, when ambient air is received in the cannula, and/or when the nasal cannula is not connected to an oxygen source , to name a few.
[00206] In exemplary embodiments, tubes (eg, NO lumen 2003, trigger lumen 2004, oxygen lumen 2008, combined lumens, etc.) can be attached to the 2002 cannula nose adapter and/or device connector (eg, connection pieces 2014 and 2016) using any technique such as, but not limited to, gluing, adhesives (eg epoxy, cyanoacrylate, etc.), adhesive-solvent, insert molding and/or by any other technique.
[00207] Referring to FIG. 24, reducer 2012 can allow a transition between, and/or connection between, tubes of different dimensions (eg different outer diameters, different inner diameters, etc.) so the tubing, for example closer to the patient, can be optimized for patient comfort (eg increasing flexibility, reducing outer diameter dimensions, etc.) and/or for Cjlic 0 dcSci I ipcPihO pnθUiiidtiCO of Each Cannula Lumen can be optimized using various diameters, eg to optimize the comfort of the cannula by minimizing the diameters of tubes located proximal to the patient's head. NASAL ADAPTER
[00208] Referring to FIGS. 25A-25Q various views of various 2002 exemplary nasal cannula adapters are pictured. FIG. 25A shows the side of the cannula nose adapter 2002 where the 2008 oxygen lumen connects to the cannula nose adapter 2002. FIG. 25B shows the two D-shaped openings for the 2003 NO lumen and the 2004 trigger lumen. FIG. 25C shows each projection of the nasal cannula connecting piece having a central lumen for NO and two outer lumens for oxygen and triggering.
[00209] In exemplary embodiments, the cannula nose adapter and/or at least one of the cannula nose adapter and/or cannula may have properties of a material (e.g., durometer, etc.) selected to provide comfort, ensuring structural and pneumatic integrity (eg, of cannula nosepiece, at least some of cannula nosepiece, at least some of cannulae, etc.). For example, to provide comfort, ensuring structural and pneumatic integrity, the cannula nose adapter and/or at least one of the cannula nose adapter and/or cannula may have about 30 to 70 durometer and/or about 50 Durometer (Shore A).
[00210] In exemplary embodiments, cannula nose adapter 2002 includes three lumens in a 2515 "tornado" design that can allow sufficient rigidity for the nasal nostrils, yet still allow the nostrils to be partially compressible, for example, because of the lines of splitting for the 2008 oxygen lumen and 2004 trigger lumens may be decompensated (eg, not aligned across the center of the 2003 NO delivery lumen). This compression capability can allow the nasal projection to be more flexible and comfortable than other tri-lumen cannula projection designs.
[00211] In exemplary modalities, the tornado can also encapsulate the smaller NO 2004 lumen, nasal nostrils can be designed to ensure optimal and/or desired insertion distance, and/or to increase comfort the nasal cannula can be tapered to the base to the extremity and/or can be arched (eg, inwards towards the nasal openings). In exemplary embodiments, this ideal and/or desired insertion distance can be approximately 0.1 inches to approximately 0.6 inches and/or about 0.40 inches.
[00212] In exemplary embodiments, the geometry of the oxygen lumen output (eg on the cannula nose adapter) can be designed to reduce auditory frequency noise (eg, about 20 hz to 15 khz), for example , by activating the output of the oxygen lumen. In addition, noise reduction can also be achieved by modifying the lumen durometer carrying oxygen to prevent auditory gap oscillation and noise due to oxygen flow and/or by selecting an oxygen lumen geometry that does not generate noise (eg vibration , resonance, etc.).
[00213] Referring to FIGS. 26A - 26C, cross-sectional views show several exemplary configurations for nasal cannula nostrils. For example, FIG. 26A depicts a "tornado" pattern. FIGS 26B-26D depict additional configurations that may include at least some of the benefits disclosed for the "tornado" configuration. For example, other configurations may allow sufficient rigidity for the nasal nostrils and may allow the nostrils to be partially compressible and/or other configurations which may provide at least some of the benefits disclosed above are within the scope of the present invention.
In exemplary embodiments, the outer diameter of the cannula nasal adapter nostrils can be minimized to increase patient comfort. Given this outer dimension, the dimensions of the various lumens (eg trigger lumen, NO lumen, 02 lumen etc.) can be selected to not only receive optimization (eg as discussed in this document), but can also be selected be limited in size to account for patient comfort. For example, while it is beneficial for optimization to have larger outside diameter nostrils (for example, an outside diameter of about 0.25 inches or more), the cannula nostrils can have an outside diameter of less than and/or about 0 .2 inches for patient comfort.
[00215] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a tri-lumen cannula (e.g., about 7 feet in length) may have tubing with an NO lumen having an ID of approximately 0.069 inches, a trigger lumen having an ID of about 0.089 inches, and an O2 lumen having an ID of approximately 0.089 inches with at least some of the lumens reducing in the cannula nosepiece (by for example, with a background length of approximately 0.59 inches) and/or reducing (eg, reducing again) in one of the nostrils (eg having a length of about 0.47 inches) of a nosepiece. cannula. For example, in the cannula nosepiece the NO lumen can be reduced to an ID of about 0.049 inches, the trigger lumen can have an ID of about 0.089 inches, and/or the O2 lumen can have an ID of about of 0.089 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen can be reduced to an ID of about 0.038 inches, the trigger lumen can be reduced to an ID of about 0.079 inches, and/or the lumen of 02 can be reduced to a Dl of approximately 0.079 inches. In addition, prior to the connecting piece and/or reducer the NO lumen may have an ID of approximately 0.063 inches, the trigger lumen may have an ID of about 0.089 inches, and the O2 lumen may have an ID of approximately 0.132 inches .
[00216] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a tri-lumen cannula (e.g., about 3 feet in length) may have tubing with an NO lumen having an ID of approximately 0.064 inches, a trigger lumen having an ID of about 0.084 inches, and an O2 lumen having an ID of approximately 0.084 inches with at least some of the lumens reducing in the cannula nosepiece (by for example, with a background length of approximately 0.59 inches) and/or reducing (eg, reducing again) in one of the nostrils (eg having a length of about 0.47 inches) of a nosepiece. cannula. For example, in the cannula nosepiece the NO lumen can be reduced to an ID of about 0.044 inches, the trigger lumen can have an ID of about 0.084 inches, and/or the O2 lumen can have an ID of about of 0.084 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen can be reduced to an ID of about 0.036 inches, the trigger lumen can be reduced to an ID of about 0.074 inches, and/or the lumen of 02 can be reduced to a Dl of approximately 0.074 inches. Also, before the connecting piece and/or reducer the DO lumen may have an ID of approximately 0.064 inches, the trigger lumen may have an ID of about 0.084 inches, and the O2 lumen may have an ID of approximately 0.127 inches .
[00217] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a tri-lumen cannula (e.g., about 15 feet in length) may have tubing with an NO lumen having an ID of approximately 0.074 inches, a trigger lumen having an ID of about 0.094 inches, and an O2 lumen having an ID of approximately 0.094 inches with at least some of the lumens reducing in the cannula nosepiece (by for example, with a background length of approximately 0.59 inches) and/or reducing (eg, reducing again) in one of the nostrils (eg having a length of about 0.47 inches) of a nosepiece. cannula. For example, in the cannula nosepiece the NO lumen can be reduced to an ID of about 0.054 inches, the trigger lumen can have an ID of about 0.094 inches, and/or the O2 lumen can have an ID of about of 0.094 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen can be reduced to an ID of about 0.04 inches, the trigger lumen can be reduced to an ID of about 0.084 inches, and/or the O2 lumen can be reduced to an ID of approximately 0.084 inches. Also, before the connecting piece and/or reducer the NO lumen may have an ID of approximately 0.074 inches, the trigger lumen may have an ID of about 0.094 inches, and the O2 lumen may have an ID of approximately 0.137 inches .
[00218] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a quad-lumen cannula (e.g., about 7 feet long) may be tubing with at least one NO lumen having an ID of approximately 0.069 inches, at least one trigger lumen having an ID of about 0.089 inches, and an O2 lumen having an ID of approximately 0.089 inches with at least some of the lumens reducing in the nosepiece of cannula (eg with a fundu piano compπii iβπto of approximately 0.59 inches) and/or reducing (eg, reducing again) in one of the nostrils (eg having a length of approximately 0.47 inches ) of a nasal cannula adapter. For example, in the cannula nosepiece the NO lumen(s) may be reduced to an ID of about 0.049 inches, the triggering lumen(s) may m) have an ID of about 0.089 inches, and/or the O2 lumen may have an ID of about 0.089 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen(s) can be reduced to an ID of about 0.038 inches, the lumen(s) ) trigger(s) can be reduced to an ID of approximately 0.079 inches, and/or the 02 lumen can be reduced to an ID of approximately 0.079 inches. Also, before the connecting piece and/or reducer the NO lumen(s) may have a Dl of approximately 0.069 inches, the trigger lumen(s) may have an ID of about 0.089 inches and the O2 lumen may have an ID of approximately 0.132 inches.
[00219] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a quad-lumen cannula (e.g., about 3 feet in length) may have tubing with at least one NO lumen having an ID of approximately 0.064 inches, at least one trigger lumen having an ID of about 0.084 inches, and an O2 lumen having an ID of approximately 0.084 inches with at least some of the lumens reducing in the nosepiece of cannula (eg having a background length of approximately 0.59 inches) and/or reducing (eg reducing again) into one of the nostrils (eg having a length of approximately 0.47 inches) of cannula nose adapter. For example, in the cannula nosepiece the NO lumen(s) may be reduced to an ID of about 0.044 inches, the triggering lumen(s) may m) have an ID of about 0.084 inches, and/or the O2 lumen may have an ID of about 0.084 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen(s) can be reduced to an ID of about 0.036 inches, the lumen(s) ) trigger(s) can be reduced to an ID of approximately 0.074 inches, and/or the O2 lumen can be reduced to an ID of approximately 0.074 inches. Also, before the connecting piece and/or reducer the NO lumen(s) may have a Dl of approximately 0.064 inches, the trigger lumen(s) may have an ID of about 0.084 inches and the O2 lumen may have an ID of approximately 0.127 inches.
[00220] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a quad-lumen cannula (e.g., about 15 feet in length) may have tubing with at least one NO lumen having an ID of approximately 0.074 inches, at least one trigger lumen having an ID of about 0.094 inches, and an O2 lumen having an ID of approximately 0.094 inches with at least some of the lumens reducing in the nosepiece of cannula (eg having a background length of approximately 0.59 inches) and/or reducing (eg reducing again) into one of the nostrils (eg having a length of approximately 0.47 inches) of cannula nose adapter. For example, in the cannula nosepiece the NO lumen(s) may be reduced to an ID of about 0.054 inches, the triggering lumen(s) may m) have an ID of about 0.094 inches, and/or the O2 lumen may have an ID of about 0.094 inches. Still following the above example, in one of the cannula nosepiece nostrils the NO lumen(s) can be reduced to an ID of about 0.04 inches, the lumen(s) Trigger(s) can be reduced to an ID of approximately 0.084 inches, and/or the O2 lumen can be reduced to an ID of approximately 0.084 inches. Also, before the connecting piece and/or reducer the NO lumen(s) may have a Dl of approximately 0.074 inches, the trigger lumen(s) may have an ID of about 0.094 inches and the O2 lumen may have an ID of approximately 0.137 inches.
[00221] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a dual-lumen cannula (e.g., about 7 feet long) may be tubing with a combined NO/trigger lumen having an ID of approximately 0.07 inches and an O2 lumen with an ID of approximately 0.089 inches with at least some of the lumens decreasing in the cannula nosepiece (eg with a flat length of bottom of approximately 0.59 inches) and/or reduce (e.g., reduce again) in one of the nostrils (e.g., having a length of about 0.47 inches) of cannula nosepiece. For example, in the cannula nosepiece the combined NO/trigger lumen can be reduced to an ID of about 0.05 inches and/or the O2 lumen can have an ID of about 0.089 inches. Still following the above example, in one of the cannula nosepiece nostrils the combined NO/trigger lumen can be reduced to an ID of about 0.04 inches and/or the O2 lumen can be reduced to an ID of approximately 0.079 inches. Each of these dimensions for the combined NO/trigger lumen can be increased slightly (eg by a few thousand), for example, to reduce trigger signal attenuation. Also, before the connecting piece and/or reducer the combined NO/trigger lumen may have an ID of approximately 0.07 inches, and the O2 lumen may have an ID of approximately 0.132 inches.
[00222] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a dual-lumen cannula (e.g., about 3 feet long) may be tubing with a combined NO/trigger lumen having an ID of approximately 0.064 inches, and an O2 lumen with an ID of approximately 0.084 inches with at least some of the lumens decreasing in the cannula nosepiece (e.g., with a plane length of bottom of approximately 0.59 inches) and/or tapping (e.g., tapping back) into the nostrils (e.g. having a length of about 0.47 inches) of cannula nosepiece. For example, in the cannula nosepiece the combined NO/trigger lumen can be reduced to an ID of about 0.044 inches and/or the O2 lumen can have an ID of about 0.0084 inches. Still following the above example, in one of the cannula nosepiece nostrils the combined NO/trigger lumen can be reduced to an ID of about 0.036 inches and/or the O2 lumen can be reduced to an ID of approximately 0.074 inches . Each of these dimensions for the combined NO/trigger lumen can be increased slightly (eg by a few thousand), for example, to reduce trigger signal attenuation. Also, before the connecting piece and/or reducer the combined NO/trigger lumen may have an ID of approximately 0.064 inches, and the O2 lumen may have an ID of approximately 0.127 inches.
[00223] By way of example, taking into account patient comfort as well as at least some or all of the optimization metrics disclosed in this document, a dual-lumen cannula (e.g., about 15 feet long) may be tubing with a combined NO/trigger lumen having an ID of approximately 0.074 inches, and an O2 lumen with an ID of approximately 0.094 inches with at least some of the lumens decreasing in the cannula nosepiece (e.g., with a plane length of bottom of approximately 0.59 inches) and/or tapping (e.g., tapping back) into the nostrils (e.g. having a length of about 0.47 inches) of cannula nosepiece. For example, in the cannula nosepiece the combined NO/trigger lumen can be reduced to an ID of about 0.054 inches, and/or the O2 lumen can have an ID of about 0.094 inches. Still following the above example, in one of the cannula nosepiece nostrils the combined NO/trigger lumen can be reduced to an ID of about 0.040 inches, and/or the O2 lumen can be reduced to an ID of about 0.084 inches. Each of these dimensions for the combined NO/trigger lumen can be increased slightly (eg, by a few thousand of an inch), for example, to reduce trigger signal attenuation. Also, before the connecting piece and/or reducer the combined NO/trigger lumen can have an ID of approximately 0.074 inches, and the O2 lumen can have an ID of approximately 0.137 inches. TRAMPOLINE
[00224] In exemplary embodiments, a 2002 nasal cannula may include a flexible support bridge or 2517 "trampoline" that can cushion the nasal septum. The flexible support bridge 2517 can provide increased patient comfort by, for example, increasing the contact surface area between the cannula and the nasal septum and/or patient comfort can be increased because the fork bridge can be designed to bypass the nasal septum.
[00225] In exemplary embodiments, the flexible support bridge 2517 may be an element (eg, a free-floating element) that can be supported at both ends by the forks of the nasal cannula. Rather than having the patient's nose (eg, nasal septum) rest on a 2518 central bridge member normally found in nasal cannulas (eg, the one separating the nostrils from a nasal cannula; a hard plastic connection, sometimes curved, between the nostrils of a nasal cannula; etc.), the flexible support bridge 2517 can be an element (for example, in addition to the central bridge 2518, crossing at least part of the central bridge 2518, crossing from one nostril to other nostril, etc.) in contact with the patient's septum, thus providing at least greater comfort to the patient. In exemplary embodiments, flexible support bridge 2517 may "sag" and/or "bend" toward central bridge member 2518 when the cannula is used. The fact that the flexible support bridge "sags" and/or "bends" 2517 can alleviate transient forces in the nasal septum due to patient movement or cannula movement. "Giving" and/or "folding" can also increase the surface area of contact with the nasal septum, which, in turn, can reduce the force on the nasal septum at any point, thus increasing comfort ( for example, since comfort can be negatively affected by the increased stitch load on the nasal septum).
[00226] In exemplary embodiments, the flexible support bridge 2517 can restrict the depth of insertion of the nostrils, for example, as mentioned above, to an ideal and/or desired insertion distance of approximately 0.1 inch, to approximately 0. 6 inch and/or approximately 0.40 inch. By way of example, this distance may be shorter than the length of the nostrils extending from the central 2518 bridge.
[00227] In exemplary embodiments, the nasal cannula piece may include a flap 2519 between the nostrils (e.g., extending from the center bridge 2518) that can allow the nasal cannula connecting piece to properly fit the upper lip. Flap 2519 can provide an additional measure of patient comfort by, for example, orienting the nostrils so that the nostrils point inwards towards the nasal openings and/or can distribute force over the upper lip to an area wider surface area, thus increasing patient comfort.
[00228] Referring to FIGS. 20 and 27, in exemplary embodiments, the nasal cannula may include a 2010 switching member, described in more detail below. In exemplary embodiments, the 2010 switching member can be a plunger that can be included and can be used to adjust the length of the cannula section close to the nosepiece, for example, to increase patient comfort by ensuring that the cannula fits. around the user's head.
[00229] In exemplary embodiments, the nasal cannula may further include ear pads that can, for example, slide over and/or be built into the cannula tubing at the point where the cannula tubing surrounds the ears to increase conformation and/or ear pads can be foam tube extrusions that may have cracks so that they can slide over the cannula tubing.
[00230] While this exemplary nasal cannula may be described as having certain components, some or all of these components may be optional, eliminated, and/or may be combined and/or separated again. In addition, the nasal cannula may have some of the other components or materials described in this document. CANNULA KEYING
[00231] During the purge and/or leak procedure that can be used to clean the nasal cannula of air and other gases prior to NO delivery, the air/gases may be purged by the gas flow which contains NO through the nasal cannula. However, due to the reaction of NO and oxygen in the air, this leakage procedure can produce NO2. Indeed, it may be important that the patient is not using the nasal cannula during the purge and/or leakage procedure, for example, so that NO2 cannot be administered to the patient.
[00232] Referring again to FIG. 20, one or more embodiments of the present invention may provide a 2010 switching element in the nasal cannula. Such a switch element can be attached near the nostrils of the nasal cannula, such as between 5 and 25 inches into the nostrils of the cannula. One or more exemplary embodiments of this switching element can be seen referring to the 2010 element, as shown in FIG. 20. The switch element can be supplied as a plunger that can fit onto the patient's chest and/or neck when the cannula is used by the patient.
[00233] Referring to FIG. 28, the 2010 switching element may need to be plugged into the 2803 NO distribution device with a key slot or a 2804 keyhole and/or this may need to be done during the pouring procedure. Due to the proximity between the switching device and the nostrils, the nostrils of the nasal cannula cannot be in the patient's nostrils when the switching element is plugged into the NO delivery device.
[00234] In one or more exemplary implementations of an NO delivery device with a keyhole and a nasal cannula with a keying element, the NO delivery device can perform the following functions:a. The NO delivery device can prepare the patient to remove the cannula and insert the switching element contained in the cannula into a keyhole in the NO.b delivery device. The keyhole can detect the presence of the key in the keyhole. Exemplary methods for detecting the presence of the switch include, but are not limited to, electronic detection (eg, light beam detector, activated switch, IR detection, magnetic detection, etc.) or mechanical detection (eg, microswitch) ç. The NO distribution device can ensure that the key is in the keyhole before performing the leakage procedure and can be programmed to not perform the maneuver if the key is not in the keyhole. d. The NO delivery device can perform the leaking procedure and inform the user of the completion of the procedure.e. The NO delivery device can allow the user to remove the key from the keyhole to initiate NO treatment.
[00235] In exemplary embodiments, the switch element and/or key slot can be used to ensure that the patient is not using the nasal cannula during the purge and/or leak procedure. In exemplary embodiments, the keying element and/or key slot can be used to ensure the authenticity of the cannula, at the very least, and the expiration of the cannula, at the very least. For example, the switch element and/or key slot can be used to limit the number of users of the cannula and/or not allow patients to reuse the cannula. For another example, in case it is necessary to ensure that patients do not use the cannula, the switching element and/or key slot can be used to prevent users from using a defective cannula.
[00236] It will be understood that any of the above lessons (eg trampoline, flap, paratube, connecting piece, oxygen connecting piece, reducer, switching member, switching, bolus, cannula constructs, nosepiece, etc.) can be combined with any of the other pneumatic configurations, cannula configurations and/or lessons and/or modalities described in this document. For example, the lessons above (eg trampoline, flap, paratube, connecting piece, oxygen connecting piece, reducer, switching member, keying, bolus, cannula constructs, nosepiece constructs, etc.) can be used with monolumen cannulas, dual lumen cannulas, trilumen cannulas, quadlumen cannulas, and/or any other lesson and/or modality described in this document.
[00237] Referring to FIGS. 29-30, an example of retrograde flow during the inspiration movement along with the pulse distribution is shown in FIG. 29 and an example of retrograde flow during inspiration and expiration movements is shown in FIG. 30.
[00238] Referring to FIGS. 31 and 32A, 32B and 32C, retrograde flow for various nasal cannula configurations was tested. Typical nasal cannulas delivering to both nostrils result in significant retrograde flow, as shown in Test 1 of FIG. 31. The configuration of the nasal cannula from Test 1 is shown in FIG. 32A. For Test 2, the interconnection between the two nostrils was occluded in order to increase the distance between the nostrils to approximately 19 inches in the expectation that this would eliminate retrograde flow. The configuration of the nasal cannula from Test 2 is shown in FIG. 32B. As shown in Test 2 of FIG. 31, although the total volume of the retrograde flow may have been reduced, it has not been eliminated. Additional occlusion of the passage with a distance of 7 feet between the nostrils, as shown in FIG. 32C, had minimal additional impact, as shown in Test 3 of FIG. 31. Surprisingly, it was found that the only way tested that completely eliminated retrograde flow was when separate circuits were used to deliver NO to each of the nostrils (ie, a dual-channel delivery system).
[00239] The document attached to US Provisional Application No. 61/856,367, filed July 19, 2013, as Appendix 1, entitled "Exploratory Evaluation of Nitrogen Dioxide Formation in Candidate Nitric Oxide Delivery Lumena", examined the anticipated NO2 concentration to be present in the iNO delivery lumen of trilumen cannulas made of various materials. Appendix 1 attached to US Provisional Application No. 61/856,367, filed July 19, 2013 is incorporated herein by reference in its entirety; by extension, it is not inconsistent with the present invention. The experimental technique involved in the flow of 2440 ppm nitric oxide gas (equilibrium nitrogen) through multiple tubes (of three types of materials) arranged in parallel, so that proximal (based on the circuit without the tubes) and distal readings of the NO2 content of the effluent could be made using a NO2 bank of CAPs. Parallel tubes were used to improve the signal to noise ratio (ie, to increase the NO2 signal strength) of the data and a final mathematical calculation of the individual tube NO2 change was obtained. Nitric oxide flux through the parallel tubing banks was adjusted to achieve a residence time of 7.57 min/tube (eg, based on a 50 kg patient with dosage adjusted to 0.003 mg/kg*h with an 84-inch long, 0.076-inch inner diameter iNO manifold). The expected “per tube” NO2 increase for the three types of material tested is shown below.
Treatment Methods
[00240] The invention in this document can reduce retrograde flow, ensure accurate dose delivery and/or minimize NO2 formation and, used in conjunction with a delivery device, can be used for the treatment and/or prevention of hypertension pulmonary hypertension secondary to COPD and/or pulmonary hypertension such as PAH and/or pulmonary hypertension secondary to IPF and/or pulmonary hypertension secondary to sarcoidosis.
[00241] For safe and effective use, the disclosed cannula can be used with the disclosed delivery device, and the like, and/or nitric oxide. One of skill in the art will appreciate that the use of a cannula other than the disclosed cannula in conjunction with the disclosed delivery device, and the like, and/or nitric oxide may increase risks and/or reduce and/or eliminate effective use. Indeed, the cannula of the present invention may be needed to deliver nitric oxide to PAH, IPF and/or COPD.
[00242] Any of the nasal cannulas described in this document can be used in nitric oxide treatment to treat the appropriate diseases. For example, the cannulas can be for treatment with pulsed NO to treat chronic obstructive pulmonary disease (COPD) or pulmonary arterial hypertension (PAH). For these diseases, the delivery of proper dose amounts and the proper dose time can be very important. For COPD, NO may need to be pulsed early in inspiration, such as the first half of inspiration. If, for example, NO is not delivered in the right amount or at the right time, hypoxic reverse vasoconstriction can occur, which could worsen the patient's medical condition. Furthermore, the amount of dose can be very important for PAH, as sudden discontinuation of treatment can lead to serious conditions such as rebound hypertension. Thus, the significant dilution of the NO dose should be minimized for these diseases. Any of the cannula materials, configurations or methods described herein can be used to decrease the NO dose dilution during NO treatment.
[00243] In exemplary embodiments, the lumens (e.g., tubes) of the cannula may carry back to the patient and/or be secured together to produce a single central element between the cannula nosepiece and the device, which can provide a profile cut. It will be understood that when describing a plurality of lumens (eg two lumens, three lumens, four lumens, etc.) all lumens can be included in a single cannula.
[00244] In exemplary embodiments, the cannula elements can be fabricated using any of the techniques disclosed herein and/or using techniques known in the art. For example, cannula lumens (eg tubes), nose piece, key member, connectors, reducers and any combination and/or additional separation and/or any cannula elements described in this document can be manufactured using whether extrusion techniques, molding techniques and/or using any other manufacturing technique.
[00245] It will be understood that each nasal cannula lumen and/or collective nasal cannula lumen profile cut may have any shape, such as, for example, but not limited to, circular, parabolic, ellipsoidal, square, rectangular, triangular and/or any other profile cut shape and/or any other regular or irregular shape to minimize dose dilution. For the sake of ease, sometimes the cut profile and/or geometry is described as circular, parabolic and/or ellipsoidal and/or the cut profile is described as diameter, inner diameter or the like. This is merely for ease and is in no way intended as a limitation. When one or more areas of the cut profile are not circular, the ratio of the inside diameters can be the square root of the ratio of the surface areas of the two lumen sections.
It will be understood that any of the above forms can be used for the pulsed and/or non-pulsed delivery of a therapeutic gas (eg NO). For example, any of the above modalities that refer to pulsed delivery of a therapeutic gas, where applicable, can be used with non-pulsed delivery of a therapeutic gas and vice versa. For reasons of ease, sometimes reference can be made to the fact of being pulsed or non-pulsed. This is merely for ease and is in no way intended as a limitation.
[00247] Reference throughout this descriptive report to "a modality", "certain modalities", "one or more modalities", "exemplary modality" or "exemplary modalities" means that a certain feature, structure, material or characteristic described in connection to the embodiment is included in at least one embodiment of the invention. Thus, the appearance of phrases such as "in one or more modalities", "in certain modalities", "in a modality", "exemplary modality" and/or "exemplary modalities" in several places throughout this specification does not refer , necessarily, to the same modality of the invention. In addition, specific features, structures, materials and characteristics can be combined in any appropriate way in one or more modalities.
[00248] It will be understood that some of the steps described can be rearranged, separated and/or combined without departing from the scope of the invention. For the sake of ease, the steps are sometimes presented sequentially. This is merely for ease and is in no way intended as a limitation.
[00249] It will be understood that any of the elements and/or embodiments of the described invention may be rearranged, separated and/or combined without departing from the scope of the invention. For the sake of ease, sometimes several elements are described separately. This is merely for ease and is in no way intended as a limitation.
[00250] Although the present disclosure has been described in reference to 3 specific embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It will be apparent to those skilled in the art that various modifications and variations can be made to the methods and apparatus of the present invention without departing from the spirit and scope of the invention. Thus, it is intended that the present invention include such modifications and variations as are within the scope of the appended claims and their equivalents.

权利要求:
Claims (12)
[0001]
1. Nasal cannula for delivering therapeutic gas to a patient in need thereof, comprising: a first lumen, a second lumen and a third lumen: the first lumen being a nitric oxide lumen (1604) for delivering a first therapeutic gas comprising oxide nitric for a patient in need thereof; the second lumen being a trigger lumen (1606); and the third lumen being an oxygen lumen (1608) for delivering a second therapeutic gas comprising oxygen to the patient; and the nitric oxide lumen (1604), the actuation lumen (1606) and the oxygen lumen (1608) attached to a nasal cannula adapter (1602), the nasal cannula adapter (1602) allowing the separation of the flow passages to the patient for the nitric oxide lumen (1604) and the oxygen lumen (1608), such that nitric oxide and oxygen do not mix in the nasal cannula adapter, characterized by the fact that the nitric oxide lumen (1604) has an inner diameter that is smaller than the inner diameters of the trigger lumen (1606) and oxygen lumen (1608), but is larger than the inner diameter of the nitric oxide lumen in the nasal cannula adapter (1602).
[0002]
2. Nasal cannula according to claim 1, characterized in that the nasal cannula (i) is configured to reduce the dilution of one or more of the first and second therapeutic gases delivered to the patient or (ii) is configured to be placed in fluid communication with at least one system for delivering one or more of the first and second therapeutic gases, or both, to the patient.
[0003]
3. Nasal cannula according to claim 1 or 2, characterized in that the nasal cannula is configured to reduce the distribution of nitrogen dioxide to the patient.
[0004]
4. Nasal cannula, according to any one of claims 1 to 3, characterized in that it is configured for use in the treatment of pulmonary hypertension.
[0005]
5. Nasal cannula according to any one of claims 1 to 4, characterized in that it is configured for use in the treatment of at least one of pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), pulmonary hypertension such as pulmonary arterial hypertension (PAH), pulmonary hypertension secondary to idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension secondary to sarcoidosis.
[0006]
6. Nasal cannula according to any one of claims 1 to 5, characterized in that the first lumen of therapeutic gas to deliver the nitric oxide has a length between approximately six feet to eight feet with an internal diameter of approximately 0. 01 inches to approximately 0.10 inches.
[0007]
7. Nasal cannula according to any one of claims 1 to 6, characterized in that the nitric oxide flow passage in the nasal cannula adapter (1602) comprises a first pin, a second pin and a background, the first pin being in fluid communication with the second pin via the background, and the total volume of the first pin, second pin and background is less than 0.035 mL.
[0008]
8. Nasal cannula, according to any one of claims 1 to 7, characterized in that the cannula comprises a barrier material with a low oxygen transmission rate, which lies between
[0009]
9. Nasal cannula according to one of claims 1 to 8, characterized in that the nasal cannula additionally comprises a fourth lumen: the fourth lumen being another nitric oxide lumen to deliver the first therapeutic gas comprising nitric oxide to the patient; and wherein the first lumen delivers the first therapeutic gas to one nostril of the patient, and the fourth lumen delivers the first therapeutic gas to the other nostril of the patient.
[0010]
10. Nasal cannula, according to any one of claims 1 to 9, characterized in that it comprises one or more of the following characteristics: (i) at least one check valve in fluid communication with the first lumen of therapeutic gas, (ii) ) a cannula wrench, (iii) a sequestering material and (iv) a flexible support bridge.
[0011]
11. Nasal cannula according to any one of claims 1 to 8, characterized in that the first lumen is configured to deliver the first therapeutic gas to both nostrils of the patient.
[0012]
12. Nasal cannula according to any one of claims 1 to 11, characterized in that the third lumen is configured to distribute the second therapeutic gas to both nostrils of the patient.

类似技术:

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BR112015013095B1|2021-08-17|NASAL CANNULA FOR DISTRIBUTION OF THERAPEUTIC GAS TO A PATIENT

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法律状态:
2018-05-15| B25A| Requested transfer of rights approved|Owner name: THERAKOS, INC. (US) |

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2018-05-29| B25A| Requested transfer of rights approved|Owner name: MALLINCKRODT CRITICAL CARE FINANCE INC. (US) |

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2018-06-12| B25A| Requested transfer of rights approved|Owner name: MALLINCKRODT PHARMA IP TRADING D.A.C. (IE) |

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2018-06-26| B25A| Requested transfer of rights approved|Owner name: MALLINCKRODT IP (IE) |

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2018-07-10| B25A| Requested transfer of rights approved|Owner name: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED (IE) |

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2018-11-21| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-11-26| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2021-05-11| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-08-17| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 04/12/2013, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201261733134P| true| 2012-12-04|2012-12-04|

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US61/733,134|2012-12-04|

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US201361784238P| true| 2013-03-14|2013-03-14|

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US61/784,238|2013-03-14|

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US201361856367P| true| 2013-07-19|2013-07-19|

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US61/856,367|2013-07-19|

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PCT/US2013/073082|WO2014089188A1|2012-12-04|2013-12-04|Cannula for minimizing dilution of dosing during nitric oxide delivery|

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