Cannula for minimizing dilution of dosing during nitric oxide delivery.
Abstract
La presente invención se refiere en general a, entre otras cosas, sistemas, dispositivos, materiales y métodos que pueden mejorar la exactitud y/o precisión de la terapia de óxido nítrico por, por ejemplo, la reducción de la dilución del óxido nítrico inhalado (NO). Como se describe aquí, NO dilución puede producirse debido a varios factores. Para reducir la dilución de un destinado NO dosis, varias cánulas nasales ejemplares, las configuraciones neumáticas, los métodos de fabricación, y métodos de uso, etc. se describen.

Term
7.2 yearsleft in the term
Expires 4 December 2033.
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12 claims: 10 independent, 2 dependent
- 1Reivindicaciones 1. Una cánula nasal para el suministro de gas terapéutico a un paciente en necesidad del mismo, que comprende:un primer lumen, un segundo lumen y un tercer lumen: el primer lumen siendo un lumen de óxido nítrico para el suministro de un primer gas terapéutico que comprende óxido nítrico a un paciente en necesidad del mismo, el segundo lumen siendo un lumen de activación, y el tercer lumen siendo un lumen de oxígeno para el suministro de un segundo gas terapéutico al paciente;y el lumen de óxido nítrico, el lumen de activación y el lumen de oxígeno que se agregan a una cánula de puente nasal, la cánula de puente nasal que permite trayectorias de flujo separadas al paciente para el lumen de óxido nítrico, y el lumen de oxígeno de tal forma que el óxido nítrico y el oxígeno no se mezclan en la cánula de puente nasal, caracterizado en que el lumen de óxido nítrico tiene un diámetro interior que es menor que los diámetros interiores del lumen de activación y el lumen de oxígeno pero mayor que un diámetro interior de la trayectoria de flujo del lumen de óxido nítrico en la cánula de puente nasal.
- 2La cánula nasal de la reivindicación 1, en donde la cánula nasal (i) está configurada para reducir la dilución de uno o más d los primero y segundo gases terapéuticos suministrados al paciente o (ii) está configurada para ser 114 colocada en comunicación fluida con al menos un .......... suministro de uno o más de los primero y segundo gases de terapéutico al paciente, o ambos.
- 3La cánula nasal de las reivindicaciones 1 o 2, en donde la cánula nasal está configurada para reducir el suministro de dióxido de nitrógeno al paciente.
- 4La cánula nasal de cualquiera de las reivindicaciones 1 a 3, estando configurada para el uso en el tratamiento de la hipertensión pulmonar.
- 5La cánula nasal de cualquiera de las reivindicaciones 1 a 4, estando configurada para su uso en el tratamiento de al menos uno de hipertensión pulmonar secundaria a enfermedad pulmonar obstructiva crónica (EPOC), hipertensión pulmonar tal como la hipertensión arterial pulmonar (HAP), hipertensión pulmonar secundaria a la fibrosis pulmonar e hipertensión pulmonar secundaria a la sarcoidosis.
- 6La cánula nasal de cualquiera de las reivindicaciones 1 a 5, en donde el primer lumen de gas terapéutico para suministro de óxido nítrico es de aproximadamente 1.8288 metros (seis pies) a aproximadamente 2.4384 metros (ocho pies) de longitud teniendo un diámetro interno de aproximadamente 0.254 mm (0.01 pulgadas) a aproximadamente 2.54 mm (0.10 pulgadas).
- 7La cánula nasal de cualquiera de las reivindicaciones 1 a 6, en donde la trayectoria de flujo de óxido nítrico en la cánula de puente nasal comprende una primera punta, una segunda 115 punta y un plano posterior, con la primera punta fluida con la segunda punta por medio del plano posterior y el volumen total de la primera punta, la segunda punta y el plano posterior siendo menor que 0.035 mL.
- 8La cánula nasal de cualquiera de las reivindicaciones 1 a 7, en donde la cánula comprende un material de pared que tiene una velocidad de transmisión de oxígeno baja que está entre (¢¢)(0.02 54 mm) (¢¢)(0.0254 mm) 0.001 (24 hrs)(64516 mm 2 )(/lT M) ( (24 hrs)(100 in z )(XTM) ) y 10 (24ftrs)(64516mm J )(ATM) W(m«) ( (24 /trs)(100 ίη 2 )(ΛΤΜ)' )
- 9La cánula nasal de cualquiera de las reivindicaciones 1 a 8, en donde la cánula comprende, además, un cuarto lumen:el cuarto lumen siendo otro lumen de óxido nítrico para el suministro del primer gas terapéutico que comprende óxido nítrico al paciente;y en donde el primer lumen suministra el gas terapéutico a una fosa nasal del paciente y el cuarto lumen suministra el primer gas terapéutico a otra fosa nasal del paciente.
- 10La cánula nasal de cualquiera de las reivindicaciones 1 a 9, que además comprende uno o más de:(i) al menos una válvula de retención en comunicación fluida con el primer lumen de gas terapéutico, (ii) una llave de cánula, (iii) un material eliminador, y (iv) un puente de soporte flexible.
- 11La cánula nasal de cualquiera de las reivindicaciones 1 a 8, en donde el primer lumen suministra el primer gas terapéutico a ambas fosas nasales del paciente. 116
- 12La cánula nasal de cualquiera de las rei a 11, en donde el tercer lumen suministra el segundo gas terapéutico a ambas fosas nasales del paciente. 117
Independent claims12
465 paragraphs in 46 sections, as filed
(54) Title: CANNULA TO MINIMIZE THE DISSOLUTION OF THE DOSAGE DURING THE ADMINISTRATION OF NITRIC OXIDE.
(54) Title: CANNULA FOR MINIMIZING DILUTION OF DOSING DURING NITRIC OXIDE DELIVERY.
(57) Summary
The present invention generally relates to, among other things, systems, devices, materials, and methods that can improve the accuracy and / or precision of nitric oxide therapy by, for example, reducing the dilution of inhaled nitric oxide ( NOT). As described here, NO dilution can occur due to several factors. To reduce dilution of an intended NO dose, various exemplary nasal cannulas, pneumatic configurations, manufacturing methods, and methods of use, etc. They describe.
(57) Abstract
The present invention generally relates to, amongst other things, systems, devices, materials, and methods that can improve the accuracy and / or precision of nitric oxide therapy by, for example, reducing the dilution of nhaled nitric oxide (NO). As described herein, NO dilution can occur because of various factors. To reduce the dilution of an ¡ntended NO dose, various exemplary nasal cannulas, pneumatic configurations, methods of manufacturing, and methods of use, etc. are disclosed.
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PATENT TITLE No. 360652
MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Damastown Industrial Estate, Mulhuddart, Dublin 15, IRELAND
CANNULA TO MINIMIZE THE DISSOLUTION OF THE DOSAGE DURING THE ADMINISTRATION OF NITRIC OXIDE.
CIP: CPC:
A61M16 / 00; A61M16 / 06; A61M16 / 08; A61M16 / 10; A61M16 / 12; A61M16 / 20
A61M16 / 009; A61M16 / 06; A61M16 / 08; A61M16 / 10; A61M16 / 104;
A61M16 / 122; A61M16 / 125; A61M16 / 204: A61M16 / 208
FLANAGAN; SIMON FREED; JOHN KLAUS; THOMAS KOHLMANN; MARTIN
CRAIG
D. MEGLASSON; MANESH NAIDU; PARAG SHAH
REQUEST
Number:
MX / a / 2015/007017
International Presentation Date:
December 2013
PRIORITY
Country:
US
US
US
Date:
December 2012 March 2013 July 2013
Number:
61/733,134
61/784,238
61/856,367
Validity: Twenty years
Expiration Date: December 4, 2033
Issue Date: November 12, 2018
The reference patent is granted based on articles 1 ', 2 "section V, 6th section III. and 59 of the Industrial Property Law.
In accordance with article 23 of the Industrial Property Law, the present patent has a validity of twenty non-extendable years, counted from the filing date of the international application and will be subject to the payment of the fee to maintain the rights. .
Who subscribes e! This title is made based on the provisions of articles 6 fractions III and 7 'bis 2 of the Industrial Property Law (Official Gazette of the Federation (DOF) 06/27/1991. reformed ci 08/02 / 1994, 10/25/1996. 12/26/1997. 05/17/1999. 01/26/2004, 06/16/2005. 01/25/2006, 05/06/2009, 06/01/2010, 06/18/2010, 06/28/2010, 01/27/20'2, 04/09/2012, 06/01/2016 and 03/13/2018): Articles 1, 3 'section V subsection a), 4 and 12' sections I and III of the Regulations of the Mexican Institute of Industrial Property (DOF 14/12/1999, amended on 07/01/19 2002, 07/15/2004, 07/28/2004 and 09/07/2007); articles Γ, 3 ', 4 ·.<sup>r</sup>·· '· fiaccic- V iibso h). '6 i-: it; cit> iies I and III and 30 of the Organic Statute of the Mexican Institute of Industrial Property! (DOF 27/12/1999. Amended on 10/10/2002, 07/29/2004. 08/04/2004 and 09/13/2007): 1, 3 'and 5 "subsection a) of the Agreement that delegates powers in the Deputy Directors General. Coordinator. Divisional Directors. Holders of the Regional Offices. Divisional Deputy Directors, Departmental Coordinators and other subordinates of the Mexican Institute of Industrial Property. (DOF 12/15/1999. Amended on 02/04/2000, 07/29/2004, 08/04/2004 and 09/13/2007).
This letter is signed with an advanced electronic signature (FIEL), based on articles 7 BIS 2 of the Industrial Property Law; 3 of its Regulations, and 1 section: III, 2 section V, 26 BIS and 26 TER of the Agreement establishing the guidelines for the use of the Electronic Payment and Services Portal (PASE) of the Mexican Institute of Industrial Property, in the procedures indicated.
THE DIVISIONAL DIRECTOR OF PATENTS
NAHANNY CANAL REYES
<img file="MX360652B_D0001.tif" />
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Arenal No. 550, Floor 1, Pueblo Santa Mana Tepopan, Xochwaco,
Mexico City, (55) 53340700 www.goo.rnxftmpi
<img file="MX360652B_D0002.tif" />
MX / 2019/1350
CANNULATION TO MINIMIZE THE DISSOLUTION OF THE DOSII
1> Í LA ÍKOf 1WAD INDUSTRIAL
THE NITRIC OXIDE ADMINISTRATION
TECHNICAL FIELD
The present invention is generally concerned with improving the accuracy and / or precision of nitric oxide therapy, reducing dilution of inhaled nitric oxide, and / or securing mixing within the patient's nose.
BACKGROUND
Nitric oxide (NO) gas, when inhaled, dilates the blood vessels in the lungs, improves blood oxygenation, and reduces pulmonary hypertension. Because of this, some administer nitric oxide as a therapeutic gas in inspiratory respiratory gases for patients with pulmonary hypertension.
Typically, inhaled NO is delivered via a gas carrier from a high pressure source (eg, a pressurized cylinder) to the patient at or near ambient pressure via a breathing tube to the Ventilator Unit. Bound / Dependent Intensive Therapy or anesthesia patients or a nasal cannula for patients with spontaneous breathing. 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 dilution of the dose may occur.
Accordingly, there is a need for new methods and apparatuses for preventing dilution of the dosage in the supply line of a supply apparatus, as well as methods of manufacturing such apparatuses.
SHORT DESCRIPTION
Aspects of the present invention relate to the improvement of nasal cannulas that minimize flow and / or retrograde permeation of oxygen, air, and / or other gases during NO therapy while allowing delivery of NO to a or both nostrils of the nostril. Such cannulas can reduce the dilution of the delivered dose by using cannula materials and / or coatings that limit the diffusion of oxygen through the cannula walls and / or use cannula configurations to prevent the co-supply mixture from 02 and NO and / or reduce retrograde flow through the end of the patient's cannula.
Aspects of the present invention also relate to methods of minimizing dilution of the NO dose. Other aspects of the present invention relate to treatment methods using these cannulas and / or delivery methods. Other aspects of the present invention relate to methods of manufacturing multi-lumen cannulas and their nasal bridge cannulas.
In exemplary embodiments, a nasal cannula of the present invention may be for delivery of 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 can also include a nasal bridge cannula.
The first lumen may be able to supply
<img file="MX360652B_D0003.tif" />
therapeutic gas to a patient in need thereof, the second lumen may be able to transmit a pressure change to a pressure change sensor and / or the respiration sensor, the third lumen may be able to supply a second therapeutic gas to the patient, and / or the nasal bridge cannula may include separate flow paths to the patient in the first lumen, the second lumen, and the third lumen. At least one therapeutic gas can be nitric oxide.
In exemplary embodiments, a nasal cannula of the present invention can be used for the therapeutic delivery of gas to a patient. The nasal cannula can include a first lumen, a second lumen, and / or a third lumen. The first lumen may be a first therapeutic gas lumen for delivery of a first therapeutic gas to a patient, the second lumen may be an activation lumen, and the third lumen may be a second therapeutic gas lumen for delivery to the patient of a second therapeutic gas. In addition, a nasal bridge cannula can allow separate flow paths to the patient for the first therapeutic gas lumen, the activation lumen, and / or the second therapeutic gas lumen.
In exemplary modalities, 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 for delivery of the first and / or or second therapeutic gases to the patient. The nasal cannula can inhibit the mixture of nitric oxide and oxygen and / or the nasal cannula can reduce ..... of nitrogen dioxide to the patient.
In exemplary modalities, one or more of the patient's first and second therapeutic gases for the treatment of pulmonary hypertension. In exemplary modalities, the nasal cannula can deliver the first and / or second therapeutic gases 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 may be nitric oxide and the second therapeutic gas may be oxygen and / or the first therapeutic gas lumen for nitric oxide delivery may be less than the second therapeutic gas lumen for oxygen delivery. and / or the activation lumen. In exemplary modalities, the first therapeutic gas lumen may be for nitric oxide delivery and / or may be about 1.8288 meters (six feet) to about 2.4384 meters (eight feet) long having an internal diameter of approximately 0.254000 mm (0.01 inch) to approximately 2.54000 mm (0.10 inch). In exemplary modalities, the triggering lumen may be about 1.8288 meters (six feet) to about 2.4384 meters (eight feet) long having an internal diameter of about 1.2700 mm (0.05 inches) to about
5.0800 mm (0.20 inch).
In exemplary embodiments, the first therapeutic gas may be γ / nitric oxide or the nasal bridge cannula may include a nitric oxide flow path that may have an internal diameter that may be less than an internal diameter of the first therapeutic gas lumen.
In exemplary modalities, the first therapeutic gas may be nitric oxide and / or the nasal bridge cannula may include a nitric oxide flow path having a volume that may be less than about 10% of a minimum pulse volume of the Nitric oxide.
The cannula can include a wall material that has a low oxygen transmission rate that (cc) (0.0254 mm) (24 / irs) (64516 mm<sup>2</sup>) (ATM) ((ccymÍQ (24 hrs) (100 in<sup>2</sup>) (ATM)) and can be between 0.001 (ce) (0.0254 mm) (24 hrs) (64516 mm<sup>¿</sup>) (ATM) ((cc) (mil) (24 hrs) (ioo in<sup>2</sup>XATM) 'j
In exemplary embodiments, the cannula may further include a fourth lumen which may be another first therapeutic gas lumen for delivery of the first therapeutic gas to the patient.
Furthermore, the first lumen can supply the first therapeutic gas to one nostril of the patient, and the fourth lumen can supply the first therapeutic gas to another nostril of the patient. In exemplary embodiments, the cannula may include at least one check valve in fluid communication with the first therapeutic gas lumen, a cannula wrench, a scavenger material, and / or a flexible support bridge that cushions the patient's nasal septum.
<img file="MX360652B_D0004.tif" />
In exemplary embodiments, an invention cannula can be used for the delivery of therapeutic gas to a patient. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The first lumen may be a first therapeutic gas lumen for delivery of a first therapeutic gas to a patient, the second lumen may be an activation lumen, and / or the third lumen may be a second therapeutic gas lumen for delivery of a second therapeutic gas to the patient. The first therapeutic gas lumen, the activation lumen, and the second therapeutic gas lumen can be added to a nasal bridge cannula. The nasal bridge cannula can allow separate flow paths to the patient for the first therapeutic gas lumen, the activation lumen, and / or the second therapeutic gas lumen. The first therapeutic gas lumen may have an internal diameter that may be smaller than an internal diameter of the second therapeutic gas lumen and an internal diameter of the activation lumen and / or the first therapeutic gas lumen may have an internal diameter that may be larger than an internal diameter of the flow path for the first therapeutic gas lumen in the nasal bridge cannula.
In exemplary modalities, 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 delivery of the first and / or second therapeutic gases for the patient. The nasal cannula can inhibit the oxide mixture (7., IB ................
Nitric and oxygen and / or nasal cannula can reduce nitrogen dioxide to the patient.
In exemplary modalities, one or more of the patient's first and second therapeutic gases for the treatment of pulmonary hypertension. In exemplary modalities, the nasal cannula can deliver the first and / or second therapeutic gases 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 modalities, the first therapeutic gas lumen can be for nitric oxide delivery and can be about 1.8288 meters (six feet) to about 2.4384 meters (eight feet) long that has an internal diameter of about 0.254000 mm (0.01 inches) to approximately 2.54000 mm (0.10 inches). The activation lumen can be about 1.8288 meters (six feet) to about 2.4384 meters (eight feet) long that has an internal diameter of about 1.2700 mm (0.05 inches) to about 5.0800 mm (0.20 inches).
In exemplary modalities, the first therapeutic gas may be nitric oxide, and the nasal bridge cannula may include a nitric oxide flow path that has a volume that may be less than about 10% of a minimum pulse volume of the nitric oxide pulse. . The cannula can include a wall material that has a transmission rate of
<img file="MX360652B_D0005.tif" />
0.001 <<sup>2</sup> (cc) (mtl) (24 firs) (ioo ίη<sup>2</sup>) (ΑΤΜ)) and 10 (24 hrs) (64516 mm<sup>2</sup>) (XTM) (24 ftrs) (100 in<sup>2</sup>) (ATM) 'j
In exemplary embodiments, the cannula can include at least one check valve in fluid communication with the first therapeutic gas lumen, a cannula wrench, a catching material, and / or a flexible support bridge that cushions the patient's nasal septum. *
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 may be a first therapeutic gas lumen for supplying nitric oxide gas to a patient, the second lumen may be an activation lumen, and the third lumen may be a second therapeutic gas lumen for supplying one or more oxygen gases and air gas for the patient. The first therapeutic gas lumen, the activation lumen, and / or the second therapeutic gas lumen can be added to a nasal bridge cannula, the nasal bridge cannula can allow separate flow paths to the patient during the first therapeutic gas lumen , the activation lumen, and / or the second lumen of therapeutic gas. The flow path for the first therapeutic gas lumen for delivery of nitric oxide to the patient may have a volume in the nasal bridge cannula 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 internal diameter that can be smaller than the internal one of the second therapeutic gas lumen and an internal diameter of the activation lumen and / or the first therapeutic gas lumen can have an internal diameter that can be greater than an internal diameter of the flow path for the first lumen of therapeutic gas in the nasal bridge cannula.
In exemplary modalities, a method for treating pulmonary hypertension may include supplying nitric oxide gas to a patient in need thereof, in which nitric oxide can be delivered through a nasal cannula, in which the Nasal cannula 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 fibrosis idiopathic pulmonary (IPF), and / or pulmonary hypertension secondary to sarcoidosis.
In exemplary modalities, nitric oxide can be newly pulsed on inspiration and / or administered in the first half of inspiration. In exemplary modalities, nitric oxide can be delivered by pulsed inhalation to patients with spontaneous breathing, nitric oxide can be given at the start of inspiration, the nitric oxide dose can be approximately 0.010 mg / kg / hr, and / or the c supply at the start of inspiration through a pulse width of less than 260 milliseconds. In exemplary embodiments, the method may further comprise supplying the patient with oxygen.
In exemplary embodiments, a nitric oxide delivery method of the present invention can be used for the treatment of pulmonary hypertension. The method may include supplying nitric oxide gas to a patient, in which nitric oxide can be delivered through a nasal cannula. The nasal cannula can include a first lumen, a second lumen, and a third lumen. The first lumen may be a first therapeutic gas lumen for supplying a nitric oxide gas to a patient, the second lumen may be an activation lumen, and the third lumen may be a second therapeutic gas lumen for supplying oxygen gas to the patient. In addition, a nasal bridge cannula can allow separate flow paths to the patient during the first therapeutic gas lumen, the activation lumen, and / or the second therapeutic gas lumen. The second lumen may be to detect the onset of inspiration and / or a change in pressure.
In exemplary modalities, 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 for delivery of the first and / or patient's second therapeutic gases. The first therapeutic gas lumen for the supply of nitric oxide may be less than the therapeutic gas lumen for the supply of oxygen and the activation lumen. The first lumen of therapeutic gas may have an Inner Diameter Dimension that can be selected to be substantially small and thus reduce dilution of nitric oxide by reducing NO transit time through the cannula while also bei ng substantially lo Large enough not to cause significant back pressure and not to substantially distort nitric oxide pulses and / or the activation lumen may have a Dimension Inner diameter that can be selected to be substantially small, while also being substantially large enough to reduce delay and distortion of pressure signals. The nasal bridge cannula may include a nitric oxide flow path that may have an internal diameter that may be less than an internal diameter dimension of the first therapeutic gas lumen.
In exemplary performances, the cannula can include at least one check valve in fluid communication with the first therapeutic gas lumen, a cannula wrench, a catching material, and / or a flexible support bridge that cushions the patient's nasal septum. The cannula can include a wall material that has a low oxygen transmission rate (cc) (0.0254 mm) (cc) (mil) that can be between 0.001 (<sup>24ftrs</sup>)(<sup>64S16mm2</sup>) (4TM) ((2 + ζιη) (ΐοοίη<sup>2</sup>) (ΛΓΜ)) and 10 (cc) (0.0254 mm) (cc) (mU) (24ftrs) (645i6mm<sup>2</sup>) (4TM) ((24Ars) (iooίπ<sup>2</sup>) (ΛΤΜ) '). In exemplary embodiments, the cannula may further include a fourth lumen as the first therapeutic gas lumen for delivery of the first therapeutic gas to the patient. Furthermore, the first lumen can supply the first therapeutic gas to one nostril of the patient, and the fourth lumen can supply the first therapeutic gas to another nostril of the patient.
BRIEF DESCRIPTION OF THE DRAWINGS
The features 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, wherein:
Figure 1 shows an exemplary nasal cannula in accordance with the exemplary embodiments of the present invention;
Figure 2A shows an exemplary flow directionality of NO gas during delivery to patients, in accordance with exemplary embodiments of the present invention;
Figure 2B shows an exemplary retrograde flow path, in accordance with exemplary embodiments of the present invention;
Figures 3A and 3B show an exemplary mono-lumen cannula according to exemplary embodiments of the present invention;
Figures 4 and 5A show an exemplary double lumen cannula and / or exemplary pneumatic trajectories for NO, oxygen, and activation lumens, in accordance with exemplary embodiments of the present invention;
Figure 5B shows a bridge cannula of a double lumen cannula and / or pneumatic trajectories, in accordance with exemplary embodiments of the present invention;
Figures 6A and 6B show exemplary pneumatic trajectories for NO, oxygen, and activation lumens in a tri-lumen cannula, in accordance with exemplary embodiments of the present invention;
Figures 6C and 7 show exemplary nasal bridge cannulas of a tri-lumen cannula and / or pneumatic trajectories, in accordance with exemplary embodiments of the present invention;
Figures 8Ά and 8B show examples of pneumatic trajectories for NO, oxygen, and activation lumens in a four-lumen cannula, according to exemplary embodiments of the present invention;
Figures 8C and 8D show exemplary nasal bridge cannulas of a four-lumen cannula and / or pneumatic trajectories, in accordance with exemplary embodiments of the present invention;
Figure 9A shows an exemplary duckbill check valve in accordance with exemplary embodiments of the present invention;
Figures 9B and 9C show exemplary flapper and / or hinge check valves in accordance with exemplary embodiments of the present invention;
Figure 10 shows an exemplary nasal cannula with an umbrella valve or a flap valve for NO delivery, according to exemplary embodiments of the present
Figures 11A and 11B show examples of valves incorporated in the NO supply line, in accordance with exemplary embodiments of the present invention;
Figure 12 shows exemplary flow from a blocked nostril to another patient's nostril, in accordance with exemplary embodiments of the present invention;
Figure 13 shows the injection of NO into an ambient air flow in each nostril, in accordance with exemplary embodiments of the present invention;
Figures 14A-14B show exemplary configurations of dual channel supply systems, in accordance with exemplary embodiments of the present invention;
Figure 15 shows the components of the exemplary device for exemplary embodiments of a dual channel supply system, in accordance with exemplary embodiments of the present invention;
Figure 16 shows an exemplary nasal cannula with a nasal bridge for tri-lumen cannula, in accordance with exemplary embodiments of the present invention;
Figure 17 shows a tri-lumen nasal bridge cannula prior to assembly, in accordance with exemplary embodiments of the present exemplary invention;
Figure 18 shows an exemplary nasal tip of the tri-lumen mounted nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figures 19A-19B show a perspective and two-dimensional representation of a NO proximal lumen nasal tip within an activation lumen, in accordance with exemplary embodiments of the present invention;
Figure 20 shows an exemplary nasal cannula, in accordance with exemplary embodiments of the present invention;
Figure 21A shows an exemplary double D-shaped tube, in accordance with exemplary embodiments of the present invention;
Figures 21B and 21C show exemplary lumina having protuberances and / or geometric inserts, in accordance with exemplary embodiments of the present invention;
Figures 22A-22E are views of connecting pieces of exemplary nasal cannula device, in accordance with exemplary embodiments of the present invention;
Figure 23 shows an exemplary oxygen connecting piece, in accordance with the exemplary embodiments of the present invention;
Figure 24 shows an exemplary reducer and / or additional line holder, in accordance with exemplary embodiments of the present invention;
Figures 25A-C show various views of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25D shows a right front top perspective view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25E shows a bottom view of a
IMPI exemplary nasal bridge, according to modalidade - · .. * the present invention;
Figure 25F shows a top view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25G shows a first side view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25H shows a second side view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 251 shows a front view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25J shows a rear view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25K shows a right front top perspective view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25L shows a bottom view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25M shows a top view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25N shows a first side view of an exemplary nasal bridge cannula, according to <exemplary of the present invention;
Figure 250 shows a second side view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 250P shows a front view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figure 25Q shows a rear view of an exemplary nasal bridge cannula, in accordance with exemplary embodiments of the present invention;
Figures 26A-26D show cross-sectional views of various exemplary nasal bridge cannula ports in accordance with exemplary embodiments of the present invention;
Figure 27 shows exemplary fasteners in accordance with exemplary embodiments of the present invention;
Figure 28 shows an exemplary NO delivery device with a key slot and a nasal cannula with a holding element, in accordance with exemplary embodiments of the present invention;
FIG. 29 illustratively depicts exemplary retrograde flows during inspiratory respiration in conjunction with impulse delivery, in accordance with exemplary embodiments of the present invention;
Figure 30 illustratively depicts exemplary retrograde flows during both inspiratory and expiratory breathing, in accordance with exemplary embodiments of the present invention;
Figure 31 illustratively depicts exemplary retrograde flows for various exemplary cannula configurations, in accordance with exemplary embodiments of the present invention;
Figures 32A-32C show exemplary cannula configurations for Tests 1-3 of Figure 31, in accordance with exemplary embodiments of the present invention;
Figure 33A shows a right front top perspective view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 33B shows a front view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 33C shows a rear view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 33D shows a first side view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 33E shows a second side view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 33F shows a top view of an exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
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Figure 33G shows a bottom view of exemplary therapeutic gas delivery, in accordance with exemplary embodiments of the present invention;
Figure 34A shows a top left side perspective view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34B shows a top right perspective view in front of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34C shows a top view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34D shows a bottom view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34E shows a front view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34F shows a rear view of another exemplary therapeutic gas delivery device, in accordance with exemplary embodiments of the present invention;
Figure 34G shows a first side view of another exemplary therapeutic gas delivery device; in accordance with exemplary embodiments of the present invention; and
Figure 34H shows a second side view of another therapeutic gas delivery device according to exemplary embodiments of the present invention.
DETAILED DESCRIPTION
The present invention generally relates to, inter alia, systems, devices, materials, and methods that can improve the accuracy and / or precision of nitric oxide therapy by, for example, reducing the dilution of inhaled therapeutic gases such as nitric oxide (NO) and / or limiting mixing of inhaled therapeutic gases prior to delivery to the patient's nose. As described here, dilution of NO can occur due to various factors such as, but not limited to, mixing of NO with oxygen and / or air. To reduce dilution of a dose of NO intended, various exemplary nasal cannulas, pneumatic configurations, methods of manufacture, and methods of use, etc. are described. For example, the various exemplary nasal cannulas, pneumatic configurations, manufacturing methods, and methods of use, etc., of the present invention can reduce the mixing of NO with oxygen and / or air (eg, prior to be supplied to the patient's nose, etc.) thus reducing the dilution of the doses of NO intended.
Due to the unique nature of NO delivery, many factors must be considered to ensure the accurate and precise delivery of NO doses to the patient. Unlike the supply of other gases, such as oxygen (02), the dosage of NO can be particularly susceptible to uawa> <»íñ>
dilution because, among other things, the volume will be less than 1 ml (for example, a substantially small dose that can be lost even at room temperature) and / or can NOT be reactive with 02 present in the ambient air and / or co-administered with 02 producing nitrogen dioxide (N02). Furthermore, the NO supply time can also be more critical (for example, for efficiency) than the timing of other gases (for example, supply 02), so there is a need to reduce the dilution of NO and ensure that the initiation of a patient's respiration can be accurately determined as soon as possible and / or to ensure that the waveform of the NO dose is not Significantly distort during travel through the nasal cannula from the NO delivery device to the patient. In addition, it may need to be considered in the design of the nasal cannula, for example, because the nasal cannula can be used for extended periods of time for the comfort of the patient.
Various cannulas, systems, and methods of the present invention may be used, modified, and / or linked with various systems for the delivery of pharmaceutical gas to a patient and / or for the delivery of a pulse of pharmaceutical gas to a patient. For example, the various cannulas, systems, and methods of the present invention can be used, modified, and / or attached to at least the therapeutic gas delivery systems illustratively depicted in the figures. 33A-34H. The various cannulas, systems, and methods of the present disclosure may use, modify, and / or be linked to the teachings
<img file="MX360652B_D0006.tif" />
Use of US Patent No.: 7523752 titul ¿.. lx * method of supplying a pharmaceutical gas to a patient, content of which is incorporated herein by reference in its entirety.
Referring to Figure 1, generally, that of a NO delivery system (100) can be delivered to a patient through a nasal cannula (101). The nasal cannula (101) can receive NO at relatively low volumetric concentrations in a gas carrier of, for example, a therapeutic gas (eg, NO) delivery device (103) and / or the nasal cannula (101) can receive oxygen and / or ambient air (sometimes referred to simply as oxygen, 02, etc.) from an oxygen / ambient air supply (105). A commonly used gas carrier is nitrogen because nitrogen is not reactive with NO, but other inert carrier gases, such as helium, may be used.
Supplying the NO / N2 gas mixture (sometimes referred to simply as nitric oxide, NO, etc.) to the patient typically requires that the NO gas path from a high pressure source of NO (eg, a cylinder to pressure, pressurized cylinder attached with NO delivery device (103), etc., to the patient at or near ambient pressure, for example, via an attached ICU ventilator delivery tube / dependent and / or anesthesia patients and / or via a nasal cannula for spontaneously breathing patients. It will be understood that various techniques and / or embodiments of the invention described herein can be used for a delivery tube and / or a ca like other apparatus such as nasal pillows and / or nasal masks, to name a few. For ease, sometimes only one cannula is shown and / or described. This is merely for ease and is in no way intended to be a limitation.
This previously described NO transit will ideally 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 accomplished. Specimens, oxygen and / or ambient air may enter the supply system (100) at a number of points such as, but not limited to:
• During transit time within delivery device (103) (eg, due to oxygen diffusion through pneumatic interfaces such as elastomeric O-rings in the interior tires of delivery device, etc.);
• During the transit of the NO gas through the nasal cannula (101) (for example, as a diffusion through the cannula wall, nose cannula bridge, connectors, reducer, union joints, etc.) ;
• During the inhalation / exhalation cycle when a conduction pressure gradient can reverse the flow into the nasal cannula of the NO supply lumen producing a mixture within the nasal cannula (101) with ambient air and / or exhaled gas ;
i • During the inhalation / exhalation cycle when NO and Air / 02 mix in the patient's nostrils;
• During connection of the high pressure source (for example, a pressure cylinder, etc.) to the supply device (for example, as a cylinder replacement, small amounts of gas can be trapped in the pneumatic supply system, etc.) ; and • During the high pressure manufacturing cylinder filling operation the source of NO in which a substantially pure mixture of NO and gas carrier can be sought, but not easily achievable.
Dilution of NO during pulsed therapy can NOT be problematic because only a substantially small volume of NO can be administered to the patient. For example, gas that contains NO can be supplied in pulses that can be less than one (1) milliliter (mi). With substantially small pulse volumes, even small volumes of retrograde flow and / or diffuse gases can be significant, for example, due to the small dose it can NOT be easily diluted. Of course the larger volumes of NO can also be diluted.
Minimization of NO / O2 CONTACT BY DIFFUSION OF 02:
Minimization of NO TRANSIT TIME
One or more embodiments of the present invention relates to nasal cannulas targeting N0 / 02 contact sources (eg, one or more of the above NO / O2 contact sources) and thereby dilution. ....<sup>.</sup> by mixing NO with 02, etc.) of the intended dose of NO by minimizing the contact time of NO with 02, through the time of minimizing the transit time through the cannula, minimizing the transit of oxygen through the cannula walls, and / or minimizing the amount of 02 that comes in contact with NO. Referring to FIG. 1, addressing at least the dilution of NO of the intended dose, described in greater detail below, oxygen transit can be minimized through any lumina wall of the cannula (101) such as , but not limited to, the cannula walls associated with an activation lumen (104), the NO lumen (106), the 02 / air lumen (108), and / or any combination and / or additional separation of them, to name a few. Also, by targeting at least dilution of the targeted NO doses, oxygen transit can be minimized through any lumina wall of the cannula (101), such as, but not limited to, the associated cannula walls with a nasal bridge cannula (102), a key member (110), the reducer (112), connection piece (114), oxygen piece connection (116), and / or any combination and / or additional separation of them, to name a few.
Small DI Lumen
In one or more embodiments, the cannulas can be provided to include a smaller internal diameter (El) of the delivery tube / lumen for NO to, for example, reducing the dilution of the intended doses of NO.
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MEXICAN INSTITUTE ..... ...........................
Small DI tIctttM can reduce the transit time of NO molecules through the cannula. This in turn can reduce the time available for mixing with the oxygen that can diffuse through the cannula walls and the internal oxidation of NO to NO2.
For example, to reduce dilution of targeted NO doses by minimizing NO transit time through the cannula, the ID of the delivery tube / lumen for the
It can NOT be from about 0.254000 mm (0.01 inch) to about 2.54000 mm (0.10 inch) and / or about
0.7620000 mm (0.03 inch) to approximately 2.0320 mm (0.08 inch). In exemplary modalities, the delivery tube ID / lumen for NO can be selected to ensure reduced NO transit time (eg, reduction of NO dilution, etc.), while not resulting in significant back pressure and / or pulse shape NO distortion and / or waveform NO distortion (discussed in more detail below). In order to reduce transit time, as well as not significantly causing back pressure and / or distortion, the DI for the supply tube / lumen for NO cannot be substantially less than about 0.7620000 mm (0.03 inch), for example, for a cannula that has a length of approximately 1.8288 meters (six feet) to 2.4384 meters (eight feet). For shorter lengths a smaller ID can be used and / or for longer lengths a larger ID can be used as resistance
<img file="MX360652B_D0007.tif" />
distortion
<img file="MX360652B_D0008.tif" />
can
II be a function of both tube ID and length
In exemplary embodiments, the short tube / lumen DI for NO delivery (eg, such as nostril cannulas, shorter nasal cannulas, etc.) may have a substantially lower tube ID than for supply / lumen for NO, which can also have a small DI substantially as described above, with no significant back pressure and / or NO pulse shape and / or waveform distortion occurring.
In exemplary embodiments, the potential for the NO a 02 exposure time can be minimized using other techniques such as, but not limited to, increasing the rate of NO delivery through the NO lumen. The velocity of NO through the lumen of NO can be increased, for example, by increasing the pressure gradient within the system and / or by reducing the diameter of the tube. Although the speed of NO can be increased to reduce the exposure time from NO to 02, the speed can be forced to be minimized so that the pulse shape is not distorted substantially, the patient does not experience discomfort, and / or by factoring in any other competitive metric.
It will be understood that any of the above teachings (eg, the small ID for the lumen of the NO supply tube, etc.) can be combined with any of the other pneumatic configurations, cannula configurations, and / or teachings and / or or modalities described in this document. For example, previous teachings (for example
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for delivery tube / lumen for NO, etc.) can be used with the mono-lumen cannulas described below, the double lumen cannulas, tri-lumen cannulas, quadlumen cannulas, and / or any other teachings and / or modalities described in this document.
Materials to limit oxygen diffusion and / or remove 02 and / or
NO2
Today, many use polyvinyl chloride (PVC) and / or silicone as a common material for the construction of nasal cannulas; However, oxygen can diffuse through the lumen walls of these nasal cannulas. To minimize the oxygen contact that occurs due to oxygen diffusion, permeation, and / or transmission through the cannula walls, the cannula wall materials can be selected to minimize the diffusion rate oxygen, the permeability rate, and / or the oxygen transmission rate (TTO). In exemplary embodiments, the cannula wall may include a material with a low oxygen diffusion coefficient, permeability number, and / or oxygen transmission rate (TTO). For example, the cannula wall may include a material that can have an oxygen transmission rate (TTO) of from about 0.0002540cm (0.001 inch) to about 25.40000cm (10 inch). for example, using the following units:
(cc) (thousand) (24 hrs) (10Q in<sup>2</sup>) (ATM) (cc) (0.0254 mm) (24 hrs) (64516 mm<sup>2</sup>) (ATM) where:
cc refers to the cubic centimeters (mi) of oxygen that flows through a square of material;
One thousand refers to one thousand 0.0002540cm (0.001 inch) thick) of the square of material, which is equal to 0.0254mm;
ATM refers to the number of atmospheric pressure atmospheres;
hrs refers to the allowable duration for oxygen flow; and
64516mm<sup>2</sup> (645.1600cm<sup>2</sup>) (100in<sup>2</sup>) refers to the surface of the square of material.
Sometimes, when describing the diffusion of oxygen, permeability, and / or transmission through the cannula walls and / or materials of the cannula, only one of the diffusion rates, the coefficients of diffusion, permeability rates, permeability ratings and / or TTR. It will be understood that the reference to any of the previous terms, if applicable, can be used with and / or substituted by any of the previous terms, and the like. For ease of use, sometimes only one and / or some of the above terms are described. This is merely for ease and is in no way intended to be a limitation.
In exemplary embodiments, (eg, the material for the cannula tube, the nasal bridge cannula, etc.), cannula and / or miscellaneous materials can be adjusted to cope with permeation 02 along with patient comfort.
<img file="MX360652B_D0009.tif" />
ΜΡΙ
In exemplary embodiments, the cannulas are used using polyurethane and / or similar soft material. Exemplary embodiments, the polyurethane and / or similar soft material may include an additive to improve resistance to oxygen diffusion and / or tube coaxially positioned over at least part of the NO-filled cannula with a gas that provides resistance to diffusion of oxygen supply. The cannulas can be coaxially constructed and the lining of a tube and / or co-extrusion of two or more materials (eg, to form the tube, etc.). Of course other construction methods and / or techniques are within the scope of the description.
Examples of at least some of the materials that can be used for construction and / or that have desired oxygen permeability properties include, but are not limited to, polymers, such as polyvinylidene chloride (PVDC), ethylene, and alcohol vinyl (EVOH), polyamide (PA), polyvinylidene difluoride (PVDF), fluorinated polyurethane, Nylon 6, Nylon 12, and / or similar materials, to name a few. Furthermore, PVC can be used as the cannula material with one or more materials and / or additives, such as oxygen resistant polymers, which are 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 accomplished with co-extrusion dies and / or the use of other known techniques.
<img file="MX360652B_D0010.tif" />
They can take one of a number of potential forms, such as, but not limited to:
• homogeneous and / or individual material extrusions that can be used at least one material with low oxygen permeability characteristics;
• Co-extrusion of two or more polymers, one or more of the polymers that have low oxygen permeability characteristics;
• Surface treatment / surface coatings on the materials / tube with such coatings may have low oxygen permeability characteristics;
• The mixtures; and • Eliminators / Acquirers / Purifiers.
Extrusions of homogeneous and / or individual material with low oxygen permeability: In exemplary modalities, materials such as polyvinylidene chloride (PVDC, trade name Saran®), ethylene vinyl alcohol (EVOH), Nylon 6, Nylon 12, and / or any homogeneous and / or individual extrusions of material with low oxygen permeability can be used for the cannula material. Other materials are envisioned with these properties, and the use of compatible substitute oxygen permeation extrusion compatible material is within the scope of this invention.
Co-extrusions of two or more polymers: In exemplary embodiments, tube-in-tube and / or multi-ply configurations can be constructed using co-extrusions of two or more polymers. For example, two or more poi ........
minus one with low oxygen permeation properties, can be co-extruded (eg, using common co-extrusion methods known in the art) to construct a tube-in-tube or multi-layer sandwich configuration. The low oxygen permeability layer may include described herein (eg, polymers such as those listed in the previous section) and / or other polymers with similar characteristics. Since these polymers may or may not co-extrude with other polymers, it may be necessary to extrude an intermediate polymer or so-called tie layer. Exemplary co-extruded polymers can include, but are not limited to, PVC / EVOH / PVDC, PVC / EVOH / PFDF, fluorinated polyurethane / EVOH / PVDC, and fluorinated 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 / Nylonl2, bonding layer polymers, any combination and / or separation of themselves, and / or any other material that can be used with co-extrusions of two or more polymers.
In exemplary embodiments, the co-extrusions may be superimposed in a specific order, for example, to reduce oxygen penetration and / or diffusion and / or for construction purposes. For example, if an adhesive used (eg, in joining cannula components, etc.) joins PVC to PVC, then the outer layer of a co-extrusion exposed to such adhesive may be PVC. Furthermore, additional polymers (eg, which may have reduced water vapor contact properties) such as, but not limited to, EVOH may be sandwiched within water-resistant and / or hydrophobic inner and / or outer extrusion layers to minimize contact of the internal compound with steam.
Surface Treatment / Surface Coatings on Tubing: In exemplary modalities, 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 that can be layered thin (a few microns or less) thick. For example, the silica coatings can be from about 0.001 micron to about 10 microns and / or from about 0.01 micron to about 1 micron, and / or about 0.04 microns.
In exemplary embodiments, the silica coatings can be deposited on plastic in layers that can be substantially thin enough so that the flexibility of the plastic is not materially affected. It will be understood that any reasonable technique can be used for the deposition of said materials. For example, low-cost deposition can be achieved using the treatment of i>
chemical vapor deposition. Of course, or deposition of these coatings may also be used such as, but not limited to, electron beam and thermal evaporation, DC sputtering, plasma-assisted reactive spraying, any combination and / or additional separation thereof, and / or any technique capable of deposition.
In exemplary embodiments, other coatings such as, but not limited to, thermosetting epoxy-amine coatings, epoxy-amine coatings, etc. can be used. The coatings can be applied and / or provided using techniques described herein and / or known techniques.
Mixtures: In exemplary embodiments, the materials can be mixed together to obtain the beneficial properties of one or the other materials and / or used as a cannula material. In exemplary embodiments, nylon 6 and EVOH, which can be bonded together in co-extrusions without the need for a tie coat, can be used as a mixed cannula material. Other blends may include, but are not limited to, Nylon 6 with amorphous nylon and Nylon 6 with HDPE. Of course other blends can be used.
In exemplary embodiments, a posterior material can be coated over an anterior material. As an example, when two materials are not compatible with co-extrusion due to different melting temperatures, one polymer can be extruded first and the second polymer can be heated and coated on the first in a subsequent operation.
Eliminators / acquirers: In exemplary embodiments, scavengers can be coated inside the lumen (for example, by cooking the liquid in a liquid slurry of the scavenger inside the lumen, by condensing the scavenger inside the lumen by evaporation, absorption / adsorption to the inner surface of the lumen using a liquid or gaseous scavenger source, by chemical bonding of the scavenger to the inner surface of the cannula, etc.) and / or the eliminator can be packaged inside the connecting device and / or nasal bridge, for example, as a stopper (for example, a stopper with at least one hole to allow gas flow through it, etc. .) to remove oxygen and / or nitrogen dioxide. These scavengers can include, but are not limited to, compounds such as activated alumina, ascorbic acid, and / or any other scavenger. The potential drawbacks to this approach include the finite useful life of the removal material. This drawback can be overcome by factoring the duration of use of the cannula in the design. At least one possible additional drawback may be that any plug configuration for gas transit through a scavenger may distort the waveform of the gas. In view of these described plugs it can be designed to minimize such waveform distortion. Any method can be used to coat the inside 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 thereon so that it is then on the inner wall of the tube.
In exemplary embodiments, the activated alumina can be used in the cannula, for example, as a coating inside the lumen, as a plug accessory, and / or used in any other way, for example, to trap nitrogen dioxide. With a thin layer of coated alumina inside the lumen, the effect can not only be a reduction in the rate of oxygen permeation, but can also be successful in trapping nitrogen dioxide. Activated alumina and / or other scavengers can also be made in the form of a tight stopper in the tube, for example, in an area in close proximity to the patient's nostrils. The plug can be designed to minimize pressure drop and / or to maintain the shape of the nitric oxide pulse wave. The high activated alumina surface area can effectively wash nitrogen dioxide from the gas mixture. In addition, the remover 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 (for example, such that it can be removed when the cannula is changed) and / or the design life of the eliminator can be matched by duration of anticipated and / or actual use of the cannula.
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 ability, adequate pore sizes, sufficient physical strength for the shape to hold mpic ^ dI, and / or that cannot generate po. · ........ *;<sub>F </sub>materials that can be thrown or uncoupled from the cannula that can act on the capacity of the washing material. It is further understood that the internal filtrate can be used to contain spilled compounds to prevent aspiration into the respiratory system. Examples of wash materials include, but are not limited to, zeolites, silica-alumina, activated carbon / carbon, and adsorbents that may have solid base sites on the surface. For the sake of ease, activated alumina is sometimes described as a scrubbing material. This is merely for ease and is in no way intended to be a limitation.
In exemplary embodiments, a reducing agent can be applied to the surface of the wash material, for example, to improve its ability to trap and / or reduce nitrogen dioxide to nitric oxide. Such reducing agents include, but are not limited to, ascorbic acid.
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 / or additional separation of the same, and / or any other additive. The additives can work to remove oxygen and / or provide a barrier to permeation within the polymer matrix, either of which can result in the reduction of oxygen penetrating through the material. Oxidizable plastics (eg PET or polyamide) can react with oxygen that can be permeated through the polymer. Oxygen that can be permeated through the membrane can react with the oxidizable plastic before passing through the cannula and / or react with NO. Nanoclays (eg, which may tend to have a plaque morphology) can provide a barrier to permeation, eg, when properly dispersed within the polymer matrix. When dispersed, diffusion may need to occur around the plates, which can result in a tortuous path through the polymer, effectively reducing gas permeability.
It will be understood that any of the above teachings (eg, materials, etc.) can be combined with any of the other pneumatic configurations, cannula configurations, and / or teachings and / or modalities described herein. For example, the above teachings (eg, materials, etc.) can be used with the single-lumen cannulas described below, double-lumen cannulas, three-lumen cannulas, four-lumen cannulas, and / or any other teachings and / or modalities described in this document.
CONFIGURATIONS
Retrograde flow
Referring to Figures 2A-2B, it was surprisingly 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
IΜ ΡI flows into the nasal cannula (for example, in and / or cei; ··· .. * from the nasal bridge (200)). This gas flow in the nasal cannula can be between two nasal cannulas (eg, nasal cannulas (202) / (203)) by displacing the resident nitric oxide gas and / or pushing the nitric oxide gas out of the cannula so that displaced and / or pushed nitric oxide cannot be administered to the patient and / or can be mixed with the flow of gas and / or other gases, thus diluting NO in the intended dose. Furthermore, retrograde flow may depend on factors such as, but not limited to, the pressure difference between the nostrils during inhalation and exhalation. The pressure difference between the nostrils can 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), the placement of the nostrils, and the degree of imbalance between the nasal flow during breathing, to name a few. Accordingly, one or more embodiments of the present invention relate to nasal cannulas that can minimize retrograde flow and / or dilution resulting from retrograde flow in the nasal cannula.
As shown in Figure 2A, during normal pulse delivery, NO flows out of both nostrils (202) / (203) of the cannula nozzle (200). However, during at least the static phase between pulses, retrograde flow may occur. For example, during the static phase, ambient and exhaled air can flow in a circular motion and / or reverse flow through a hole in the chamber.
<img file="MX360652B_D0011.tif" />
and exits through the other nasal cannula port (203) as shown in Figure 2B.
This retrograde flow may result in dilution and / or lavage of NO in the nostrils and / or the flow path, which may cause a delay and / or reduction in the delivered dose. Furthermore, this retrograde flow can result in oxygen in the air and / or exhaled gas stream mixing with NO to a greater degree and / or reacting with nitric oxide in the nasal cannula, which can cause formation of NO2 that dilutes the concentration of NO. Therefore, to reduce retrograde flow (for example, which can result in the formation of N02 that dilutes NO doses and which can act as a known respiratory irritant, etc.), the volume of mixed nitric oxide potential either with exhaled gas and / or ambient gas it can be minimized.
Taking note of the foregoing, the amount of dilution resulting from retrograde flow may be dependent on the volume of the lumen associated with the supply of NO (for example, the lumen of NO; the lumen of combined and activation NO; lumen of combined NO, activation and 02 / air; etc.) in the nasal bridge cannula (eg, flow path), where retrograde flow may occur. The segment where retrograde flow can occur can be any shape. For ease, this segment where retrograde flow occurs is sometimes described as U-shaped, and the like. This is merely for ease and is in no way intended to be a limitation.
In exemplary modalities, the dimensions <
(eg, DI size, ID shape, etc.) of the lumen associated with NO delivery (eg, the lumen of NO; lumen of combined NO and activation; lumen of combined NO, activation, and 02 / air; etc.) in the nasal bridge cannula (eg, flow path) can be selected to reduce the volume of the U-shaped region thereby minimizing the volumetric potential exchange associated with flow and / or retrograde dilution resulting from retrograde flow. Furthermore, in exemplary embodiments, such optimal DI dimensions may vary as a function of the volume of NO gas delivered. As an 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 be lost due to retrograde flow.
One or more embodiments of the present invention limits the internal volume of this U-shape to no more than a small percentage (eg, 10%, 5%, 20%, etc.) of the minimum dose volume (eg. 0.035 ml for a 0.35 ml boost 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 phase) . Following the example above, for a minimum 10% dose volume of 0.035 ml, the ID of the lumen within the U-segment may be no more than 0.11684 cm (0.046 íñ>
inches) given a tooth length of 0.80 inches) and a nose gap of 1.60020 cm (0.63 inches). Therefore, for a lumen ID significantly greater than 0.11684 cm (0.046 inch) it may not be advantageous to maintain dose volume precision for minimum dose volumes of 0.35 ml.
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 higher volumes or lower minimum doses appropriately, systems with different tooth lengths, and / or tooth spacing systems, to name a few. One skilled in the art can perform the calculations necessary to determine the DI required to provide a desired volume in the U-shaped segment such that it does not exceed 10% of the dose volume. Furthermore, depending on the precision required for dosing, the internal U-volume or other available volume for cross flow may be, but is not limited to, less than 50%, 45%, 40%, 35%, 30%, 25 %, 20%, 15%, 10%, 5%, 4%, 3%, 2% or 1% of the dose volume, to name a few.
For example, if the U-shape is made up of two nostrils and a posterior plane, the maximum dimensions such that the volume of U does not exceed 20% of the volume of the minimum dose can be calculated using the following formula, in The baseplate refers to the length of the lumens within the nasal bridge cannula and / or that forms the base of the U-shape:
íñ>
Minimum dose Volume> 5 [2n (Tooth diameter) + π (Base plate Diameter / 2)<sup>2</sup> * (motherboard length)]
Therefore, if the minimum dose is known, the dimensions of the U-section of the cannula can be calculated. To dose accuracies other than 20%, the volume ratio factor of 5 can be changed accordingly with the volume ratio factor equal to [100 / (100% dose accuracy)].
In exemplary embodiments, during exhalation and / or prior to inhalation (eg, felt and / or detected by the delivery device, etc.) the U-shaped volume in the nasal bridge cannula can be purged with a pulse of NO substantially equal to the volume of U. This may cause the volume of U to fill substantially with NO (eg, after exhalation). In addition, this NO volume filler in U can be administered to the patient during the next inhalation, for example, ensuring early delivery of NO to the patient to provide optimal clinical efficacy (eg, as discussed below).
In exemplary modalities, retrograde flow can be reduced by at least reducing the DI of the NO delivery lumen at the nasal tip (eg, NO flow path) so that resistance to flow through the NO lumen at the tip nasal can be increased. By observing this configuration, under the same pressure differential, the flow into the NO lumen of the nasal tips can be reduced compared to teeth with a larger lumen. This may result in reduced cross flow under at least these conditions, for example, because the DI of the lumen d can produce resistance to gas flow that can be inversely proportional to the fourth power of the radius of the lumen by the law of Poiseuille.
In exemplary embodiments, retrograde flow can be reduced through the use of valves and / or check valves, for example, as discussed in more detail below.
Sometimes, the NO lumen described herein can be described as being optimized for a minimum impulse volume of 0.35 ml and / or 10% allowable error resulting in a permissible U-shaped volume in the NO lumen ( for example, 0.035 ml of dosage). In exemplary modalities, changes in this minimum pulse volume and / or the optimal range of pulse volume can affect at least the size of the NO lumen. For example, if the minimum pulse volume is lower due to, for example, using higher nitric oxide concentrations, the internal diameter of the NO lumen and / or U volume can be decreased to ensure the 10% target. of mistake. For example, the lumen and / or volume of U can NOT be decreased by considering various metrics for optimization such as, but not limited to, pulse shape. In addition, for example, the minimum pulse volume must be increased due to, for example, the use of a lower concentration of nitric oxide, so the internal diameter of the NO lumen and / or U volume can be increased. For example, the lumen and / or volume U of NO 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 lumen of NO and / or volume of large (for example, about 0.1 ml to about 0.5 ml) then small pulses of volume may not be able to be delivered accurately, delivery may be delayed, can occur. dilution, and / or other problems may occur due to the unique nature of the NO supply.
MINIMIZE DELAY AND / OR DISTORTION
In order for nitric oxide delivery systems (for example, which can propel nitric oxide gas to patients) to have optimal clinical efficacy, it may be necessary to deliver a pulse or flow of nitric oxide to the patient in the early inspiratory phase however possible and / or with a desired flow waveform (eg pulse shape). Taking note of this, delays can be pneumatic and / or should be minimized because, for example, patient pressure signals can be used as an indication of patient inspiratory effort and / or the beginning of patient inspiration. Furthermore, distortion of pulse or flow waveforms can be and / or should be minimized, since, for example, the shape and / or time of the waveform can be linked to clinical efficacy. Accordingly, one or more embodiments of the present invention relate to 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 they minimize distortion of flow waveforms.
In exemplary modalities, the cannula lumen attached to activation (eg, activation lumen; combined activation and NO lumen; combined activation, NO and 02 / air lumen, etc.) can be configured to minimize 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 lumen cross section attached with activation can be selected to reduce delay and / or distortion and / or size The cross section can be increased and / or maximized to reduce delays and / or distortions.
In exemplary modalities, the cannula lumen attached to the NO supply (eg, NO lumen; NO and activation lumen combined; NO, activation and 02 lumen / air combined; etc.) can be configured to minimize distortion flow of waveforms. To minimize distortion of flux waveforms from lumen cross section attached to the supply it cannot be increased and / or maximized and / or the shape of the cross section can be selected to reduce delay and / or distortion. In addition, in exemplary embodiments, to minimize distortion of the flow of NO-linked lumen waveforms, delivery can be done with reduced compliance, i.e., having greater stiffness. For example, to minimize flow distortion of waveforms, the lumen attached to the NO supply can be made of a substantially rigid material. The ι
Material stiffness can be selected eg compliance while still factoring in at least patient comfort.
COMPETITION METRICS
In at least some embodiments, the cannula can be configured such that at least one lumen can be for NO delivery and be for activation (eg, single-lumen cannulas, double-lumen cannulas, etc.). These settings may require optimization of the lumen for both NO delivery and activation to have minimal dilution of the NO dose, as well as to allow the activation signal to propagate to the device without substantial attenuation in the spectral band of respiration human (eg 0-4 Hz). This can be substantially difficult, as these may be the competing metrics for optimization. For example, in order to deliver a pulse and / or NO flow early in the inspiratory phase, reduce pneumatic lags, reduce flow waveform distortion, reduce delay and / or distortion of pressure signals , reduce the volume of NO mix and / or NO oxidation to the nostril, and / or address any other desired properties (for example, for a combined total of NO / activation lumen) various proficiency metrics of the lumen DI can be optimized such as, but not limited to:
to. Reduce NO2 formation -> Reduce lumen DI;
b. Maintain volumetric dosing accuracy
NO II -> Reduce lumen DI;
c. Reduce NO flow distortion -> Increase lumen DI; and
d. Minimize attenuation of the activation signal or delay -> Increase the lumen DI.
In exemplary embodiments, the cannulas of the present invention having combined NO / activation lumen configurations may require that the optimal geometry (eg, shape, size, etc.) of NO / activation lumen be involved for, eg, supplying pulses and / or NO flows in the early inspiratory phase, reducing pneumatic delays, reducing distortion of flow waveforms, reducing delay and / or distortion of pressure signals, reduce the volume of NO mixed in the mouthpiece, and / or oxidation of NO in the nostril. Such involvement may be necessary for cannulas of the present invention that have been combined with NO / activation lumen (eg, single-lumen cannulas, double-lumen cannulas, etc.). However, the cannulas of configurations of the present invention having at least three lumens (eg, three lumen cannula, four lumen cannula, etc.), as discussed below, may allow dedicated lumens to supply NO longer the trigger signal and may, in at least some cases, allow a dedicated 02 / air supply lumen. As such, for cannulas of the present invention with lumens dedicated to NO delivery and activation (eg, three lumen cannulas, four lumen cannulas, etc.), the optimized NO lumen may be less i. <sub>L</sub> j that the optimized activation lumen is already beneficial to have a larger activation lumen to ensure at least minimal signal attenuation, whereas it may be beneficial to have a smaller NO lumen to reduce at least NO dilution. As such, cannulas of the present invention having NO / activation lumen combinations (eg, mono-lumen, double-lumen cannulas, etc.) and cannulas of the present invention having dedicated NO lumens for delivery and Dedicated to activation lumens (for example, three lumen cannulas, four lumen cannulas etc.) can have different geometries when optimized.
By way of example, in addition to ensuring volumetric dosing accuracy (eg, described above with respect to minimizing dilution resulting from retrograde flow), the DI of the combination of NO / activation lumens can be designed to reduce and / or o not produce distortion of gas flow and / or undue delay in signal propagation, for example, from the patient to the device (for example, described above with respect to minimizing delay and / or distortion of pressure signals). Such distortion and / or delay can occur due to pneumatic tubes that can behave like first-order low-pass filters like tires and attenuate larger components of the frequency signal. Modifying the inside diameters can change the band-pass characteristics of the filtering effect. However, as noted above, the internal diameter (for example, in the U) can be set to a certain
Maximum ID based on the required supply accuracy of the system.
In view of at least the above, in exemplary modalities, to minimize the effects of the potentially attenuated frequency pressure signal: (1) the ascending diameter (near the device) of the combined NO / lumen activation of cannulas herein Invention can be adjusted to widen (eg, optimize) the pass band of the cannula features and / or (2) trigger the initiation of NO pulse delivery (eg, via the delivery device) may have the typical threshold pressure triggering strategy (for example, the pressure signal may be attenuated and / or delayed by the pneumatic filtering effect of the cannula construction) and therefore may be advantageous supplement / replace this trigger threshold pressure with a pressure trigger based on strategic triggering based on a sloping pressure pattern indicative of patient effort. Such pressure drop based on activation strategy in the presence of significant signal attenuation may be more responsive (eg, faster) to patient effort. It will be understood that to minimize the effects of potentially attenuated / delayed pressure, the combined NO / lumen descending diameter of the cannulas of the present invention can be adjusted to widen (eg, optimize) the band pass of the features combined cannula; however, this can produce an undesirable side effect of the bridge size>
The nasal cannula is increased, making the cannula less comfortable for the patient.
In exemplary modalities, the rising diameter of the combined NO / activation lumen can be adjusted to extend the band-pass characteristics of the cannula to ensure that the compressible volume that is not needed may not be available upstream of the fossa restriction nasal (for example, ID restriction of 0.1168400 cm (0.046 inch), etc.). This can reduce the compressible volume in the cannula and / or effectively increase the band pass characteristics of the cannula.
In exemplary modalities, activation of dose delivery (eg, by delivery device) may be based on a pressure pattern of slope indicative of patient effort and / or slope may be reduced in magnitude by characteristics of pipeline filtering, however, the slope may still be present for algorithmic trigger decisions (eg, by the delivery device). In exemplary modalities, activation methodologies may not be based on pressure thresholds, instead, triggering methodologies may be based on pressure slope trends that can also be used to improve the overall timely delivery of the dosage to the patient. It will be understood that an implementation of such activation may be optional.
MONO-LUMEN CANNULA
<img file="MX360652B_D0012.tif" />
Referring to Figure 3A, in modality the nasal cannula can have at least one lumen (i.e., a mono-lumen cannula (300)) that can deliver nitric oxide to the same lumen as used for oxygen delivery and / or activation of a delivery device (303). The use of the mono-lumen cannula (300), in a single lumen, oxygen and / or the ambient air flow (305) can be delivered to a patient with intermittently pulsed doses of NO (307) in the flow. This same lumen can also be used for activation. Using this technique, retrograde flow can be substantially reduced, for example, because 02 and / or air can effectively clean the nasal bridge to the cannula after each pulse of NO, or because the individual lumen can be a closed system. in the device after the valve is closed and therefore flow into the cannula lumen can be prevented. However, using this technique, oxygen and / or air (305) can be in contact with NO (307) within the lumen of cannula (300) and react (eg, forming N02) thereby diluting NO of the expected dose.
In exemplary embodiments, a gas carrier can be used as a buffer (eg, isolate) NO 02 and / or a gas carrier can be used to increase the effective volume of the delivered dose, eg, to reduce time NO transit in the cannula. This gas buffer can diffuse into the NO dose and / or surround the NO dose (eg, spatially before and after).
Referring to Figure 3B, in exemplary modalities, ι
> To reduce the dilution of NO (307) with the o: ”(305) within the NO / Lumen of 02, a buffering agent (309) can be supplied between NO (307) and oxygen (305). By way of example, the first oxygen can be supplied through the NO / lumen of 02, then a buffering agent (for example, an inert gas, nitrogen gas, etc.) can be supplied, then the NO can be supplied, then another buffering agent can be supplied, and then oxygen can be supplied. The buffering agent can reduce the interaction between NO and oxygen, thereby reducing the dilution of NO, for example caused by the formation of NO2.
In exemplary embodiments, by using a buffer gas to transport NO into the cannula the amount of contact between NO with 02 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 02 such that it can act as a buffer for any trapped 02 and / or the volume of gas delivered can be increased thereby decreasing the time that the NO dose is at cannula. In exemplary embodiments, the buffer gas may include oxygen, however the diameter of the cannula lumen may be small enough that the cross section of the NO dose exposed to 02 can be minimized and / or the diameter can be as small as Large enough to ensure that the dose pulse shape cannot be distorted substantially.
In exemplary embodiments, a buffer gas can be provided by using the age gas mixture left after an oxygen concentrator system that has removed 02 from the air.
It will be understood that the disclosed buffer can be used with any multi-lumen cannula (eg double lumen cannula, three lumen cannula, four lumen cannula, etc.) where NO and 02 can be supplied therein. lumen. For example, a double lumen cannula can have an activation lumen and a combined NO / Lumen of 02 where NO can be intermittently pulsed at 02 with a buffer that separates NO and 02.
In exemplary embodiments, the monolume internal diameter (eg, combined NO / Lumen of 02, combined NO / 02 / Lumen of activation, etc.) can be configured to be substantially small, for example, to reduce residual gas from the mixture. As previously discussed, lumens should include different functions (eg NO supply, activation, 02 supply, etc.) may have competing metrics for optimization. For optimization, the dimensions of the monolume cross section may require an engagement between at least some of these competency metrics. For example, because the mono-lumen has a combined N0 / lumen of activation and / or NO / 02 / lumen of combined activation, the optimal geometry (eg, shape, size, etc.) of the mono-lumen may require the involvement between at least some competence metrics for, for example, supplying pulses and / or NO flows in the early inspiratory phase, reducing tires, reducing distortion of flow waveforms, reducing the delay and / or distortion of the pressure signals, reducing the volume of NO mixed to the nasal bridge cannula, and / or oxidation of NO to the nasal bridge cannula. Considering at least the competing metrics for optimization, in at least some modalities, the internal diameter of the mono-lumen (for example, NO / Lumen of 02 combined, NO / 02 / Lumen of combined activation, etc.) can be less than about (0.1778000cm) 0.07 inch.
DOUBLE LUMEN CANNULA
Referring to Figure 4, in exemplary embodiments, the nasal cannula can have at least two lumens (i.e., a double lumen cannula (400)) that can deliver nitric oxide in a separate lumen (eg, NO lumen ( 404)) at least one lumen (406) that can supply oxygen (eg, from the oxygen / air supply (405)) and / or that can trigger the delivery device (eg, delivery device (403)) . The NO lumen can deliver therapeutic NO gas from a NO delivery device (403) to the patient (eg, in the activation cannula (402)). The two lumens can be added in a single nasal bridge cannula (eg, activation cannula (402)) which can have separate flow paths for each lumen.
In exemplary embodiments, the lumen (eg, of the double lumen cannula) carrying the gas-containing nitric oxide may have a substantially internal diameter that may be less than the other lumen (eg, the activation lumen, lumen of oxygen, etc.). In at least these modalities, having a substantially small internal diameter for the lumen transporting NO to the cannula can reduce dilution by at least the following mechanisms: (i) minimize the mixture of oxygen and NO due to a reduction in retrograde flow in small DI that carries NO with lumen due to smaller DI; (ii) minimize the volume of the mixing gas mass because the volume of NO gas per unit length can be reduced by having a small Lumen of NO DI; and / or (iii) a small lumen-bearing DI of NO that can produce a narrow stream of gas flow that can effectively minimize 02 / NO mixing during NO delivery and / or can minimize 02 / NO mixing during the delivery of NO to much further into the nasal cavity. Similar mechanisms for dilution reduction can be achieved by reducing the DI of the NO supply lumen used in other multi-lumen cannulas described in this document (for example, three lumen cannulas, four lumen cannulas, etc.). .
In exemplary embodiments, the diameter of the small lumens can be minimized so that it can be as small as reasonably possible without producing confusing upward effects on the device's flow delivery mechanics. For example, in one or more modalities, the NO lumen may have a DI in the range of approximately
<img file="MX360652B_D0013.tif" />
0.02540000cm (0.01 inch) to approximately inch) and / or from approximately 0.07620000cm approximately 0.2032000cm (0.08 inch).
Furthermore, in one or more modalities, the oxygen lumen and / or activation lumen (for example, the
DI in the range of about dedicated activation, etc.) can have a about 0.1270000cm (0.05 inch)
0.5080000cm (0.20 inch) and / or approximately .2032000cm (0.08 inch).
Referring to Figures 5A-5B, in exemplary embodiments, a double lumen cannula may have a first lumen (502) for supplying oxygen and a second lumen (504) for supplying NO and transmitting the signal. pressure for delivery device activation sensor (505). In this configuration, the first lumen (502) can transport oxygen from an oxygen concentrator / conservator (507) to the nozzle (506) of the cannula. The second lumen 504 can supply NO from the nitric oxide delivery device to the patient and / or can supply the trigger signal based on the patient's pressure to activate the sensor of the nitric oxide delivery device. Both lumens can be constructed to connect (eg, a tee) to both pits (508) / (510) and thus be in seamless communication with both the noses (508) / (510).
The first lumen can carry oxygen which is built with a lumen ID diameter geometry consistent with industry standards. For example, nasal cannulas with a nominal 6 bpm oxygen supply capacity can
have a lumen of oxygen and NO with a diameter of approximately 0.2032000cm (0.08 inch) at or near the nozzle. Accordingly, in one or more modalities, the oxygen lumen may have an internal diameter in the range of about 0.1270000cm (0.05 inch) to about
0.5080000cm (0.20 inch) and / or approximately 0.2032000cm (0.08 inch.)
The second lumen to carry NO and activation can be built on the basis of involvement of competition metrics (eg as mentioned above). For example, because the second lumen combines carrying NO and activation, the optimal geometry (eg, shape, size, etc.) of the second lumen may require engagement between at least some competency metrics, for example, supplying the pulses. and / or NO flows in the early inspiratory phase, reduce pneumatic delays, reduce distortion of flow waveforms, reduce delay and / or distortion of pressure signals, reduce the volume of NO mixed to the nasal bridge cannula, and / or the oxidation of NO to the nasal bridge cannula. Considering at least proficiency metrics for optimization, in at least some modalities, the combined NO lumen / activation lumen geometry of the double lumen cannula may be in the range of approximately 0.2032000cm (0.08 inch). In exemplary embodiments, the internal diameter of the second lumen may be dictated by volumetric dosing precision considerations, the second lumen may have a Di in the range
IMPI of about 0.02540000cm (0.01 about 0.2540000cm (0.10 inch), and / or the second lumens can have a DI in the range of about 0.02540000cm (0.01 inch) to about 0.1524000cm (0.06 inch) with risable piping adjust to optimize (for example, expand, etc.) the system's bandpass performance.
In exemplary embodiments, a double lumen cannula can have a first lumen for NO delivery and a second lumen for 02 delivery and transmit the pressure signal to the activation sensor of the delivery device. In this configuration, the lumen of NO can be substantially small (for example, having dimensions similar to those of the NO lumen (described below in a three lumen cannula) and / or 02 combined and causing the lumen to have an internal diameter in the range of about 0.1778000 cm (0.07 inch) to about 0.3556000 (0.14 inch) and / or from about 0.07620000 cm (0.03 inch) to about 0.2032000 (0.08 inch) in the nasal bridge cannula. In exemplary embodiments, a dual lumen cannula can have a first lumen for delivery of NO and 02 and a second lumen for transmission of the pressure signal to the activation sensor of the delivery device. In this configuration, the first lumen for delivery of NO and 02 can use similar techniques for delivery of NO and 02 to the same lumen, for example, as described herein with reference to a single-lumen cannula.
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THREE LUMEN CANNULA
Referring to Figures 6A-7, in exemplary embodiments, the nasal cannula can have at least three lumens (i.e., a three-lumen cannula (600)): a lumen that can supply nitric oxide to one lumen (for example , lumen of NO (604)), eg, from a delivery device (eg, delivery device (603)); another lumen which may be for activation of (eg, activation lumen (606)), eg, the delivery device (eg, delivery device (603)); and another lumen that can supply 02 in a lumen (eg, 02 lumen (608)), eg, from a 02 / air source (eg, conservative and / or concentrator (605)). All three lumens can be aggregated into a single nasal bridge cannula (eg, nasal cannula (602)) which can have separate flow paths for each lumen and / or at least one lumen.
The NO lumen may be a dedicated lumen that can transport therapeutic gas comprising NO from a NO delivery device (603) to the patient (eg, through the nostrils (610) / (612) to the cannula of nasal bridge (602)). The oxygen lumen can be a dedicated lumen that can carry 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) to the nasal bridge cannula (602)). The oxygen source may be a
<img file="MX360652B_D0014.tif" />
IMPI pulsation of oxygen (eg such as a ... - * oxygen) and an oxygen / constant flow device (eg such as an oxygen concentrator) and / or may be a port on the NO delivery device which provides the oxygen enriched gas. The activation lumen can be a dedicated lumen that allows the propagation of activation signals from the patient to the NO delivery device (603).
In exemplary embodiments, the nasal cannula can connect the oxygen lumen to an oxygen source (for example, an oxygen pulsation device, an oxygen conservator, a constant flow oxygen device, an oxygen concentrator, etc.) and / or the NO nasal cannula can connect the oxygen lumen to an oxygen source (for example, for patients not receiving supplemental oxygen). For patients who do not receive supplemental oxygen, the oxygen lumen may be removed and / or may be partially removed. For example, the oxygen lumen may be partially conserved to support the oxygen side of the cannula that goes around the patient's head while the lumen portion provides the connection to an oxygen source (for example, a flexible oxygen connection outside the reducer) can be removed. The removal and / or partial removal of the oxygen lumen can be done similarly for other multi-lumen cannulas described herein (eg, double lumen cannulas, four lumen cannulas, etc.).
Referring to Figures 6C and 7, an exemplary exemplary cannula, accessory suitable for bridging the pneumatic trajectories and / or lumens by partitions and / or diaphragms that can nasal and / or the nostril of the cannula. The can be separated being inside the bridge NO supply can cross the bridge through a lower gas resistance source to higher resistance holes that can be included in the nostrils cannulae. In exemplary modalities, each lumen can be separated by a diaphragm septum within the nasal bridge cannula and / or within the nostril cannulas to avoid mixing of fluid streams in the separate lumens.
All three lumens can be extruded through a single die producing a multi-lumen tube, can be extruded into a single multi-cavity extrusion, can be extruded separately, and fixed together in a para-tube arrangement described here, and / or using any other reasonable technique. Similar techniques can be used for other multi-lumen cannulas described in this document (eg, double lumen cannulas, four lumen cannulas, etc.).
Referring to Figure 7, in exemplary embodiments, the NO / tube supply lumen (604) can decrease in internal diameter (ID) at least once when it is about to, and / or just after, entering the nasal cannula (602). Consequently, in one or more modalities, the pneumatic resistance may be greater in the nostrils of the nasal cannula than in the tube that carries NO from the NO delivery device to the nasal bridge cannula. In exemplary modalities, the
IMPIC
INDUSTRIAL * .........
O σ »o ca (Λ h» of DI of the dedicated NO supply lumen may allow advantages such as, but not limited to:
• short gas transit times;
Inspiratory / expiratory reduction phase retrograde flow of ambient air in the example lumen, reduced according to the Knudsen diffusion which states that the diffusion rate is proportional to the mean length of free path of the gas molecule that can be reduced with smaller ID);
• Increased gas-to-gas resistance (for example, smaller ID tubes produce resistance to gas flow that can be inversely proportional to the fourth power of the tube's radius by Poiseuille's law); and • Reduction of the volume in the tee circuit of the NO supply lumen.
This can reduce the potential for retrograde flow, reduce the volume of retrograde flow, and / or reduce the contact and / or duration of contact between NO and other oxygen-including gases in the cannula, to name a few. This in turn can reduce the dilution of NO and / or therefore increase the precision of the delivered dose of NO. Accordingly, in exemplary modalities, the ID of the NO lumen may be from about 0.02540000cm (0.01 inch) to about 0.2540000cm (0.10 inch) and / or about 0.1778000cm (0.07 inch).
The lumen DI of NO can decrease from a maximum DI to a
Minimum ID, for example, to at least reduce cross flow and / or increase comfort of exemplary modalities, the ratio of the minimum DI to the maximum DI of the lumen of NO may 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 the minimum ID to the maximum lumen ID of NO can be used for other multi-lumen cannulas (for example, double lumen, three lumen, four lumen, etc.) described in this document that may have lumens. dedicated NO supply and / or combined NO supply and activation lumens.
The DI of the activation lumen can be comparatively much larger than the DI of the NO lumen. The DI of the activation lumen can be substantially larger so that the activation pressure drop to inhalation can be transmitted through this cannula lumen with the least possible loss of signal magnitude and / or phase delay to the device. NO supply which in turn can use this pressure signal to supply the NO pulse. Accordingly, in exemplary modalities, the ID of the activation lumen can be from about 0.1270000cm (0.05 inch) to about 0.5080000cm (0.20 inch) and / or about 0.2032000cm (0.08 inch). In exemplary modalities, the ratio of the DI of the NO lumen to the DI of the activation lumen may 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 :fifteen,
1:20, 01:25, and / or 1:30. to name a few.
The oxygen lumen can also be more ......
lumen of NO, for example, to minimize resistance to oxygen flow and / or to reduce the rate of gas flow in the nostrils which can serve to interfere with the activation pressure signal due to the effects of gas flow (eg, such as from the Bernoulli principle) and / or to reduce the high frequency (eg hearing range) of resonance with high-speed oxygen transit to reduce noise associated with oxygen delivery. Accordingly, in exemplary modalities, the ID of the oxygen lumen can be from about 0.1270000cm (0.05 inch) to about 0.5080000cm (0.20 inch) and / or about 0.2032000cm (0.08 inch). In exemplary modalities, the ratio of the DI of the NO lumen to the DI of the oxygen lumen may 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.
FOUR-LUMEN CANNULA
Referring to Figures 8A-8D, in the exemplary modalities, the nasal cannula can have at least four lumens (i.e., one four-lumen (800) cannula) - two lumens that can deliver nitric oxide in one lumen (for example , lumen of NO (804A) and (804B)), eg, from a delivery device (eg, delivery device (803)); another lumen which may be for activation (for example, activation lumen (806)), for example the delivery device (for
<img file="MX360652B_D0015.tif" />
<img file="MX360652B_D0016.tif" />
example, delivery device (803)); and another supply 02 in a lumen (eg, 02 lumen (808)), eg, from a 02 / air source (eg, conservative and / or concentrator (805)). All four lumens can be aggregated into a single nasal bridge cannula (eg, nasal bridge cannula (802)) which can have separate flow paths for each lumen and / or at least one lumen.
In exemplary modalities, such as the pneumatic configurations discussed above, this configuration can separate the pneumatic NO, oxygen, and activation pathways. Furthermore, in exemplary embodiments, the NO flow delivery paths to each nostril can be kept separate and distinct and / or have their own pneumatic supply source in the NO delivery device.
Referring to Figure 8D, an exemplary four lumen cannula having the above configuration can be constructed in the nasal bridge cannula where the four lumen cannula can fuse the lumen of the cannula into a single umbilical canal between the cannula of nasal bridge and device, for example, as can be done similarly with the three lumen cannula. Similar to the three lumen cannula (eg, as described with reference to at least Figure 7), the lumen / NO delivery tube (804A) and (804B) may decrease in internal diameter (DI) by at least once when they are about to, and / or just after, that the tube enters the nasal cannula (802). Consequently, in one or more modalities, the pneumatic resistance may be greater in the nostrils of the nasal cannula than in the tube that carries the NO delivery device to the nasal bridge cannula.
In exemplary modalities, the dimensions of the activation lumen (806), oxygen lumen (808), NO lumens (804A) and (804B) may be similar to the respective lumens in the three lumen cannula and / or the geometry of These lumens can provide similar benefits to those described above with respect to the three lumen cannula.
In addition to the above benefits, the four lumen cannula configuration can, among other things, prevent gas movement through the connected supply loop (eg tee) 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 four lumen cannula may require a dedicated pneumatic circuit for each NO lumen.
In exemplary modalities, the four lumen cannula configuration can include two activation lumens (for example, one for each of the nostrils), as well as a NO supply lumen and a 02 supply lumen. Of course other configurations are within the scope of the invention.
CHECK VALVES AND VALVES
In one or more embodiments, a nasal cannula (eg, single lumen cannula, multi-lumen cannula, any of the nasal cannulas described herein, etc.) may include one or more check valves that can be located in, and / or fluid with, the nitric oxide supply line. Furthermore, in exemplary embodiments, one or more check valves located in, and / or in fluid communication with, the nitric oxide supply line may be combined with any of the described multilumen configurations. Check valves can be used, among other things, to prevent retrograde movement of gas in the NO supply lumen during inhalation / exhalation. The check valves can be any low cracking pressure check valve that can be placed at some point and / or in fluid communication with the NO supply path. Such check valves may include, but are not limited to, duckbill valves, binder valves and / or any other valve.
With reference to Figure 9A, example of duckbill valve (902) and / or with reference to Figures 9B to 9C of the binder valves (904) illustratively illustrated that they can be used in accordance with the nasal cannulas of the present invention. These check valves may be miniature check valves, for example, so that they may be dimensioned to fit within the NO supply lumen and / or be in fluid communication with the NO supply lumen and / or may be constructed outside of the lumen itself by appropriate molding and / or splitting of the lumen outlet during the molding and / or manufacturing process.
Referring to Figure 10, in one or more embodiments, the NO delivery cannula and / or the lumen may have a small fin and / or glue check valve that can be located in the nozzle (1002) of the cannula and / or that may allow delivery of NO pulses to the general nose / mouth area during the NO pulse device. This configuration may allow NO to flow into one and / or both open nostrils by inhalation and / or may restrict retrograde flow into the NO lumen (eg, during exhalation). The 02 and / or activation lumen can be combined or kept separate from the NO lumen, for example, to reduce any adverse impact of the signal / noise ratio on the performance of the activation lumen due to oxygen flow. Such a flap valve configuration can prevent the retrograde flow of oxygen in the NO delivery path, thus reducing the potential for dose dilution. A diaphragm and / or other barrier can separate the NO supply line from the 02 / activation line in the nasal bridge cannula, for example, to avoid mixing.
In one or more embodiments, the nasal cannula can incorporate an impermeable and / or semipermeable membrane that can be movable or fixed and / or can be actively or passively moved when necessary. Furthermore, the membrane can separate the NO-containing gas or material from the 02 containing gas or material, for example, until the NO needs to be delivered to the patient. This membrane can reduce contact time, surface area, and / or rate of diffusion between NO and 02-containing gases. This can reduce NO2 formation, which can dilute the expected NO supply concentration.
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With reference to Figure 11A, in one or:
of the invention, a normally closed valve (1100) (eg, a duckbill valve, check valve, pressure valve, etc.) substantially at, and / or near the end of the NO containing cannula, the NO lumen and / or nostril can prevent air from coming into contact with the NO-containing gas inside the cannula, for example, until the valve opening can be activated (for example, a drop in pressure caused by the patient's inhalation or by the positive pressure caused by the delivery device when trying to deliver the NO-containing gas to the patient). When the valve opening is activated, NO can be delivered to the patient.
In one or more embodiments, a system may be used and / or provided to expel gas or other NO-containing material that comes into contact with 02 containing gas or material, which might otherwise have formed NO2 in this mixture. The system may then allow another part of the NO-containing gas or material having minimal or no N02 to be supplied to the patient.
Referring to Figure 11B, in one or more embodiments of the invention, the system and / or nasal cannulas may include and / or be in fluid communication with an electromechanical valve system (1104) that can drive, for example, pump a fixed or adjustable amount of gas mixture that can contain N02 through a separate hole in the cannula that opens to the patient. The system can then pump the gas or NO containing material to the patient.
It will be understood that any of the above teachings (eg, check valves, check valve configurations, membranes, valves, electromechanical valve systems, etc.) can be combined with any of the other pneumatic configurations, cannula configurations, and / or or teachings and / or modalities described in this document. For example, the above teachings (eg, check valve configurations, etc.) may be used with the single lumen cannulas or multi-lumen cannulas described herein and / or any other teachings and / or modalities described herein. .
MINIMIZE NO / O2 CONTACT DURING CONNECTION TO THE SOURCE
One or more embodiments of the present invention relate to nasal cannulas and / or systems that reduce contact NO / O2 during connection of the high pressure source (eg, a pressure cylinder, etc.) to the delivery device (eg one or more of the above sources of oxygen / contact NO) and thereby dilution of the intended dose of NO using a three-way valve. For example, the nasal cannulas and / or systems of the present invention may include a three-way valve with a port to the environment that can be configured so that the three-way valve opens to room temperature after the bottle is connected. to remove (eg blow off) oxygen.
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PROPORTIONAL SUPPLY OF THE NASAL HOLES
Referring to Figures 12-13, one or more embodiments of the present invention relate to nasal cannulas and / or systems that address the problem of drug loss (eg, to the environment) when dispensing a drug. gaseous (eg, in the form of pulsed nitric oxide, etc.) through a nasal cannula due to at least one partially occluded nasal passage (eg, as shown in Figure 12). By way of examples of such a problem, if one side of the nose (for example, the nose (1201)) is occluded (for example, occlusion (1203)) and the drug is being administered on both sides of the nose to through a cannula / delivery system (1200) that does not discriminate part of the drug that goes to any of the nostrils (for example, nostrils (1205)), then there can be no loss of the drug due to the occluded nostril . In addition, there may be other unintended consequences such as the reaction of the therapy gas that is not used with other materials and / or compounds that may come into contact with the gas.
Inadequate dosing may be a particular problem when the delivery of drug therapy in conjunction with limited amounts, such as when it was pulsed (for example, when it was synchronously administered to a patient's breathing pattern and rhythm) through a single lumen exiting the delivery device which in turn can then be broken down somewhere before reaching the patient. Furthermore,>
this may be a particular problem because, i of the drug through a single lumen is divided, then the dose can be equal or substantially equally divided into two streams regardless of the obstruction in the nose below the division. Thus, a significant part (eg, up to half) of the dose cannot be administered to the patient and / or may remain in the vicinity of blocked or obstructed nostrils.
One or more embodiments of the present invention relate to nasal cannulas and / or systems that solve or minimize the above problem by, for example, providing approximately proportional delivery of therapy to each of the nostrils with proportional delivery to the air and gas flow in the nostrils and / or inversely proportional to the resistance in the nostrils. This can be accomplished by using the motive force of the patient's breathing, which can be generally and approximately proportional to the air / gas flow rate in each of the nostrils, to divide and / or pull the gas of therapy that is proportionally in the patient's nose and subsequently in the patient's lungs. This system can deliver the dose to a patient in such a way as to ensure that the appropriately assigned or adjusted dose can be delivered proportional to the airflow in each nostril (or inversely proportional to the resistance of each nostril) such that the partial or complete blockage (either permanent or transient) of one or both nostrils does not affect the amount of drug administered to the patient.
For example, the cannula / lumen may be designed to deliver a desired amount of the therapeutic gas such that the administered dose can be injected and / or delivered in a flowing inspiratory air stream, driven by the patient's breathing, with such division of flow. , down from the drug delivery point, proportional to the amount of air entering each nostril or simply delivered to one nostril if the flow from the other nostril is below a predetermined threshold such that the drug delivered may also be proportionally and / or approximately proportional or directed to one or the other nostril in an all-or-nothing configuration based on the upper nostril flowing into said gas flow. Air flow in a stream to the patient can be achieved by having a flow path from the ambient air (for example through a simple hole in the nasal cannula) to each nostril such that this flow path crosses the point of supply / area / volume of the drug before moving on to the dividing point leading to each nostril.
In exemplary modalities, exemplary cannula / lumen configurations can allow delivery of NO to each nostril by injecting NO into a flow of ambient air to go to each nostril (eg, as shown in Figure 13) and / or the configurations may allow beneficial cross flow between the two nostrils to be designed and / or used to help guide the
NO to the unobstructed nostril (eg with Figure 12). The delivery cannula / lumen is designed to ensure that therapeutic gas cannot be entrained or transmitted out of the patient's airflow path. The delivery cannula / lumen and patient-inspired airflow path may be designed to ensure that delivery of the drug into the air stream cannot be impeded or accelerated by the creation of lower partial pressure or back pressure or other Harmful flow patterns at the point of drug injection into the ambient air stream. The delivery cannula / lumen, the inspiratory airflow path, the division of airflow in the nostrils, and the nasal bridges for the nostrils can be designed to ensure that there can be no adequate airflow compared to other sources of air or oxygen to the patient such that the drug can be entrained and carried in the nostrils proportional or substantially proportional to the air flow in the nostrils.
INDEPENDENT SUPPLY OF THE NASAL HOLES
One or more embodiments of the present invention relate to nasal cannulas and / or systems that address the problem of insufficient dosing due to a partially or completely blocked nostril, for example, detection and / or determination of the amount of driving force in each nostril and adjusting the amount of drug delivered to each of the nostrils. This can be accomplished by using
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to ensure proportional and / or substantially proportional dosing in each nostril.
Routing of at least dual, anterior canal systems (eg, that can work with multi-lumen cannulas, such as four-lumen cannulas) can utilize at least two independent flow channels: one for each nostril. In exemplary embodiments, these independent flow channels can have drug currents tailored to the inspiration of each nostril, for example, by configuring flow channels to supply flow proportional to the attraction of each nostril with full flow to both nostrils added to the appropriate dose and / or by configuring the flow channels to supply a single orifice that works (for example, high flow from the nostril) if the flow from the occluded nostril falls below a preset threshold.
Referring to Figures 14A-14B, in order to implement a dual channel system as such, it may be necessary to have two independent flow distribution channels coupled by a single (global) controller module (eg, a control module associated with a delivery device, etc.). Each of these distribution channels may require a pressure and / or flow signal from the particular nostril of interest, as well as the ability to supply the gas to the nostril. By way of example, as illustrated in FIG. 14A, the cannula (1400) can have detection lumens (1402) and separate lumen delivery (1404) nasal (eg, a double lumen cannula, three lumen cannula, four lumen cannula, etc.). By way of another example, as illustrated in Figure 14B, cannula (1410) may be combined for detection and lumen delivery (1412) for each nostril in which the activation or detection signal of respiration the drug can be determined and / or detected and delivered through the same lumen of the cannula (eg, a single lumen cannula, a double lumen cannula, etc.) as illustrated in Figure 14B.
Referring to Figure 15, in exemplary embodiments, pneumatic systems 1500 (eg, delivery device) may be required for the cannula to be implemented to support previous lumen configurations (eg, as described above) and / or may require configurations that have (1) a pressure sensor (1502) and / or an integral flow sensor (1504) that can control each channel independently or in pneumatic isolation and / or ( 2) a flow supply mechanism that could have 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 supply channel and / or a pressure switch valve and / or flow sensor that can toggle between distribution channels and / or determine and / or detect pressure and / or flow readings for each channel in
I> isolation. The pressure and / or flow can be exemplified, using the pressure sensor (1502), integral flow sensor (1504), etc.) independently and / or differentially using one or more sensors. Furthermore, one or more valves may be actuated (eg, independently, in tandem, proportionally, etc.) to supply the appropriate amount of therapeutic gas.
In exemplary embodiments, the pneumatic channels can be controlled by a controller and / or an integrated (global) controller module that may be capable of independent control of the two channels, for example, to ensure adequate overall dosing. This controller can receive input from the pressure or flow sensor (for example, two separate pressure sensors, a single pressure sensor that can obtain the two measurements of the pressure in isolation, etc.) and can control both solenoid to achieve proper dosage.
MANUFACTURE OF MULTI-LUMEN NASAL CANNULAS
As described above, the individual lumen of a multi-lumen cannula can be manufactured separately and then affixed to each other (eg tube arrangement, etc.) and / or multiple lumens can be extruded through a single die which produces a multi-lumen tube.
According to one or more modalities, the multi-lumen nasal bridge cannula of the multi-lumen cannulas described herein can be manufactured using molding techniques.
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For example, the cannula can be fabricated for a three lumen nasal bridge t to separate oxygen, nitric oxide, and activation lumina.
Referring to Figure 16, in one or more modalities, the nasal bridge cannula (1602) for a three lumen cannula may include three lumens, two lumens with inner diameters of approximately 0.2032000cm (0.08 inch) (for example, for oxygen lumen (1608) and activation lumen (1066)) and a lumen with an internal diameter less than about 0.1143000cm (0.045 inch) (for example, for nitric oxide lumen (1604)). This configuration cannot be easily molded by typical injection molding techniques, for example, such as small lumens that may require an injector holder (approximately 0.1143000cm (0.045 inch outside diameter) that may be too small to be robust) for example, capable of supporting a substantially large number of parts without bending) in a molding tool designed for many uses.
Referring to Figure 17, at least two halves (eg, (1701) and (1702)) in urethane, PVC, silicone, and / or can be used to fabricate the multi-lumen nasal bridge cannula of a mold another low hardness elastomer with the inner part of the large lumen (1704) and (1705)) (for example, oxygen lumen, activation lumen, etc.) being defined by the larger injector / core fasteners (outer diameter of approximately 0.2032000cm (0.08 inch)) and with small medium lumen fissures (for example, (1706) and (1708)) defining the small lumen (for example, the lumen of NO). They can then be folded and joined together, preferably with a residue-free joining technique such as RF welding and / or solvent bonding, to form a nasal bridge cannula.
In exemplary embodiments, to circumvent the limitation of the injector holder with the small lumens of DI being defined by fissures in the halves, the two halves can be molded flat in a single run, for example with a band (for example, the bands (1709)) that holds the halves together and provides rough alignment during the folding and joining process. The molded halves may, in some cases, include integral cylindrical holes and the coupling flanges or other complementary members (for example, the flange (1710) and the companion flange (1712)) so that the halves can be properly aligned when fold together. The tape may also be optional, for example, if the appropriate complementary indexing members on the two halves ensure that the two parts that form the outer wall of the NO lumen can be properly aligned. The mounted nasal bridge cannula can allow three lumen inlets and can be connected (eg, tee) to each inlet lumen within the inside of the appropriate nasal bridge cannula. Of course, the nasal bridge cannula can be constructed using any reasonable technique. As an example, a nasal bridge cannula with a substantially small NO lumen can also be constructed using liquid silicone rubber injection molding (eg, a
<img file="MX360652B_D0018.tif" />
pressure at which a more robust mold tool can be achieved), and / or the use of a low molding pressure technique. Furthermore, a nasal bridge with a substantially small NO lumen can be constructed using micro-molding techniques known in the art that can be used for high-resolution production of small parts, including parts with small mold fasteners. Examples of a nasal bridge cannula with a substantially small NO lumen can be constructed using micro-molding techniques known in the art.
Referring to Figure 18, a perspective view of the nasal receptacle (eg, nasal receptacle (1716)) of the muiti-lumen nasal bridge cannula of Figure 17 is illustrated illustratively after the two halves have been assembly.
The lumen ID can be adjusted as described above. For example, the ID of the oxygen lumen can range from about 0.1270000cm (0.05 inch) to about 0.5080000cm (0.20 inch), the ID of the activation lumen can range from about 0.1270000cm (0.05 inch) to about 0.5080000cm (0.20 inches), and the lumen ID of NO can vary from about 0.02540000cm (0.01 inch) to about 0.2540000cm (0.10 inch). In one or more modalities, the DIs for the oxygen lumen and the activation lumen can both be in the range of about 0.1778000cm (0.07 inch) to about
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0.2286000cm (0.09 inch) and / or approximate meri (0.08 inch) and the lumen ID of NO can be in the range of about 0.08890000cm (0.035 inch) to about 0.1397000cm (0.055 inch) and / or about 0.1143000cm (0.045 inches).
Referring to Figure 19A-19B, within and / or before the nasal receptacle (1900) the small lumens of NO (1902) may be proximal to and / or within the larger activation lumen (1904), for example, so that any larger activation lumen tip lock (for which there cannot be no purge capacity) can be blown out / ejected by the NO pulse function. The geometry can be designed to ensure that all, and / or substantially all, of the NO in the largest activation lumen can reach the respiratory system during inspiration and / or not be left behind so that it can be pulled out during exhalation.
EXAMPLE NASAL CANNULA
Referring to Figure 20 according to exemplary modalities, a nasal cannula (2001) is shown including three separate lumens for oxygen delivery, NO delivery, and for activation of respiration. The nasal cannula may include a nasal bridge cannula (2002) for the interface with the patient's nose. The lumen of NO (2003) and the activation lumen (2004) carry NO to the patient and transmit the pressure signal, respectively. The NO lumen (2003) and the activation lumen (2004) can be both tubes (for example, D-shaped tubes), in such a way that their tubes combine a single para tube tube (2003) / (2004). The paratubo (2003) / (2004) can be connected to the NO supply device by connecting part of the nasal cannula (2014). The nasal cannula (2001) may further include the brace member (2010), reducer (2012), and / or nasal oxygen connecting bridge (2016) which is discussed in more detail below.
Referring to Figure 21A, the paratubal may be made of two tubes (eg, two D-shaped tubes). By way of example, the D-shaped tubes can be extruded separately and / or joined in a subsequent operation, for example, by adhesion (for example, adhesive, glue, etc.) and / or bonding (for example, heating , fusion, etc.) to form a single para-tube that may appear to be a single tube. Furthermore, the flat interface between the tube halves can be altered to have a flange and slot type configuration that allows easy alignment of the tubes with each other for subsequent joining operation. By way of another example, the D-shaped tubes can be extruded in a single operation and later split at the ends (eg using a splicer). Furthermore, D-shaped tube extrusions can be of the same materials and / or different materials. For example, the D-shaped NO tube may be constructed of oxygen resistant materials and / or the other D-shaped tube may be constructed of PVC and / or other materials commonly used for tube construction. The tube (2003) / (2004) can be connected to the NO supply device by the connection piece of
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Referring to Figures 2IB and 21C, in exemplary modalities, the internal diameter of the tubes (eg, NO lumen (2003), activation lumen (2004), oxygen lumen (2008), combined lumens, etc.) and / or paratubes may include geometric protrusions (eg, cores, ribs, etc.) and / or inserts (eg, flanges, etc.) to prevent complete occlusion of the tube, eg, due to flange formation in tube and / or tube compression. These geometric protuberances can be radially spaced so that they can be symmetrically and / or asymmetrically located within the tube and / or paratubo.
Referring to Figures 20 and 22A-22E, the nasal bridge cannulas (2014) can be constructed to ensure smooth communication between the patient and the device. The connecting piece can be connected to the device and / or can be designed in such a way that a unidirectional connection may be necessary (for example, in such a way that it cannot be installed backwards). In addition the connecting piece may include additional features, such as, but not limited to, a color print and / or differentially reflective area that can be used with IR detection / sensor to confirm insertion and / or the connecting piece can include a strain relief component (2202) (for example, as shown in Figures 22C-22E), which may be integral to the connecting piece, to prevent twisting of the tube, for example, as the tube comes out of the connector. Of course, other techniques can be used to ensure intersection detection. The nasal cannula connecting piece (2014) may include substantially smooth ribs and / or exteriors to aid in at least element handling and removal; releasing stresses, for example, which can be to prevent sprains. The connecting piece of the nasal cannula (2014) can be constructed to ensure that the connector seats in its cavity can be detected or seen by the user; to name a few.
Referring to Figures 20 and 23, in exemplary embodiments, the oxygen connecting piece (2016) may allow connection to external oxygen supply devices such as, but not limited to, oxygen conservators and / or concentrators. The oxygen connection piece (2016) can be designed with industry standard dimensions, for example to ensure ease of use and / or connection with oxygen supply devices. Also, the oxygen lumen (2008) can be connected to an oxygen conservator or other oxygen supply device by the oxygen connecting piece (2016).
Referring to Figures 20 and 24, the NO lumen (2003), activation lumen (2004), and the oxygen lumen (2008) may each have a smaller inner and / or outer diameter by the bridge cannula. nasal (2002) than in the relative connection pieces (2014) and (2016). Accordingly, a reducer (2012) having different dimensions and / or cross section profiles can be used. In addition, the reducer (2012) can also be used to terminate the oxygen lumen <„when no oxygen braid cable is provided, by receiving ambient air within the cannula and / or when the nasal cannula is not connected to an oxygen source, to name a few.
In exemplary modalities, tubes (eg, NO lumen (2003), activation lumen (2004), oxygen lumen (2008), combined lumens, etc.) can be attached to the nasal bridge cannula (2002) and / or device connector (eg, connecting pieces (2014) and (2016)) using any technique such as, but not limited to, bonding, adhesives (eg, epoxy, cyanoacrylate, etc.), solvent bonding , insert molding, and / or by any other technique.
Referring to Figure 24, the reducer (2012) may allow a transition between, and / or connection between, tubes of different dimensions (eg, different outside diameters, different inside diameters, etc.) so that the tubes, for example , closest to the patient, can be optimized for patient comfort (eg increased flexibility, reduced outer diameter dimensions, etc.) and / or so that the pneumatic performance of each lumen of the cannula can optimize the use of multiple diameters, for example, to optimize patient comfort by minimizing the diameters of tubes located proximal to the patient's head.
NASAL BRIDGE * i
Referring to Figures 25A-25Q, different exemplary nasal bridge cannulae (2002) are shown illustratively. Figure 25A shows the nasal bridge cannula (2002) side where the oxygen lumen (2008) connects to the cannula (2002). Figure 25B shows the two D-shaped openings for the NO lumen (2003) and the activation lumen (2004). Figure 25C shows each tip of the nasal cannula connecting piece having a central lumen for NO and two outer lumens for oxygen and activation.
In exemplary embodiments, the nasal bridge cannula and / or at least some of the nasal bridge cannula and / or cannula may have material properties (eg, durometer, etc.) selected to provide guaranteed comfort while providing structural and pneumatic integrity (eg, of the nasal bridge cannula, at least some of the nasal bridge cannula, at least some of the cannula, etc.). For example, to provide comfort while ensuring structural and pneumatic integrity, the nasal bridge cannula and / or at least some of the nasal bridge cannula and / or cannula can have from about 30 to 70 durometers and / or about 50 durometers (Shore A).
In exemplary modalities, the nasal bridge cannula (2002) can include three lumens in a tornado design (2515) that can allow sufficient stiffness for the nostrils, yet allow the nostrils to be partially compressible, for example, because the dividing lines for the oxygen lumen (2008) and activation lumen (2004) íñ>
they can be offset (eg, non-aligned lumen center of NO supply (2003)). This compressibility can allow the nose tip to be more flexible and comfortable than other three lumen cannula tip designs.
In exemplary modalities, the tornado can also encapsulate the smallest NO lumen (2004), the nostrils can be designed to ensure optimal and / or desired insertion distance, and / or to increase the comfort of the nasal cannula that can be tapered from bottom to end and / or may be arched (for example, inward toward nasal openings). In exemplary modalities, this optimal and / or desired insertion distance may be from about 0.2540000cm (0.1 inch) to about 1.524000cm (0.6 inch) and / or about 1.016000cm (0.40 inch).
In exemplary embodiments, the delineated geometry of the oxygen lumen (eg, in the nasal bridge cannula) may be designed to reduce auditory frequency noise (eg, approximately 20 Hz to 15 kHz) by, for example, narrowing the oxygen lumen output. In addition, noise reduction can also be achieved by modifying the oxygen transport lumen durometer to prevent oscillation of the hearing range and noise due to oxygen flow and / or by selecting an oxygen lumen geometry that does not generate noise (for example, vibration, resonance, etc.).
Referring to Figures 26A-26C, the cross-sectional views show various configurations and nasal cannulas. For example, Figure 26A illustratively depicts a tornado pattern. Figures 26B-26D illustratively depict additional configurations that may include at least some of the benefits described for the tornado configuration. For example, other configurations may allow sufficient stiffness for the nostrils and may allow the nostrils to be partially compressible and / or other configurations that may provide at least some of the aforementioned above-mentioned benefits that are within the scope of this invention.
In exemplary modalities, the outside diameter of the nasal bridge cannula nostrils can be minimized to increase patient comfort. Taking this outer dimension into account, the dimensions of the various lumens (eg, activation lumen, NO lumen, 02 lumen, etc.) can be selected to not only be optimized (eg, as discussed herein document), it can also be limited in size to consider patient comfort. For example, although optimizing nostrils with a larger outside diameter may be beneficial (for example, an outside diameter of approximately 0.6350000cm (0.25 inches or more), the cannula nostrils may have an outside diameter of less than and / or approximately 0.5080000cm (0.2 inch) for patient comfort.
As an example, taking into account the patient's comfort, as well as at least some and / or all the parameters for
IΜ ΡI the optimization described in this document, a
INDUSTRIAL ......... βΓ · * lumens (for example, with a length of approximately 2.133600m (7 feet) you can have tubes with a lumen of NO that has an ID of around 0.001752600m (0.069 inches) , an activation lumen that has an ID of around 0.002260600m (0.089 inch), and a 02 lumen that have an ID of around 0.002260600m (0.089 inch) with at least some of the lumens being reduced in the bridge cannula nasal (for example, having a base plate length of about 0.01498600m (0.59 inch) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of approximately 0.0119380Om (0.47 inch) of the cannula nasal bridge. For example, the nasal bridge cannula of the NO lumen can be reduced to a DI of about 0.001244600m (0.049 inches), the activation lumen can have a DI of about 0.002260600m (0.089 inches), and / or the 02 lumens can have a DI of around 0.00226060Om (0.089 inch). Even following the example above, the NO lumens cannula nostrils can be reduced to a DI of about 0.0009652000m (0.038 inches), the activation lumen can be reduced to a DI of about 0.002006600m (0.079 inches), and / or 02 lumens can be reduced to a DI of around 0.002006600m (0.079 inch). Also, before the reducer and / or connecting piece, the NO lumen can have a DI of around 0.001752600m (0.069 inches), the activation lumen can have a DI of around 0.002260600m (0.089 inches), and 02 lumens can have a DI of around 0.003352800m (0.132 inch).
As an example, taking into account the patient's comfort, as well as at least some and / or all the parameters for optimization described in this document, a three lumen cannula (for example, with a length of about 0.9144000m (3 feet) you can have tubes with a NO lumen that have an ID of around 0.001625600m (0.064 inch), an activation lumen that has an ID of around 0.002133600m (0.084 inch), and a 02 lumen that has an ID of around 0.002133600m (0.084 inch) with at least some of the lumens shrinking in the nasal bridge cannula (for example, having a base plate length of around 0.01498600m (0.59 inches) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of approximately 0.01193800m (0.47 inches) of the nasal bridge cannula. For example, in the nasal bridge cannula, the NO lumen can be reduced to a DI of about 0.001117600m (0.044 inches), the activation lumen can have a DI of about 0.002133600m (0.084 inches), and / or 02 lumens may have a DI of around 0.002133600m (0.084 inch). Even following the example above, in the cannula nostrils, the NO lumen can be reduced to a DI of about 0.0009144000m (0.036 inches), the activation lumen can be reduced to a DI of about 0.001879600m (0.074 inches) ), and / or 02 lumens can be reduced to a DI of around 0.001879600m (0.074 inch). Furthermore, before the reducer and / or connecting piece, the lumen of NO can have a Di of around 0.001625600m (0.064 inches), the lumen of to have a DI of around 0.002133600m (0.084 inches), and the lumens 02 can have a DI of around 0.003225800m (0.127 inch).
By way of example, taking into account patient comfort, as well as at least some and / or all of the optimization parameters described in this document, a three lumen cannula (for example, a length of approximately 4,572,000m (15 feet) you can have tubes with a NO lumen that have an ID of around 0.001879600m (0.074 inch), an activation lumen that has an ID of around 0.002387600m (0.094 inch), and a lumen of 02 that has an ID of around 0.002387600m (0.094 inches) with at least some of the lumens shrinking in the nasal bridge cannula (for example, which has a base plate length of around 0.01498600m ( 0.59 inch) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of approximately 0.01193800m (0.47 inch) of the nasal bridge cannula. For example, in the nasal bridge cannula, the NO lumen can be reduced to a DI of about 0.001371600m (0.054 inch), the activation lumen can have a DI of about 0.002387600m (0.094 inch), and / or 02 lumens may have an ID of around 0.002387600m (0.094 inch). Even following the example above, in the cannula nostrils the NO lumen can be reduced to a DI of about 0.001016000m (0.04 inch), the activation lumen can be reduced to a DI of about 0.002133600m (0.084 inch ), and / or 02 lumens may be reduced to
0.002133600m (0.084 inch). Also, a DI
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INDUSTRIAL * ...........
before the reducer and / or connecting piece, the lumen of NO can have a DI of around 0.001879600m (0.074 inch), the activation lumen can have a DI of around 0.002387600m (0.094 inch), and the lumens of 02 may have an ID of around 0.003479800m (0.137 inch).
By way of example, taking into account patient comfort, as well as at least some and / or all of the optimization parameters described in this document, a four lumen cannula (for example, with a length of approximately 2.133600m (7 ft.) You can have tubes with at least one lumen of NO that has an ID of around 0.001752600m (0.069 inches), at least one activation lumen that has an ID of about
0.002260600m (0.089 inch), and a 02 lumen that has an ID of around 0.002260600m (0.089 inch) with at least some of the lumens being reduced in the nasal bridge cannula (for example, having a base plate length of about 0.01498600m (0.59 inch) and / or shrinking (for example, shrinking again) in the nostrils (for example, having a length of approximately 0.01193800m (0.47 inch) of the nasal bridge cannula. For example, in the nasal bridge cannula, the NO lumen can be reduced to a DI of about 0.001244600m (0.049 inches), the activation lumen can have a DI of about 0.002260600m (0.089 inches), and / or 02 lumens may have an ID of approximately 0.002260600m (0.089 inch). Even following the previous example, in the graves
<img file="MX360652B_D0020.tif" />
<img file="MX360652B_D0021.tif" />
nasals of the nasal bridge cannula, the lumen reduce to a DI of about 0.0009652000m (0.038 inches), the activation lumen can be reduced to a DI of about 0.002006600m (0.079 inches), and / or the lumen of 02 can be reduced to a DI of around 0.002006600m (0.079 inch). Also, before the reducer and / or connecting piece, the NO lumen can have a DI of around 0.001752600m (0.069 inches), the activation lumen can have a DI of around 0.002260600m (0.089 inches), and 02 lumens can have an ID of approximately 0.003352800m (0.132 inch).
As an example, taking into account the patient's comfort, as well as at least some and / or all the optimization parameters described in this document, a four lumen cannula (for example, with a length of about 0.9144000m (3 feet) you can have tubes with at least one lumen of NO that has an ID of around 0.001625600m (0.064 inch), at least one activation lumen that has an ID of around 0.002133600m (0.084 inch), and a 02 lumen that has an ID of around 0.002133600m (0.084 inch) with at least some of the lumens shrinking in the nasal bridge cannula (for example, having a base plate length of around 0.01498600m (0.59 inches) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of approximately 0.01193800m (0.47 inches) of the nasal bridge cannula. For example, in the nasal bridge cannula, the NO lumen can be reduced to a DI of around 0.001117600m (0.044 inches), the activation lumen may have a DI of about 0.00 inches), and / or the lumens 02's may have an ID of approximately 0.002133600m (0.084 inch). Even following the example above, in the nasal bridge cannula nostrils, the NO lumen can be reduced to a DI of about 0.0009144000m (0.036 inches), the activation lumen can be reduced to a DI of about 0.001879600m (0.074 inch), and / or the lumen of 02 can be reduced to a DI of about 0.001879600m (0.074 inch). Also, before the reducer and / or connecting piece, the NO lumen can have a DI of around 0.001625600m (0.064 inch), the activation lumen can have a DI of about 0.002133600m (0.084 inch), and 02 lumens may have an ID of approximately 0.003225800m (0.127 inch).
As an example, taking into account patient comfort, as well as at least some and / or all of the optimization parameters described in this document, a four lumen cannula (for example, a length of approximately 4,572,000m (15 ft. )) You can have tubes with at least one lumen of NO that has an ID of around 0.001879600m (0.074 inch), at least one activation lumen that has an ID of around 0.002387600m (0.094 inch), and a lumen of 02 that has an ID of around 0.002387600m (0.094 inches) with at least some of the lumens shrinking in the nasal bridge cannula (for example, having a base plate length of about 0.01498600m (0.59 inches) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of about 0.C inches) of the nasal bridge cannula. For example, in the nasal bridge cannula, the NO lumen can be reduced to a DI of about 0.001371600m (0.054 inches), the activation lumen can have a Di of about 0.00238760Om (0.094 inches), and / or 02 lumens may have an ID of approximately 0.002387600m (0.094 inch). Even following the example above, in the nasal passages of the nasal bridge cannula, the lumen of NO can be reduced to a DI of about 0.001016000m (0.04 inch), the activation lumen can be reduced to a DI of about 0.002133600m (0.084 inch), and / or the lumen of 02 can be reduced to a DI of around 0.002133600m (0.084 inch). Also, before the reducer and / or connecting piece, the NO lumen can have a DI of around 0.001879600m (0.074 inches), the activation lumen can have a DI of around 0.002387600m (0.094 inches), and the 02 lumens can have an ID of approximately 0.003479800m (0.137 inch).
By way of example, taking into account patient comfort, as well as at least some and / or all of the optimization parameters described in this document, a double lumen cannula (for example, At a length of approximately 2.133600m (7 feet) you can have tubes with a combined NO / activation lumen that has a DI of around 0.001778000m (0.07 inch) and a 02 lumen that has a DI of around 0.002260600m (0.089 inches) with at least some of the lumens shrinking in the nasal bridge cannula (for example, having
I s a base plate length of around 0.
inches) and / or shrinking (eg, shrinking again) in the nostrils (eg, having a length of about 0.01193800m (0.47 inches) of the nasal bridge cannula. For example, in the nasal bridge cannula the Combined NO / trigger lumens can be reduced to a DI of approximately 0.00127000Om (0.05 inch) and / or 02 lumens can have a DI of around 0.002260600m (0.089 inch). Still following the example above, in the cannula nostrils, the combined NO / activation lumens can be reduced to a DI of about 0.001016000m (0.04 inch) and / or the 02 lumens can be reduced to a DI of about 0.002006600m (0.079 inch). Each of these dimensions for the combined NO / trigger lumens can be increased slightly (eg, by a few thousand), eg, to reduce the attenuation of the trigger signal. Also, before the reducer and / or connecting piece, the combined NO / trigger lumens can have a DI of about 0.001778000m (0.07 inch), and 02 lumens can have a DI of about 0.003352800m (0.132 inch) .
As an example, taking into account the patient's comfort, as well as at least some and / or all the parameters for optimization described in this document, a double lumen cannula (for example, with a length of about 0.9144000m (3 ft)) can have tubes with combined NO / activation lumens that have a DI of about 0.001625600m (0.064 in) and a 02 lumen that has a DI of about 0.002133600m (0.084
<img file="MX360652B_D0022.tif" />
<img file="MX360652B_D0023.tif" />
11 '-i 1 -I π -IX inches) with at least some of the nasal bridge cannula rec lumens (for example, having a base plate length of about 0.01498600m (0.59 inches) and / or shrinking (for example , shrinking again) in the nostrils (eg, having a length of approximately 0.01193800m (0.47 inches) of the nasal bridge cannula. For example, in the nasal bridge cannula the combined NO / activation lumens can be reduced to a DI of around 0.001117600m (0.044 inch) and / or the 02 lumens can have a DI of approximately 0.002133600m (0.084 inch) . Even following the example above, in the cannula nostrils, the combined NO / activation lumens can be reduced to a DI of about 0.0009144000m (0.036 inches) and / or the 02 lumens can be reduced to a DI of about 0.001879600m (0.074 inch). Each of these dimensions for the combined NO / trigger lumens can be increased slightly (eg, by a few thousand), eg, to reduce the attenuation of the trigger signal. Also, before the reducer and / or connecting piece, the combined NO / trigger lumens can have a DI of around 0.001625600m (0.064 inch), and 02 lumens can have a DI of around 0.003225800m (0.127 inch ).
By way of example, taking into account patient comfort, as well as at least some and / or all of the optimization parameters described in this document, a double lumen cannula (for example, having a length of approximately 4,572000m (15 feet) you can have tubes with a combined NO / activation lumens that have a DI of around 0.00 inches) and a lumen of 02 that has a DI of around 0.002387600m (0.094 inches) with at least some of the lumens shrinking in the nasal bridge cannula (for example, having a base plate length of around 0.01498600m (0.59 inches) and / or shrinking (for example, shrinking again) in the nostrils (eg having a length of about 0.01193800m (0.47 inch) of the nasal bridge cannula. For example, in the nasal bridge cannula the combined NO / activation lumens can be reduced to an ID of around 0.001371600m (0.054 inch) and / or 02 lumens can have an ID of around 0.002387600m (0.094 inch). Even following the example above, in the cannula nostrils, the combined NO / activation lumens can be reduced to a DI of about 0.001016000m (0.040 inch) and / or the 02 lumens can be reduced to a DI of about 0.002133600m (0.084 inch). Each of these dimensions for combined NO / trigger lumens can be increased slightly (eg, by a few thousandths of an inch), eg, to reduce attenuation of the trigger signal. Also, before the reducer and / or connecting piece, the combined NO / trigger lumens can have a DI of around 0.001879600m (0.074 inch), and 02 lumens can have a DI of around 0.003479800m (0.137 inch ).
TRAMPOLINE
In exemplary modalities, the nasal bridge cannula (2002)
100
If Τ1Τ can include a flexible support bridge or '-. . * (2517) that can cushion the nasal septum. The flexible support bridge (2517) can offer greater comfort to the patient, for example, by increasing the contact surface area between the cannula and the nasal septum, and / or the comfort of the patient can be increased because the bridge of the tip It can be designed to deviate away from the nasal septum.
In exemplary embodiments, the flexible support bridge (2517) can be an element (eg, free floating element) that can be supported at both ends by the tips of the nasal cannula. Instead of a patient's nose (eg, nasal septum) resting on a central bridge member (2518) as commonly found in nasal cannulas (eg, separating the nostrils from a nasal cannula; a connection of hard plastic, sometimes curved, between the nostrils of a nasal cannula; etc.), a flexible support bridge (2517) can be an element (for example, in addition to the central bridge (2518), which crosses the parts of the central bridge (2518), which crosses from one nostril to another nostril, etc.) which contacts the patient's septum thereby providing at least greater comfort to the patient. In exemplary embodiments, the flexible support bridge (2517) can snap and / or bend toward the center bridge element (2518) when the cannula is used. Rolling and / or bending of the flexible support bridge (2517) can soften transient forces on the nasal septum due to patient movement or cannula movement. Giving and / or bending
101
I i VI 1 I <sup>γ</sup>-N or JL JL ϊ JL JL JL & ..............- .....
It can also increase the surface area of the nasal septum, which in turn can reduce the force on the nasal septum at any point, thus improving comfort (for example, since comfort can be negatively affected by increased load on the point of the nasal septum).
In exemplary modalities, the flexible support bridge (2517) can restrict the insertion depth of the nostrils, for example, as mentioned above, to an optimal and / or desired distance of approximately 0.002540000m (0.1 inch) of insertion to about 0.01524000m (0.6 inch) and / or about 0.01016000m (0.40 inch). As an example, this distance may be shorter than the length of the nostrils that extend from the central bridge (2518).
In exemplary embodiments, the nasal bridge cannula can include a flange (2519) between the nostrils (eg, extending from the central bridge (2518)) that can allow the nasal cannula connecting piece to seat properly. on the upper lip. The flange (2519) can provide an additional measure of patient comfort by, for example, orienting the nostrils so that the nostrils point inward toward the nostrils and / or can distribute force on the lip superior over a larger surface area thus improving patient comfort.
Referring to Figures 2 0 and 27, in exemplary embodiments, the nasal cannula may include a brace member
102 ii (2010) which is described in more detail in cc exemplary modalities, the key member (2010) may be a bolus and / or it may be part of a bolus that can be included and can be used to adjust the section length cannula proximal to the nasal bridge, for example, to increase patient comfort, ensuring that the cannula fits around the user's head.
In exemplary embodiments, the nasal cannula may further include ear pads that can, for example, slide over and / or be incorporated into the cannula tube at the point where the cannula tube wraps around the ears to improve comfort. and / or the ear pads may be foam tube extrusions that may have axial grooves so that they can slide over the cannula tube.
Although this exemplary nasal cannula can be described as having certain components, any and all of these components may be optional, may be removed, and / or may be combined and / or additionally separated. Furthermore, the nasal cannula may have any of the other components or materials described herein in another way.
CANNULA WRENCH
During the purge and / or flushing procedure that can be used to clean the nasal cannula of air and other gases prior to the delivery of NO, the air / gases can be purged by flow of NO containing gas through the nasal cannula. However, due to the reaction of NO and oxygen in the air, this
103
The washing procedure can produce NO2. It may be important that the patient not use the nasal cannula during the purge and / or flushing procedure, for example, so that NO2 cannot be delivered to the patient.
Referring again to Figure 20, one or more embodiments of the present invention may provide a key element (2010) in the nasal cannula. Such a wrench element can be attached close to the nostrils of the nasal cannula, such as within 0.1270000m - 0.6350000m (5-25 inches) of the cannula holes. One or more exemplary modalities can be seen as a reference to the element (2010) as shown in Figure 20. The key element can be provided as a bolus that can stop on a patient's chest and / or neck when the cannula is used by the patient.
Referring to Figure 28, the key element (2010) may need to be connected to the NO supply device (2803) with a key or lock slot (2804) and / or it may be necessary to do this during the washing procedure. . Due to the proximity of the modulation device and nostrils, the nostrils of the nasal cannula cannot be in the nostrils of the patient's nose when the faucet element is plugged into the NO delivery device.
In one or more exemplary implementations of a NO delivery device with a lock slot and a nasal cannula with a key element, the NO delivery device can perform the following functions:
to. The NO delivery device can request the
104 patient to remove the cannula and insert the e] contained in the cannula into the lock slot in the NO delivery device.
b. The lock slot can detect the presence of the key in the lock slot. Exemplary methods for detecting the presence of the key include, but are not limited to, electronic detection (eg, lumen beam detector, flipped switch, IR detection, magnetic detection, etc.) or mechanical detection (eg, microswitch)
c. The NO supply device can ensure that the key is in the lock before performing the wash procedure and can be programmed not to perform the maneuver if the key is not in the lock slot.
d. The NO delivery device can then perform the washing procedure and inform the user of the completion of the procedure.
and. The NO delivery device can allow the user to remove the key from the lock to initiate NO therapy.
In exemplary embodiments, the key element and / or key slot can be used to ensure that the patient is not using the nasal cannula during the purge and / or flushing procedure. In exemplary embodiments, the holding element and / or key slot can be used to ensure the authenticity of at least the cannula, the expiration of at least the cannula. For example, the key element and / or key slot can be used to limit the number of uses of the cannula and / or
105 Do not allow patients to return to useful:
As another example, in case it is necessary to ensure that patients do not use the cannula, the key element and / or key slot can be used to prevent users from using a defective cannula.
It will be understood that any of the above teachings (eg, trampoline, flange, tube, connection piece, oxygen connection piece, reducer, key member, key, bolus, cannula constructions, nasal bridge constructions, etc.) they can be combined with any of the other pneumatic configurations, cannula configurations, and / or teachings and / or modalities described herein. For example, the above teachings (eg, trampoline, flange, tube, connecting piece, oxygen connecting piece, reducer, wrench member, wrench, bolus, cannula constructions, nasal bridge constructions, etc.) can be used with single lumen cannulas, double lumen cannulas, three lumen cannulas, four lumen cannulas, and / or any other teachings and / or modalities described herein.
EXAMPLES
Referring to Figures 29-30, an example of retrograde flow during inspiration breathing together with impulse delivery is shown in Figure 29 and an example of retrograde flow during both inspiratory and expiratory breathing is shown in Figure 30.
106
Μ ΡI
Referring to Figures 31 and 32a, 32b, * retrograde flow for various nasal cannula configurations. The typical nasal cannulas provided in the two nostrils result in significant retrograde flow as shown in Test 1 of Figure 31. The nasal cannula configuration of Test 1 is shown in Figure 32A. For Test 2, the interconnection between the two nostrils was occluded to increase the distance between the nostrils to approximately 5.791200m (19 inches) in the hope that they would eliminate retrograde flow. The configuration of the nasal cannula from Test 2 is shown in Figure 32B. As shown in Test 2 of Figure 31, while the total volume of retrograde flow could be reduced, it was not eliminated. In addition, the occluded pathway at a distance of 2.133600m (7 feet) between the nostrils, as shown in Figure 32C, had the least impact, as shown in Test 3 of Figure 31. Surprisingly, it was found that the only proven way to completely eliminate retrograde flow was when you
<td>they used</td><td>circuits</td><td>separated for</td><td>the</td><td>supply</td><td>NO to each</td>
<td>one of the</td><td colspan="2">nostrils (i.e.</td><td>a</td><td>system of</td><td>supply of</td>
<td colspan="2">dual channel).</td><td></td><td></td><td></td><td></td>
<td>The</td><td>document</td><td>attached to</td><td>the</td><td>request</td><td>provisional</td>
No. 61 / 856,367, filed July 19, 2013 as Appendix 1, titled Exploratory Assessment of Nitrogen Dioxide Formation in Candidate Lumens for Nitric Oxide Delivery, examined the expected NO2 concentration to be present in the supply lumen from NO to
107 through three lumen cannulas of different appendix 1 attached to provisional application N<sup>fi</sup> 61 / 856,367, filed July 19, 2013 is incorporated herein by reference in its entirety, to the extent that it is not incompatible with the present invention. The experimental technique consisted of flowing 2440 ppm of nitric oxide (nitrogen balance) gas through multiple tubes (of three types of materials) arranged in parallel such that the proximal readings (based on the circuit without the tubes) and distal of the NO2 effluent content could be taken with a plate of NO2 CAPs. Parallel tubes were used to improve the signal-to-noise ratio (i.e., to extend the power of the N02 signal) from the data and a final mathematical calculation of the individual tube with NO2 change was obtained. Nitric oxide flow through parallel tube banks was set to equalize a residence time of 7.57 min / tube (for example, based on a 50 kg patient with dosage set at 0.003 mg / kg * hr with one tube 2.133600m (84 inches) long and 0.001930400m (0.076 inches) ID diameter supply lines). The expected NO 2 rise per tube for the three types of materials tested is shown below.
<td colspan="2">NO2 Levels Supplied Per Tube</td>
<td>Tube Material</td><td>NO2 level per Tube</td>
<td>Polyvinyl chloride</td><td>12.7 ppm</td>
<td>Silicone</td><td>10.9 ppm</td>
<td>Polyurethane</td><td>6.8 ppm</td>
TREATMENT METHODS
108
I
The invention herein retrograde flow pt, ensure accurate dose delivery, and / or minimize NO2 formation and used in conjunction with a delivery device that can be used for the treatment and / or prevention of secondary pulmonary hypertension COPD and / or pulmonary hypertension such as
PAH and / or pulmonary hypertension secondary to IPF and / or pulmonary hypertension secondary to sarcoidosis.
For safe and effective use, the described cannula can be used with the described delivery device, and the like, and / or nitric oxide. One skilled 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 safety risks and / or reduce and / or eliminate effective use. Accordingly, the cannula of the present invention may be necessary for delivery of nitric oxide for HAP, IPF, and / or COPD.
Any of the nasal cannulas described in this document can be used in nitric oxide therapy to treat appropriate diseases. For example, the cannulas can be for pulsed NO therapy to treat chronic obstructive pulmonary disease (COPD) or pulmonary arterial hypertension (PAH). For these diseases, supplying the appropriate dosage amounts and the appropriate dosage schedule can be very important. For COPD, NO may need to be pulsed on early inspiration, such as the first half of inspiration. If NO, for example, is not administered in the
109 correct amount or at the right time, reversal of hypoxic vasoconstriction is possible, which could worsen the patient's condition. Furthermore, the amount of doses can be very important for PAH, because the sudden interruption of treatment can lead to serious events such as rebound hypertension. Therefore, significant dilution of the NO dose should be minimized for these diseases. Any of the cannula materials, configurations, or methods described here can be used to minimize dilution of the NO dose during NO therapy.
In exemplary modalities, the lumens (eg, tubes) of the cannula can be brought back toward the patient and / or can be fixed together to produce a substantially unique umbilical element between the nasal bridge cannula and the device, resulting in can provide a cross section. It will be understood that when a plurality of lumens are described (eg two lumens, three lumens, four lumens, etc.) all lumens may be included in a single cannula.
In exemplary embodiments, the cannula elements can be manufactured using any of the techniques described herein and / or using techniques known in the art. For example, the cannula lumens (eg, tubes), activation, faucet member, connectors, reducers, any combination and / or further separation thereof, and / or any cannula elements described in this document can be manufactured using
110 extrusion techniques
<img file="MX360652B_D0024.tif" />
manufacturing technique.
It will be understood that each lumen of the nasal cannula and / or cross section of the lumen of the collective nasal cannula can be of any shape, such as, but not limited to, circular, parabolic, ellipsoidal, square, rectangular, triangular, and / or any other cross section and / or any other regular or irregular shape to minimize dilution of the dose. To facilitate, the geometry and / or cross section is sometimes described as circular, parabolic, and / or ellipsoidal and / or the cross section is described as a diameter, ID, or the like. This is merely for ease and is in no way intended to be a limitation. When one or more cross-sectional areas are not circular, then the ratio of inside diameters can be the square root of the ratio of the surface areas of the two sections of lumens.
It will be understood that any of the above can be used for the pulsed and / or non-pulsed delivery of a therapeutic gas (eg, NO). For example, any of the above modalities referring to pulse delivery of a therapeutic gas, when applicable, can be used with the non-pulsed delivery of a therapeutic gas, and vice versa. To facilitate, sometimes, you can refer to the pressed or the not pressed. This is merely for ease and is in no way intended to be a limitation.
With reference throughout this description to a modality, certain modalities, one or more modalities, the exemplary modality, exemplary modalities modality means that a particular characteristic, structure, materials, or function described in connection with the modality is included in at least an embodiment of the invention. Therefore, the occurrences of the phrases such as in one or more modalities, in certain modalities ", in one modality, exemplary modality, exemplary modalities and / or in a modality in various places throughout this description are not necessarily referring to the same embodiment of the invention. Furthermore, the particular characteristics, structures, materials, or functions can be combined in any suitable way in one or more modalities.
It will be understood that any of the steps described can be rearranged, separated, and / or combined without departing from the scope of the invention. For ease, steps are sometimes presented sequentially. This is merely for ease and is in no way intended to be a limitation.
Furthermore, it will be understood that any of the elements and / or embodiments of the invention described can be rearranged, separated, and / or combined without departing from the scope of the invention. For ease, various elements are sometimes described separately. This is merely for ease and is in no way intended to be a limitation.
Although the present description has been described with reference to particular embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It will be evident to
MPI &
invention without
Thus
112 Those skilled in the art may make various modifications to the method and apparatus herein depart from the spirit and scope of the invention.
The present invention is intended to include modifications and variations that are within the scope of the appended claims and their equivalents.
113
Contents46
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89 members in 23 offices
Priority claims19
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| EP3173116B1 | European Patent Office (EPO) | B1 | |
| IL239099A | Israel | A | |
| IL239099B | Israel | B | |
| JP2020000889A | Japan | A | |
| AU2017265042B2 | Australia | B2 | |
| AU2020200087A1 | Australia | A1 | |
| US10556082B2 | United States of America | B2 | |
| DK3173116T3 | Denmark | T3 | |
| EP3636306A1 | European Patent Office (EPO) | A1 | |
| US2020171259A1 | United States of America | A1 | |
| ES2773718T3 | Spain | T3 | |
| MX2020010786A | Mexico | A | |
| IL277164A | Israel | A | |
| IL277164D0 | Israel | D0 | |
| IL270174A | Israel | A | |
| IL270174B | Israel | B | |
| US10918819B2 | United States of America | B2 | |
| KR20210024687A | Republic of Korea | A | |
| KR102223425B1 | Republic of Korea | B1 | |
| CN108355219B | China | B | |
| BR112015013095B1 | Brazil | B1 | |
| US2021260327A1 | United States of America | A1 | |
| KR102357044B1 | Republic of Korea | B1 | |
| KR20220019295A | Republic of Korea | A | |
| AU2022200646A1 | Australia | A1 | |
| CN108355215B | China | B | |
| KR102483889B1 | Republic of Korea | B1 | |
| KR20230010776A | Republic of Korea | A | |
| CA2892398C | Canada | C | |
| JP7227872B2 | Japan | B2 | |
| IL277164B1 | Israel | B1 | |
| US11786687B2 | United States of America | B2 | |
| ZA201804189B | South Africa | B | |
| IL277164B2 | Israel | B2 | |
| EP3636306B1 | European Patent Office (EPO) | B1 | |
| DK3636306T3 | Denmark | T3 | |
| AU2022200646B2 | Australia | B2 | |
| ES2987446T3 | Spain | T3 |
2 legal events, as the office reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | |
|---|---|---|
| Grant or registrationFG | FG | |
| Transfer or rightsGB | GB |
Numbers
- Publication
- 360652
- Publication, DOCDB
- 360652
- Publication, EPODOC
- MX360652
- Application
- 2015007017
- Application, DOCDB
- 2015007017
- Application, EPODOC
- MX20150007017
Titles
- Spanish
- CÁNULA PARA MINIMIZAR LA DISOLUCIÓN DE LA DOSIFICACIÓN DURANTE LA ADMINISTRACIÓN DEL ÓXIDO NÍTRICO.
Classification
- CPC, 24
- A61M16/0677
- A61M2202/0208
- A61M2202/0266
- A61M2202/0275
- A61M2202/0283
- A61M2205/75
- A61M2210/0618
- A61M16/101
- A61M16/122
- A61M16/125
- A61M16/204
- A61M2016/0021
- A61M2016/0027
- A61M16/0666
- A61M16/009
- A61M16/104
- A61M16/208
- A61M16/0672
- A61M2205/3331
- A61M16/1005
- A61M2205/3303
- A61M2205/0216
- A61M16/10
- A61M16/0875
- IPC, 6
- A61M16 00
- A61M16 06
- A61M16 08
- A61M16 10
- A61M16 12
- A61M16 20