DEVICE FOR THE DELIVERY OF GAS-FORMED NITROGEN MONOXIDE IN PROPORTIONAL OR PULSE OPERATION

Description

[0001] The invention relates to a device or apparatus for supplying or delivering gaseous nitric oxide (NO), and an installation for administering NO-based therapeutic gas to a patient comprising such a device or apparatus for supplying NO.

[0002] Inhaled nitric oxide or NOi is a gaseous drug commonly used to treat patients with acute pulmonary arterial hypertension, especially pulmonary vasoconstrictions in adults or children, including newborns (PPHN), as described for example by EP-A-560928 or EP-A-1516639.

[0003] A NOi therapy delivery system, commonly referred to as a patient NO therapeutic gas delivery system or simply an NO delivery system, typically includes one or more NO / N2 mixing cylinders supplying an NO delivery device that delivers the NO / N2 mixture at a controlled flow rate, a medical ventilator, i.e., a respiratory support device, to provide a breathing gas containing at least 20 to 21% vol. of oxygen, such as an O2 / N2 mixture or air, to which NO is added in the form of an NO / N2 mixture, circuit elements, for example one or more flexible gas lines, to carry the gas flows between these different pieces of equipment and to the patient, and a respiratory interface, such as a tracheal intubation tube, to deliver the gas mixture containing NO to the patient.A gas humidifier can also be used to humidify the gas mixture before administration to the patient. Such a NO administration system is shown schematically in diagram . Fig. 1 .

[0004] Such a NO delivery system is used in hospitals to administer NOi therapy and thus treat patients who need to inhale NO to treat their pulmonary arterial hypertension. Examples of such NO delivery systems are given in documents EP 3 466 473 A1, FR 2 911 281 A1, EP-A-3821929, WO-A-2012 / 094008, US-A-2015 / 320951, US-A-2015 / 273175, JP-AH11192303, WO-A-02 / 40914 and US-A-2003 / 116159.

[0005] To efficiently deliver the gas to the patient(s), the NO delivery device, which is part of the NO administration system, is generally equipped with proportional solenoid valve actuators, as taught in EP-A-659445, or on / off solenoid valves, or even a combination of both as described in EP-A-375671. These valves allow for different flow rates depending on factors such as the NO concentration to be delivered, as determined by the healthcare staff, and the concentration in the cylinders. Specifically, the higher the concentration in the cylinders, the lower the NO delivery rate must be.

[0006] Therefore, it is necessary to use extremely precise actuators in the low ranges of NO flow rates, particularly when treating children or newborns, but also allowing for higher flow rates for adult treatments that require higher concentration NO.

[0007] However, this leads to problems and drawbacks. Indeed, in order to cover the different flow ranges required, it is necessary to multiply the actuators, typically by mounting them in parallel, which leads to a more complex internal gas circuit of the NO supply device and necessarily increases its cost.

[0008] In other words, there is a need for a device or apparatus for supplying NO, typically a NO / N2 gas mixture, which does not have all or some of the aforementioned disadvantages and problems, and which is suitable for treating patients suffering in particular from pulmonary arterial hypertension.

[0009] One solution according to the invention relates to an apparatus or device for supplying (i.e., delivering) NO, typically a NO / N2 gaseous mixture, comprising: a main gas circuit for conveying a NO / N2 gas mixture, flow control means comprising (at least) a main solenoid valve arranged on said main gas circuit, and pilot means configured to control at least said at least one main solenoid valve to control the flow of NO / N2 gas mixture passing through said at least one main solenoid valve.

[0010] Furthermore, the main solenoid valve is a proportional solenoid valve with opening degrees ranging from 0 to 100%, and is configured to operate within at least two given operating ranges comprising at least: a first operating range corresponding to degrees of opening of the main solenoid valve between 0 and x% with: 0 < x% ≤ 10%, and a second operating range corresponding to degrees of opening of the main solenoid valve greater than x% (ie >x%).

[0011] Furthermore, the control means are configured to control said main solenoid valve to operate a gas supply in a different way depending on the operating range considered, namely: ▪ in pulsed mode (i.e., pulse modulation) in the first operating range so as to deliver successive gaseous pulses (IG), and ▪ in proportional mode in the second operating range,

[0012] In addition, the NO supply apparatus or device further includes a bypass circuit (or line) which connects fluidly to the main gas circuit, upstream and downstream of the flow control means and which includes secondary flow control means comprising a secondary on / off type solenoid valve and a fixed flow device.

[0013] Depending on the embodiment considered, the apparatus or device for supplying, i.e. delivering, NO of the invention may comprise one or more of the following characteristics: The first operating range is non-linear. The second operating range is linear. The control means are configured to operate the main solenoid valve in proportional mode within the second operating range, by progressively (i.e., proportionally) opening or closing the main solenoid valve to obtain the desired gas flow rate. Depending on the embodiment considered, the first operating range corresponds to opening degrees of the main solenoid valve between 0 and x%, with: 0 < x% ≤ 8%, alternatively 0 < x% ≤ 5%, alternatively 0 < x% ≤ 4%, alternatively 0 < x% ≤ 3%, or alternatively 0 < x% ≤ 2%. The control means are configured to set or adjust the duration or amplitude of each gas pulse delivered in pulsed mode, to control the gas flow rate through the main solenoid valve.The control means are configured to adjust the pulse duration for each pulse by controlling the opening time of the proportional solenoid valve. When the duration is variable, the amplitude of each pulse is fixed. The control means are configured to adjust the pulse amplitude for each pulse by controlling the degree of opening of the proportional solenoid valve. When the amplitude is variable, the duration of each pulse is fixed. The main, i.e., proportional, solenoid valve has an internal passage in fluidic communication with the main gas circuit. When the main solenoid valve is at least partially open (i.e., a non-zero degree of opening), the NO / N₂ gas mixture flows through the internal passage of the main solenoid valve either as a continuous gas flow or as gas pulses.The opening duration of the proportional solenoid valve, i.e., the pulse duration, is between approximately 5 and 200 ms. In pulsed mode, the control means are configured to command the proportional solenoid valve to deliver successive gas pulses, each with a non-zero pulse duration during which the proportional solenoid valve is in a partially open position with a degree of opening x%, such that x% < 10%, so as to allow the passage of a given quantity of NO / N₂ mixture during said pulse duration. The gas pulses are separated from each other by closing times during which the proportional solenoid valve is in the closed position, i.e., with a degree of opening x%, such that x% = 0% (i.e., closed state). The closing time is between 0 and 195 ms, preferably a non-zero closing time.The flow control means allow control of the gas flow (i.e., NO / N₂) in the main gas circuit. The main gas circuit fluidly connects at least one NO inlet port to at least one NO outlet port to convey the NO / N₂ gas mixture from said at least one NO inlet port to said at least one NO outlet port. The backup circuit includes secondary flow control means to control the gas flow (i.e., NO / N₂) in the backup circuit. The control means are configured to operate said at least one main solenoid valve of the flow control means and / or said at least one secondary solenoid valve of the secondary flow control means to control the flow of the NO / N₂ mixture passing through said at least one main solenoid valve and / or said at least one secondary solenoid valve.The secondary flow control means, comprising at least one secondary solenoid valve, are arranged on said bypass circuit. The secondary solenoid valve is of the on / off (NO / N2) type. The on / off solenoid valve is configured to adopt only two operating positions: an open position allowing the NO / N2 mixture flow and a closed position preventing any NO / N2 mixture flow. The control means are configured to control said at least one secondary solenoid valve, i.e., the on / off electrode, in pulsed mode to alternately switch said at least one secondary solenoid valve between the open position (i.e., fully open) and the closed position so as to deliver the NO / N2 mixture in the form of successive gas pulses.Each gas pulse includes a non-zero pulse duration (di) during which at least one secondary solenoid valve is in the open position and allows the passage of a quantity of NO / N₂ mixture corresponding to the predetermined fixed flow rate (Qfix) of NO / N₂ mixture delivered by the fixed flow device during the pulse duration (di) of the gas pulse in question. It further includes a fixed flow device arranged on the bypass circuit delivering a predetermined fixed flow rate (Qfix) of NO / N₂ mixture. The fixed flow device includes a calibrated orifice. The fixed flow device includes a device with a calibrated orifice delivering the predetermined fixed flow rate (Qfix). Typically, the predetermined fixed flow rate (Qfix) in the backup circuit is between 0.1 and 2 L / min, preferably between 0.1 and 1 L / min, typically on the order of 0.5 L / min.The pulse duration (di) of each gas pulse is variable but not zero, preferably between approximately 5 ms and 200 ms. The gas pulses are separated from each other by closing times (df) during which the main proportional solenoid valve and / or secondary solenoid valve are in the closed position. The closing times (df) may be of equal or variable duration. Typically, the closing times (df) range from 0 ms or greater to 195 ms. It includes storage means configured to store the predetermined fixed flow rate (Q fixed) delivered by the fixed-flow device. Preferably, the storage means are integrated with the control means. The storage means include computer memory, for example, flash memory, RAM, or other.The fixed-flow device is arranged on said bypass circuit, downstream of said at least one secondary solenoid valve. The control means are configured to determine the desired quantity of NO / N₂ mixture from the gas flow rate supplied by a medical ventilator, the desired concentration, and the NO content of the NO / N₂ mixture. The control means comprise at least one (micro)processor. Said at least one (micro)processor is arranged on an electronic board. Said at least one (micro)processor implements at least one algorithm. The main gas circuit comprises said at least one main solenoid valve and at least one flow sensor. Said at least one flow sensor is arranged upstream of said at least one main solenoid valve. Said at least one flow sensor is electrically connected to the control means. Said at least one main solenoid valve is a proportional solenoid valve controlled by the control means.It includes a mass flow controller (MFC) comprising the main solenoid valve and the flow sensor arranged on the main gas circuit. The main gas circuit includes a main NO line. Said at least one main solenoid valve and said at least one flow sensor are arranged on the main NO line. The upstream portion of the main NO line branches into two parallel sections, each comprising a gas inlet orifice for receiving a NO / N₂ mixture. The bypass line is fluidly connected to the main NO line, upstream and downstream of said flow control means so as to bypass said flow control means. The bypass circuit further includes a gas pressure-reducing device arranged upstream of said at least one secondary solenoid valve.

[0014] The invention also relates to a gas supply installation, i.e. a gas containing NO and oxygen, to a patient comprising: at least one NO / N₂ mixture source, typically one or more pressurized gas cylinders containing the NO / N₂ mixture, an NO supply device according to the invention fluidly connected to said at least one NO / N₂ mixture source, a medical ventilator configured to supply a breathing gas containing oxygen, typically at least about 20% oxygen, such as air or an N₂ / O₂ mixture, for example at least about 21% oxygen, a patient circuit to which the NO supply device according to the invention and the medical ventilator are fluidly connected to supply said patient circuit with said NO / N₂ gas mixture and said breathing gas containing oxygen, and a flow sensor arranged on the patient circuit and configured to determine (i.e.measure) and provide the control means of the NO delivery device with at least one measurement signal representative of the gas flow within the patient circuit, namely one (or more) signal or one (or more) flow or pressure measurement.

[0015] Depending on the embodiment considered, the gas supply installation of the invention may include one or more of the following features: The patient circuit includes a NO injection module supplied with a NO / N₂ mixture by the NO delivery device, preferably via an NO injection line or conduit, such as a flexible gas line. The flow sensor is arranged on an inspiratory branch of the patient circuit and is electrically connected to the control means via one or more electrical connections (e.g., cables or the like). The flow sensor (i.e., used to measure the flow rate of the respiratory gas supplied by the ventilator) is arranged on the patient circuit between the medical ventilator and the NO injection module. In one embodiment, the flow sensor is a mass flow sensor or the like. However, another type of sensor may be used provided it allows for a direct or indirect measurement of the flow rate. The flow sensor is electrically connected to the control means via one or more electrical connections, such as cables or the like.The NO supply unit is fed with a NO / N₂ gas mixture consisting of NO and nitrogen from the NO / N₂ mixing source(s). The NO delivery line of the NO supply unit carries the NO / N₂ gas mixture. The NO / N₂ gas mixture from the NO / N₂ mixing source(s) contains between 100 and 2000 ppmv of NO, typically less than 1000 ppmv of NO, the remainder being nitrogen (and possibly unavoidable impurities). The NO supply unit comprises a housing containing the main circuit, the bypass circuit, the control means, the main and secondary solenoid valves, and other components. means of power supplying electrical current to the components requiring electrical power to operate, including the NO supply device and the medical ventilator, such as means of connection to mains (110 / 220V) and / or a battery or similar.The medical ventilator includes a motorized blower (i.e., also called a turbine, compressor, or similar device) delivering the breathing gas, typically air or an oxygen / nitrogen mixture, or even pure oxygen. The NO source(s) contain a NO / N₂ gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N₂), conditioned at a pressure between 10 and 250 bar absolute, typically above 100 bar absolute (before the start of withdrawal), preferably between 100 and 1000 ppmv of NO, the remainder being nitrogen (N₂). The NO source(s) include one or more pressurized gas cylinders. The NO source includes one or more gas cylinders with a capacity between 0.5 and 50 L (water equivalent).The gas cylinder comprises a cylindrical body made of steel or aluminum alloy and is equipped with a simple valve (without a regulator) or a valve with an integrated regulator (IRR), preferably an IRR protected by a protective cover, for example, made of metal or polymer. The patient circuit comprises an inspiratory branch and an expiratory branch. The patient circuit includes flexible tubing forming the inspiratory and / or expiratory branches, typically polymer tubing. The inspiratory and expiratory branches, e.g., flexible tubing, are connected to a junction piece, such as a Y-piece. The inspiratory and / or expiratory branches are fluid-connected to a patient breathing interface, preferably via the junction piece. The patient breathing interface includes a tracheal intubation tube or breathing mask.The inspiratory and expiratory branches include flexible tubing, for example, made of polymer. The inspiratory and expiratory branches are further fluidically connected to, respectively, the inlet and outlet ports of the medical ventilator. The inspiratory branch of the patient circuit may include a gas humidifier arranged downstream of the NO injection module so as to humidify the gas before its administration by inhalation to the patient. The concentration or dosage of NO in the final gas mixture, i.e., the gas inhaled by the patient after mixing the NO / N2 mixture with the oxygen-containing breathing gas from the ventilator, such as air or an O2 / N2 mixture (approximately >20% vol.), is between 1 and 80 ppm by volume (ppmv), depending on the treated population, i.e., neonates or adults, the patient's condition, and / or the disease being treated.

[0016] The NO supply apparatus and / or gas supply system of the invention are particularly well suited for use in a therapeutic treatment method involving the administration by inhalation, particularly via a tracheal intubation tube, of a gas mixture comprising 1 to 80 ppmv of NO and at least approximately 20% vol. of oxygen, typically in the range of 10 to 20 ppmv of NO, to one or more patients (e.g., adults, children, adolescents, or neonates) requiring it, typically patients (i.e.human persons) suffering from pulmonary hypertension and / or hypoxia likely to cause pulmonary vasoconstrictions or similar, for example caused by pulmonary pathologies or disorders such as PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by cardiac surgery with extracorporeal blood circulation (ECC).

[0017] Within the scope of the invention: "ppmv" means parts per million by volume, "%vol." means percentage by volume. "NO" refers to nitrogen monoxide. "N₂" refers to nitrogen. "O₂" refers to oxygen. A "flow sensor" is understood to mean a sensor of the type that measures and provides one or more flow signals or measurements, or of the type that measures and provides one or more pressure signals or measurements, which are then converted into flow by the control means. All terms "means of" are considered entirely equivalent and interchangeable with the term "device of," for example, the term "control means" can be replaced by "control device," the term "measuring means" can be replaced by "measuring device," the term "control means" can be replaced by "control device," and so on.

[0018] The invention will now be better understood through the following detailed description, given by way of illustration but not limitation, with reference to the attached figures, among which: Fig. 1 diagram shows a therapeutic gas administration system based on NO to a patient, incorporating an NO supply device according to the invention. Fig. 2 diagram illustrates the operation of the NO supply device according to the invention. Fig. 3 diagrams the successive gas pulses resulting from the pulsed control of the secondary solenoid valve of the NO supply device Fig. 2 , Fig. 4 schematically represents the successive gas pulses resulting from controlling the width of each gas pulse in pulsed mode, during operation of the main solenoid valve within its non-linear operating range, and Fig. 5 diagrams the successive gas pulses resulting from a control of the amplitude of each gas pulse in pulsed mode, during operation of the main solenoid valve in its non-linear operating range.

[0019] Fig. 1 diagram illustrates an embodiment of a therapeutic gas administration installation 10, namely a NO-based gas mixture, to a patient, comprising an NO supply device 1 according to the present invention, in particular that diagrammed in Fig. 2 .

[0020] The installation 10 here comprises two gas sources which are two pressurized gas containers 11, namely compressed gas cylinders, arranged in parallel, each containing a gaseous mixture of NO and nitrogen (N2), i.e. a NO / N2 mixture, typically containing 225 to 2000 ppmv of NO and nitrogen (N2) for the remainder, preferably 450 to 1000 ppmv of NO, conditioned at a pressure of up to 150 bar, or even 180 or more (full container), for example a NO / N2 mixture containing 450 ppmv or 800 ppmv of NO.

[0021] The NO containers 11 supply the NO / N2 mixture to a device or apparatus for supplying NO1 according to the invention, part of whose internal architecture is schematically shown on Fig. 2 The connection is ensured by NO supply lines 12, i.e. gas pipelines, such as flexible hoses or similar. Each line 12 is connected to an NO inlet port 4 of the NO supply device 1 to supply the main gas circuit 40, 40.1, 40.2 internal to the housing 2 of the NO supply device 1 (cf. Fig. 2 ).

[0022] The NO 1 supply device also includes an oxygen inlet port 5 fluidically connected, via an oxygen supply line 14, such as a flexible hose or similar, to an oxygen source (not shown), for example a pressurized oxygen container, typically an O 2 cylinder or, alternatively, the hospital network, i.e. an oxygen supply pipeline arranged in the hospital building where the patient is being treated.

[0023] The NO1 cylinders and the O2 source, e.g., an oxygen cylinder, are preferably equipped with a gas dispensing valve 13, preferably incorporating gas pressure reduction means, i.e., an RDI or valve with integrated pressure regulator, or other gas control and / or regulation systems so as to be able to control the flow rate and / or pressure of the gas they deliver, for example, to supply a NO / N2 mixture and / or oxygen at a pressure between 3 and 6 bar. The gas dispensing valve 13 may be protected against impacts by a protective cover (not shown).

[0024] Furthermore, the installation 10 also includes a medical ventilator 30, that is to say a respiratory support device, providing a flow of respiratory gas containing oxygen in non-hypoxic quantity to patient P, that is to say at least 21% vol. of oxygen about, typically air, oxygen or an oxygen / nitrogen mixture (N2 / O2).

[0025] The medical ventilator 30 is fluidically connected to the patient via a breathing gas circuit 20 which here has two breathing branches 21, 22 since it includes an inspiratory branch 21, i.e. a gas supply line, used to bring the breathing gas to the patient and an expiratory branch 22 used to recover the CO2-enriched gas exhaled by the patient.

[0026] The two inspiratory and expiratory branches 21, 22 typically comprise flexible tubing made of polymer or similar material. The inspiratory branch 21 is fluidically connected upstream to a gas outlet 31 of the medical ventilator 30 and downstream to a junction piece 23, typically a Y-piece. Similarly, the expiratory branch 22 is fluidically connected upstream to the junction piece 23 and downstream to a gas inlet 32 ​​of the medical ventilator 30. The two inspiratory and expiratory branches 21, 22 are thus connected to each other at the junction piece 23, typically a Y-piece, which is itself in fluidic communication with a respiratory interface 28 supplying gas to the patient, such as a tracheal intubation tube, a breathing mask, or other device, preferably a tracheal intubation tube.

[0027] Of course, the medical ventilator 30 and the NO supply device 1 are normally powered by an electrical source(s), particularly their components requiring electrical power to operate, especially the control means 50 and the display 3 of the NO supply device 1, the control system (not shown) of the medical ventilator 30, i.e., the microprocessor-based electronic board(s), or any other component, including the internal motorized turbine that supplies the airflow or analog, i.e., the breathing gas. The electrical source may be mains power (110 / 220V) and / or an electric battery, preferably rechargeable.

[0028] As can be seen, the NO 1 supply device or apparatus allows the NO / N 2 mixture to be injected into the inspiratory branch 21 of the gas circuit 20, via a NO 6 injection line or conduit opening into the inspiratory branch 21 at an injection site 25, so as to produce a mixing (i.e. a dilution) of the NO / N 2 flow and the respiratory gas flow containing at least 21% of approximately O 2, i.e. air or oxygen / nitrogen mixture, delivered by the medical ventilator 30.

[0029] The NO supply device 1 includes an outlet orifice or port 9 located at the outlet of its main gas circuit 40, 40.1, 40.2 through which the NO / N 2 flow exits the housing 2 of the NO supply device 1 and enters the NO injection conduit 6 which is fluidically connected to said outlet orifice or port 9, for example via a connector or similar.

[0030] The therapeutic gas mixture obtained (i.e. at the injection site 25 and downstream of the inspiratory branch 21), that is, the final mixture, therefore contains oxygen (approximately >20 to 21% vol.), generally nitrogen, and a variable and adjustable concentration of NO, typically between 1 and 80 ppmv, due to the dilution produced during the mixing of gas streams, and possibly unavoidable impurities, such as argon, which may be present in the gas but are not desired, particularly when the gas stream from the ventilator 30 is atmospheric air rather than an O2 / N2 mixture.

[0031] Advantageously, a gas humidifier 26 is further provided, arranged on the inspiratory branch 21 downstream of the injection site 25, to humidify the therapeutic gas flow, e.g., the final NO / N₂ / O₂ mixture, by adding water vapor, before it is inhaled by the patient. This prevents or limits drying of the patient's airways during inhalation treatment. In another embodiment, the gas humidifier 26 could also be arranged upstream of the injection site 25.

[0032] Furthermore, optionally, the expiratory branch 22 used to collect exhaled gases rich in CO2 may include one or more other optional components, such as a device 29 for the removal of CO2 and / or water vapor, i.e. a CO2 and / or water trap, such as a hot tray, a filter or other, allowing the removal (at least part of) the CO2 and / or water vapor present in the gases exhaled by the patient.

[0033] As seen on Fig. 1 , it is also provided on the inspiratory branch 21, upstream of the injection site 25, a flow sensor 24, for example a mass flow sensor, connected to the NO supply device 1, in particular to the control means 50 of said NO supply device 1, via a respiratory gas flow measurement line 7 used to measure or determine the gas flow from the ventilator 30 within the inspiratory branch 21 and to supply it to the control means 50 so that they can control the quantity of NO / N 2 to be supplied.

[0034] Indeed, determining the gas flow rate from fan 30 allows, in particular, the regulation of NO passage through the NO supply device 1. This means that the flow rate of the NO / N2 mixture to be injected can be chosen based on the desired NO concentration, the composition of the NO / N2 mixture from the cylinders, and the gas flow rate (i.e., air or air / O2) from fan 30. The method for regulating the passage of NO through the NO supply device 1 is detailed below with reference to Fig. 2 notably.

[0035] Furthermore, a gas sampling line 15 fluidly connects the NO supply device 1, via a sampling inlet 8, to the inspiratory branch 21 of the respiratory gas circuit 20, via a connecting connector 27, preferably near the Y-piece 23, for example about 10 to 20 cm upstream of the Y-piece. This sampling line 15 is used to collect gas samples from within the inspiratory branch 21 to verify their conformity with the desired gas mixture to be administered to the patient, in particular with regard to its NO content but also O2, or even toxic NO2 species that may have been created by oxidation of NO molecules by oxygen.

[0036] As already stated, the NO / N2 mixture delivered by the NO1 supply device is injected (in 25) into the breathing stream containing at least 21% vol. of oxygen (e.g. air or O2 / N2 mixture) from the medical ventilator 30 before being administered by inhalation to the patient as a final breathing mixture (i.e. NO / N2 / O2 or NO / N2 / air mixture) generally containing a few ppmv or tens of ppmv of NO (ppm by volume) and at least about 21% vol. of oxygen O2, for example on the order of 1 to 80 ppmv of NO, the remainder generally being essentially nitrogen (N2), typically less than 40 ppmv of NO, for example on the order of 20 ppmv.

[0037] In order to deliver the correct quantity of NO, it is essential to be able to adjust the quantity, i.e. the flow, of the NO / N2 mixture passing through the NO supply device 1 and exiting through the NO outlet 9 before being conveyed by the NO injection line 6 to the injection site 25. This regulation is carried out by the control means 50 based not only on the measurements of the gas flow rate (i.e. air or O2 / N2 mixture) from the ventilator 30, which are carried out by the flow sensor 24 arranged on the inspiratory limb 21, but also on the desired NO content or dose set by the medical staff and the composition of the NO / N2 mixture coming from the NO cylinders 11.

[0038] To this end, as illustrated on Fig. 2 , the NO supply device or apparatus 1 includes an internal main gas circuit 40; 40.1, 40.2, i.e. passages, conduits or the like, to carry the NO / N 2 mixture entering through the gas inlet port(s) or orifice(s) 4 to (one or more) the NO outlet orifice 9, to which the NO 6 injection conduit is fluidly connected.

[0039] In the proposed embodiment, the main gas circuit 40; 40.1, 40.2 comprises a main NO line 40, the upstream part of which branches into two parallel sections 40.1, 40.2, each comprising a gas inlet orifice 4 fluidly connected to one or the other of the NO / N2 mixture cylinders 11, which supplies it with the NO / N2 mixture at the desired pressure, for example between 3 and 6 bar pressure.

[0040] The main gas circuit 40; 40.1, 40.2, in particular the main NO line 40, includes NO / N2 flow control means 42, 43 which are controlled by the (micro)processor-based control means 50 52 of the NO supply device 1. The control means or device 50 typically includes one (or more) (micro)processor(s) 52 arranged on one (or more) electronic board 53, the operation of which is explained below.

[0041] Furthermore, a bypass circuit 41, also called the "emergency circuit", connects (at 140, 141) fluidly to the main gas circuit 40; 40.1, 40.2, in particular to the main NO line 40, at an upstream connection site 140 located upstream of said flow control means 42, 43 and at a downstream connection site 141 located downstream of said flow control means 42, 43, considering the normal direction of flow of the NO / N mixture 2 (from the inlets 4 to the outlet 9), so as to bypass said flow control means 42, 43.

[0042] In other words, the bypass circuit 41 includes or constitutes a diversion line allowing the NO / N2 mixture to be diverted and prevented from passing through the flow control means 42, 43 arranged on the main gas circuit 40; 40.1, 40.2, in particular on the main NO line 40. This bypass or backup circuit 41 is used in the event of a malfunction, in particular of the main solenoid valve 42 arranged on the main gas circuit 40; 40.1, 40.2, in order to ensure delivery of the NO / N2 mixture despite this malfunction.

[0043] The bypass circuit 41, i.e., gas passage, gas conduit, or similar, includes secondary flow control means 45, 46, i.e., a secondary flow control device comprising one or more secondary solenoid valves 45, and a fixed flow device 46, i.e., delivering or supplying (downstream) a predetermined fixed gas flow rate (fixed Q). Optionally, the flow rate could be modified, in particular by using a pressure-reducing device 47, as explained below.

[0044] According to the invention, the secondary solenoid valve 45 is an on / off (ON / OFF) type solenoid valve, that is to say, it is configured to adopt only two operating positions (i.e., open / closed), namely an "open position" allowing the entire NO / N2 mixture flow to pass and a "closed position" preventing any NO / N2 mixture flow from passing. As an example, the commercial reference FAS 10mm PICOSOL on / off solenoid valve can be used as the on / off solenoid valve 45.

[0045] Otherwise, when the on / off type solenoid valve 45, i.e. the secondary solenoid valve 45, is in the open position, the entire NO / N2 mixture gas flow can pass through it and circulate freely in the bypass circuit 41 in the normal direction of gas flow, i.e. from the upstream connection site 140 to the downstream connection site 141.

[0046] Conversely, when the TOR solenoid valve, i.e. the secondary solenoid valve 45, is in the closed position, the NO / N2 mixture gas flow is interrupted and can no longer pass through it since it is stopped by this solenoid valve 45. The free circulation of gas in the bypass circuit 41 is prevented, stopped or impossible.

[0047] The secondary solenoid valve 45 is controlled by the pilot means 50 with processor 52 so as to move it from one position to another, preferably to operate a delivery of NO by pulsations or pulses, as detailed below.

[0048] Furthermore, a fixed flow device 46, typically a calibrated orifice device, is arranged on said bypass circuit 41. It allows a predetermined fixed flow Q of NO / N2 gas mixture to be delivered, that is to say a known flow, for example a flow of 0.1 to 2 L / min, for example on the order of 0.5 L / min. It is arranged downstream of the secondary solenoid valve 45, that is to say between the secondary solenoid valve 45 and the downstream connection site 141. The fixed gas flow rate Q resulting from the passage of the gas flow through the fixed flow device 46 is known and stored in storage means 51 configured to store the fixed flow rate Q, preferably the storage means 51 are integrated into the control means 50, in particular carried by the electronic board 53. The storage means 51 include computer memory, such as flash memory or other.

[0049] Preferably, the bypass circuit 41 may also include a gas regulator device 47 arranged upstream of the secondary solenoid valve 45 allowing the gas pressure to be regulated or adjusted, typically reducing it if necessary, and / or the gas flow rate.

[0050] In all cases, the storage means 51 cooperate with the control means 50, in particular with the processor(s) 52, to provide them with, among other things, the stored value of the fixed gas flow rate Q. The storage means 51 use the (i.e., at least one) stored value of the fixed gas flow rate Q to perform calculations, in particular of the pulse time (di) as explained below when it is necessary to vary the quantity of NO supplied.

[0051] In addition, the flow control means 42, 43 include a main proportional solenoid valve 42 and a flow sensor 43, i.e., flow measurement means or device, arranged on the main gas circuit 40; 40.1, 40.2, typically on the main NO line 40 of said main gas circuit 40; 40.1, 40.2. By way of example, the commercially available FAS 16mm FLATPROP proportional solenoid valve can be used as the proportional solenoid valve 42.

[0052] The flow sensor 43 is preferably arranged upstream of the proportional solenoid valve 42, considering the direction of gas flow from the inlet port(s) 4 to the outlet port 9, i.e. from the upstream connection site 140 to the proportional solenoid valve 42. The flow sensor 43 and the proportional solenoid valve 42 are electrically connected to the control means 50.

[0053] The flow sensor 43 provides the control means 50 with representative measurements of the gas flow in the main NO line 40 of the main gas circuit 40; 40.1, 40.2, immediately upstream of the proportional solenoid valve 42. Their precise operation is explained below.

[0054] In general, the control means 50 are configured to operate the main solenoid valve 42 and the secondary solenoid valve 45 in order to control the flow rate of the NO / N₂ mixture passing through these main 42 and secondary 45 solenoid valves, specifically to allow the gas flow to circulate through either of these main 42 solenoid valves (in normal operation) or secondary 45 solenoid valves (in backup operation, i.e., in case of malfunction), but never through both simultaneously. In other words, the two main 42 and secondary 45 solenoid valves are never open at the same time, so that the gas flow must necessarily circulate exclusively through one of the two.

[0055] The components of device 1 are arranged in a housing 2, that is to say a rigid external casing.

[0056] Under normal conditions, i.e. during normal operation of the NO 1 delivery device, the gas flow of the NO / N 2 gas mixture circulates in the main gas circuit 40, 40.1, 40.2, in particular in the main NO line 40, and passes through the main solenoid valve 42 since this main solenoid valve 42 is open to allow gas to circulate in the main gas circuit 40, 40.1, 40.2, in particular in the main NO line 40, while the secondary solenoid valve 45 is closed to prevent any gas circulation in the bypass circuit 41 which includes the secondary solenoid valve 45.

[0057] Conversely, in the event of a problem, for example a fault in the flow sensor 43 or a malfunction of the main solenoid valve 42, the NO / N2 gas mixture flow is diverted to the bypass circuit 41, which then acts as a backup circuit. The main solenoid valve 42 then closes to stop / prevent any gas flow through it, i.e., in the portion of the main NO line 40 comprising the flow control means 42 and 43, including the main solenoid valve 42, which is schematically located between the upstream connection point 140 and the downstream connection point 141.

[0058] In order to be able to better control the flow of the NO / N 2 gas mixture supplied by the NO 1 delivery device, i.e. delivered in particular by the outlet port 9 which is located at the outlet of its main gas circuit 40, 40.1, 40.2, when this gas flow circulates in the bypass circuit 41, i.e. in backup mode, the secondary solenoid valve 45 which is an on / off type solenoid valve is controlled in pulsed mode by the control means 50, i.e. it does not deliver a continuous flow of NO / N 2 but small doses or pulses of gaseous NO / N 2.

[0059] When the control means 50 control the secondary solenoid valve 45 to deliver gaseous pulses or "pulses" of gas into the bypass circuit 41, i.e. downstream of the secondary solenoid valve 45, the main solenoid valve 42 is closed to prevent its passage by the gas flow, i.e. the NO / N2 mixture flow.

[0060] More specifically, the control means 50 are configured, e.g. programmed, to control the secondary solenoid valve 45 in pulsed mode so as to alternately, e.g. over time, between open and closed positions and thus deliver the NO / N2 mixture in the form of successive gaseous pulses, e.g. "pulses" of gas.

[0061] The gas pulses can be controlled. Indeed, each gas pulse includes or is characterized by a pulse time (di) of non-zero duration (ie > 0 msec) during which the secondary solenoid valve 45 is in the open position and thus allows the passage of a desired quantity of NO / N 2 mixture, i.e. its passage by a given quantity of gas, towards the fixed flow device 46 arranged on said bypass circuit 41, downstream of the secondary solenoid valve 45 which is a TOR solenoid valve controlled by the pilot means 50.

[0062] The desired quantity of NO / N2 mixture is therefore variable since it corresponds to the predetermined fixed flow rate (Q fixed) of NO / N2 mixture delivered by the fixed flow device 46 during the pulse time (di) of the gas pulse considered, i.e. the time during which the secondary solenoid valve 45 is in the open position and allows the passage of gas.

[0063] In other words, the proportion or quantity of NO / N2 mixture passing through the secondary solenoid valve 45 of the TOR type can be controlled by playing with the pulse time (di) of each gas pulse considered since the fixed flow device 46 delivers a predetermined, i.e. known, fixed flow (Q fixed) of NO / N2 mixture.

[0064] The pulse time (di) of each gas pulse is calculated or determined by the control means 50 based in particular on the desired gas flow rate (Q desired) but also on the NO content of the NO / N2 mixture and on one (or more) predefined and generally memorized flow rate, in particular in case of fault of the sensor 24.

[0065] So, Fig. 3 schematically represents a plurality of successive gaseous pulses IG obtained over time (t) by controlling the opening / closing of the secondary solenoid valve 45 of the TOR type in pulsed mode.

[0066] We see that each gas pulse IG has a non-zero (i > 0 msec) but variable duration or pulse time (di) so as to deliver variable doses or quantities of NO / N 2 mixture and thus obtain a desired gas flow rate (Q desired) downstream of the fixed flow device 46. Typically, the pulse times (di) can reach about 200 msec.

[0067] Furthermore, according to the invention, in normal operation (i.e. without any malfunction), when this gas flow does not circulate in the bypass circuit 41, the control of the flow through the proportional solenoid valve 42 arranged on the main gas circuit 40, 40.1, 40.2 is done proportionally.

[0068] In general, the proportional solenoid valve 42 is configured to have opening degrees ranging from 0 to 100% where: 0% corresponds to a total closure of the solenoid valve 42 preventing any passage of gas flow, 100% corresponds to a total opening of the solenoid valve 42 allowing a maximum flow of gas flow, and the intermediate values ​​between 0 and 100% correspond to intermediate degrees of opening, i.e. partial openings of the solenoid valve 42 allowing the passage of non-zero gas flow rates but less than the maximum flow rate of the gas flow.

[0069] In this case, the control means 50 are configured to control the proportional solenoid valve 42 differently depending on whether this proportional solenoid valve 42 is in its linear operating range or in its non-linear operating range.

[0070] Indeed, the proportional solenoid valve 42 is configured to operate within (at least) two given operating ranges between 0 and 100%, namely: a first operating range, i.e. non-linear, also called "low" corresponding to degrees of opening of the proportional solenoid valve 42 between 0 and x% with: 0 < x% ≤ 10%, preferably 0 < x% ≤ 5%, for example between 0 and 1% (i.e. x% = 1%), and a second operating range, i.e. linear, corresponding to degrees of opening greater than x%, i.e. between x% and at least 85%, for example between x% and 90%, for example between 1 and 90%, typically between 10 and 90% of its operating range.

[0071] Optionally, the proportional solenoid valve 42 can be configured to operate according to a third operating range, i.e. non-linear, also called "high" corresponding to degrees of opening close to 100%, for example at least 80%, preferably at least 90%, for example between 90% and 100%.

[0072] In all cases, according to the invention, the control means 50 are configured to control the proportional solenoid valve 42 to operate a gas supply, i.e., a NO / N2 mixture, in a different way depending on the operating range considered, i.e., depending on the degree of opening of the proportional solenoid valve 42, namely: in proportional mode in the second operating range, i.e. linear range, that is to say for degrees of opening greater than x%, typically between 1 and 90%, for example between 1% and 90% (x%=1%) or between 10% and 90% (x%=10%), and in pulsed mode or pulse modulation in the first operating range, i.e. non-linear range, that is to say between 0 and x%, with x% ≤ 10%, by between 0 and 10% (x%=10%) or between 0 and 1% (x%=1%).

[0073] Of course, x% can take values ​​between 1 and 10%, for example 2%, 3%, 4%, 5%, 7%... or other.

[0074] Therefore, it appears that: In proportional mode, the gas flow through solenoid valve 42 is continuous; in pulsed mode, the gas flow through solenoid valve 42 takes the form of successive gas pulses (IG), therefore is discontinuous.

[0075] This is illustrated in Fig. 4 et Fig. 5 , where the IG pulses or gas pulses delivered by the proportional solenoid valve 42 have been schematically represented in order to obtain the desired gas flow rate (Q desired) downstream of the proportional solenoid valve 42.

[0076] On these Fig. 4 &5, the first operating range which is non-linear goes from 0 to 1% (x%=1%) and the second operating range which is linear goes from 1 to approximately 90%.

[0077] In Fig. 4 We can see that it is possible to fix, adjust or modulate the gas flow supplied by playing on the width of each gas pulse IG (i.e. width of the IGs on the graph) which corresponds to the time (i.e. the duration) of opening of the proportional solenoid valve 42. Indeed, the longer the opening time of the proportional solenoid valve 42, the greater the quantity of gas (i.e. flow) which can pass through it, during each pulse IG, and vice versa.

[0078] Furthermore, in Fig. 5We can see that it is also possible to fix, adjust or modulate the gas flow supplied by playing on the amplitude of each gas pulse IG (i.e. its height of IG on the graph), which corresponds to the degree of opening of the proportional solenoid valve 42. Indeed, the higher the degree of opening (x%) of the proportional solenoid valve 42 (for example close to 1% when x=1%), the larger its opening / passage cross-section, therefore more gas can pass through it during each IG pulse, and vice versa.

[0079] By varying the amplitudes and / or widths of the gas pulses, we can deliver a quantity of NO that corresponds to the desired gas flow rate (desired Q).

[0080] This control of the amplitude or duration of the gas pulses IG is operated by the control means 50 which control the proportional solenoid valve 42, in particular according to the desired gas flow rate, which depends on the flow rate of the gas containing oxygen (> approx. 20% vol) delivered by the fan 30 measured by the flow sensor 24, such as an air flow or O2 / N2 gas mixture, the concentration of NO in the NO / N2 gas mixture supplying the device 1 and the desired dosage, i.e. the desired NO content in the final gas mixture resulting from the mixing of the gas containing oxygen (> approx. 20% vol) delivered by the fan 30 and the NO / N2 flow from the device 1.

[0081] The NO supply apparatus 1 and / or the gas supply installation of the invention 10 are used to perform an inhalation administration, in particular via a tracheal intubation tube, of a gas mixture comprising 1 to 80 ppmv of NO, typically in the order of 10 to 20 ppmv of NO, and at least 20% vol. about oxygen to a patient in need (e.g. adult, child, adolescent or neonate, including a premature one), typically a patient (i.e. a human being) suffering from pulmonary hypertension and / or hypoxia likely to cause pulmonary vasoconstrictions or similar, for example caused by pulmonary pathologies or disorders such as PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by cardiac surgery with the patient being placed under extracorporeal blood circulation (ECC).

Claims

1. A NO supply apparatus (1) comprising: - a main gas circuit (40; 40.1, 40.2) for conveying an NO / N gas mixture, - flow control means (42, 43) comprising a main solenoid valve (42) arranged on the main gas circuit (40; 40.1, 40.2), and - control means (50) configured to control at least said one main solenoid valve (42) to control the flow rate of NO / N□ gas mixture passing through said main solenoid valve (42), characterized in that: - the main solenoid valve (42) is a proportional solenoid valve having opening degrees between 0 and 100%, and is configured to operate in at least two given operating ranges comprising at least: ▪ a first operating range corresponding to degrees of opening of the main solenoid valve (42) between 0 and x% with: 0 < x% ≤ 10%, and ▪ a second operating range corresponding to opening degrees of the main solenoid valve (42) > x%, and - the control means (50) are configured to control said main solenoid valve (42) to operate a gas supply differently according to the operating range in question, namely: ▪ in pulse mode in the first operating range so as to deliver successive gas pulses (IG), and ▪ in proportional mode in the second operating range, - and it further comprises a bypass circuit (41) fluidly connected to the main gas circuit (40; 40.1, 40.2), upstream and downstream of the flow control means (42, 43) and comprising secondary flow control means (45, 46) comprising a secondary solenoid valve (45) of the on / off type and a fixed flow device (46).

2. Apparatus according to claim 1, characterized in that the control means (50) comprise at least one microprocessor arranged on an electronic card.

3. Apparatus according to claim 1, characterized in that the first operating range corresponds to degrees of opening of the main solenoid valve (42) between 0 and x%, where: 0 < x% ≤ 5%.

4. Apparatus according to claim 1, characterized in that the control means (50) are configured to set or adjust a duration or amplitude of each gas pulse (IG) delivered in pulse mode, to control the gas flow rate through said main solenoid valve (42).

5. Apparatus according to claim 4, characterized in that the control means (50) are configured to adjust, for each pulse, the pulse duration (IG) by controlling the opening duration of the proportional solenoid valve (42).

6. Apparatus according to claim 4, characterized in that the control means (50) are configured to adjust, for each pulse, the pulse duration (IG) by controlling the amplitude of each pulse (IG) by controlling the degree of opening (x%) of the proportional solenoid valve (42).

7. Apparatus according to claim 5, characterized in that the opening duration of the proportional solenoid valve (42) is between 5 and 200 msec.

8. Apparatus according to claim 5 or 6, characterized in that, in pulsed mode, the control means (50) are configured to control the proportional solenoid valve (42) to deliver successive gas pulses, each gas pulse having a non-zero pulse duration (di) during which the proportional solenoid valve (42) is in a partially open position with an opening degree x%, such that x% < 10%, of , so as to allow the passage of a given quantity of NO / N(2)mixture during said pulse duration (di).

9. Apparatus according to claim 8, characterized in that the pulse time (di) of each gas pulse (IG) is of variable non-zero duration.

10. Apparatus according to claim 9, characterized in that the pulse time (di) of each gas pulse (IG) is between 5 and 200 msec.

11. Apparatus according to claim 1, characterized in that the fixed flow device (46) comprises a calibrated orifice.

12. Apparatus according to claim 11, characterized in that the secondary solenoid valve (45) of the on / off type is controlled in pulsed mode by the control means (50).

13. Apparatus according to claim 12, characterized in that the secondary solenoid valve (45) is configured to adopt only two operating positions comprising an open position allowing the NO / N2 mixture flow to pass through and a closed position preventing any passage of the NO / N2 mixture flow .

14. Apparatus according to claim 11, characterized in that the fixed flow device (46) comprises a calibrated orifice device delivering a predetermined fixed flow rate (Qfixed ) between 0.1 and 2 L / min.

15. Installation for providing NO (10) to a patient, comprising: - at least one source (11) of NO / N□ mixture, - an NO supply apparatus (1) according to one of the preceding claims, fluidly connected to said at least one source (11) of NO / N mixture, - a medical ventilator (30) configured to supply a respiratory gas containing oxygen, typically at least approximately 20% oxygen, such as air or a N / O mixture, - a patient circuit (20) to which the NO supply apparatus (1) and the medical ventilator (30) are fluidly connected to supply said patient circuit (20) with said NO / N gas mixture and said oxygen-containing respiratory gas, respectively, and - a flow sensor (24) arranged on the patient circuit (20) and configured to determine and supply to the control means (50) of the NO supply apparatus (1) at least one measurement signal representative of the gas flow within the patient circuit (20).