Pulsed-mode nitrogen monoxide gas delivery device

Abstract

Title of the Invention: Pulsed-Mode Nitric Oxide Gas Delivery Apparatus. The invention relates to a NO delivery apparatus (1) comprising a main gas circuit (40; 40.1, 40.2) with flow control means (42, 43) including at least one main solenoid valve (42), and a bypass circuit (41) connecting (140, 141) to the main gas circuit (40; 40.1, 40.2) by bypassing the flow control means (42, 43). Secondary flow control means (45, 46) including at least one on / off secondary solenoid valve (45) are arranged on the bypass circuit (41). A fixed-flow device (46) is arranged on the bypass circuit (41). Control means (50) control the secondary solenoid valve (45) in pulsed mode to alternately switch it between open and closed positions so as to produce a NO / N2 mixture in the form of successive gaseous pulses having a pulse time (di) of non-zero duration.Installation for supplying NO (10) to a patient including the device (1). Figure of the abstract: Figure 2.

Description

Title of the invention: Device for delivering gaseous nitrogen monoxide in pulsed mode

[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, particularly pulmonary vasoconstrictions in adults or children, including newborns (PPHN), as described for example by EP-A-560928 or EP-A-1516639.

[0003] A NOi treatment implementation installation, commonly called a NO-based therapeutic gas delivery installation for a patient or more simply an NO delivery installation, classically comprises one or more NO / N2 mixing cylinders supplying an NO delivery device which 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 21% vol. of oxygen about, 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 breathing interface, such as a tracheal intubation tube, to provide 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 setup is shown schematically in [Fig. 1].

[0004] Such a NO delivery system is used in a hospital setting 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-A-3821929, WO-A-2012 / 094008, US-A-2015 / 320951, US-A-2015 / 273175, JP-A-H11192303, WO-A-02 / 40914 and US-A-2003 / 116159.

[0005] In order to efficiently deliver the gas to the patient(s), the NO supply device that is part of the NO administration installation is generally equipped with proportional solenoid valve type actuators, as taught by EP-A-659445, or on / off solenoid valves, or even a combination of the two as described by EP-A-375671, which allow different flow rate values ​​to be generated This depends in particular on the NO concentration to be delivered, as determined by the healthcare staff, and the concentration of the cylinders. Specifically, the higher the concentration in the cylinders, the lower the NO delivery rate should 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 higher flow rates for adult treatments which 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 complexity of the internal gas circuit of the NO supply device and necessarily to its cost.

[0008] In other words, there is a need for an apparatus or device for supplying NO, typically a gaseous mixture of NO / N2, which does not have all or some of the aforementioned disadvantages and problems, which is suitable for the treatment of 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 fluidly connecting at least one NO inlet port to at least one NO outlet port to convey a NO / N2 mixture (i.e., a gaseous mixture) from said at least one NO inlet port to said at least one NO outlet port, - flow control means comprising at least one main solenoid valve, arranged on said main gas circuit, - a bypass circuit, also called a "backup circuit", which connects fluidly to the main gas circuit, upstream and downstream of said flow control means in order to bypass said flow control means, - secondary flow control means comprising at least one secondary solenoid valve, arranged on said bypass circuit, and - control means configured to control 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 rate of NO / N2 mixture passing through said at least one main solenoid valve and / or said at least one secondary solenoid valve,

[0010] and wherein: - said at least one secondary solenoid valve is an on / off type solenoid valve configured to adopt only two positions of operation comprising an open position allowing the flow of NO / N2 mixture and a closed position preventing any passage of NO / N2 mixture flow. - it further comprises a fixed flow device arranged on said bypass circuit delivering a predetermined fixed flow rate (Qflxe) of NO / N2 mixture, and - the control means are configured to control said at least one secondary solenoid valve in pulsed mode to alternately switch said at least one secondary solenoid valve between the open and closed positions so as to deliver the NO / N2 mixture in the form of successive gaseous pulses,

[0011] where each gaseous pulse comprises a pulse time (di) of non- zero during which said at least one secondary solenoid valve is in the open position and permits the passage of a desired quantity of NO / N2 mixture corresponding to the predetermined fixed flow rate (Qflxe) of NO / N2 mixture delivered by the fixed flow device during the pulse time (di) of the gas pulse considered.

[0012] 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. - By "flow sensor", we mean a sensor of the type measuring and providing one or more flow signals or measurements, or of the type measuring and providing one or more pressure signals or measurements which are then converted into flow by the control means. - All terms "means of" are considered to be totally 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"...

[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 features: - the fixed flow device includes a calibrated orifice device delivering the predetermined fixed flow rate (Qflxe). Typically, the predetermined fixed flow rate (Qfixe) is between 0.1 and 2 L / min, preferably between 0.1 and 1 L / min, typically in the order of 0.5 L / min. the pulse time (di) of each gaseous pulse is of variable non-zero duration, preferably between 5 msec and approximately 200 msec. the gas pulses are separated from each other by closing times (df) during which said at least one secondary solenoid valve is in the closed position. The closing times (df) have equal or variable durations. Typically, closing times (df) have durations ranging from greater than 0 msec to as high as 195 msec. It includes storage means configured to store the predetermined fixed flow rate (Qfixe) delivered by the fixed flow rate device. Preferably, the storage devices are integrated into the control devices. The means of storage include computer memory, for example flash memory. the fixed flow device is arranged on said bypass circuit, downstream of said at least one secondary solenoid valve. The fixed flow device delivers a gas flow at a predefined fixed flow rate. The control means are configured to determine the desired amount 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 include at least one (micro)processor. the main gas circuit includes 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 pilot means. the main gas circuit includes a main NO line. said at least one main solenoid valve and at least one flow sensor are arranged on the main NO line. - the upstream part of the main NO line branches into two parallel sections, each including a gas inlet port to receive 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 regulator 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 source of NO / N2 mixture, typically one or more pressurized gas cylinders containing the NO / N2 mixture, - a NO supply device according to the invention fluidly connected to said at least one NO / N2 mixing source, - a medical ventilator configured to provide a breathing gas containing oxygen, typically at least about 21% oxygen, such as air or an N2 / O2 mixture, - 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 to the control means of the NO delivery device, at least one measurement signal representative of the gas flow within the patient circuit, namely one (or more) signal or one (or more) measurement of flow or pressure.

[0015] Depending on the embodiment considered, the gas supply installation of the invention may comprise one or more of the following features: - the patient circuit includes a NO injection module supplied with NO / N2 mixture by the NO supply 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 links (e.g. cables or similar). - 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 of the mass flow sensor type or similar. 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 links, such as cables or the like. The NO supply device is fed with a NO / N2 gas mixture consisting of NO and nitrogen from the NO / N2 mixture source(s). The NO delivery line from the NO supply device 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 device comprises a housing, in which are arranged 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) delivering the breathing gas, typically air or an oxygen / nitrogen mixture, or even pure oxygen. the NO source(s) contains 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 abs, typically more than 100 bar abs (before the start of withdrawal), preferably between 100 and 1000 ppmv of NO, the remainder being nitrogen (N2). The NO source(s) includes one (or more) pressurized gas cylinder(s). the NO source includes one (or more) gas cylinders with a capacity of 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 regulator) or with an integrated regulator or RDI, preferably an RDI protected by a protective cover, for example made of metal or polymer. The patient circuit includes an inspiratory branch and an expiratory branch. - the patient circuit includes flexible conduits forming the inspiratory limb and / or the expiratory limb, typically polymer tubing. - the inspiratory branch and the expiratory branch, e.g. flexible conduits, are connected to a junction piece, such as a Y-piece. - the inspiratory limb and / or the expiratory limb are fluidly connected to a patient respiratory interface, preferably via the junction piece. - The patient respiratory interface includes a tracheal intubation tube or respiratory mask. - the inspiratory branch and the expiratory branch include flexible conduits, for example made of polymer. - the inspiratory branch and the expiratory branch are further fluidically connected to, respectively, outlet and inlet 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 be able 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 which is inhaled by the patient, after mixing the NO / N2 mixture with the breathing gas containing oxygen from the ventilator, such as air or an O2 / N2 mixture (>21% vol. approx.), is between 1 and 80 ppm by volume (ppmv), depending on the population treated, i.e. newborns or adults, the condition of the patient and / or the disease to be treated.

[0016] The NO supply apparatus and / or gas supply installation 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 21% vol. of approximately oxygen, typically in the range of 10 to 20 ppmv of NO, to one or more patients (e.g., adults, children, adolescents, or neonates) in need of it, typically patients (i.e.human persons) suffering from pulmonary hypertension and / or hypoxia likely to cause pulmonary vasoconstriction or similar conditions, 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] The invention will now be better understood with reference to the following detailed description, given by way of illustration but not limitation, with reference to the accompanying figures, among which:

[0018] [Fig-1] schematically illustrates a therapeutic gas administration system based on NO to a patient incorporating a NO delivery device according to the invention,

[0019] [Fig.2] schematically illustrates the operation of the NO supply device according to the invention,

[0020] [Fig.3] schematically illustrates the successive gas pulses resulting from the pulsed control of the secondary solenoid valve of the NO supply device of [Fig.2],

[0021] [Fig.4] schematically illustrates the successive gas pulses resulting from control of the width of each gas pulse in pulsed mode, during operation of the main solenoid valve within its non-linear operating range, and

[0022] [Fig.5] schematically illustrates the successive gas pulses resulting from amplitude control of each gas pulse in pulsed mode, during operation of the main solenoid valve within its non-linear operating range.

[0023] [Fig.1] schematically illustrates an embodiment of a therapeutic gas delivery system 10, namely a gas mixture based on NO, to a patient comprising a NO supply device 1 according to the present invention, in particular that schematically shown in [Fig.2].

[0024] It comprises here 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 from 225 to 2000 ppmv of NO and nitrogen (N2) for the remainder, preferably from 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.

[0025] The NO containers 11 supply the NO / N2 mixture to a NO supply device or apparatus 1 according to the invention, part of whose internal architecture is schematically shown in [Fig. 2]. The connection is made by NO supply lines 12, i.e., gas lines, such as flexible hoses or the like. 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 (see [Fig. 2]).

[0026] The NO supply device 1 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 O2 cylinder or, alternatively, the hospital network, i.e. an oxygen supply pipeline arranged in the hospital building where the patient is treated.

[0027] The NO₂ cylinders 11 and the O₂ source, e.g., an oxygen cylinder, are preferably equipped with a gas dispensing valve 13, preferably incorporating gas pressure-reducing 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).

[0028] Furthermore, the installation 10 also includes a medical ventilator 30, that is to say a respiratory assistance device, providing a flow of respiratory gas containing oxygen in non-hypoxic quantity to the patient P, that is to say at least 21% vol. of oxygen about, typically air, oxygen or an oxygen / nitrogen (N2 / O2) mixture.

[0029] The medical ventilator 30 is fluidically connected to the patient via a breathing gas circuit 20 which here has two breathing branches 21, 22 given that 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.

[0030] 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.

[0031] Of course, the medical ventilator 30 and the NO supply device or apparatus 1 are normally electrically powered by an electrical power source(s), in particular their components requiring electrical power to operate, in particular the control means 50 and the screen 3 of the NO supply device 1, the control system (not shown) of the medical ventilator 30, i.e. microprocessor electronic board(s), or any other component, in particular the An internal motorized turbine supplies the airflow or similar gas. The power source can be mains electricity (110 / 220V) and / or an electric battery, preferably rechargeable.

[0032] As can be seen, the NO supply device or apparatus 1 allows the NO / N2 mixture to be injected into the inspiratory branch 21 of the gas circuit 20, via an NO injection line or conduit 6 opening into the inspiratory branch 21 at an injection site 25, so as to produce a mixing (i.e. a dilution) of the NO / N2 flow and the respiratory gas flow containing at least 21% of O2 approximately, i.e. air or oxygen / nitrogen mixture, delivered by the medical ventilator 30.

[0033] 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 / N2 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.

[0034] The therapeutic gas mixture obtained (i.e. at the injection site 25 and downstream of the inspiratory branch 21), i.e. the final mixture, therefore contains oxygen (approximately >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, or even possible unavoidable impurities, such as argon for example, which may be present in the gas but are not desired, in particular when the gas stream from the ventilator 30 is atmospheric air rather than an O2 / N2 mixture.

[0035] Advantageously, a gas humidifier 26 is further provided, arranged on the inspiratory branch 21 downstream of the injection site 25, for humidifying 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 the 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.

[0036] Furthermore, optionally, the expiratory branch 22 used to collect exhaled gases rich in CO2 may include one or more other optional components, such as for example a device 29 for removing 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) of the CO2 and / or water vapor present in the gases exhaled by the patient.

[0037] As can be seen in [Fig. 1], a flow sensor 24, for example a flow sensor of the type, is also provided on the inspiratory branch 21, upstream of the injection site 25 mass, connected to the NO 1 supply device, in particular to the control means 50 of said NO 1 supply device, via a breathing gas flow measurement line 7 used to measure or determine the gas flow from the ventilator 30 within the inspiratory limb 21 and to supply it to the control means 50 so that they can control the quantity of NO / N2 to be supplied.

[0038] Indeed, determining the gas flow rate from the fan 30 makes it possible in particular to regulate the passage of NO through the NO supply device 1, that is to say, to be able to choose the flow rate of NO / N2 mixture to be injected according to the desired NO content, the composition of the NO / N2 mixture coming from the cylinders and the gas flow rate (i.e. air or air / O2) coming from the fan 30. The way of regulating the passage of NO through the NO supply device 1 is detailed below with reference to [Fig.2] in particular.

[0039] 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 to O2, or even to toxic NO2 species that may have been created by oxidation of NO molecules by oxygen.

[0040] As already stated, the NO / N2 mixture delivered by the NO supply device 1 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.

[0041] 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 measurements of the gas flow rate (i.e. air or O2 / N2 mixture) coming from the ventilator 30, which are taken by the flow sensor 24 arranged on the inspiratory limb 21, but also on the desired concentration or dose of NO. fixed by the nursing staff and the composition of the NO / N2 mixture from the NO 11 bottles.

[0042] To this end, as illustrated in [Fig.2], the NO supply device or apparatus 1 comprises an internal main gas circuit 40; 40.1, 40.2, i.e. passages, conduits or the like, to convey the NO / N2 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 injection conduit 6 is fluidly connected.

[0043] 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.

[0044] 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 control means 50 of the NO supply device 1, i.e. control means or device, typically comprising one (or more) (micro)processor(s) 52 arranged on one (or more) electronic card 53, the operation of which is explained below.

[0045] Furthermore, a bypass circuit 41, also called a "backup 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 / N2 mixture (from the inlets 4 to the outlet 9), so as to bypass said flow control means 42, 43.

[0046] In other words, the bypass circuit 41 includes or constitutes a bypass line to divert the NO / N2 mixture and prevent it 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.

[0047] The bypass circuit 41, i.e., gas passage, gas conduit, or the like, 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 45, i.e., delivering or supplying (downstream) a predetermined fixed gas flow rate (Qfixe). Optionally, the flow rate could be modified, in particular by means of a pressure-reducing device 47, as explained below.

[0048] According to the invention, the secondary solenoid valve 45 is an on / off (ON / OFF) type solenoid valve, that is to say, one which is configured to adopt only two operating positions (i.e., open / closed), namely an "open position" allowing the flow of NO / N2 mixture and a "closed position" preventing any flow of NO / N2 mixture. By way of example, the commercially available FAS 10mm PICOSOL on / off solenoid valve can be used as the on / off solenoid valve 45.

[0049] Otherwise, when the on / off type solenoid valve, i.e. the secondary solenoid valve 45, is in the so-called "open position", the 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. in the direction from the upstream connection site 140 to the downstream connection site 141.

[0050] Conversely, when the on / off type solenoid valve, i.e. the secondary solenoid valve 45, is in the closed position, the NO / N2 mixture gas flow can no longer pass through it since it is stopped by this solenoid valve 45. Its free circulation in the bypass circuit 41 is prevented, stopped or impossible.

[0051] 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, and to deliver NO by pulses or bursts, as detailed below.

[0052] Furthermore, a fixed flow device 46, typically a calibrated orifice device, is arranged on said bypass circuit 41. It allows a predetermined fixed flow Qflxe 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 Qfixe 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 Qfixe, 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.

[0053] In addition, the bypass circuit 41 may also include a gas pressure 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.

[0054] In all cases, the storage means 51 cooperate with the control means 50, in particular with the processor(s) 52, to provide them, among other things, with the stored value of the fixed gas flow rate Qfixe. The storage means 51 use the (i.e., at least one) stored value of the fixed gas flow rate Qfixe to operate calculations, including the pulse time (di) as explained below when it is necessary to vary the amount of NO supplied.

[0055] In addition, the flow control means 42, 43 include a proportional solenoid valve 42 and a flow sensor 43, i.e., means or a flow measurement device, arranged on the main NO line 40 of the 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.

[0056] 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 point 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. 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.

[0057] Generally, the control means 50 are configured to control 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, in particular to allow the gas flow to circulate through one or the other of these main 42 and secondary 45 solenoid valves, but never through both at the same time. In other words, the two main 42 and secondary 45 solenoid valves are never open simultaneously, so that the gas flow must necessarily circulate exclusively through one of the two.

[0058] The components of the device 1 are arranged in a housing 2, that is to say a rigid external casing.

[0059] Under normal conditions, i.e. during normal operation of the NO 1 delivery device, the gas flow of the NO / N2 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.

[0060] Conversely, in the event of a problem, for example in the event of a fault in the flow sensor 43, 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 moving to the closed position to stop / prevent any circulation of the gas flow through the main solenoid valve 42, that is to say in the portion of main line of NO 40 comprising the flow control means 42, 43, including the main solenoid valve 42, which is located schematically between the upstream connection sites 140 and downstream connection sites 141.

[0061] According to the invention, in order to be able to better control the flow of the NO / N2 gas mixture supplied by the NO delivery device 1, 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, 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 / N2 but small doses or pulses (i.e. bursts) of gaseous NO / N2.

[0062] When the control means 50 control the secondary solenoid valve 45 to deliver gaseous pulses or "pumps" 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.

[0063] 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 move it, e.g. over time, into the open position and into the closed position and thus deliver the NO / N2 mixture in the form of successive gaseous pulses, e.g. of "pumps" of gas.

[0064] The gas pulses can be controlled. Indeed, each gas pulse comprises 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 / N2 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.

[0065] The desired quantity of NO / N2 mixture is therefore variable since it corresponds to the predetermined fixed flow rate (Qfixe) 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.

[0066] 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 on the pulse time (di) of each gas pulse considered since the fixed flow device 46 delivers a predetermined fixed flow (Qfixe), i.e. known, of NO / N2 mixture.

[0067] 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 (Qdesired) 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 the event of a fault of the sensor 24.

[0068] Thus, [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.

[0069] It can be seen that each gas pulse IG has a non-zero (i.e. > 0 msec) but variable duration or pulse time (di) so as to deliver variable doses or quantities of NO / N2 mixture and thus obtain a desired gas flow rate (Qdesired) downstream of the fixed flow device 46. Typically, the pulse times (di) can reach about 200 msec.

[0070] According to another aspect, the invention also relates to the control of the flow through the proportional solenoid valve 42 arranged on the main gas circuit 40, 40.1, 40.2, when this gas flow does not circulate in the bypass circuit 41.

[0071] In this case, the control means 50 can be configured to control said proportional solenoid valve 42 to regulate the gas flow depending on whether the proportional solenoid valve 42 is in its linear operating range or in its non-linear operating range.

[0072] Indeed, the proportional solenoid valve 42 is configured to operate in (at least) two given operating ranges comprising: - a non-linear operating range referred to as "low" corresponding to degrees of opening of the proportional solenoid valve 42 between 0 and x% with: 0 < x% < 10%, for example between 0 and 1% (i.e., x% = 1%), and - a linear operating range corresponding to degrees of opening of the latter between x% and 90%, for example between 1 and 90%, typically between 10 and 90% of its operating range.

[0073] In this case, 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 proportional mode within the linear operating range, i.e. between, for example, 1 and 90%, and - in pulsed mode or in pulse modulation in the non-linear operating range, i.e. for example between 0 and 1%.

[0074] This is illustrated in [Fig.4] and [Fig.5], where the IG pulses or gases delivered by the proportional solenoid valve 42 are schematically represented in order to obtain the desired gas flow rate (Qdesired) downstream of the proportional solenoid valve 42.

[0075] In [Fig.5], it can be seen that it is possible to modulate the amplitude of each gas pulse IG (i.e. its height of IG on the graph) by playing on the degree of opening of the proportional solenoid valve 42. Indeed, the higher the degree of opening of the proportional solenoid valve 42, i.e. close to 1%, the larger its opening / passage cross-section, therefore more gas can pass through it during each pulse IG, and vice versa.

[0076] Furthermore, in [Fig.4], it can be seen that it is possible to modulate the width of each gas pulse IG (i.e., the width of the IGs on the graph) by playing on the time (i.e., the duration) of the 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 that can pass through it during each pulse IG, and vice versa.

[0077] By varying the amplitudes and / or widths of the pulses, it is possible to deliver a quantity of NO that corresponds to the desired 'average' flow rate (Qdesired)-

[0078] 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 but also the NO content of the NO / N2 mixture and the flow rate of the gas containing oxygen (> approx. 21% vol) delivered by the fan 30 measured by the flow sensor 24, such as an air flow or O2 / N2 mixture.

Claims

1. Demands NO supply apparatus (1) comprising: - a main gas circuit (40; 40.1, 40.2) fluidly connecting at least one NO inlet port (4) to at least one NO outlet port (9) to convey a NO / N2 mixture from said at least one NO inlet port (4) to said at least one NO outlet port (9), - flow control means (42, 43) comprising at least one main solenoid valve (42), arranged on said main gas circuit (40; 40.1, 40.2), - a bypass circuit (41) connecting (140, 141) fluidly to the main gas circuit (40; 40.1, 40.2), upstream and downstream of said flow control means (42, 43) so as to bypass said flow control means (42, 43), - secondary flow control means (45, 46) comprising at least one secondary solenoid valve (45), arranged on said bypass circuit (41), and - control means (50) configured to control said at least one main solenoid valve (42) of the flow control means (42, 43) and / or said at least one secondary solenoid valve (45) of the secondary flow control means (45, 46) to control the flow of NO / N2 mixture passing through said at least one main solenoid valve (42) and / or said at least one secondary solenoid valve (45), in which: - said at least one secondary solenoid valve (45) is an on / off type solenoid valve configured to adopt only two operating positions comprising an open position allowing the flow of NO / N2 mixture and a closed position preventing any flow of NO / N2 mixture, - it further comprises a fixed flow device (46) arranged on said bypass circuit (41) delivering a predetermined fixed flow rate (Qfixe) of NO / N2 mixture, and - the control means (50) are configured to control said at least one secondary solenoid valve (45) in pulsed mode to alternately switch said at least one secondary solenoid valve (45) between the open and closed positions so as to deliver the NO / N2 mixture in the form of successive gaseous pulses,where each gas pulse includes a pulse time (di) of non-zero duration during which said at least one secondary solenoid valve (45) is in the open position and permits the passage of a desired quantity of NO / N2 mixture corresponding to the predetermined fixed flow rate (Qflxe) of NO / N2 mixture delivered by the fixed flow device (46) during the pulse time (di) of the gas pulse considered, characterized in that the pulse time (di) of each gas pulse (IG) is variable and the pulse time (di) has a duration between 5 and 200 msec.,

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

3. Apparatus according to any one of claims 1 or 2, characterized in that the gas pulses (IG) are separated from each other by closing times (df) during which said at least one secondary solenoid valve (45) is in the closed position.

4. Device according to claim 1 or 2, characterized in that it comprises storage means (51) configured to store the predetermined fixed flow rate (Qfixe) delivered by the device at

5.

6.

7.

8.

9.

10. fixed flow rate (46), preferably the storage means (51) are integrated into the control means (50). Apparatus according to claim 4, characterized in that the predetermined fixed flow rate (Qfixe) delivered by the fixed flow rate device (46) is between 0.1 and 2 L / min. Apparatus according to claim 1, characterized in that the fixed flow device (46) is arranged on said bypass circuit (41), downstream of said at least one secondary solenoid valve (45). Apparatus according to claim 1, characterized in that the main gas circuit (40; 40.1, 40.2) comprises said at least one main solenoid valve (42) and at least one flow sensor (43). Apparatus according to claim 1, characterized in that said at least one main solenoid valve (42) is a proportional solenoid valve controlled by the piloting means (50). Device according to claim 1, characterized in that the control means (50) comprise at least one processor. Installation for supplying NO (10) to a patient comprising: - at least one source (11) of NO / N2 mixture, - a NO supply device (1) according to one of the claims 1 to 9, fluidly connected to said at least one source (11) of NO / N2 mixture, - a medical ventilator (30) configured to supply a breathing gas containing oxygen, typically at least about 21% oxygen, such as air or an N2 / O2 mixture, - a patient circuit (20) to which the NO supply device (1) and the medical ventilator (30) are fluidly connected to supply said patient circuit (20) with said NO / N2 gas mixture and said breathing gas containing oxygen, respectively, and - a flow sensor (24) arranged on the patient circuit (20) and configured to determine and provide to the control means (50) of the NO delivery device (1), at least one measurement signal representative of the gas flow within the patient circuit (20).

Images