WO2006000812A1

WO2006000812A1 - Breathing device

Info

Publication number: WO2006000812A1
Application number: PCT/GB2005/002524
Authority: WO
Inventors: John Dingley
Original assignee: Uws Ventures Limited
Priority date: 2004-06-26
Filing date: 2005-06-25
Publication date: 2006-01-05
Also published as: GB0414375D0

Abstract

A device for administering a controlled fixed amount of a gas such as carbon monoxide to a patient as a therapeutic treatment.

Description

Breathing Device

The present invention relates to a device which enables a measured amount of a gas to be breathed in by a patient. An example of such a gas would be carbon monoxide.

There is evidence in medical literature that carbon monoxide may, in low dose, be a useful medicament, References (1-5). Carbon monoxide is traditionally thought of as a poisonous gas; this is because it has a very high affinity for haemoglobin contained within red blood cells. Functioning haemoglobin is necessary for transport of oxygen from the lungs to the tissues and, if too many of the haemoglobin oxygen binding sites become bound to carbon monoxide (as carboxyhaemoglobin), the oxygen carrying capacity of the blood is reduced, leading to death in extreme cases of carbon monoxide poisoning; for example from car exhaust fumes, malfunctioning gas heaters etc.

However, it is also true that smokers might have typically 5% carboxyhaemoglobin and at this level it does not appear to have toxic effects.

Recently it has been discovered that carbon monoxide is an important mediator of cellular processes within the body; it may have a role as an anti-inflammatory drug. Uses for such a drug might be, for example, inflammatory bowel disease such as Crohn's disease, maintenance therapy in asthma and chronic obstructive pulmonary disease among others.

When breathing air, the carbon monoxide bound as carboxyhaemoglobin dissociates only slowly from the haemoglobin over several hours. The blood carboxyhaemoglobin level will halve in approximately 4-5 hours breathing air.

In order that carbon monoxide can be used as a therapeutic agent a patient would need to inhale a small known, accurately repeatable, calculated dose of carbon monoxide at regular intervals e.g. approximately 4 hours, so that a low but predictable level of carboxyhaemoglobin could be maintained in the blood in a safe manner, with minimal risk of overdose.

Devices have already been described for delivery of known doses of carbon monoxide for the purpose of measuring blood volume [5,6]. These involve re- breathing oxygen from a flexible bag, removing the exhaled carbon dioxide with a chemical scrubbing agent and then injecting the desired volume of carbon monoxide into this system such that it is all taken up into the blood after a short period of re- breathing this gas mixture.

Such a device to use carbon monoxide would not be particularly practical for routine use at intervals of several hours for periods of weeks, months or even years as a medicament.

Also known is a "spacer" device used by some asthmatic patients; these hollow devices are designed so that a metered dose of aerosol drug is sprayed into the cavity, after which the contents are inhaled (air plus aerosol droplets). Some patients prefer this to inhaling the aerosol directly. However such a device cannot deliver a repeatable known volume of gas (carbon monoxide) over and over again.

We have now devised a device which enables a measured volume of gas to be delivered to a patient.

According to the invention there is provided a device enabling a user to inhale a fixed repeatable volume of a gas, which device comprises a hollow tube adapted to contain a fixed volume of the gas which volume is equal to the volume of the gas to be inhaled. Preferably there are valves at each end of the tube, which valves have a space between them equal to the volume of gas to be inhaled and which valves are adapted to prevent diffusion of the gas from the tube prior to inhalation. This allows the intended volume of gas to be stored, at least for a short time after filling or loading the tube with the gas before inhalation of the gas by a patient.

Preferably the device comprises a hollow tube within which there are two one way valves defining a space of pre-determined volume between the valves, one valve being an inlet valve only allowing gas to enter the space between the valves and the other valve being an outlet valve only allowing gas to exit from the space between the valves, there being a gas inlet located between the valves to allow gas to enter the space between the valves and a gas outlet upstream of the outlet valve; the valves remaining closed when there is no pressure gradient across them.

The valves should have a low opening pressure e.g. 0.5 to 3 cm water, typically about 2cm water. Examples of suitable valves are weighted discs, lightly spring loaded discs, or "duck bill" valves.

The device can have a detachable mouthpiece above the outlet valve or a mouthpiece can form part of the device.

The volume of gas enclosed in the tube between the inlet and outlet valves is substantially equivalent to the volume of gas desired for delivery to the patient. The desired gas volume to be delivered to any given patient will determine this enclosed volume when the tube is constructed.

The use of the device is described with reference to carbon monoxide, but the device can be used with any gas or vapour which is inhaled by a patient. To fill the tube with the carbon monoxide, the carbon monoxide enters the tube through the gas inlet from a suitable supply e.g. a compressed cylinder of carbon monoxide and the minimum volume of carbon monoxide is equivalent to the volume between the valves. Any excess carbon monoxide delivered will escape through the outlet valve to the atmosphere. The tube therefore functions as a fixed volume reservoir of carbon monoxide.

The volume between the valves can be adjustable; for example by forming the tube in two sections which can be screwed together or pushed together to adjust the enclosed volume of gas.

Use takes place in two phases; a first phase where the device is filled or primed with the desired carbon monoxide dose and a second phase when the patient inhales the carbon monoxide dose from the invention.

1. Priming device with carbon monoxide. An aliquot of carbon monoxide is flushed into the device through the gas inlet, the inlet valve remains closed and so air in the tube is displaced out of the tube through the outlet valve by the entering carbon monoxide and rises up the tube and any excess carbon monoxide also subsequently leaves the tube through the outlet valve and escapes into the atmosphere.

The filling device (such as a compressed cylinder or single-shot cartridge of carbon monoxide) is now removed from the gas inlet. The gas inlet can have a manual filler cap to be replaced when the tube has been filled with carbon monoxide, or have a self-sealing mechanism which seals the inlet automatically when the carbon monoxide filling system is removed from it. In the case of a single-shot cartridge, it can be left connected to the filling mechanism. The tube now contains a known and repeatable volume of carbon monoxide trapped between the closed valves ready for inhalation by the patient. If a single-shot cartridge is used, then the gas inlet could take the form of a hollow spike or similar device which pierces the cartridge, allowing the dose of pressurised carbon monoxide stored within the cartridge to enter the gas inlet.

Before use by the patient the mouthpiece is connected to the gas outlet; this can be fixed to the gas outlet or form part of the gas outlet.

2. Patient inhales the carbon monoxide dose, In one embodiment of use the patient breathes out (exhales) fully. The patient then places his/her lips around the mouthpiece and takes a deep breath in (inspiration). During inspiration, the inlet valve opens and the volume of carbon monoxide enclosed in the tube between the valves is drawn into the lungs followed by a large volume of air entering the tube as the inlet valve also opens allowing the air to enter.

Preferably the patient then holds their breath for a predetermined time to allow most of the inhaled carbon monoxide to transfer to the blood flowing through the lungs during this breath holding manoeuvre. The vast majority of the carbon monoxide that enters the blood in this way will bind to the haemoglobin in the red blood cells to form carboxyhaemoglobin (COHb). Carbon monoxide has a very high affinity for haemoglobin and dissociates from it only very slowly when breathing air. After this manoeuvre the device is removed from the mouth and the patient then breathes out and continues to breathe air normally.

The tube is preferably circular and narrow in diameter in relation to its length so that the carbon monoxide entering during the filling process displaces the air above it out though the top via the outlet valve without significantly mixing with this air. If the tube were wide and short, far more carbon monoxide would have to be injected at its base through the gas inlet to produce a tube filled with pure carbon monoxide. This problem would be due to the mixing of the carbon monoxide with the air already in the tube. By making the tube long and narrow, this problem is largely circumvented. Preferably the length to diameter of the tube is from 30 to 1 to 10 to 1 and a typical dimension for the tube is a length of 20 to 30 cm and a diameter 1 to 2 cm.

Preferably there is a safety device which prevents the patient from breathing carbon monoxide, which is poisonous in excess, when the device is being filled under any conditions and this guards against misuse by a patient. One embodiment of a safety device is a sliding valve which is arranged so that, if the carbon monoxide gas inlet is open, the mouthpiece becomes occluded and vice-versa. In this embodiment, before the patient breathes in, the sliding valve is moved to a position so the carbon monoxide gas inlet is now occluded and the mouthpiece is open. The patient can now inhale the carbon monoxide from the device via the mouthpiece in the same manner as described previously followed by a large volume of air entering through the inlet valve. Another example of a safety device comprises the gas inlet being mounted within the inlet of the mouthpiece and connected to the tube in the space between the inlet and outlet valves so that when filling the device (e.g. from a cylinder of compressed carbon monoxide) it functionally enters the base of the tube just above the inlet valve so displacing any air within the tube upwards and out through the outlet valve. Excess carbon monoxide escapes from the mouthpiece via the outlet valve. The key feature of this design is that if a filling system is attached to the gas inlet then it is impossible to place the mouthpiece in the mouth during this filling process as the gas inlet is within the mouthpiece opening. This therefore provides safety from accidental inhalation of carbon monoxide while the tube is being filled with carbon monoxide ready for the intended inhalation manoeuvre.

In another embodiment of the invention there is a removable end cap incorporating the inlet valve, which cap has a lower hollow spike above the valve. The tube has a second upper hollow spike located beneath the outlet valve. The carbon monoxide is provided by a cartridge which can fit within the tube, each end of which can be pierced by a sharp spike. In use, the end cap is removed, the cartridge placed in the tube and the end cap replaced so the lower spike pushes against the bottom of the cartridge and penetrates the cartridge and the cartridge is pressed against the upper spike which penetrates the upper end of the cartridge, so each of the sharp spikes penetrate their respective ends of the cartridge. The patient then inhales and the carbon monoxide in the cartridge is drawn up through the upper hollow spike, through the outlet valve and into the lungs. This is followed by the inrush of a large volume of air via the inlet valve and then through a lower hollow spike into the lower end of the cartridge.

The volume of carbon monoxide contained within the cartridge ideally is that which is needed by the patient; this provides a "one-shot" dose of carbon monoxide. The carbon monoxide in the cartridge is preferably at substantially ambient (atmospheric) pressure. The internal volume of the device tube between the inlet and outlet valves is, in this embodiment substantially the same as the internal volume of the gas cartridge, the contents of which is at ambient pressure.

This volume, the internal volume of the device contained between the inlet and outlet valves, therefore, as in the above embodiments, represents the maximum possible volume of carbon monoxide that can be inhaled by the patient. Any excess carbon monoxide, for example due to the gas in the cartridge inadvertently being under pressure due to a manufacturing error, would leave via the outlet valve prior to the device being placed in the mouth. This embodiment has the advantage that the loading system, i.e. the cartridge, contains only a single dose of gas and may be a more user friendly way to load or fill the tube with carbon monoxide than a multiple dose compressed gas cylinder.

Alternatively the cartridge can contain carbon monoxide under pressure. In this embodiment the size of the cartridge is smaller but the mass of carbon monoxide injected into the device from the cartridge must, as a minimum, still be equivalent to the dose of carbon monoxide intended for inhalation by the patient. The upper spike is located part way down the tube and the system operates as above. As the cartridge is pressurised, it can be made smaller and easier to carry than the ambient pressure cartridge. The volume of the tube still determines the maximum volume of carbon monoxide inhaled by the patient and so the cartridge needs to contain enough carbon monoxide to fill the tube. If it contains slightly more, this does not affect the delivered dose, as any excess carbon monoxide is vented via the outlet valve prior to the device of the invention being placed in the mouth of the patient. The delivered dose is therefore accurate and repeatable, even if the masses of carbon monoxide in each cartridge vary slightly. This makes the cartridges easier to manufacture.

In a further embodiment the cartridge can be exterior to the tube and the tube can have spring loaded inlet and outlet valves which will work in any spatial orientation. The cartridge is connected to the tube by hollow spikes.

In use a single-use carbon monoxide cartridge is used which has an internal volume equal to the volume of carbon monoxide required by the patient each time he/she inhales gas from the device. This is necessary because in this embodiment the volume of carbon monoxide that can be inhaled is no longer determined by the volume of the enclosing tube as described above, but by the volume of carbon monoxide contained within the cartridge. The single-use carbon monoxide cartridge can contain carbon monoxide at substantially ambient pressure.

The cartridge is forced by the operator onto the two hollow spikes and preferably, the cartridge has an internal baffle arranged such that gas entering via the inlet hollow spike has to flow down one side of the cartridge and up the other side to reach the hollow spike connected to the outlet valve and mouthpiece. The baffle arrangement is such that the gas flow path through the cartridge during the inhalation manoeuvre is functionally a long tube so that the carbon monoxide in the cartridge is efficiently displaced by the incoming air though the inlet valve, with minimum mixing occurring, regardless of the external shape of the cartridge design. This ensures that, when the patient breathes gas from the device, the cartridge is rapidly emptied of the carbon monoxide contained within it such that it enters the lungs at an early stage during the inspiratory manoeuvre.

This embodiment has the advantage that the invention is very small and pocket-sized. The volume of carbon monoxide inhaled is determined by the cartridge size. It is envisaged that the cartridges would be rectangular in shape. This would make them easier to carry and they would pack together more efficiently in any storage container.

In a further embodiment of the invention the carbon monoxide is stored in a deformable container, the internal volume of which is reduced to expel the carbon monoxide from the container to the device of the invention. The container can be in the form of a deformable tube/cartridge analogous to a toothpaste tube or any other similar container.

Alternatively the internal volume of the container can be reduced by other means e.g. by use of a piston to expel the carbon monoxide. During the loading of the tube with carbon monoxide from the container, any excess carbon monoxide would safely emerge from one end of the inhalation device tube before the inhalation manoeuvre was performed by the patient.

It is preferred however that the volume of carbon monoxide contained in the deformable tube cartridge system described above would be equal to the desired dose of carbon monoxide required for the patient. In this embodiment it is possible that the volume of the inhalation tube could be less than the intended dose of carbon monoxide for inhalation by the patient, and function primarily as a convenient mouthpiece. This is because, with practice, a patient could exhale fully, then slowly inhale gas from the mouthpiece/inhalation tube while slowly squeezing the contents of the deformable tube cartridge such that its contents entered the mouth. On completion of squeezing and emptying the contents of the deformable tube cartridge of carbon monoxide into the mouth in this way, the patient would then continue to inhale fully and perform a breath hold to allow uptake of the majority of the inhaled carbon monoxide dose into the blood from the lungs.

Preferably there is a timing device which prevents the re-use of the device within a specified time period and optionally can also prevent over frequent use within a given time period; this device can be an electronic timing or "lockout" device. This prevents inhalation of any gas from the device within a preset time limit that starts at the time of inhalation of the previous dose of carbon monoxide, by obstructing the inhaled gas pathway through the inhalation system by an electronic valve or similar means. The purpose of this safety device is to prevent repeated doses of carbon monoxide being taken in error by a patient at intervals shorter than those prescribed by the physician. Although the above embodiments all deliver a correct repeatable volume/dose of carbon monoxide every time the device is used, this additional feature would prevent erroneous overdose of carbon monoxide by the patient due to over-frequent use of the device.

In all above described embodiments of the device where hollow "spikes" are described which pierce the single-shot gas cartridge, the spikes could be functionally replaced by any suitable gas tight union system between the device and the gas cartridge.

The invention also provides a method for treating people which comprises administering to them a controlled volume of carbon monoxide, preferably in repeated doses at set time intervals and the device of the invention would enable this to be carried out.

The invention is illustrated in the accompanying drawings in which Figs. 1 to 3 show one embodiment of the invention Figs. 4 and 5 show one type of safety device Figs. 6 and 7 show a second type of safety device Figs. 8 and 9 show a second embodiment of the invention Figs. 10 to 13 show an embodiment using a compressed gas cartridge Figs. 14 to 16 show an embodiment using a single shot cartridge at ambient pressure Figs. 17 to 19 show an embodiment using a single shot cartridge with compressed gas Figs. 20 to 22 show the use of an external single shot cartridge of gas and Fig. 23 shows the use of a deformable cartridge.

Referring to fig. 1, a tubular conduit (1) is constructed that is relatively long in relation to its width. Its length might typically be 20-30cm while its cross sectional area might typically be 1-2 cm . It contains a unidirectional valve at each end, valve (2) being an outlet valve and valve (3) being an inlet valve. These valves have a low opening pressure (typically 2cm.H₂O) and remain closed when there is no pressure gradient across them. The volume of gas enclosed in the tube (1) between valves (2) and (3) is substantially equivalent to the volume of carbon monoxide desired for delivery to the patient, so long as the valves are functionally located near to each end of the tube (1). The desired carbon monoxide volume to be delivered to any given patient will determine the design of this enclosed volume when tube (1) is constructed. There is a carbon monoxide inlet (4) through which carbon monoxide is added to tube (1). The minimum volume of carbon monoxide that must enter through inlet (4) from the carbon monoxide storage system (such as a compressed cylinder or single-shot cartridge of carbon monoxide) will be the same as the volume of gas enclosed in tube (1) between valves (2) and (3). Any volume of carbon monoxide delivered in excess of this will escape through valve (2) to the atmosphere during the filling process and will not be inhaled by the patient during the inhalation of carbon monoxide phase described below. The tube (1) therefore functions as a fixed volume reservoir of carbon monoxide.

The tube (1) is intentionally narrow in diameter so that the carbon monoxide entering its base during the filling process displaces the air above it out though the top via valve (2) without significantly mixing with this air. If the tube (1) were wide and short, far more carbon monoxide would have to be injected at its base through inlet (4) to produce a tube (1) filled with pure carbon monoxide. This problem would arise due to the mixing of the carbon monoxide with the air already in tube (1). By making tube (1) long and narrow, this problem is largely circumvented.

The use of the device is shown in figs. 2 and 3: there are two phases of use; a first phase where the device is filled or primed with the desired carbon monoxide dose and a second phase when the patient inhales the carbon monoxide dose from the device.

Phase 1 Priming device with carbon monoxide - Figure 2 An aliquot of carbon monoxide is flushed into the device of the invention through the inlet (4). Valve (3) remains closed and so the air (5) rises up the tube (1) ahead of the incoming carbon monoxide (6) which is displacing it out through valve (2). Any excess carbon monoxide also subsequently leaves tube (1) through valve (2) and escapes to the atmosphere. In this figure we can see that a mouthpiece (7) has been added. The filling device (such as a compressed cylinder or single-shot cartridge of carbon monoxide) is now removed from (4). Inlet (4) can have a manual filler cap to be replaced when tube (1) has been filled with carbon monoxide, or have a self- sealing mechanism which seals the inlet (4) automatically when the carbon monoxide filling system is removed from it. The tube (1) now contains a known and repeatable volume of carbon monoxide trapped between closed valves (2) and (3) ready for inhalation by the patient. In the case of a single-shot pressurised cartridge, the inlet (4) might take the form of a hollow spike or similar mechanism that pierces the material of the cartridge or otherwise makes a gas-tight union with it.

Phase 2 Patient inhales the carbon monoxide dose - Figure 3 : This is a suggested method of use, although others may be possible. The patient breathes out (exhales) fully. The patient then places his/her lips around the mouthpiece (7) and takes a deep breath in (inspiration). During inspiration, valve (2) opens and the volume of carbon monoxide (6) enclosed in tube (1) between valves (2) and (3) is drawn into the lungs followed by a large volume of air (5) entering the base of tube (1) as valve (3) also opens allowing the air to enter. The patient then holds their breath for a predetermined time to allow most of the inhaled carbon monoxide to transfer to the blood flowing through the lungs during this breath holding manoeuvre. The vast majority of the carbon monoxide that enters the blood in this way will bind to the haemoglobin in the red blood cells to form carboxyhaemoglobin (COHb). Carbon monoxide has a very high affinity for haemoglobin and dissociates from it only very slowly when breathing air. After this manoeuvre the device of the invention is removed from the mouth and the patient then breathes out and continues to breathe air normally. This process is repeated at intervals of several hours (as the carbon monoxide slowly dissociates from the haemoglobin) to maintain a low but predictable level of COHb in the blood at all times to achieve the desired therapeutic effect.

Referring to figures 4 to 7, two safety devices are shown as Safety Device A (Figures 4 and 5) and Safety Device B (Figures 6 and 7). These devices are described as examples which could be added to the basic concept above to prevent a patient being able to breathe from the mouthpiece while the tube (11) is being filled with carbon monoxide. This is desirable to achieve one of the original target aims of the invention which was that the patient could not accidentally breathe in any carbon monoxide while the device of the invention was being primed or filled with carbon monoxide from the filling device (such as a compressed cylinder of carbon monoxide). The reason this is desirable is that carbon monoxide, in excess, is poisonous.

Such safety devices are especially desirable if using any form of filling mechanism that deliberately injects slightly more carbon monoxide into the device than intended for inhalation by the patient, where the excess carbon monoxide is intended to leave the device via the outlet valve prior to the inhalation manoeuvre being performed by the patient. They are less important if the filling mechanism is designed so that exactly the correct dose of carbon monoxide is injected into the device and no more. Such safety devices are considered here because it is likely that a single-shot cartridge for example with a slight excess of carbon monoxide contained within, would be cheaper to manufacture and be capable of being used by a wide range of patients with differing prescribed doses of carbon monoxide per inhalation episode. The design of the inhalation device enclosed volume between inlet and outlet valves would determine the carbon monoxide dose actually delivered to the patient, not the mass of carbon monoxide contained within the loading cylinder or single-shot cartridge system. Single-shot cartridges delivering exactly the correct dose of carbon monoxide for the patient might be more expensive to manufacture and might have to be customised for any given patient. While this is a more desirable design therefore, it may be that a storage cylinder/single-shot cartridge delivering a slight excess of carbon monoxide to the device is the most commercially practical design, and that the accompanying inhalation device contains the mechanism that determines the exact dose of carbon monoxide given to the patient, with suitable safety devices incorporated.

Safety Device A Priming device with carbon monoxide - Figure 4 Carbon monoxide enters via the filler port (14); this has been relocated to be adjacent to the mouthpiece (7) but note that the carbon monoxide still functionally enters the tube (11) near the base just above valve (3) so that any air above it is displaced upwards and out through valve (2). A sliding valve (18) is arranged so that if the carbon monoxide filler port is open, the mouthpiece becomes occluded and vice- versa.

The rube (11) is filled as in Figure 4 with carbon monoxide via the filler port (14). The air is displaced upwards from tube (11) as the carbon monoxide enters, passes out through valve (12) as in previous embodiments but is allowed to escape through a port (19) within the sliding valve mechanism (18). This means that no carbon monoxide can exit from the mouthpiece while the tube (11) is being filled with carbon monoxide via port (14) even if an excess of carbon monoxide is delivered to tube (11).

Patient inhales the carbon monoxide dose - Figure 5 In readiness for the inspiration manoeuvre, the sliding valve (18) is moved to its alternative position; the carbon monoxide filler port (14) is now occluded and the mouthpiece is open again. The patient can now inhale the carbon monoxide (16) from tube (11) via the mouthpiece in the same manner as described previously followed by a large volume of air (15) entering valve (3).

Safety Device B Priming device with carbon monoxide- Figure 6 In this safety embodiment the filler port for carbon monoxide (24) is mounted within the inlet of the mouthpiece (27). As carbon monoxide enters port (24) from the filling device (such as a cylinder or single-shot cartridge of compressed carbon monoxide) it functionally enters the base of tube (21) just above valve (23) so displacing any air within tube (21) upwards and out through valve (22). Excess carbon monoxide escapes from the mouthpiece via valve (22) subsequently. The key feature of this design is that if a filling system is attached to port (24) then it is impossible to place the mouthpiece (27) in the mouth during this filling process as the filler port (24) is within the mouthpiece opening. This therefore provides safety from accidental inhalation of carbon monoxide while the tube (21) is being filled with carbon monoxide ready for the intended inhalation manoeuvre.

The patient should be trained not to try to inhale from the device while it is being primed with carbon monoxide. However such safety features help prevent accidental mishap from misuse of the equipment.

In this embodiment the filler port (24) would either have a screw cap or preferentially be self-sealing as the filler mechanism is removed from it. Patient inhales the carbon monoxide dose - Figure 7 During the inhalation manoeuvre, the carbon monoxide (26) volume in tube (21) trapped between valves (22) and (23) is breathed into the lungs through the mouthpiece (27), followed by a large volume of air (25) entering tube (21) from its base via valve (23).

Another embodiment is shown in figures 8 to 9.

Priming device with carbon monoxide- Figure 8 Instead of tube (1) being a long relatively thin tube, it is now arranged in a folded form (31). One way to achieve this would be to assemble the device as a small box, containing baffles that would allow it to functionally still be a long tube. The volume of gas enclosed between valves (32) and (33) would, as before, represent the volume of carbon monoxide intended for delivery to the patient during the inhale/breath hold manoeuvre. Tube (31) is, as before, primed with carbon monoxide (36) by gas added from a filling system (such as a cylinder or single-shot cartridge of compressed carbon monoxide) via a filling port (34). As before this gas enters the tube (31) at its functional base, just above valve (33). Air is displaced along tube (31) and escapes from the mouthpiece (37) via valve (32) followed by any excess carbon monoxide during the filling process. Safety device B in this example prevents the device of the invention being placed in the mouth while it is being filled. However any similar safety interlock device could be used with this embodiment of the main invention. This embodiment shows a variation of the original design intended to make a more compact pocket-sized device.

Patient inhales the carbon monoxide dose - Figure 9 The carbon monoxide filling port (34) has either a cap or a self-sealing mechanism which activates when the filling system is removed from it. The patient breathes out fully. The patient places his/her lips around the mouthpiece (37) and breathes in fully from the device of the invention. The carbon monoxide (36) enclosed within tube (31) by valves (32) and (33) is drawn into the lungs first via valve (32) followed by a large volume of air (35) entering the base of tube (31) via valve (33).

The patient then holds his/her breath for a predetermined time to allow most of the carbon monoxide in the lungs to transfer to the blood and become bound as COHb. The device is removed from the mouth and the patient continues to breathe air normally.

Another embodiment is shown in figures 10,11,12,13 which provides a detailed description of filling processes from a pressurised container or single-shot cartridge.

Referring to figure 10, a small pressurised cylinder or single-shot cartridge (40) of carbon monoxide is used to fill the tube (41) with carbon monoxide via the filling port (44). The tube (41) starts off filled with ambient air (45). The compressed gas cylinder is self-sealing, similar to a butane cigarette lighter refill cylinder. The nozzle of the cylinder (40) is placed into the filler port just above valve (43).

Referring to figure 11, the cylinder (40) is pushed hard into the filler port. This causes carbon monoxide (46) to be ejected from the cylinder (40) into the tube (41). Valve (43) stays closed but valve (42) opens and allows the displaced air (45) to leave tube (41) to be replaced by carbon monoxide (46).

Referring to figure 12, eventually tube (41) becomes filled with carbon monoxide (46). The volume of the tube (41) therefore is the determinant of the volume of carbon monoxide (46) that will subsequently be inhaled by the patient. The volume of carbon monoxide (46) ejected from the cylinder (40) will NOT determine how much carbon monoxide is subsequently inhaled, just so long as enough carbon monoxide has been added to tube (41) to fill it completely. Therefore no bolus volume metering device is needed on cylinder (40). Referring to figure 13, the cylinder (40) has been removed from carbon monoxide inlet port (44). The cylinder self-seals ideally. Port (44) is shown capped off here, however it could also preferentially be of a self-sealing design. The patient inhales the gas from tube (41) by placing his/her lips around mouthpiece (47) and inhaling as previously described. The carbon monoxide (46) in tube (41) is now inhaled into the lungs via valve (42). This is followed by a large volume of air (45) entering tube (41) via valve (43).

Alternatively, referring to figures 10-13, the pressurised cylinder (40) could be replaced by a single-shot pressurised gas cylinder or cartridge. Such a cylinder or cartridge could contain enough carbon monoxide such that, on connection to filling port (44), a sufficient mass of carbon monoxide enters tube (41) to fill it, with any excess carbon monoxide exiting via valve (42). Alternatively such a cylinder or cartridge would contain sufficient carbon monoxide under pressure such that, when it ejects its contained carbon monoxide into tube (41) via port (44), an exact dose of carbon monoxide required by the patient is delivered to tube (41). In the case of a pressurised single-shot cartridge, the filler port (44) could take the form of a hollow spike that pierces the material of the cartridge, or similar gas tight connection system, so allowing it to discharge its contained carbon monoxide into the tube (41). It is possible that a single-shot carbon monoxide cylinder or cartridge could remain connected to such a gas inlet port during the subsequent inhalation manoeuvre with no ill effect. The gas inlet port in that circumstance would not then require the use of an end-cap or self-sealing mechanism.

Another embodiment is shown in figures 14 to 16 which show an embodiment where tube (51) is filled with carbon monoxide (56) from a disposable container containing gas at substantially ambient (atmospheric) pressure.

Referring to figure 14, in this embodiment there is a tube (51) with a removable end cap. In the removable end cap there is placed the lower air inlet valve (53) and also a hollow rigid sharp spike (62). In the upper part of tube (51) there is found, as in the above embodiments, a non-return valve (52) and in addition, a hollow rigid sharp spike (63).

Into the open lower end of tube (51) it is envisaged that a cartridge (61) of carbon monoxide (56) gas is inserted. This cartridge is made of a material that can be pierced by the sharp spikes (62) and (63). Alternatively only the ends of this cartridge (61) are made of a material that can be pierced by the sharp spikes (62) and (63). The carbon monoxide (56) in this cartridge (61) is at substantially ambient (atmospheric) pressure. The volume of carbon monoxide (56) and therefore the internal volume of the cartridge (61) is the same as the volume of carbon monoxide that is intended for delivery to the lungs of the patient.

Referring to figure 15, as the end-cap is screwed onto tube (51), the two sharp spikes (62) and (63) pierce the respective ends of cartridge (61). The cartridge substantially fills the volume in tube (51) between valves (52) and (53). This volume therefore, as in the above embodiments, represents the maximum possible volume of carbon monoxide (56) that can be inhaled by the patient as any excess carbon monoxide would leave via valve (52) prior to the device being placed in the mouth.

Referring to figure 16, the mouthpiece (57) is now placed in the mouth of the patient and the patient inhales. The carbon monoxide (56) in the cartridge (61) is now drawn up through the upper hollow spike (63), through valve (52) and into the lungs. This is followed by the inrush of a large volume of air via valve (53) and then through hollow spike (62) into the lower end of the cartridge.

This embodiment has the advantage that the loading system i.e. the cartridge (61) only contains a single dose of gas and may be a more user friendly way to load or fill the tube (51) with carbon monoxide than a multiple dose compressed gas cylinder (40) would be (as described above and in figures 10-13). Another embodiment is shown in figures 17 to 19 which show an embodiment where a single use cartridge (11) of carbon monoxide (6) is used which is pressurised.

Referring to figure 17, as in the embodiment above (Figures 14,15,16) there is a tube (51) with removable end-cap, one way valves at each end (52 and 53) and upper and lower hollow spikes (62 and 73) for penetration of a single-use cartridge (71) filled with carbon monoxide (66). In this embodiment the cartridge is physically of smaller volume than tube (61) and the carbon monoxide (66) within the cartridge (71) is under pressure. However, because the cartridge is of single-use, the mass of carbon monoxide (66) in the cartridge is at least as great as the intended dose for the patient. Preferentially, for safety, the volume of tube (51) is, as previously described, the same as the volume of carbon monoxide intended for delivery to the patients lungs. During the filling process any excess carbon monoxide may leave through valve (52) before the patient inhales any carbon monoxide (66) from the device. The determinant of the volume of tube (51) is the maximum allowable volume of carbon monoxide that can be breathed in during one dosing episode with the device.

As the cartridge (71) is smaller than the volume of tube (51) as it now contains pressurised gas, the hollow spikes (62 and 73) are closer together than in figures 14,15,16.

Referring to figure 18, the end cap is screwed onto the base of tube (51) and the two hollow spikes (62 and 73) pierce the respective ends of the cartridge (71). Valve (53) stays closed at this point but as the pressurised carbon monoxide (66) escapes from the cartridge (71) it displaces any remaining air within the tube (51) out through valve (52). The whole of tube (51) now contains carbon monoxide (66) and the device of the invention is now ready for carbon monoxide (66) to be inhaled from it by the patient. Referring to figure 19, the mouthpiece (57) is now placed in the mouth of the patient and the patient inhales. The carbon monoxide (66) in the cartridge (71) plus tube (51) is now drawn up through valve (52) and into the lungs. This is followed by the inrush of a large volume of air via valve (53) and then through hollow spike (62) into the lower end of the cartridge.

This embodiment has the advantage that the loading system i.e. the cartridge (71) only contains a single dose of gas and may be a more user friendly way to load or fill the tube (51) with carbon monoxide than a multiple dose compressed gas cylinder (40) would be (as described above and in figures 10-13). As the cartridge (71) is pressurised, it can be made smaller and easier to carry than the ambient pressure cartridge described above in figures 14,15,and 16. The volume of tube (51) still determines the maximum volume of carbon monoxide inhaled by the patient and so the cartridge needs to contain enough carbon monoxide to fill tube (51). If it contains slightly more, this does not affect the delivered dose, as any excess carbon monoxide is vented via valve (52) prior to the device of the invention being placed in the mouth of the patient. The delivered dose is therefore accurate and repeatable, even if the masses of carbon monoxide in each cartridge vary slightly. This makes the cartridges easier to manufacture.

Another embodiment is shown in figures 20 to 22 which show an embodiment where the carbon monoxide single-use cartridge is connected to, rather than trapped within, the inhalation device.

Referring to figure 20, a much smaller device is shown here which still incorporates features described previously. This has the advantage of being very easily portable. The device of the invention has a mouthpiece (57) as before, an outlet valve (72) to the mouthpiece and an air inlet valve (83). In this example both valves (72) and (83) are lightly spring loaded and will work in any spatial orientation. The device of the invention also contains two hollow spikes (92 and 93). A single-use carbon monoxide (86) cartridge (84) is used which has an internal volume equal to the volume of carbon monoxide required by the patient each time he/she inhales gas from the device of the invention. This is necessary because in this embodiment the volume of carbon monoxide (86) that can be inhaled is no longer determined by the volume of the enclosing tube (51) described in all the previous embodiments, but by the volume of carbon monoxide contained within the cartridge (84). The single-use carbon monoxide cartridge (84) contains carbon monoxide at substantially ambient pressure.

Referring to figure 21, the cartridge (84) is forced by the operator upon the two hollow spikes (92) and (93). It is preferable that the cartridge has an internal baffle arranged such that gas entering via hollow spike (93) has to flow down one side of cartridge and up the other side to reach hollow spike (92). The baffle is designed such that the gas flow path through the interior of the cartridge functionally takes the form of a long tube, regardless of the shape of the exterior of the cartridge. This ensures that the contained carbon monoxide is efficiently displaced by the air coming into the cartridge through the inlet valve, with little mixing of the two gases. This ensures that when the patient breathes gas from the device of the invention, the cartridge is rapidly emptied of the carbon monoxide contained within it such that it enters the lungs early during the inspiratory manoeuvre.

Referring to figure 22, the patient now places the mouthpiece (87) into the mouth and inhales. The carbon monoxide (86) within the cartridge (84) is now drawn into the lungs via the hollow spike (92) and then the one-way valve (72). This is followed by a large volume of air entering via valve (83) and hollow spike (93).

This embodiment has the advantages that the device of the invention is very small and pocket-sized. The volume of carbon monoxide inhaled is determined by the cartridge size. The cartridges, it is envisaged, would be rectangular in shape. This makes them easier to carry and they would pack together more efficiently in any storage container.

Referring to fig. 23 as in the embodiment of fig. 1 an aliquot of carbon monoxide is flushed into the device of the invention through the inlet (4). In this embodiment the carbon monoxide enters through gas inlet (4) by the patient squeezing a deformable tube reservoir (15) to expel the carbon monoxide. Valve (3) remains closed and so the air (5) rises up the tube (1) ahead of the incoming carbon monoxide (6) which is displacing it out through valve (2). Any excess carbon monoxide also subsequently leaves tube (1) through valve (2) and escapes to the atmosphere. It is preferred however that the volume of carbon monoxide contained in the deformable tube cartridge system (15) described above would be equal to the desired dose of carbon monoxide required for the patient. If this were the case then in this embodiment it is possible that the volume of the inhalation tube (1) could safely be less than the intended volume of carbon monoxide for inhalation by the patient, and function primarily as a convenient mouthpiece, and possibly valves 2 and 3 could be omitted. This is because, with practice, a patient could exhale fully, then slowly inhale carbon monoxide + air from the mouthpiece/inhalation tube (1) while simultaneously slowly squeezing the contents of the deformable tube such that all its contents entered the mouth and then lungs. On completion of squeezing and emptying the contents of the deformable tube of carbon monoxide into the mouth/lungs in this way, the patient would then continue to inhale fully and perform a breath hold to allow uptake of the majority of the inhaled carbon monoxide dose into the blood from the lungs.

In all above described embodiments of the device where hollow "spikes" are described which pierce the single-shot gas cartridge, the spikes could be functionally replaced by any suitable gas tight union system between the device and the gas cartridge. References

1) Dolinay T, Szilasi M, Liu M, Choi AM. Inhaled carbon monoxide confers anti-inflammatory effects against ventilator-induced lung injury. Am J Respir Cr it Care Med. 1994; May 13.

2) Ryter SW, Morse D, Choi AM. Carbon monoxide: to boldly go where NO has gone before. Sci STKE 2004; (230): RE6.

3) Nakao A, Kobayashi E, Tanaka N, Murase N. Protective effect of carbon monoxide for organ injury. Nippon Geka Gakki Zasshi. 2004; 105(4): 309-13.

4) Sarady JK, Zuckerbraun BS, Bilban M, Wagner O, Usheva A, Liu F, Ifedigbo E, Zamora R, Choi AM, Otterbein LE. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 2004; 18(7): 854-6.

5) Christensen P, Eriksen B, Henneberg SW. Precision of a new bedside method for estimation of the circulating blood volume. Acta Anaesthesiol Scand. 1993;37(6):622-7.

6) Dingley J. Foex BA, Swart M, Findlay G, Desouza PR, Wardrop C, Willis N, Smithies M, Little RA. Blood volume determination by the carbon monoxide method using a new delivery system: Accuracy in critically ill humans and precision in an animal model. Critical Care Medicine 1999; 27(11): 2435- 2441.

Claims

1. A device enabling a user to inhale a fixed repeatable volume of a gas, which device comprises a hollow tube having a gas inlet and a gas outlet which tube is adapted to contain a fixed volume of the gas between the inlet and outlet, which volume is equal to the volume of the gas to be inhaled.

2. A device as claimed in claim 1 in which there are valves at each end of the tube one valve being a gas outlet valve connected to the gas outlet, which valves have a space between them equal to the volume of gas to be inhaled and which valves are adapted to prevent diffusion of the gas from the tube prior to inhalation.

3. A device as claimed in claim 2 enabling a user to breathe a fixed repeatable volume of a gas, which device comprises a hollow tube having two one way valves in the tube defining a space of pre-determined volume between the valves, one valve being an inlet valve only allowing gas to enter the space between the valves and the other valve being an outlet valve only allowing gas to exit from the space between the valves, there being a gas inlet located between the valves to allow gas to enter the space between the valves and a gas outlet connectable to a mouthpiece upstream of the outlet valve; the valves remaining closed when there is no pressure gradient across them.

4. A device as claimed in claims 2 or 3 in which the valves have an opening pressure of 0.5 to 3 cm water.

5. A device as claimed in claims 2, 3 or 4 in which the valves are weighted discs, lightly spring loaded discs, or "duck bill" valves.

6. A device as claimed in any one of the preceding claims in which the device has a detachable mouthpiece above the outlet valve or there is a mouthpiece above the outlet valve which forms part of the device.

7. A device as claimed in any one of claims 3 to 6 in which the volume of gas enclosed in the tube between the inlet and outlet valves is substantially equivalent to the volume of gas desired for delivery to the patient.

8. A device as claimed in any one of claims 3 to 7 in which the volume of gas between the valves is adjustable.

9. A device as claimed in claim 8 in which the tube is formed in two sections which can be screwed together or pushed together to adjust the enclosed volume of gas.

10. A device as claimed in any one of the preceding claims in which the length of the tube is greater than its maximum cross sectional diameter.

11. A device as claimed in claim 10 in which the tube is substantially circular and the length to diameter of the tube is from 30 to 1 to 10 to 1.

12. A device as claimed in any one of the preceding claims in which there is a safety means which prevents the patient from breathing excess gas.

13. A device as claimed in any one of the preceding claims in which there is a safety means which prevents the patient from breathing the gas whilst the device is being filled with the gas.

14. A device as claimed in claims 12 or 13 in which the safety means is a mechanical interlock such that, when the device is being filled with gas, the gas flows to the gas outlet.

15. A device as claimed in claims 12 or 13 in which the gas outlet is connected to a mouthpiece and in which the safety means comprises the gas inlet being located within the inlet of the mouthpiece and being connectable to the tube in the space between the inlet and outlet valves.

16. A device as claimed in any one of claims 3 to 15 in which there is a removable end cap incorporating the inlet valve, which cap has a lower hollow inlet means located above the valve, the tube having a second upper hollow outlet means located beneath the outlet valve so that, if a cartridge of gas is located within the tube, the ends of the cartridge can be connected to the inlet and outlet means by a gas tight union to release the gas.

17. A device as claimed in claim 16 in which the inlet and outlet means comprise hollow spikes which pierce the cartridge.

18. A device as claimed in claims 16 or 17 in which the gas in the cartridge is at substantially atmospheric pressure and the cartridge contains the desired volume of gas intended for inhalation by the patient.

19. A device as claimed in any one of claims 16 to 18 in which, if the gas in the cartridge is under pressure, the upper outlet means is located part way down the tube.

20. A device as claimed in any one of the preceding claims which is adapted to be connected to an external cartridge of gas.

21. A device as claimed in claim 20 in which the tube has a spring loaded inlet and outlet means and the gas inlet outlet means incorporate a gas-tight union adapted to be connected to a cartridge of gas.

22. A device as claimed in claim 21 in which the spring loaded inlet and outlet means comprise hollow spikes.

23. A device as claimed in claim 22 in which the cartridge has an internal baffle arranged such that when the cartridge is connected to the inlet and outlet means, gas entering via the inlet means flows down one side of the cartridge and up the other side to reach the outlet means connected to the outlet valve and mouthpiece.

24. A device as claimed in claim 22 in which the baffle and cartridge are configured so that the gas flow pathway through the cartridge functionally takes the form of a continuous tube, regardless of the design or shape of the outside of the cartridge.

25. A device as hereinbefore described with reference to the drawings.

26. A device as claimed in any one of the preceding claims in which there is a timer safety device which prevents the re-use of the device within a specified time period and can prevent over frequent use within a given time period.

27. A device as claimed in claim 26 in which the timer safety device is a timing or "lockout" device which prevents inhalation of any gas from the device within a preset time limit that starts at the time of inhalation of the previous dose of gas by obstructing the inhaled gas pathway through the inhalation system by an electronic valve or similar means.

28. A method for treating people which comprises administering to them a controlled volume of carbon monoxide.

29. A method as claimed in claim 28 in which repeated doses of carbon monoxide are given to a patient at pre-determined time intervals.

30. A method as claimed in claims 29 or 30 in which the device as claimed in any one of claims 1 to 27 is used to give the patient a controlled volume of carbon monoxide.

31. A method as claimed in any one of claims 28 to 30 in which the patient holds their breath for a predetermined time to allow at least most of the inhaled carbon monoxide to transfer to the blood flowing through the lungs.