Synthesis of nitric oxide gas for inhalation.

SYNTHESIS OF NITRIC OXIDE GAS FOR INHALATION

Field of the Invention

This invention is related to the synthesis of nitric oxide gas for inhalation.

Background of the Invention

Nitric oxide (NO) is a crucial mediator of many biological systems, and is known to mediate the control of blood pressure in systemic and pulmonary arteries, help the immune system to kill invading parasites that enter cells, inhibit the division of cancer cells, transmits signals between brain cells, and contributes to the death of brain cells that can weaken people with strokes or heart attacks. Nitric oxide also mediates the relaxation of smooth muscle present, for example, in the walls of blood vessels, bronchi, the gastrointestinal tract, and the urogenital tract. Administration of nitric oxide gas to the lung by inhalation has been shown to produce localized smooth muscle relaxation to treat pulmonary hypertension, pneumonia, hypogemic respiratory failure of the newborn, etc., without causing systemic side effects.

Inhaled nitric oxide is a powerful local pulmonary vasodilator that improves the level of

RZF .: 2S0035

<img file="MX370384B_D0001.tif" />

perfusion ventilation, thus increasing the efficiency of oxygen delivery to injured lungs, and increases arterial oxygen tension. Breathing nitric oxide combines a rapid onset of action that occurs within seconds with the absence of systemic vasodilation. Once inhaled, it is NOT diffused through the pulmonary vasculature into the bloodstream, where it is rapidly inactivated in combination with hemoglobin. Therefore, the vasodilatory effects of inhaled nitric oxide are limited to the pulmonary vasculature. The ability of nitric oxide to dilate pulmonary vessels selectively provides therapeutic advantages in the treatment of acute and chronic pulmonary hypertension. NO Inhalation has also been used to prevent reperfusion injury in ischemia after PCI in adults with heart attacks. NO Inhalation can produce systemic anti-inflammatory and anti-platelet effects by increasing levels of circulating NO biometabclites and other mechanisms.

US Patent No. 5,396,882 to Zapol, which is incorporated by reference herein, describes the electrical generation of nitric oxide (NO) from ambient pressure air for medical purposes. As described in US Patent No. 5,3 96,882, an air inlet port of the system is used to continuously introduce air into the arc flash region.

Brief Description of the Invention

In some aspects, one method includes collecting information related to one or more conditions of a respiratory system associated with a patient. The method also includes determining one or more control parameters based on the information collected. The method also includes initiating a series of external arcs to the

<td>even patient &lt;</td><td>to generate nitric oxide</td><td>with</td><td>base</td><td>in</td><td>the</td>

<td>parameters of The</td><td>certain control. modalities may include</td><td>a</td><td>or more</td><td>of</td><td>the</td>

<td>following. The</td><td>associated conditions</td><td>with</td><td>he</td><td colspan="2">system</td>

Respiratory may include one or more of the oxygen concentration of a reactive gas, a flow rate of the reactive gas, a volume and timing of an inspiration, the oxygen concentration of a product gas, the nitric oxide concentration of the product gas, the nitrogen dioxide concentration of the product gas, the ozone concentration of the product gas, the nitric oxide concentration of an inhaled gas and the nitrogen dioxide concentration of the inhaled gas.

The volume and timing of an inspiration can be received from a fan.

A pulse train can initiate the series of electric arcs and the pulse train can include groups of pulses

<img file="MX370384B_D0002.tif" />

that have pulses with different pulse widths.

The pulse width of initial pulses in one of the pulse groups may be wider than other pulses in the pulse group.

The series of electric arcs can generate a reduced level of nitrogen dioxide.

The series of electric arcs can generate a reduced level of ozone.

The reduced · level of nitrogen dioxide can be further reduced by a scrubber that includes one or more of KaOH, CaOH, CaCO3 and NaOH.

The reduced level of nitrogen dioxide may have a concentration that is less than 2 0%, 10%, 6%, or 5% of a concentration of the nitric oxide generated.

The series of electric arcs can be generated by electrodes that include a noble metal.

The series of electric arcs can be generated by electrodes that include iridium.

The series of electric arcs can be generated by electrodes that include nickel.

In some additional aspects, an apparatus includes a chamber having an inlet valve to receive a reactive gas and an outlet valve to supply a product gas. The device also includes a sensor to collect information related to one or more conditions.

<img file="MX370384B_D0003.tif" />

of a respiratory system associated with a patient. The apparatus also includes a controller to determine one or more control parameters based on the collected information. One or more pairs of electrodes are included in the apparatus and are placed inside the chamber to initiate a series of electrical arcs external to the patient to generate nitric oxide based on the determined control parameters.

Modalities may include one or more of the following.

Conditions associated with the respiratory system may include one or more of the reactive gas oxygen concentration, a reactive gas flow rate, a volume and timing of an inspiration, the product gas oxygen concentration, the oxide concentration nitric oxide of the product gas, the nitrogen dioxide concentration of the product gas, the ozone concentration of the product gas, the nitric oxide concentration of an inhaled gas, the nitrogen dioxide concentration of the inhaled gas and the pressure in the chamber.

The volume and timing of an inspiration can be received from a fan.

A pulse train can initiate the series of electric arcs, and the pulse train can include groups of pulses that have pulses with different pulse widths.

The pulse width of initial pulses in one of the pulse groups may be wider than other pulses in the pulse group.

The series of electric arcs can generate a reduced level of nitrogen dioxide.

The series of electric arcs can generate a reduced level of ozone.

The series of electric arcs can be started when the chamber has a pressure greater than 1 ATA or less than 1 ATA.

The apparatus may also include a scrubber to further reduce the reduced level of nitrogen dioxide, and the scrubber may include one or more of KaOH, CaOH, CaCO3, and NaOH.

The reduced level of nitrogen dioxide may have a concentration that is less than 20%, 10%, 6%, or 5% of a concentration of the nitric oxide generated.

The electrodes can include a noble metal.

The electrodes can include iridium.

Electrodes can include nickel.

In some additional aspects, an apparatus includes a chamber having an inlet valve to receive a reactive gas and an outlet valve to supply a product gas. The apparatus also includes a piston positioned within the chamber and configured to move along a length of the chamber to adjust the pressure in the chamber. The apparatus also includes a sensor to collect information related to one or more conditions of a respiratory system associated with a patient. The apparatus includes a controller to determine one or more control parameters based on the collected information. One or more pairs of electrodes are included and placed within the chamber to initiate a series of electrical arcs external to the patient to generate nitric oxide based on the determined control parameters.

Modalities may include one or more of the following.

<td>The associated conditions</td><td>with</td><td colspan="2">θΐ. S1. S Ü STitci.</td>

<td>respiratory may include one or more of</td><td colspan="2">concentration</td><td>of</td>

<td>reactive gas oxygen, a velocity</td><td>of</td><td>flow</td><td>gas</td>

<td>reagent, a volume and timing of</td><td>a</td><td>inspiration,</td><td>the</td>

<td>gas oxygen concentration</td><td>of</td><td>product,</td><td>1 a</td>

<td colspan="2">nitric oxide concentration of the gas</td><td>ϊ product,</td><td>the</td>

<td>nitrogen dioxide concentration of</td><td>gas</td><td>of product,</td><td>the</td>

product gas ozone concentration, the concentration

<td>oxide</td><td>nitric of</td><td>a</td><td>inhaled gas,</td><td>the</td><td>concentration of</td>

<td>dioxide</td><td>nitrogen</td><td>of</td><td>1 inhaled gas</td><td>and</td><td>the pressure in the</td>

<td>CcUTlt3.T? Cl _to</td><td>The volume</td><td>and</td><td>synchronization</td><td>of</td><td>an inspiration</td>

they can be received from a fan.

Cm

A pulse train can initiate series of electric arcs, and the pulse train can include groups of pulses that have pulses with different pulse widths.

The pulse width of initial pulses in one of the pulse groups may be wider than other pulses in the pulse group.

The series of electric arcs can generate a reduced level of nitrogen dioxide.

The series of electric arcs can generate a reduced level of ozone.

The series of electric arcs can be started when the chamber has a pressure greater than 1 ATA or less than 1 ATA.

The apparatus may also include a scrubber to further reduce the reduced level of nitrogen dioxide, and the scrubber may include one or more of KaOH, CaOH, CaCO3, and NaOH.

The reduced level of nitrogen dioxide may have a concentration that is less than 20%, 10%, 6%, or 5% of a concentration of the nitric oxide generated.

The electrodes can include a noble metal.

Electrons can include iridium.

Electrodes can include nickel.

The details of one or more embodiments of the invention are set forth in the accompanying figures and the

<img file="MX370384B_D0004.tif" />

next description. Other features, objects, and advantages of the invention will be apparent from the description and figures, and from the claims.

Brief Description of the Figures

Figure 1 is a block diagram of a respiratory system for producing NO.

Figure 2 is an example of a NO generator.

Figure 3 is an example of a NO generator

Figure 4 illustrates a device for concentrating oxygen.

Figure 5 illustrates a device for cooling a gas.

Figure 6 is an example of a NO generator.

Figure 7 is an example of a NO generator.

Figure 8 is an example of a NO generator.

Figure 9A is a photograph showing an example of a respiratory system for producing NO.

Figure 9B is a photograph of a NO generator.

Figure 10 illustrates a representation of a pulse train and a group of pulses.

Figure HA shows average current and voltage as a function of sparks per second.

Figure 11B shows average energy as a function of sparks per second.

<img file="MX370384B_D0005.tif" />

Figures 12A-12B show voltage and current traces during two sparks from one spark / second discharge.

Figure 13 shows NO and NO2 concentrations using various electron materials Using various electrode materials.

Figure 14 shows NO and NO2 concentrations at various reactive gas oxygen concentrations.

<td></td><td>The</td><td>figure 15 shows</td><td>concentrations of</td><td>NO</td><td>and</td>

<td>N0₂</td><td>to several The</td><td>concentrations of figure 16 shows</td><td>reactive gas oxygen. concentrations of</td><td>NO</td><td>and</td>

<td>NO2</td><td>to several The</td><td>concentrations of figure 17 shows</td><td colspan="3">reactive gas oxygen. ozone levels to various</td>

oxygen concentrations.

<td>Figure 18 shows</td><td>the</td><td>levels</td><td>of</td><td>ozone a</td><td>several</td>

<td>oxygen concentrations. Figure 13 shows</td><td>the</td><td>levels</td><td>of</td><td>ozone a</td><td>several</td>

<td>oxygen concentrations. Figure 20 shows</td><td>the</td><td>levels</td><td>of</td><td>ozone a</td><td>several</td>

<td>oxygen concentrations. Figure zl shows</td><td colspan="3">concentrations</td><td>not</td><td>and NO2 to</td>

various concentrations of reactive gas oxygen.

Figure 22 shows a test setup to measure NO and NO2 levels in a hypobaric chamber at various atmospheric pressures.

Figure 23 shows NO and NO2 levels at various atmospheric pressures.

Figure 24 is a flow chart.

Figure 25 illustrates an example of a computing device 5 and a mobile computing device that can be used to implement the operations and techniques described herein.

Equal reference symbols in the different figures indicate similar elements.

Detailed description of the invention

Synthesis of NO for inhalation is accomplished by electrically creating sparks from a reactive gas that includes N2 and O2 (eg, air), thereby forming a product gas that includes electrically synthesized NO. Synthesis can be accomplished under hypobaric or hyperbaric conditions. As used herein, hypobaric refers generally to a pressure less than 1 ATA (absolute atmosphere) and hyperbaric to a pressure greater than 1 ATA. The product gas can include a medically acceptable level of NO2 20 (for example, usually less than 5 ppm, and sometimes less than 1-2 ppm). The product gas can be inhaled either with or without reducing the NO2 concentration in the product gas. The apparatus described here for nitric oxide synthesis can be portable, lightweight, self-powered, and can be used to provide product gas for therapeutic use, with a NO concentration in the range of 0.5 ppm to 500 ppm and a concentration NO2 less than 1% of the NO concentration, or even less (eg less than 1%) after using a scrubber.

Figure 1 shows an example of a respiratory system 100 to produce NO. A reactive gas (eg, air, or a mixture of 10-90% oxygen in nitrogen) enters a NO 102 generator, and a product gas (including NO) leaves the NO 102 generator. The NO generator 102 includes electrodes 106 and a controller 110. If the reactive gas is a gas other than air, the NO generator 102 may include an oxygen level sensor 112. NO production is proportional to the concentration of oxygen and nitrogen and maximum at approximately 50% oxygen at atmospheric pressure (1 ATA). The oxygen level sensor 112 may be an electrode configured to detect an oxygen concentration in the reagent gas, as described in more detail below. Electrodes 106 generate sparks in the presence of the reactive gas to produce NO 104, as described here.

Figure 2 shows an example of a NO 2 00 generator. The NO 200 generator includes a chamber 202 having an inlet valve 204 and an outlet valve 206. In some cases, a filter 208 is coupled to the NO generator. 200, such that a gaseous mixture including NOz and O2 entering the chamber through inlet valve 204 is filtered to remove particulate matter (eg, dust) or water vapor. Chamber 202 includes electrodes 210. Electrodes 210 are separated by a space, and one of the electrodes is coupled to a voltage source 212. Voltage source 212 is suitable for creating a spark or corona discharge capable of forming NO from N2 and 0₂ between electrodes 210. Examples of voltage source 212 include, but are not limited to, a piezo crystal, a battery (eg, a motorcycle battery), a solar cell, a wind generator, or other suitable source for producing a current in the order of nanoamps or milliamps and a voltage of 1 to 25 KV (for example, a power of 1 to 100 watts), or a voltage of 1 to 10 kV or 1 to 5 kV.

When the NO 2 00 generator is used for hypobaric or hyperbaric NO synthesis, chamber 202 can be a cavity in a positive displacement pump. As shown in Figure 2, chamber 2 02 may be a cavity in a piston pump and has a variable volume defined by the position of piston 214 in cylinder 216. Piston 214 is coupled to actuator 218. In one example , the actuator 218 includes an eccentric mechanism driven by a rod or shaft. Actuator 218 is driven by a prime mover 220 in a reciprocal manner.

The primary motor 220 may be, for example, a motor or machine (for example, an electric or gasoline or diesel powered motor) arranged to displace the piston 214 with respect to the cylinder 216 as an actuator 218. The seal 222 prevents the air flow into or out of chamber 202 between piston 214 and cylinder 216. Thus, when both the inlet valve 2 04 and the outlet valve 2 06 are closed, the movement of the piston 214 away from the electrodes 210 by the actuator 218 increases the volume of the chamber 202, thus reducing the pressure in the chamber 202 to a pressure below atmospheric pressure and reducing a concentration of gases (for example, Na and Oa in a reactive gas present in the chamber. Conversely, movement of piston 214 toward electrodes 210 by actuator 218 reduces the volume of chamber 202, thereby increasing the pressure in chamber 202 to a pressure above atmospheric pressure and increasing the pressure and concentration. of gases in a reactive gas present in the chamber. Because NO production is proportional to oxygen concentration, pressure in chamber 202 can have an effect on NO production. For example, when chamber 202 has a relatively high pressure (eg 2 ATA), NO production is increased.

Inlet valve 204 can be exposed to the environment such that, with the inlet valve open, ambient air (or other N2-containing reagent gas and

O2) enters chamber 2 02. With air in chamber 2 02, the inlet valve is closed and piston 214 moves 5 away from electrodes 210, thereby increasing the volume of chamber 202 and reducing pressure inside chamber 2 02 up to one px'ession below atmospheric pressure. As the volume of chamber 2 02 increases, the concentration of O2 in the chamber falls below the concentration of O2 in air at atmospheric pressure (eg, falls below 21% by volume). Actuator 218 can be controlled to increase a volume of chamber 202 by a factor of 2, 3, 4, etc., thereby reducing a pressure in chamber 202 to a fraction (eg, 1/2, 15 1/3 , 1/4, etc.) of atmospheric pressure. Although the pressure in chamber 202 is below atmospheric pressure, voltage source 212 initiates sparks or corona discharges through electrodes 210, thereby electrically generating NO. After sparks or corona discharges, actuator 218 continues its reciprocal cycle, and outlet valve 206 is opened to release product gas containing electrically generated NO. In this way, inlet valve 204 and outlet valve 206 operate out of phase with each other, such that outlet valve 2 06 is closed when inlet valve 104 is

<img file="MX370384B_D0006.tif" />

open, and inlet valve 204 is closed when outlet valve 206 is open.

Conversely, with air in inlet 202, the inlet valve is closed and piston 214 moves toward electrodes 210, thereby reducing the volume of chamber 202 and increasing the pressure within chamber 202 to a pressure above atmospheric pressure. As the volume of chamber 202 is reduced, the pressure (concentration) of O2 in the chamber rises above the pressure (concentration) of O2 in air at atmospheric pressure (for example, it rises above 21% by volume) . Actuator 218 can be controlled to reduce a volume of chamber 202 to a fraction of 1/2, 1/3, 1/4, etc., thereby increasing a pressure in chamber 202 to 2, 3, 4, etc. times the atmospheric pressure &lt;Although the pressure in chamber 202 is above atmospheric pressure, voltage source 212 initiates sparks or corona discharges through electrodes 210, thereby generating NO electrically.

In some examples, ex: a NO generator electrodes (eg, electrodes 10) can be duplicated for safety purposes to provide a replacement. Electrodes 210 can be doubled or tripled for increased energy and NO production with large tidal volumes.

Briefly referring to Figure 13, the

<img file="MX370384B_D0007.tif" />

210 electrodes can contain iridium, tungsten, stainless steel, or nickel, to name a few. In some examples, electrodes 210 containing a noble metal (eg iridium) produce the smallest NOa / NO ratio.

Figure 3 shows an example of a generator of

<td>NO 300.</td><td>He</td><td colspan="2">generator</td><td>NO 3 00 includes components of the.</td>

<td>generator</td><td>of</td><td>NO</td><td>2 00, like</td><td>was described with respect to the</td>

<td>figure 2,</td><td>with</td><td>the</td><td>source 302</td><td>coupled to the inlet valve</td>

204 and arranged to provide a reactive gas to chamber 202. In some cases, source 302 is an apparatus arranged to provide a reactive gas with a Cb concentration of less than 21% by volume or less than 2 0% by volume. In some cases, source 302 is an apparatus arranged to provide a reactive gas with an O2 concentration greater than 21 volume% but not greater than 90 volume%. For example, source 302 can include a cylinder of N2 or an inert gas (eg, argon or helium) and a mechanism for mixing the N2 or inert gas with air or a source containing enriched oxygen at a selected ratio to achieve a desired concentration of O2, N2 and / or other components in the reagent gas supplied to chamber 202. In some examples, an oxygen cylinder, an oxygen concentration, or an oxygen generator is used to raise the oxygen concentration in the reagent gas. Reactive gas is typically supplied to chamber 202 at a pressure of 1 ATA (1.03 kgf / cm²) (absolute atmosphere) or above (for example, slightly above, at 3 ATA (3.09kgf / cm²)) to avoid mixing the reactive gas with air. Before entering chamber 202, reactive gas from source 302 can pass through an equilibration bag 304, kept slightly above atmospheric pressure. A bleed valve 306 may be present to allow the pressure of the reactive gas to be kept close to atmospheric pressure.

In some cases, source 302 includes an oxygen concentrator, oxygen generator, or oxygen cylinder. Figure 4 illustrates an oxygen concentrator 400, in which pressurized air enters oxygen concentrator 400 through inlet 4 02 and passes through molecular sieve 404, producing oxygen enriched gas (for example, having at minus 30% by volume or 50% by volume of Ch. The exhaust gas, which has a concentration of O₂ lower than that of ambient air and a concentration of N₂ greater than that of ambient air, exits oxygen concentrator 400 through valve 406 and is supplied to inlet valve 204.

In some cases, source 302 includes an apparatus for cooling air (for example, a copper tube heat exchanger), such that the air at a temperature less than ambient temperature (for example, a temperature approaching to 0^or K) is provided to chamber 202 through valve 204, and the spark or corona discharge is present in a chilled reactive gas having a temperature less than ambient temperature. Source 302 can operate to cool air by refrigeration or heat exchange methods generally known in the art. FIG. 5 illustrates an example of a cooling device 500, in which air or another reactive gas (eg, a mixture of air and N2 or an inert gas, such as argon, helium, or the like) flows through the coil. 502 and is cooled by refrigerant 504, which enters chamber 506 through inlet 508 and leaves the chamber through outlet 510. Coil 502 may be a heat conducting tube such as, for example, copper tube. Refrigerant 504 can be, for example, liquid or a cyclic refrigerant (for example, chlorofluorocarbon or hydrochlorofluorocarbon).

In certain cases, one or more implementations of source 302 as described above with respect to FIG. 3 combine to form a gas mixture. For example, source 302 may include a cylinder of N2 or an inert gas (eg, argon or helium) and a mechanism to mix the N2 or inert gas with air at a selected ratio to achieve * a desired concentration of N2 such as measured, for example, with a sensor including an electrode, as well as an apparatus for cooling the reagent gas before the reagent gas is supplied to chamber 202. An apparatus for cooling the reactive gas can cool the reactive gas at more than one location (eg, at the regulator or cylinder head of a gas cylinder, at valve 204, and the like).

In other embodiments, as shown in Figure 6, a NO 600 generator includes a constant volume chamber 602. In some cases, inlet valve 204 is exposed to the environment such that, with the inlet valve open, Ambient air enters chamber 602 (eg, through filter 208). Inlet valve 204 and outlet valve 206 can be synchronized such that a gaseous mixture flows into chamber 602 through valve 204, and the inlet valve is closed before sparks or corona discharges are initiated . Outlet valve 206 is typically closed while inlet valve 2 04 is open, and may open before, during, or after the onset of sparks or corona discharges. In certain cases, constant volume chamber 602 is coupled to source 302, and reactive gas is provided to chamber 602 by source 302. Filter 208 can be placed between source 302 and chamber 602 (eg, between source 302 and balance bag 304, as illustrated or between bleed valve 306 and inlet valve 2 04, as shown in Figure 3). The exhaust from an oxygen concentrator can be used to supply a reactive gas that has a reduced O2 content to chamber 602. The O2 generator can be operated in an environment that has an ambient pressure of less than 1 ATA (l-03kgf /was²) (for example, at high altitude). Alternatively, constant volume chamber 602 is coupled to pump 604 through valve 606. Pump 604 may be, for example, a positive displacement pump such as a lobe pump or vane pump, arranged to reduce the gas pressure in chamber 602, thereby decreasing the concentration of O2 and N2 in the reactive gas in chamber 602. Similarly, pump 604 can be arranged to increase the gas pressure in chamber 602, thereby increasing the concentration of O2 and N2 in the reactive gas in chamber 602 to achieve higher levels of NO generation.

FIG. 7 shows an example of a NO 700 generator. The NO 700 generator 'includes components of the NO 500 generator, such as that described with respect to FIG. 6, with source 302, as described with respect to FIG. 3, coupled to 1st inlet valve 204 and arranged to provide reactive gas to chamber 602. As indicated with respect to Figure 6, • IXSSSSS · can NOT be selectively synthesized in chamber 602 at ambient pressure, at reduced pressure, or at increased pressure achieved with pump 604.

Product gas leaving chamber 202 or 606 through outlet valve 206 of NO 200, 300, 600, and 700 generator includes electrically generated NO, and may include low levels of NO₂ and O3. In some cases, the effluent product or gas can be calibrated to a piston to raise the pressure of the. gas produced for injection into a ventilator, or coupled to an endotracheal tube for continuous injection or inspiration-coupled injection proportional to airway flow. Product gas can be briefly stored at atmospheric pressure (for example, stored for seconds before direct inhalation by a patient through a mask, before injection into an air stream for ventilation, or prior to use. to drive a fan Product gas can be mixed into fan gases In certain cases product gas can be treated to reduce a concentration of one or more components in the gas. In one example, the product gas combines with ambient or pressurized air or oxygen to produce a lower effective concentration of NO. In some examples, the product gas is treated to remove one or more unwanted by-products (eg, NCb and Cb) by contacting the product gas with a scrubber (eg, scrubber 226). In some examples, scrubber 226 includes one or more of KaOH, CaOH, CaCOj, and NaOH.

Referring to FIG. 2, scrubber 226 can be put into a cartridge 228 to process produced gas from outlet valve 206. Cartridge 228, scrubber 226, or both, may be replaceable due to the absorption capabilities. limited scrubber material. Scrubber 226 can indicate its degree of absorption (ie how close the scrubber is to maximum absorption) by changing color. In some examples, at a concentration of 80 ppm NO in the product gas, a scrubber 226 having a volume of 100 ml can reduce the NOz concentration to approximately 0 ppm.

In certain cases, including NO 300 and 700 generator imprementations in which exhaust gas from an oxygen concentrator is used for hypobaric synthesis of NO, the product gas leaving chamber 202 or 602 through the Outlet 206 can be combined with pure O2-enriched air from the oxygen or O2 concentrator from a source to form a gaseous mixture that includes a medically effective medicinal level of NO in O2-enriched air, with low NO2 levels. One or more methods of treating the product gas can be combined in any order such that, for example.

<img file="MX370384B_D0008.tif" />

NO₂ is removed from a product gas exiting chamber 202 or 602 through outlet valve 206 to produce a gaseous mixture, and this gaseous mixture is then combined with O2-enriched air from an oxygen concentrator, or a Product gas leaving chamber 202 or 602 through outlet valve 206 combines with O2-enriched air from an oxygen concentrator to form a gas mixture, and then NOa is removed from the gas mixture. The final mixture can be subjected to scrubbing again to remove NO2.

In some cases, the concentration of one or more components in the product gas can be adjusted by varying the flow of gas through the inlet valve, by varying the spark or discharge frequency, by varying the voltage or current supplied to the electrodes, as described in more detail below, or by adding several series of spark electrodes.

FIG. 8 illustrates a respiratory system 800 for electrical NO synthesis in which product gas from the NO 802 generator outlet valve 206 is provided to monitor 840. Monitor 804 may collect information related to one or more conditions associated with respiratory system. The NO generator 802 can be any NO generator described herein. Monitor 804 may include one or more sensors to evaluate a concentration of one or more components in the product gas. In some examples, the sensors use electrodes, chemiluminescent or UV absorbing media to measure the concentration of NO, NO2, O3, O2, or any combination thereof. In some cases, the 804 monitor provide feedback to the NO 802 generator or source 302 to adjust NO output, reduce N0 output₂ u 03, etc. For example, a valued concentration of NO is used to adjust the flow or concentration of reactive gas or a gas that will be mixed with the reactive gas (eg, Na, an inert gas, air, or Oz) within the chamber (eg. , chamber 202 or 602), the electrode size, separation or temperature, the spark frequency, or voltage, maximum current or limiting current of a NO generator. In one example, if an evaluated concentration of NO is higher than desired, the flow of gas into the chamber can be increased accordingly, thereby reducing the concentration of NO in the product gas. In some examples, a gas pump causes gas to flow into the chamber. Monitor 804 may include a gas flow sensor to measure the flow rate of the gas entering the chamber.

As described herein, a generator of

It does NOT produce breathing gas with a NO concentration between 0.5 ppm and 500 ppm (for example, at least 0.5 ppm and up to 1 ppm, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm, or 500 ppm). The gas produced can be diluted before inhalation. The gas can be used to oxidize hemoglobin ex vivo (for example, in a transfusion of stored blood) or inhaled by adults, children, or newborns to therapeutically treat respiratory disorders by selective pulmonary vasodilation, including pulmonary fibrosis, infection, malaria, heart attack. myocardium, stroke, pulmonary hypertension, neonates with persistent pulmonary hypertension and other conditions in which respiration of NO to oxidize hemoglobin or to supply NO metabolites in the circulation is valuable. In some cases, the NO generator can be used to supply breathing gas to humans experiencing pulmonary hypertension and hypoxia as a result of explosive decompression from an airplane or spacecraft, to treat high altitude pulmonary edema and / or to treat any medical condition at high altitude by sparks or air corona discharge in a hypobaric environment, with advantages including rapid hypobaric synthesis of a breathable therapeutic gas including NO in the absence of gas cylinders.

In some embodiments, for example when using a NO generator to provide input to a fan,

<img file="MX370384B_D0009.tif" />

NO generator operation (for example, timing and frequency of spark or corona discharge, opening and closing of inlet and outlet valve, and the like) is synchronized with inspiratory pressurization or gas flow in the airway (for example, as measured by a hot wire anemometer or pneumotachograph), such that the required amount of gas supplemented with NO for respiration is produced and injected when required. This coordinated production of NO for medical purposes provides the added advantage that NO is breathed as it is produced in an oxygen-containing gas mixture, allowing less time for NO to oxidize to NOa prior to inhalation. When NO occurs, it only lasts for a short period of time. After the short period of time, it begins to oxidize to create NO2 which, when dissolved in water, forms nitric acid and nitrate salts. If it does NOT occur long before a user is ready to inhale it, NO can be oxidized in these toxic products at the time of inspiration. Nitric acid and nitrate salts can damage components of the NO generator as well as the lungs. In combination with spontaneous ventilation, inhalation can be monitored by Mg from the diaphragm, or a thoracic or abdominal impedance band, or various airway flow sensors, or taken directly from the ventilator software activation program, and NO The generator can be electrically injected into the respiratory gas at the start of inspiration through the nose or trachea with a tube or mask.

Figure 9Ά shows an example of a respiratory system 900 for producing NO. In some embodiments, it is NOT produced electrically under ambient conditions, or hypobaric or hyperbaric conditions. Respiratory system 900 includes an energy source 902 and camera 904. Various components (eg, an oscilloscope) can make electrical measurements of respiratory system 900. In some embodiments, the energy source. 902 It is a battery, and the 900 respiratory system is portable and usable. Fig. 9E shows an example of a NO 916 generator of the respiratory system 900. The reactive gas is supplied to chamber 904 through inlet 908, and product gas exits chamber 904 through outlet 910. Power source 902 is coupled to electrodes 906 in chamber 904 to generate sparks between them. Power source 902 can be operatively coupled to pulse generator 912. Sparks through electrodes 906 form NO in chamber 904 as described herein. For a NO generator such as the NO 916 generator, a 1 kV to 10 kV spark across electrodes 906 for 10-30 milliseconds has a current in microamps, requiring less than 2 0 W or less than 10 W, based on the averaging over the pulse duration length. Averaging power consumption over a longer time (for example, 1 second) would produce a lower average power consumption (for example, an order of magnitude of 2 less, or around 0.1 W to 1 W).

The systems for producing NO described herein, including the respiratory system 900 and others, may also include a controller 914. Controller 914 coordinates the activation of a voltage source to supply a series of electrical pulses to the electrodes (eg, 805 electrodes, thus generating NO). The electrodes can be composite or galvanized with a material that is capable of optimally producing NO with minimal unwanted toxic by-products. In some examples, the electrodes include a noble metal such as iridium. Controller 914 can be coupled to pulse generator 912 and at least a portion of NO 916 generator (eg, electrodes 906) and can control parameters such as spark frequency, spark duration, and the like to generate the required amount of NO and minimum amount of unwanted toxic by-products (for example, NOj, O3) ·

Controller 914 can be configured to receive information from one or more sensors in respiratory system 900. Controller 914 can use information received from sensors to determine one or more control parameters for respiratory system 900. For example, sensor readings Oxygen level 112 can be used by controller 914 to determine the one or more control parameters. The respiratory system 900 may include a tidal volume or respiratory gas flow sensor (eg, a thermistor, a hot wire anemometer) to measure the volume, timing, and oxygen concentration of inspired gas. The controller can receive information from the ventilator related to inspiration ventilation time or inspired oxygen concentrations. In some cases, controller 914 may determine control parameters based on one or more of i) information received from a monitor (eg, monitor 804 of FIG. 8 to assess the concentration of components in the product gas or fan, such as the concentration of NO and N0₂; (ii) concentration of components in the reactive gas (for example, oxygen concentration);

iii) operating parameters of the NO 900 generator; iv) pressure, in chamber 202 (for example, especially for embodiments where the NO 200, 300 generator includes a piston 214 for adjusting the pressure in chamber 2C2); v) flow rate of the reactive gas; vi) actual or expected volume of an inspiration, and vii) whether the NO produced will be diluted with other respiratory gases (eg oxygen),

<img file="MX370384B_D0010.tif" />

to name a few.

The NO 900 generator can supply all or a portion of the product gas at the extremely high respiration rate of a high frequency oscillatory fan (HFOV). The NO 900 generator can supply all or a portion of the product gas to a positive pressure ventilator, an anesthesia machine, a continuous positive airway pressure apparatus, or a manual resuscitator, to name a few.

Human adults normally breathe 10-20 times per minute, each breath lasting

3-6 seconds. Typically, about one half to one third of the duration of the breath is inspiration. On average, each breath has a tidal volume of approximately 500 ml. In children, each breath typically has less volume, but breathing occurs at a higher rate. Thus, in the average adult, approximately 10-20 breaths per minute with one second of breaths allow spark generation intervals of approximately 10 seconds per minute.

The expected volume of an inspiration can be calculated using previous tidal volume measurements. For example, controller 914 can determine that the expected tidal volume of a subsequent inspiration will be equal

<img file="MX370384B_D0011.tif" />

to the tidal volume measurement for the latest inspiration. The 914 Controller can also average the tidal volumes of various previous inspirations to determine the expected tidal volume of a subsequent inspiration. In some examples, the 914 controller may obtain an expected tidal volume value from the fan.

Implementations of the .914 controller may include digital electronic circuits, or computer software, firmware, or hardware, including the structures described in this specification and their structural equivalents, or combinations of one or more of them. An optical or electrical sensor can be incorporated into the device to observe and report the occurrence of sparks, and to give an alarm if sparks are not occurring. For example, controller 914 may be a microprocessor-based controller (or control system) as well as an electromechanical-based controller (or control system). Instructions and / or logic in the controller may be implemented as one or more computer programs, i.e. one or more computer program instruction modules, encoded on a computer storage medium for execution by, or to control operation of, a data processing apparatus. Alternatively or in addition, the program instructions may be encoded into an artificially generated propagated non-transient signal, for example, a machine-generated electrical, optical or electromagnetic signal that is generated to encode information for transmission to a suitable receiving device for its execution by a data processing apparatus.

Controller 914 can include clients and servers and / or master and slave controllers. A client and server are generally far from each other and typically interact through a communication network. The client and server relationship originates by virtue of computer programs running on the respective computers and having a client-server relationship with each other. In some aspects, controller 914 represents a main controller (eg, master) communicatively coupled via communication elements (eg, wired or wireless) with each of the components of a NO generator. Controller 914 can be configured to adjust related parameters, duration, and spark frequency based at least in part on the composition of the product gas produced in the chamber.

FIG. 10 shows a representation of a pulse train 1000 that is triggered by controller 914. Controller 914 can determine one or more control parameters to create a pulse train. Figure 10 also shows a close-up view of one of the groups of

<img file="MX370384B_D0012.tif" />

pulses 1002 from pulse train 1000. Electric pulses are supplied to the electrodes (eg, electrodes 906), and electrodes 906 generate a series of sparks (sometimes called electric arcs). The timing of the pulses (and the resulting sparks) is controlled by the 914 controller, and can be optimized to produce the required amount of NO while producing minimal NOz and O3. In some examples, controller 914 causes a greater amount of NO to be produced if NO is to be further diluted with other respiratory gases (eg, oxygen). Several sparks make up a group of pulses, and several groups of pulses make up the pulse train. Thus, pulse train 1000 initiates the series of electric arcs.

Variables B and N control the total energy that is created by electrodes 906. Variable N sets the number of sparks per group of pulses, and variable B sets the number of groups of pulses per second. The values ​​for B and N influence the amount of NO, NOa and O3 that is created. Values ​​for B and N also influence how much heat is produced by electrodes 806. Larger values ​​of either B or N create more NO and cause Ioselectrodes 906 to produce more heat.

Variables E, F, H and P control the timing of the sparks produced in each group of pulses. Variable H is the high time of a pulse (for example, the amount of time the voltage source is activated for each electrical pulse). The high time is sometimes called the pulse width. High time and pulse width can be visually represented on a graph of a pulse voltage over a period of time. The high pulse width and time are measured from the time the pulse voltage exceeds a voltage threshold until the pulse voltage falls below the voltage threshold, and are generally in the order of microseconds. The longer the voltage source is activated for a particular electrical pulse, the greater the visual representation of the width of the particular electrical pulse.

P is the amount of time between pulses. Thus, P minus H represents a period of time when no pulses are present (for example, the voltage source is not active). Larger H values ​​and smaller P values ​​result in the 906 electrodes producing more energy. When electrodes 906 create a spark, plasma is established. The plasma temperature is proportional to the amount of energy produced by electrodes 906. In some examples, for the plasma to be produced, the reactive gas has both nitrogen and oxygen content.

B is typically in the range of 5-80 groups of pulses per second, N is typically in the range of

1-50 sparks per pulse group, P is typically in the range of 10-800 microseconds and H is typically in the range of 5-600 microseconds.

The chemical reactions that cause NO and NO2 to be produced are a function of plasma temperature. That is, higher plasma temperatures results in higher production of NO and NO2. However, the relative proportions of NO and NO2 produced vary across different plasma temperatures. In some examples, the sparks generated by the first two pulses in a group of pulses set the plasma. The first two sparks can have a high time that is longer than the sparks produced by the rest of the pulses in the pulse group. The amount of time that the first two pulses are extended is represented by variables E and F, respectively. Sparks generated by pulses beyond the first two pulses require less energy to maintain the plasma, so the high time of subsequent pulses (represented by variable H) may be shorter to prevent the plasma temperature from rising too high. . For example, although a relatively high plasma temperature can result in increased NO and NO2 production, the relatively high plasma temperature may not be ideal for producing the desired proportions of NO and NO2. The material of the electrodes 906 can play a large role in determining the amount of energy required to create a particular spark, thus affecting the ratio of NO2 / NO produced. In some examples, tungsten electrodes produce a relatively high NO2 / NO ratio, nickel electrodes produced a lower NO2 / NO ratio, and iridium electrodes produce an even lower NO2 / NO ratio, as shown. in figure 13.

Each spark that is generated creates a particular amount of NO. NO is diluted in the volume of gas produced. To ensure that the NO concentration in the inspired gas is at the expected level, controller 914 receives information from the volume sensor, mentioned above, to determine control parameters to maintain an adequate inspired NO concentration.

Controller 914 can be configured to communicate with the NO generator wirelessly (eg, via Bluetooth. Controller 914 can also be configured to communicate with external devices (eg, a computer, tablet, smartphone, or the like. Devices External devices can then be used to carry out functions of the 914 controller or to help the 914 controller carry out functions.

In some examples, controller 914 may disable certain components of the NO generator during, before, or after a series of sparks is generated. In some examples, the 914 controller may also include features to: i) detect and stop unwanted sparks; ii) confirm that a series of sparks is safe before triggering the series of sparks; iii) verify that the timing values ​​are checked against timing value backups after each series of sparks is generated to detect corruption in timing variables; and iv) determine if multiple sync backups are corrupt.

The results achieved with a NO generator (eg, NO 916 generator) are described with respect to Figures 11 to 13.

Figure 11A is an 1100 average voltage and current graph showing the average current and voltage versus sparks / second for the NO 916 generator. Figure 11B is a 1102 average energy graph showing the average energy versus sparks / second for the NO 916 generator. The average and peak energy current between 0.5 and 2 sparks / second, and the average voltage drops over the same interval. Figure 12A shows oscilloscope traces 1200 for voltage (upper trace) and current (lower trace) during two sparks of a 1 spark / second discharge. Figure 12B shows oscilloscope traces 1202 for voltage (upper trace) and current (lower trace) traces for 1 spark discharge / second with a spark duration (single spark) of 27 msec.

Figure 13 shows the concentrations of NO and NO2 from a NO generator (eg, NO 916 generator of Figure 9B) using various electrode materials. Test conditions included the use of a .635 cm (> {) rod, a 2.0 mm electrode gap, constant air flow at 5 L / min, and a FÍO2 of 0.21. For the tungsten electrode, B = 40 groups of pulses per second, n = 30 sparks per group of pulses, P = 100 microseconds and H = 20 microseconds. For nickel electrodes, B-35 groups of pulses per second, N = 40 sparks per group of pulses, H = 18Q microseconds and P = 70 microseconds. For iridium electrodes, B ~ 35 groups of pulses per second, N = 40 sparks per group of pulses, H-180 microseconds and P = 80 microseconds.

Figure 14 shows NO and NO2 concentrations at various reactive gas oxygen concentrations from the NO generator using mini spark plug (Micro Viper 23 with 6mm HEX and 10-40 THRD, Rimfire, Benton City, WA) with formation of sparks continues.

Figure 15 shows NO and NO2 concentrations at various reactive gas oxygen concentrations from the NO generator using an iridium spark plug (ACDelco 41-101, Waltham, MA) with continuous sparking.

Figure 16 shows concentrations of NO and NOs at various concentrations of reactive gas oxygen from the NO generator using iridium spark plug with intermittent sparking.

Ozone (O3) is a powerful oxidant that has many oxidation related industrial and consumer applications. However, its high oxidation potential causes damage to the mucous membranes and respiratory tissues in animals. This makes ozone a potent respiratory and pollutant hazard near ground level. Ozone is formed from atmospheric electrical discharges, and reacts with NO to form nitric dioxide (NO2) and O2 or reacts with N2 to produce NO and O2. In some examples, ozone levels are higher with continuous sparking than with intermittent sparking, and also increase with increasing O2 concentrations.

Figure 17 shows O3 levels at various O2 concentrations using the mini spark plug or iridium spark plug with continuous sparking. In this example, B ~ 60 groups of pulses per second, N = 50 sparks per group of pulses, P-140 microseconds, H = 40 microseconds, and the air flow rate is 5 L / min.

Figure 18 shows O3 levels at various O2 concentrations using the mini spark plug and iridium spark plug with intermittent sparking triggered on each breath starting with inspiration, or just before inspiration began. In this example, B = 60 groups of pulses per second, N = 50 sparks per group of pulses, P = 140 microseconds, H = 40 microseconds, and the air flow rate is 5 L / min.

Figure 19 shows O3 levels at various O2 concentrations using the mini spark plug and iridium spark plug with continuous sparking. In this example, B = 35 groups of pulses per second, N ~ 25 sparks per group of pulses, P-240 microseconds, H-100 microseconds, and the air flow rate is 5 L / min.

Figure 20 shows O3 levels at various O2 concentrations using the mini spark plug and iridium spark plug with intermittent sparking triggered on each breath starting with inspiration, or just before inspiration started. In this example, 3 = 35 groups of pulses per second, N-25 sparks per group of pulses, P = 240 microseconds, H = 100 microseconds, and the air flow rate is 5 L / min.

Figure 21 shows NO and NO2 concentrations at various reactive gas oxygen concentrations using an oxygen concentrator. In this example, B-5 ​​groups of pulses per second, N = 25 sparks per group of pulses, P = 200 microseconds, H = 60 microseconds and the flow rate of

<img file="MX370384B_D0013.tif" />

air 5 L / min.

Figure 22 shows a test environment for measuring NO and NO2 levels in a 22 00 hypobaric chamber at various atmospheric pressures. The test results are shown in Figure 25. To create a negative pressure (eg ATA medium, 1/3 ATA) within the 2400 hypobaric chamber, the inlet and outlet valves were closed and a piston was moved away of the spark plug. The spark plug then ignited for 30 seconds. In this example, B = 100 groups of pulses per second, N-10 sparks per group of pulses, P = 140 microseconds, H-10 microseconds. The piston was then transferred to the spark plug to bring the pressure in the 22 00 hypobaric chamber back to 1 ATA. The outlet valve was opened, and gas samples were taken in a 3L breathing bag as the piston was moved further into the spark plug. The gas samples collected were analyzed with Sievers Ν0Ά Í280 immediately after collection.

Referring to Figure 24, a flowchart 2400 depicts a controller operations arrangement (eg, controller 914, shown in Figure 9A). Typically, the operations are executed by a processor present in the controller. However, operations can also be performed by multiple processors present in the controller. Although typically executed by a single controller, in some arrangements, the operation execution may be spread across two or more controllers.

Operations include collecting 2402 information related to one or more triggering events associated with a respiratory system. For example, the respiration sensor 804 of FIG. 8 can collect information related to one or more triggering events associated with a respiratory system. Conditions associated with the respiratory system include one or more of the oxygen concentration of an inlet gas (eg, reagent gas), an inlet velocity of the reagent gas flow, a volume of gas, and the frequency of a

<td>inspiration,</td><td>the</td><td>pressure on a</td><td>camera</td><td>of</td><td>he</td><td>system</td>

<td>respiratory,</td><td>and</td><td>concentration</td><td colspan="2">oxygen</td><td>of</td><td>a gas</td>

<td colspan="2">product before respiratory.</td><td>and after the The operations</td><td>mixture too</td><td>in</td><td colspan="2">the system include the</td>

<td>determination</td><td>24C</td><td colspan="2">í4 of one or more parameters of</td><td colspan="2">control</td><td>based</td>

in the information collected. For example, controller 914 of FIG. 9A can determine one or more control parameters. Control parameters can create a pulse train.

Operations also include initiating a series of 2406 arcs external to the patient to generate nitric oxide based on the determined control parameters. For example, electrodes 906 in Figure

9Β can initiate a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters. The control parameters can control the times of the series of electric arcs. In some examples, conditions associated with the respiratory system also include the amounts of NO and NO2 generated by the series of arcs (for example, amounts of NO and NO2 previously generated).

Fig. 25 shows an example of an example of a computing device 2500 and an example of a mobile computing device 2550, which can be used to implement the operations and techniques described herein. For example, a portion or all of the operations of a controller (eg, controller 914 shown in FIG. 9A) may be performed by computer device 2500 and / or mobile computer device 3850. The computing device 2500 is designed to represent various forms of digital computers, including, for example, personal computers, desktops, workstations, personal digital assistants, servers, blade servers, central processors, and other suitable computers. The 2550 computing device is designed to represent various forms of mobile devices, including, for example, personal digital assistants, tablet computing devices, phones

<img file="MX370384B_D0014.tif" />

cell phones, smart phones and other similar computing devices. The components shown here, their connections and relationships, and their functions, are intended to be examples only, and are not intended to limit the implementations of the techniques described and / or claimed in this document.

Computing device 2500 includes processor 2502, memory 2504, storage device 2506, high-speed interface 2508 that connects to memory 2504 and high-speed expansion ports 2510, and high-speed interface 2512 that connects to a 2514 low-speed bus and 2506 storage device. Each of the components 2502, 2504, 2506, 2508, 2510 and 2512 are interconnected using multiple buses, and can be mounted on a common motherboard or in other ways as appropriate. Processor 2502 can process instructions for execution within computing device 2500, including instructions stored in memory 2504 or storage device 2506 to visually display graphical data for a GUI on an external input / output device, including, for example, 2516 visual presenter coupled to 2508 high-speed interface. In some implementations, multiple processors and / or multiple buses can be used, as appropriate, along with various memories and memory types. Also, various devices:

2500 computational devices can be connected, with each device providing portions of the necessary operations (eg, as a server bank, a group of blade servers, or a multi-processor system).

Memory 2504 stores data within computing device 2500. In one implementation, memory 2508 is a volatile memory unit or units. In another implementation, memory 2504 is a nonvolatile memory unit or units. Memory 2504 can also be another form of computer readable medium, including a magnetic or optical disc.

Storage device 2506 is capable of providing mass storage for computing device 2500. In one implementation, the storage device 2506 may be or contain a computer readable medium, including, for example, a floppy disk device, a hard disk device, an optical disk or device, or a tape device, a memory flash or other similar solid state memory device, or an arrangement of devices, including devices on a storage area network or other configurations. A computer program product can be tangibly incorporated into a data carrier. The computer program product may also contain instructions that, when executed, perform one or more methods, including, for example, those described above. The data carrier is a computer or machine readable medium, including, for example, memory 2504, storage device 2506, processor memory 2502, and the like.

High-speed controller 2508 handles high bandwidth operations for computing device 2500, while low-speed controller 2512 handles less bandwidth intensive operations. This role assignment is an example only. In one implementation, the high-speed controller 2508 is coupled to memory 2504, visual presenter 2516 (eg, through a graphics processor or accelerator), and high-speed expansion ports 2510, which can accept! multiple expansion cards (not shown). In the implementation, the low speed controller 2512 is coupled to the storage device 2506 and low speed expansion port 2514. The low-speed expansion port, which can include multiple communication ports (for example, USB, Bluetooth®, Ehternet, Wireless Ethernet), can be coupled to one or more input / output devices, including, for example, a keyboard, pointing device, scanner, or network device including, for example, a switch or router, for example, via a network adapter.

<img file="MX370384B_D0015.tif" />

The computing device 2500 can be implemented in a number of different ways, as shown in the figure. For example, it can be deployed as a standard 2520 server, or multiple times on a group of these servers. It can also be implemented as part of a 2524 rack server system. In addition or as an alternative, it can be implemented on a personal computer including, for example, a 2522 laptop. In some examples, components of computing device 2500 may be combined with other components in a mobile device (not shown), including, for example, device 2550. Each of these devices may contain one or more computing devices 2500, 2550, and a complete system can be made up of several computing devices 2500, 2550 that communicate with each other.

The computing device 2550 includes a processor 2552, memory 2564, an input / output device that includes, for example, visual presenter 2554, communication interface 2566, and transceiver 2568, among other components. Device 2550 can also be provided with a storage device, including, for example, a micro-unit or other device, to provide additional storage. Each of the 2550, 2552, 2564, 2554, 2566, and 2568 components are

Interconnected using various buses various components can be mounted on a common motherboard or in other ways as appropriate.

Processor 2552 can execute instructions within computing device 2550, including instructions stored in memory 2564. The processor can be implemented as a set of chips including separate and multiple analog and digital processors. The processor may provide, for example, coordination of the other components of the 2550 device, including, for example, control of user interfaces, applications run by the 2550 device, and wireless communication by the 2550 device.

Processor 2552 can communicate with a user through control interface 2558 and visual display interface 2556 docked with visual presenter 2554. Visual presenter 2554 can be, for example, a TFT LCD (Liquid Crystal Display). Thin Film transistor) or an OLED (Organic Light Emitting Diode), or other suitable display technology. Visual display interface 2556 may comprise suitable circuits for exciting visual presenter 2554 to present graphic or other data to a user. The control interface. 2558 can receive commands from a user and convert them for presentation to the 2552 processor.

Furthermore, external interface 2562 can communicate with processor 2542, thereby enabling near-area communication of device 2550 with other devices. External interface 2562 can provide, for example, wired communication in some implementations, or wireless communication in other implementations, and various interfaces can also be used.

Memory 2564 stores data within computing device 2550. Memory 2564 can be implemented as one or more than one computer-readable medium or media, a volatile memory unit or units, or a nonvolatile memory unit or units. Expansion memory 2574 can also be provided and connected to device 2550 through an expansion interface 2572, which may include, for example, a SIMM (Individual Online Memory Module) card interface. This 2574 expansion memory can provide additional storage space for the 2550 device, or it can also store applications or other data for the 2550 device. Specifically, the 2574 expansion memory can include instructions to carry out or complement the processes described above, and can also include secure data. Thus, for example, the expansion memory 2574 can be provided as a security module for the 2550 device, and can be programmed with instructions to allow the safe use of the 2550 device. In addition, secure applications can be provided through SIMM cards. , along with additional data, including, for example, putting identification data on the SIMM card in a secure and non-modifiable manner.

The memory may include, for example, flash memory and / or NVRAM memory, as described below. In one implementation, a computer program product is tangibly embedded in a data carrier. The computer program product contains instructions that, when executed, perform one or more methods, including, for example, those described above. The data carrier is a computer or machine readable medium, including, for example, memory 2564, expansion memory 2574 and / or processor memory 2552, which can be received, for example, on the transceiver 2568 or external interface 2562.

Device 2550 can communicate wirelessly through communication interface 2566, which can include digital signal processing circuits when needed. Communication interface 2566 can provide communications under various modes or protocols, including, for example, GMS forest calls, SMS, EMS or MMS, CDMA, TEMA, PDC, WCDMA, CDMA2000 or GPRS messages, among others. This communication can occur, for example, through the radio frequency transceiver 2568.

Additionally, short-range communication may occur, including, for example, using a Bluetooth®, WiFi, or other such transceiver (not shown). In addition, the GFS (Global Positioning System) receiver module 2570 can provide additional wireless navigation and location related data to the 2550 device, which can be used as appropriate with applications running on the 2550 device. Sensors and modules such as cameras, microphones, compasses, accelerators (for orientation detection), etc., can be included in the device.

The 2550 device can also communicate audibly using a 2560 audio codee, which can receive spoken data from a user and convert usable digital data. The audio code 2560 can itself generate audible sound for a user, including, for example, through a loudspeaker, for example, in a handset of the 2550 device. This sound may include sound from voice phone calls, may include recorded sound (for example, voice messages, music files, and the like), and may also include sound generated by applications operating on the 2550 device.

The 2550 computing device can be implemented in a number of different ways, as shown in the figure. For example, it can be implemented as a 2580 cell phone. It can also be implemented as part of a 2582 smartphone, personal digital assistant, or other similar mobile device.

Various implementations of the systems and techniques described here can be accomplished in specially designed digital electronic circuits, integrated circuits, ASICs (application specific integrated circuits, hardware, firmware, computer software, and / or combinations thereof. This different implementation in one or more computer programs that are executable and / or interpretable in a programmable system including at least one programmable processor, which can be special or general purpose, coupled to receive data to instructions from, and to transmit data and instructions to, a storage system, at least one

<td>device</td><td>entry,</td><td>and at least</td><td>a device</td>

<td>departure.</td><td></td><td></td><td></td>

<td>These</td><td>programs</td><td>computer</td><td>(also known</td>

<td>like programs,</td><td>software,</td><td>applications of</td><td>software or codes)</td>

they include machine instructions for a programmable processor, and can be implemented in a high-level, goal-oriented and / or procedural programming language, and / or in machine / assembly language. As used herein, the terms machine-readable medium and computer-readable medium refer to a product of

<img file="MX370384B_D0016.tif" />

computer program, apparatus and / or device (eg, magnetic disks, optical disks, memory, Programmable Logic Devices (PLDs)) used to provide machine instructions and / or data to a programmable processor, including a machine-readable medium that receive machine instructions.

To provide interaction with a user, the systems and techniques described here can be implemented in a computer that has a visual display device (for example, a CRT (Catholic Ray Tube) or monitors the liquid crystal display LCD. Visually data to the user and a keyboard and pointing device (for example, a mouse or trackball) by which the user can provide input to the computer . Other types of devices can be used to provide interaction with a user as well; for example, feedback provided to the user may be from sensory feedback (eg, visual feedback, auditory feedback, or tactile feedback); and user input can be received in one form, including acoustic, voice or touch input.

The systems and techniques described here can be implemented in a computer system that includes a back-end component (for example, as a data server), or that includes a middleware component (for example, an application server, and / or include a front end component (for example, a client computer that has a user interface or a web browser through which a user can interact with an implementation of the systems and techniques described here, or a combination of these front-end, middleware, or front-end components. The components of the system can be interconnected by a form or means of digital data communication (for example, a communication network). Examples of communication networks include a local area network (LAN), a wide area network (WAN), and the Internet.

The computer system can include clients and servers. A client and server are generally far from each other and typically interact through a communication network. The client-server relationship originates by virtue of computer programs running on respective computers and having a client-server relationship with each other.

In some implementations.es, the engines described here can be separated, contained or incorporated in an individual or combined engine. The engines illustrated in the figures are not intended to limit the systems described herein to software architectures.

<img file="MX370384B_D0017.tif" />

shown in the figures.

<td>It is noted that</td><td>with relationship</td><td>he</td><td>on the date,</td><td>e 1</td>

<td>best method known for the</td><td>applicant</td><td>for</td><td>carry</td><td>the</td>

<td>practice the said invention,</td><td>is the one who re</td><td>sulta</td><td>clear of</td><td>the</td>

present description of the invention.