CN1099997A - Generation of nitric oxide from air for medical uses - Google Patents
Generation of nitric oxide from air for medical uses Download PDFInfo
- Publication number
- CN1099997A CN1099997A CN93119286.2A CN93119286A CN1099997A CN 1099997 A CN1099997 A CN 1099997A CN 93119286 A CN93119286 A CN 93119286A CN 1099997 A CN1099997 A CN 1099997A
- Authority
- CN
- China
- Prior art keywords
- air
- gas
- mixture
- arc chamber
- inhaler
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The system can produce the mixture of NO and air. A electric arc chamber is provided by electrodes with air gap and a circuit provides the electrodes with high voltage to make them generate arc discharge, so that generates the mixture of NO and air. After purification, the mixture is mixed with other gas and/or medicinal agent for lung and then supplied to different organs.
Description
The present invention relates to a kind of produce medical and method and system air or the blended nitrogen oxide of other gas.
Nitrogen oxide (NO) for many biologys system be vital (G.Kolada, The New York Times, on July 2nd, 1991).Kolada points out that nitrogen oxide is the media of controlling blood pressure, help immune system to kill and invade intracellular parasite, stop the cancerous cell division, between brain cell, transmit signal, and can or enjoy pause dancing (Huntington) patient's the brain cell of mortality of the court of a feudal ruler to the apoplexy of weakness and have effect.
Shown that adjustable the separating of nitrogen oxide loosen pipe smooth muscle (people such as K.M.Desai, Nature, the 351st volume, on June 6th, 1991, the 477th page).The neurotransmitter of the practical a kind of non-epinephrine of the testimony of a witnesies such as Desai, non-cholinergic (NANC) is well suited for reconciling the segregate stomach that loosens Cavia porcellus, and they point out that also this NANC neurotransmitter is undistinguishable with deutero-nitrogen oxide from the L-arginine.Authors' conclusion is that nitrogen oxide is a kind of conclusive common amboceptor that smooth muscle loosens probably.
Smooth muscle is present on the wall that for example blood vessel, bronchus, gastrointestinal system and urogenital system are united.Partial smooth muscle is loosened and do not produce systemic side effects by sucking nitrogen oxide taking in the lung.This feature can be used for treating bronchoconstriction and pulmonary hypertension, pneumonia or the like.
Present known nitrogen oxide is a kind of important abiogenous local cells hormone, and so-called Intradermal obtains loosens the factor.This factor has generation in many cells (be endotheliocyte, be lining on blood vessel, bronchus, large intestine, bladder, uterus and other cavity organs) by the nitric oxide synthase (be known as an enzyme family now, have six kinds of enzymes at least) that comes from arginine.In case nitrogen oxide is released, it will with rapid combination of black thuja acid cyclase in the smooth muscle cell, increase cycloguanosine acid phosplate (cyclo GMP), lowered intracellular calcium concentration, thereby caused loosening of smooth muscle.
The nitrogen oxide that sucks as being confirmed in some animal and humans' type testing research, is a kind of effective local pulmonary vascular relaxation medicine and bronchodilator, does not have general action.Nitrogen oxide can improve the ventilation matching of infusion liquid greatly, thereby has improved the oxygen that decreases the lobe of the lung and carried usefulness, has improved the oxygen concentration of tremulous pulse.So far, NO has the agent of this optionally unique lung blood vessel function thereby for the acute and chronic lung disease of treatment bronchus constriction and Vasoconstriction great potential is arranged.
Bronchiectasis medicine is the medicine that is used for alleviating the aviation reaction, perhaps is used for the bronchospasm that causes because of various diseases on the contrary, for example the chronic obstructive pulmonary disease of asthma, deterioration, allergy and anaphylaxis and other or the like.Used several bronchodilatation medicines,, its toleration and undesirable side effect have been arranged respectively with its model of action difference.
Beta-agonists is representative with epinephrine and isoproterenol, increases the fast cry of certain animals cyclase of gland concentration and produce cell internal ring adenine nucleotides phosplate (AMP) by costimulatory receptor to cause bronchiectasis.They can come dispenser by aerosol, oral or non-intestinal.Take these medicaments and can cause the very big action of the heart that is harmful to, for example tachycardia, cardiopalmus, blood pressure change and other side effect comprise anxiety, action tremor, feel sick and headache.Newer β 2-selective antagonist, salbutamol for example, side effect is less, and property of medicine effect is also slow.
Elixicon is compared bronchiectasis effectiveness with beta antagonists less, and (therapeutic toxic window) is narrower for the malicious window of treatment.Mechanism corresponding to the bronchiectasis medicine of theophylline may be by ring AMP.The side effect that is caused by theophylline generally is nervous, nauseating, vomiting.Anorexia and headache.In addition, if taking dose is very big, theophylline can cause arrhythmia and heart attack.
The anticholinergic medicine, for example atropine methyl nitrate and ipratropium bromide are good and side effect is less by the aerosol drug delivery bronchodilator effect.But its property of medicine effect is slow, may require 60 to 90 minutes just can reach bronchiectasic peak value.
The nitrogen oxide unique distinction is, it has that the property of medicine in seconds works rapidly concurrently and the advantage that do not have general action.In case suck, it spreads in the blood flow by the lung blood vessel, combine with hemoglobin and passivation rapidly.Therefore, the bronchiectatic activity of the nitrogen oxide of suction is limited on the inlet channel and the vasorelaxation action of the nitrogen oxide that sucks only is limited on the lung blood vessel.
This property that nitrogen oxide is selectively expanded pulmonary artery also can be used for the treatment of acute or chronic pulmonary arteriotony, pulmonary artery blood pressure are defined as average pulmonary artery blood pressure and are higher than normal value 12 to 15 millimetress of mercury.
The generation of acute pulmonary artery blood pressure is owing to the sudden anoxia of reaction causes pulmonary vascular contraction, because the anoxia that causes of pneumonia, pulmonary infarction or acidosis for example, acute pulmonary artery blood pressure is a kind of potential reversible phenomenon, successfully treats the burst factor and can make the lung blood pressure become normal.But the persistency anoxia is directed at the nonvolatil structural change of lung blood vessel, and the chronic pulmonary arteriotony then.The main cause of chronic pulmonary arteriotony is an obstructive disease of lung, the multiple Microembolism of recurrent, heart disease, and as mitral stenosis, or atrial septal defect, and spontaneous former pulmonary artery blood pressure disease.The pulmonary artery blood pressure is also relevant with other several fatal situations, for example senile respiratory distress syndrome and neonate persistency pulmonary artery blood pressure.
So far, attempted, comprised Nitroprusside, Aprelazine, nifedipine, mercaptomethyl propionyl proline and other or the like with several vasodilator drugs treatment pulmonary artery blood pressures.The main limitation of these medicaments is that it all reduces the blood pressure of lung and whole body indiscriminately.In contrast, the vasorelaxation action that the nitrogen oxide of suction produces is only limited to pulmonary artery, thereby has brought a kind of revolutionary advantage for treating.
Described a kind of inhaler in No. 07/767234, the U.S. Patent application and be used for nitric oxide delivery, this application was accepted in JIUYUE in 1991 on the 23rd, and transferred the applicant, classified it as list of references at this.
The present invention is to provide a kind of system that produces the mixture of medical nitrogen oxide and air or other gases.This system only uses air and a power supply to produce nitrogen oxide when an arc discharge.The present invention can in all case produce nitrogen oxide without restriction.
A kind of portable inhaler that patient can carry system of the present invention will go Anywhere to him or she, and uses symptom, acute respiratory failure or the reversibility lung vasoconstriction syndrome of inhaler treatment asthmatic attack or other bronchoconstrictions.In addition, patient can change the suction volume of nitrogen oxide because of the variation of his or her medical condition.
System of the present invention can be in medical treatment or uses during emergency treatment, is used to produce NO, and is transported in the certain organs of human body with the blended NO that reaches effective treatment concentration of other gases.Nitrogen oxide diastole smooth muscle immediately almost after sending to; And the effect of nitrogen oxide only limits in the organ of being treated.
An object of the present invention is to provide a kind of inhaler, generation is used for the air of respiratory therapy or the mixture of other gas NO; This inhaler uses a power supply to produce electric arc between a pair of electrode that is separated by air-gap.Air constantly is introduced in the arc chamber that electrode is housed by an air intlet.This inhaler has a circuit to be used for providing high voltage to electrode, and wherein, high-tension peak value is enough to produce electric arc between the air-gap of electrode.Arc discharge produces nitrogen oxide.The nitrogen oxide that generates mixes with air to export by one and is sent and is sucked by patient.
The preferred embodiment of this purpose of the present invention can comprise be positioned in the arc chamber by two axial electrodes of metal bar system collimatedly, its tip by adjustable air-gap separately, the circuit of inhaler comprises a high-tension transformer, its primary coil and a power supply join, and the RCL circuit of a parallel connection and secondary, the high-tension coil of transformator are connected in parallel.The resistive element of RCL circuit in parallel comprises the high-field electrode that is separated by air-gap.The air intlet of inhaler has a filter, is used for filtering through the air intlet inhaled air entering arc chamber to stop droplet or solid particle.The size requirements of inhaler can be portable and weight approximately less than 1 kilogram.
The preferred embodiment of this purpose of the present invention can also comprise a purifier, is used to remove the nitrogen dioxide and the ozone of the low content that generates in arc chamber.The setting of purifier should make the gas that leaves arc chamber pass through purifier from being forced to it before inhaler discharges.Outlet has a mouthpiece, is used for directly sucking from arc chamber being forced to the admixture of gas of sending through purifier.
The preferred embodiment of this purpose of the present invention can also comprise air intlet parts, it has the limiting orifice of a series of selections, be used to make the adjustable air of flow to enter suction inlet, and when sucking human body, this air mixed mutually with the admixture of gas that comes out from arc chamber by mouthpiece.Purifier contains O
3And NO
2Cleanser, for example, soda lime or calcium barium absorbent.
The preferred embodiment of this purpose of the present invention can also comprise an air pump, is used to force admixture of gas to export from outlet by purifier.Admixture of gas just can enter in the oxygen face mask or be forced to and send into room or cell then, for example in the couveuse.
But another object of the present invention provides the system of the mixture of a kind of continuous production air and nitrogen oxide, is used for the treatment of the medical disease that an organ of human body is directly sent into this mixture in requirement.There is an arc chamber in this system, and it has a pair of electrode that is separated by an air-gap, produces nitrogen oxide by arc discharge is arranged between electrode.This system also comprises a circuit, is used for providing high-tension electricity to electrode.High-tension peak value is enough to produce electric arc between air-gap.This system has an air intlet to be used for continuously air being introduced arc chamber.Gas delivery system be used for purifying and transmit generated with air or the blended nitrogen oxide of other gas in the organ of human body, for example use a kind of mechanically ventilated device or respirator that this mixture (other gases are for example anaesthetized gas and also can be added) is delivered in the lung.
The preferred embodiment of this purpose of the present invention can also comprise a gas feed manifold, the gas that is used to introduce through selecting enters this induction system, the gas that is used for through selecting accurately mixes with the nitrogen oxide gas mixture of generation, and the admixture of gas after mixing with the induction system transmission.
The preferred embodiment of this purpose of the present invention can also comprise a gas analyser (for example, the NOx chemiluminescent analyzer), is used to analyze each component concentrations of the described admixture of gas that is transmitted by induction system.A regulator system is connected with the gas feed manifold with analyser, is used for regulating by predetermined prescription metering the concentration of each component gas (for example, breathing the oxygen of usefulness) of introducing induction system.
Other features and advantages of the present invention are come from the description of hereinafter preferred embodiment and claim as can be seen.
Fig. 1 is the sectional schematic diagram of a kind of portable inhaler embodiment of the present invention.
Fig. 2 represents to be used for the simplified schematic diagram of the high-pressure generating circuit of embodiment.
Fig. 3 is the schematic cross-sectional view that is used for the large-scale inhaler embodiment in room.
Fig. 4 be used for the treatment of with the urgent rescue facility in the schematic cross-sectional view of inhaler system implementation plan.
Fig. 5 is the schematic cross-sectional view of another embodiment, is used for NO is delivered to the Different Organs of human body, comprises being used to help the mechanically ventilated device breathed.
Fig. 6 is an explanation NO air-flow concentration to the function relation figure of average current in the high-tension transformer primary coil and the air mass flow by arc chamber.Interelectrode gap is 3 millimeters, and V is an air mass flow among the figure, rise/minute, and the concentration of NO is 1,000,000 volume contents (PPM).
Fig. 7 is an explanation NO air-flow concentration to the function relation figure of electric current in the high-tension transformer primary coil and the air mass flow by arc chamber.Electrode gap is 5 millimeters, and V is an air mass flow among the figure, rise/minute, the concentration of NO is 1,000,000 volume contents (PPM).
Fig. 8 is owing to injecting the sheep suction NO who wakes that U46619 has acute pulmonary artery blood pressure disease, at the variation diagram of the different experiments stage pulmonary artery pressure that sucks NO.NO shows significant lung vasodilation performance by discharge generation.
Fig. 1 illustrates a portable inhaler, has the air inlet 2 that makes air admission arc chamber 4.Import 2 comprises a check valve and a kind of 0.22 micron filter 3 of being made by Millipore company.This filter is removed to be present in and is sucked airborne antibacterial and undesirable composition.Arc chamber 4 usefulness electrically insulating materials are made, and two electrodes of axially placing 5 are arranged, and are separated by air-gap 9.One high-pressure generating circuit 7 is connected with electrode 5.Arc chamber 4 is connected with a soda lime filter 13, and this filter is attached to induction chamber 14 places.Induction chamber 14 is introduced parts 15 by a mouthpiece 17 with by the air that the aperture of a series of selectable restrictions is formed.Each aperture has a filter 16, is used for filtering having airborne drop and solid particle.Gas passage system (comprising import 12, filter 3,13,16 and induction chamber 14) is designed to and can not sucked by patient by resistance ground.Can use different types of filter 3,16 according to inhaler environment of applications situation.Inhaler seals with the shell 19 that a Teflon manufactures, or seals with other high voltage insulating materials.The operation of the on and off switch 11 control inhalers of tape light 12.
Referring to Fig. 2, a high-pressure generating circuit 7 comprises that one has booster transformer 24 elementary, secondary coil.Primary coil is connected secondary coil with power supply 21--and high-tension coil 25 RCL circuit in parallel with joins.The voltage of being introduced by power supply 21 rises into high pressure through autotransformer 23 adjustings and at secondary coil 25.Other produce the circuit of high energy voltage, and for example Tesla coil also can use.Electric energy temporarily is stored in the capacitor 26, charges to breakdown voltage, subsequently by air-gap 9 discharges.The air-gap 9 that is limited by two electrodes 5 has determined the resistance that two electrodes are provided with.The width of breakdown voltage (about 20kv) and air-gap and the shape of electrode 5 are proportional.
Arc discharge produces the plasma that is confined between the air-gap.In plasma, oxygen and nitrogen molecule break, atomic ionization and generate ozone and NO.The sub-fraction nitrogen oxide is subsequently oxidized to higher oxide, forms nitrogen dioxide.But this process is only more remarkable at the temperature ascent stage.The concentration of NO, NO2 and O3 is decided by the persistent period of the width and the electric arc of air-gap, and represents with volume part per million (ppm).
When inhaler was worked, gas was sucked away from arc chamber 4, by soda lime filter 13 and suction chamber 16, sucked this admixture of gas by patient through mouthpiece 17.Soda lime filter 13 is removed deleterious NO2 and O3 from admixture of gas, prevent that them from entering suction inlet, so gaseous mixture only contains original air and NO.Meanwhile additional air enters inhaler by import 2 and is inhaled into arc chamber 4, arc discharge ionization N2 subsequently and O2 molecule and form NO, NO2 and O3, and this process repeats.The concentration of the NO that produces in the arc discharge chamber is between 10 to 250ppm, and this resistance that depends on air-gap 9 is decided with being transported to the energy of electrode 5.The NO concentration range (for portable inhaler) that medical effect is arranged is from about 1ppm to 180ppm.For making the NO concentration in the inhaler reach these numerical value, used an other air mixing import 15 of the opening that has one group of different size.Patient automatically mixes the gas of arc chamber with the air that enters import 15 mutually by mouthpiece 17 breathing gas of inhaler.Change the concentration of NO, the perforate that patient can select different size for use is passed import 15 and is entered air capacity in the suction chamber 16 to increase or to reduce.In another embodiment, patient can not oneself suck gas, and an air pump 18 of configuration or other pressure sources (for example, rebreather) force admixture of gas to leave inhaler in suction chamber 16.This moment a mouthful pump can be connected on the tracheal intubation or trachea choosing mouthful intubate on.This electric power NO generator can be connected on the pneumatic multiple dose inhaler of a standard (MDi), and the latter can spray a kind of bronchiectasis medicine (for example Arubendol, corticosteroid, etc.) of chemosynthesis in import 15.In several seconds subsequently, direct bronchiectatic activity takes place in the NO by electrical production of suction, produces secular bronchiectatic activity with MDi.To increase the curative effect of MDi like this,, improve sending to of medicine because NO has expanded bronchus.Also can be other imbedibility medicines, for example surfactant, mucopolysaccharidase or the like inject (perhaps before NO, perhaps with NO) with the NO of electrical production.
In an embodiment preferred, inhaler is the portable hand-held battery powered device of light weight, and size is less than about 20 * 20 * 10 centimetres.The patient who suffers from asthma or pulmonary artery blood pressure disease can be with this inhaler, and according to his or his needs use it.At first, patient may need to suck heavy dose of nitrogen oxide, and for example concentration is the nitrogen oxide (in air) of 150ppm, and this can accomplish by closing air intlet 15.When patient's bronchus and/or lung vasodilation, he or she can reduce concentration by selecting a bigger perforate.Hand held inhaler provides a kind of unrestricted NO the source.
In another preferred embodiment, inhaler is a kind of big system that uses in the room.Referring to Fig. 3, an air pump 32 forces air to enter an arc chamber 35.Remove to appear at a filter 31 at import 30 places and suck airborne unwanted component, identical with portable inhaler embodiment, arc chamber is manufactured by electrically insulating material, and two electrodes 36 that separated by air-gap are arranged.Electrode 36 is connected on the high-tension circuit 34, by 110v, 60Hz(or 220v, the 50Hz of a standard) the supply socket power supply.The nitrogen oxide that generates in arc discharge, nitrogen dioxide and ozone are forced through a soda lime filter 38.Filter 38 is absorption of N O2 and O3 from admixture of gas, and (for example, O2) mutually blended nitrogen oxide is pumped out outlet 39, and the latter can be connected with a face shield with air or other gas.For another embodiment preferred, the admixture of gas of generation is pumped in the couveuse or in the room by exporting 39.
In another embodiment preferred, inhaler be a kind of in medical treatment or emergency aid and treatment facility used device.The size of inhaler is decided according to its special purposes.Bigger device is powered portable inhaler 9v battery with the 110v60Hz supply socket of standard.Referring to Fig. 4, used a kind of air collector and actuator 40 with the air of supplying with 17 pounds/square inch of pressure in NO generation system.Similar to another embodiment, this system has an import 42, to have the arc chamber 44 and a soda lime filter 48 of electrode 46.NO and Air mixing gas generate according to mode as hereinbefore.In addition, there is one 5 liters mixed gas bag 50 in this system, is connected with outlet 58.Mix gas bag 50 be used for mixing from enter the mouth 59 air of coming in from the rich N2 gaseous mixture of enter the mouth 52 oxygen that enter or oxygen.The mixture of air, oxygen and NO is incorporated on a rebreather or the oxygen mask through outlet 58.An oxygen intake component (Fio2) quantifier 56 is connected in the outlet 58 to measure the volume ratio of oxygen.
In another preferred embodiment, the invention provides a system that is used for medical facilities, for example in the special nursing facility or emergency room in.Referring to Fig. 5, this system has used a pressure to be about 50 pounds/square inch air source 60.The arc chamber of this big system can comprise more than a pair of electrode so that increase the volume of production of nitrogen oxide.The setting of this device similar in Fig. 1,3 and 4.There is the air of pressure to be introduced into the arc chamber 64 that is provided with electrode 66 through an actuator 62.The unwanted pair of product (being NO2 and O3) that one soda lime filter 68 absorbs in the arc discharge process.The mixture of air and NO with a Bird agitator 70 with mix mutually from 72 oxygen of coming in that enter the mouth.A FiO2 quantifier 74 is connected to the ratio of measuring oxygen in the outlet 76.This system by a reference power supply power (110v, 60Hz).In addition, this device has an automatic regulator system to be connected with air intake to be connected with air pump with a gas analyser.Gas analyser is being monitored the quantity of nitrogen oxide in the admixture of gas that is transported to human organ and other gases; In addition, analyser is being controlled the automatic regulator system to keep the science concentration of NO according to definite plan.This embodiment can be received on the mechanically ventilated device, and being used for provides NO admixture of gas to the ventilation treatment.
In the outlet 76 various auxiliary devices (not shown among Fig. 5) can be installed, be transported on the designated organ with mixture with all gases and NO.For example export 76 the device of a kind of NO of conveying to the Foley catheter end head can be installed, so that conduit inserts urinary system or bladder becomes easy.
Example 1
Be respectively electrode gap shown in Fig. 6 and 7 and be 3 and the test curve of the device of 5mm.The air of different flow (V) (scope is from 1 liter/minute to 10 liters/minute) is introduced arc chamber.The electric current of transformer primary winding changes to 1.25mA to increase the power of high-tension circuit from 250 μ A.The output object of arc chamber is incorporated in the NOx chemiluminescence gas analyser, to determine the content of different nitrogen oxides.
Referring to Fig. 6, the concentration of NO is represented with megabit content, and unidirectional adjusting ground increases along with the energy of supplying with electrode (it has the air gap of 3mm).The highest NO concentration is that 1 liter/timesharing obtains at air-flow (V); The concentration of the air mass flow NO of Zeng Daing will reduce again.
For air gap is 5mm, can observe trend much at one, is shown among Fig. 7.But, because air gap is bigger, the plasma that arc discharge produces is also bigger, thereby the concentration of the NO of arc discharge generation is also higher.Breakdown potential medium and the necessary voltage that produces electric spark between two electrodes are approximately 20 kilovolts.The higher breakdown voltage of the big more then requirement of electrode separation.
The content of the ozone that produces in the arc discharge is measured with a kind of ultraviolet luminosity ozone analyzer.The NO generation systems of spark gap 3mm is 2 liters/timesharing produces 0.01ppm in arc discharge chamber a ozone in air mass flow.This O3 concentration is lower than the ozone exposure limit value of occupational safety of U.S. Ministry of Labour and the conclusion of healthy office really.Similarly, the measurement concentration of NO2 also very low (concentration of＜2% NO).
Selected operation is about 1.1mA when adopting the air mass flow of about 1.51/m.Yet these parameters depend on shape, air humidity and the other factors of electrode.
Example 2
The male Dorset sheep of one 30 kilogram weight has been implemented the tracheostoma postoperative, inserts a slenderness ratio and be 7 pulmonary artery Swan-Ganz intubate and femoral arteriography, so that monitor the arteriotony of lung and whole body incessantly.The sheep that wakes constantly is injected into the U46619(Upjohn drug company of 0.6 microgram/kg/minute and produces), a kind of stable thromboxane can be simulated and be produced acute pulmonary artery contraction and hypertension symptom.Inject U46619 and make pulmonary artery blood pressure (PAP) rise 79%, 19mmHg is raised to 33mmHg from meansigma methods.Be used to produce the arc chamber of mixture of air and NO and circuit with shown in Figure 4 identical.In case suck the air of 10ppmNO content, PAP reduces by 25%, drops to 25mmHg at once, confirmed that NO(is produced by 5mm air-gap HVDC electric spark) vasorelaxation action.Fig. 8 shows the NO(that sucks variable concentrations and is measured by chemoluminescence method) with the relation curve of mean P AP.When the increasing electric current obtained 15ppm suction NO concentration, PAP dropped to the level of 23mmHg.Continuation increasing suction NO amount reaches 40ppm and can further reduce PAP, reaches the 18mmHg level of not injecting U46619.Then, in the lung of sheep, only carry air, owing to the effect of not revolted of U46619 preserved material makes PAP be elevated to 34mmHg rapidly.In the process of the test of whole suction NO, systemic arterial blood pressure (SAP) still keeps 94mmHg constant.What SAP remained unchanged fact proved that sucking NO only has dilating effect in the part of pulmonary circulation blood vessel.
Other embodiments of the present invention are all in the scope of claims.With regard to " air " of indication in claims, both comprised common air, also comprise other gaseous mixtures that contain N2 and O2.Various other gases, anesthetis for example, the bronchiectasis medicine of delivery of supplemental oxygen, other classes (for example, multiple dose inhaler), or the medicine of other treatment lung (for example, surfactant, mucopolysaccharidase, various anti-inflammatory agent), or the like, also can add among the NO and Air mixing gas of embodiment of the present invention production.
Claims (25)
1, a kind of inhaler that is used for the generation mixture of respiratory system treatment, wherein this mixture comprises air and nitrogen oxide, and described inhaler uses an air and a power supply, and described inhaler comprises:
Arc chamber with a pair of electrode that is separated by air-gap is used for producing nitrogen oxide by arc discharge between described electrode,
One is used for providing highly compressed circuit to described electrode, and described high pressure has a peak value to be enough to produce electric arc between described air-gap,
Gas feed part that is used for providing continuously the described arc chamber of air admission and
The exit portion that the mixture that is used to discharge described generation smokes to patient.
2, the inhaler of claim 1, the described electrode of wherein said arc chamber are two axially metal bars of collimation, and their tip is separated by described air-gap.
3, the inhaler of claim 2, wherein said circuit comprises:
One has the elementary high-tension transformer that is connected in power supply,
A RCL circuit in parallel is parallel to secondary, the high-pressure side of described high-tension transformer, and the resistive element of wherein said RCL circuit in parallel comprises the high-field electrode that is separated by described air-gap.
4, claim 1,2 or 3 inhaler, wherein said air intlet partly comprises a filter, is used to filter the air by described import department, enters described arc chamber to stop drop or solid particle.
5, the inhaler of claim 4, the size of wherein said inhaler are less than about 20 * 20 * 10cm, and its weight is less than about 1kg.
6, the inhaler of claim 4, comprising
One purifier is used to remove the nitrogen dioxide and the ozone that generate in described arc chamber, the setting of described purifier be for make gas leave described arc chamber be forced through before from described inhaler, discharging described purifier and
One mouthpiece in described exit is used for directly sucking described admixture of gas from described arc chamber through described purifier.
7, the inhaler of claim 6, wherein further comprise air intlet parts, it has the limiting orifice of a series of selections, the air that is used for controlling flow is incorporated into described suction inlet place, and uses the described admixture of gas that obtains from described arc chamber to mix with described air when sucking described mixture by described mouthpiece.
8, the inhaler of claim 6, wherein said purifier contains the cleanser for O3 and NO2.
9, claim 1 or 2 inhaler further comprise
One purifier is used to remove the nitrogen dioxide and the ozone that generate in described arc chamber, the setting of described purifier be for make admixture of gas leave described arc chamber be forced through described purifier and
One air pump is used to force described admixture of gas to discharge from described exit.
10, be used for the system that continuously preparation comprises the mixture of air and nitrogen oxide, described mixture directly need be delivered to patient's organ for medical therapy, described system comprises
Arc chamber with a pair of electrode that is separated by air-gap is used for producing nitrogen oxide by arc discharge between described electrode,
One is used for providing highly compressed circuit to described electrode, and described high pressure has a peak value to be enough to produce electric arc between described air-gap,
One be used for providing continuously gas feed part that air or row's ventilation enter described arc chamber and
Mixture that is used to discharge described generation induction system to the organ of human body.
11, the system of claim 10, wherein said induction system are specially on the specific organ of the described mixture to of direct discharge.
12, the system of claim 11, further comprise a gas feed manifold, be used for selected gas is incorporated into described induction system, described mixture is mixed with the gas of described selection and discharge described mixture by described induction system.
13, claim 12 further comprises
One gas analyser, be used to analyze described each composition of admixture of gas of discharging by described induction system concentration and
One regulating system is connected on described analyser and the described gas feed manifold, is used for introducing according to predetermined prescription measure control the concentration of described each composition of induction system.
14, a kind of preparation is used for the method for the mixture of respiratory system treatment, and wherein this mixture comprises air and nitrogen oxide, and described method is used an air and a power supply, and wherein step comprises:
By the arc chamber of air intlet introducing air admission one inhaler,
Provide high voltage to by air-gap separately and place on the electrode assembly of described arc chamber, described high pressure has a peak value to be enough to produce electric arc between described air-gap,
By between described electrode by the arc discharge of described high-voltage charging produce nitrogen oxide and
Discharge the mixture of described generation by an outlet.
15, the method for claim 14 wherein further comprises in order to prevent that drop or solid particle from entering described arc chamber, filters the step of the air of introducing through described import department.
16, the method for claim 14 wherein further comprises the nitrogen dioxide and the ozone that produce in order to remove in described arc discharge process, purify the step of the gas of sucking-off from described arc chamber.
17, the method for claim 14 comprises further wherein from the nitrogen oxide of described arc chamber inspiration and the described mixture of air and carries out blended step with the air of introducing through air intlet parts that these parts have the limiting holes of a series of selections.
18, the method for claim 14 wherein further comprises the nitrogen dioxide and the ozone that produce in order to remove in described arc discharge process, purify the step of the gas of inspiration from described arc chamber.
19, the method for claim 14 wherein further comprises and uses an air pump to force described admixture of gas to be discharged from described outlet.
20, a kind of preparation is used for the method for the nitrogen oxide of medical therapy, and by directly the described admixture of gas of organ particular delivery being carried out, wherein step comprises:
Introduce air and enter into the arc chamber of described system through an air intlet,
Provide high voltage to by air-gap separately and place on the electrode assembly of described arc chamber, described high pressure has a peak value to be enough to produce electric arc between described air-gap,
By between described electrode by the arc discharge of described high-voltage charging produce nitrogen oxide and
To use with the nitrogen oxide of the blended described generation of air of passing through an induction system and discharge, this induction system design is the certain organs that is used for described admixture of gas is transported to patient's health.
21, the method for claim 20, wherein said nitrogen oxide is transported on the certain organs.
22, the method for claim 20, comprise further that wherein the selected gas of guiding enters into described induction system through a gas feed manifold, the mixture that produces with described nitrogen oxide and air mixes with the gas of described selection, and the step of discharging described mixture by described induction system.
23, the method for claim 22, wherein further step comprises:
Analyze the described admixture of gas by described induction system discharge each composition concentration and
According to the concentration that each composition that enters into described induction system is regulated in predetermined prescription metering, a use therein regulating system is connected on gas analyser and the described gas feed manifold.
24, claim 1 or 10 device wherein further comprise the device that described mixture is added assist gas.
25, the method for claim 14 wherein further comprises the step of described mixture being added assist gas.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR9303645A BR9303645A (en) | 1993-08-31 | 1993-08-31 | Food product manufacturing process |
| CN93119286.2A CN1099997A (en) | 1993-08-31 | 1993-09-10 | Generation of nitric oxide from air for medical uses |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR9303645A BR9303645A (en) | 1993-08-31 | 1993-08-31 | Food product manufacturing process |
| CN93119286.2A CN1099997A (en) | 1993-08-31 | 1993-09-10 | Generation of nitric oxide from air for medical uses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1099997A true CN1099997A (en) | 1995-03-15 |
Family
ID=36869975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93119286.2A Pending CN1099997A (en) | 1993-08-31 | 1993-09-10 | Generation of nitric oxide from air for medical uses |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1099997A (en) |
| BR (1) | BR9303645A (en) |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6617355B1 (en) * | 1997-05-21 | 2003-09-09 | The University Of Virginia Patent Foundation | Treating asthma by preventing and/or accomodating S-nitrosothiol breakdown |
| CN102781825A (en) * | 2009-12-23 | 2012-11-14 | 皇家飞利浦电子股份有限公司 | Method for generating nitric oxide |
| CN103648975A (en) * | 2011-05-04 | 2014-03-19 | N2应用有限公司 | Energy efficient process for producing nitrogen oxide |
| CN104394923A (en) * | 2012-03-30 | 2015-03-04 | 密执安大学评议会 | Nitric oxide delivery devices |
| CN105283213A (en) * | 2013-03-15 | 2016-01-27 | 通用医疗公司 | Inspiratory synthesis of nitric oxide |
| CN105431191A (en) * | 2013-03-15 | 2016-03-23 | 通用医疗公司 | Synthesis of nitric oxide gas for inhalation |
| CN105473166A (en) * | 2013-10-31 | 2016-04-06 | 奥里根股份有限公司 | Methods for using nitric oxide in a plasma state to treat medical conditions and diseases |
| CN105726292A (en) * | 2014-08-26 | 2016-07-06 | 皇甫起万 | Device for generating steam containing nitric oxide |
| CN106604735A (en) * | 2014-06-13 | 2017-04-26 | 奥里根股份有限公司 | Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals |
| CN107073239A (en) * | 2014-10-20 | 2017-08-18 | 通用医疗公司 | System and method for synthesizing nitric oxide |
| CN109310842A (en) * | 2016-03-25 | 2019-02-05 | 通用医疗公司 | Delivery system and method for electric plasma synthesis of nitric oxide |
| US10239038B2 (en) | 2017-03-31 | 2019-03-26 | The General Hospital Corporation | Systems and methods for a cooled nitric oxide generator |
| US10286176B2 (en) | 2017-02-27 | 2019-05-14 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US10328228B2 (en) | 2017-02-27 | 2019-06-25 | Third Pole, Inc. | Systems and methods for ambulatory generation of nitric oxide |
| CN111588951A (en) * | 2019-02-21 | 2020-08-28 | 陈之硕 | Plasma aerosol inhalation device and use of plasma liquid |
| US11045620B2 (en) | 2019-05-15 | 2021-06-29 | Third Pole, Inc. | Electrodes for nitric oxide generation |
| WO2021252401A1 (en) * | 2020-06-07 | 2021-12-16 | Alti, Llc | Nitric oxide generation, delivery, and monitoring system |
| US11479464B2 (en) | 2019-05-15 | 2022-10-25 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11571538B2 (en) | 2012-03-30 | 2023-02-07 | The Regents Of The University Of Michigan | Gas delivery devices |
| US11691879B2 (en) | 2020-01-11 | 2023-07-04 | Third Pole, Inc. | Systems and methods for nitric oxide generation with humidity control |
| US11827989B2 (en) | 2020-06-18 | 2023-11-28 | Third Pole, Inc. | Systems and methods for preventing and treating infections with nitric oxide |
| US11833309B2 (en) | 2017-02-27 | 2023-12-05 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11975139B2 (en) | 2021-09-23 | 2024-05-07 | Third Pole, Inc. | Systems and methods for delivering nitric oxide |
-
1993
- 1993-08-31 BR BR9303645A patent/BR9303645A/en not_active Application Discontinuation
- 1993-09-10 CN CN93119286.2A patent/CN1099997A/en active Pending
Cited By (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6617355B1 (en) * | 1997-05-21 | 2003-09-09 | The University Of Virginia Patent Foundation | Treating asthma by preventing and/or accomodating S-nitrosothiol breakdown |
| CN102781825B (en) * | 2009-12-23 | 2016-03-09 | 皇家飞利浦电子股份有限公司 | Produce nitric oxide production method |
| CN102781825A (en) * | 2009-12-23 | 2012-11-14 | 皇家飞利浦电子股份有限公司 | Method for generating nitric oxide |
| CN103648975A (en) * | 2011-05-04 | 2014-03-19 | N2应用有限公司 | Energy efficient process for producing nitrogen oxide |
| CN103648975B (en) * | 2011-05-04 | 2015-12-02 | N2应用有限公司 | Produce the high energy efficiency technique of nitrogen oxide |
| US9221682B2 (en) | 2011-05-04 | 2015-12-29 | N2 Applied As | Energy efficient process for producing nitrogen oxide |
| US9872953B2 (en) | 2012-03-30 | 2018-01-23 | The Regents Of The University Of Michigan | Nitric oxide delivery devices |
| CN104394923A (en) * | 2012-03-30 | 2015-03-04 | 密执安大学评议会 | Nitric oxide delivery devices |
| US11571538B2 (en) | 2012-03-30 | 2023-02-07 | The Regents Of The University Of Michigan | Gas delivery devices |
| US10293133B2 (en) | 2013-03-15 | 2019-05-21 | The General Hospital Corporation | Inspiratory synthesis of nitric oxide |
| US10279139B2 (en) | 2013-03-15 | 2019-05-07 | The General Hospital Corporation | Synthesis of nitric oxide gas for inhalation |
| US10646682B2 (en) | 2013-03-15 | 2020-05-12 | The General Hospital Corporation | Inspiratory synthesis of nitric oxide |
| CN105431191A (en) * | 2013-03-15 | 2016-03-23 | 通用医疗公司 | Synthesis of nitric oxide gas for inhalation |
| US10434276B2 (en) | 2013-03-15 | 2019-10-08 | The General Hospital Corporation | Inspiratory synthesis of nitric oxide |
| US10773047B2 (en) | 2013-03-15 | 2020-09-15 | The General Hospital Corporation | Synthesis of nitric oxide gas for inhalation |
| CN105283213B (en) * | 2013-03-15 | 2018-10-16 | 通用医疗公司 | Nitric oxide production air-breathing synthesis |
| CN105283213A (en) * | 2013-03-15 | 2016-01-27 | 通用医疗公司 | Inspiratory synthesis of nitric oxide |
| CN109331311A (en) * | 2013-03-15 | 2019-02-15 | 通用医疗公司 | Nitric oxide production air-breathing synthesis |
| US12011544B2 (en) | 2013-03-15 | 2024-06-18 | The General Hospital Corporation | Inspiratory synthesis of nitric oxide |
| CN109663193A (en) * | 2013-03-15 | 2019-04-23 | 通用医疗公司 | For the synthesis of the nitric oxide gas of sucking |
| CN105473166A (en) * | 2013-10-31 | 2016-04-06 | 奥里根股份有限公司 | Methods for using nitric oxide in a plasma state to treat medical conditions and diseases |
| CN106604735A (en) * | 2014-06-13 | 2017-04-26 | 奥里根股份有限公司 | Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals |
| CN105726292A (en) * | 2014-08-26 | 2016-07-06 | 皇甫起万 | Device for generating steam containing nitric oxide |
| CN105726292B (en) * | 2014-08-26 | 2017-12-26 | 皇甫起万 | For generating vapoury nitric oxide production equipment |
| CN116177503A (en) * | 2014-10-20 | 2023-05-30 | 通用医疗公司 | System and method for synthesizing nitric oxide |
| CN107073239A (en) * | 2014-10-20 | 2017-08-18 | 通用医疗公司 | System and method for synthesizing nitric oxide |
| US11497878B2 (en) | 2014-10-20 | 2022-11-15 | The General Hospital Corporation | Systems and methods for synthesis of nitric oxide |
| CN109310842A (en) * | 2016-03-25 | 2019-02-05 | 通用医疗公司 | Delivery system and method for electric plasma synthesis of nitric oxide |
| US11617850B2 (en) | 2016-03-25 | 2023-04-04 | The General Hospital Corporation | Delivery systems and methods for electric plasma synthesis of nitric oxide |
| CN109310842B (en) * | 2016-03-25 | 2022-08-19 | 通用医疗公司 | Delivery system and method for electric plasma synthesis of nitric oxide |
| US10532176B2 (en) | 2017-02-27 | 2020-01-14 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US10695523B2 (en) | 2017-02-27 | 2020-06-30 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11911566B2 (en) | 2017-02-27 | 2024-02-27 | Third Pole, Inc. | Systems and methods for ambulatory generation of nitric oxide |
| US11033705B2 (en) | 2017-02-27 | 2021-06-15 | Third Pole, Inc. | Systems and methods for ambulatory generation of nitric oxide |
| US11833309B2 (en) | 2017-02-27 | 2023-12-05 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US10286176B2 (en) | 2017-02-27 | 2019-05-14 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11376390B2 (en) | 2017-02-27 | 2022-07-05 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US10328228B2 (en) | 2017-02-27 | 2019-06-25 | Third Pole, Inc. | Systems and methods for ambulatory generation of nitric oxide |
| US10576239B2 (en) | 2017-02-27 | 2020-03-03 | Third Pole, Inc. | System and methods for ambulatory generation of nitric oxide |
| US11524134B2 (en) | 2017-02-27 | 2022-12-13 | Third Pole, Inc. | Systems and methods for ambulatory generation of nitric oxide |
| US10946163B2 (en) | 2017-02-27 | 2021-03-16 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11007503B2 (en) | 2017-03-31 | 2021-05-18 | The General Hospital Corporation | Systems and methods for a cooled nitric oxide generator |
| US10239038B2 (en) | 2017-03-31 | 2019-03-26 | The General Hospital Corporation | Systems and methods for a cooled nitric oxide generator |
| CN111588951A (en) * | 2019-02-21 | 2020-08-28 | 陈之硕 | Plasma aerosol inhalation device and use of plasma liquid |
| CN111588951B (en) * | 2019-02-21 | 2022-08-09 | 陈之硕 | Plasma aerosol inhalation device and use of plasma liquid |
| US11478601B2 (en) | 2019-05-15 | 2022-10-25 | Third Pole, Inc. | Electrodes for nitric oxide generation |
| US11479464B2 (en) | 2019-05-15 | 2022-10-25 | Third Pole, Inc. | Systems and methods for generating nitric oxide |
| US11045620B2 (en) | 2019-05-15 | 2021-06-29 | Third Pole, Inc. | Electrodes for nitric oxide generation |
| US11691879B2 (en) | 2020-01-11 | 2023-07-04 | Third Pole, Inc. | Systems and methods for nitric oxide generation with humidity control |
| WO2021252401A1 (en) * | 2020-06-07 | 2021-12-16 | Alti, Llc | Nitric oxide generation, delivery, and monitoring system |
| US12059531B2 (en) | 2020-06-07 | 2024-08-13 | Alti Llc | Nitric oxide generation, delivery, and monitoring system |
| US11827989B2 (en) | 2020-06-18 | 2023-11-28 | Third Pole, Inc. | Systems and methods for preventing and treating infections with nitric oxide |
| US11975139B2 (en) | 2021-09-23 | 2024-05-07 | Third Pole, Inc. | Systems and methods for delivering nitric oxide |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9303645A (en) | 1995-04-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1099997A (en) | Generation of nitric oxide from air for medical uses | |
| EP0630270B1 (en) | Nitric oxide from air for medical uses | |
| AU2020256426B2 (en) | Systems and methods for the synthesis of nitric oxide | |
| JP6968192B2 (en) | Systems and methods for cooled nitric oxide generators | |
| US5635160A (en) | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions | |
| Clay et al. | Wastage of drug from nebulisers: a review | |
| DE60000325T2 (en) | Therapeutic use of a helium / oxygen mixture, especially for the treatment of asthma | |
| Matthys | Chlorofluorocarbon-free aerosol therapy in patients with pulmonary airflow obstruction | |
| DE102022002797A1 (en) | Dosing device for adding at least one pharmaceutically active substance to a breathing gas provided extracorporeally, device for providing a breathing gas with such a dosing device and method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |