Abstract:
A delivery system utilizing a diffusion membrane that regulates the concentration of medical gases that are administered to a patient. A storage vessel contains a neat or pure medical gas under pressure that is in fluid communication with a diffusion membrane. The medical gas is then dispensed at a specified rate by diffusion across a membrane into a carrier gas. The concentration is kept constant by regulating the pressure and carder gas flow. Typical applications are for inhaled gases that are used in patient treatment and care.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of Invention 
         [0002]    The invention generally relates to the storage and dispensing of therapeutic levels of medical gases for inhalation by patients. Specifically this is a system that stores and delivers a specified dose of medical gas over time to a patient via inhalation. 
         [0003]    2. Description of related art 
         [0004]    The administration of inhaled nitric oxide (NO) to patients is currently being investigated for its therapeutic effect. The use of NO has a vasodilatory effect on such patients and is particularly of importance in the case of newborns having persistent pulmonary hypertension. In such cases, the administration of NO has significantly increased the oxygen saturation in such infants. 
         [0005]    The actual administration of NO is generally carried out by its introduction into the patient as a gas along with other normal inhalation gases given to breathe the patient. Such commercially available supplies are provided in cylinders under pressure and may be at pressures of about 2000 psi and consist of a mixture of NO in nitrogen with a concentration of NO of between about 800-2000 ppm, As such, therefore, some means must be used to reduce the pressure of the supply to acceptable levels for a patient and &amp;so to very precisely meter the amount of the NO and nitrogen mixture so that the desired concentration of NO is actually administered to the patient. Such administration must also be added in sympathy with the respiration pattern of the patient. 
         [0006]    The concentration administered to a patient will vary according to the patient and the need for the therapy but will generally include concentrations at or lower than 150 ppm. There is, of course, a need for that concentration to be precisely metered to the patient since an excess of NO can be harmful to the patient. In addition, the administration must be efficient in a timely manner in that NO is oxidized in the presence of oxygen to nitrogen dioxide and which is a toxic compound. Therefore, care in its administration is paramount, 
         [0007]    Current known methods of such administration, therefore have been limited somewhat to clinical situations where attending personnel are qualified from a technical sense to control the mixing and administration of the NO to a patient, Such methods have included the use of a forced ventilation device, such as a mechanical ventilator where a varying flow of breathing gas is delivered to the patient as well as gas blenders or proportioners that supply a continuous flow of the breathing gas to the patient to which NO has been added. 
         [0008]    In the former case, the use of a ventilator is constrained in that the user must know the precise flow from the ventilator and then the amount of NO to be added is determined on a case-to-case and moment-to-moment basis. Furthermore, the flow profile in forced ventilation varies continuously thereby making it impossible to track the flow manually. In the use of the latter gas blenders, the introduction of the NO containing nitrogen has been accomplished through the use of hand adjustment of a gas proportioner in accordance with a monitor that reads the concentration of NO being administered to the patient. Thus the actual concentration is continuously being adjusted by the user in accordance with the ongoing conditions of the apparatus providing the breathing mixture, 
         [0009]    While such modes of providing a known concentration of NO to the patient may be acceptable from a closely controlled and monitored clinical setting, it is advantageous to have a system that could be used with various means of providing the breathing gas, whether by mechanical means such as a ventilator, or by the use of a gas proportioner and which could automatically adjust for that particular equipment and assure the user that the desired, proper concentration of NO is being administered to the patient. 
         [0010]    U.S. Pat. No. 5,558,083 discloses a nitric oxide delivery system that is useable with any of a variety of gas delivery systems that provide breathing gas to a patient. The system detects the flow of gas delivered from the gas delivery system at various times and calculates the flow of a stream of nitric oxide in a diluent gas from a gas control valve, The flow of gas from the gas delivery system and the flow established from the flow control valve create a mixture having the desired concentration of nitric oxide for the patient, The system does not have to interrogate the particular gas delivery system being used but is an independent system that can be used with various flows, flow profiles and the like from gas delivery systems. 
         [0011]    Another method of dilution consists of pre-diluting the nitric oxide with nitrogen and filling a pressurized steel tank. The drawbacks of this method is the tanks are necessarily large to provide enough gas to complete the treatment, there are multiple dilution steps necessary to create the correct dilution with more chance for errors. The method that is described here is direct dilution method using physical constants to control the process. Direct dilution avoids potential errors. It also allows the delivery system to use a concentrated gas thereby reducing the size of the equipment and creating a potentially portable device. 
       SUMMARY 
       [0012]    A delivery system utilizing a diffusion membrane that regulates the concentration of medical gases that are administered to a patient. A storage vessel contains a neat or pure medical gas under pressure that is in fluid communication with a diffusion membrane. The medical gas is then dispensed at a specified rate by diffusion across a membrane into a carrier gas. The concentration is kept constant by regulating the pressure and carder gas flow. Typical applications are for inhaled gases that are used in patient treatment and care. 
         [0013]    Advantages of the system may include one or more of the following. The system provides control the administration and concentration of drugs via inhalation for the treatment of various medical conditions. In particular nitric oxide is a gas that is used in the treatment of several medical conditions. The system using a diluting gas to allow control of the nitric oxide concentrations to safe and therapeutic levels without the use of nitrogen as a diluent the concentration of the gas. 
         [0014]    These and other features and advantages of the present invention will be more apparent from the detailed description of the preferred embodiment set forth below, taken in conjunction with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]      FIG. 1  shows an exemplary nitric oxide delivery system. 
           [0016]      FIG. 2  shows an exemplar)/ process for regulating and delivering the as to the patient. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0017]    The invention consists of a vessel ( 2 ) that is initially loaded with a medical gas at a pressure greater than atmospheric. The size of the vessel and the pressure control the quantity of medical gas that is available for patient treatment. As a consequence small vessels with very high pressures can contain large amounts of medical gas. The pressure is dependent on the stability of the gas under pressure. Also the gas could exist as a liquid if the temperature and pressure is below the critical point of the gas. This can be advantageous for medical gases that require a significant dose over time. A large amount of the therapeutic gas could be contained in a small vessel as a liquid that would vaporize over time. 
         [0018]    The vessel is attached directly to a pressure regulator ( 6 ) that controls the outlet pressure of the medical gas. The pressure regulator is of the diaphragm type. The diaphragm and other materials that come in contact with the medical gas are of a material that no chemical, catalytic or absorptive interaction takes place between the material and the medical gas. The pressure range is set to a pressure that maintains the diffusion rate of the medical gas through the membrane at the desired therapeutic level, The pressure is measured by means of a pressure-sensing device ( 3 ) that measures gauge pressure. The gauge pressure is one of the control points of the system that modifies the medical gas administration rate. 
         [0019]    The diffusion membrane ( 7   a ) is housed in a containment device ( 7 ) that supports the membrane and can withstand the pressure that is provided by the outflow from the pressure regulator. The membrane itself is comprised of a material that can withstand pressure without tearing or otherwise succumbing to mechanical stress. It also must be of a molecular structure that allows the diffusion of a selected medical gas across its thickness. 
         [0020]    The variables involved in selecting the diffusion membrane for a specific gas are molecular composition, area and thickness. Materials that are appropriate for the diffusion membrane are typically polymers. The polymeric structure lends itself to creating diffusion pathways that are gas specific. The thicknesses of polymeric materials are easily controlled through material processing. The thickness of the polymer material is proportional to the diffusion rate as is the area. Changing the physical dimensions of the containment device can vary the area of the membrane that is exposed to the pressure of the medical gas thereby allowing more or less of the gas to reach a patient. 
         [0021]    The physical configuration of the polymer membrane is not limited to a flat sheet. It can also be pleated, tubing, multi-lumen tubing or any physical configuration that allows a pressure differential to exist across the membrane. 
         [0022]    Polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), amorphous polymers, fluorinated ethylene propylene (FEP), low-density polyethylene (LDPE) and polysilylacetalenes were excellent candidates for use in regulating the diffusion of medical gases. The final selection criteria of the polymer are based on chemical stability with regard to the medical gas, adsorption and physical strength of the material. The material must be chemically stable under the pressure and temperature conditions while being intimately in contact with the medical gas. Excessive adsorption of the medical gas by the polymer can cause decreased or complete cessation of diffusion over time. The polymer membrane material must also be able to withstand the anticipated pressure and temperatures without loss of structural integrity. 
         [0023]    The dilution gas is provided by a pump ( 10 ) or other source of dilution gas and the flow is regulated. The flow is measured by a device such as a hot wire flow transducer ( 9 ). 
         [0024]    As an example a preferred embodiment uses a PDMS polymer with a thickness of 0.003 inches that regulates the medically therapeutic gas nitric oxide. The pure nitric oxide is loaded into a steel vessel at 120 PSI and the pressure regulated between 1 and 10 PSI. The area of the membrane was set at 1735 sq mm. With a diluent gas of air flowing at  3  liters/min the nitric oxide was able to be delivered in concentrations from 5 to 80 ppm to a patient via nasal cannula. 
         [0025]      FIG. 2  shows an exemplary process for providing gas to a patient. First, the medical gas is placed under pressure ( 102 ) and the pressure is regulated ( 104 ). The user sets the rate of gas diffusion through the membrane ( 106 ). The gas is allowed to diffuse through the membrane ( 108 ), and dilution gas is also flowed through the system ( 110 ). The diffusion gas stream is provided to the dilution gas stream ( 112 ), The medical gas is diluted to the specified concentration and flow rate and delivered to the patient ( 114 ). 
         [0026]    The system also includes various controls, alarms and safety devices to prevent excess concentrations of NO2 in the administration of NO to the patient, including means to shut down the NO system or to reduce the NO concentration to the patient to a safer level. The NO delivery system may thus provide an alarm or other appropriate action in the event of an increase in the NO level beyond a predetermined level, a decrease in O2 below a predetermined level and/or an increase of NO2 above a predetermined level. Depending on the severity of the alarm condition, an alarm may sound or the entire system may be controlled to alleviate the unsafe condition sensed. 
         [0027]    Finally, in the event of a loss of pressure in the supply at any time, electronics can activate a purge valve to purge the system of any other gases that may be in the supply line and refill the supply lines from cylinder or tank  2  to the purge valve with fresh NO nitrogen. In this way, the system is recharged with the correct supply gas and no extraneous gases, such as ambient air, will be introduced into the system to cause error. 
         [0028]    Accordingly, through the use of the present NO delivery system, the concentration of NO delivered to the patient may be established, either by the selection by the user, or set by a predetermined value by the system itself, and that desired value Will be transmitted to the patient without any interrogation of the gas delivery device. The system is thus independent and may be readily used with any mechanical ventilator, gas proportioning device or other gas delivery system to deliver a known, desired concentration of NO to a patient. 
         [0029]    Numerous further variations and combinations of the features discussed above can be utilized without departing from the spirit of the invention as defined by the claims. Accordingly, the foregoing description of the preferred embodiment should be taken by way of illustration rather than by way of limitation of the invention as claimed.