METHOD AND DEVICE FOR PRODUCING A HYPOXIC GAS MIXTURE

Abstract: A gas mixture used in normobaric hypoxia therapy is produced by oxygen depletion of atmospheric gas compressed up to 10 atm. The gas separation unit comprises a stack of flat polymeric membranes made of a thermoplastic resin having an oxygen permeability of 0.5 to 1.5 10<-10> ml.cm/cm<2>.s.cmHg. 20 to 60 % wt. of polysiloxane and hydrocarbon oil, which are compatible with this resin at an elevated temperature, are dispersed in the resin.

Description: METHOD AND DEVICE FOR PRODUCING A HYPOXIC GAS MIXTURE Field of Invention The invention concerns the methods for obtaining a gas mixture used for interrupted normobaric hypoxia and may be used in practical medicine in medical treatment with gas mixtures with a reduced oxygen content. Background of Invention The interrupted normobaric hypoxia method is based on inhalation by a patient in predetermined conditions and according to a preset method alternately of atmospheric air and a gas mixture impoverished of oxygen and containing it in the quantity of 8 to 20% by volume. A method and device are known for interrupted normobaric hypoxia. The device contains a compressor the outlet of which is connected with a gas-separation apparatus implemented on the basis of hollow polymeric fibres. The gas-separation apparatus is connected by means of a pipeline through a flow meter and a humidifier with a means of connection to a patient implemented as a gas chamber or gas room. Besides, the device contains a system for regulation of the hypoxia parameters with a means controlling the state of the patient. By means of this device, a method of obtaining a gas mixture is realized for interrupted normobaric hypoxia and of delivery of it to a patient which consists in impoverishment of atmospheric air of oxygen by means of its compression in a compressor and passing through a polymeric membrane implemented on the basis of polymeric fibres followed by delivery through a flowmeter and a humidifier to the patient (see USSR author's certificate No. 1526). The main disadvantage of these method and device is impossibility of automatic regulation of choice of individual patient state parameters, lack of additional filtration of gas mixture, which does not allow to have a high-quality composition of hypoxic gas mixture. A method of obtaining of gas mixture is also known for interrupted normobaric hypoxia including impoverishment of atmospheric air in oxygen by means of its compression in a compressor to the pressure of 2 to 10 atm, passing it through a gas-separation element containing polymeric membrane based on hollow fibre of 4-methyl pentene-1 followed by delivery of the mixture through a filter, a flowmeter, a humidifier, and a mask to the patient. A device is also known for obtaining a gas mixture for interrupted normobaric hypoxia containing a shell, connections for introduction and withdrawal of the gas mixture, and, connected in series, a compressor, a gas- separation element containing polymeric membrane implemented on the basis of hollow fibres of 4-methyl pentene-1, a filter, a pipeline with a flowmeter, a humidifier, a mask with valves for breathing, an automatic system for regulation of conditions, and a means for control of the state implemented as a transmitter of oxygen in the patient's organism (see in the same place European patent No. class published ). The main disadvantages of the above method and device are an insufficiently high productivity of the process as well as the complete air-tightness of the membrane, which does not allow the possibility of gas escape localization to be assured, which in turn hampers the effective utilization of the gas-separation element. Summary of the Invention The task assumed as a basis of creation of this invention is creation of a method and a device for obtaining a gas mixture for interrupted normobaric hypoxia which have a high productivity and assure the possibility of localization of gas leakage through the membrane. The task raised is solved by the method of obtaining a gas mixture for interrupted normobaric hypoxia including impoverishment of atmospheric air in oxygen by its compression in a compressor up to 2 to 10 atm, passing through a gas-separation element containing polymeric membrane, and subsequent delivery of the mixture through a filter, a flowmeter, a humidifier, and a mask to the patient, in which the gas-separation element consists of units of 10 to 24 flat polymeric membranes implemented of thermoplastic resin having the oxygen permeability of 0.5 to 1.5 x 10" 10 ml.cm/cm 2 .s.cm Hg in which 20 to 60% by mass of polysiloxane and hydrocarbon oil compatible with this resin at an elevated temperature are dispersed. In this case, a membrane is used which contains as thermoplastic resin a polymer chosen from the group: 4-methyl pentene- 1, polyethylene, polyisobutylene, and poly-cis-isoprene. Besides, a membrane is used which contains as polysiloxane polydimethylsiloxane. At the same time, a membrane is used which contains polybutene as hydrocarbon oil. The task raised is also solved by the device for obtaining a gas mixture for interrupted normobaric hypoxia which contains a shell, connections for introduction and withdrawal of the gas mixture, connected in series compressor, a gas-separation element containing polymeric membrane, a filter, a pipeline with a flowmeter, a humidifier, a mask with valves for breathing, an automatic system of regulation of the conditions, and a means for control of the state implemented as an oxygen transmitter in the patient's organism, in which the gas-separation element is implemented as a packing consisting of alternately located seals as a frame and flat membrane elements in the shape of a parallelepiped clutched between two plates equipped with channels connected with pipes for introduction and withdrawal of the gas mixture, each membrane element consisting of two flat polymeric membranes located from both sides of a porous support having at one end, in the distance of 70 to 80% of its width, one recess, and these membranes are hermetically assembled around one hole inside the recess and the recesses of the consecutive membrane elements are located in staggered rows. Each two adjacent membrane elements are connected in series into a unit separated from an adjacent unit by a plate, the adjacent units being connected in parallel by the pipe for introduction of the gas mixture. In this case two adjacent membrane elements are connected together with two rigid plates each of which has a hole located opposite the holes of the membrane elements. The membrane elements contain polymeric membranes made of a polymer chosen from the group: 4-methyl pentene-1, polyethylene, polyisobutylene, and poly-cis-isoprene. As a porous support for polymeric membranes, filter paper, thick felt, nylon are used. The invention essence consists in creation of the method and device for obtaining a gas mixture for interrupted normobaric hypoxia which allow a constant, stable composition of the hypoxic gas mixture to be assured at the oxygen content range in it of 7 to 20% vol. , a high productivity of the process being assured, about 2 to 4 times as great as that of the known method of obtaining of the gas mixture. The method of obtaining of the gas mixture for interrupted normobaric hypoxia is as follows: the initial air is compressed up to 2 to 10 atm in a membrane compressor and is delivered into a gas-separation element consisting of flat membranes, elements and units. The gas mixture leaving the gas-separation element, not passed through polymeric membrane and impoverished in oxygen passes through a filter, a gas mixture flowmeter, and a humidifier into the patient's mask for breathing with hypoxic gas mixture. Into the gas-separation element, an automatic regulation unit is built in which is connected with an oxygen content transmitter measuring the oxygen content in the patient's organism. The gas-separation element according to this invention contains inside an enclosed housing an alternating packing of frame seals and membrane elements in the shape of a parallelepiped located and clutched between two plates equipped with channels connected with pipes for introduction and withdrawal of the gas flow. In this case, each membrane element consists of two polymeric flat membranes located from both sides of a porous support having at one end, in the distance of 70 to 80% of its width, at least one recess, and the two membranes are hermetically assembled around at least one hole inside this recess, and these recesses are arranged in staggered rows at consecutive membrane elements. Besides, the gas-separation element according this invention has preferably one or more intermediate plates which contain on each of their opposite surfaces a stretched hole the position of which corresponds to that of the holes of an adjacent membrane element, these stretched holes being connected with the outlet pipe on the side surface of the plate and these connecting pipes being located symmetrically to the plate centre. Branch pipes allow the connecting pipes to be connected with proper collectors. Two adjacent membrane elements are preferably connected with each other by intermediate plates forming membrane units which are sub-assemblies. The end and intermediate plates are identical. Brief Description of Drawings Fig. 1 shows the diagram of the apparatus for obtaining a gas mixture for normobaric hypoxia; Fig. 2 (Fig. 2A, 2B, 2C) shows the general view of the apparatus for obtaining a gas mixture for normobaric hypoxia, with front and back covers removed; Fig. 3 shows the general front view of the gas-separation element; Fig. 4 shows the top view of the gas-separation element, represented on the fig. 3; Fig. 5 shows the vertical view of the gas-separation element; Fig. 6 shows the top view of the frame seal; Fig. 7 shows a partial view in the section along A-B-C-D element represented in Fig. 6; Fig. 8 shows a partial section of a membrane element; Fig. 9 (Fig. 9A, 9B) shows the view and respectively a partial section along E-E of the plate (Fig. 9A). Fig. 10 shows a section of two sub-assemblies with the flowsheet. Description of Preferred Embodiments The apparatus for obtaining a gas mixture for interrupted normobaric hypoxia represented in Fig. 1 contains compressor 1, gas separation element 2, compressor with electric drive 3, filter 4, receiver 5, condensate discharge outlet connection 6, safety valve 7, compressed air supply unions 9 and 10, choke 11, regulator 8, 12 and 22, gas separation element with flat membranes 13, humidifier 14, compensator 15, respiration valve 16, respiration mask 17, gas mixture inlet connection 18, gas discharge outlet connection 19, gas analyser 20, testing pipe union 21, choke 23, niche for the humidifier 24, gills 25, regulator 26 knob 12, control and indication board 27. The gas-separation element represented in Fig. 2 and follows includes an enclosed space formed by rigid bed 28 and housing 29 imagined as transparent to represent comfortably. The bed and housing are assembled with help of fixing devices (not shown), and air-tightness is assured by seal 30). The bed and housing form an air-tight enclosed space. Inside this space, there is packing 31 limited with two end plates 32 and 33. It is clutched between bed 28 and rigid plate 34 with help of a number of threaded rods 35 and huts 36. Its position is set by means of two interacting centering rods 37 and 38. Two headers 39 and 40, respectively, for introduction of the flow to be processed and for withdrawal of the flow processed are arranged from both sides of packing 31. They pass through bed 28 and are connected on the outside with respective connecting pipes 41 and 42. Header 39 is connected by branch pipe 43 with channel 44 inside plate 32, and header 40 is connected by branch pipe 45 with channel 44 inside plate 33. Channels 47 and 48 are represented in Fig. 8. Besides, connecting pipe 49 connects the internal part of the enclosed space with the environment and allows, in that way, the flow to be withdrawn which passed through membranes and is named "permeate". Packing 31 is formed (Fig. 5 and follows) by overlapping alternately frame seals 50 and membrane elements 51. Seals 50 and membrane elements 51 are flat and have the external profile in the shape of a parallelepiped rectangular, which allows membranes to be used practically with no wastes, based on continuous bands. They have diagonally opposite notches 52 and 63 or 4 and 55 which allow their location on centering rods 37 and 38 to be exactly determined. Fig. 7 shows the relative arrangement of membrane element 51. Each membrane element 51 is located between two frame seals 50 and contains two membranes 56 disposed from both sides of porous support 57, usually soft, in which there is at least one recess 58 near one end. Several recesses arranged across may be made. But it is preferable to make only one recess 58, of a stretch shape, arranged in the cross direction to the support. The total length of the recessed zones usually covers between 60 and 70%, preferably 65%, of the support width. Two membranes 56 are assembled hermetically, for example, with help of sticking or hot melting together, inside each recess (this zone is represented in Fig. 6 by a dotted line 59. It is obvious that two connected membranes may be replaced by one membrane folded up. They have in zone 59 where they are assembled hermetically one or more holes 60. Membrane elements 51 are arranged "in knave" (alternately in opposite positions) as it is represented in Fig. 10. End plates 32 and 33 usually have the shape of a parallelepiped, and their dimensions are similar to those of membrane elements 51. Two diagonally opposite holes 61 and 62 allow their arrangement on centering rods 37 and 38 to be realized. Two side channels 44 and 46 symmetric to the plate centre are located in the plate thickness, at each its end. Each of these channels ends on the opposite surface of the plate in cross, stretched holes 62 and" 63. The position of these holes is determined in such a way that they coincide with the position of holes 60 of the membrane elements. Packing 31 consists of two membrane units S x and S 2 , each of which contains several membrane elements 51. Two membrane units are separated with an intermediate plate (P) identical to end plates 32 and 33. The membrane units S 1 and S 2 are connected with feed header 39 by branch pipes 43 located also in parallel. Permeate leaves the packing at the periphery of the membrane elements in the direction of the arrows shown in Fig. In such a way, the circulation of initial air may take place inside of a membrane unit, successively from one element 51 to another and in parallel between each membrane units. This assures a great flexibility in utilization and allows the membrane unit in which leakage is discovered to be localized and isolated. The gas-separation element 2 may be manufactured with help of the most different materials. In this case, the housing 29 and the bed 28 may be made of thermoplastic materials such as polyvinylchloride, polyvinylaceto- chloride, or polymethylmetacrylate. As a material to manufacture a porous support, filter paper, thick felt, nylon are used. The membranes 56 are implemented of 4- methyl pentene-1, polyethylene, polyisobutylene, and poly- cis-isoprene. The following examples, with no limitation of the volume of the invention protection, illustrate the results achieved in realization of the method and the device for obtaining a gas mixture for interrupted normobaric hypoxia. Example 1 (Membrane 56) A suspension of 2000 g of polydimethylsiloxane oil with the viscosity of 10 cSt at 25°C and of 2000 g of commercial polymer of 4-methyl pentene-1 the permeability constant for oxygen of which is equal to 3.6 x 10" 9 is prepared which is then heated for 1 hour at 260 to 270°C while agitating vigorously. A transparent viscous (melted) solution is obtained which is left alone in order that air bubbles leave it and burst on its surface. Then 3200 g of dichloromethane is introduced into the mixture. The mixture obtained in such a way is distributed on the surface of a glass billet so that a 500 μm thick layer is obtained. The glass billet is left in air at the normal temperature for 7 to 15 minutes. In this time, dichloromethane evaporates and formation of polymeric film on the glass surface is assured. Then the film on the glass billet is submerged in a tank with methanol at 23°C. In 5 to 7 minutes the billet is pulled out and left in air at 25°C. In 2 hours, one makes sure that the membrane has become hard and removes the billet. The obtained membrane has the total thickness of 10 to 100 μm. The pore volume is about 60% to the total volume of the membrane. The membrane has an elevated permeability for 0 2 , N 2 , and other gases which is about 13 times as great as that of non-modified polymer. Example 2 (Membrane 56) A mixture is prepared of 1000 g of polydimethyl¬ siloxane oil with the viscosity of 5 cSt, 1000 g of commer¬ cial polybutylene oil with the molecular weight of 320, and 300 g of polyethylene powder with the molecular weight of 200,000 and the permeability constant for oxygen of 4 x 10 "10 ml.cm/(cm 2 .s.cm Hg). In this case, this mixture is pressed at 175°C into 25 to 125 μm thick membranes under the pressure of the plates of 70.3 kg/cm 2 . On cooling, the membranes are washed with xylene to remove polybutylene oil and then submerged in polymethylsiloxane oil with the viscosity of 10 cSt at 25 β C. The finished membranes have the permeability 7 times as great as that of non-modified polyethylene. Example 3 (gas-separation element 2) A membrane 56 prepared according to example 1 is located into a gas-separation element implemented according to the design in conformity with this invention. The gas-separation element represented in Fig. 2 contains 16 membrane elements 51 laid onto each other and connected successively inside an air-tight housing. Each element 51 is composed of two membranes 56 implemented according to the method of example 1, arranged from both sides of 0.12 mm thick filter paper, and sealed up thermal¬ ly at 140 β C inside recess. The total thickness of the membrane is equal to about 200 μm, and the thickness of the selective layer of the membrane is equal to 2 μm. The porous layer of the membrane is located opposite filter paper. The rectangular membranes with the dimensions of 115 x 200 mm have 4 aligned holes of 4 mm dia. in a rec tangular thermally sealed zone with the dimensions of 8 x 68 mm. The useful surface of each membrane is equal to 1 dm 2 . Seals (50), 1 mm thick, are manufactured of "way- 40" hard rubber. The above gas-separation element covered with a polyvinylchloride housing 29 is put into an apparatus for obtaining a gas mixture for interrupted normobaric hypoxia. Example 4 (An apparatus for obtaining a gas mixture for interrupted normobaric hypoxia as shown in Fig. 1) Initial air containing 21% vol. 0 k and 79% vol. N 2 is compressed in a membrane compressor and is delivered into a gas-separation element implemented according to example 3. The gas flow leaving the gas-separation element, impov¬ erished in oxygen, and not passed through the membrane is delivered through a regulating valve, a pipeline, a filter, a gas mixture flowmeter, and a humidifier into a patient's mask. The gas separation variables are automatically regulated by a built-in unit, and an oxygen transmitter measuring the oxygen content of the patient's blood allows the patient's health state to be looked after. A series of experiments is carried out at t = 24°C, the initial air being delivered to the membrane under an elevated pressure and the gaseous permeate flow being withdrawn under the pressure of 745 mm Hg. The results obtained are indicated in the Table, the flowrates being expressed in 1/hour reduced to the normal conditions of temperature and pressure (0°C, 760 mm Hg). The abbrevi¬ ations used have the meanings as follows: A - air delivery flowrate (at 21% vol. of oxygen); B - flowrate of the gas mixture not passed through the membranes; C - oxygen content, per cent, in F; D - permeate flowrate (gas mixture passed through the membranes); Y - oxygen content, per cent, in D. Table P A F X D Y (bar) 6 980 930 20.4 47 36.5 8 925 870 20.3 53 36.5 8.9 1050 1000 20.1 48 36 11 1060 1000 - 60 38 3.65 990 940 20.1 50 36.5 3.65 215 163 16.8 52 33.5 3.65 73 23 7.8 49 27.0 The utilisation of the obtained gas mixture for interrupted normobaric hypoxia is realized as follows: Example 5 (Medical treatment) The inhalation of the hypoxic gas mixture obtained in example 4, which contains 9.5 ± 0.5% vol. of oxygen and 90.5 ± 0.5% vol. of nitrogen is realized as follows. In the first day, the inhalation of the hypoxic mixture is carried out 5 times for 3 minutes each time with a 3-minute pause for breathing with atmospheric air. The total hypoxic time is 15 minutes. In the second day, 6 times for 3 with a 2-minute pause. The total time is 18 minutes. In the third day, 7 times for 4 minutes with a 2- minute pause. The total time is 28 minutes. In the fourth day, eight times for 4 minutes with a 2-minute pause. The total time is 32 minutes. In the fifth day, 9 times for 4 minutes with a 2-minute pause. The total time is 36 minutes. In the 6th day, 9 times for 5 min. with 2-min. pause. The total time is 45 min. In the 7th day, 10 times for 5 with 2-min. pause. The total time is 50 min. In the 8th day, 11 times for 5 with 2-min. pause. The total time is 55 min. From the 9th to the 11th day 12 times for 5 with 2-min. pause. The total time is 60 min. In the 12th day,5 times for 6 with 2-min. pause. The total time is 30 min. In the 13th day, 6 times for 6 with 2-min. pause, 36 min. In the 14th day, 6 times for 8 with 2-min. pause, 48 min. In the 15th day, 7 times for 8 with 2-min. pause, 56 min. In the 16th day, 5 times for 10 with 2-min. pause, 50 min. In the 17th day, 6 times for 10 with 2-min. pause, 60 min. From the 18th to the 20th days, 6 times for 10 with 2-min. pause, 60 min. After the 20th seance, the treatment is realized depending on the patient's clinical data. After the 20th seance, 3 times a week 3 to 6 times for 10 minutes with 2-min. pause during 2 weeks. And then 2 times a week in the same conditions during 1 week. In 3 to 4 months, the complete course of treatment is repeated once more.

Claims: CLAIMS 1. Method of producing a gas mixture for interrupted normobaric hypoxia including impoverishment of atmospheric air in oxygen by its compression in a compressor up to 2 to 10 atm, passing it through a gas-separation element containing polymeric membrane, and subsequent delivery of the mixture through a filter, a flowmeter, a humidifier, and a patient's mask, characterised by the fact that to increase the process productivity the gas-separation element consists of units of flat polymeric membranes made of a thermoplastic resin having the oxygen permeability of 0.5 to 1.5 x 10" 10 ml.cm/cm 2 .s.cm Hg in which 20 to 60% wt. of polysiloxane and hydrocarbon oil is dispersed which are compatible with this resin at an elevated temperature. 2. Method according to claim 1, characterised by the fact that a membrane is used which contains as thermoplastic resin a polymer chosen from the group: 4- methyl pentene-1, polyethylene, polyisobutylene, and poly- cis-isoprene. 3. Method according to claims 1 and 2, characterised by the fact that a membrane is used which contains polydimethylsiloxane as a polysiloxane. 4. Method according to claims 1 to 4, characterised by the fact that a membrane is used which contains polybutene as a hydrocarbon oil. 5. Device for realization of the method according claim 1, containing a shell, connections for introduction and withdrawal of the gas mixture, connected in series compressor, a gas-separation element containing polymeric membrane, a filter, a pipeline with a flowmeter, a humidifier, a mask with valves for breathing, an automatic system of regulation of the process variables, and a means for controlling the state implemented es a transmitter of oxygen in the patient's organism, characterised by the fact that, to assure the possibility of localization of gas leakage through the membrane, the gas-separation element is implemented as a packing consisting of alternately located seals in the shape of a frame and flat membrane elements in the shape of a parallelepiped clutched between two plates equipped with channels connected with the connecting pipes for introduction and withdrawal of the gas mixture, each of the membrane elements consisting of two flat polymeric membranes arranged on both sides of a porous support having at one end, in the distance of 70 to 80% of its width, one recess, and these membranes are hermetically assembled around one hole inside the recess, and the recesses of subsequent membrane elements are arranged in staggered rows. 6. Device according claim 5, characterised by the fact that each two adjacent membrane elements are connected into a unit separated from an adjacent unit with a plate, the adjacent units being connected in parallel with the connecting pipe for introduction of the gas mixture. 7. Device according claims 5 and 6, characterised by the fact that two adjacent membrane elements are connected together with two rigid plates, each of which has a hole located opposite the holes of the membrane elements. 8. Device according to claims 5 to 7, characterised by the fact that the membrane elements contain polymeric membranes made of a polymer chosen from the group: 4- methyl pentene-1, polyethylene, polyisobutylene, poly-cis- isoprene. 9. Device according to claims 5 to 8, characterised by the fact that as a porous support for polymeric membranes filter paper, thick felt, nylon are used.

Inventors: STAEBLER REGULA, TKATCHOUK ELENA N, STAEBLER, REGULA, TKATCHOUK, ELENA N.
Applicants: STAEBLER REGULA, TKATCHOUK ELENA N, TRADOTEC SA, STAEBLER, REGULA, TKATCHOUK, ELENA N., TRADOTEC S.A.
Application year: 1993
Main classification: A61M16
IPC codes: A61M16, B01D53, B01D63, B01D69, B01D71