Application of organic-inorganic composite membrane in manufacturing ECMO equipment

Abstract

The invention relates to an application of an organic-inorganic composite membrane in manufacturing ECMO equipment. In the ECMO process, vein blood of a patient is led out of a body, oxygenation and carbon dioxide removal are conducted through the artificial lung, then the vein blood is infused back into the body of the patient, and therefore the purposes of assisting respiration and heart functions are achieved. The carbon dioxide permeability and the separation selectivity of the membrane lung are very excellent; moreover, the membrane lung material has very strong hydrophobicity and very good chemical stability, so that the membrane lung material has good blood compatibility and is beneficial to reducing immunoreaction and prolonging the service life, thereby improving the safety of ECMO and reducing the use cost of the membrane lung.

Description

Technical Field

[0001] The present invention relates to an ECMO technology based on an organic-inorganic composite membrane lung material, belonging to the technical field of membrane separation. Background Art

[0002] Clinical results show that patients with pneumonia caused by the new coronavirus will suffer from acute respiratory distress syndrome (ARDS) when their condition is critical. At this time, extracorporeal membrane oxygenation (ECMO) equipment needs to be used for auxiliary treatment in a timely manner. At present, the industry generally recognizes that poly-4-methyl-pentene (PMP) is the best raw material for manufacturing membrane lungs, but this material is also monopolized by Membrana, a subsidiary of 3M, and the price has remained high. Membrane lungs need to be replaced after a period of continuous use, resulting in very high costs for ECMO consumables. Therefore, the development of efficient, stable and renewable membrane lung alternative materials will hopefully break the monopoly of foreign technology products, promote the independent research and development and production of ECMO equipment in my country, and reduce the treatment costs of a large number of critically ill patients. Membrane lung materials need to have good gas exchange performance, good blood compatibility, and low cost. Among them, blood compatibility refers to the required response of blood to exogenous substances or materials, generally referring to the compatibility between materials and blood components. When plasma proteins, blood cells, and endothelial cells in the blood come into contact with non-autologous materials, a series of reactions may occur, including affecting the human coagulation system and immune system, ultimately leading to thrombosis or hemolysis. Therefore, membrane lung materials need to meet the requirements of low physiological toxicity and good blood compatibility. After contact with blood, they will not cause blood damage, coagulation, platelet adhesion caused by hemoglobin adsorption, hemoglobin denaturation, and endothelial cell damage. The evaluation criteria include the following three aspects: preventing thrombosis, coagulation formation, and not hindering platelet function.

[0003] References

[0004] [1]Guerin C, Albert RK, Beitler J, et al. Prone position in ARDSpatients: why, when, how and for whom,

[0005] Intens Care Med,2020,46(12):2385-2396.

[0006] [2]Jang E, Lee JH, Hong S, et al. An unprecedented c-oriented DDR@MWWzeolite hybrid membrane: new insights into H-2-permselectivitiesviasixmembered-ring pores, J Mater Chem A, 2020, 8(28): 14071-14081.

[0008] [3]Sakamaki I, Morinaga Y, Tani H, et al.Monitoring of viral load by RT-PCR caused decision making to continue ECMO therapy for a patient with COVID-19, J Infect Chemother, 2020, 26(12): 1324-1327.

[0009] [4]Stefania Crotti M D.Spontaneous Breathing during ExtracorporealMembrane Oxygenation in Acute Respiratory Failure,CRITICAL CARE MEDICINE,2017,126:678. Summary of the invention

[0010] The present invention provides an ECMO technology based on an organic-inorganic composite membrane lung material, and specifically relates to the types of membrane lung materials, surface modification methods and gas separation performance. Based on the regular pores and high porosity of the organic-inorganic composite membrane lung material, the CO2 / O2 exchange used in the ECMO process exhibits very high gas permeability and separation selectivity, and the organic-inorganic composite membrane has strong hydrophobicity and good chemical stability, which is beneficial to reducing immune response and extending the service life of the membrane lung, thereby improving the safety of ECMO and reducing the cost of using the membrane lung.

[0011] Application of organic-inorganic composite membranes in the manufacture of ECMO equipment.

[0012] The organic-inorganic composite film is an interface composite film.

[0013] The material of the organic-inorganic composite membrane is PMP, all-silicon molecular sieve membrane, such as DDR, MFI, CHA and other molecular sieve membranes.

[0014] The organic-inorganic composite membrane is in the form of hollow fibers.

[0015] The channel diameter of the hollow fiber is 0.1-3 mm.

[0016] An ECMO device based on an organic-inorganic composite membrane, wherein the membrane lung material used is an organic-inorganic composite membrane.

[0017] The organic-inorganic composite membrane is installed in a shell-and-tube assembly, and the shell side is connected to a blood pumping device, and the tube side is connected to an oxygen source gas source.

[0018] Also included: an anticoagulant adding device for adding anticoagulant to blood.

[0019] The anticoagulant is sodium citrate.

[0020] Beneficial Effects

[0021] Compared with most organic and inorganic membranes, organic-inorganic composite membranes have regular pore sizes, continuous and dense membrane layers, good chemical stability, high mechanical strength, and high CO2 permeability coefficients and separation selectivity. Using organic-inorganic composite membranes as membrane lung materials is beneficial to improving oxygenation performance and reducing membrane preparation costs, making it easier to achieve miniaturization and low cost of membrane lungs.

[0022] ECMO membrane materials based on organic-inorganic composite membranes have regular pores, high porosity, high gas permeability, and CO2 / O2 separation selectivity that is very close to the diffusion selectivity of the human alveolar membrane itself. Membrane lung materials are highly hydrophobic, chemically stable, and blood compatible. They can reduce immune responses and extend service life, and can withstand high temperatures or ultraviolet disinfection and sterilization, making them feasible for recycling. Compared with commercial membrane lung materials, they have higher separation efficiency, longer service life, and are renewable. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 How artificial lungs work

[0024] Figure 2 Flow chart of simulated gas exchange in laboratory DETAILED DESCRIPTION

[0025] In order to solve the problems that common membrane materials are incompatible with blood and CO2 / O2 separation selectivity is not high, the present invention adopts an organic-inorganic composite membrane. Figure 1The whole set of artificial lung function device is composed of a gas agitator, an oxygenator (including an organic-inorganic composite membrane), and a vacuum pump. After the oxygen and air are mixed by the gas agitator, due to the pressure gradient, the two gases enter the oxygenator, and the gases are separated after passing through the membrane in the oxygenator. The oxygen enters the blood phase and enters the human body through the blood flow to participate in other circulations. The waste gas after the circulation re-enters the oxygenator through the action of the pump, is adsorbed by the membrane, exchanges with oxygen, enters the air side and is discharged from the body.

[0026] The specific operation process is as follows:

[0027] (1) The oxygen-deficient patient's blood and oxygen source gas flow into the two sides of the membrane lung respectively. After the blood contacts the membrane surface, the CO2 in the blood diffuses from the membrane side through the pores of the membrane lung to the carrier side. At the same time, the O2 on the carrier side diffuses through the microporous channels of the membrane lung to the blood on the membrane side for oxygenation.

[0028] (2) Blood flows along the surface of the membrane lung, and the shear flow rate of the blood on the membrane surface is controlled by a blood pump. At the same time, the flow rate of the oxygen source gas is controlled by a flow controller to obtain an optimized O2 permeation rate and separation selectivity.

[0029] (3) When participating in blood circulation, a filter needs to be placed in the blood supply line to remove thrombus components.

[0030] Figure 2 It shows the whole set of laboratory simulated gas exchange flow chart. CO2 and O2 are mixed with blood through mass flow controller, bubbling reactor and then the oxygen content is tested before gas exchange. Then the test module is used to test the blood after gas exchange. Then the oxygen content in the blood after gas exchange is tested. P1 is a small peristaltic pump used to make blood participate in circulation. V1 is a liquid tank. B13 and B14 are CO2 and O2 respectively. Different proportions of exchange can be carried out by changing the ratio.

[0031] The specific experimental process is: artificial blood is used, and organic-inorganic composite membrane is used as membrane lung material, and the O2 partial pressure is adjusted to 5.0kPa and the CO2 partial pressure is adjusted to 6.5kPa to serve as oxygen-poor blood; at the same time, the O2 partial pressure is adjusted to 13.0kPa and the CO2 partial pressure is adjusted to 3.0kPa to serve as oxygen-rich blood; the temperature of the entire system is maintained at 410K by a thermostat, and after the gas oxygenation process, the O2 and CO2 fluxes and separation performance are calculated.

[0032] Indicator parameters Organic-inorganic composite membrane lung materials Commercialized membrane lung material (3M Company) Inner and outer diameter (mm) 3.8 / 1.0 0.4 / 0.2 Tensile strength(N) >30N(breaking load) 9.87N <![CDATA[O2 flux (mol / s / m 2 / Pa)]]> <![CDATA[5.391×10 -9 ]]> <![CDATA[1.578×10 -8 (N2 for comparison)]]> <![CDATA[CO2 flux (mol / s / m 2 / Pa)]]> <![CDATA[1.078×10 -7 ]]> <![CDATA[1.498×10 -8 ]]> <![CDATA[CO2 / O2 selectivity]]> 20 50

[0033] Table 1 shows that compared with 3M's poly-4-methylpentene membrane lung material, the organic-inorganic composite membrane lung material has high mechanical strength, high CO2 permeation flux and high separation selectivity, and is expected to become an alternative ECMO membrane lung material. In addition, the organic-inorganic composite membrane has better operating stability than commercial membrane lung materials during the separation process. After 56 hours of operation, its main separation operating parameters are as follows:

[0034] Indicator parameters Organic-inorganic composite membrane lung materials <![CDATA[O2 flux (mol / s / m 2 / Pa)]]> <![CDATA[6.472×10 -9 ]]> <![CDATA[CO2 flux (mol / s / m 2 / Pa)]]> <![CDATA[9.698×10 -8 ]]> <![CDATA[CO2 / O2 selectivity]]> 15

Claims

1. Application of organic-inorganic composite membranes in the manufacture of ECMO equipment.

2. The use according to claim 1, characterized in that: The material of the membrane is an organic-inorganic composite membrane.

3. The use according to claim 1, characterized in that: The organic membrane of the organic-inorganic composite membrane is a PMP membrane, and the inorganic membrane is an all-silicon molecular sieve membrane, such as DDR, MFI, CHA and other molecular sieve membranes.

4. The use according to claim 1, characterized in that: The organic-inorganic composite film is an interface composite film.

5. The use according to claim 1, characterized in that: The channel diameter of the hollow fiber is 0.1-3 mm.

6. An ECMO device based on an organic-inorganic composite membrane, characterized in that: The membrane lung material used is an organic-inorganic composite membrane.

7. The ECMO device according to claim 6, characterized in that: The material of the organic-inorganic composite membrane is PMP, all-silicon molecular sieve membrane, such as DDR, MFI, CHA and other molecular sieve membranes.

8. The ECMO device according to claim 6, characterized in that: The organic-inorganic composite membrane is installed in a shell-and-tube assembly, and the shell side is connected to a blood pumping device, and the tube side is connected to an oxygen source gas source.

9. The ECMO device according to claim 6, characterized in that: Also includes: Anticoagulant addition equipment, used to add anticoagulants to blood.

10. The ECMO device according to claim 9, characterized in that: The anticoagulant is sodium citrate.

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