A blood purification device combining membrane separation and perfusion coupling

Abstract

The present invention discloses a blood purification device coupled with membrane separation and perfusion, comprising a blood inlet, a blood outlet, a pre-flushing liquid outlet, a pre-flushing liquid inlet, a plasma separation unit shell, a plasma separation membrane assembly, an inlet and outlet filtration device, a plasma perfusion unit shell, a plasma perfusion adsorption resin, a primary filtration device, a secondary filtration device and an upper end cover. The core of the plasma separation unit is a plasma separation membrane, and the core of the plasma perfusion unit is a plasma perfusion adsorption resin. The device integrates the functions of plasma separation and plasma perfusion. After plasma separation, plasma perfusion adsorption is performed to remove target toxins, thereby improving the safety and effectiveness of blood purification while simplifying the operating procedures, preventing blood loss and bacterial infection risks caused by operation, and greatly reducing treatment costs. The two functions do not require extracorporeal circulation pipeline connection, reducing the amount of extracorporeal blood circulation, and reducing the risk of complications such as hypotension.

Description

Technical Field

[0001] The invention relates to the field of medical devices, in particular to a blood purification device coupling membrane separation and perfusion. Background Art

[0002] The prognosis of liver failure is extremely poor, with a mortality rate of up to 80%. At present, the most effective and practical method for treating liver failure clinically is to use a combination of non-biological artificial livers, such as molecular adsorption recirculation system and Prometheus system. However, due to its high cost, it is difficult to promote its application. The commonly used method is to use a single treatment mode such as plasma exchange, hemodialysis, plasma perfusion, etc., but a single mode is difficult to completely replace the liver function to effectively remove the large amount of toxic metabolites accumulated in the body and the activation or induction of inflammatory mediators and cytokines.

[0003] Plasma exchange is to separate the patient's plasma from the blood using a plasma separator, and use normal fresh frozen plasma to replace the plasma containing a large amount of toxins in the body of patients with liver failure, thereby effectively removing various toxic substances in the body, such as large molecular pathogens, small and medium molecular toxins, and supplementing allogeneic plasma or substances required by the body (such as albumin, coagulation factors and opsonins, etc.), temporarily replacing the detoxification function of liver cells, blocking the vicious cycle between toxins and liver dysfunction, improving the clinical symptoms of patients with liver disease, reducing complications such as bleeding, and providing a good internal environment for liver regeneration and liver function recovery. However, blood resources are currently in short supply, and the sources of substances required by the body such as albumin are limited and expensive.

[0004] Due to the poor biocompatibility of plasma perfusion adsorption resin, whole blood perfusion is not yet popular. Currently, the clinical plasma perfusion process requires the use of plasma separators and plasma perfusion devices and their supporting extracorporeal circulation pipelines (such as Figure 2 As shown in the figure, first use a plasma separator to separate blood cells from plasma, then lead the plasma to the plasma perfusion device through an extracorporeal pipeline, and the plasma containing various toxins and pathogenic factors is removed after plasma perfusion, and then the blood in the two devices is returned to the body together. In the process, autologous plasma can be fully utilized, and a large amount of exogenous plasma and other blood products are not required, and there is no possibility of infection with new diseases. However, the process requires two sets of blood purification pipelines to be used with two devices. There are many connecting ports between the pipelines, which increases the risk of failure of the connecting ports, causing blood loss and bacterial infection; the circulation pipeline and the two devices need to be filled with blood, so the amount of extracorporeal blood circulation is large, which increases the risk of complications such as hypotension in patients receiving treatment; the plasma perfusion device needs to be pre-flushed before use. In order to avoid affecting the plasma separator, after the plasma perfusion device is pre-flushed alone, the pipeline used for pre-flushing needs to be disassembled and then connected to the plasma separator, which increases the complexity of the operation, and the risk of bacteria and viruses in the air contaminating the pipeline increases during the disassembly process. Summary of the invention

[0005] In view of the deficiencies in the prior art, the technical problem to be solved by the present invention is to provide a blood purification device that couples membrane separation with perfusion.

[0006] The technical solution of the present invention to solve the technical problem is to provide a blood purification device coupled with membrane separation and perfusion, characterized in that the device comprises a blood inlet end, a blood outlet end, a pre-flushing liquid outlet end, a pre-flushing liquid inlet end, a plasma separation unit shell, a plasma separation membrane assembly, an inlet and outlet filter device, a plasma perfusion unit shell, a plasma perfusion adsorption resin, a primary filter device, a secondary filter device and an upper end cover;

[0007] The plasma perfusion unit shell has a liquid outlet and a liquid inlet, the inner diameter of the shell gradually decreases from the liquid outlet to the liquid inlet, and the liquid outlet is provided with an upper end cover; the upper end cover is provided with a blood outlet; the plasma separation unit shell extends into the plasma perfusion unit shell through the liquid inlet end of the plasma perfusion unit shell, and is sealed with the plasma perfusion unit shell; plasma perfusion adsorption resin is filled between the plasma separation unit shell and the plasma perfusion unit shell; a blood inlet end is provided at the end of the plasma separation unit shell; a plasma separation membrane assembly is provided inside the plasma separation unit shell for separating blood cells and plasma in the blood; the plasma separation membrane assembly is formed by casting a plurality of plasma separation membranes with sealed ends, one end of the membrane is connected to the blood inlet end, and the other end is connected to the blood outlet end; The side wall of the separation unit shell near the blood inlet end is a primary filter device, which is used for the passage of plasma and at the same time blocks the passage of plasma perfusion adsorption resin; the inner wall of the secondary filter device is fixedly connected to the outer wall of the plasma separation unit shell, and the outer wall is fixedly connected to the inner wall of the plasma perfusion unit shell, which is used for the passage of plasma and at the same time blocks the passage of plasma perfusion adsorption resin; the priming liquid outlet end is arranged at the upper end of the side wall of the plasma perfusion unit shell, located below the secondary filter device, and is connected to the plasma perfusion adsorption resin; the priming liquid inlet end is arranged at the lower end of the side wall of the plasma perfusion unit shell; the blood inlet end, the blood outlet end, the priming liquid outlet end and the priming liquid inlet end are all provided with inlet and outlet filter devices, which are used to prevent the smallest particles shed from the plasma perfusion adsorption resin from entering the blood reinfusion system.

[0008] Compared with the prior art, the present invention has the following beneficial effects:

[0009] (1) The device integrates the functions of plasma separation and plasma perfusion. After plasma separation, plasma perfusion is performed to remove target toxins by adsorption, thereby improving the safety and effectiveness of blood purification while simplifying the operation process, preventing blood loss and the risk of bacterial infection caused by operation, and greatly reducing treatment costs. The two functions do not require the connection of extracorporeal circulation pipelines, reducing the amount of extracorporeal circulating blood and reducing the risk of complications such as hypotension.

[0010] (2) The shell of the plasma perfusion unit is similar to a conical cavity structure, and the shell of the plasma separation unit is a cylindrical structure. This structural design makes the resin at the blood outlet end more than the resin at the blood inlet end, and the formation of cavities during the adsorption process can be avoided when the separated plasma flows from the blood inlet end to the blood outlet end; at the same time, by affecting the flow direction of the liquid, the formation of cavities can be effectively avoided during the perfusion process, thereby increasing the contact rate between plasma endotoxins and resin and improving the adsorption removal efficiency.

[0011] (3) The core of the plasma separation unit is the plasma separation membrane, and the core of the plasma perfusion unit is the plasma perfusion adsorption resin. Depending on the type of disease to be treated and the target toxin, the pore size of the plasma separation membrane and the type of plasma perfusion adsorption resin can be adjusted accordingly. Therefore, this device can be used for different types of diseases by simply replacing the membrane and resin.

[0012] (4) For patients with multiple diseases, it is necessary to select two or more plasma perfusion adsorption resins. The volume of the plasma perfusion unit shell can be expanded and loaded with several different types of plasma perfusion adsorption resins, thereby achieving the purpose of multiple effects at one time, reducing the patient's treatment costs and the pain caused by multiple plasma perfusion treatments.

[0013] (5) The inlet and outlet filtration devices can prevent the smallest particles shed from the plasma perfusion adsorption resin from entering the blood reinfusion system, ensuring safety of use.

[0014] (6) The upper end cover is a transparent arc-shaped structure, and the blood outlet end is located in the center, which is convenient for the discharge of air in the shell during the pre-flushing process. The design of the transparent upper end cover makes it easy to observe whether the gas in the shell is completely discharged. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A schematic diagram of the overall structure of a device according to an embodiment of the present invention;

[0016] Figure 2 It is a schematic diagram of the clinical plasma perfusion treatment process in the prior art;

[0017] Figure 3 The present invention is a schematic diagram of the process of using the device of the present invention for clinical plasma perfusion treatment.

[0018] In the figure: 1. blood inlet; 2. blood outlet; 3. pre-flushing liquid outlet; 4. pre-flushing liquid inlet; 5. plasma separation unit shell; 6. plasma separation membrane assembly; 7. inlet and outlet filtration devices; 8. plasma perfusion unit shell; 9. plasma perfusion adsorption resin; 10. primary filtration device; 11. secondary filtration device; 12. upper end cover. DETAILED DESCRIPTION

[0019] The specific embodiments of the present invention are given below. The specific embodiments are only used to further illustrate the present invention in detail and do not limit the protection scope of the claims of this application.

[0020] The present invention provides a blood purification device coupled with membrane separation and perfusion (hereinafter referred to as the device, see Figure 1 ), characterized in that the device comprises a blood inlet end 1, a blood outlet end 2, a priming liquid outlet end 3, a priming liquid inlet end 4, a plasma separation unit housing 5, a plasma separation membrane assembly 6, an inlet and outlet filter device 7, a plasma perfusion unit housing 8, a plasma perfusion adsorption resin 9, a primary filter device 10, a secondary filter device 11 and an upper end cover 12;

[0021] The plasma perfusion unit shell 8 is a smooth transparent arc-shaped hollow cone-shaped structure with a large opening liquid outlet end and a small opening liquid inlet end. The inner diameter of the shell gradually decreases from the liquid outlet end to the liquid inlet end. The liquid outlet end is provided with an arc-shaped transparent upper end cover 12, which is transparent so as to facilitate observation of whether the gas in the plasma perfusion unit shell 8 is exhausted. The liquid inlet end is used to place the plasma separation unit shell 5; the center of the upper end cover 12 is provided with a blood outlet end 2; the plasma separation unit shell 5 is cylindrical, and extends into the plasma perfusion unit shell 8 through the liquid inlet end of the plasma perfusion unit shell 8, and is connected with the plasma perfusion unit shell 8. The plasma separation unit shell 5 and the plasma perfusion unit shell 8 are fixedly sealed and connected to form a sealed integral shell; a plasma perfusion adsorption resin 9 is filled between the plasma separation unit shell 5 and the plasma perfusion unit shell 8; a blood inlet end 1 is provided at the end of the plasma separation unit shell 5, and the blood inlet end 1 is located outside the plasma perfusion unit shell 8; a plasma separation membrane assembly 6 is provided inside the plasma separation unit shell 5 for separating blood cells and plasma in the blood, and the blood cells are located in the plasma separation membrane assembly 6; the plasma separation membrane assembly 6 is formed by capping and casting a plurality of plasma separation membranes (preferably hollow fiber membranes), and one end of the membrane is connected to the blood inlet end 1 The other end is connected to the blood outlet port 2; the side wall of the plasma separation unit shell 5 near the blood inlet port 1 is a primary filter device 10, which is used for the passage of plasma while blocking the passage of plasma perfusion adsorption resin 9 and its detached particles or generated fragments, which affects the plasma separation membrane; the inner wall of the secondary filter device 11 is fixedly connected to the outer wall of the plasma separation unit shell 5, and the outer wall is fixedly connected to the inner wall of the plasma perfusion unit shell 8, which is used for the passage of plasma while blocking the passage of plasma perfusion adsorption resin 9 and its detached particles or generated fragments; the pre-flushing liquid outlet port 3 is set at the plasma perfusion unit shell 8. The upper end of the side wall of the unit shell 8 is close to the blood outlet end 2, is located below the secondary filtering device 11, and is connected to the plasma perfusion adsorption resin 9, and is used for discharging the priming liquid during the priming process; the priming liquid inlet end 4 is arranged at the lower end of the side wall of the plasma perfusion unit shell 8, and is located outside the primary filtering device 10, and is used for the entry of the priming liquid during the priming process; the blood inlet end 1, the blood outlet end 2, the priming liquid outlet end 3 and the priming liquid inlet end 4 are all provided with an inlet and outlet filtering device 7, which is used to prevent the smallest particles shed from the plasma perfusion adsorption resin from entering the blood reinfusion system, so as to ensure the safety of use.

[0022] The filtration apertures of the primary filter device 10 and the secondary filter device 11 are the same and both are larger than the filtration apertures of the inlet and outlet filter devices 7; the filtration apertures of the inlet and outlet filter devices 7 are smaller than the smallest particles shed by the plasma perfusion adsorption resin, and the particle size of such particles is 15 to 25 microns.

[0023] The inlet and outlet filter device 7 is a circular sheet filter, which is fixed to the blood inlet end 1, the blood outlet end 2, the pre-flushing liquid outlet end 3 and the pre-flushing liquid inlet end 4 by ultrasonic welding.

[0024] The primary filter device 10 is an area formed by densely opening small through holes in the plasma separation unit shell 5; the primary filter device 10 should be as close to the blood inlet end 1 as possible. In this embodiment, the distance between the primary filter device 10 and the plasma separation membrane sealing end on one side of the blood inlet end 1 is 0.5 cm.

[0025] A hollow cylindrical filter screen may be provided around the primary filter device 10, and both upper and lower ends of the filter screen are fixed to the plasma separation unit housing 5 by ultrasonic welding to further ensure safety in use.

[0026] The secondary filtering device 11 is a circular sheet filter; the inner surface of the circular ring is fixedly connected to the outer wall of the plasma separation unit shell 5 by ultrasonic welding, and the outer surface is fixedly connected to the inner wall of the plasma perfusion unit shell 8 by ultrasonic welding.

[0027] The membrane-forming polymer of the plasma separation membrane is polyvinylidene fluoride, polysulfone, polyvinyl alcohol, polypropylene, cellulose acetate or nylon, etc., preferably a hollow fiber membrane. The membrane pore size is 0.1-1 μm, and the size of the plasma perfusion unit shell 8 is adjusted accordingly according to the pore size of the plasma separation membrane assembly 6; when the plasma separation unit is a plasma separator, the inside of the plasma perfusion unit shell 8 is larger, and more plasma perfusion adsorption resin 9 is filled; when the plasma separation unit is a component plasma separator, the inside of the plasma perfusion unit shell 8 is smaller, and less plasma perfusion adsorption resin 9 is filled; both methods can achieve the removal of toxic substances and pathogenic factors.

[0028] The plasma perfusion adsorption resin 9 is an activated carbon type, a neutral macroporous resin, an ion adsorption resin or an immunoadsorption resin with a specific functional group, etc.; the target toxins are bilirubin, endotoxin, inflammatory cytokines (TNF-a, IL-1, IL-6, IL-8, etc.), low-density lipoprotein, cholesterol, triglycerides, immune factors, etc. According to different target toxins, the pore size of the corresponding plasma separation membrane and the type of plasma perfusion adsorption resin 9 can be adjusted. The plasma perfusion adsorption resin 9 can select a resin with specific or non-specific adsorption to the target toxin according to the type of disease being treated, such as a plasma perfusion adsorption resin that specifically or non-specifically adsorbs bilirubin (for patients with severe jaundice, to remove total bilirubin and direct bilirubin), a plasma perfusion adsorption resin that specifically or non-specifically adsorbs endotoxins and inflammatory cytokines (for patients with endotoxemia, sepsis, and inflammatory response syndrome, to remove endotoxins and inflammatory cytokines), a plasma perfusion adsorption resin that specifically or non-specifically adsorbs low-density lipoprotein (for patients with hyperlipidemia, to remove low-density lipoprotein , cholesterol, triglycerides), specific or non-specific adsorption of immune pathogenic factors plasma perfusion adsorption resin (for patients with immune diseases such as systemic lupus erythematosus, to remove pathogenic factors in the patient's blood, such as IgG, IgM and other autoantibodies and immune complexes); for patients with multiple diseases, who need to choose two or more plasma perfusion adsorption resins 9, the volume of the plasma perfusion unit shell 8 can be expanded and several different types of plasma perfusion adsorption resins 9 can be loaded to achieve the purpose of multiple effects at one time, thereby reducing the patient's treatment costs and the pain caused by multiple plasma perfusion treatments.

[0029] The blood inlet port 1, the blood outlet port 2, the priming liquid outlet port 3 and the priming liquid inlet port 4 are all medical Luer connectors and are equipped with screw caps; sealing gaskets are arranged in the screw caps, which are respectively tightened with their respective ports to achieve the sealing of the entire device; the circumferential side surfaces of the screw caps are all provided with anti-slip convex ribs.

[0030] The working principle and workflow of the present invention are:

[0031] (1) Device priming: close the blood inlet 1 and the blood outlet 2, first open the priming liquid inlet 4, and priming with a certain amount of physiological saline or other pretreatment liquid. When the plasma perfusion unit shell 8 is filled with liquid, open the priming liquid outlet 3, and adjust the speed of the priming liquid outlet 3 and the priming liquid inlet 4; after the priming is completed, close the priming liquid outlet 3 and the priming liquid inlet 4; after the priming is completed, use the switch of the matching extracorporeal circulation pipeline to seal the priming liquid outlet 3 and the priming liquid inlet 4, without the risk of bacterial and viral contamination of the pipeline;

[0032] (2) Blood purification treatment: open the blood inlet end 1 and the blood outlet end 2, the blood inlet end 1 is connected to the human artery, and the blood outlet end 2 is connected to the human vein for return to the body; human blood enters through the blood inlet end 1, and the blood cells and plasma in the blood are separated by the screening principle of the plasma separation membrane in the plasma separation unit shell 5 (the blood cells cannot pass through the plasma separation membrane and are retained on the inner side of the membrane, and the plasma components can be separated to the outer side of the membrane through the plasma separation membrane); the blood cells flow out directly through the blood outlet end 2 through the membrane channel for return, and the separated plasma containing toxins enters the plasma perfusion unit shell 8 through the primary filtration device 10. The plasma is gradually filled between the plasma separation unit shell 5 and the plasma perfusion unit shell 8 from bottom to top, and contacts with the plasma perfusion adsorption resin 9. The plasma perfusion adsorption resin 9 uses the characteristic functional groups or pore size on the surface to adsorb the target toxins on the plasma perfusion adsorption resin 9, thereby achieving the purpose of removing plasma endotoxins; after being filtered by the secondary filtration device 11, the purified plasma and the blood cells in the plasma separation membrane assembly 6 flow out of the device through the blood outlet end 2 to implement autologous blood return.

[0033] Any matters not described in the present invention are applicable to the prior art.

Claims

1. A blood purification device coupling membrane separation and perfusion, characterized in that The device comprises a blood inlet end, a blood outlet end, a pre-flushing liquid outlet end, a pre-flushing liquid inlet end, a plasma separation unit shell, a plasma separation membrane assembly, an inlet and outlet filter device, a plasma perfusion unit shell, a plasma perfusion adsorption resin, a primary filter device, a secondary filter device and an upper end cover; The plasma perfusion unit shell is a curved transparent hollow cone-shaped structure with a large opening liquid outlet end and a small opening liquid inlet end. The inner diameter of the shell gradually decreases from the liquid outlet end to the liquid inlet end, and an upper end cover is provided at the liquid outlet end; the upper end cover is curved and transparent, and the blood outlet end is provided at the center of the upper end cover; the plasma separation unit shell is cylindrical; the plasma separation unit shell extends into the plasma perfusion unit shell through the liquid inlet end of the plasma perfusion unit shell, and is sealed and connected to the plasma perfusion unit shell; plasma perfusion adsorption resin is filled between the plasma separation unit shell and the plasma perfusion unit shell; a blood inlet end is provided at the end of the plasma separation unit shell; a plasma separation membrane assembly is provided inside the plasma separation unit shell for separating blood cells and plasma in the blood; the plasma separation membrane assembly is formed by casting a plurality of plasma separation membranes with sealed ends, one end of the membrane is connected to the blood inlet end, and the other end is connected to the blood outlet end; Part of the side wall near the blood inlet end is a primary filter device, which is used for the passage of plasma and at the same time blocks the passage of plasma perfusion adsorption resin; the primary filter device is an area formed by dense through holes in the plasma separation unit shell, and the distance between the primary filter device and the plasma separation membrane sealing end on one side of the blood inlet end is 0.5 cm; the inner wall of the secondary filter device is fixedly connected to the outer wall of the plasma separation unit shell, and the outer wall is fixedly connected to the inner wall of the plasma perfusion unit shell, which is used for the passage of plasma and at the same time blocks the passage of plasma perfusion adsorption resin; the pre-flushing liquid outlet end is arranged at the upper end of the side wall of the plasma perfusion unit shell, located below the secondary filter device, and communicated with the plasma perfusion adsorption resin; the pre-flushing liquid inlet end is arranged at the lower end of the side wall of the plasma perfusion unit shell; the blood inlet end, the blood outlet end, the pre-flushing liquid outlet end and the pre-flushing liquid inlet end are all provided with inlet and outlet filter devices, which are used to prevent the smallest particles falling off the plasma perfusion adsorption resin from entering the blood reinfusion system.

2. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The filtration apertures of the primary filtration device and the secondary filtration device are the same and both are larger than the filtration apertures of the inlet and outlet filtration devices; the filtration apertures of the inlet and outlet filtration devices are smaller than the smallest particles shed by the plasma perfusion adsorption resin.

3. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The inlet and outlet filter device is a circular sheet filter, which is fixed to the blood inlet end, the blood outlet end, the pre-flushing liquid outlet end and the inside of the pre-flushing liquid inlet end by ultrasonic welding.

4. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that A hollow cylindrical filter screen is arranged in the circumference of the primary filter device, and the upper and lower ends of the filter screen are fixed to the plasma separation unit shell by ultrasonic welding.

5. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The secondary filtering device is a circular sheet filter; the inner surface of the circular ring is fixedly connected to the outer wall of the plasma separation unit shell by ultrasonic welding, and the outer surface is fixedly connected to the inner wall of the plasma perfusion unit shell by ultrasonic welding.

6. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The plasma separation membrane is a hollow fiber membrane with a pore size of 0.1-1 μm.

7. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The blood inlet end, blood outlet end, priming liquid outlet end and priming liquid inlet end are all medical Luer connectors and are equipped with screw caps; sealing gaskets are arranged inside the screw caps, which are respectively tightened with their respective ports to achieve the sealing of the entire device; the circumferential side surfaces of the screw caps are all provided with anti-slip ribs.

8. The blood purification device coupled with membrane separation and perfusion according to claim 1, characterized in that The working process of the device is: (1) Priming of the device: close the blood inlet and the blood outlet, open the priming liquid inlet, and priming with the pretreatment liquid. When the plasma perfusion unit shell is filled with liquid, open the priming liquid outlet, and adjust the speed of the priming liquid outlet and the priming liquid inlet; after the priming is completed, close the priming liquid outlet and the priming liquid inlet; (2) Blood purification treatment: open the blood inlet and blood outlet, connect the blood inlet with the human artery, and return the blood outlet to the body; human blood enters through the blood inlet, and separates blood cells and plasma through the plasma separation membrane in the plasma separation unit shell; blood cells flow out directly through the blood outlet through the membrane channel and are returned to the body, and plasma enters the plasma perfusion unit shell through the primary filtration device. The plasma gradually fills the space between the plasma separation unit shell and the plasma perfusion unit shell, and contacts with the plasma perfusion adsorption resin, which adsorbs the target toxins; after passing through the secondary filtration device, the purified plasma and the blood cells in the plasma separation membrane assembly flow out through the blood outlet and are returned to the body.

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