CN106267423B - People's Rh positive red blood cell absorber - Google Patents
People's Rh positive red blood cell absorber Download PDFInfo
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- CN106267423B CN106267423B CN201610540878.3A CN201610540878A CN106267423B CN 106267423 B CN106267423 B CN 106267423B CN 201610540878 A CN201610540878 A CN 201610540878A CN 106267423 B CN106267423 B CN 106267423B
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
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Abstract
The present invention relates to people's Rh positive red blood cell absorbers of medical domain, it is characterized in that cleaning the positive O-shaped red blood cell of fresh Rh with 4 DEG C and 37 DEG C of physiological saline, remove immune antibody or the natural antibody of erythrocyte surface attachment, after detection antigenicity, cell precipitation is assembled into cylindrical adsorption device made of high-biocompatibility material, to 4/5, add 3.5% mannitol alserver's solution, make red blood cell concentration up to 80%, jog mixes, sealing, it sets 4 DEG C and saves periodically use, sieve is arranged in exit in clarifier therein, constitute the defence line for preventing cell fragment from filtering out, after blood plasma filtration, Rh antibody is combined into fixed compound by Rh positive red blood cell therein, the red cell debris that is destroyed and it is in combination made of macromolecular complex be cleaned the sieve detention of device, removal is caused a disease The blood plasma of substance is fed back after filtering out from clarifier, to treat blood group incompatibility Hemolysis by removing blood plasma Rh antibody.
Description
Technical field
The present invention relates to people's Rh positive red blood cell absorbers of medical domain, are mainly used for female tire blood group incompatibility pregnant woman blood plasma
In anti-fetal red blood cells antibody and red blood cell lysate removing.
Background technique
Fetus inherits the gene element of father and each half of mother, and fetal red blood cells can carry the antigen from male parent,
The blood group for showing as fetus is different from parent.After the red blood cell of fetus enters the blood circulation of parent, the immune of parent is induced
System generates antibody, and antibody enters fetal circulation system by placenta, in conjunction with fetal red blood cells, breaks fetal red blood cells
It is bad, lead to female tire blood group incompatibility hemolytic disease of fetus an d neonate.
Human erythrocyte's blood group has 26 kinds, including the blood groups such as abo blood group, Rh blood group and MN, Lew, Kell and Fya, but
The blood group of female tire blood group incompatibility Hemolysis can be caused with Rh blood group and abo blood group to be most common.Rh blood group antigens are dyed by No. 1
The allele of 3 pairs of close linkages determines on body, shares 6 kinds of antigens, i.e. C and c, D and d, E and e.Due to D antigen quilt earliest
It was found that antigenicity is most strong, therefore clinically all D antigen positive persons are known as the Rh positive, and no D antigen person is known as Rh feminine gender.Rh blood group
The antigenicity of antigen determines the severity of Hemolysis, and D antigen can cause serious Hemolysis, secondly be E antigen, again for
C, the antigenicity of c and e antigen, d antigen is most weak, and anti-d antibody there is no to find at present.The frequency of Rh feminine gender in China's Chinese Han Population
About 0.4%, and the frequency of ethnic group of the Northwest Rh feminine gender is up to 10% or more.
Although the incidence that abo blood group does not conform to is very high, fetus haemolysis incidence is very low, even if haemolysis occurs, symptom is also
Relatively light, few that nuclear icterus and oedema occurs, the gestational period is not necessarily to specially treated.And Rh blood group incompatibility is although rare, but it causes mother
The severity extent of tire blood group incompatibility Hemolysis will overweight abo blood group and not conform to, so the diagnosis and prevention to Rh blood group incompatibility are extremely
It is important.Rh blood group incompatibility generates the Rh antibody (the anti-D of IgG) of a large amount of anti-fetal red blood cells due to parent, into fetus body in after it is broken
Bad a large amount of fetal red blood cells, make fetus severe anemia, anoxic, heart failure, hepar damnification, Hypoproteinemia, anasarca, chest
Water, ascites even Intrauterine Fetal Death.In non-neonate, Rh blood group incompatibility haemolysis does not conform to compared with abo blood group there is morning jaundice time, most
Early to occur after birth in 12 hours, majority appeared in 24 hours.Due to haemolysis generate a large amount of bilirubin cannot in time from
Liver excludes, and aggravates icterus neonatorum, and a large amount of bilirubin penetrates into brain cell and causes nuclear icterus, often die of severe anemia,
Heart failure, nuclear icterus, the death rate are very high.
Although Rh antibody, which enters the rear red blood cell by destroying fetus in fetus body, can cause serious Hemolysis, certain
A little pregnant woman also can be by injecting Rh antibody in advance come Rh (D) positive red blood cell sensitization body of pre- anti-intrusion, and then can prevent Rh
The generation of Hemolysis.Since current most countries have forbidden carrying out D antigen with volunteer immune, the source of the polyclonal anti-D of Ig
It is extremely limited, and utilize the anti-D of Epstein-Barr virus conversion human B lymphocyte secretion Ig or Epstein-Barr virus conversion combination cell fusion preparation
The anti-D of Ig, because in vivo using EBV conversion bone-marrow-derived lymphocyte strain or hybridoma cell strain secretion the anti-D of Ig there are still much ask
Topic, such as contained EBV have potential pathogenic；It may be with pathogen such as HIV and hepatitis virus；It is produced with hybridoma technology
The anti-D albumen containing source of mouse of Ig easily causes allergic reaction or the oncogene with mouse, so by directly injecting Ig in vivo
Anti- D is just restricted to prevent Rh Hemolysis.
Clinically mainly there are pregnancy period plasma exchange, fetal transfusion, termination to the treatment of female tire blood group incompatibility Hemolysis at present
Gestation and neonatal exchange transfusion treatment.Anti- D potency needs to consider intrauterine transfusion 32 or more, and fetal transfusion includes that fetus is intraperitoneal defeated
Blood and the intravascular blood transfusion of fetus, all have certain risk, and none is proved effectively；Hyperbilirubinemia of newborn person can be used
The drug therapies such as blue light illumination, intravenous injection of immunoglobulin, Blood exchanging therapy, Blood exchanging therapy are still that treatment newborn is molten when necessary
The main method of blood disease；Anti- D potency is 64 or more during gestation, need to consider replacement therapy of blood plasma, pregnant woman blood plasma displacement be exactly
The haemocyte and blood plasma that method separation pregnant woman is filtered in extracorporal circulatory system access, remove blood plasma and with the displacement liquid of equivalent (fresh ice
Freeze blood plasma or 5% albumin) supplement feedback, each 2 000~3 000ml of replacement amount, 20~30ml/min of speed, treatment time
2~4h, every 1~3d are treated 1 time；Or pregnant woman's whole blood about 400ml is taken every time, its blood plasma about 300ml, supplement etc. are removed after low-temperature centrifugation
Measure homotype fresh plasma, also defeated Autoerythrocyte (RBC).Plasma exchange can proportionally be reduced with the plasma volume being removed and be caused a disease
The titre (potency) of antibody, so as to extend fetus in female intracorporal survival and growth and development time, terminal pregnancy can be postponed
Time is the good selection that the pregnant woman of female tire ABO, Rh or other blood group incompatibilities prevents miscarriage in treatment in clinical early stage, has preferable
Curative effect, also without other adverse reactions.But plasma exchange can only remove the partial antibody in blood, cannot stop the continuation of antibody
Generate, the female tire blood group incompatibility Hemolysis occurred can not be reversed, need to carry out incessantly plasma exchange just it is effective, only fit
Pregnant woman or spouse for fetus edema once to occur before gestation 20~22 weeks are the homozygote person of pathogenic antigens, especially
While removing part pathogenic antibody, a large amount of blood plasma (multiple beneficial composition) is also eliminated together, although making with displacement liquid
Supplement, but can not supply completely and be removed blood plasma and its various beneficials, and the displacement liquid measure substituted is big, expense is high
Expensive, supplement allosome blood plasma easily causes the various side effects such as infectious disease and infusion reaction, and which limits the generally developments of plasma exchange.
So there is an urgent need to a kind of only removal pathogenic antibody, not removing blood plasma and its multiple beneficial composition, without using blood
Starch the treatment new method of female tire blood group incompatibility Hemolysis cheap, safe, without side-effects of displacement liquid.
Summary of the invention
In order to solve the problems, such as to attack the treatment for the female tire blood group incompatibility Hemolysis being unable to long, present inventors have proposed the present invention.
The invention aims to provide people's Rh positive red blood cell absorber；Another object is to provide for the preparation of absorber
And application method.
The object of the present invention is achieved like this: by Blood Transfusion Services by the acquisition requirement of component blood transfusion, preparing fresh Rh
Positive " O " type Red Blood Cells Concentrate, respectively with physiological saline cleaning 4 times under conditions of 4 DEG C and 37 DEG C, to remove erythrocyte surface
Immune antibody that may be present or natural antibody take cell precipitation to assemble high-biocompatibility material after detection antigenicity
3.5% mannitol alserver's solution is added until 4/5 in manufactured cylindrical adsorption device, makes red blood cell concentration up to 80%, jog
It mixes, sealing is set 4 DEG C and saved backup, and is respectively provided with cell screen clothes in the top and the bottom of absorber, top diameter is 500 mesh, and bottom diameter is 50
200 aim cell strainers are arranged in mesh, liquid outlet, constitute the second defence line for preventing cell fragment from entering circulation, liquid disengaging
Mouthful and mesh screen between be arranged buffer area so that extracorporal circulatory system stabilization, when blood plasma flows through absorber, Rh antibody is by Rh therein
Positive red blood cell is combined into fixed immune complex, the red cell debris that is destroyed and it is in combination made of macromolecular it is immune
Compound is adsorbed the sieve detention of device, removes after the blood plasma of morbid substance is filtered out from absorber and feeds back in vivo, removes blood with this
Starch Rh antibody and red blood cell lysate.
Rh antibody is the virulence factor of female tire Rh blood group incompatibility Hemolysis, and Rh (D) positive red blood cell is the natural of Rh antibody
Antigen, can in conjunction with Rh antibody and by absorption remove, the present invention chooses the positive O-shaped red blood cell of Rh, in low temperature and at room temperature with
Physiological saline cleaning to remove the natural and immunity blood group antibody of erythrocyte surface, but retain the antigenicity for adsorbing Rh antibody and
The natural antibody for not adsorbing anti-A and anti-B, being followed by 3.5% mannitol alserver's solution is that medium assembles absorber, is easy to
It periodically saves, Rh (D) positive red blood cell is easy to get, and preparation method is easy, and the spy because being provided with multiple minimum entrance micropores
The absorber sieve of system forms Rh positive red blood cell to the barrier properties of red cell debris and macromolecular antigen antibody complex
The double purified barrier for adsorbing Rh antibody and absorber mesh screen mechanical stop red blood cell lysate, flows through the blood plasma of absorber
In Rh antibody and the red blood cell lysate of haemolysis patient be adsorbed removing, purified blood plasma is fed back, with this realize by
Rh antibody from the treatment removed in vivo, be it is a kind of only remove pathogenic antibody and red blood cell dissolved matter, do not remove blood plasma and its more
The treatment of female tire blood group incompatibility Hemolysis cheap, safe, without side-effects without plasma exchange liquid of kind beneficial is newly square
Method.
Specific embodiment
Fig. 1 is the application schematic diagram of the people's Rh positive red blood cell absorber proposed according to the present invention.
Fig. 2 is the schematic diagram of internal structure of the plasma separator proposed according to the present invention.
Fig. 3 is the schematic diagram of internal structure of the immuno absorbence device proposed according to the present invention
In Fig. 1, one end of arterial blood line pipe (1) is connected with arteries, and the other end is through heparin pump (2) and blood pump
(3) it is connected with plasma separator (4), plasma separator (4) absorber in parallel with 2 through blood plasma pump (6) and circulation line (7)
(8), absorber (9) is connected, and is then successively connected with circulation line (10), venous line (5), the other end of venous line (5)
It is connected with vein blood vessel.
In Fig. 2,1 is plasma separator, and 2 be plasma separator inner cavity, and 3 be the micropore on the tube wall of plasma separator inner cavity, 4
Being cannot be by the haemocyte of micropore (3), and 5 be the small molecule blood plasma components that can pass through micropore (3), and 6 be plasma separator exocoel,
7 be blood plasma outflux, and 8 be switchable valve.
In Fig. 3,1 is absorber, and 2 be the Rh positive red blood cell in absorber, and 3 be the Rh antibody into absorber, 4
Rh antibody by Rh positive red blood cell in conjunction with and the antigenantibody complex that is formed, 5 be RBC fragment.
Below with reference to Fig. 1, Fig. 2 and Fig. 3, the embodiment of people Rh positive red blood cell absorber proposed by the present invention is made detailed
Thin description.
One, the preparation of Rh (D) positive red blood cell
1, the acquisition of Rh (D) positive red blood cell
(1) positive " O " the type red blood cell of fresh concentration Rh (D) is bought from Blood Transfusion Services of Zhejiang Province；(2) newborn has been extracted
Positive " O " type erythrocyte of Rh (D) in vitro discarded Cord blood.
2, main agents and effect
The formula of 3.5% mannitol alserver's solution are as follows: take mannitol 17.5g, citric acid trisodium 1.5g, citric acid
0.2g, glucose 7.93g, sodium dihydrogen phosphate 0.94g, adenine 0.14g, sodium chloride 4.97g, are dissolved in the distilled water of 500ml.
Wherein mannitol dilutes Red Blood Cells Concentrate viscosity, increases cell membrane stability, prevents haemolysis.Sodium citrate and blood or blood plasma
In Ca2+ combine the soluble calcium citrate for being formed and being difficult to dissociate, reduce Ca2+ in blood, to inhibit coagulation process,
Anticoagulation is generated, and has protective effect to red blood cell, the generation of haemolysis can be prevented.Citric acid prevents in red blood cell additive
Glucose coking forms buffering pair with sodium citrate, adjusts and stablizing solution pH.Glucose is the main energetic of erythrocyte metabolism
Source, under normal circumstances, the 90% of glucose generate ATP by pentose phosphate pathway by anerobic glycolysis, 10%, provide red thin
Born of the same parents' energy maintains its service life.Activity level of the blood ATP during 4 DEG C of storages can be improved in adenine.Red blood cell is to adenine
It needs to be special, adenine can be changed into adenosine phosphate (AMP) by it, and further phosphorylation generates ATP, be red blood cell
Metabolic vigor provides energy-rich compound source, greatly prolongs holding time of the blood at 4 DEG C.Sodium chloride adjusts solution infiltration
Pressure is isotonic solution, provides appropriate sodium ion for red blood cell.Sodium dihydrogen phosphate prevents erythrocyte aggregation, is energy metabolism of erythrocyte
Phosphate is provided, 2,3-DPG decrease speed is slowed down.
Anti- D standard items and Rh (D) normal erythrocytes are purchased from Guangzhou Lian Tai Bioisystech Co., Ltd.
3, preparation method
(1) positive " O " the type Red Blood Cells Concentrate of fresh Rh is prepared, is taken by the acquisition requirement of component blood transfusion by Blood Transfusion Services
The positive O-shaped red blood cell of the fresh Rh of sufficient amount, respectively under conditions of 4 DEG C and 37 DEG C, with the centrifugation speed of 1500r/min × 5min
Degree is cleaned red blood cell 4~5 times with isometric physiological saline, to remove the abo blood group and Rh blood that erythrocyte surface may adhere to
Type and other immune antibodies or natural antibody.
(2) detection of antigenicity: 1. by red blood cell and 37 DEG C of incubation 5min of anti-D standard items, centrifuging and taking supernatant detects anti-D
Standard items potency reduces numerical value to determine the antigenicity of red blood cell.Specific method is: 10, test tube are taken, respectively number 1~10, the
Erythroprecipitin 1.0ml is added in 1 pipe, then other each pipes plus physiological saline 0.5ml inhale erythroprecipitin 0.5ml from the 1st pipe and add
Enter to the 2nd pipe, 0.5ml to the 3rd is inhaled after mixing and is managed, the 10th pipe is diluted to same operation, finally pipe is sucked out 0.5ml and discards, often
Pipe plus anti-D standard items 0.5ml, 37 DEG C of incubation 5min are mixed gently after centrifugation, to there is agglutination completely, almost without free cell
Maximum dilution multiple represent the antigenicity of red blood cell, extension rate is bigger, and antigenicity is stronger, and the ability of absorption Rh antibody is got over
By force.Supernatant antibody titer can also be measured with Rh (D) normal erythrocytes to determine the antigenicity of red blood cell；2. being marked with Rh (D)
Quasi- red blood cell determination supernatant antibody titer, it is red blood cell that anti-D standard items potency (known), which subtracts supernatant antibody titer,
Antigenic (potency).Supernatant antibody titer detection method are as follows: take 10 test tubes, respectively number 1~10, physiology salt is added in each pipe
Water 1ml takes supernatant 1ml to be added to removal 1ml after the 1st pipe mixes and goes to the 2nd pipe, is diluted to the 10th pipe with same operation, most
Pipe is sucked out 1ml liquid and discards afterwards, and the 40 μ l of serum diluted is mixed with 10 μ l of Rh (D) normal erythrocytes, is incubated for 10 minutes, from
The agglutination pipe of 5 minutes interpretation results of the heart, maximum dilution multiple is antigenic (potency), and potency should be 1: 1500 or more.
Two, the preparation of absorber
1, preparation principle
It is because the free Rh antibody in pregnant woman blood plasma enters fetal blood the present invention is based on female tire Rh blood group incompatibility Hemolysis
It destroys caused by fetal red blood cells, and Rh antibody can be combined absorption, and absorption by corresponding native antigen, that is, Rh positive red blood cell
The shell of device can be made into mechanism preparation of the sieve for only allowing specific small molecule to pass through to stop bigger molecule to pass through.
2, material is prepared
It selects and the close high-biocompatibility material of Human vascular endothelial, it is desirable that good biocompatibility, no complement activation,
No inflammation reaction, the change without leucocyte, blood platelet, blood oxygen pressure, complement C 3 C5a.It is required that passing through covalent, grafting, polymerization etc.
Method improves the influence of the uniformity, hydrophily, reduction of material surface to blood coagulation and oxidative stress.Add parent in absorber inner surface
Hydrogel such as solidifies 2 methylacryoyloxyethyl phosphocholines-butyl methacrylate in cellulose acetate film, passes through control
Wet-spinning procedure and generate CA/PMB30, CA/PMB80 and CA/PMB30-80, biocompatibility can be improved.By certain anticoagulants
Matter is solidificated in carrier or absorber inner surface, can inhibit blood clotting, reduces heparin dosage even realization no-rod tractor, such as by liver
Element is aggregated on polyacrylonitrile-polyethyleneimine film, can reduce the allergic reaction of allergic constitution；Heparin covalent is integrated to polyethers
Sulfone surface can keep the mechanical property of polyether sulfone and improve the anticoagulation function of absorber inner surface.On cellulose acetate film altogether
Valence solidifies linoleic acid film, or the linoleic acid for being covalently bound to polyacrylic acid is grafted onto polysulfones film surface, can have preferably
Histocompatbility and anticoagulant effect.
3, the specification of adsorber enclosure
The hydrostatic column that the bottom diameter for being made 50mm × 60mm is small, top diameter is big, or rectangular, infundibulate is made, volume about 200
~300ml, top and the bottom are equipped with cell screen clothes, and top diameter sieve mesh number is 500 mesh, and bottom diameter sieve mesh number is 50 mesh, liquid outlet
Place's setting mesh number is 200 aim cell strainers, constitutes the second defence line for preventing cell fragment from entering circulation, liquid entrance
It is equipped with buffer area between mesh screen, is conducive to the stability of system circulation.
4, the filling of adsorbent
Rh prepared by the present invention (D) positive red blood cell is taken, absorber is packed into, until 4/5, the red thin of 3.5% mannitol is added
Born of the same parents save liquid, make red blood cell concentration up to 80%, and jog mixes, and sealing is set 4 DEG C and saved backup.
Three, the preparation of plasma separator
1, it preparation principle: is prepared according to the molecular size of haemocyte and blood plasma components.Such as visible component (blood in blood of human body
Cell) size are as follows: normocyte is about 7 microns (μm), is the discoid cell of concave-concave；Leucocyte is divided into 5 kinds, neutrality
About 12 μm of granulocyte, eosinophil is more bigger, and basophilic granulocyte and neutrophil leucocyte are close, and 6-8 μm of small lymphocyte,
Approximate with red blood cell, monocyte is maximum, and about 15-20 μm.Blood platelet is disc, 1~4 micron of diameter to 7~8 microns not
Platelet mean diameter Deng, people is 2-4 micron, 0.5~1.5 micron of thickness.
2 prepare material: poly-vinegar non-woven fabrics, acetate fiber, absorbent cotton etc. can be selected, it is desirable that good biocompatibility, hardly
Activating complement, the change for not causing inflammatory reaction, not causing leucocyte, blood platelet, blood oxygen pressure, complement C 3, C5a.It can pass through
Covalently, the methods of be grafted, polymerize improve the structure of material, adjust the microinhomogeneities on surface, hydrophily, reduction to blood coagulation and
The influence of oxidative stress, the generation to improve sieving adequacy and biocompatibility, reduction complication.
3 specifications: for the shape of separator, cylindricality knot can be prepared into as filter core with materials such as acetate fiber or absorbent cotton
Structure is prepared into the shapes such as flat structure as filter core with materials such as poly-vinegar non-woven fabrics；By haemocyte and blood plasma components to be separated
Molecular size determines aperture.The high height of plasma separator according to the present invention property stabilization, good biocompatibility, permeability
Hollow fibre type filter is made in Molecularly Imprinted Polymer, and hollow-fiber film diameter is 270~370 μm, and film thickness is 50 μm, and aperture is
0.2~0.6 μm, fibre length is 13.5~26 μm.Blood plasma filtration is only permitted in the hole, but can stop all cell components.
Four, application of the invention
Extracorporal circulatory system branch need to be collectively constituted with associated components.
1, the component and purposes of extracorporal circulatory system branch
(1) absorber: internal Rh (D) positive red blood cell is for removing Rh antibody；The mesh screen of adsorber enclosure inlet and outlet
Have the function of filtering out the macromolecular complex that RBC fragment, Rh antibody and RBC fragment are formed.
(2) washed corpuscles and blood plasma plasma separator: are used for.
(3) sound pulse pressure monitors: in addition the main stopping state to dynamic monitoring absorber micropore of arterial blood pressure monitoring is used
To monitor extracorporal circulatory system thrombus, solidification and the variation of pressure.When blood flow deficiency, angiosthenia will be reduced；When having blood coagulation, thrombus
When formation, especially absorber blockage of the micro orifice, angiosthenia will be increased；Vein pressure monitoring is used to monitor the pressure of pipeline blood reflux
Power, when absorber blockage of the micro orifice, blood coagulation, thrombosis, blood flow deficiency and venous return syringe needle fall off, vein pressure will
Decline, if bloody path return pipe distortion blocking or reflux syringe needle block, vein pressure will be increased.
(4) air monitering (Air Detector): the air bubble for monitoring blood pathway generally uses ultrasonic listening
Principle, in order to avoid patient occur air embolism and be arranged.When having monitored air bubble, detection system can drive it is dynamic,
Vein bloody path folder carrys out blocking blood flow, prevents dangerous generation.
(5) blood pump (Blood Pump): for pushing blood circulation going on smoothly with maintenance therapy, usual blood pump part
Often there is rotary test speed function, to monitor the blood circumstance of patient, therefore blood pump runner and the setting of groove spacing are accurate, and
It needs often to adjust, the case where according to bloody path pump line, spacing is generally set as 3.2~3.3mm, can not be too loose, otherwise it can make
It is inaccurate at blood flow detection；Also can not be too tight, it otherwise will cause pipe breakage.
(6) heparin pump (Heparin Pump): heparin pump is equivalent to the micro-injection pump clinically applied, to continue to
Injecting heparin in sieving pipeline (patient blood) contacts with air since the blood of patient recycles in vitro, is easy to happen blood coagulation
Phenomenon anticoagulative can be occurred using heparin pump.
It additionally include temperature control system, liquid mixing system, off gas system, monitored conductivity system, ultrafiltration monitoring and leakage
The parts such as blood monitoring.In short, on the basis of constitution system of the invention crucial, be expected to be further development of automation, hommization,
Personalization, modularization, automatic monitoring and regulation, liquid crystal display voluntarily judge that the micro computers such as alarm reason and ring off signal are handled
System.
2, application method of the invention
(1) it installs: with each portions such as sterile working connecting components, including plasma separator, absorber and each circulation line.
(2) it is vented: with sterile saline filling liquid separator, absorber and each circulation line, excluding separator, absorber
And its gas, bubble in circulating line, it goes through, confirmation after gas, bubble without using.
(3) lead to liquid: arterial blood line pipe 1 being connected to the arteries of AIDS patient, in operation the row of going through again
Whether gas is complete, and whether liquid stream is unobstructed, and flow liquid in pipe is avoided to pollute.
(4) anticoagulant: to be injected from heparin pump into liquid stream anti-coagulants (heparin), be for the first time 2500 ∪ or 20~30 ∪/kg.
(5) start: arterial blood line pipe (1) is connected to the arteries of curer, venous line (5) are connected curer's
Then vein blood vessel opens blood pump, blood flow is 100~150ml/min, such as Fig. 1, when arterial blood is through arterial blood line pipe
(1) enter plasma separator (4), the blood plasma separated reaches absorber through circulation line (7) under the action of blood plasma pump (6)
(8), wait be full of blood plasma, about 10 minutes, blood plasma is begun releasing, is flowed out through circulation line (10), it is synchronous that blood is perfused to absorber (9)
Slurry, when the blood plasma in absorber (8) has nearly flowed, starts again at perfusion blood plasma, and absorber (9) begins releasing blood plasma at this time,
Two absorbers (8) in parallel, absorbers (9) are alternately.Such as Fig. 2, when blood to be separated enters plasma separator (1)
When inner cavity (2), the effect through valve (8) can enter the outer of separator by the small molecule blood plasma and its composition (5) of micropore (3)
Chamber (6) is then flowed out through plasma outlet port (7), and cannot be flowed out by the haemocyte (4) of micropore (3) through valve (8).Such as Fig. 3,
When Rh antibody (3) enters absorber (1) with blood plasma, it is multiple that the Rh positive red blood cell (2) being adsorbed in device is combined into antigen-antibody
Close object (4) and no longer move down, the red cell debris (5) that is destroyed and it is in combination made of macromolecular antigen-antibody it is compound
The haemocyte that object cannot be separated by the mesh screen that absorber exports by detention, purified blood plasma and plasma separator converges
It is fed back after conjunction, so until the plasma circulation amount (usually 9L) being previously set, treatment just ends, if mating computer journey
Sequence control, entire therapeutic process is controlled by computer, and can detect working condition at any time, using can it is more convenient, automation and
Safety.
Five, the verifying of practical application of the present invention
In order to verify the effect of absorber removes Rh antibody, the present invention devises easy test method: taking the 2.5 of sterilizing
× 300mm Westergren's blood sedimentation tube 9 draws Rh (D) positive red blood cell and is precipitated to 250mm scale, suitable through 100 followed by drawing
Heat preservation becomes semisolid after agarose is cooling, can consolidate red blood cell in 42 DEG C of 1.0% spare agarose C1-4B after DEG C dissolving
It is scheduled in pipe, easy garden cylindricality absorber is made with this.In addition the fresh frozen plasma 200mL of Zhejiang Province center blood station is bought
And Rh antibody (the anti-D type serum dry powder standard items of people, Guangzhou Lian Tai Bioisystech Co., Ltd), be made into 1: 200 with fresh plasma,
1: 300,1: 600 antibody titer, routinely Rh (anti-D) titre detection method (reference book), it is above-mentioned further to detect confirmation
Whether prepared antibody titer is consistent, and (Rh) antibody (titre) before referred to as filtering, antibody is injected separately into 3 before then respectively taking 10ml to filter
The upper end blank pipe of branch blood sedimentation tube collects efflux after flowing through the red blood cell in blood sedimentation tube, (Rh) antibody after referred to as filtering, by normal
It advises Rh (anti-D) titre detection method and confirms titre, then respectively pass through antibody after filter in the blood sedimentation tube containing Rh (D) positive red blood cell
Make the 2nd time to filter out, be so repeated 3 times filtration and antibody titer detection, as a result (table 1) illustrates, the easy absorption of Rh antibody filtration
After device, most of Rh antibody is adsorbed by corresponding Rh (D) positive red blood cell, and after the 1st time, the 2nd time, the 3rd filtration, Rh is anti-
The average titer of body respectively from 1: 367 before filter be reduced to filter after 1: 183,1: 58,1: 29, illustrate with filter number increasing
Add, Rh antibody can be adsorbed constantly by Rh (D) positive red blood cell and be removed, so that reaching reduces pregnant woman (newborn) blood plasma Rh antibody
Titre and the purpose for treating female tire blood group incompatibility Hemolysis.
The filtration of 1 Rh antibody of table contains titre testing result (1/x) before and after the absorber of Rh (D) positive red blood cell
Claims (6)
1. a kind of people's Rh positive red blood cell absorber for medical domain, which is characterized in that the absorber passes through circulation pipe
Road is successively connected with blood plasma pump, plasma separator, blood pump and heparin pump and constitutes vitro Adsorption Rh antibody device, the suction
Adnexa is column, and sieve is arranged in its exit, 80% prepared with 3.5% mannitol alserver's solution is perfused inside it
Positive " O " the type red blood cell of the Rh of concentration, positive " O " the type red blood cell of the Rh are cleaned through 4 DEG C and 37 DEG C of physiological saline respectively
And eliminate immunity and natural antibody.
2. people Rh positive red blood cell absorber according to claim 1, which is characterized in that the Rh antibody refers to Ig anti-D, Ig
The anti-anti- anti-c of C and Ig of E, Ig anti-e, Ig.
3. people Rh positive red blood cell absorber according to claim 1, which is characterized in that positive " O " type of the Rh is red thin
Born of the same parents play a part of to adsorb Rh antibody.
4. people Rh positive red blood cell absorber according to claim 1, which is characterized in that the shell volume of the absorber
For 200~300ml, top and the bottom are equipped with cell screen clothes, and top diameter cell screen clothes mesh number is 500 mesh, and bottom diameter cell screen clothes mesh number is
50 mesh, it is 200 aim cell strainers that mesh number, which is arranged, in liquid outlet.
5. people Rh positive red blood cell absorber according to claim 1, which is characterized in that 3.5% mannitol it is red
Cell-preservation liquid is mannitol 17.5g, citric acid trisodium 1.5g, citric acid 0.2g, glucose 7.93g, sodium dihydrogen phosphate
0.94g, adenine 0.14g, sodium chloride 4.97g, are dissolved in the distilled water of 500ml.
6. -5 any people's Rh positive red blood cell absorbers are preparing answering in vitro Adsorption device according to claim 1
With, which is characterized in that the vitro Adsorption device include arterial blood line pipe (1) one end through heparin pump (2) and blood pump (3) with
Plasma separator (4) is connected, plasma separator (4) absorber in parallel with two through blood plasma pump (6) and first circulation pipeline (7)
(8,9) it is connected, is then successively connected with second circulation pipeline (10), venous line (5).
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610540878.3A CN106267423B (en) | 2016-07-01 | 2016-07-01 | People's Rh positive red blood cell absorber |
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| CN106267423B true CN106267423B (en) | 2019-02-19 |
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| CN109157695A (en) * | 2018-07-19 | 2019-01-08 | 翁炳焕 | Based on the female tire blood group incompatibility therapeutic device for removing pathogenic antibody |
| CN111713487B (en) * | 2020-06-30 | 2021-10-08 | 上海市血液中心 | Reagent erythrocyte preservation system and preparation method thereof |
Citations (4)
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|---|---|---|---|---|
| CN1436083A (en) * | 2000-05-31 | 2003-08-13 | 塞鲁斯公司 | Preparation of pathogen inactivated solution of red blood cells having reduced immunogenicity |
| CN102316899A (en) * | 2008-12-17 | 2012-01-11 | 法国分裂暨生物科技实验室 | Use of an immunoglobulin G (IgG) concentrate depleted of anti-A and anti-B antibodies for treating neonatal jaundice caused by maternal-foetal incompatibility with respect to the ABO system |
| CN102816237A (en) * | 2012-06-27 | 2012-12-12 | 新疆德源生物工程有限公司 | Preparation method of human anti-D immunoglobulin |
| CN105056325A (en) * | 2015-08-07 | 2015-11-18 | 王晓芝 | Novel plasma filtering and adsorbing system |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014025895A1 (en) * | 2012-08-08 | 2014-02-13 | Arryx, Inc. | Methods and devices for immunodiagnostic applications |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1436083A (en) * | 2000-05-31 | 2003-08-13 | 塞鲁斯公司 | Preparation of pathogen inactivated solution of red blood cells having reduced immunogenicity |
| CN102316899A (en) * | 2008-12-17 | 2012-01-11 | 法国分裂暨生物科技实验室 | Use of an immunoglobulin G (IgG) concentrate depleted of anti-A and anti-B antibodies for treating neonatal jaundice caused by maternal-foetal incompatibility with respect to the ABO system |
| CN102816237A (en) * | 2012-06-27 | 2012-12-12 | 新疆德源生物工程有限公司 | Preparation method of human anti-D immunoglobulin |
| CN105056325A (en) * | 2015-08-07 | 2015-11-18 | 王晓芝 | Novel plasma filtering and adsorbing system |
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