CN106166311B - A kind of plasma purification system and its application - Google Patents
A kind of plasma purification system and its application Download PDFInfo
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- CN106166311B CN106166311B CN201610769868.7A CN201610769868A CN106166311B CN 106166311 B CN106166311 B CN 106166311B CN 201610769868 A CN201610769868 A CN 201610769868A CN 106166311 B CN106166311 B CN 106166311B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1621—Constructional aspects thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/362—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity
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- A—HUMAN NECESSITIES
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- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0415—Plasma
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/04—General characteristics of the apparatus implanted
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/75—General characteristics of the apparatus with filters
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Abstract
The present invention relates to a kind of novel blood purification systems, including ligands specific 1 (immunosorbent) (1), histocompatbility carrier (3), ligand 2 (2) and plasma purifier.The ligands specific 1 still keeps its immunologic competence, ligand 1 is partially embedded in carrier surface, ligand 1 can be specifically bound with the specific virulence factor (antibody) in blood, make a large amount of virulence factors that reference state, only a small amount of morbid substance be kept to be scattered in blood plasma in free state.Periodically carrier protein is removed together with virulence factor by plasma purifier specific binding ligand 2.The present invention can specifically bind the virulence factor in blood, it is in reference state to make it, to make the virulence factor of free state keep low concentration state for a long time, reduces tissue involved, it interrupts in vivo " immune storm ", reduces patients blood plasma and purify number, reduce complication rate.
Description
Technical field
The present invention relates to field of medical technology, specifically, being a kind of plasma purification system and its application.
Background technology
Plasma purification therapy is primarily referred to as largely removing morbid substance in blood plasma in a short time, improves patient clinical disease
Shape, to achieve the purpose that treat disease.Many selectivity for being directed to different morbid substances have been developed on this basis at present
The technology that filtration is removed or absorption is removed, including plasma exchange, Cured by Double Filtration Plasmapheresis plasma purification technology (double-filtration
Plasmapheresis, DFPP), cold filtration method, hot filtration method, the heparin-induced LDL precipitation method, plasma adsorption technology (plasma
Absorption, PA) etc..Technology application range has also been extended to hundreds of disease of each system.Rheumatological disease
Often there are the virulence factors such as a variety of autoantibodies, complement, immune complex, inflammatory factor in patient's body, with plasma purification
Therapy can specifically remove above-mentioned virulence factor, and then achieve the purpose that treat disease.
Rheumatological disease patient's body can not be removed in time since virulence factor generates excessive or body, cause to cause a disease
The serological concentration of the factor extends and builds up at any time, and as indicated by a broken line in fig. 1, plasma purification used is treated currently on the market
Rule is regularly to be filtered out virulence factor displacement/dialysis/absorption/in vitro by plasma purification therapy, such as Fig. 1 solid lines institute
Show, virulence factor serum-concentration is presented fluctuation and sexually revises.Thus such patient needs long-term, rule row plasma purification just to can guarantee
Virulence factor is cleared up in time, in addition, plasma purification therapy, required fresh plasma are more, frequency is high, expensive, complication is more：
Low blood pressure, allergic reaction, haemolysis, hypertension, arrhythmia cordis etc..
The present invention provides a kind of novel plasma purification mode.It, will for certain specific rheumatological disease
It is embedded into carrier surface with the antibody of virulence factor specific binding, and regular injections make virulence factor keep to patient's body
Reference state rather than free state, thus the virulence factor serum-concentration of free state is as shown by the dash line in figure 2, when carrier surface antibody is whole
After being combined, virulence factor is just gradually in rising trend.If it is net that the node before rising occurs in virulence factor carries out blood plasma
Change, the virulence factor of reference state is cleared out in vitro together with carrier, then virulence factor concentration is relatively steady, as Fig. 2 is shown in solid.
Invention content
The purpose of the present invention is being directed to deficiency in the prior art, a kind of plasma purification system is provided.
Another purpose of the present invention is to provide a kind of novel plasma purification mode.
To achieve the above object, the technical solution adopted by the present invention is that：
A kind of plasma purification system, including carrier and external plasma purifier, the carrier surface absorption specificity are matched
Body -1 and ligands specific -2；The ligands specific -1 keeps its immunologic competence, ligand -1 to be partially embedded in carrier surface,
It can be specifically bound with the specific morbid substance in blood, a large amount of morbid substances is made to keep reference state, only a small amount of morbid substance
It is scattered in blood plasma in free state；The external plasma purifier specific binding ligand 2 is by carrier together with virulence factor one
It rises and removes.
Further, the carrier is liposome, bio-compatibility albumen, artificial red cells, large biological molecule or macromolecule
Gel particle can largely be present in normal human blood without causing immunological rejection for a long time.
Further, the ligands specific -1 is polyclonal antibody, monoclonal antibody, 4- mercaptoethyls pyridine, sulfuric acid Portugal
Glycan, tryptophan, phenylalanine, polyanion, polylysine, the albumin that methylates, Clq, anti-LDL antibody, anti-IgE are anti-
Body, antinuclear antibodies ligand, extractibility antigen, DNA, core Zhou Yinzi, MAG/SPGP, gangliosides, immune complex.
Further, the ligands specific -1 is adsorbed or is embedded in inside carrier surface or liposome, artificial coating, specifically
Property ligand -1 adsorbance be 105-106/；The absorption of ligand -2 is embedded in carrier surface, and the adsorbance of ligand -2 is far small
In the adsorbance of ligand -1.
Further, the plasma purifier is filtering device, liposome adsorption column, chromatographic column；In plasma purifier
The antibody that a large amount of distributions can be specifically bound with ligand -2.
Further, the present invention also provides a kind of improved plasma purification system, including carrier and external plasma purifier,
Carrier surface absorption specificity ligand -1, the carrier exist in the form of micro-capsule；The ligands specific -1 keeps it
Immunologic competence, ligand -1 are partially embedded in carrier surface, can be specifically bound with the specific morbid substance in blood, are made a large amount of
Morbid substance keeps reference state, only a small amount of morbid substance to be scattered in blood plasma in free state；The external plasma purifier
Including activated carbon or filtration film filter.APA coatings are filtered by activated carbon or filtration membrane, AchRab is filtered with carrier
It crosses, other compositions are fed back again into human body.Further, the carrier is polyvinyl alcohol hydrogel particle, the ligands specific-
1 is 4- mercaptoethyl pyridines；The carrier is to carry polyvinyl alcohol gel particle sodium alginate-polylysine-sodium alginate micro-capsule
Form, preparation method is as follows：Polyvinyl alcohol hydrogel is taken, by 4- mercaptoethyls pyridine adsorption in polyvinyl alcohol hydrogel table
Face, adsorbance 105-106/, it is 10 that hydrogel ultrasonic machine, which is vibrated into mean size,6-109KD particles；By gel particle
With the sodium alginate of a concentration of 15g/L with volume ratio for 1：15 ratio is uniformly mixed, and draws into 20ml syringes.With electrostatic liquid
Drop method is 10kV, fltting speed 8.5ml/min, tack needle diameter 1mm in encystation voltage, and syringe needle is 1cm's from liquid level
Under the conditions of, the mixed liquor prepared is instilled into 0.1mol/L CaCl2In solution, calcium alginate microsphere is formed, after standing 10min
It removes supernatant, after brine 3 times, sodium alginate micro ball input 0.8g/L is gathered in left lysine solution and is shaked
5min removes supernatant, and brine 3 times shakes 5min in the sodium alginate soln of input 1.5g/L, removes supernatant
Liquid and with brine is finally liquefied capsule heart 5min with 55mmol/L sodium citrate solutions, with brine, i.e.,
.
Further, the load polyvinyl alcohol gel particle sodium alginate-polylysine-sodium alginate micro-capsule, in 150r/
Average mechanical breakage rate after min shakings 72h is 4.5%.
Further, the plasma purification system can make virulence factor in patients blood plasma be maintained at low concentration state for a long time, resistance
Only tissue involved aggravates, and significantly reduces required plasma purification number, significantly reduces complication rate, and it is net to reduce blood plasma
The amount of antibody is set in makeup, reduces cost.
To realize above-mentioned second purpose, the technical solution adopted by the present invention is that：
A kind of novel carriers plasma purification mode, including carrier and external plasma purifier, the carrier surface absorption
Ligands specific -1 and ligands specific -2；The ligands specific -1 keeps its immunologic competence, ligand -1 be partially embedded in
Carrier surface can be specifically bound with the specific morbid substance in blood, so that a large amount of morbid substances is kept reference state, only on a small quantity
Morbid substance is scattered in free state in blood plasma；The external plasma purifier is filtering device, liposome adsorption column, chromatography
Column；The antibody that largely distribution can be specifically bound with ligand -2 in plasma purifier；The plasma purification mode is as follows：
(1) carrier protein is periodically injected intravenously or instils, and ligand -1 is specifically bound with the virulence factor in blood into knot
Close state；
(2) when carrier is close to or up to saturation, promoting circulation of blood external liquid circulation；
(3) when blood flows through plasma purifier by circuit, ligand -2 and the antigen binding quilt in plasma purifier
Isolate blood plasma；
(4) blood plasma after detaching is fed back into human body, supplements new carrier and the plasma composition of loss again.
The plasma purification method can make in patients blood plasma virulence factor be maintained at low concentration state for a long time, prevent tissue by
Tired degree aggravates, and significantly reduces required plasma purification number, significantly reduces complication rate, and it is anti-to reduce plasma purifier
The amount of body, reduces cost.
The invention has the advantages that：
1, carrier of the invention is large biological molecule existing for human body itself, can be largely present in blood of human body for a long time,
The antibody -1 of embedding thereon can be specifically bound with virulence factor into reference state, reduce the concentration of free state virulence factor.And with
Past plasma purification mode the concentration of free state virulence factor could can only be dropped to when regular plasma purifies normal range (NR) with
It is interior.
2, carrier of the invention can largely combine virulence factor, and it is in reference state to make it, and it is net significantly to reduce required blood plasma
Change number, significantly reduce complication rate.
3, antibody -1 of the invention can select different antibody -1 according to not same disease, therefore indication is extremely wide.For example,
Antibody -1 is AchR (acetylcholinergic receptor) antigenic determinant, then adsorbable AchRAb (acetylcholine receptor antibodies), treatment weight
Disease myasthenia；If antibody -1 is phenylalanine, dextran sulfate, anti-igg Fc antibody, then adsorbable anti-DNA antibody, CIC, wolf
Sore anticoagulant substances etc. are used for systemic lupus erythematosus.
Description of the drawings
Attached drawing 1 is the variation of virulence factor serum-concentration in plasma purification therapy in the prior art, and virulence factor serum is dense
Degree is presented fluctuation and sexually revises.
Attached drawing 2 be the present invention novel plasma purification system in virulence factor serum-concentration variation, the antibody-on carrier
1 can specifically bind with virulence factor into reference state, reduce the concentration of free state virulence factor.
Attached drawing 3 is carrier structure schematic diagram of the present invention.
Attached drawing 4 is the schematic diagram that virulence factor of the present invention adsorbs narrow body protein by antibody -1.
Attached drawing 5 is fundamental diagram of the present invention.
Attached drawing 6 is plasma adsorption purifier sectional view of the present invention.
Attached drawing 7 is adsorption column sectional view of the present invention.
Attached drawing 8 is adsorption column sectional view of the present invention.
Attached drawing 9 is that the structure of present invention load polyvinyl alcohol gel particle sodium alginate-polylysine-sodium alginate micro-capsule is shown
It is intended to.
Specific implementation mode
The invention will be further elucidated with reference to specific embodiments.It should be understood that these embodiments are merely to illustrate this hair
It is bright rather than limit the scope of the invention.In addition, it should also be understood that, after having read the content of the invention recorded, art technology
Personnel can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Fixed range.
Reference numeral and component part involved in attached drawing is as follows：
1. ligands specific -1
2. ligands specific -2
3. carrier
4. virulence factor
5. power plant
6. external plasma purifier
7. drainage tube
8. adsorption column
9. adsorptive purifier inflow entrance
10. adsorptive purifier outflux
11. polyvinyl alcohol gel particle
12. sodium alginate-polylysine-sodium alginate microcapsule membrane.
The plasma purification system of 1 present invention of embodiment
Fig. 3-Fig. 8 is please referred to, Fig. 3 is carrier structure schematic diagram of the present invention, and Fig. 4 is that virulence factor of the present invention passes through ligand-1
The schematic diagram of absorption carrier, Fig. 5 are fundamental diagrams of the present invention, and Fig. 6 is plasma adsorption purifier sectional view of the present invention, Fig. 7
It is adsorption column sectional view of the present invention, Fig. 8 is adsorption column sectional view of the present invention.
The plasma purification system includes carrier and external plasma purifier, and the adsorption specificity of the carrier is matched
Body -1 and ligands specific -2, ligands specific -1 keep its immunologic competence, and ligand -1 is partially embedded in carrier surface, can be with
Specific morbid substance specific binding in blood, makes a large amount of virulence factors keep reference state, only a small amount of virulence factor is in trip
Amorph is scattered in blood plasma.The carrier is liposome, biomembrane, bio-compatibility albumen, artificial red cells, biological composite wood
Material, large biological molecule, biological composite hydrogel, chitosan or polyvinyl alcohol (PVA), can largely be present in normal human's blood for a long time
Without causing immunological rejection in liquid.The ligands specific -1 can be polyclonal antibody, monoclonal antibody, 4- sulfydryl second
Yl pyridines, dextran sulfate, tryptophan, phenylalanine, polyanion, polylysine, the albumin that methylates, Clq, anti-LDL
Antibody, anti-IgE antibodies, antinuclear antibodies ligand, extractibility antigen, DNA, core Zhou Yinzi, MAG/SPGP, gangliosides are exempted from
Epidemic disease compound etc..Ligands specific -1 is adsorbed or is embedded in inside carrier surface or liposome, artificial coating, ligands specific -1
Adsorbance be 105-106/；The ligand -2 can be specific antibody, and ligand -2 adsorbs or is embedded in carrier surface, matches
The adsorbance of body -2 is less than the amount of ligand -1, is 102-103/.The external plasma purifier is filtering device, liposome
Adsorption column, chromatographic column；The antibody that largely distribution can be specifically bound with ligand -2 in plasma purifier.Carrier is instilled into patient
In blood, the ligands specific -1 of carrier surface absorption can a large amount of virulence factors of the sorption cycle in blood, make it from free
State is converted into reference state, when carrier adsorption amount reaches saturation, the external plasma purification of row, referring to Fig. 3, drainage tube (7) both ends point
Not with human body arteriovenous anastomosis (detailed process can be found in haemodialysis principle), blood pumps out in vitro through power plant, flows through suction
Attached purifier.The antigen that can be largely combined with ligand -2 is distributed in adsorption column in adsorptive purifier, referring to Fig. 5,6,
Virulence factor is adsorbed on carrier in purifier, and other compositions are fed back again into human body.
By taking the treatment of the plasma purification of systemic loupus erythematosus as an example, ligands specific -1 can be phenylalanine, sulphur in Fig. 1
Sour glucan, tryptophan, albumin A, anti-igg Fc antibody, polymyxin B etc., can specific adsorption virulence factor (4), that is,
Anti-DNA antibody, CIC, Lupus anticoagulant, LDL, IgG, permeability factor etc..Ligands specific -2 can be polylysine.It will
A large amount of carriers for being embedded with phenylalanine, dextran sulfate etc. are periodically, regularly intravenous infusion enters blood of human body, can a large amount of sorption cycles
The virulence factors such as the Lupus anticoagulant in blood, make it be converted into reference state from free state.When carrier adsorption amount reaches full
And when, the external plasma purification of row, referring to Fig. 3, (detailed process can be found in human body arteriovenous anastomosis respectively at drainage tube (7) both ends
Haemodialysis principle), blood pumps out in vitro through power plant, flows through adsorptive purifier.Adsorption column in adsorptive purifier
The antigen that can be largely combined with ligand -2 is inside distributed with, referring to Fig. 5,6, virulence factor is adsorbed on carrier in purifier,
Other compositions are fed back again into human body.Again by carrier is regular, regularly intravenous infusion enters blood of human body.
Advantages of the present invention：
1, carrier of the invention is large biological molecule existing for human body itself, autoimmune rejection will not be caused to react, can
Largely it is present in blood of human body for a long time, the ligand -1 embedded thereon can be specifically bound with virulence factor into reference state, reduced
The concentration of free state virulence factor.And previous plasma purification mode can only could cause a disease free state when regular plasma purifies
The concentration of the factor drops within normal range (NR).
2, carrier of the invention can largely combine virulence factor, and it is in reference state to make it, and required plasma purification is greatly reduced
Number significantly reduces complication rate, reduces blood plasma aequum.In contrast, previous simple plasma exchange but needs a large amount of new
Blood slurry, the risk of hematogenous infectious disease are higher.
3, ligand -1 of the invention can also be designed as polyclonal antibody not just for monoclonal antibody, such as anti-LDL antibody,
Anti-alpha-fetoprotein antibody, Anti-HBsAg antibody antibody etc..Thus, indication is extremely wide, can be directed to rheumatological disease, certain non-rheumatism are exempted from
Epidemic disease disease and emergency treatment acute disease etc..
2 myasthenia gravis plasma purification system of embodiment
By taking the treatment of the plasma purification of myasthenia gravis as an example, ligand -1 is 4- mercaptoethyl pyridines, can specific adsorption cause
Cause of disease (4), that is, anti-acetylcholine receptor antibodies (AchRab).First, vectorette is prepared, carrier is by 4- mercaptoethyls
Pyridine, polymer gel particle, coating composition.The raw material of polymeric particles can be polyacrylamide gel, poly- isopropyl propylene
Amide, agar, alginate, chitosan, glucan, nitrocellulose etc., by taking polyvinyl alcohol (PVA) hydrogel as an example.
(1) PVA can pass through crosslinking with radiation, chemical agent crosslinking, the repeatedly preparation of the methods of freeze-thaw：Proportioning weighs PVA, takes
Deionized water is stirred together for PVA, is placed under 85~90 DEG C of constant temperatures and is dissolved completely, is put into -20 DEG C of refrigerator freezing 24
Hour, then thaw at RT 1 hour, referred to as once freezes, melt and dissolved cycle.Prepare various concentration, identical respectively in this way
The PVA hydrogels of cycle-index and same concentrations, different cycle-indexes.
(2) use investment, absorption method, combined techniques or crosslinking fixation by appropriate 4- mercaptoethyls pyridine and PVA water-settings
Cementing conjunction.It is 10 that the hydrogel ultrasonic machine made, which is vibrated into mean size,6-109The particle of kD.
(3) sodium alginate-polylysine-sodium alginate (APA) coating is made：Gel particle prepared by step 2 with it is dense
It with volume ratio is 1 that degree, which is the sodium alginate of 15g/L,：15 ratio is uniformly mixed, and draws into 20ml syringes.With electrostatic drop
Method is 10kV, fltting speed 8.5ml/min, tack needle diameter 1mm in encystation voltage, and syringe needle is from the item that liquid level is 1cm
Under part, the mixed liquor prepared is instilled into 0.1mol/L CaCl2In solution, calcium alginate microsphere is formed, is removed after standing 10min
It removes supernatant, after brine 3 times, sodium alginate micro ball input 0.8g/L is gathered in left lysine solution and shakes 5min,
Supernatant is removed, brine 3 times shakes 5min in the sodium alginate soln of input 1.5g/L, removes supernatant simultaneously
With brine, finally liquefied capsule heart 5min with 55mmol/L sodium citrate solutions, with brine to get package
The APA of gel particle.Carry structure such as Fig. 9 institutes of polyvinyl alcohol gel particle sodium alginate-polylysine-sodium alginate micro-capsule
Show.
(4) micro-capsule film-strength：APA micro-capsules prepared by step 3 are taken to set physiological saline with 100 micro-capsule/groups, in 37 DEG C,
150r/min shakes, and respectively at 1,2,4,8,12,24,36,48h sampling, investigates microcapsule membrane mechanical strength.Parallel laboratory test 3 times, meter
Calculate micro-capsule mechanical damage rate.As a result show that the average mechanical breakage rate of 72h microcapsule membranes is 4.5%.100 micro-capsule/groups are taken, super
The ultrasonic power of sound washer is ultrasound 1h under conditions of 500W, and APA micro-capsules do not occur breakage, continuous ultrasound 2h, under microscope
The averaging ultrasound breakage rate for observing and being calculated cyst membrane is 5.0%.
(5) take appropriate carrier and 5% glucose solution and other medical accessories be mixed and made into mixed liquor, intravenous infusion enters human body
Blood.Carrier is distributed in intravascular, is constantly recycled with blood flow, the AchRAb of the cycle in blood plasma by the hole on APA coatings into
Enter in coating, combined with 4- mercaptoethyl pyridines, by a large amount of sorption cycles in APA coatings, it is made to be converted into knot from free state
State is closed, adsorbable 10 in each coating5-106A AchRAb.When carrier adsorption amount reaches saturation, the external plasma purification of row, ginseng
See Fig. 3, drainage tube (7) both ends are respectively with human body arteriovenous anastomosis (detailed process can be found in haemodialysis principle), and blood is through dynamic
Power apparatus pumps out in vitro, flows through adsorptive purifier, and adsorptive purifier includes activated carbon or filtration film filter.Pass through work
Property charcoal or filtration membrane filter APA coatings, and AchRab is filtered across with carrier, and other compositions are fed back again into human body.
Advantages of the present invention：
1, carrier outer layer of the invention is artificial coating, antigen is free of, because without causing autoimmune response, Bu Huichen
Product is in vascular wall；" tired " will not be combined in coating with itself AchR after AchRAb is adsorbed by high-molecular gel, to avoid certainly
The destruction of body AchR avoids the exacerbation of myasthenia gravis from the root cause.
2, carrier of the invention can largely receive AchRAb, and it is in reference state, primary blood plasma the next day greatly reducing to make it
The frequency of purification significantly reduces required plasma purification number (becoming the 1 time/1-2 months from 1 time/2 days), significantly reduces concurrently
Disease rate.
3, the present invention be expert at external plasma purification when since only artificial coating need to be removed, the amount of artificial coating is AchRAb
The 1/10 of amount5-106, therefore clearance rate higher, shorten cardiopulmonary bypass time, reduce complication rate, required adsorption column amount it is lower,
Greatly reduce cost.Plasma treatment amount can mention higher level from 9L.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, under the premise of not departing from the method for the present invention, can also make several improvement and supplement, these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (7)
1. a kind of plasma purification system, which is characterized in that including carrier and external plasma purifier, the carrier surface absorption
Ligands specific -1 and ligands specific -2；The ligands specific -1 keeps its immunologic competence, and ligands specific -1 can be with
Specific virulence factor specific binding in blood, makes a large amount of virulence factors keep reference state, only a small amount of virulence factor is in trip
Amorph is scattered in blood plasma；The external plasma purifier specific binding specificity ligand -2 is by carrier together with virulence factor
It removes together.
2. plasma purification system according to claim 1, which is characterized in that the carrier is liposome, biomembrane, artificial red
Cell, Biocomposite material, large biological molecule, chitosan or polyvinyl alcohol (PVA), can largely be present in normal human's blood for a long time
Without causing immunological rejection in liquid.
3. plasma purification system according to claim 1, which is characterized in that the ligands specific -1 be polyclonal antibody,
Monoclonal antibody, 4- mercaptoethyls pyridine, dextran sulfate, tryptophan, phenylalanine, polyanion, polylysine, methyl
Change albumin, Clq, antinuclear antibodies ligand, extractibility antigen, DNA, core Zhou Yinzi, gangliosides, immune complex.
4. plasma purification system according to claim 1, which is characterized in that the ligands specific -1 is adsorbed in carrier table
Face, ligands specific -1 is for largely adsorbing virulence factor, adsorbance 105-106/；The ligands specific -2 is adsorbed in
Carrier surface is adsorbed in when for removing in vitro in adsorption column, and the adsorbance of ligands specific -2 is much smaller than ligands specific -1
Adsorbance.
5. plasma purification system according to claim 1, which is characterized in that the external plasma purifier is that filtration fills
It sets, liposome adsorption column, chromatographic column；Largely distribution can be with the specific binding of ligands specific -2 in external plasma purifier
Antibody.
6. plasma purification system according to claim 1, which is characterized in that the carrier is polyvinyl alcohol hydrogel particle,
The ligands specific -1 is 4- mercaptoethyl pyridines；The carrier is to carry the poly- bad ammonia of polyvinyl alcohol gel particle sodium alginate-
The form of acid-sodium alginate micro-capsule, preparation method are as follows：Polyvinyl alcohol hydrogel is taken, 4- mercaptoethyl pyridine adsorptions are existed
Polyvinyl alcohol hydrogel surface, adsorbance 105-106/, it is 10 that hydrogel ultrasonic machine, which is vibrated into mean size,6-
109The particle of kD；By the sodium alginate of gel particle and a concentration of 15g/L with volume ratio for 1：15 ratio is uniformly mixed, and is inhaled
It is taken into 20ml syringes；It is 10kV, fltting speed 8.5ml/min, tack needle diameter in encystation voltage with electrostatic drop generation
The mixed liquor prepared under conditions of syringe needle is 1cm from liquid level, is instilled 0.1mol/L CaCl by 1mm2In solution, formed
Calcium alginate microsphere removes supernatant after standing 10min, and after brine 3 times, sodium alginate micro ball is put into 0.8g/L
Gather and shake 5min in left lysine solution, remove supernatant, brine 3 times is molten in the sodium alginate for putting into 1.5 g/L
It shakes 5min in liquid, remove supernatant and uses brine, finally with the 55mmol/L sodium citrate solutions liquefaction capsule heart
5min, with brine to get.
7. plasma purification system according to claim 6, which is characterized in that the load polyvinyl alcohol gel particle alginic acid
Sodium-polylysine-sodium alginate micro-capsule, the average mechanical breakage rate after 150 r/min shake 72h is 4.5%.
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