CN106166311A - A kind of novel plasma purification system and application thereof - Google Patents
A kind of novel plasma purification system and application thereof Download PDFInfo
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- CN106166311A CN106166311A CN201610769868.7A CN201610769868A CN106166311A CN 106166311 A CN106166311 A CN 106166311A CN 201610769868 A CN201610769868 A CN 201610769868A CN 106166311 A CN106166311 A CN 106166311A
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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
- 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
- A61M2205/02—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 system, including ligands specific 1 (immunoadsorbent) (1), histocompatibility carrier (3), part 2 (2) and plasma purifier.Described ligands specific 1 still keeps its immunologic competence, ligand 1 is partially embedded in carrier surface, ligand 1 can be specific binding with the specific virulence factor (antibody) in blood, makes a large amount of virulence factor keep combined state, and only a small amount of morbid substance is that free state is scattered in blood plasma.Periodically carrier protein is removed together with virulence factor by plasma purifier specific binding ligand 2.The present invention can virulence factor in specific binding blood, making it is combined state, so that the virulence factor of free state keeps low concentration state for a long time, reduces tissue involved, interrupt internal " immunity storm ", reduce patients blood plasma and purify number of times, reduce complication rate.
Description
Technical field
The present invention relates to field of medical technology, specifically, be a kind of novel plasma purification system and application thereof.
Background technology
Plasma purification therapy is primarily referred to as removing morbid substance in blood plasma the most in a large number, improves patient clinical disease
Shape, thus reach to treat the purpose of disease.Have been developed in many selectivitys for different morbid substance at present on this basis
Filter and remove or the technology of adsorption removal, including plasmapheresis, Cured by Double Filtration Plasmapheresis plasma purification technology (double-filtration
Plasmapheresis, DFPP), cold filtration method, hot filtration method, the heparin-induced LDL sedimentation method, plasma adsorption technology (plasma
Absorption, PA) etc..Technology range of application has been extended to hundreds of disease of each system the most.Rheumatological disease
The most often there is the virulence factors such as multiple autoantibody, complement, immune complex, inflammatory factor, use plasma purification
Therapy can specifically remove above-mentioned virulence factor, and then reaches to treat the purpose of disease.
Rheumatological disease produces too much due to virulence factor in the patient or body cannot be removed in time, causes pathogenic
The serological concentration of the factor extends in time and builds up, and as indicated by a broken line in fig. 1, plasma purification used in the market is treated
Rule is to be replaced/dialyse by virulence factor/adsorb/filter out external termly by plasma purification therapy, such as Fig. 1 solid line institute
Showing, virulence factor serum-concentration presents undulatory property and changes.Thus this type of patient needs for a long time, rule row plasma purification guarantee
Virulence factor is cleared up in time, it addition, plasma purification therapy, required fresh plasma is many, frequency is high, expensive, complication is many:
Hypotension, anaphylaxis, haemolysis, hypertension, arrhythmia etc..
The present invention provides a kind of novel plasma purification mode.For certain specific rheumatological disease, can
The antibody specific binding with virulence factor is embedded into carrier surface, and regular injections is in the patient, makes virulence factor keep
Combined 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 combined, virulence factor is the most in rising trend.If it is clean to occur that the node before rising carries out blood plasma at virulence factor
Change, clear out together with carrier external by the virulence factor of combined state, then virulence factor concentration is relatively steady, as Fig. 2 is shown in solid.
Summary of the invention
It is an object of the invention to for deficiency of the prior art, it is provided that a kind of novel plasma purification system.
Another purpose of the present invention is to provide a kind of novel plasma purification mode.
For achieving the above object, the present invention adopts the technical scheme that:
A kind of novel plasma purification system, including carrier and external plasma purifier, the absorption of described carrier surface is special
Property part-1 and ligands specific-2；Described ligands specific-1 keeps its immunologic competence, and part-1 is partially embedded in carrier
Surface, can be specific binding with the specific morbid substance in blood, makes a large amount of morbid substance keep combined state, causes a disease the most on a small quantity
Material is that free state is scattered in blood plasma；Described external plasma purifier specific binding ligand 2 by carrier together with pathogenic because of
Son is removed together.
Further, described carrier is liposome, bio-compatibility albumen, artificial red cells, biomacromolecule or macromolecule
Gel particle, can be present in the most in a large number in normal human blood and not cause immunological rejection.
Further, described ligands specific-1 is polyclonal antibody, monoclonal antibody, 4-mercaptoethyl pyridine, sulphuric acid Portugal
Polysaccharide, tryptophan, phenylalanine, polyanion, polylysine, the albumin that methylates, Clq, anti-LDL antibody, anti-IgE resist
Body, antinuclear antibody part, extractibility antigen, DNA, core Zhou Yinzi, MAG/SPGP, ganglioside, immune complex.
Further, described ligands specific-1 adsorbs or is embedded in inside carrier surface or liposome, artificial peplos, special
The adsorbance of property part-1 is 105-106/；Described part-2 adsorbs or is embedded in carrier surface, and the adsorbance of part-2 is the least
Adsorbance in part-1.
Further, described plasma purifier is filtering device, liposome adsorption column, chromatographic column；In plasma purifier
The antibody that distribution can be specific binding with part-2 in a large number.
Further, the present invention also provides for the plasma purification system of a kind of improvement, including carrier and external plasma purifier,
Described carrier surface absorption ligands specific-1, described carrier is presented in microcapsule；Described ligands specific-1 keeps it
Immunologic competence, part-1 is partially embedded in carrier surface, can be specific binding with the specific morbid substance in blood, makes a large amount of
Morbid substance keeps combined state, and only a small amount of morbid substance is that free state is scattered in blood plasma；Described external plasma purifier
Including activated carbon or filter membrane defecator.Being filtered by APA peplos by activated carbon or filter membrane, AchRab is filtered with carrier
Crossing, other compositions are fed back into human body again.Further, described carrier is polyvinyl alcohol hydrogel granule, described ligands specific-
1 is 4-mercaptoethyl pyridine；Described carrier is to carry polyvinyl alcohol gel granule sodium alginate-polylysine-sodium alginate microcapsule
Form, its preparation method is as follows: take polyvinyl alcohol hydrogel, by 4-mercaptoethyl pyridine adsorption at polyvinyl alcohol hydrogel table
Face, adsorbance is 105-106/, hydrogel ultrasonic machine is vibrated into mean size is 106-109KD granule；By gel particle
Mix homogeneously with the sodium alginate that concentration the is 15g/L ratio with volume ratio as 1:15, draw into 20ml syringe.Use electrostatic liquid
Dripping method, is 10kV at encystation voltage, and fltting speed is 8.5ml/min, tack pin diameter 1mm, and syringe needle is 1cm's from liquid level
Under the conditions of, the mixed liquor prepared is instilled 0.1mol/L CaCl2In solution, form calcium alginate microsphere, after standing 10min
After removing supernatant, brine 3 times, sodium alginate micro ball is put into 0.8g/L and gathers in left lysine solution and shake
5min, removes supernatant, brine 3 times, shakes 5min, remove supernatant in the sodium alginate soln putting into 1.5g/L
Liquid with brine, finally liquefies capsule heart 5min with 55mmol/L sodium citrate solution, with brine, i.e.
?.
Further, described load polyvinyl alcohol gel granule sodium alginate-polylysine-sodium alginate microcapsule, at 150r/
Average mechanical breakage rate after min shaking 72h is 4.5%.
Further, in described plasma purification system can make patients blood plasma, virulence factor is maintained at low concentration state for a long time, resistance
Only tissue involved increases the weight of, and reduces required plasma purification number of times significantly, significantly reduces complication rate, and it is clean to reduce blood plasma
The amount of gasifying device antibody, reduces cost.
For realizing above-mentioned second purpose, the present invention adopts the technical scheme that:
A kind of novel carriers plasma purification mode, including carrier and external plasma purifier, described carrier surface adsorbs
Ligands specific-1 and ligands specific-2；Described ligands specific-1 keep its immunologic competence, part-1 be partially embedded in
Carrier surface, can be specific binding with the specific morbid substance in blood, makes a large amount of morbid substance keep combined state, the most on a small quantity
Morbid substance is that free state is scattered in blood plasma；Described external plasma purifier is filtering device, liposome adsorption column, chromatography
Post；The antibody that in plasma purifier, a large amount of distributions can be specific binding with part-2；Described plasma purification mode is as follows:
(1) the regular intravenous injection of carrier protein or instillation, part-1 is specific binding with the virulence factor in blood to be become to tie
Close state；
(2) when carrier is close to or up time saturated, promoting the circulation of blood external liquid circulation；
(3) blood flows through plasma purifier through loop, and the part-2 antigen in plasma purifier is combined quilt
Isolate blood plasma；
(4) blood plasma after separating feeds back into human body, again supplements the plasma fraction of new carrier and loss.
In described plasma purification method can make patients blood plasma, virulence factor is maintained at low concentration state for a long time, stops tissue to be subject to
Tired degree increases the weight of, and reduces required plasma purification number of times significantly, 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, the carrier of the present invention is the biomacromolecule that human body self exists, and can be present in the most in a large number in blood of human body,
Embed antibody-1 thereon can specific binding with virulence factor become combined state, reduce free state virulence factor concentration.And with
Past plasma purification mode the concentration of free state virulence factor can only could be dropped to when regular plasma purifies normal range with
In.
2, the carrier of the present invention can combine virulence factor in a large number so that it is in combined state, reduces required blood plasma significantly clean
Change number of times, significantly reduce complication rate.
3, the antibody-1 of the present invention can select different antibody-1 according to not same disease, and therefore indication is the widest.Such as,
Antibody-1 is AchR (acetylcholinergic receptor) antigenic determinant, the most adsorbable AchRAb (acetylcholine receptor antibodies), treatment weight
Disease myasthenia；If antibody-1 is phenylalanine, dextran sulfate, anti-igg Fc antibody, the most adsorbable anti-DNA antibody, CIC, wolf
Skin ulcer anticoagulant substanceses etc., for systemic lupus erythematosus.
Accompanying drawing explanation
Accompanying drawing 1 is the change of virulence factor serum-concentration in plasma purification therapy in prior art, and virulence factor serum is dense
Degree presents undulatory property and changes.
Accompanying drawing 2 be the present invention novel plasma purification system in the change of virulence factor serum-concentration, the antibody on carrier-
1 can specific binding with virulence factor become combined state, reduce free state virulence factor concentration.
Accompanying drawing 3 is carrier structure schematic diagram of the present invention.
Accompanying drawing 4 is that virulence factor of the present invention adsorbs the schematic diagram of narrow body protein by antibody-1.
Accompanying drawing 5 is fundamental diagram of the present invention.
Accompanying drawing 6 is plasma adsorption purifier profile of the present invention.
Accompanying drawing 7 is adsorption column sectional view of the present invention.
Accompanying drawing 8 is adsorption column profile of the present invention.
The structure that accompanying drawing 9 carries polyvinyl alcohol gel granule sodium alginate-polylysine-sodium alginate microcapsule for the present invention is shown
It is intended to.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is expanded on further.Should be understood that these embodiments are merely to illustrate this
Bright rather than limit the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention records, art technology
The present invention can be made various changes or modifications by personnel, and these equivalent form of values fall within the application appended claims equally and limited
Fixed scope.
The reference and the ingredient that relate in accompanying drawing are as follows:
1. ligands specific-1
2. ligands specific-2
3. carrier
4. virulence factor
5. power set
The most external plasma purifier
7. drainage tube
8. adsorption column
9. adsorptive purifier inflow entrance
10. adsorptive purifier flow export
11. polyvinyl alcohol gel granules
12. sodium alginate-polylysine-sodium alginate microcapsule membranes.
The plasma purification system of embodiment 1 present invention
Refer to Fig. 3-Fig. 8, Fig. 3 is carrier structure schematic diagram of the present invention, and Fig. 4 is that virulence factor of the present invention is by part-1
The schematic diagram of absorption carrier, Fig. 5 is fundamental diagram of the present invention, and Fig. 6 is plasma adsorption purifier profile of the present invention, Fig. 7
Being adsorption column sectional view of the present invention, Fig. 8 is adsorption column profile of the present invention.
Described plasma purification system includes carrier and external plasma purifier, and the surface adsorption specificity of described carrier is joined
Body-1 and ligands specific-2, ligands specific-1 keeps its immunologic competence, and part-1 is partially embedded in carrier surface, can be with
Specific morbid substance in blood is specific binding, makes a large amount of virulence factor keep combined state, and only a small amount of virulence factor is trip
Amorph is scattered in blood plasma.Described carrier is liposome, biomembrane, bio-compatibility albumen, artificial red cells, biological composite wood
Material, biomacromolecule, biological composite aquogel, chitosan or polyvinyl alcohol (PVA), can be present in normal human's blood the most in a large number
Liquid does not cause immunological rejection.Described 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 antibody part, extractibility antigen, DNA, core Zhou Yinzi, MAG/SPGP, ganglioside or exempt from
Epidemic disease complex etc..Ligands specific-1 adsorbs or is embedded in inside carrier surface or liposome, artificial peplos, ligands specific-1
Adsorbance be 105-106/；Described part-2 can be specific antibody, and part-2 adsorbs or is embedded in carrier surface, joins
The adsorbance of body-2, less than the amount of part-1, is 102-103/.Described external plasma purifier is filtering device, liposome
Adsorption column, chromatographic column；The antibody that in plasma purifier, a large amount of distributions can be specific binding with part-2.Carrier is instilled patient
In blood, the ligands specific-1 of carrier surface absorption can sorption cycle virulence factor in blood in a large number so that it is from dissociating
State is converted into combined state, when carrier adsorption amount reaches saturated, and the external plasma purification of row, see Fig. 3, drainage tube (7) two ends are divided
Not and human body arteriovenous anastomosis (idiographic flow can be found in hemodialysis principle), blood pumps out external through power set, flows through suction
Attached purifier.The antigen that in a large number can with part-2 be combined is distributed in adsorption column in adsorptive purifier, see Fig. 5,6,
Virulence factor is adsorbed in purifier with carrier, and other compositions are fed back into human body again.
As a example by the plasma purification of systemic lupus erythematosus (sle) is treated, in Fig. 1, ligands specific-1 can be phenylalanine, sulfur
Acid glucosan, tryptophan, protein A, anti-igg Fc antibody, polymyxin B etc., can specific adsorption virulence factor (4), namely
Anti-DNA antibody, CIC, Lupus anticoagulant, LDL, IgG, permeability factor etc..Ligands specific-2 can be polylysine.Will
Be embedded with in a large number the carrier of phenylalanine, dextran sulfate etc. periodically, the most quiet instillation blood of human body, can sorption cycle in a large number
The virulence factors such as the Lupus anticoagulant in blood so that it is be converted into combined state from free state.When carrier adsorption amount reaches full
And time, the external plasma purification of row, see Fig. 3, (idiographic flow can be found in human body arteriovenous anastomosis respectively at drainage tube (7) two ends
Hemodialysis principle), blood pumps out external through power set, flows through adsorptive purifier.Adsorption column in adsorptive purifier
The antigen that in a large number can with part-2 be combined inside is distributed, see Fig. 5,6, virulence factor is adsorbed in purifier with carrier,
Other compositions are fed back into human body again.Again by carrier periodically, the most quiet instillation blood of human body.
Advantages of the present invention:
1, the carrier of the present invention is the biomacromolecule that human body self exists, and autoimmune rejection will not be caused to react, can
Be present in a large number in blood of human body for a long time, embed part-1 thereon can specific binding with virulence factor become combined state, reduce
The concentration of free state virulence factor.And free state could can only be caused a disease by conventional plasma purification mode when regular plasma purifies
Within the concentration of the factor drops to normal range.
2, the carrier of the present invention can combine virulence factor in a large number so that it is in combined state, and required plasma purification is greatly reduced
Number of times, significantly reduce complication rate, reduce blood plasma aequum.By contrast, conventional simple plasmapheresis but needs a large amount of new
Blood is starched, the risk of hematogenous infectious disease is higher.
3, the part-1 of the present invention is not just for monoclonal antibody, can also be designed as polyclonal antibody, as anti-LDL antibody,
Anti-alpha-fetoprotein antibody, Anti-HBsAg antibody antibody etc..Thus, indication is extremely wide, can exempt from for rheumatological disease, some non-rheumatism
Epidemic disease disease and emergency treatment emergency case etc..
Embodiment 2 myasthenia gravis plasma purification system
As a example by the plasma purification of myasthenia gravis is treated, part-1 is 4-mercaptoethyl pyridine, can specific adsorption cause
Cause of disease (4), namely anti-acetylcholine receptor antibodies (AchRab).First, preparing vectorette, carrier is by 4-mercaptoethyl
Pyridine, polymer gel particle, peplos form.The raw material of polymeric particles can be polyacrylamide gel, poly-isopropyl propylene
Amide, agar, alginate, chitosan, glucosan, celluloid etc., as a example by polyvinyl alcohol (PVA) hydrogel.
(1) PVA can be prepared by methods such as crosslinking with radiation, chemical agent crosslinkings, repeatedly freeze-thaw: proportioning weighs PVA, takes
Deionized water, is stirred together for PVA, is placed under 85～90 DEG C of constant temperatures dissolving completely, puts into the refrigerator freezing 24 of-20 DEG C
Hour, then thaw at RT 1 hour, it is referred to as circulation the most freezing, melt and dissolved.Prepare variable concentrations, identical the most respectively
Cycle-index and same concentrations, the PVA hydrogel of different cycle-index.
(2) use investment, absorption method, combined techniques or crosslinking fixation by appropriate 4-mercaptoethyl pyridine and PVA water-setting
Cementing conjunction.The hydrogel ultrasonic machine made is vibrated into mean size is 106-109The granule of kD.
(3) sodium alginate-polylysine-sodium alginate (APA) peplos is made: gel particle step 2 prepared is with dense
The sodium alginate that degree the is 15g/L ratio mix homogeneously with volume ratio as 1:15, draws into 20ml syringe.Use electrostatic drop
Method, is 10kV at encystation voltage, and fltting speed is 8.5ml/min, tack pin diameter 1mm, and syringe needle is the bar of 1cm from liquid level
Under part, the mixed liquor prepared is instilled 0.1mol/L CaCl2In solution, form calcium alginate microsphere, remove after standing 10min
Remove supernatant, after brine 3 times, sodium alginate micro ball put into 0.8g/L and gathers in left lysine solution and shake 5min,
Remove supernatant, brine 3 times, the sodium alginate soln putting into 1.5g/L shakes 5min, removes supernatant also
With brine, finally with 55mmol/L sodium citrate solution liquefaction capsule heart 5min, with brine, obtain parcel
The APA of gel particle.Carry structure such as Fig. 9 institute of polyvinyl alcohol gel granule sodium alginate-polylysine-sodium alginate microcapsule
Show.
(4) microcapsule membrane intensity: take the APA microcapsule of step 3 preparation, with 100 microcapsule/groups, put normal saline, in 37 DEG C,
150r/min shakes, respectively at 1, and 2,4,8,12,24,36,48h samplings, investigate microcapsule membrane mechanical strength.Parallel laboratory test 3 times, meter
Calculate microcapsule mechanical damage rate.The average mechanical breakage rate of result display 72h microcapsule membrane is 4.5%.Take 100 microcapsule/groups, super
The ultrasonic power of sound washer is ultrasonic 1h under conditions of 500W, and breakage does not occurs in APA microcapsule, and continuous ultrasound 2h, under microscope
The averaging ultrasound breakage rate observing and being calculated cyst membrane is 5.0%.
(5) take appropriate carrier and the glucose solution of 5% and other medical accessories are mixed and made into mixed liquor, quiet instillation human body
Blood.Carrier is distributed in Ink vessel transfusing, constantly circulates with blood flow, and the AchRAb of the circulation in blood plasma enters in the hole on APA peplos
Enter in peplos, be combined with 4-mercaptoethyl pyridine, by a large amount of sorption cycle in APA peplos so that it is be converted into knot from free state
Close state, in each peplos adsorbable 105-106Individual AchRAb.When carrier adsorption amount reaches saturated, the external plasma purification of row, ginseng
See Fig. 3, drainage tube (7) two ends respectively with human body arteriovenous anastomosis (idiographic flow can be found in hemodialysis principle), blood is through dynamic
Power apparatus pumps out external, flows through adsorptive purifier, and adsorptive purifier includes activated carbon or filter membrane defecator.By work
Property charcoal or filter membrane by APA peplos filter, AchRab is filtered across with carrier, and other compositions are fed back into human body again.
Advantages of the present invention:
1, the carrier outer layer of the present invention is artificial peplos, without antigen, because of without causing autoimmune response, Bu Huichen
Amass in blood vessel wall；" it is stranded " in peplos after AchRAb is adsorbed by high-molecular gel, will not be combined with self AchR, thus avoid certainly
The destruction of body AchR, avoids increasing the weight of of myasthenia gravis from root.
2, the carrier of the present invention can receive AchRAb in a large number so that it is in combined state, blood plasma once next day of greatly reducing
The frequency purified, reduces required plasma purification number of times (becoming the 1 time/1-2 month from 1 time/2 days) significantly, significantly reduces concurrently
Disease rate.
3, the present invention be expert at external plasma purification time owing to only artificial peplos need to be removed, the amount of artificial peplos is AchRAb
The 1/10 of amount5-106, therefore clearance rate is higher, shorten cardiopulmonary bypass time, reduce complication rate, required adsorption column amount lower,
Greatly reduce cost.Plasma treatment amount can mention higher level from 9L.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, on the premise of without departing from the inventive method, it is also possible to makes some improvement and supplements, and these improve and supplement and also should be regarded as
Protection scope of the present invention.
Claims (9)
1. a novel plasma purification system, it is characterised in that include carrier and external plasma purifier, described carrier surface
Absorption ligands specific-1 and ligands specific-2；Described ligands specific-1 keeps its immunologic competence, ligands specific-1
It is partially embedded in carrier surface, can be specific binding with the specific virulence factor in blood, make a large amount of virulence factor keep combining
State, only a small amount of morbid substance is that free state is scattered in blood plasma；Described external plasma purifier specific binding ligand 2 will
Carrier is removed together with virulence factor.
The most novel plasma purification system, it is characterised in that described carrier is liposome, biomembrane, life
Thing compatibility albumen, artificial red cells, Biocomposite material, biomacromolecule, biological composite aquogel, chitosan or polyethylene
Alcohol (PVA), can be present in the most in a large number in normal human blood and not cause immunological rejection.
The most novel plasma purification system, it is characterised in that described ligands specific-1 is Anti-TNF-α
Body, monoclonal antibody, Fc fragment, part, polyclone antigen, monoclonal antibodies, 4-mercaptoethyl pyridine, dextran sulfate, color
Propylhomoserin, phenylalanine, polyanion, polylysine, the albumin that methylates, Clq, anti-LDL antibody, anti-IgE antibodies, anti-core resist
Body part, extractibility antigen, DNA, core Zhou Yinzi, MAG/SPGP, ganglioside, immune complex.
The most novel plasma purification system, it is characterised in that the absorption of described ligands specific-1, embedding
In carrier surface or be contained in inside liposome, artificial peplos, ligands specific-1 is for adsorbing virulence factor, adsorbance in a large number
It is 104-106/, suction type is antigen-antibody combination, antibodies, Fc combination, hydrophobic binding, electrostatical binding；Described join
Body-2 adsorbs or is embedded in carrier surface, is adsorbed in adsorption column when external removing, and the adsorbance of part-2 is much smaller than joining
The adsorbance of body-1.
The most novel plasma purification system, it is characterised in that described external plasma purifier is for selecting
Property adsorber, filter, chromatographic column；The part that in plasma purifier, a large amount of distributions can be specific binding with part-2.
The most novel plasma purification system, it is characterised in that described carrier is polyvinyl alcohol hydrogel
Grain, described ligands specific-1 is 4-mercaptoethyl pyridine；Described carrier relies carrying polyvinyl alcohol gel granule sodium alginate-poly-
The form of propylhomoserin-sodium alginate micro-capsule, its preparation method is as follows: take polyvinyl alcohol hydrogel, by 4-mercaptoethyl pyridine adsorption
On polyvinyl alcohol hydrogel surface, adsorbance is 105-106/, hydrogel ultrasonic machine is vibrated into mean size is 106-
109The granule of kD；Gel particle is mixed homogeneously with the sodium alginate that concentration the is 15g/L ratio with volume ratio as 1:15, inhales
It is taken into 20ml syringe；With electrostatic drop generation, being 10kV at encystation voltage, fltting speed is 8.5ml/min, tack pin diameter
1mm, the mixed liquor prepared, under conditions of liquid level is 1cm, is instilled 0.1mol/L CaCl by syringe needle2In solution, formed
Calcium alginate microsphere, stands and removes supernatant after 10min, after brine 3 times, sodium alginate micro ball is put into 0.8g/L
Gather and left lysine solution shakes 5min, removing supernatant, brine 3 times, molten at the sodium alginate putting into 1.5g/L
Liquid shakes 5min, removes supernatant and with brine, finally with the 55mmol/L sodium citrate solution liquefaction capsule heart
5min, with brine, to obtain final product.
The most novel plasma purification system, it is characterised in that described load polyvinyl alcohol gel granule Sargassum
Acid sodium-polylysine-sodium alginate micro-capsule, the average mechanical breakage rate after 150r/min shaking 72h is 4.5%.
8. a novel carriers plasma purification mode, it is characterised in that include carrier and external plasma purifier, described carrier
Surface adsorption ligands specific-1 and ligands specific-2；Described ligands specific-1 keeps its immunologic competence, part-1
Subpackage is embedded in carrier surface, can be specific binding with the specific morbid substance in blood, makes a large amount of morbid substance keep combined state,
Only a small amount of morbid substance is that free state is scattered in blood plasma；Described external plasma purifier is filtering device, liposome suction
Attached column, chromatographic column；The antibody that in plasma purifier, a large amount of distributions can be specific binding with part-2；Described plasma purification mode
As follows:
(1) the regular intravenous injection of carrier or instillation, part-1 specific binding with the virulence factor in blood become combined state；
(2) when carrier is close to or up time saturated, promoting the circulation of blood external liquid circulation；
(3) blood flows through plasma purifier through loop, and part-2 combines with the antigen in plasma purifier and separated
Go out blood plasma；
(4) blood plasma after separating feeds back into human body, again supplements the plasma fraction of new carrier and loss.
9., according to the plasma purification system described in claim 1-7, plasma purification mode described in claim 8, its feature exists
In, in can making patients blood plasma, virulence factor is maintained at low concentration state for a long time, stops tissue involved to increase the weight of, subtracts significantly
Few required plasma purification number of times, significantly reduce complication rate, and the amount of antibody and need to mend needed for reducing plasma purifier
The plasma volume filled, reduces cost, reduces Clinical practice threshold.
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| EP4548941A4 (en) * | 2022-08-12 | 2025-08-27 | Gogen Tech Ltd | System for recovering antigen in a solvent and method for recovering antigen in a solvent |
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| CN106166311B (en) | 2018-07-13 |
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