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EP3952945A1 - Procédé et dispositif d'épuration du sang - Google Patents

Procédé et dispositif d'épuration du sang

Info

Publication number
EP3952945A1
EP3952945A1 EP20718276.7A EP20718276A EP3952945A1 EP 3952945 A1 EP3952945 A1 EP 3952945A1 EP 20718276 A EP20718276 A EP 20718276A EP 3952945 A1 EP3952945 A1 EP 3952945A1
Authority
EP
European Patent Office
Prior art keywords
blood plasma
blood
plasma
value
anion exchanger
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20718276.7A
Other languages
German (de)
English (en)
Inventor
Peter MANDRY
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
B Braun Avitum AG
Original Assignee
B Braun Avitum AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by B Braun Avitum AG filed Critical B Braun Avitum AG
Publication of EP3952945A1 publication Critical patent/EP3952945A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • 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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3479—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate by dialysing the filtrate
    • 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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496—Plasmapheresis; Leucopheresis; Lymphopheresis
    • 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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
    • 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
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3324—PH measuring means

Definitions

  • the present invention relates to a method for purifying blood
  • the invention further relates to the use of a diethylaminoethyl (DEAE) anion exchanger, in particular a DEAE anion exchanger with tentacle technology, for purifying
  • DEAE diethylaminoethyl
  • Lung cancer is the cause of death. Sepsis is the third most common cause of death in Germany.
  • the Sepsis Competence Network gives the following figures: 550,000 illnesses, 146,000 deaths per year, death rate 26.5%. From a global perspective, sepsis is a common cause of death according to the data from the Sepsis Competence Network: around 1,500,000 diseases occur annually, which lead to 500,000 deaths, which corresponds to a death rate of 33.3%.
  • LTA lipoteichoic acid
  • LPS lipopolysaccharides
  • DNA deoxyribonucleic acid
  • RNA ribonucleic acid
  • Viruses, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from the blood of a patient is known from the prior art, ion exchange chromatography using ion exchangers or ion adsorbers.
  • DNA deoxyribonucleic acid
  • RNA ribonucleic acid
  • anion exchangers remove pathogenic substances such as endotoxins, viruses, deoxyribonucleic acid (DNA) and
  • RNA Ribonucleic acid
  • essential blood components such as clotting factors
  • Acute phase proteins belong and are therefore in some cases only slowly reproduced, which is why the unintentional removal of these proteins has particularly serious and long-lasting consequences for patient safety.
  • H.E.L.P. apheresis heparin-induced extracorporeal LDL precipitation
  • Plasma obtained is precipitated by adding acetate buffer for acidification and heparin, LDL (low density lipoprotein) cholesterol, fibrinogen and lipoprotein (a).
  • the precipitate is then removed from the treated plasma using a special filter and excess heparin by adsorption. Finally, bicarbonate dialysis is performed to restore the plasma to its initial volume and a physiological pH. The purified plasma is combined with the blood cells and returned to the patient.
  • the H.E.L.P. Apheresis is mainly used for the treatment of severe, otherwise therapy-refractory lipid metabolism disorders and theological diseases, such as sudden hearing loss.
  • a method for supporting the liver function is known from the prior art, in which the pH value of the blood plasma is increased and decreased in order to reduce the strength of the binding of protein-bound molecules to albumin.
  • the pH value of the blood plasma is increased and decreased in order to reduce the strength of the binding of protein-bound molecules to albumin.
  • Anion exchangers are ion exchangers in which a cationic group (cation) is covalently bound to a solid, insoluble matrix, while the neutralizing anion (neutral) is only ionically bound and can therefore be exchanged for other anions.
  • a cationic group cation
  • neutral neutralizing anion
  • Anion exchangers (anion exchange chromatography) is an important tool for the analysis and binding of proteins and nucleic acids or their components, the peptides, amino acids, oligonucleotides and mononucleotides.
  • anion exchangers are aminoethyl, diethylaminoethyl (DEAE), quaternary aminoethyl (QAE) and quaternary ammonium groups, coupled to cellulose, agarose (agar), dextran (dextrans) or polystyrene. DEAE cellulose is often used.
  • Diethylaminoethyl (DEAE) ion exchangers with tentacle technology have a very high binding capacity and binding strength and are therefore particularly effective in removing pathogens and endotoxins even with complex solutions such as human plasma.
  • DEAE ion exchangers are among the most effective known
  • Endotoxin and virus binders are used with great success in technology, especially in biotechnology, chemical engineering and process technology.
  • Tentacle technology uses special gels for chromatography, which have thread-like structures, the so-called tentacles. These tentacles carry charges over their entire length and can thus carry the substances to be separated, e.g. Proteins, depending on their load, hold or
  • Binding than normal gels which have a smaller surface.
  • DEAE ion exchangers also known as DEAE adsorbers
  • LTA lipoteichoic acid
  • LPS Lipopolysaccharides
  • Blood clotting is switched off and the patient can bleed to death.
  • the present invention is based on the object of alleviating or eliminating the problems known from the prior art.
  • the present invention is based on the object of providing a clinically applicable method and a device for effective blood purification with high patient safety at the same time.
  • Another aspect of the present invention relates to the use of a DEAE anion exchanger according to claim 12.
  • One aspect of the invention relates to a method for purifying blood, in particular blood plasma, with the steps:
  • the core idea of the invention is that by means of the adjustment of the pH, the charge of proteins, such as, for example, coagulation factors, is selectively and consciously changed and adjusted.
  • the adsorption on the ion exchanger and thus the removal of proteins, such as the coagulation factors, from the blood depends on the charge of the proteins / molecules.
  • the predetermined protein is preferably a coagulation factor, for example factor I, factor II, factor IV, factor V, factor VI, factor VII, factor VIIa, factor VIII, factor IX, factor X, factor XI or factor XII.
  • the method for purifying blood is preferably carried out or used in the context of an extracorporeal blood treatment.
  • Coagulation factors are amphoteric proteins, i. Proteins that have both positive and negative charges. The predominant charge depends on the pH of the solution in which the protein / molecule is located.
  • the isoelectric point denotes the pH value at which the number of positive and negative charges of an amphoteric protein / molecule is exactly the same on a statistical average and the entire protein / molecule is therefore electrically neutral.
  • the blood plasma After the blood has been separated into blood plasma and blood cells, the blood plasma initially has a physiological pH of approx. 7.4. Most coagulation factors have a negative charge at a physiological pH of around 7.4. If the pH value of the plasma is shifted towards lower pH values (i.e. into the acidic range), the negative charge of the coagulation factors is reduced. If the pH of the blood plasma reaches the isoelectric point of a certain protein / molecule, e.g. of a coagulation factor, the charge of this specific protein / molecule is neutral and the protein / molecule or the coagulation factor is no longer adsorbed by the ion exchanger and no longer removed from the blood plasma.
  • a certain protein / molecule e.g. of a coagulation factor
  • Non-amphoteric molecules such as LPS, LTA, other endotoxins and viruses generally do not change their charge depending on the pH of the solution in which the endotoxins are located. you are therefore adsorbed by the ion exchanger largely independently of the pH of the surrounding solution.
  • the core idea of the invention to adjust the charge of at least one predetermined protein by adjusting the pH value of the solution surrounding this protein to the pH value corresponding to the isoelectric point of the predetermined protein is applicable to any chromatography method which is electrically charged on the interaction Components (such as ions) is based.
  • the electrically neutral predetermined protein becomes when the pH of the solution surrounding the predetermined protein reaches the isoelectric point of the
  • chromatography process e.g. ion exchange chromatography
  • electrically charged components e.g. ions
  • other undesirable blood plasma components such as e.g. Endotoxins, the electrical charge of which is not neutral, but predominantly positive or predominantly negative, are retained by means of the chromatography process and effectively removed from the blood plasma.
  • the pH value to which the pH value of the blood plasma is adjusted preferably corresponds to the isoelectric point of the predetermined protein except for
  • the pH of the blood plasma can also be adjusted to a pH which is lower than the isoelectric point of the predetermined protein.
  • the predetermined protein is a
  • Coagulation factor, in particular factor II, and / or the pH value of the blood plasma is adjusted to a pH value which is lower than the isoelectric point of the coagulation factor.
  • the pH of the blood plasma can be adjusted by means of a direct or indirect supply of protons (H + ) to the blood plasma, for example in the form of an acidic solution or as a solid and / or by means of dialysis of the blood plasma with an acidic buffer, in particular an acetate buffer , respectively.
  • H + protons
  • hydroxide ions can also be removed from the blood plasma.
  • the pH value of the blood plasma can be neutralized by means of a direct or indirect supply of hydroxide ions (OH-) to the blood plasma and / or by means of dialysis of the blood plasma with a basic buffer, in particular a bicarbonate buffer.
  • Dialysis of the blood plasma with a basic buffer, in particular a bicarbonate buffer has the advantage that excess fluid can be removed from the blood plasma.
  • protons (H + ) can also be withdrawn from the blood plasma.
  • the blood plasma is treated by means of anion exchange chromatography, preferably using a DEAE anion exchanger, in particular a DEAE anion exchanger with tentacle technology.
  • Anion exchange chromatography is limited, but also includes other types of ion exchange chromatography, such as the
  • Cation exchange chromatography or also various multimodal chromatographies, which preferably include ion exchange chromatography.
  • Ion exchangers in which an anionic group (anion) is covalently bound to a solid, insoluble matrix, while the neutralizing cation (neutral) is only ionically bound and therefore exchangeable with other cations.
  • a number or a plurality of predetermined proteins can also be taken into account.
  • the different predetermined proteins of the plurality of proteins can each have different isoelectric points.
  • ion exchange chromatography takes into account the isoelectric points of all proteins of the majority of proteins.
  • the pH of the blood plasma is adjusted to a pH at which all proteins of the plurality of predetermined proteins have a desired charge (positive, neutral, negative).
  • the pH of the blood plasma can be adjusted to an average value of the pH values corresponding to the isoelectric points of the proteins of the plurality of predetermined proteins.
  • the pH of the blood plasma can be adjusted to an average value of the pH values corresponding to the isoelectric points of the proteins of the plurality of predetermined proteins.
  • Blood plasma can also be adjusted to the lowest or the highest of the pH values corresponding to the isoelectric points of the proteins of the plurality of predetermined proteins.
  • Another aspect of the present invention relates to a program product which, when read by a device, causes a device to carry out a method according to the invention.
  • a program product which, when read by a device, causes a device to carry out a method according to the invention.
  • Another aspect of the invention relates to a blood treatment machine, in particular an apheresis machine, which is designed or configured to carry out a method according to the invention.
  • Such a blood treatment machine has, for example:
  • Ion exchanger which is preferably an anion exchanger
  • a dialyzer fluidically connected downstream of the ion exchanger, by means of which dialysis can be carried out using acidic or basic dialysis fluid.
  • the ion exchanger is preferably an anion exchanger
  • DEAE anion exchanger for example a DEAE anion exchanger, in particular a DEAE anion exchanger with tentacle technology.
  • the ion exchanger can also be used for multimodal chromatography, for example with additional hydrophobic
  • Feed device / mixing pump take place, which the blood plasma directly or indirectly supplies protons (H + ), for example in the form of an acidic solution or as a solid.
  • the pH can also be adjusted by means of dialysis of the blood plasma with an acidic buffer, in particular an acetate buffer.
  • an acidic buffer in particular an acetate buffer.
  • a dialyzer fluidly connected upstream of the ion exchanger can be provided, by means of which dialysis using acidic
  • Dialysis fluid (and in principle also basic dialysis fluid) can be carried out.
  • the pH of the blood plasma can be neutralized by means of the
  • Feed device / mixing pump take place, which directly or indirectly supplies hydroxide ions (OH-) to the blood plasma, for example in the form of a basic solution or also as a solid.
  • OH- hydroxide ions
  • the pH of the blood plasma can also be neutralized by means of dialysis of the blood plasma with a basic buffer, in particular a bicarbonate buffer.
  • Dialysis of the blood plasma with a basic buffer, in particular a bicarbonate buffer has the advantage that excess fluid can be removed from the blood plasma.
  • a dialyzer downstream of the ion exchanger is preferably provided, by means of which dialysis can be carried out using basic dialysis fluid (and in principle also acid dialysis fluid) .
  • Another aspect of the invention relates to the use of a DEAE anion exchanger, in particular a DEAE anion exchanger
  • the present invention makes it possible to use anion exchangers, in particular DEAE anion exchangers, in particular DEAE anion exchangers with tentacle technology, for extracorporeal blood treatment / for extracorporeal preparation / purification of blood or blood plasma.
  • Blood plasma can thus be effectively and selectively purified from endotoxins without important components of the blood plasma, such as e.g. Clotting factors are removed from the blood plasma unintentionally.
  • the method according to the invention can be used, for example, in blood banks for treating donor blood.
  • a method according to the invention can also be used in the context of an extracorporeal blood treatment.
  • the invention relates to a method with the steps:
  • the blood plasma can be neutralized by any method, for example by adding a base, OH ions, by removing the H + ions or by means of a basic buffer such as a bicarbonate buffer.
  • the pH of the blood plasma can be reduced by adding H + ions in various forms, for example by adding an acid such as HCl or a buffer with an acidic pH such as an acetate buffer.
  • Has passed through ion exchangers can by adding a base, e.g. NaOH or by dialysis with a basic buffer, e.g. a bicarbonate buffer.
  • a base e.g. NaOH
  • a basic buffer e.g. a bicarbonate buffer
  • an acetate buffer with a pH of approx. 4 is added to the plasma and the pH of the plasma is thus lowered to a pH of approx. 5.
  • the blood plasma then flows through the ion exchanger.
  • Bicarbonate buffer preferably flows through this on the dialysate side.
  • a bicarbonate buffer is used as the dialysis fluid.
  • the blood plasma is physiological
  • Composition including a physiological pH value and blood coagulation factors present in the blood plasma
  • Composition is effectively cleaned of any endotoxins previously contained in the blood plasma, such as LPS, LTA, viruses, etc.
  • 1 shows, by way of example, the adsorption of various coagulation factors on a DEAE anion exchanger at a physiological pH value of the blood plasma.
  • FIGS. 3a-b illustrate the pH-dependent adsorption of various coagulation factors on a DEAE anion exchanger.
  • FIG. 4 shows an example of a device according to the invention.
  • Factors II, IX and X of the blood coagulation cascade were effectively adsorbed by the DEAE anion exchanger and largely removed from the blood. At a point in time t1, the measurable amount of the coagulation factors II, IX and X in the blood plasma is zero. The global coagulation status thus fell to a dangerously low level after treatment with the DEAE anion exchanger.
  • Coagulation factors II and X were no longer adsorbed by the DEAE anion exchanger after a volume of plasma (approx. 3L, after a point in time t2 in FIG. 1) had passed through. Therefore, the amounts of coagulation factors II and X increase after time t2 in FIG. 1.
  • the amounts of coagulation factors II, IX and X remain stable and there is no adsorption on the DEAE anion exchanger.
  • the collapse of the curves at time t3 in FIG. 2 is an artifact and is due to a dilution effect of the rinsing solution present in the system.
  • FIGS. 3a-b illustrate the pFI-dependent adsorption of the
  • Coagulation factors factor I, factor II, factor IV, factor V, factor VI, factor VII, factor VIla, factor VIII, factor IX, factor X, factor XI and factor XII to a DEAE anion exchanger The position of the vertical arrows on the pFI scale shows the isoelectric point of the respective coagulation factors.
  • 3a shows the adsorption of the coagulation factors when the blood plasma has a pH of about 7.4.
  • 3b shows the adsorption of the coagulation factors when the blood plasma has a pH of about 5.1.
  • DNA Deoxyribonucleic acid
  • RNA ribonucleic acid
  • Ion exchange chromatography can therefore selectively influence the adsorption or binding behavior of amphoteric proteins / molecules such as coagulation factors in such a way that these proteins / molecules are not adsorbed or removed from the blood plasma, while non-amphoteric proteins / molecules such as pathogens and endotoxins continue to be effectively adsorbed and thus removed from the blood plasma.
  • Fig. 4 shows schematically the structure of an inventive
  • Blood treatment machine an apheresis machine.
  • the blood machine is connected or can be connected to a patient via a blood inflow line and a blood outflow line.
  • the blood from the blood supply line is pumped through a first feed pump 5 and then flows further into a two
  • Blood cells are separated, the blood plasma from an outlet of the
  • Plasma filter 1 flows out and the blood cells from another outlet of the
  • Plasma filter 1 flow out.
  • the blood plasma separated by the plasma filter 1 is further in a
  • the blood plasma treated in this way is fed from the feed device / mixing pump 2 to a valve / shut-off device for controlling the flow. From there it flows on into an ion exchanger 3, which in this embodiment is an anion exchanger, preferably an anion exchanger with tentacle technology.
  • the blood plasma flows through a blood side of a dialyzer 4, the dialysate side of the dialyzer 4 being supplied with a bicarbonate buffer from another fluid supply / source 6 as dialysis fluid
  • Blood plasma is further fed through a third dialyzer 4 downstream
  • Feed pump 5 promoted and then with the blood cells from the plasma filter 1
  • the treated blood then continues to flow through an air trap with a
  • Air detector in which air bubbles are detected and removed, and flows to another downstream valve / shut-off device to control the
  • the blood treatment machine has a plasma filter 1 for separating blood into blood plasma and blood cells, a supply device / mixing pump 2 fluidly connected downstream of the plasma filter 1 for setting the pH of the Blood plasma, an ion exchanger 3 downstream of the feed device / mixing pump 2, which is preferably an anion exchanger, and a dialyzer 4 fluidically downstream of the ion exchanger 3, by means of which dialysis can be carried out using acidic or basic dialysis fluid.
  • an acetate buffer with a pH of 4 provided by a fluid supply / source 6 is added to the blood plasma by means of the feed device / mixing pump 2 in order to bring the pH of the blood plasma to a Lower the pH value by approx. 5.
  • the blood plasma then flows through a valve / a shut-off device into the ion exchanger 3, which in this embodiment is an anion exchanger, preferably an anion exchanger with tentacle technology.
  • the blood plasma flows through the dialyzer 4. This is flowed through on the dialysate side with a bicarbonate buffer provided by another fluid supply / source 6 and conveyed by a second delivery pump 5 as dialysis fluid. A neutral physiological pH value of the blood plasma is thus restored by the dialyzer 4 and additional liquid is removed from the blood plasma.
  • the purified blood plasma is then reunited with the blood cells from the plasma filter 1 by a third feed pump 5.
  • the pooled and purified blood flows through an air trap with an air detector and another downstream valve / shut-off device and finally from the blood treatment machine back to the patient.

Landscapes

  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Vascular Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • External Artificial Organs (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un procédé d'épuration du sang, comportant les étapes qui consistent à : séparer le plasma sanguin des cellules sanguines, ajuster le pH du plasma sanguin jusqu'à un pH s'approchant d'un point isoélectrique au moins d'une protéine prédéterminée, traiter le plasma sanguin au moyen de la chromatographie d'échange ionique, neutraliser le pH du plasma sanguin, grouper le plasma sanguin et les cellules sanguines. L'invention concerne également un dispositif pour exécuter un procédé de ce type.
EP20718276.7A 2019-04-11 2020-04-07 Procédé et dispositif d'épuration du sang Pending EP3952945A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102019109646.4A DE102019109646A1 (de) 2019-04-11 2019-04-11 Verfahren und Vorrichtung zur Reinigung von Blut
PCT/EP2020/059832 WO2020207992A1 (fr) 2019-04-11 2020-04-07 Procédé et dispositif d'épuration du sang

Publications (1)

Publication Number Publication Date
EP3952945A1 true EP3952945A1 (fr) 2022-02-16

Family

ID=70277379

Family Applications (1)

Application Number Title Priority Date Filing Date
EP20718276.7A Pending EP3952945A1 (fr) 2019-04-11 2020-04-07 Procédé et dispositif d'épuration du sang

Country Status (5)

Country Link
US (1) US20220347366A1 (fr)
EP (1) EP3952945A1 (fr)
CN (1) CN113874055A (fr)
DE (1) DE102019109646A1 (fr)
WO (1) WO2020207992A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022115390A1 (fr) * 2020-11-25 2022-06-02 Cytostorm, Inc. Systèmes et procédés de séparation, d'adsorption et de distribution de plasma extracorporels
CN114602237B (zh) * 2022-03-10 2023-11-28 华兰生物工程股份有限公司 一种从人血浆或人血浆衍生原料中去除内毒素的方法

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AT507847B1 (de) * 2009-01-22 2011-12-15 Fresenius Medical Care De Gmbh Sorptionsmittel zum entfernen proteingebundener substanzen
AT507846B1 (de) * 2009-01-22 2011-12-15 Fresenius Medical Care De Gmbh Sorptionsmittel für endotoxine
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AU2012304763A1 (en) * 2011-09-06 2014-03-06 Medimmune Llc Methods for processing coagulation factors
CN106267401B (zh) * 2016-08-31 2018-12-18 武汉仝干医疗科技股份有限公司 基于中空纤维管的物理人工肝纳米碳甲壳素复合物吸附反应器
CN108743924B (zh) * 2018-06-13 2021-10-08 苏州良辰生物医药科技有限公司 一种固定化蛇毒凝血因子激活剂及活化凝血因子的制备方法

Also Published As

Publication number Publication date
US20220347366A1 (en) 2022-11-03
WO2020207992A1 (fr) 2020-10-15
CN113874055A (zh) 2021-12-31
DE102019109646A1 (de) 2020-10-15

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