WO2000059551A1 - Inactivation photodynamique de virus dans des liquides biologiques - Google Patents

Inactivation photodynamique de virus dans des liquides biologiques Download PDF

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Publication number
WO2000059551A1
WO2000059551A1 PCT/EP2000/002845 EP0002845W WO0059551A1 WO 2000059551 A1 WO2000059551 A1 WO 2000059551A1 EP 0002845 W EP0002845 W EP 0002845W WO 0059551 A1 WO0059551 A1 WO 0059551A1
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WIPO (PCT)
Prior art keywords
blood
phase
plasma
biological fluid
viruses
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PCT/EP2000/002845
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German (de)
English (en)
Inventor
Gerhard Saalmann
Peter Saalmann
Norbert H. Brockmeyer
Klaus Hoffmann
Peter Altmeyer
Darius Alamouti
Original Assignee
Gerhard Saalmann
Peter Saalmann
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Publication date
Application filed by Gerhard Saalmann, Peter Saalmann filed Critical Gerhard Saalmann
Priority to AU38163/00A priority Critical patent/AU3816300A/en
Publication of WO2000059551A1 publication Critical patent/WO2000059551A1/fr

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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
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0088—Liquid substances
    • 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
    • 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
    • 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
    • A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
    • A61M1/3683—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents

Definitions

  • the invention concerns a device and a process for the inactivation of viruses in biological fluids, especially for the inactivation of viruses - especially HIN - in blood and blood products in which photosensitizers, preferably phenothiazine dyes, especially toluidine blue or methylene blue, are added to the biological fluid.
  • photosensitizers preferably phenothiazine dyes, especially toluidine blue or methylene blue
  • European patent 0 491 757 Bl shows a process for the inactivation of viruses in blood in which the solutions or suspensions to be treated are mixed with phenothiazine dyes and subsequently bombarded with electromagnetic radiation.
  • the phenothiazine dyes are used in a concentration of 0.1 to 2 M, and the irradiation takes place directly in transparent containers such as blood pouches which are used for collecting and storing blood.
  • Phenothiazine dyes react with the membrane structures of sheathed viruses or with the viral DNA and RNA and damage them under the influence of visible light.
  • EP 0 471 794 Bl shows the use of xanthene or thiazine dyes for the production of a pharmaceutical agent for the selective inactivation of the HIV in vivo or in vitro without significant toxicity for cells or the patient.
  • the xanthene or thiazine dyes were tested on peripheral blood mononuclear cells. The treated cells were irradiated after treatment with dye. Testing on whole blood or plasma was not reported.
  • US Patent No. 4,737,140 to Lee et al. shows an irradiation chamber for extracorporeal phototherapy of blood.
  • the apparatus collects and separates blood on a continuous basis as it is withdrawn from a patient and returns unwanted portions to the patient. The remainder is passed through an irradiation chamber where it is subjected to phototherapy.
  • the patent is directed to cancer treatment. The use of dyes and the treatment of viral infections are not shown. Infection by the human immunodeficiency virus (HIV) induces directly or indirectly an immunity weakness which is most clearly reflected in the loss of the CD4-positive T-lymphocytes. Other cells which carry CD4 receptors are the monocytes, macrophages, dendritic cells, microglia and nerve cells.
  • HIV human immunodeficiency virus
  • HIV disease and AIDS which are characterized especially by the occurrence of opportunistic infectious diseases, dermatoses and tumors.
  • therapy is now administered not only based on the CD4 cell count/ ⁇ l or the appearance of HIV-associated diseases but also based on the virus load (HIV-RNA copies/ml). It is known that patients with a high virus load display a progressing course of the disease. In the meanwhile, a large number of preparations have become available for therapy. The goal of the therapy must be to lower the virus load by at least two logio steps or to bring it below the limits of detection.
  • the invention has as an objective, developing a device and a process for reducing the viral load of biological fluids - especially the blood of a patient ⁇ which achieves a significant reduction in the viral load of the biological fluid without major functional impairments of the lymphocytes of the blood.
  • viral load is meant the number of viable active virus copies in the blood in terms of copies per unit volume.
  • the present invention pertains to a device or for the inactivation of viruses in biological fluids, especially for the inactivation of viruses — especially HIV - in blood and blood products, in which photosensitizers, preferably phenothiazine dyes, especially toluidine blue or methylene blue, are added to the biological fluid with: a single-part or multi-part pump and transport device for collecting the biological fluid from a blood circulation, for passing the biological fluid through a conduit system and for returning the biological fluid to the blood circulation, a separating device for separating the biological fluid into different liquid phase and/or liquid and solid phases, especially for separation into blood plasma and corpuscular elements; in which the conduit system and/or a container connected to the conduit system are designed to be transparent at least in some segments; and with a light source for emitting electromagnetic radiation, especially of the visible spectrum, onto the light- permeable conduit system segment or the light-permeable container.
  • photosensitizers preferably phenothiazine dyes, especially toluidine blue or
  • Fig. 1 is a schematic drawing of the device of the present invention.
  • Fig. 2 is a schematic drawing of an alternative embodiment of the device of the present invention.
  • a single-part or multi-part transport device for collecting the biological fluid from the blood circulation, for passing the biological fluid through a conduit system, and for returning the biological fluid to the blood circulation.
  • the blood is taken from the blood circulation of the patient in order to be directly bombarded with visible light in the transparent conduit system or container or in the separating device.
  • the blood may be any blood that can be infected with a virus, although the present invention will be most useful with mammals. Typical mammals with which the present invention is useful include humans, dogs, cats, cows, pigs, monkeys, apes, sheep, goats, horses, rodents, mice, rats, and rabbits.
  • the invention makes use of a separating device for dividing the blood up into different liquid phases, especially plasma and corpuscular components, where then only the plasma phase is irradiated with visible light. After this all phases of the blood are returned together or separately to the blood circulation.
  • the process is also suitable for the treatment, from containers of any kind, of biological fluids that can be divided into phases and can be brought together again after the application of the "phototherapy".
  • the blood of a patient can be irradiated with UV radiation (see U.S. Patent 4,737,140).
  • the present invention is a vast improvement over such older technologies.
  • UV irradiation is a therapy procedure introduced long ago in which the skin is irradiated with ultraviolet radiation (UV-A or UV-B). The effect can be improved with the aid of locally or systemically administered photosensitizers in combination with UV-A radiation (PUVA therapy).
  • PUVA therapy extracorporeal PUVA therapy
  • ECP extracorporeal PUVA therapy
  • venous blood is collected through a cannula in the same manner as for blood donation.
  • the blood is then sent into the extracorporeal system.
  • the white blood corpuscles are separated from the red blood corpuscles and the blood platelets by a centrifugation or other separation step.
  • the red blood corpuscles and blood platelets are preferably immediately reinfused back into the patient.
  • the light source and the separating device are combined for design simplification into a single structural unit.
  • the centrifuge or the filtration unit has light-permeable walls, at least in segments, and a light source is aligned in such a way that the electromagnetic radiation strikes at least one of the liquid phases through the light-permeable walls of the centrifuge. In this way a separate irradiation unit can be omitted.
  • the radiation unit can be used to produce desired wavelengths of electromagnetic radiation.
  • This radiation should preferably be in the range of 380 to 780 nm to correspond to the absorption spectrum of different thiazine dyes.
  • the spectrum of radiation of the light source more preferably includes the wavelengths from 550 to 700 nm.
  • the emitted radiation spectrum of the light source should have its highest intensity approximately in the range of the absorption maximum of the dyes used in each case, and this will vary with the particular dyes used.
  • a sufficiently long irradiation time is achieved by widening the light-permeable conduit system in the region of the light incidence pe ⁇ endicular to the light incidence in such a way that, due to the enlargement of the cross section of the conduit system related to this, the flow velocity in the conduit system of the biological fluid in it is reduced.
  • the cross- sectional area of the conduit is increased, to decrease the linear velocity of the fluid.
  • this increase in the cross-sectional area must be balanced. If the increase is too great, the radiation may not reach all of the fluid in the conduit. Therefore, the widening of the conduit must be tempered.
  • a second transparent area may be introduced to allow for greater phototherapy. In such a case, the same light source may be used, or an additional light source may be added.
  • a vein adapter or sensor can be connected preferably to the reservoir interface.
  • a temperature regulating device wired into the conduit system for regulating the temperature of the biological fluid makes the necessary cooling of the blood possible.
  • the device preferably includes a metering device connected into the conduit system for releasing the dyes into the biological fluid.
  • the invention also creates a new application for known drugs, that being the application of phenothiazine dyes, especially toluidine blue or methylene blue, for the production of a drug for the inactivation of viruses in a therapy process of the type explained below.
  • the invention also creates a process for inactivation of viruses in biological fluids, especially for the inactivation of viruses — especially HIV — in blood and blood products, which involves adding photosensitizers to the biological fluid, preferably phenothiazine dyes, especially preferably toluidine blue or methylene blue, with the following steps: the biological fluid is separated by a separating device into different liquid phases and/or liquid and solid phases, especially into blood plasma and corpuscular elements, one of the liquid phases (i.e. plasma) is bombarded with electromagnetic radiation, especially of the visible spectrum, until part of the viruses present in the blood has been essentially destroyed or deactivated, and the liquid and/or solid phases are brought together again after irradiation and/or mixed with each other again.
  • photosensitizers preferably phenothiazine dyes, especially preferably toluidine blue or methylene blue
  • the biological fluid is separated by a separating device into different liquid phases and/or liquid and solid phases, especially into blood plasma and corpus
  • the irradiation is performed on the blood fraction which is free, or substantially free, of red corpuscles to prevent destruction of those cells.
  • the invention is also especially suited for devising a process for the inactivation of viruses in biological fluids, especially for the inactivation of viruses - especially HIV ⁇ in blood and blood products.
  • Photosensitizers preferably phenothiazine dyes, especially preferably toluidine blue or methylene blue, added to the biological fluid.
  • the blood is taken from a blood circulation and, before or after being taken from the circulation, the phenothiazine dyes are added to the blood.
  • the venous blood is separated in the separating device into a first phase with the main component plasma and a second phase with the main component co ⁇ uscular elements.
  • the first (plasma) phase with a small - especially scarcely measurable - content of white blood co ⁇ uscles, is irradiated with electromagnetic radiation, especially of the visible spectrum, until the viruses present in this blood phase have been largely destroyed or deactivated by the electromagnetic radiation.
  • the two liquid phases and/or liquid and solid phases are returned to the circulation after irradiation.
  • the invention further teaches a use of photosentisizers, especially phenothiazine dyes for producing a drug for inactivating virusses in according with a method of one of the preceeding claims.
  • Figure 1 illustrates a device 2 for inactivation of viruses in biological fluids, especially for the inactivation of viruses — especially HIV — in blood and blood products.
  • blood refers to whole blood
  • blood products refers to any portion or portions of whole blood, including, but not limited to, erythrocytes, leukocytes, plasma, or any other portion or fraction of whole blood.
  • the blood is passed from a container 4 (or directly from the blood circulation of a patient) through a valve 6 in a conduit 8 of a conduit system.
  • a pump 10 is connected to the conduit 6 with which the blood can be pumped in the conduit 8 in both directions.
  • Behind the pump 8 a conduit branch 12 with a valve 6 makes it possible to add an anticoagulant from a feeder device 14 designed for this task.
  • the feeder device 14 or another (not shown here) feeder device may, if necessary, also be utilized for the direct addition of the thiazine dyes to the blood of the patient.
  • the pumped-in blood is fed via a third valve 6c and a conduit branch 16 into a centrifuge or a filtration device 18 (e.g., a PRISMA TM CFR microfiltration unit trademark of HOSPAL GmbH, Brettergartenstr. 16 90477 Nuremberg, Germany).
  • the centrifuge or the filtration device 18 makes it possible to separate the fed-in blood into two liquid phases and/or liquid and solid phases.
  • One of these phases (with a high content of red blood co ⁇ uscles) is sent via the branch line 20 with a valve 6d to a return pouch 22 or directly back to the container 4 or a patient's circulation.
  • the other phase is sent via a branch line 24 with a valve 6d to a plasma container 26.
  • From the plasma container 26 the blood plasma is then sent through an irradiation cycle 28 with inflow line 30, pump 32, irradiation unit 34 with (not shown) cooling and return line 36.
  • the blood is returned from the plasma container 26 via the centrifuge or filtration device 18 and the return pouch 22 and a return branch line 38 with valve 6f as well as the pump 10 and conduit 8 with the valves in the appropriate position to container 4 or to the blood circulation of a patient.
  • the example in Figure 2 differs from this example of embodiment essentially in the fact that the blood is passed from the pump 10 directly to a centrifuge/irradiation unit combination 40 where the lamp segment 42 emits light onto the centrifuge part 44 with walls with light-permeable segments.
  • the photosensitizer is most conveniently in an aqueous solution of between 0.1 and 10%, preferably 0.5 to 5%, most preferably about 1% sensitizer. Any concentration may be used, however higher concentrations are difficult to work with as small errors in measurement dramatically affect dosage. Similarly, low concentrations add unnecessary volume to the treatment dosage. Of course, the volume used is dependent on the sensitizer concentration.
  • the photosensitizer may be toluidine blue or methylene blue (MB).
  • the radiation source should operate with visible light (380-780 nm).
  • Fluorescent tubes e.g. Phillips TL-M 115 W/3 RS
  • quartz lamps with which the plasma is irradiated for 1 h with 50,000 lux are suitable.
  • the temperature regulating system maintains a temperature of a maximum of 30°C.
  • An additional advantage of this therapy is the fact that other viruses can also be inactivated (he ⁇ es simplex, he ⁇ es zoster, influenza, vesicular stomatitis, Semliki forest, adeno, polio, cytomegalo, etc.).
  • the leukocytes/lymphocytes conversely, are not or only slightly influenced by it. Coagulation proteins and blood constituents remain intact.
  • venous blood is taken from the patient.
  • the white blood co ⁇ uscles are separated from the red blood co ⁇ uscles and the blood platelets by a centrifugation step (ca. 4800 ⁇ m + 5%).
  • the red blood co ⁇ uscles and the blood platelets are immediately reinfused back into the patient. These cycles are repeated until one has collected max. 15% of the total blood volume (therefore max. ca. 600 ml) of plasma including solitary leukocytes. Because of the above-mentioned cycles, a high blood volume throughput and accordingly a high HIV virus concentration in the collected plasma is guaranteed.
  • a conventional coagulation-inhibiting drug such as heparin is added to the collected venous blood so that the blood does not clot and clog the machine when flowing through the system of hoses.
  • a sterile 50 ⁇ l solution of MB in water for injection is added.
  • the final concentration of MB is 1 ⁇ M.
  • This photoactive substance has a strong affinity for the surface structures of viruses and viral nucleic acids and can therefore bind to them. When exposed to light it absorbs energy and transfers it to the molecules to which it is bound. Ultimately this results in the denaturing of the components of the virus shell or breaks in the strands of the viral HIV RNA. Highly reactive oxygen radicals are also involved in this process. It has also been demonstrated that the dyes interfere with transcription and translation (of DNA and RNA) in darkness as well as in a weak or a strong light.
  • the plasma is irradiated for 1 hour by the light source (50,000 lux).
  • the time necessary for destruction or inactivation of viruses will depend on many factors including the particular virus, the dye concentration, the particular dye used, the temperature, the light intensity, and the wavelength used, among others. This process is temperature dependent, i.e. the operating temperature must be between 20 and 30°C so that any proteins still present are not destroyed.
  • the treatment could be performed initially several times daily. The therapy cycle is repeated, depending on the virus load of the patient, from initially, e.g., five times weekly to once per month.
  • This experiment shows the virus inactivation properties of methylene blue and light in plasmas from four different patients.
  • HIV RNA in the treated plasma could be detected quantitatively. HIV was found to be especially susceptible to the photo-inactivation step. The intensity of the total inactivation for HI viruses in the presence of methylene blue, however, depends on the duration of the exposure. In order to investigate what exposure times are sufficient for photoinactivation of HIV, 10 test tubes containing plasma were exposed at 27°C for different times.
  • the second example illustrates the effect of the photodynamic therapy on the lymphocyte population.
  • lymphocyte differential count of a healthy subject is analyzed. From the reference range, it can be seen that this lymphocyte differential count is well within the normal range.
  • a conventional photodynamic therapy was performed with this patient's plasma (including lymphocytes):
  • Venous blood is taken from a monkey infected with a simian analog of HIN.
  • the blood is separated using a centrifuge, and the platelets and red blood cells
  • the total blood volume is gathered as plasma. To the plasma is added
  • controlling device to maintain a temperature between 20 and 30°C.
  • the plama may be tested to
  • the treatment can be performed

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  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Biodiversity & Conservation Biology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • External Artificial Organs (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

L'invention concerne un appareil et un procédé d'inactivation de virus dans des liquides biologiques, notamment pour l'inactivation de virus -- en particulier le VIH -- dans le sang et les produits sanguins, le procédé consistant à ajouter des colorants à base de phénothiazine, notamment du bleu de toluidine ou du bleu de méthylène, au liquide biologique. On utilise un dispositif monopièce ou multipièces de pompage et de transport pour prélever le liquide biologique dans un réceptacle ou dans le système circulatoire, puis on fait passer le liquide biologique dans un système de conduits avant de le retourner dans le réceptacle ou le système circulatoire. Un dispositif de séparation permet de séparer le liquide biologique en une phase liquide et une phase corpusculaire. Une source lumineuse émet un rayonnement électromagnétique dans le spectre visible sur un segment du système de conduits perméable à la lumière.
PCT/EP2000/002845 1999-04-01 2000-03-31 Inactivation photodynamique de virus dans des liquides biologiques WO2000059551A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU38163/00A AU3816300A (en) 1999-04-01 2000-03-31 Photodynamic inactivation of viruses in biological fluids

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19914850A DE19914850A1 (de) 1999-04-01 1999-04-01 Vorrichtung und Verfahren zur Inaktivierung von Viren in biologischen Flüssigkeiten
DE19914850.3 1999-04-01

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WO2000059551A1 true WO2000059551A1 (fr) 2000-10-12

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DE (1) DE19914850A1 (fr)
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004103443A1 (fr) * 2003-05-22 2004-12-02 Beijing Jingjing Medical Equipment Co., Ltd. Methode permettant d'inactiver un virus dans le sang en circulation, et ses applications dans le traitement des maladies virales
CN100393371C (zh) * 2003-05-30 2008-06-11 富瑞森尼尔斯医护德国有限公司 含胆红素液体之体外照射装置
CN101386606B (zh) * 2007-09-10 2013-08-07 中国医学科学院药物研究所 3-氨基-7-二烷基胺基取代吩噻嗪类化合物及其制法和用途
RU2558432C2 (ru) * 2012-09-27 2015-08-10 Закрытое акционерное общество "Лазеры и оптические системы" Способ инактивации патогенов
US20150283318A1 (en) * 2011-04-12 2015-10-08 Tianxin Wang Methods to detect and treat diseases

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112386717B (zh) * 2020-12-11 2022-05-24 西安市中心医院 一次性血液病毒灭活装置

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WO1990007952A1 (fr) * 1989-01-10 1990-07-26 Emil Bisaccia Procedes de traitement et vaccins
WO1991003933A1 (fr) * 1989-09-13 1991-04-04 Blutspendedienst Der Landesverbände Des Deutschen Roten Kreuzes Niedersachsen, Oldenburg Und Bremen G.G.M.B.H. Procede de desactivation de virus dans du sang et des produits du sang
US5304113A (en) * 1986-11-21 1994-04-19 The Mcw Research Foundation, Inc. Method of eradicating infectious biological contaminants
US5597722A (en) * 1993-01-28 1997-01-28 Baxter International Inc. Method for inactivating pathogens in compositions containing cells and plasma using photoactive compounds and plasma protein reduction
WO1997022245A1 (fr) * 1995-12-19 1997-06-26 Baxter International Inc. Systemes et procedes d'elimination du plasma des contaminants libres ou entraines

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
US5304113A (en) * 1986-11-21 1994-04-19 The Mcw Research Foundation, Inc. Method of eradicating infectious biological contaminants
WO1990007952A1 (fr) * 1989-01-10 1990-07-26 Emil Bisaccia Procedes de traitement et vaccins
WO1991003933A1 (fr) * 1989-09-13 1991-04-04 Blutspendedienst Der Landesverbände Des Deutschen Roten Kreuzes Niedersachsen, Oldenburg Und Bremen G.G.M.B.H. Procede de desactivation de virus dans du sang et des produits du sang
US5597722A (en) * 1993-01-28 1997-01-28 Baxter International Inc. Method for inactivating pathogens in compositions containing cells and plasma using photoactive compounds and plasma protein reduction
WO1997022245A1 (fr) * 1995-12-19 1997-06-26 Baxter International Inc. Systemes et procedes d'elimination du plasma des contaminants libres ou entraines

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004103443A1 (fr) * 2003-05-22 2004-12-02 Beijing Jingjing Medical Equipment Co., Ltd. Methode permettant d'inactiver un virus dans le sang en circulation, et ses applications dans le traitement des maladies virales
US8808977B2 (en) 2003-05-22 2014-08-19 Beijing Jingjing Medical Equipment Co., Ltd Method of inactivating virus in circular blood and its applications in treating viral diseases
CN100393371C (zh) * 2003-05-30 2008-06-11 富瑞森尼尔斯医护德国有限公司 含胆红素液体之体外照射装置
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