WO1995000631A1 - Systeme pour inactiver les virus du sang - Google Patents

Systeme pour inactiver les virus du sang Download PDF

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Publication number
WO1995000631A1
WO1995000631A1 PCT/US1994/007018 US9407018W WO9500631A1 WO 1995000631 A1 WO1995000631 A1 WO 1995000631A1 US 9407018 W US9407018 W US 9407018W WO 9500631 A1 WO9500631 A1 WO 9500631A1
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WO
WIPO (PCT)
Prior art keywords
blood
virucidal
reagent
blood product
mixture
Prior art date
Application number
PCT/US1994/007018
Other languages
English (en)
Inventor
Henrietta Margolis-Nunno
Bernard Horowitz
Original Assignee
New York Blood Center, Inc.
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 New York Blood Center, Inc. filed Critical New York Blood Center, Inc.
Priority to EP94921349A priority Critical patent/EP0707633A4/fr
Priority to JP7503052A priority patent/JPH09500015A/ja
Priority to AU72113/94A priority patent/AU698154B2/en
Priority to KR1019950705876A priority patent/KR960703167A/ko
Publication of WO1995000631A1 publication Critical patent/WO1995000631A1/fr
Priority to FI956078A priority patent/FI956078A/fi
Priority to NO955291A priority patent/NO955291L/no

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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
    • A61M1/3687—Chemical treatment
    • 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
    • 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
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • 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
    • A61M1/3686—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 by removing photoactive agents after irradiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • 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
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0439—White blood cells; Leucocytes
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/20—Pathogenic agents
    • A61M2202/206—Viruses
    • 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

Definitions

  • the present invention relates to a continuous-flow or semi-continuous flow system that accomplishes both virus inactivation of blood or a blood product and virucidal reagent removal from treated blood or a blood product.
  • Blood can contain each of several different viruses including but not limited to hepatitis B virus (HBV), non-A, non-B hepatitis virus (NANBHV), cytomegalovirus, and immunodeficiency viruses. It is highly desirable to inactivate these viruses in the course of preparing blood products and prior to the therapeutic application of blood and blood fractions. The potential for transmission of these viruses presents a danger not only to potential recipients of blood and blood fractions, but can also pose a danger to persons involved in the preparation and administration of blood and blood products. Both physical (e.g., heat, irradiation) and chemical (e.g., aldehydes, organic solvents, detergents, etc.) methods have been used to inactivate viruses in mammalian blood and blood fractions.
  • HBV hepatitis B virus
  • NANBHV non-A
  • NANBHV non-B hepatitis virus
  • cytomegalovirus cytomegalovirus
  • immunodeficiency viruses immunodefici
  • Solvent/ detergent treatment under appropriate conditions of temperature and contact time effectively disassembles viruses that have envelope proteins associated with lipid, while having negligible effect on the molecular conformations and biological activities of sensitive blood plasma proteins.
  • Merocyanine, beta-propiolactone and cis-platin are among other agents that are applied to blood to inactivate viruses, though by mechanisms other than envelope disruption.
  • virus kill might be complete in the bulk of the blood or blood component, a single droplet of blood, if not adequately treated, contains sufficient virus to infect the recipient.
  • the activatable virucidal compounds and their breakdown products should be mostly or completely removed prior to infusion to reduce concerns about adverse toxicity and mutagenicity of these compounds.
  • unit-to-unit variation in treatment conditions should be minimized to ensure a uniformly high virucidal action, on the one hand, and unharmed blood components, on the other.
  • the virus sterilization system needs to be cost effective, both in terms of the cost of disposables and in labor costs.
  • the amount of photoactive porphyrin or hematoporphyrin compound in the mixture is expressly limited to non-toxic amounts and the reference does not teach or suggest that it is advantageous to remove the photoactive porphyrin or hematoporphyrin remaining in the mixture after the irradiation treatment.
  • the inventive virucidal treatment method is rapid, uniformly treats each droplet of blood or blood product, and is convenient.
  • Whole blood as well as blood components red blood cell concentrates, platelet concentrates, fresh frozen plasma, cryoprecipitates, etc.
  • red blood cell concentrates, platelet concentrates, fresh frozen plasma, cryoprecipitates, etc. can be virucidally treated, either as single units or preferably with the pooling of 2-25 units prior to treatment.
  • the invention furthermore relates broadly to a continuous or semi-
  • continuous flow system for processing blood or a blood product to inactivate any virus contained therein, said system comprising optically transparent tubing arranged in a predetermined flow path, said flow path being interrupted by:
  • the inventive flow system permits the pooling of blood or a blood product prior to treatment with dyes together with visible light or compounds known to react with nucleic acids, the in-line use of hydrophobic filters or hydrophobic resins to remove unreacted virucidal compound together with its breakdown products, and the in-line distribution of the treated blood or blood product into single or multiple storage containers.
  • the virucidal compound is a dye or photoactive compound or any other compound that interacts with nucleic acid, for example, merocyanine, beta-propiolactone, cis- platin, a phthalocyanine or a psoralen, e.g., aminomethyl-trimethyl psoralen (AMT), and after treatment such compound is removed by hydrophobic interaction chromatography or by a filter containing hydrophobic ligands, any residual virucidal compound which cannot be separated from the blood or blood product has lost the capacity to interact with nucleic acid and is no longer virucidal or mutagenic.
  • AMT aminomethyl-trimethyl psoralen
  • blood or blood products treated with such compounds in accordance with the teachings of the present invention will be particularly well tolerated by humans or other biological systems in which the treated blood or blood product is to be used, e.g., in tissue cultures.
  • This also means that it is now possible to utilize such compounds in the context of a continuous or semi-continuous process for the processing of blood and blood products with reasonable certainty that the treated blood and blood products will be substantially free of virus and also well-tolerated by human patients.
  • the invention also relates to a process for processing blood or a blood product to inactivate any virus contained therein, said process comprising:
  • virucidal reagents that pass through the hydrophobic ligand are apparently altered (by a structural change which may or may not involve its covalent binding to protein or lipids) in such a way that the virucidal reagent has lost its ability to interact with nucleic acid and, thereafter, tests negative in an Ames test for mutagenicity and also is incapable, for example, of inactivating virus upon further irradiation with UVA.
  • Figure 1 is a schematic of the inventive component system.
  • Blood is made up of solids (cells, i.e., erythrocytes, leukocytes, and platelets) and liquid (plasma).
  • the cells contain potentially valuable substances
  • the plasma is composed mainly of water, salts, lipids and proteins.
  • the proteins are divided into groups called fibrinogen, serum globulins and serum albumin.
  • Typical antibodies (immune globulins) found in human blood plasma include those directed against infectious hepatitis, influenza H, etc.
  • Cells found in blood include red cells, various types of leukocytes or white cells, and platelets. Fractionation of cell types typically utilizes centrifugation, but may involve other forms of differential sedimentation through addition of rouleaux enhancing agents such as hydroxyethyl starch, separations based on immunological specificity, etc. Leukocytes may be removed from other cells through the use of leukocyte removing filters.
  • Proteins found in human plasma include prealbumin, retinol-binding protein, albumin, alpha-globulins, beta-globulins, gamma-globulins (immune serum globulins), the coagulation proteins (antithrombin III, prothrombin, plasminogen, antihemophilic factor (factor VIII), fibrin-stabilizing factor (factor XIII), fibrinogen), immunoglobulins (immunoglobulins G, A, M, E and D), and the complement components.
  • coagulation proteins antithrombin III, prothrombin, plasminogen, antihemophilic factor (factor VIII), fibrin-stabilizing factor (factor XIII), fibrinogen
  • immunoglobulins immunoglobulins
  • Proteins found in blood cell fraction include hemoglobin, fibronectin, fibrinogen, enzymes of carbohydrate and protein metabolism, platelet derived growth factor, etc.
  • the synthesis of other proteins can be induced, such as interferons and growth factors.
  • a comprehensive list of inducible leukocyte proteins can be found in S. Cohen, E. Pick, J.J. Oppenheim, Biology of the Lymphokines, Academic Press, New York (1979).
  • the present invention is particularly directed, inter alia, to producing a protein-containing composition such as blood plasma, cryoprecipitates, blood plasma fractions, etc., which is substantially free of infectious virus, yet which retains a substantial amount of enzymatically or biologically active (undenatured) protein and from which process chemicals have been removed so that the resultant composition contains no more than physiologically acceptable levels of such process chemicals.
  • a protein-containing composition such as blood plasma, cryoprecipitates, blood plasma fractions, etc.
  • Non-limiting examples of "blood or blood products” for use according to the present invention include whole blood, blood plasma, blood plasma fractions, precipitates from blood fractionation.
  • Contemplated is the treatment of concentrates of whole blood cells, red cells, white cells (leukocytes), platelets, platelet rich plasma, platelet poor plasma, cryoprecipitate, serum, and concentrates of granulocytes, monocytes, or lymphocytes or other cells capable of producing interferon, tumor necrosis factor (TNF), or other immune modulators or lymphokines, or the media separated from such concentrates or suspensions.
  • TNF tumor necrosis factor
  • a protein-containing composition particularly whole blood plasma or whole blood serum having an extent of inactivation of virus greater than 6 logs of virus, such as AIDS virus (HIV I), hepatitis B virus and non-A, non-B hepatitis virus, having a retention of functional activity for particularly biologically active proteins of at least 45%, preferably at least 75%, more preferably at least 85%, even more preferably at least 95%, and most preferably 98% to 100%, and having no more than physiologically acceptable levels of process chemicals.
  • virus HIV I
  • hepatitis B virus hepatitis B virus and non-A, non-B hepatitis virus
  • Coagulation factor activity is retained at more than 60% of its original level and preferably more than 75 to 85%, and most preferably at more than 90 to 98% of its original level.
  • the inventive flow system is designed as a system of component treatment stations or zones linked by conventional tubing (2 in Fig. 1) and the blood or blood product is made to flow through such tubing by the action of gravity or by a pump.
  • the blood or blood product will normally first be fed from a donor or satellite bag (1 in Fig. 1) to a pooling container (3 in Fig. 1), in which it is possible, if desired, to pool the blood or blood product, e.g., 2-25 units thereof, prior to treatment. Pooling of blood units is preferable since pooling of blood increases the overall cost efficiency of the process.
  • the virucidal reagent or other process chemicals can either be added upstream of the pooling container, to the pooling container, or downstream of the pooling container. The only requirement is that the virucidal reagent should be added to the blood or blood product before the blood or blood product is fed to an irradiation zone.
  • virucidal reagent or other process chemicals will, of course, be chosen from among those known to be useful in the context of viral inactivation processes, particularly sterilization processes for blood or blood products.
  • Non- limiting examples of virucidal reagents or other process chemicals include various dyes, e.g., benzporphyrin derivatives, merocyanine 540, methylene blue, and phthalocyanines, compounds known to principally react with nucleic acids, an example of which is the class of psoralen derivatives, di- or trialkylphosphates, detergents, surfactants, antioxidants, e.g., glutathione, and
  • quenchers type I or type II or compounds, such as the flavonoids, which are known to quench both type I and type II reactions.
  • the mixture is then fed to an irradiation zone (4 in Fig. 1) where the mixture is then subjected to irradiation by a suitable irradiation source (5 in Fig. 1).
  • a suitable irradiation source 5 in Fig. 1.
  • the type and conditions of irradiation are well known to those of ordinary skill in the art. See, for example, U.S. Patent Application No. 08/069,235, filed May 28, 1993, the entire contents of which are incorporated herein by reference.
  • the exposure time is controlled by the flow rate and the volume of tubing in the irradiation path. The exposure time should be set for that period of time conventionally deemed necessary to effect maximum virus inactivation.
  • tubing optically transparent to the particular irradiation source utilized and to flow such tubing in a serpentine flow path through the irradiation zone.
  • virucidal compounds can be added to the bag containing the blood component to be treated and the bag exposed to irradiation.
  • the blood or blood product is fed to a station (6 in Fig. 1) whereby removal of the virucidal reagent and other process chemicals from the blood or blood product is effected.
  • the means for removing the virucidal reagent and other process chemicals comprises a filter or cartridge or chromatography column which contains hydrophobic groups capable of binding the virucidal reagent or process chemicals without adversely affecting labile components of the blood or blood product. More preferably, the filter or cartridge or chromatography column contains a compound containing C-6 to C- 24 chains. Particularly preferred is a compound containing octadecyl (C18) chains.
  • the compounds are those described in U.S. Patent No. 5,094,960 and the removal of the virucidal reagent and process chemicals is substantially as described therein.
  • a cartridge is utilized, which is in-line with or integrated into a leukocyte removal filter.
  • the blood or blood product is then fed into single or multiple storage containers (7 in Fig. 1), e.g., blood bags, and then stored until use.
  • single or multiple storage containers e.g., blood bags
  • advantageous use can be made of a multi-position valve.
  • Example 1 Batch treatment of red blood cell concentrates (RBCC) with aluminum phthalocyanine tetrasulfonate (AIPCS 4 ) and removal of AIPCS 4 by hydrophobic filtration
  • AIPCS 4 and reduced glutathione (GSH) at final concentrations of 10 ⁇ M and 4 mM, respectively, are added aseptically to each of four units of ABO, Rh blood group matched RBCC.
  • the units are exposed to 176 J/cm2 visible light either individually or on pooling into a pooling container. After irradiation, the units are aseptically connected to a nylon filter modified by addition of C18 hydrophobic ligands.
  • the treated RBCC pass through the filter, which removes unreacted AIPCS 4 and its by-products, and is collected into a single blood bag of sufficient size (0.8-1 liter) to hold all four units.
  • the blood bag is sealed and stored at 4°C until provision for transfusion.
  • RBCC Eight units of ABO, Rh-matched RBCC are aseptically attached to a sterile manifold, which at the outlet contains a static mixing device into which both RBCC and AlPcS 4 flow.
  • the RBCC are passed through a hydrophobic filter, connected in series, and designed to remove the virucidal reagent and its break-down products. Finally, the RBCC are distributed into 1-4 blood bags by way of a multi-position valve, and the bags sealed.
  • PCs platelet concentrates
  • a similar system to that described in Examples 1 and 2 can be employed when treating a PC pool, substituting 50 ⁇ g/mL aminomethyl-trimethyl psoralen (AMT) or other psoralen for AlPcS 4 , 0.5 mM rutin for GSH, and 60 J/ cm 2 UVA for visible light.
  • AMT aminomethyl-trimethyl psoralen
  • GSH 0.5 mM rutin
  • UVA 60 J/ cm 2 UVA for visible light.
  • Fresh frozen plasma (FFP) is thawed and 1 ⁇ M methylene blue and 0.5 mM glutathione added by means of a static mixer. The FFP is then subjected to irradiation with fluorescent light at 150,000 lux for 2 hours. Antihemophilic factor (AHF) and fibrinogen recovery exceed 85%.
  • AHF Antihemophilic factor
  • fibrinogen recovery exceed 85%.
  • Cryoprecipitates (8) are thawed and aseptically pooled and 1% tri(n- butyl)phosphate and 1% Triton X-100 are added to the pooling bag. After 4 hours mixing at 30°C on a rocker, the cryoprecipitates are passed through a sterile hydrophobic filter containing C18 functional groups and collected into a final bag and frozen. AHF recovery is 75%.
  • Example 6 C18 Chromatography of AMT and UVA treated platelet concentrates: Effects on platelet integrity and AMT removal
  • Example 7 C18 passage eliminates the virucidal activity of residual AMT
  • PC samples containing 50 ⁇ g/mL AMT and 0.35 mM rutin were irradiated with UVA (7-10 mW/cm2) as indicated (UVAi).
  • Samples were passed (+C18) or not passed (-C18) through C18 and vesicular stomatitis virus (VSV) was added (1:10) prior to the second irradiation (UVA 2 ).
  • VSV vesicular stomatitis virus
  • Example 8 Passage through C18 eliminates the capability of residual AMT to form adducts with nucleic acids
  • PC or plasma samples, treated with 50 ⁇ g/ml AMT and 0.35 mM rutin with and without 90 minutes UVA and with and without passage through C18 were evaluated for their ability to induce frame-shift or base substitution mutations in bacterial "Ames tester" strains. (Ames test was performed by Microbiological Associates Inc., Rockville, Maryland.)

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Abstract

L'invention concerne un système fonctionnant en continu ou en semi-continu qui simultanément inactive les virus du sang et élimine le réactif virucide du sang traité. Le procédé consiste à réunir le sang, puis à effectuer sur celui-ci un traitement avec les colorants combiné à la lumière visible ou avec des composés connus pour leur aptitude à réagir avec des acides nucléiques, puis à utiliser en aval des filtres ou des colonnes de chromatographie à caractère hydrophobe pour enlever le composé virucide n'ayant pas réagi ainsi que ses produits de dégradation, et enfin à conditionner le sang traité dans un récipient unique ou dans une pluralité de récipients. On a pu observer que les composés virucides résiduels qui ne peuvent pas être séparés du sang par les groupes hydrophobes des filtres ou des colonnes de chromatographie perdent leur capacité d'interaction avec les acides nucléiques et ne sont plus virucides ou mutagènes.
PCT/US1994/007018 1993-06-23 1994-06-22 Systeme pour inactiver les virus du sang WO1995000631A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP94921349A EP0707633A4 (fr) 1993-06-23 1994-06-22 Systeme pour inactiver les virus du sang
JP7503052A JPH09500015A (ja) 1993-06-23 1994-06-22 血液のウィルス不活性化のためのシステム
AU72113/94A AU698154B2 (en) 1993-06-23 1994-06-22 System for viral inactivation of blood
KR1019950705876A KR960703167A (ko) 1993-06-23 1994-06-22 혈액내 바이러스 불활성화 시스템(system for viral inactivation of blood)
FI956078A FI956078A (fi) 1993-06-23 1995-12-18 Järjestelmä veren virusten inaktivoimiseksi
NO955291A NO955291L (no) 1993-06-23 1995-12-22 System for viral inaktivering av blod

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US8177493A 1993-06-23 1993-06-23
US08/081,774 1993-06-23

Publications (1)

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WO1995000631A1 true WO1995000631A1 (fr) 1995-01-05

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PCT/US1994/007018 WO1995000631A1 (fr) 1993-06-23 1994-06-22 Systeme pour inactiver les virus du sang

Country Status (9)

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EP (1) EP0707633A4 (fr)
JP (1) JPH09500015A (fr)
KR (1) KR960703167A (fr)
AU (1) AU698154B2 (fr)
CA (1) CA2165065A1 (fr)
FI (1) FI956078A (fr)
NO (1) NO955291L (fr)
WO (1) WO1995000631A1 (fr)
ZA (1) ZA944488B (fr)

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0684763A1 (fr) * 1993-12-17 1995-12-06 Baxter International Inc. Procede et appareil destines au traitement d'un fluide organique
WO1996040857A1 (fr) * 1995-06-07 1996-12-19 Cerus Corporation Procedes et dispositif pour l'extraction des psoralenes des produits sanguins
WO1997003706A1 (fr) * 1995-07-14 1997-02-06 Croix-Rouge De Belgique Procede et installation d'inactivation de contaminants presents dans des produits sanguins
WO1997018844A1 (fr) * 1995-11-21 1997-05-29 Pall Corporation Procede et systeme d'inactivation utilises dans des fluides biologiques
US5660731A (en) * 1994-11-08 1997-08-26 Pall Corporation Filter for separating photoactive agent
EP0892599A1 (fr) * 1996-04-09 1999-01-27 Therakos, Inc. Procede d'elimination de psoralenes dans des fluides biologiques
US5952235A (en) * 1997-04-14 1999-09-14 Case Western Reserve University Detection of teratogen exposure
WO2000003751A1 (fr) * 1998-07-16 2000-01-27 Shanbrom Technologies Llc Elimination de colorants desinfectants
EP0776668A3 (fr) * 1995-11-28 2000-06-21 Aventis Behring Gesellschaft mit beschränkter Haftung Procédé pour éliminer les composés aromatiques des solutions
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US8900805B2 (en) 2008-04-09 2014-12-02 Cerus Corporation Quenching methods for red blood cell pathogen inactivation
WO2015158776A1 (fr) * 2014-04-15 2015-10-22 Boehringer Ingelheim International Gmbh Procédés, appareils et systèmes d'inactivation continue de virus pendant la fabrication de produit biologique
US9259525B2 (en) 1998-01-06 2016-02-16 Cerus Corporation Adsorbing pathogen-inactivating compounds with porous particles immobilized in a matrix
US9782707B2 (en) 2014-03-24 2017-10-10 Fenwal, Inc. Biological fluid filters having flexible walls and methods for making such filters
US9796166B2 (en) 2014-03-24 2017-10-24 Fenwal, Inc. Flexible biological fluid filters
US9809799B2 (en) 2012-06-29 2017-11-07 Emd Millipore Corporation Methods for inactivating viruses during a protein purification process
US9968738B2 (en) 2014-03-24 2018-05-15 Fenwal, Inc. Biological fluid filters with molded frame and methods for making such filters
US10159778B2 (en) 2014-03-24 2018-12-25 Fenwal, Inc. Biological fluid filters having flexible walls and methods for making such filters
US10376627B2 (en) 2014-03-24 2019-08-13 Fenwal, Inc. Flexible biological fluid filters

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AU698154B2 (en) 1998-10-22
KR960703167A (ko) 1996-06-19
AU7211394A (en) 1995-01-17
NO955291L (no) 1996-02-22
FI956078A0 (fi) 1995-12-18
CA2165065A1 (fr) 1995-01-05
EP0707633A1 (fr) 1996-04-24
NO955291D0 (no) 1995-12-22
FI956078A (fi) 1996-02-14
JPH09500015A (ja) 1997-01-07
EP0707633A4 (fr) 1996-08-14
ZA944488B (en) 1995-02-15

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