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WO2003105990A2 - Materiau filtrant pour toxines, bacteries, virus et autres substances physiologiques nocives - Google Patents

Materiau filtrant pour toxines, bacteries, virus et autres substances physiologiques nocives Download PDF

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Publication number
WO2003105990A2
WO2003105990A2 PCT/EP2003/005957 EP0305957W WO03105990A2 WO 2003105990 A2 WO2003105990 A2 WO 2003105990A2 EP 0305957 W EP0305957 W EP 0305957W WO 03105990 A2 WO03105990 A2 WO 03105990A2
Authority
WO
WIPO (PCT)
Prior art keywords
filter material
material according
aryl
alkyl
acids
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.)
Ceased
Application number
PCT/EP2003/005957
Other languages
German (de)
English (en)
Other versions
WO2003105990A3 (fr
Inventor
Hans-Uwe Wolf
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to AU2003245917A priority Critical patent/AU2003245917A1/en
Priority to EP03737999A priority patent/EP1526910A2/fr
Publication of WO2003105990A2 publication Critical patent/WO2003105990A2/fr
Publication of WO2003105990A3 publication Critical patent/WO2003105990A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3204Inorganic carriers, supports or substrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3206Organic carriers, supports or substrates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/20Pathogenic agents
    • A61M2202/203Bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/20Pathogenic agents
    • A61M2202/206Viruses

Definitions

  • the invention relates to a filter material for toxins, bacteria, viruses and other physiological pollutants, which can be used in hemoperfusion to rid the blood of such pollutants.
  • the filter material is based on compounds from the class of calixarenes and reosrcinarene.
  • Hemoperfusion is one of the (most effective measures for extracorporeal elimination of toxins and pollutants.
  • hemoperfusion In contrast to hemodialysis, hemoperfusion is able to eliminate lipophilic substances that are not suitable for dialysis from the blood. However, hemoperfusion is usually superior to substances capable of dialysis. An important side effect, which has not yet been eliminated, is the undesired adsorption of throinocytes, which can be in a range up to about 40%.
  • a filter material which consists of a compound of the general formula I
  • R H, alkyl, aryl, alkyloxy, aryloxy, amine, amide, carboxylic acids and sulfonic acids with • 1 to 12 carbon atoms, amino acids, sugar or crown ether,
  • Ri H, alkyl, aryl, alkyloxy, aryloxy, amine, amide, carboxylic acids and sulfonic acids with 1 to 12 carbon atoms, sulfonamides, amino acids, sugars, crown ethers, cyclodextrins, purine bases or pyridine bases,
  • R H, alkyl, aryl, alkyloxy, aryloxy, amine, amide, carboxylic acids and sulfonic acids with 1 to 12 carbon atoms or amino acids
  • Ri H, alkyl, aryl, alkyloxy, aryloxy, amine, amide, carboxylic acids and sulfonic acids with 1 to 12 carbon atoms, sulfona ide, amino acids, sugar, crown ethers, cyclodextrins, purine bases or pyrimidine bases,
  • R 2 * alkyl or aryl
  • R 3 and 4 0, where R 3 and R are bridged together via methylene, ethylene or quinoxaline
  • the designated aromatic systems can be any heteroatoms, e.g. B. 0, S, N, have.
  • the peculiarity of the solution according to the invention is based on the fact that the macromolecules used from the group of the calixarenes and resorcinarenes are easily accessible synthetically and can be modified universally. So you can open them up. Optimize various requirements regarding the substance classes of the toxins to be eliminated. It is particularly interesting in view of the fact that a large number of substances have hitherto been insufficiently eliminated, for example B. Paraquat and Diquat.
  • any matrices known from the prior art can be used as the carrier.
  • the filter material it is also possible for the filter material to contain or consist of biomatrixes such as cotton or cellulose.
  • Micelle formers or compounds from the group cyclodextrins are preferably contained as additives.
  • cyclodextrins are significantly more polar and hydrophilic than calixarenes or resorcinarenes, which means that. certain applications a higher hydrophilicity of the filter material than can be realized.
  • the calixarenes or resorcinarenes of the general formulas I and II must be modified depending on the pollutant to be eliminated.
  • the modification takes place from the point of view of optimizing the interaction between the filter material and the relevant target molecule, ie. H. the pollutant.
  • hydrophilic groups in the compounds are necessary to ensure water solubility.
  • modification options of the filter material are to be mentioned here only by way of example in order to implement special applications. This includes, on the one hand, modifying the filter material with sugars that can interact with bacteria, making them accessible for hemoperfusion, so that they can be filtered out of physiological fluids. By modifying the filter material with amino acids, an interaction with viruses can also be made possible, so that these can also be separated using hemoperfusion.
  • the filter material provides that the compound of the general formulas I and II are modified with antibodies. This enables the rapid elimination of antigens due to antigen-antibody interactions. With aggressive viruses in particular, there is the possibility of removing antigens from the organism until the immune system has stabilized.
  • the filter material is based on the fact that the compounds of the general formulas I and II have a high temperature resistance, which can be exploited in such a way that recyclable filter materials can be provided.
  • Appropriate thermal treatment thermally decomposes the pollutants eliminated from the blood, while the compounds of the general formulas I and II contained in the filter material remain stable. Such thermal treatments are preferably carried out above 300 ° C. Compared to the filter materials known from the prior art, the inventive materials thus have a significantly higher thermal stability.
  • the filter material is preferably integrated into common filter devices. This includes, for example, cartridges, frits, disks or membranes.
  • the filter material according to the invention is preferably used for the hemoperfusion of physiological liquids.
  • Blood, plasma or urine are only examples of physiological fluids.
  • the subject according to the invention is intended to be explained in more detail with reference to the following figure and the examples, without restricting it to the exemplary embodiments mentioned.
  • 1 shows a schematic structural model of the tetrasulfonic acid calix [4] arene-paraquat complex.
  • a paraquat molecule shows the incorporation of a paraquat molecule into a tetrasulfonic acid calix [4] arene system.
  • the paraquat is bound to the filter material via different interactions. This includes a cation-OH interaction 1, a cation- ⁇ interaction 2, a CH- ⁇ interaction 3 and a ⁇ - ⁇ interaction 4.
  • the complex formation constant is very large and can be in the range 10 5 are up to 10 ⁇ . This means that paraquat is stored irreversibly and can thus be permanently removed from the bloodstream, for example by hemoperfusion.
  • the sulfuric acid is added all at once to the calix [4] arene in a 100 ml three-necked flask with gas inlet and outlet devices.
  • the apparatus is flushed with argon and the reaction mixture is stirred at 80 ° C. for about 4 hours.
  • the course of the reaction is followed by taking a sample and checking the solubility in water. If the mixture is soluble in water without a residue, the reaction is stopped.
  • the crude product is filtered off with a glass frit (4 A), dissolved in methanol (in order to remove remaining sulfuric acid) and precipitated with ethyl acetate.
  • the white precipitate is dried in an oil pump vacuum-
  • Paraquat is a very effective contact herbicide and as such has been widely used for many decades.
  • the toxic effect on plants is based on the inhibition of photosynthesis by the formation of radical intermediates which prevent the NADP reduction. This hinders the transmission of energy. It is 'non-toxic to rapidly oxygen, reduced well waser- soluble compounds, whereby it is a good way to carry out the control of weeds in time selectively and relatively umweitschonend' in the field in the presence of light and.
  • Paraquat has repeatedly resulted in numerous acute and chronic poisonings in humans when used in agriculture or when attempting suicide. Symptoms such as eye damage, kidney and liver damage, gastritis and lung diseases occur until death from suffocation. Therapeutic measures are limited because there is no specific antidote. Adsorption on activated carbon or carbon filters is weak, which is why stronger interactions with adsorbents are sought.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Inorganic Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Anesthesiology (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un matériau filtrant pour toxines, bactéries, virus et autres substances physiologiques nocives, qui peut être utilisé lors d'une hémoperfusion pour extraire des substances nocives de ce type de fluides physiologiques. Ce matériau filtrant est basé sur des composés de la classe des calixarène et résorcinarène. Lesdits fluides physiologiques sont par exemple du sang, du plasma ou de l'urine.
PCT/EP2003/005957 2002-06-12 2003-06-06 Materiau filtrant pour toxines, bacteries, virus et autres substances physiologiques nocives Ceased WO2003105990A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003245917A AU2003245917A1 (en) 2002-06-12 2003-06-06 Filter material for toxins, bacteria, viruses, and other harmful physiological substances
EP03737999A EP1526910A2 (fr) 2002-06-12 2003-06-06 Materiau filtrant pour toxines, bacteries, virus et autres substances physiologiques nocives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10226099A DE10226099A1 (de) 2002-06-12 2002-06-12 Filtermaterial für Toxine, Bakterien, Viren und andere physiologische Schadstoffe
DE10226099.0 2002-06-12

Publications (2)

Publication Number Publication Date
WO2003105990A2 true WO2003105990A2 (fr) 2003-12-24
WO2003105990A3 WO2003105990A3 (fr) 2004-04-01

Family

ID=29718988

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2003/005957 Ceased WO2003105990A2 (fr) 2002-06-12 2003-06-06 Materiau filtrant pour toxines, bacteries, virus et autres substances physiologiques nocives

Country Status (4)

Country Link
EP (1) EP1526910A2 (fr)
AU (1) AU2003245917A1 (fr)
DE (1) DE10226099A1 (fr)
WO (1) WO2003105990A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8556085B2 (en) 2010-11-08 2013-10-15 Stuart Bogle Anti-viral device

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989008092A1 (fr) * 1988-02-29 1989-09-08 The Flinders University Of South Australia Separation de composes organiques contenus dans des fluides
US5312837A (en) * 1991-01-29 1994-05-17 Genelabs Technologies, Inc. Method of treating viral infections with aryl macrocyclic compounds
AU4803393A (en) * 1992-08-06 1994-03-03 Genelabs Technologies, Inc. Inhibition and treatment of infection by enveloped virus with calix(n) arene compounds
AU1545395A (en) * 1994-01-24 1995-08-08 Stephen J. Harris Calixarene-based compounds having antibacterial, antifungal, anticancer-hiv activity
EP0883432A1 (fr) * 1996-02-28 1998-12-16 Transdiffusia S.A. Procede de recuperation de composes volatils de faible masse moleculaire
JPH11209740A (ja) * 1998-01-19 1999-08-03 Kurita Water Ind Ltd ハロゲン化エチレン化合物の分離剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8556085B2 (en) 2010-11-08 2013-10-15 Stuart Bogle Anti-viral device

Also Published As

Publication number Publication date
AU2003245917A8 (en) 2003-12-31
DE10226099A1 (de) 2004-01-08
AU2003245917A1 (en) 2003-12-31
WO2003105990A3 (fr) 2004-04-01
EP1526910A2 (fr) 2005-05-04

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