WO2008083680A2 - Utilisation de fractions de cohn-oncley ii/iii et/ou iii pour produire une préparation pharmaceutique destinée à traiter et prévenir des manifestations organiques dans le cadre de maladies auto-immunes - Google Patents

Utilisation de fractions de cohn-oncley ii/iii et/ou iii pour produire une préparation pharmaceutique destinée à traiter et prévenir des manifestations organiques dans le cadre de maladies auto-immunes Download PDF

Info

Publication number
WO2008083680A2
WO2008083680A2 PCT/DE2008/000043 DE2008000043W WO2008083680A2 WO 2008083680 A2 WO2008083680 A2 WO 2008083680A2 DE 2008000043 W DE2008000043 W DE 2008000043W WO 2008083680 A2 WO2008083680 A2 WO 2008083680A2
Authority
WO
WIPO (PCT)
Prior art keywords
use according
iii
agent
cohn
treatment
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/DE2008/000043
Other languages
German (de)
English (en)
Other versions
WO2008083680A3 (fr
Inventor
Torsten Matthias
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
Publication of WO2008083680A2 publication Critical patent/WO2008083680A2/fr
Anticipated expiration legal-status Critical
Publication of WO2008083680A3 publication Critical patent/WO2008083680A3/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the invention relates to the use of Cohn-Oncley fractions II / III and III for the preparation of a pharmaceutical preparation for the treatment of organ manifestations in autoimmune diseases, in particular glomerulonephritis and / or Wegener's granulomatosis.
  • SLE lupus erythematosus
  • SLE lupus erythematosus
  • antibodies are formed against the body's own components of the cell interior, which are e.g. In the case of tissue lesions, emerge from the closed cell, while the immune system considers it foreign to the body and fights it. This creates a fatal reaction cycle.
  • SLE occurs predominantly for the first time in young women. The occurrence in the total population is about 1: 2000, in females between 20 and 30 years about 1: 700. About half of the patients develop chronic glomerulonephritis, the most common cause of SLE death in the past.
  • This generalized autoimmune disease of unexplained aetiology is usually associated with the formation of numerous autoantibodies, immune complexes, and changes in the complement system.
  • Common clinical complaints are arthritides, skin inflammations such as erythema, changes in the blood count, nephritides, pleuritides, pericarditis and endocarditis, such as the Libmann-Sachs syndrome, as well as neurological and psychological disorders.
  • the course of the disease is variable and often fatal after decades of chronic course.
  • glomerulonephritis develops in the late phase. It is one of the most serious organ complications in SLE, which is usually the main cause of chronic dialysis kidney failure.
  • a special subform of this disease is the so-called steroid-resistant glomerulonephritis, which is no longer treatable even with high cortisone doses.
  • EP 0413 188 A2 describes a process for the preparation of intravenously tolerated immunoglobulin preparations which are chemically non-modifiable and which contain more than 5% IgM and more than 10% IgA, based on the total immunoglobulin content. These preparations thus obtained have a low anticomplementary activity.
  • the globulins are thereby obtained by means of a Cohn-Oncley fraction Il / III or III and purified by anion chromatography. Impurities are already removed in the precipitation with 0.5 to 5% octanoic acid at pH 4-6.
  • the object of the invention is therefore to provide an easily obtainable and readily available agent for the treatment and prevention of organ manifestations in autoimmune diseases.
  • a further object of the invention is to provide such an agent for the treatment and prevention of glomerulonephritis, in particular primary glomerulonephritis and / or Wegner's granulomatosis.
  • the invention also has the object of providing a means by which consequential damage of lupus erythematosus, in particular the development of glomerulon or lupus nephritis, can be prevented or symptoms that have already appeared can be alleviated or completely eliminated.
  • Oncley Group Il / III are included in particular in substances containing the organzer destroying antibodies of autoimmune diseases, in particular the
  • Glomeruli of the kidney can be treated. Such a fraction also contains anti-ds DNA antibodies among other components.
  • Such Cohn-Oncley fractions are usually obtained by pooling donor sera, with mostly 3,000 to 10,000 and sometimes even 100,000 sera from healthy donors being used.
  • pooled sera contain a myriad of different substances, especially proteins and lipoproteins. They also contain so-called "natural” antibodies, which are formed by the body without immunization even in the absence of an immunizing antigen.
  • the majority of such antibodies are IgG, which are distributed in a variety of also intravenously administered preparations from various companies.
  • Natural antibodies are polyreactive and bind with a variety of different antigens.
  • Typical precipitants are alcohols and polyalcohols, such as ethanol, propanol and isopropanol, and also polyols, such as, for example, ethylene glycol or propanediol.
  • ketones such as acetone
  • Other precipitating agents are carboxylic acids, especially C 5 - to C 2 - carboxylic acids, C 7 to C 9, especially the octanoic acid or Ca prylklare are particularly preferred.
  • Such precipitation solutions are usually buffered.
  • Typical buffers are known in the art, with phosphate buffered solution or buffers containing phosphates, especially alkali and alkaline earth phosphates, such as di- and tricalcium phosphate, are particularly preferred.
  • the precipitation is carried out in a sour environment, i. H. at a pH ⁇ 7.2, with pHs ⁇ 6, especially ⁇ 5.5 being preferred.
  • Particularly preferred are precipitates at a pH below 5, especially below 4.5, d. H. at values of about 4 or even lower.
  • the particular mole fraction of the organic precipitating agent to be used is readily ascertainable by the skilled person and is for example between 18 and 40% by volume for the ethanol, corresponding to a mole fraction of 0.0624 to 0.163, with a mole fraction of 0.0907 +/- 0.015 being especially is preferred. It is most preferred to carry out the precipitation according to the usual description of Cohn and Oncley at a mole fraction of 0.091 ethanol in the presence of calcium triphosphate. Another preferred. Method is the Precipitation in the presence of nucleotide phosphate, in particular of polynucleotide phosphates.
  • the serum and the precipitate are carried out in the presence of an inactivating agent for microorganisms, pathogenic germs and other disease-causing agents.
  • an inactivating agent for microorganisms, pathogenic germs and other disease-causing agents.
  • a typical inactivating agent is, for example, ⁇ -propiolactone, which is also used to increase the iV. Compatibility is used. Of course, this compatibility can also be carried out with any other suitable pharmaceutical acceptable agents.
  • the Cohn-Oncley fractions used in the invention by means of chromatographic methods, such as.
  • anion exchangers immobilized with protein A and / or protein G absorbents or increased its concentration of the remaining components, such as anti-ds DNA IgM.
  • composition prepared according to the invention is preferably at least partially freed from with precipitated IgA and IgG antibodies or their concentration depleted. This can be z. Example by means of the abovementioned mentioned chromatographic methods as well as by chromatography according to the molecular size.
  • the agent prepared according to the invention is freed of protein fractions having a molecular weight ⁇ 180 kDa, preferably ⁇ 200 kDa, in particular ⁇ 300 kDa.
  • the agent obtained according to the invention can be administered both intravenously and subcutaneously, intramuscularly, intrapleurally or intraperitoneally. It has been shown that the agent according to the invention can also be administered orally by means of suitable administration methods and Galenic processing. In this case, it is preferably processed in such a way that, by means of processes known to the person skilled in the art, digestion or degradation by means of proteases or other denaturation in the upper intestinal region, especially in the stomach and in the pancreas, is avoided.
  • subcutaneous or intramuscular or intraperitoneal administration of the composition according to the invention is particularly effective, it is also readily administered intravenously, whereby it can be administered as needed both rapidly and in larger doses, as in intramuscular or subcutaneous administration are not possible.
  • the pharmaceutical agent produced according to the invention is also suitable for complementary therapy together with other known agents for the treatment of SLE, in particular anti-inflammatory agents such as aspirin and / or corticosteroids and also cytostatics, in particular cyclophosphamide, azathioprine or mycophenolate mofetil.
  • anti-inflammatory agents such as aspirin and / or corticosteroids
  • cytostatics in particular cyclophosphamide, azathioprine or mycophenolate mofetil.
  • the invention thus also relates to a pharmaceutical combination pack for the simultaneous or time-staggered administration of an IgM-containing agent prepared according to the invention together with a further anti-inflammatory drug, an immunosuppressive drug and / or a cytostatic drug.
  • a pharmaceutical combination pack for the simultaneous or time-staggered administration of an IgM-containing agent prepared according to the invention together with a further anti-inflammatory drug, an immunosuppressive drug and / or a cytostatic drug.
  • the therapeutic agent prepared according to the present invention it is possible to treat a variety of clinical diseases of lupus erythematosus, such as nephritis, especially glomerulonephritis, including persistent proteinuria and acute and chronic renal failure as well as other organ manifestations such as butterfly erythema, mucous ulcer, Polyarthritis, in particular non-deforming polyarthritis, arthralgias, articular effusions, serositides such as pleurisy and pericarditis
  • the treatment by means of plasmapheresis ie a plasma exchange by means of apparative removal of autoantibodies (immunoapheresis)
  • a plasma exchange by means of apparative removal of autoantibodies can be combined with the administration of the agent prepared according to the invention, or by means of the fractions used according to the invention, appropriate apheresis devices can be produced.
  • appropriate apheresis devices can be produced.
  • mice represent a standard animal model that forms typical autoantibodies, with spontaneous glomerulonephritis developing after 6 to 8 months. From such mice, three treatment groups of 10 mice each were formed. Each A: was a control group that received no therapy.
  • B a group receiving intravenously administered 300 ⁇ g (in terms of protein content) of the agent obtained according to the invention at weekly intervals from 4 months of age.
  • C a group receiving a subcutaneous injection of 300 ⁇ g each of the agent of the invention from 4 months of age at weekly intervals.
  • mice had died after an average of 32 +/- 2 weeks. Both the animals treated by intravenous administration (Group B) and the animals treated by subcutaneous administration (Group C) achieved an average survival of 37.5 +/- 3 weeks. This effect is all the more surprising since the mice developed an allergic reaction against the administered human proteins. Despite this induced allergy, a clear survival rate was found in the mice treated according to the invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Developmental Biology & Embryology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne une préparation pharmaceutique destinée à traiter et à prévenir des manifestations organiques dans le cadre de maladies auto-immunes, la préparation pouvant être obtenue par utilisation de fraction Il/Ill et/ou III d'un fractionnement de Cohn Oncley à partir de sérums de donneurs humains. Une telle préparation peut également être utilisée en tant que combinaison d'au moins un agent anti-inflammatoire, d'au moins un agent immunosuppresseur et/ou d'au moins un agent cytostatique pour application simultanée et/ou décalée dans le temps.
PCT/DE2008/000043 2007-01-10 2008-01-10 Utilisation de fractions de cohn-oncley ii/iii et/ou iii pour produire une préparation pharmaceutique destinée à traiter et prévenir des manifestations organiques dans le cadre de maladies auto-immunes Ceased WO2008083680A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007001521.8 2007-01-10
DE102007001521A DE102007001521A1 (de) 2007-01-10 2007-01-10 Verwendung von Cohn-Oncley-Fraktionen II und II/III zur Behandlung des systemischen Lupus erythematodes

Publications (2)

Publication Number Publication Date
WO2008083680A2 true WO2008083680A2 (fr) 2008-07-17
WO2008083680A3 WO2008083680A3 (fr) 2009-12-03

Family

ID=39509709

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2008/000043 Ceased WO2008083680A2 (fr) 2007-01-10 2008-01-10 Utilisation de fractions de cohn-oncley ii/iii et/ou iii pour produire une préparation pharmaceutique destinée à traiter et prévenir des manifestations organiques dans le cadre de maladies auto-immunes

Country Status (2)

Country Link
DE (1) DE102007001521A1 (fr)
WO (1) WO2008083680A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011124668A1 (fr) 2010-04-08 2011-10-13 Universitätsspital Basel Immunoglobuline issue du plasma pour l'utilisation dans le traitement et la prévention du syndrome inflammatoire de reconstitution immune (iris)
CN104958761A (zh) * 2010-05-26 2015-10-07 巴克斯特国际公司 从血浆制备富含IgG的组合物的方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2901822A1 (de) * 1979-01-18 1980-07-31 Biotest Serum Institut Gmbh Verfahren zur herstellung einer fuer die intravenoese applikation geeigneten immunglobulinloesung, die igm in ankonzentrierter form enthaelt
DE3927111C3 (de) 1989-08-17 1994-09-01 Biotest Pharma Gmbh Verfahren zur Herstellung nicht modifizierter intravenös verabreichbarer IgM- und/oderIgA-haltiger Immunglobulinpräparate
IL140155A (en) * 1998-06-09 2005-12-18 Statens Seruminstitut Process for producing immunoglobulins for intravenous administration and other immunoglobulin products
JP4685238B2 (ja) * 1998-06-09 2011-05-18 ツエー・エス・エル・ベーリング・アクチエンゲゼルシヤフト 静脈投与用免疫グロブリン及び他の免疫グロブリン生成物の製造法
US20020098182A1 (en) * 2000-09-28 2002-07-25 Richard Weisbart Treatment of immune-mediated diseases by oral administration of plasma fractions enriched in immunoglobulin G
DE10127712A1 (de) * 2001-06-07 2002-12-19 Torsten Witte Anwendung von IgM-Antikörpern gegen dsDNA beim systemischen Lupus erythematodes mit Nephritis

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011124668A1 (fr) 2010-04-08 2011-10-13 Universitätsspital Basel Immunoglobuline issue du plasma pour l'utilisation dans le traitement et la prévention du syndrome inflammatoire de reconstitution immune (iris)
CN104958761A (zh) * 2010-05-26 2015-10-07 巴克斯特国际公司 从血浆制备富含IgG的组合物的方法
CN104958761B (zh) * 2010-05-26 2021-01-01 百深公司 从血浆制备富含IgG的组合物的方法

Also Published As

Publication number Publication date
WO2008083680A3 (fr) 2009-12-03
DE102007001521A1 (de) 2008-07-17

Similar Documents

Publication Publication Date Title
DE2936047C2 (fr)
DE2751717C2 (fr)
DE2606118C2 (de) Verfahren zur Herstellung eines gereinigten Gamaglobulins und intravenös verabreichbares Arzneimittel
EP0122909B1 (fr) Fraction contenant de l'immunoglobuline-G
EP0659767B2 (fr) Procédé de préparation d'un concentré d'immunoglobuline G anti-D et compositions pharmaceutiques qui le contiennent
DE3927111C3 (de) Verfahren zur Herstellung nicht modifizierter intravenös verabreichbarer IgM- und/oderIgA-haltiger Immunglobulinpräparate
EP0013901B1 (fr) Procédé de préparation d'une solution injectable par voie intraveineuse d'immunoglobuline, contenant de l'IgM concentrée
DE3825429A1 (de) Intravenoes verabreichbares polyklonales immunglobulin-praeparat mit hohem igm-gehalt und verfahren zu seiner herstellung
DE3426903A1 (de) Eine immunglobulinpraeparation in kombination mit einer anderen pharmakologisch wirksamen praeparation zur verwendung bei der behandlung von krankheiten
EP0085747B2 (fr) Immunoglobuline humaine pour administration intraveineuse et son procédé de préparation
DE3927112C1 (fr)
DE2837168A1 (de) Verfahren zur herstellung einer fuer die intravenoese anwendung geeigneten immunglobulinloesung
EP0835880A1 (fr) Procédé de préparation d'un médicament contenant de l'IgM administrable par voie intraveineuse
CH684164A5 (de) Intravenös anwendbare Immunglobulinlösung.
DE2639012B2 (de) Immuntherapeutikum zur Prophylaxe und Therapie von Pseudomonas aeruginosa-Infeklionen
DE3430320A1 (de) Verfahren zur herstellung von immunglobulin-praeparaten mit verminderter komplementaktivitaet
DE102007001521A1 (de) Verwendung von Cohn-Oncley-Fraktionen II und II/III zur Behandlung des systemischen Lupus erythematodes
EP0120835A2 (fr) Procédé d'inactivation de substances provoquant des réactions d'incompatibilité
EP1397158B1 (fr) UTILISATION D'ANTICORPS IgM ANTI-ADN NATIF EN CAS DE LUPUS ERYTHEMATEUX DISSEMINE AVEC NEPHRITE
WO1997025352A1 (fr) PROCEDE D'ISOLATION DES IMMUNOGLOBULINES G et A
DE60118409T2 (de) Herstellungsverfahren von immunglobulinen, die gegen menschliche thymozyten gerichtet sind
DE2533183C3 (de) Verfahren zum Herstellen gereinigter Immunglobuline
DE2532276C3 (de) Verfahren zur Reinigung von Human-Antilymphozytenserum
DE2733923B2 (de) Verfahren zur Gewinnung von Humanalbumin
AT226372B (de) Dessaggregiertes Gammaglobulin und Verfahren zu seiner Herstellung

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08706744

Country of ref document: EP

Kind code of ref document: A2

122 Ep: pct application non-entry in european phase

Ref document number: 08706744

Country of ref document: EP

Kind code of ref document: A2