DK144679B - PROCEDURE FOR THE EXTRACTION OF INTRAVENOUS COMPATIBLE GAMMA LOBULINES - Google Patents
PROCEDURE FOR THE EXTRACTION OF INTRAVENOUS COMPATIBLE GAMMA LOBULINES Download PDFInfo
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- DK144679B DK144679B DK584375AA DK584375A DK144679B DK 144679 B DK144679 B DK 144679B DK 584375A A DK584375A A DK 584375AA DK 584375 A DK584375 A DK 584375A DK 144679 B DK144679 B DK 144679B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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Description
144679144679
Opfindelsen angår en fremgangsmåde til udvinding af intravenøskompatible gammaglobulinerr fra et udfældet gammaglobulin-råbundfald fra blod, ved hvilken den antikomplementære gammaglobulinbestanddel i en vandig opløsning af råbundfaldet bindes til en vandopløselig polymer og udfældes, hvorefter det indtil da i opløsning forblivende, intravenøskompatible gammaglobulin udfældes.The invention relates to a method of recovering intravenous compatible gamma globulins from a precipitated gamma globulin raw precipitate in which the anticomplementary gamma globulin component is bound to a water-soluble polymer in an aqueous solution and precipitates, until it remains intact in gummy bile until dissolved.
Blod er en væske, som består af faste og flydende bestanddele.Blood is a liquid which consists of solid and liquid constituents.
Til de faste bestanddele hører røde og hvide blodlegemer såvel som blodpladerne. Plasmaet eller den flydende del af blodet indeholder ca. 90$ vand og lo$ faste stoffer. Til de i plasmaet opløste stoffer hører bl.a. gammaglobulin, som anvendes til behandling og prophylaxe af infektioner. Til isolering af gammaglobulin må alle andre i plasmaet tilstedeværende substanser fjernes i størst mulig udstrækning, for at der skal opnås et så vidt muligt rent gammaglobulin.The solid constituents include red and white blood cells as well as the platelets. The plasma or liquid part of the blood contains approx. $ 90 water and lo $ solids. Among the substances dissolved in the plasma include gamma globulin used to treat and prophylaxis of infections. To isolate gamma globulin, all other substances present in the plasma must be removed to the greatest extent possible in order to obtain as far as possible pure gamma globulin.
Til fældning og isolering af gammaglobulin fra blod anvender man navnlig en under betegnelsen "COHN-metode" kendt fremgangsmåde (COHN et al., J. Amer. Chem. Soc·, Vol. 68, 1946, pp. 459-475; Vol.In particular, for the precipitation and isolation of gamma globulin from blood, a method known under the term "COHN method" is used (COHN et al., J. Amer. Chem. Soc., Vol. 68, 1946, pp. 459-475; Vol.
72, 195o, pp. 465-474). Denne fremgangsmåde går ud fra et af forskellige blodprøver blandet plasma. Den er i princippet en fraktioneret fældning under forskellige betingelser. X det første trin bliver ved t 3° C og en pH-værdi på 7»2 med en ethanoltilsætning på 8$ først hovedsagelig udskilt fibrinogen som første sediment. Den resterende væske fældes i et andet trin med ca. 19$ ethanol ved pH 5»6. Bundfaldet indeholder overvejende gammaglobulin. Til rensning af dette som COIIN-fraktion II-III betegnede bundfald opløses dette atter og 144679 2 fældes ved pH 5 med 8/o ethanol. Den resterende væske fældes derefter påny med 25/» ethanol ved pH 7*2, Det herved dannede bundfald består af mindst 9o0/0 gammaglobulin. Bundfaldet optages i en egnet bufferløsning og er efter sterilfiltrering klar til anvendelse på mennesker.72, 195o, pp. 465-474). This procedure is based on one of various blood samples mixed with plasma. It is in principle a fractional precipitate under different conditions. X at the first step, at t 3 ° C and a pH of 7 »2 with an ethanol addition of $ 8, fibrinogen is first primarily excreted as the first sediment. The remaining liquid is precipitated in a second step by approx. 19 $ ethanol at pH 5 »6. The precipitate contains predominantly gamma globulin. To purify this precipitated as COIIN fraction II-III, this is dissolved again and precipitated at pH 5 with 8% ethanol. The remaining liquid is then re-precipitated with 25 µl of ethanol at pH 7 * 2. The resulting precipitate consists of at least 900/0 gamma globulin. The precipitate is taken up in a suitable buffer solution and, after sterile filtration, is ready for use in humans.
Det har vist sig, at gammaglobulinpræparater, som er udvundet på den ovenfor beskrevne måde eller på anden måde, i talrige tilfælde er antikomplementært virksomme, så at der ved intravenøs indgivelse opstår komplikationer på grund af legemsreaktioner.It has been found that gamma globulin preparations, obtained in the manner described above or otherwise, are in many cases anticomplementary, causing complications due to body reactions by intravenous administration.
Man har derfor allerede forsøgt at forøge intravenøskompatibiliteten af gammaglobuliner. Som eksempler skal nævnes følgende, fra litteraturen kendte fremgangsmåders 1. Behandling med egnede enzymer 2. Hydrolyse ved høj hydrogenionkoncentration (f.eks. ved pH 4,o) 3. Modificering med β-propiolacton.Therefore, attempts have already been made to increase the intravenous compatibility of gamma globulins. Examples of the following are known from the literature of methods 1. Treatment with suitable enzymes 2. Hydrolysis at high hydrogen ion concentration (eg at pH 4, o) 3. Modification with β-propiolactone.
Det har imidlertid vist sig, at de kendte fremgangsmåder modificerer gammaglobulinmolekyleme og ændrer dem således i deres kemiske struktur, at deres virksomhed formindskes og deres gennemsnitlige opholdstid i organismen forkortes.However, it has been found that the known methods modify the gamma globulin molecules and change them in their chemical structure to reduce their activity and shorten their average residence time in the organism.
Ved en anden kendt fremgangsmåde (GB patentskrift 1 372 953) går man ud fra et gammaglobulin-råbundfaid, der f.eks. er fremkommet ved cryoethanol-fraktionering ifølge COHN, og som indeholder både intravenøstkompatible og antikomplementære gammaglobulin-be s tand-dele. De antikomplementære bestanddele bindes i en vandig opløsning af råbundfaldet ved hjælp af et vandopløseligt salt eller en vandopløselig, lineær, trådformet, uladet polymer, hvorved de danner et uopløseligt kompleks, som bundfældes, f.eks. ved hjælp af polyethy-lenglycol. Da der imidlertid ved denne bundfældning ikke kan foretages en nøjagtig adskillelse mellem ønskede og uønskede bestanddele, er det til opnåelse af en fuldstændig bundfældning af de antikomplementære bestanddele nødvendigt at anvende fældningsmidlet i en sådan mængde, at der også bundfældes en vis mængde rene globuliner. Den kendte fremgangsmåde er derfor forholdsvis uøkonomisk.Another known method (GB patent 1,372,953) is based on a gamma globulin crude base fluid, e.g. has been obtained by cryoethanol fractionation according to COHN, which contains both intravenously compatible and anti-complementary gamma globulin denticles. The anticomplementary constituents are bound in an aqueous solution of the raw precipitate by a water-soluble salt or a water-soluble, linear, filamentous, uncharged polymer, thereby forming an insoluble complex, which is precipitated, e.g. using polyethylene glycol. However, since this precipitation cannot be accurately separated between desired and undesirable constituents, it is necessary to use a complete precipitate of the anticomplementary constituents in such an amount that a certain amount of pure globulins is also precipitated. The known method is therefore relatively uneconomical.
Opfindelsen har til formål at tilvejebringe en fremgangsmåde af den indledningsvis angivne art, ved hvilken ulemperne ved de kendte fremgangsmåder afhjælpes, og som således bevirker en minimal ændring af gammaglobulinmolekylernes struktur og reducerer den antikomplementære virksomhed af præparatet i sammenligning med kendte præparater, og som giver et maksimalt udbytte af rent, intravenøskompatibelt gammaglobulin.The invention has for its object to provide a method of the kind described in the preamble, by which the disadvantages of the known methods are remedied, thus effecting a minimal change in the structure of the gamma globulin molecules and reducing the anticomplementary activity of the composition in comparison with known compositions, maximum yield of pure, intravenously compatible gamma globulin.
3 1446793 144679
Ifølge opfindelsen opnås dette ved, at der som vandopløselig polymer til binding af den antikomplementære gammaglobuliribestand-del anvendes hydroxyethylstivelse (HES) med en molekylvægt på looo - 900.000 og i en koncentration på 1 - 30 vægt-$ i opløsningen, der har en pH-værdi på 3,^ - 8,0. Et optimalt resultat opnås ifølge opfindelsen ved anvendelse af HES i den vandige opløsning i en mængde på 8-10 vægt-$. PH-værdien holdes hensigtsmæssigt ved 6,5-6,9.According to the invention, this is achieved by using as a water-soluble polymer for bonding the anti-complementary gamma globuli component, hydroxyethyl starch (HES) having a molecular weight of 1000 - 900,000 and at a concentration of 1 to 30% by weight in the solution having a pH value of 3, ^ - 8.0. An optimum result is achieved according to the invention by using HES in the aqueous solution in an amount of 8-10 wt. The PH value is suitably kept at 6.5-6.9.
Efter opløsning af gammaglobulinråbundfaldet i den bufrede HES-opløsning tilsættes til den sidstnævnte blanding polyet-hylenglycol (PEG) indtil en koncentration på 10$. Efter tilsætning af PEG sker en udfældning af de substanser, som er bundet til HES, og som indeholder de antikomplementære bestanddele af gammaglobulinråbundfaldet· De udfældede uønskede bestanddele fjernes ved centrifugering. Den resterende væske blandes i en fraktioneret fældning ved pH 7,2 med yderligere 20$ PEG. Efter tilsætningen udfældes de ønskede bestanddele af gammaglobulin-rå-bundfaldet og kan udvindes ved centrifugering. Det fremkomne bundfald bringes i en fysiologisk natriumchloridopløsning på en koncentration af 5»2$ æggehvidestof.After dissolving the gamma globulin precipitate in the buffered HES solution, the polyethylene glycol (PEG) mixture is added to a concentration of $ 10. After addition of PEG, the precipitates of the substances bound to the HES which contain the anti-complementary constituents of the gamma globulin raw precipitate · The precipitated undesirable constituents are removed by centrifugation. The remaining liquid is mixed in a fractional precipitate at pH 7.2 with an additional 20 $ PEG. After the addition, the desired constituents of the gamma globulin crude precipitate are precipitated and can be recovered by centrifugation. The resulting precipitate is brought into a physiological sodium chloride solution at a concentration of 5 »2 $ egg white.
I det følgende forklares de enkelte fremgangsmådetrin endnu engang på grundlag af et udførelseseksempel.In the following, the individual process steps are explained again on the basis of an exemplary embodiment.
Fraskillelse af gammaglobulinet.Separation of the gamma globulin.
Man går ud fra en samlet plasma, til hvilken der tilsættes 8$ ethanol til udfældning ved en pH-værdi på 7,2 ved * 3° C, Derved udskilles fraktion I. Til den resterende væske tilsættes derefter ved •4· 5°c og en pH-værdi på 5»8 19$ ethanol. Derved udskilles fraktion II-III, som består af gammaglobuliner. Bundfaldet opløses atter og fældes påny ved pH 5 med 8$ ethanol. Den resterende væske fældes derefter påny med 25$ ethanol ved pH 7»2. Det herved dannede bundfald (fraktionll) består af mindst 9o$ gammaglobulin.A total plasma is added to which 8 $ ethanol is added to precipitate at a pH of 7.2 at * 3 ° C, thereby separating fraction I. To the remaining liquid is then added at 4 ° 5 ° c. and a pH of 5 »8 19 $ ethanol. This separates fraction II-III, which consists of gamma globulins. The precipitate is dissolved again and precipitated again at pH 5 with 8 $ ethanol. The remaining liquid is then re-precipitated with 25 $ ethanol at pH 7 »2. The precipitate thus formed (fraction II) consists of at least 90 µg of gamma globulin.
Formindskelse af den antikomplementære virksomhed.Decrease in the anti-complementary activity.
Gammaglobulinbundfaldet opløses påny i en buffret vandig opløsning ved pH 6,7 i en koncentration på ca. 6$, hvorhos der til den vandige opløsning er tilsat ca. lo$ hydroxyethylstivelse med en molekylvægt på ca. 400.000, målt på grundlag af viskositetsmålinger. Denne tilsætning muliggør en adskillelse mellem antikomplementære bestanddele og intravenøskompatible gammaglobuliner.The gamma globulin precipitate is redissolved in a buffered aqueous solution at pH 6.7 at a concentration of ca. About $ 6, to which about aqueous solution is added approx. hydroxyethyl starch having a molecular weight of approx. 400,000, measured on the basis of viscosity measurements. This addition enables a separation between anticomplementary components and intravenous compatible gamma globulins.
4 1446794 144679
Overføring til en fysiologisk kogsaltopløsning.Transfer to a physiological saline solution.
Efter tilsætning af 10$ polyethylenglykol med en molekylvægt på ca. 4000, hvorved de antikomplementære bestanddele bundfældes, centrifugeres blandingen. Deh resterende væske blandes med 20$ p o ly ethyl engly ko 1, også med en molekylvægt på ca. 4000, hvorved også de intravenøskompatible bestanddele bundfældes. Det således udvundne bundfald fracentrifugeres og bringes i en fysiologisk kogsaltopiø.sning til en koncentration på 5,2$ æggehvidestof og sterilfiltreres derefter. Opløsningen er herefter klar til terapeutisk brug.After the addition of 10 $ polyethylene glycol with a molecular weight of approx. 4000, whereby the anti-complementary constituents are precipitated, the mixture is centrifuged. The remaining liquid is mixed with 20 $ p o ly ethyl engly cow 1, also with a molecular weight of approx. 4000, thereby also precipitating the intravenous compatible components. The precipitate thus recovered is centrifuged and brought into a physiological boiling salt solution to a concentration of 5.2 $ egg white and then sterile filtered. The solution is then ready for therapeutic use.
På tegningen viser fig. 1 strukturformlen for hydroxyethylstivelse (HES), fig. 2 immun-elektrophorese-diagrammer (iEP) af forskellige gammaglobuliner henholdsvis af normalsera, som er fremstillet efter kendte henholdsvis den ny fremgangsmåde, hvorhos den øvre halvdel af diagrammet i hvert af tilfældene viser IEP-diagram-mer for normal-blodsera, medens den nedre halvdel af diagrammerne viser følgende substansers a) standard-gammaglobulin, b) proteolytisk modificeret gammaglobulin, c) betapropiolacton-modificeret gammaglobulin, d) gammaglobulin fremstillet ved fremgangsmåden ifølge opfindelsen.In the drawing, FIG. 1 shows the hydroxyethyl starch structural formula (HES); 2 immuno-electrophoresis (iEP) diagrams of various gamma globulins respectively of normal sera prepared according to known and novel methods respectively, wherein the upper half of the diagram shows in each case IEP diagrams for normal blood sera while the lower one half of the diagrams show the following substances a) standard gamma globulin, b) proteolytically modified gamma globulin, c) betapropiolactone modified gamma globulin, d) gamma globulin prepared by the method of the invention.
Ved alle prøverne ifølge diagrammerne a) til c) drejer det sig dm et i handelen værende modificeret præparat. Disse prøver viser foruden gammaglobulinlinjen (langstrakt seglfornet linje i højre side af diagrammet) også yderligere æggehvidestofbestanddele af det menneskelige blod. Gammaglobulinlinjerne er ved prøverne a) og b) vist uskarpt på grund af den kemiske modificering. Prøven c) viser en i forhold til gammaglobulinlinjen i sammenligningsserummet forandret position.All samples according to diagrams (a) to (c) are a commercially modified preparation. In addition to the gamma globulin line (elongated sickle-like line on the right side of the diagram), these samples also show additional egg white constituents of the human blood. The gamma globulin lines are blurred by samples a) and b) due to the chemical modification. Sample c) shows a changed position relative to the gamma globulin line in the comparison serum.
I modsætning hertil viser sig klart, at prøven d) består praktisk talt udelukkende af rent gammaglobulin, da spektrets seglformede linje tydeligt er indeholdt i normalserummet.In contrast, the sample (d) clearly shows that it consists almost entirely of pure gamma globulin, since the sickle-like line of the spectrum is clearly contained in the normal serum.
Af diagrammerne kan ses, at det ved fremgangsmåden ifølge opfindelsen udvundne gammaglobulin er praktisk taget loo$ rent og fuldstændig svarer til gammaglobulinet i det oprindelige blodserum.From the diagrams it can be seen that the gamma globulin recovered by the method according to the invention is practically lucid and completely corresponds to the gamma globulin in the original blood serum.
Det sidstnævnte betyder, at molekylerne ikke er modificeret eller kemisk forandret.The latter means that the molecules are not modified or chemically altered.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2500076 | 1975-01-02 | ||
| DE2500076A DE2500076C3 (en) | 1975-01-02 | 1975-01-02 | Process for the production of intravenously tolerated gamma globulins |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK584375A DK584375A (en) | 1976-07-03 |
| DK144679B true DK144679B (en) | 1982-05-10 |
| DK144679C DK144679C (en) | 1982-10-11 |
Family
ID=5935911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK584375A DK144679C (en) | 1975-01-02 | 1975-12-22 | PROCEDURE FOR THE EXTRACTION OF INTRAVENOUS COMPATIBLE GAMMA LOBULINES |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS5512001B2 (en) |
| AT (1) | AT344883B (en) |
| AU (1) | AU505416B2 (en) |
| BE (1) | BE837211A (en) |
| CA (1) | CA1058075A (en) |
| DD (1) | DD121875A5 (en) |
| DE (1) | DE2500076C3 (en) |
| DK (1) | DK144679C (en) |
| EG (1) | EG11987A (en) |
| ES (1) | ES443982A1 (en) |
| FR (1) | FR2296429A1 (en) |
| GB (1) | GB1495159A (en) |
| IE (1) | IE43449B1 (en) |
| IL (1) | IL48766A (en) |
| IN (1) | IN143525B (en) |
| NL (1) | NL179824C (en) |
| PL (1) | PL99599B1 (en) |
| SE (1) | SE437470B (en) |
| SU (1) | SU576898A3 (en) |
| ZA (1) | ZA758050B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984004309A1 (en) * | 1983-05-02 | 1984-11-08 | Pharmacia Ab | Process in the purification of biologically active substances |
| DK151609B (en) * | 1976-02-07 | 1987-12-21 | Armour Pharma | PROCEDURE FOR THE EXTRACTION OF INTRAVENOST COMPATIBLE GAMMAGLOBULIN |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6016406B2 (en) * | 1976-08-06 | 1985-04-25 | マイヤ−、ル−イス、コ−バル | Method for producing intravenously administrable gamma globulin and gamma globulin prepared thereby |
| US4124576A (en) * | 1976-12-03 | 1978-11-07 | Coval M L | Method of producing intravenously injectable gamma globulin |
| GB1603244A (en) * | 1977-05-20 | 1981-11-18 | Max Planck Gesellschaft | Medicaments for the suppression of pathological processes |
| JPS5822085B2 (en) * | 1977-07-19 | 1983-05-06 | 株式会社ミドリ十字 | Intravenous gamma globulin preparations |
| AT359641B (en) * | 1978-09-19 | 1980-11-25 | Immuno Ag | METHOD FOR PRODUCING AN INTRAVENOUS ADMINISTRABLE ANTIBODY-CONTAINING IMMUNOGLOBULIN PREPARATE |
| EP0019403B1 (en) * | 1979-05-10 | 1985-07-31 | American Hospital Supply Corporation | Hydroxyalkyl-starch drug carrier |
| US4396608A (en) * | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
| ATE19735T1 (en) * | 1982-02-08 | 1986-05-15 | Schweiz Serum & Impfinst | INTRAVENOUSLY DELIVERABLE HUMAN IMMUNOGLOBULIN AND METHOD OF PRODUCTION THEREOF. |
| US4482483A (en) * | 1983-04-06 | 1984-11-13 | Armour Pharmceutical Company | Composition of intravenous immune globulin |
| US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| DE19907257A1 (en) * | 1999-02-21 | 2000-09-14 | Bernd Horst Meier | Means for controlling the diffusion of injection solutions |
| DE10040707A1 (en) * | 2000-08-17 | 2002-03-14 | Braun Melsungen Ag | Injectable aqueous medicament, containing colloid, e.g. hydroxyethyl starch, to modulate mobility, diffusion, pharmacokinetic and electrophoretic properties of active agent and improve effectiveness |
| DE10303974A1 (en) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid β (1-42) oligomers, process for their preparation and their use |
| KR101667623B1 (en) | 2005-11-30 | 2016-10-19 | 애브비 인코포레이티드 | Monoclonal antibodies against amyloid beta protein and uses thereof |
| PL1954718T3 (en) | 2005-11-30 | 2015-04-30 | Abbvie Inc | Anti-a globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| EP2124952A2 (en) | 2007-02-27 | 2009-12-02 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
| MX336196B (en) | 2010-04-15 | 2016-01-11 | Abbvie Inc | Amyloid-beta binding proteins. |
| MX358739B (en) | 2010-08-14 | 2018-09-03 | Abbvie Inc Star | Amyloid-beta binding proteins. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE348942B (en) * | 1970-06-02 | 1972-09-18 | Statens Bakteriologiska Labor | |
| DE2234069A1 (en) * | 1971-07-16 | 1973-02-08 | South African Inventions | METHOD OF MANUFACTURING A PURIFIED GAMMA GLOBULIN |
| ZA738779B (en) * | 1972-11-27 | 1974-10-30 | Baxter Laboratories Inc | Production of gamma globulin |
| JPS49101516A (en) * | 1973-01-13 | 1974-09-25 |
-
1975
- 1975-01-02 DE DE2500076A patent/DE2500076C3/en not_active Expired
- 1975-12-16 NL NLAANVRAGE7514627,A patent/NL179824C/en not_active IP Right Cessation
- 1975-12-18 SE SE7514388A patent/SE437470B/en not_active IP Right Cessation
- 1975-12-22 DK DK584375A patent/DK144679C/en active
- 1975-12-23 AT AT981675A patent/AT344883B/en active
- 1975-12-26 FR FR7539814A patent/FR2296429A1/en active Granted
- 1975-12-27 JP JP15974275A patent/JPS5512001B2/en not_active Expired
- 1975-12-29 GB GB53020/75A patent/GB1495159A/en not_active Expired
- 1975-12-29 DD DD190614A patent/DD121875A5/xx unknown
- 1975-12-30 ZA ZA00758050A patent/ZA758050B/en unknown
- 1975-12-30 IL IL48766A patent/IL48766A/en unknown
- 1975-12-30 ES ES443982A patent/ES443982A1/en not_active Expired
- 1975-12-30 IE IE2826/75A patent/IE43449B1/en unknown
- 1975-12-30 CA CA242,734A patent/CA1058075A/en not_active Expired
- 1975-12-30 IN IN2413/CAL/75A patent/IN143525B/en unknown
- 1975-12-30 BE BE6045314A patent/BE837211A/en not_active IP Right Cessation
- 1975-12-30 AU AU87921/75A patent/AU505416B2/en not_active Expired
- 1975-12-30 EG EG775/75A patent/EG11987A/en active
- 1975-12-31 SU SU7502306354A patent/SU576898A3/en active
-
1976
- 1976-01-01 PL PL1976186289A patent/PL99599B1/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK151609B (en) * | 1976-02-07 | 1987-12-21 | Armour Pharma | PROCEDURE FOR THE EXTRACTION OF INTRAVENOST COMPATIBLE GAMMAGLOBULIN |
| WO1984004309A1 (en) * | 1983-05-02 | 1984-11-08 | Pharmacia Ab | Process in the purification of biologically active substances |
Also Published As
| Publication number | Publication date |
|---|---|
| EG11987A (en) | 1981-12-31 |
| IL48766A (en) | 1979-11-30 |
| PL99599B1 (en) | 1978-07-31 |
| JPS5191321A (en) | 1976-08-10 |
| AU8792175A (en) | 1977-07-14 |
| CA1058075A (en) | 1979-07-10 |
| AT344883B (en) | 1978-08-10 |
| AU505416B2 (en) | 1979-11-22 |
| SE437470B (en) | 1985-03-04 |
| GB1495159A (en) | 1977-12-14 |
| FR2296429A1 (en) | 1976-07-30 |
| BE837211A (en) | 1976-06-30 |
| ATA981675A (en) | 1977-12-15 |
| DE2500076C3 (en) | 1982-11-18 |
| FR2296429B1 (en) | 1978-12-01 |
| ES443982A1 (en) | 1977-07-16 |
| NL7514627A (en) | 1976-07-06 |
| NL179824B (en) | 1986-06-16 |
| IL48766A0 (en) | 1976-02-29 |
| DD121875A5 (en) | 1976-09-05 |
| DE2500076B2 (en) | 1979-02-22 |
| IE43449B1 (en) | 1981-02-25 |
| DE2500076A1 (en) | 1976-07-08 |
| SE7514388L (en) | 1976-07-05 |
| ZA758050B (en) | 1976-12-29 |
| DK584375A (en) | 1976-07-03 |
| IE43449L (en) | 1976-07-02 |
| IN143525B (en) | 1977-12-17 |
| NL179824C (en) | 1986-11-17 |
| DK144679C (en) | 1982-10-11 |
| SU576898A3 (en) | 1977-10-15 |
| JPS5512001B2 (en) | 1980-03-29 |
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