Abstract: A process is indicated for improving the accuracy and reproducibility of the data measured in immunometric tests which are carried out using microtitration plates and in which a pipetting drift is observed. Correction is made by pipetting in a test control in a multiple determination at the start and at the end of a series of samples for examination, and deriving, from the change in the values measured in this multiple determination, a correction factor, varying from the start to the end, for the intermediate samples under examination.
Type:
Grant
Filed:
December 15, 1989
Date of Patent:
August 11, 1992
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Hans-Detlef Dopatka, Bernhard Giesendorf
Abstract: A process for removing toxins from solutions of proteins, in which an aqueous solution of a protein which contains a buffer substance, a chelating agent and a detergent is subjected to an ion exchange chromatography, is described.
Abstract: A process for the preparation of a material for affinity chromatography is described, in which a sulfated polysaccharide is bonded to a carrier material which has amino groups.For this purpose, a sulfated polysaccharide is treated with an oxidizing agent which oxidizes glycols to aldehydes, with cleavage of the carbon chain, and this modified sulfated polysaccharide is allowed to react with a carrier which has amino groups.It is possible using the described affinity material to adsorb proteins which bind to sulfated polysaccharides from solutions of these proteins and, where appropriate, then to desorb them, for example antithrombin III from blood plasma.
Abstract: Erythropoietin (EPO) peptides and the use thereof for preparing epitope-specific anti-EPO antibodies are described. Also described are corresponding anti-EPO antibodies which take the form of polyclonal antibodies (antisera) or of monoclonal antibodies. These antibodies are suitable for purifying EPO, EPO derivatives or EPO peptides. The epitope-specific anti-EPO antibodies according to the invention can also be used for the detection of EPO and, in particular, for the epitope-specific detection of EPO. Additionally described are anti-idiotype antibodies which imitate a receptor region of EPO. Finally, pharmaceuticals which contain the said EPO peptides, anti-EPO antibodies or anti-idiotype antibodies, and diagnostic aids for the detection of EPO or of anti-EPO antibodies, are described.
Abstract: An agent for the therapy or prophylaxis of disturbances of hemostasis, which contains tissue protein PP4, a process for the purification of PP4 by means of a hydrophobic adsorbent which is insoluble in water, and a process for the pasteurization of a solution containing PP4 in the presence of calcium ions and of at least one mono- or oligosaccharide or sugar alcohol and, where appropriate, of an amino acid, and the use of PP4, are described.
Abstract: Compounds of the formula I ##STR1## in which X denotes a hydrogen atom, a group which irreversibly masks the terminal amino group, or a protecting group which is conventional in peptide chemistry, such as, for example, Boc-, Z- or Fmoc-,A and B may be identical or different and denote an alipha-, beta- or gamma-amino acid which comprises 2 to 15 carbon atoms and up to 4 nitrogen atoms, 2 sulfur atoms and 6 oxygen atoms and whose side chain may be substituted, and B, if appropriate, denotes a dipeptide formed from these amino acids,C denotes arginine, lysine, tryrosine, phenylalanine or tryptophane, and their homologs,R.sub.1 and R.sub.2 are identical or different and denote a hydrogen atom or an alkyl radical having up to 4 carbon atoms,R.sub.3 to R.sub.8 are identical or different and denote hydrogen, an alkyl radical, an alkoxy radical or a hydrogen radical,Y denotes oxygen, andAn.sup.- denotes an anion,and their water-soluble salts, and a process for their preparation are described.
Abstract: The invention relates to magnetic protein conjugates of the formula IM--NH--CO--(CH.sub.2).sub.n --S--P' Iwith n=1-6, preferably with a n=1 or 2 and particularly preferably with n=1, in which M is a dispersible, magnetically reacting material or particle which carries amino groups, and P' is a protein, to a process for the preparation thereof and to the use thereof for the specific removal of cells or soluble antigens, receptors, substrates, cofactors or carbohydrate determinants from aqueous salt solutions or body fluids or as part of a diagnostic method or as a diagnostic aid, preferably for the removal of cells, preferably for bone marrow depletion or for HLA typing.
Abstract: An agent for the therapy of hemophilia A which is resistant to treatment with factor VIII is described, and is obtainable by maintaining a mixture of factor VIII, antithrombin III, a phospholipid and calcium ions in an aqueous solution at a temperature of from 1.degree. to 45.degree. C. for at least one minute, adding factor IX, and maintaining the solution at a temperature offrom 1.degree. to 45.degree. C. until addition of a sample of this solution to an inhibitor plasma results in a partial thromboplastin time (PTT) of 15 to 30 seconds, where appropriate adding a polyol and, where appropriate, an amino acid, and, where appropriate, drying the solution.
Abstract: Compounds of the general formula I ##STR1## in which R.sup.1 represents a hydrogen atom or an alkyl group of the formula CH.sub.3 (CH.sub.2).sub.n --where n=0 to 5,R.sup.2 represents a hydrogen atom when X is a carbamoyl group, an alkyl group having 1 to 6 carbon atoms, a group, bonded in an ether-like fashion, of the formula R.sup.3 --O--CH.sub.2 --(CHR.sup.4).sub.m --CH.sub.2 -- in whichR.sup.3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms,R.sup.4 is a hydroxyl group or an alkyloxy group having 1 to 3 carbon atoms, and m is 0 to 2, represents a group, bonded in an ether-like fashion, of the formula H--(CH.sub.2).sub.a --(O--(CH.sub.2).sub.b).sub.c -- where a=0 to 4, b=1 to 4 and c=1 to 7, orR.sup.2 represents a radical, bonded in a O-glycoside fashion of the formula ##STR2## in whichR.sup.5, R.sup.6 and R.sup.7, independently of one another, are a hydrogen atom or a hydroxyl group, andR.sup.
Type:
Grant
Filed:
August 28, 1990
Date of Patent:
February 25, 1992
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Cenek Kolar, Konrad Dehmel, Hans Peter Kraemer
Abstract: R.sup.2 is H or OH;R.sup.3 is H, OH, OCH.sub.3, CH.sub.3 or NH.sub.2 ;Rhu 4 is H, OH, OCH.sub.3, NH.sub.2 or ##STR2## The compounds of the formula I are prepared by fermentation of the strain Streptomyces parvulus DSM 40722 in the presence of substituted benzoic acids of the general formula II ##STR3## where R.sup.1 is H or OH;R.sup.2 is H or OH;R.sup.3 is H, OH, OCH.sub.3, CH.sub.3 or NH.sub.2 ;R.sup.4 is H, OH, OCH.sub.3 or NH.sub.2,and they inhibit Leukocyte elastase and can be used as pharmaceuticals.
Type:
Grant
Filed:
December 2, 1988
Date of Patent:
January 7, 1992
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Axel Zeeck, Ralf Thiericke, Hans Zahner, Gerhard Dickneite, Hans H. Sedlacek
Abstract: Chromogenic substrates for the detection of hydrolyzing enzymes, processes for the preparation of these chromogenic substrates and the use of the chromogenic substrates.The quantification of hydrolyzing enzymes for diagnostic purposes has to date been carried out by determination of the amounts of a fluorescent or highly absorbent chromogenic dyestuff liberated in the hydrolytic reaction, detection of which has in part been possible exlusively by instruments or in the neutral to alkaline pH range. After enzymatic hydrolysis, the chromogenic substrates according to the invention lead to highly sensitive and specifically measurable signals regardless of the pH range.Azo dyestuff compounds with the general formulaA--N.dbd.N--B (OR)in which A) and B) have the meanings given in claim 1 andR) is a radical which can be liberated by enzymatic hydrolysis, excluding a carbonyl radical,are provided.After enzymatic hydrolysis, highly sensitively and specifically measurable signals are obtained regardless of the pH range.
Abstract: The invention relates to synthetic peptides which have amino acid sequences which correspond, in whole or in part, to the amino acid sequence of prothrombin and are antigenic, to the use thereof for the immunization of an animal and for the purification of specific antibodies, to antibodies against these peptides, and to the use of the antibodies for the determination of the fragments F.sub.2 /F.sub.1+2.
Abstract: In the preparation of parenteral solutions for the therapy and prophylaxis of thromboses and embolisms, because of the poor solubility of t-PA hitherto either the infusion of very large volumes has been necessary, or else a solution with a low volume and a high t-PA concentration has been prepared at the expense of setting up a non-physiologically low pH of 2 to 5.Hence, the present invention relates to a process for the preparation of a solution of high concentration of a protein having plasminogen activator activity, where an increase in stability and solubility is achieved by adding at least two substances from the group of D- and/or L-amino acids, their salts, derivatives or homologs. This invention also relates to a process for the pasteurization of a protein solution having t-PA activity, and to a t-PA-containing solution prepared by the claimed process, and to the use of this solution as a fibrinolytic in human and veterinary medicine.
Abstract: The invention relates to a method for the determination of the activity of serine proteases and serine protease inhibitors in plasma or other biological fluids.The only methods hitherto available for rapid and accurate determination of the content of serine proteases or serine protease inhibitors have been very time-consuming and methodologically demanding. In the method according to the invention for the determination of the activity of serine proteases or serine protease inhibitors, specific inhibitors are inactivated by addition of at least one oxidizing agent and, where appropriate, at least one detergent. The addition of an omega-aminocarboxylic acid enhances and observed effects when the serine protease is plasmin.
Abstract: An agglutination method for the detection of antibodies against streptococcal deoxyribonuclease B is described, in which carrier-bound antibodies against streptococcal DNase B are mixed with a solution of streptococcal DNase which contains a protease inhibitor, and the sample in which the antibodies are to be detected, as well as an agent suitable for this method.
Abstract: 7-O-Glycosyl-rhodomycins which correspond to the general formula I below ##STR1## in which the radicals have the following meaning: R.sup.1 is a hydrogen atom or a hydroxyl group,R.sup.2 is a hydrogen atom or a C.sub.1 -C.sub.4 -alkyl group,R.sup.3 a hydroxyl group, an O-acyl protective group or the methyloxycarbonyl group,R.sup.4 is a hydrogen atom, an O-acyl protective group, an azido group, amino or trifluoroacetylamino group, a di-C.sub.1 -C.sub.4 -alkylamino group or cyanomethylamino group andR.sup.5 is an azido group, amino or trifluoroacetylamino group, a di-C.sub.1 -C.sub.4 -alkylamino group or cyanomethylamino group,where acyl protective group denotes an acetyl, mono-, di- or trihalogenoacetyl group with fluorine or chlorine as halogen or the p-nitrobenzoyl group, and a process for the preparation thereof and the use thereof as pharmaceuticals, are described.
Type:
Grant
Filed:
December 18, 1989
Date of Patent:
September 17, 1991
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Cenek Kolar, Hans P. Kraemer, Konrad Dehmel
Abstract: Insulin derivatives of the general formulae I and IIX--(Y.sub.1 --S--S--Y.sub.2 --Z--"Insulin").sub.m IA--S--Y.sub.3 --Z--"Insulin" IIin whichX is a radical of a physiologically tolerated carbon compound,Y.sub.1, Y.sub.2 and Y.sub.3 are, independently of one another, a chemical bond or an organic chemical bridge,S is a sulfur atom,"Insulin" denotes the biologically active peptidic portion of a natural, semisynthetic or synthetic insulin or an insulin which has been prepared by genetic engineering, or one of its biologically active analogs without the inessential amino group,Z is an amino group which is inessential for the biological activity of insulin,A is a hydrogen atom or the radical of a mercapto-containing, physiologically tolerated hydrocarbon compound, andm is an integer from 1 to 20,agents containing these derivatives, a process for the preparation of these derivatives, and their use for the treatment of metabolic disorders, are described.
Type:
Grant
Filed:
March 15, 1989
Date of Patent:
September 17, 1991
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Hartmut Lobermann, Eric P. Paques, Norbert Heimburger
Abstract: Glutamine-containing peptides, a process for the preparation thereof, and the use thereof Peptides of the structureH-A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -Gln-A.sub.6 -Lys-Val-A.sub.9 -A.sub.10 -NH.sub.2 (I)in which A.sub.1 =Val, LeuA.sub.2 =Gly, SerA.sub.3 =Pro, HypA.sub.4 =Gly, SerA.sub.6 =Gly, SerA.sub.9 =Leu, Ile andA.sub.10 =Gly, Ala,and the salts thereof, and a process for the preparation thereof, are described. These peptides act as substrates of blood coagulation factor XIII and can be used for the quantification of this enzyme and for detecting reactions in which activated blood coagulation factor XIII is produced, consumed or inhibited.
Abstract: The invention relates to a method for the purification of the a subunit of factor XIII by affinity chromatography, to a therapeutic composition containing the latter, and to the use of the therapeutic composition.Factor XIII has hitherto been purified either by methods which are technically very elaborate or else by use of toxic affinity chromatography materials. The invention has the aim of providing an improved method for the purification of the a subunit of factor XIII.Factor XIII is obtained according to the invention by a method in which the a subunit of factor XIII is reversibly bound to a matrix suitable for disulfide exchange reactions and is removed from the matrix by reaction with a reducing agent. The method according to the invention makes it possible to provide the biologically active a subunit of factor XIII in high purity.
Type:
Grant
Filed:
March 9, 1989
Date of Patent:
September 10, 1991
Assignee:
Behringwerke Aktiengesellschaft
Inventors:
Hartmut Lobermann, Jurgen Romisch, Werner Stuber
Abstract: A process for the production of a preparation of blood coagulation factor VIII which makes it possible to obtain a pasteurized product which is virtually free of immunoglobulins, isoagglutinins, fibronectin and coagulable fibrinogen is described.A product of this type can be used for the treatment of blood coagulation disturbances.