Boehringer Mannheim Gmbh

Gunter Weimann

Hans-Georg Batz

Wolfgang Gruber

Klaus Stellner

August W Wahlefeld

Erich Haid

Ulfert Deneke

Elli Rauscher

Alexander Hagen

Erich Bernt

Fritz Stahler

Hans-Ralf Linke

Michael Nelboeck-Hochstetter

August Wilhelm Wahlefeld

Joachim Ziegenhorn

Elmar Bosies

Sigmar Klose

Rudi Gall

Josef Maier

Uwe Bicker

Ulrich Neumann

Klaus Muhlegger

Wulf Pahlke

Eugen Schaich

Jurgen Horn

Albert Roder

Klaus Beaucamp

Walter Schneider

Brigitte Draeger

Dieter Jaworek

Michael Nelbock-Hochstetter

Helmut Determann

Gerhard Michal

Karl-Heinz Botsch

Michael Stoltz

Michal Gerhard

.alpha.-Amylase is determined by the enzymatic splitting of an .alpha.-amylase substrate and measurement of a fission product, wherein there is used as a substrate a maltoheptaose compound of the formula ##STR1## wherein R is a glucoside, phenylglucoside, mononitrophenylglucoside, dinitrophenylglucoside, sorbitol or gluconic acid group. Reagents comprising such a substrate and a system for the determination of a fission product formed from the amylase substrate by .alpha.-amylase, are also provided. A process for the preparation of a maltoheptaose will Bacillus macerans amylase, free of p-nitrophenyl-alpha-glucoside splitting activity is disclosed.

Process for preparing a maltoheptaose derivative

.alpha.-Amylase is determined by the enzymatic splitting of an .alpha.-amylase substrate and measurement of a fission product, wherein there is used as a substrate a maltoheptaose compound of the formula ##STR1## wherein R is a glucoside, phenylglucoside, mononitrophenylglucoside, dinitrophenylglucoside, sorbitol or gluconic acid group. Reagents comprising such a substrate and a system for the determination of a fission product formed from the amylase substrate by .alpha.-amylase, are also provided.

Process and reagent for the determination of .alpha.-amylase

The present invention provides phospholipids of the general formula: ##STR1## wherein X is a valency bond, an oxygen or sulphur atom or a sulfonyl, sulfinyl, phenylene, cycloaklylene, carbonylamino, aminocarbonyl, ureido or carbonyl group, R.sub.1 is a hydrogen atom or a straight-chained or branched, saturated or unsaturated aliphatic hydrocarbon radical containing up to 18 carbon atoms, which is optionally substituted one or more times by halogen, alkoxy, alkylthio, alkanesulfinyl, alkanesulfonyl, carbalkoxy or phenyl, R.sub.2 is a straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon radical containing up to 18 carbon atoms, which is optionally substituted one or more times by halogen, alkoxy, alkylthio, alkanesulphinyl, alkanesulphonyl, carbalkoxy or phenyl, Y is an oxygen atom or a --O--CO--O--, --O--CO--NH-- or --O--CS--NH-- group, R.sub.3 is a straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon radical containing 2 to 8 carbon atoms, which can also be part of a cycloalkane ring system and is optionally substituted one or more times by hydroxyl, halogen, alkylthio, alkanesulphinyl, alkanesulfonyl, nitrile, alkoxycarbonyl, carboxamido optionally substituted by alkyl radicals, cycoalkyl, optionally substituted phenyl or alkoxy, which in turn is optionally substituted by phenyl, hydroxyl, alkoxy, alkylthio, alkanesulfinyl, alkanesulfonyl, optionally acylated amino, alkoxycarbonyl, nitrile or carboxamido optionally substituted by alkyl radicals, Z is an oxygen or sulfur atom, R.sub.4 is a straight-chained or branched alkylene radical containing 2 to 5 carbon atoms and R.sub.5 is a hydrogen atom or a lower alkyl radical, with the proviso that when X is a valency bond, R.sub.1 and R.sub.2 together represent an unsubstituted, straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon chain containing up to 18 carbon atoms, Y, R.sub.4 and R.sub.5 have the above-given meanings and Z is an oxygen atom, R.sub.3 cannot be a propylene or 2-methylpropylene chain optionally substituted by hydroxyl, alkoxy or benzyloxy and with the proviso that when X is a valency bond, R.sub.1 and R.sub.2 together signify an alkyl radical containing up to 18 carbon atoms and substituted by halogen or phenyl, Y and Z are oxygen atoms and R.sub.4 and R.sub.5 have the above-given meanings, R.sub.3 cannot be a propylene or 2-hydroxypropylene chain; and the pharmacologically acceptable salts thereof. The invention also provides pharmaceutical compositions containing such compounds, having cancerostatic action without inducing thrombocyte aggregation.

Phospholipid compound

Sulfur-containing phospholipid compounds of the formula ##STR1## pharmaceutical compositions having anti-tumor activity which include said phospholipid compounds, and the method of use for combating tumors, of said phospholipid compounds.

Sulfur-containing phospholipid compounds and therapeutic compositions

New reactive asymmetrical dicarboxylic acid ester compounds of the formula ##STR1## wherein R.sub.1 is an alkyl radical containing up to 3 carbon atoms or is a digoxin or digitoxin residue, R.sub.2 and R.sub.3, which may be the same or different, are alkoxy radicals containing up to 3 carbon atoms or together represent an oxygen atom, X is a cyanomethoxy, succinimide-N-oxy, N-methyl-pyridiniumoxy, 2,4-dinitrophenoxy, 2,4,5-trichlorophenoxy, pentachlorophenoxy, phenylthio, p-nitrophenoxy, p-nitrophenylthio, piperidyl-N-oxy, phthalimido-N-oxy or benztriazol-N-oxy radical and n is 2, 3, 4 or 5, are useful for the preparation of reagents for the investigation of cardiac glycosides (Digitalis glycosides).

Reactive asymmetrical dicarboxylic acid esters and reagents for the

Method for determining .alpha.-amylase by incubating with a starch substrate, wherein the substrate is based upon particulate starch derivatized with detectable groups for the determination of .alpha.-amylase, the substrate consisting of superficially cross-linked starch or amylose grains having a regulated, reduced swellability, said grains having a diameter of from 0.01 to 0.20 mm; these grains are prepared by suspending non-swollen grains in a solution with only enough cross-linking agent to achieve superficial cross-linking and then derivatizing the grains with the detectable groups for the determination of .alpha.-amylase.

Method for the determination of .alpha.-amylase

Novel method for the determination of .alpha.-amylase which method comprises contacting a sample suspected of containing .alpha.-amylase with a starch derivative carrying a substituent capable of dyestuff-forming coupling; separating from the resulting starch-containing phase the low molecular weight soluble fission products formed by splitting of said starch derivative by .alpha.-amylase; coupling the said couplable substituent with another dyestuff forming component; and measuring the dyestuff so formed as a measure of the initial .alpha.-amylase content.

New hydroxy-succinimide ester compounds of the formula ##STR1## wherein X is selected from a carboxy-succinimide ester group and radicals of the general formulae: ##STR2## A is -O-CH.sub.2 -CH.sub.2 when n is 2 and X is a succinimide ester group but otherwise is a single bond;

Hydroxy-succinimide ester compounds

Novel alkylolamides of iodizable amino acids of the formula ##STR1## wherein, R.sup.1 is hydroxybenzyl, dihydroxybenzyl or imidazol-4-yl-methyl and

Alkylolamides of iodizable amino acids and immune test reagents

An agent for the elimination of turbidity in serum, especially in serum samples wherein photometric measurements are to be made, consisting essentially of one or more mono- or di-esters of polyethylene glycol and fatty acids of 9 to 14 carbon atoms with at most 8 ethylene oxide units per fatty acid moiety in the molecule, said esters having an HLB value of from 8 to 12.8.

Eliminating turbidity in serum undergoing photometric assay

New hydroxy-succinimide ester compounds of the formula ##STR1## wherein X is selected from a carboxy-succinimide ester group and radicals of the general formulae: ##STR2## A is --O--CH.sub.2 --CH.sub.2 when n is 2 and X is a succinimide ester group but otherwise is a single bond;

Crystalline salts of .beta.-nicotinamide-adenine-dinucleotide (.beta.-NAD), particularly alkali metal salts thereof are prepared in good yield and high quality to provide an analytically useful .beta.-NAD form.

Crystalline metal salts of .beta.-nicotinamide-adenine-dinucleotide

New reactive asymmetrical dicarboxylic acid ester compounds of the formula ##STR1## wherein R.sub.1 is an alkyl radical containing up to 3 carbon atoms or is a digoxin or digitoxin residue, R.sub.2 and R.sub.3, which may be the same or different, are alkoxy radicals containing up to 3 carbon atoms or together represent an oxygen atom, X is a cyanomethoxy, succinimide-N-oxy, N-methyl-pyridiniumoxy, 2,4-dinitrophenoxy, 2,4,5-trichlorophenoxy, pentachlorophenoxy, phenylthio, p-nitrophenoxy, p-nitrophenylthio, piperidyl-N-oxy, phthalimido-N-oxy or benztriazol-N-oxy radical and n is 2, 3, 4 or 5. are useful for the preparation of reagents for the investigation of cardiac glycosides (Digitalis glycosides).

Dicarboxylic acid esters of cardiac glycosides

In a conventional method for the quantitative determination of substances, particularly in serum, which, by action of an oxidase thereon, combine with oxygen to form hydrogen peroxide and wherein the hydrogen peroxide formed is converted, in the presence of methanol and catalase, to formaldehyde, the formaldehyde is reacted with hydrazone in the presence of ferric chloride, and the dye thus formed is determined photometrically, the improvement comprising using as the hydrazone, 3-methyl-2-sulfonylbenzothiazolone-hydrazone; use of this hydrazone results in the formation of a very easily soluble dye and is suited for use in automatic analyzers.

Method and reagent for the determination of substances forming hydrogen

Carrier-bound macromolecular compounds, especially bioactive macromolecular compounds, are produced by reacting a macromolecular compound A with a coupling compound B containing at least one reactive function capable of coupling with compound A and at least one further reactive function capable of polymerization, adding to the resulting coupled reaction product AB an unswollen molecular sieve material having cross-linking sufficient to exclude penetration by compound A, and polymerizing the polymerizable group of the coupled product AB in the molecular sieve material to form a polymer body in the molecular sieve material and fix compound A on the surface of the molecular sieve material. Compound A can be, e.g., an enzyme, antibody or hormone, and coupling compound B typically contains, as the coupable function, an alkylation or acylation group such as oxirane, ethyleneimine, halide, acid halide, azide or anhydride groups, and, as the polymerizable function, a carbon-carbon or carbon-oxygen double bond.

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Tutzing, Germany

Gunter Weimann