Boehringer Mannheim Gmbh

Roche Diagnostics Gmbh

Roche Diagnostics Operations, Inc.

F. Hoffmann-la Roche Ag

Axel Schmidt

Herbert Von Der Eltz

Elli Rauscher

Dieter Heindl

Martina Junius-Comer

Hans-Peter Josel

Rupert Herrmann

Manfred Kubbies

Hartmut Merdes

Klaus Muhlegger

Helmgard Gauhl

Klaus Kaluza

Gunter Pappert

Hans-Georg Ihlenfeldt

Rudolf Gompper

Heribert Maerz

Joachim Hones

Volker Leitenberger

Gerhard Hoss

Bernhard Virnekas

Ernst Selbertinger

Angelika Kurrle-Weitenhiller

Methods for the synthesis of N-substituted pyridinium compounds by using an N-heteroaryl substituted pyridinium salt (Zincke salt) and reacting it with a nucleophilic amine are provided. Novel purine-substituted pyridyl compounds, which may be useful reagents in the above reaction, are also disclosed.

Method and substances for preparation of N-substituted pyridinium compounds

The invention concerns stable aqueous solutions containing one or several nucleoside triphosphates wherein the respective solution has a pH value of more than 7.5 and contains no additional substances with a stabilizing effect. The nucleoside triphosphate solutions are used in particular for DNA synthesizing reactions such as e.g. RT-PCR, cycle sequencing, random priming and nick translation. One of the most important applications of such solutions containing deoxy-nucleoside triphosphates (d-NTP) is their use in the polymerase chain reaction (PCR).

Stabilized aqueous nucleoside triphosphate solutions

The invention concerns the use of redox-active compounds for the production of detection reagents for a method for the determination of an analyte as well as reagent kits that contain these redox-active compounds. In addition new redox-active compounds are disclosed.

Redox-active compounds and their use

A preservative mixture in particular for preserving diagnostic test liquids, contains the sodium salt of mercaptopyridine-N-oxide together with a further preserving substance. A diagnostic test kit according to the invention contains mercaptopyridine-N-oxide sodium salt, a compound from the isothiazolone group and in particular 2-alkyl-3-(2H)isothiazolone hydrochloride with 1 to 8 C atoms in the 2-alkyl group or a preservative mixture according to the invention as the preservative for one or several test liquids of the test kit.

Preservative mixture for diagnostic test liquids

The invention concerns new indophenyl-substituted maltose derivatives, their use for the determination of the enzymatic activity of .alpha.-amylase and reagents for the determination of .alpha.-amylase which contain the new indophenyl-substituted maltose derivatives as the enzyme substrate.

Indophenol substituted maltooligosides as .alpha.-amylase substrates

Diazapentalene derivatives as a specific reagent for thiol compounds

Combination composed of 2-methyl-4-isothiazolin-3-one hydrochloride and 5-bromo-5-nitro-1,3-dioxane for the elimination of microbes as well as for the preservation of column materials in aqueous solutions. The biocidal mixture is preferably added at concentrations of 0.001 to 0.3% (w/v).

Preservation of column materials in aqueous solutions

The invention concerns a complex of cyclodextrin and an organic biocide, wherein the organic biocide has a maximum water-solubility of 0.15% (w/v) at a temperature of 25.degree. C., a process for the production of the complex as well as the use of the complex for preserving aqueous solutions. In addition the invention concerns a diagnostic test solution which contains at least one complex according to the invention and a preserved diagnostic test kit which comprises test reagents and at least one complex according to the invention.

Cyclodextrin-biocide complex

The present invention provides a process for the specific determination of pancreatic .alpha.-amylase in the presence of salivary .alpha.-amylase in body fluids by reaction with a system for the detection of .alpha.-amylase with the use of an inhibitor for salivary .alpha.-amylase, wherein, as substrate, there is used a compound of the general formula:-- ##STR1## in which R.sub.1 is a straight-chained or branched alkyl or alkoyl radical containing up to 6 carbon atoms, a cycloalkyl or cycloalkoxyl radical containing 3 to 6 carbon atoms or a benzoyl, benzyl or phenyl radical which is optionally hydrophilically substituted, R.sub.2 is a hydrogen atom or in which R.sub.1 and R.sub.2 together form a methylene bridge, the hydrogen atoms of which, independently of one another, can each be substituted by an alkyl radical containing up to 5 carbon atoms or a phenyl radical, n is 1, 2 or 3 and X is an optically determinable residue. The present invention also provides a reagent for the specific determination of pancreatic .alpha.-amylase, as well as new compounds for use in the above process and reagent.

Process and reagent for the specific determination of pancreatic

The present invention is concerned with a combination for the preservation of diagnostic tests, characterized by a content of at least two components selected from the group comprising 2-methyl-4-isothiazolin-3-one hydrochloride, 2-hydroxypyridine-N-oxide, chloroacetamide, (N,N-methylene-bis-(N-(1-hydroxymethyl-2,5-dioxo-4-imidazolidinyl))-urea and 5-bromo-5-nitro-1,3-dioxan. The present invention is also concerned with a preserved diagnostic test kit, comprising test reagents and at least two preservation agents selected from the group comprising 2-methyl-4-isothiazolin-3-one hydrochloride, 2-hydroxypyridine-N-oxide, chloroacetamide, (N,N-methylene-bis-(N-(1-hydroxymethyl)-2,5-dioxo-4-imidazolidinyl))-urea and 5-bromo-5-nitro-1,3-dioxan.

Composition for preservation of diagnostic test reagents

The present invention provides a process for the specific determination of pancreatic .alpha.-amylase in the presence of salivary .alpha.-amylase in body fluids by reaction with a system for the detection of .alpha.-amylase with the use of an inhibitor for salivary .alpha.-amylase, wherein, as substrate, there is used a compound of the general formula: ##STR1## in which R.sub.1 is a straight-chained or branched alkyl or alkoyl radical containing up to 6 carbon atoms, a cycloalkyl or cycloalkoxyl radical containing 3 to 6 carbon atoms or a benzoyl, benzyl or phenyl radical which is optionally hydrophilically substituted, R.sub.2 is a hydrogen atom or in which R.sub.1 and R.sub.2 together form a methylene bridge, the hydrogen atoms of which, independently of one another, can each be substituted by an alkyl radical containing up to 5 carbon atoms or a phenyl radical, Gluc is a glucose molecule, n is 1, 2 or 3 and X is an optically determinable residue. The present invention also provides a reagent for the specific determination of pancreatic .alpha.-amylase, as well as new compounds for use in the above process and reagent.

The present invention provides compounds of the general formula ##STR1## wherein R.sub.1 is a hydrogen atom, a methyl, ethyl, propyl, isopropyl, butyl, tert. butyl or 1-alkoxyalkyl radical or an optionally hydrophilically substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, tetrahydropyranyl, piperidinyl, N-methyl substituted piperidinyl or N-ethyl substituted piperidinyl, pyridinyl, thiophenyl or 1,1-dioxo-tetra- hydrothiopyranyl radical or an amino group which is optionally substituted by the same or different substituents selected from methyl, ethyl, propyl and isopropyl radicals. R.sub.2 is an oligoglucoside residue with 2, 3 or 4 glucose units and X is a hydrogen atom or an optically determinable residue. The present invention also provides processes for the preparation of compounds (I) and reagents for the determination of .alpha.-amylase containing them. Furthermore, the present invention provides a process for the determination of .alpha.-amylase using a compound of general formula (I).

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Munchen, Germany

Axel Schmidt