US3917452A - Diagnostic agent for the detection of peroxidatively active substances - Google Patents

Diagnostic agent for the detection of peroxidatively active substances Download PDF

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US3917452A
US3917452A US52666174A US3917452A US 3917452 A US3917452 A US 3917452A US 52666174 A US52666174 A US 52666174A US 3917452 A US3917452 A US 3917452A
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test strip
activator compound
pyridyl
formula
composition
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Walter Rittersdorf
Werner Guthlein
Hans-Georg Rey
Peter Rieckmann
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Roche Diagnostics GmbH
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Roche Diagnostics GmbH
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/26Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/28Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2326/00Chromogens for determinations of oxidoreductase enzymes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/805Test papers
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/904Oxidation - reduction indicators

Abstract

Test strips for the detection of peroxidatively active substances in body fluids, e.g., for the detection of blood in urine, comprising a carrier containing A. A HYDROPEROXIDE; B. AT LEAST ONE CHROMOGEN; AND C. AS AN ACTIVATOR A COMPOUND OF THE FORMULA:

WHEREIN R1 is pyridyl or phenyl, optionally substituted by lower alkyl or alkoxy, and R2 is hydrogen or lower alkyl.

Description

' United States Patent 1 Rittersdorf et al.

[ 1 Nov. 4, 1975 [73] Assignee: Boehringer Mannheim GmbH,

Mannheim, Germany 22 Filed: Nov. 25, 1974 21 Appl. No.: 526,661

[30] Foreign Application Priority Data Dec. 20, 1973 Germany 2363344 [52] US. Cl. 23/230 B; 23/253 TP; 195/103.5;

[51] Int. CL? .,C07D 213/24; GOIN 31/22; GOIN 33/16 [58] Field of Search 23/230 B, 253 TP; 195/103.5; 252/408; 260/240 D, 240 E [56] References Cited UNITED STATES PATENTS 3,558,435 1/1971 Rey et a1. .4 23/230 B X 3,630,847 12/1971 Rey et a1 23/230 B X 3,654.179 4/1972 Bauer i 23/230 B X 3,654.180 4/1972 Bauer 23/230 B X 3.853.471 12/1974 Rittersdorf et al. 23/230 B Primary Examiner-Robert M. Reese Attorney, Agent, or FirmBurgess, Dinklage & Sprung [57] ABSTRACT Test strips for the detection of peroxidatively active substances in body fluids, e.g., for the detection of blood in urine, comprising a carrier containing a. a hydroperoxide;

b. at least one chromogen; and

c. as an activator a compound of the formula:

wherein R is pyridyl or phenyl, optionally substituted by lower alkyl or alkoxy, and R is hydrogen or lower alkyl.

25 Claims, No Drawings DIAGNOSTIC AGENT FOR THE DETECTION OF PEROXIDATIVELY ACTIVE SUBSTANCES The present invention relates to a test strip for the de tection of very small amounts of blood and of other peroxidatively-active substances in the body fluids.

The detection of small amounts of blood, which cannot be seen by the naked eye, in urine, feces and vomit is very important for the diagnosis of hemorrhages in the stomach, intestines and urinary tract. Such hemorrhages are caused, for example, by tumors, ulcers or inflammations in the organs in question. Furthermore, due to the .influence of certain hemolytic toxins, free hemoglobin can also occur in the urine and plasma. Blood and hemoglobin are .peroxidatively-active, i.e., they liberate oxygen from hydroperoxides and transfer it to certain acceptors. Myoglobin, which is also peroxidatively-active, is found, for example, in the urine after a cardiac infarct. Furthermore, blood occurs especially frequently in the urine when calculi are present in the bladder or kidneys. I

For asensitive detection of all of these substances, their peroxidate action is especially suitable. The oxygen liberated from a hydroperoxide is thereby transmitted to a chromogen which is oxidized to a color mate rial and thus indicates the presence of the peroxidative ly-active substances. This reaction has been used for quite a long time in medicinal and forensic analysis, especially for the detection of blood. As a rule, the reaction is carried out in a test tube or as a spot test, hydrogen peroxide usually being employed as the hydroper oxide. As chromogen, there is usually employed benzidine, o-tolidine or leucomalachite green.

Rapid test compostions are absorbent carriers, usually papers, which are impregnated with all the reagents needed for the detection reaction and which, after simply dipping into the body fluid to be tested, show a color reaction. Because of the great importance which these rapid tests have recently achieved, they have also been developed in various ways for the detection of blood in body fluids.

Since, for the detection of blood, the sensitivity of the rapid test is of decisive importance, various attempts have already been made to increase the sensitivity of the known detection reactions by means of additives. Thus, for example, German Pat. Spec. No. 1,242,905 describes test papers which, as activating additives, contain certain quinoline derivatives, preferably quinine. It is certainly asserted that the sensitivity can be considerably increased by means of these additives but, according to our own investigations, it is practically impossible, with the so improved tests strips, to detect, for example, blood in a concentration of 5 erythrocytes /mm", which would be necessary for a differentiation between normal and pathological values.

We have now found that test papers for the detection of peroxidatively-active substances with a previously unachievably high sensitivity are obtained by utilizing certain vinylpyridine compounds as activators.

The vinyl pyridine compounds showing this efficacious action are of the formula wherein R is pyridyl or phenyl, optionally substituted by lower alkyl or alkoxy, and

R is hydrogen or lower alkyl.

Preferred compounds of general formula (I) are those in which R, is hydrogen. The lower alkyl and alkoxy radicals can contain up to 4 carbon atoms, the methyl and methoxy radicals being preferred.

Thus, according to the present invention, there is provided a test strip for the detection of peroxidativelyactive substances in body fluids, comprising a carrier containing a hydroperoxide, at least one chromogen and, as activator, at least one compound of general formula (I).

The sensitivity of the detection reaction is increased by some of the compounds of general formula (I) to such an extent that it is even possible to detect individual erythrocytes in urine, which are visible on the test paper as colored dots. Thus, for example, with the use of a-styryl-pyridine, it is possible to produce a test paper with which it is possible to detect 5 erythrocytes/mm urine. This corresponds to a blood dilution of 1110.

Of course, not all of the compounds of general formula (I) possess activating properties of the same degree. Thus, it is possible to adjust the sensitivity of, for example, a blood test in accordance with practical requirements. For example, test strips of increasing activity are obtained when, as activator, there are used the following compounds in the given order:

2-( phenylvinyl )-4-methylpyridine Pyridyl-Z-pyridyl-4-ethylene 2-( methylphenylvinyl)-pyridilne 2-(4-methoxyphenylvinyl) pyridine di-(pyridyl-2)-ethylene pyridyl-2-pyridyl-3-ethylene oz-styryl-pyridine.

The activating agent used according to the present invention can be employed in amounts of about 0.05 1.0g, preferably of 0.2 0.5g, per ml. ofimpregnation solution.

Further components of a rapid test for blood are an organic hydroperoxide, an oxidation indicator (chromogen), a buffer and a surface-active agent, as well as, if desired, a phosphoramide, for example phosphoric acid trimorpholide, for stabilization, as well as conventional adjuvants.

As hydroperoxides, there can be used, for example, diisopropyl-benzene hydroperoxide or 2,5-dimethylhexane-2,S-dihydroperoxide, and as indictors, there can be used, for example, those of the benzidine series, such as o-tolidine, or those of the heterocylic azine series, such as bis-(N-ethyl-quinol-Z-one)-azine or (N- methyl-benz-thiazol-2-one)-(1-ethyl-3-phenyl-5- methyltriazol-Z-one)-azine (see German Pat.Spec No. 1,648,840).

The indicator (chromogen) can be used in amounts of from 0.05 g., preferably of 0.2 1.0 g., per 100 ml. impregnation solution.

As buffer, there can be used, for example, a citrate. phosphate, phthalate or succinate buffer. the pH value and capacity being so chosen that. after dipping the test strip into a body fluid, a pH value of 4 7. preferably 5 3 6, is obtained thereon.

it is also advantageous to add to the formulation small amounts (for example about 0.05 0.5 g. per 100 ml.) ofa complex-forming agent, for example, sodium metaphosphate or ,ethylenediamine-tetraacetic acid, in order to avoid falsely positive reactions which could be caused bytraces of metals.

Since the test papers can, because of the relatively large amounts 7 of water-soluble substances present, tend to bleed, it is practical to add to the formulation a thickening agent, for example, methyl cellulose and, in particular, polyvinylpyrrolidone, preferably in amounts of about 0.5 5 g. per 100 ml. g I

wetting agent, there is preferably used a longchainedorganic sulphate or sulphonate, for example sodium 'dodecyl-benzenesulphonate, dioctyl sodium sulphosuccinate or sodium lauryl sulphate, which, as is known, stabilizes radical cations, such as oxidized otolidine. The wetting agent can be added to the impregnation solutionin amounts of from 0.5 5%, preferably of'l 3%. I

For the production of the test strips according to the present invention, absorbentcarriers, for example, filter paper, cellulose or synthetic fibre fleeces, can be impregnated with solutions of the reagents'in readily volatile liquids. This is preferably carried out in two or three separate steps. Thus, for example, impregnation is first carried out with a solution which contains a hydroperoxide, wetting agent, buffer and optionally a thickening agent. Thereafter, impregnation is carried out witha solution of an indicator and of an activator of general formula (1).

After drying, the test strips according to the present invention are cut up into strips and preferably sealed between a synthetic resin film and a fine-mesh material in the manner described in German Pat. Spec. No. 2,118,455.

For the detection of peroxidatively-active substances in feces, it is also possible to incorporate the activators according to the present invention, together with the reagents, in a water-stable film in the manner described in German Pat. Spec. No. 1,598,153. This has the advantage that the surface of the test strip can, for readingoff the color reaction, be cleaned by simply wiping it.

The following Examples are given for the purposes of illustrating the present invention:

g, EXAMPLE 1:

Filter paper is successively impregnated with the following solutions and dried'at' 40C.:

Solution 1 152M citrate buffer of pH 5.25

-con tinued g, v

distilled water ad l00.0 ml.

Solution 2.

o-tolidine 0.3 g. o-stilhazole 0.2 g. toluene ad l00.0 ml.

A'white test paper is obtained which, upon dipping into blood-containing urine, becomes blue-green colored after about 5 20 seconds. If the erythrocytes are intact, then the papers are blue-green speckled. If hemolysis has taken place or if free hemoglobin was initially present in the urine, then the papers are uniformly blue-green colored. The sensitivity is about 5 erythrocytes/mm or the corresponding amount of hemoglobin. A lower number of intact'er'ythrocytes can, under certain circumstances, still bring about'individual green dots on the test paper. The sensitivity with regard to myoglobin corresponds to that for hemoglobin.

Example 2:

Filter paper is impregnated with the followingsolutions and dried at 40C.:

Solution 1 Test papers are obtained with'practically the same properties as those described in Example I. The sensitivety is between about 5 and 20 erythrocytes/mm .'de-

creasing with the compound (I) used in the given order:

Compound I used:

pyridyl-2-pyridyl-3-ethylene di-(Pyridyl-Z)-ethylene 2-(4-methoxyphenylvinyl)-pyridine 2-(4-methylphenylvinyll-pyridine pyridyl-2-pyridyl-4-ethylene -continucd 2-( phenylvinyl 4-methylpyridine.

All the abovementioned compounds are known from the literature.

It will be understood that the foregoing specification and examples are illustrative but not limitative of the present invention inasmuch as other embodiments within the spirit and scope of the invention will suggest themselves to those skilled in the art.

What is claimed is:

1. Test strip composition for the detection of peroxidatively-active substances in body fluids, comprising a carrier containing a hydroperoxide, at least one chromogen and, as an activator, a compound of the formula:

wherein R is pyridyl or a phenyl optionally substituted by lower alkyl or alkoxy; and

R is hydrogen or lower alkyl.

2. Test strip as claimed in claim 1 and wherein R in the formula of said activator compound is pyridyl.

3. Test strip as claimed in claim 1 wherein R in the formula of said activator compound is phenyl.

4. Test strip as claimed in claim 1 wherein R in the formula of said activator compound is pyridyl substituted by methyl or methoxy.

5. Test strip as claimed in claim 1 wherein R in the formula of said activator compound is phenyl substituted by methyl or methoxy.

6. Test strip as claimed in claim 1 wherein R in the formula of said activator compound is hydrogen.

7. Test strip as claimed in claim 1 wherein R in the formula of said activator compound is methyl.

8. Test strip as claimed in claim 1 wherein said activator compound is Z-(phenylvinyl)-4-methylpyridine.

9. Test strip as claimed in claim 1 wherein said activator compound is pyridyl-2-pyridyl-4-ethylene.

10. Test strip as claimed in claim 1 wherein said activator compound is 2-(4-methylphenylvinyl)-pyridine.

11. Test strip as claimed in claim 1 wherein said activator compound is 2-(4-methoxyphenylvinyl)-pyridine.

12. Test strip as claimed in claim 1 wherein said activator compound is di-(pyridyl-2)-ethylene.

13. Test strip as claimed in claim 1 wherein said activator compound is pyridyl-2-pyridyl-3-ethylene.

14. Test strip as claimed in claim 1 wherein said activator compound is a-styryl-pyridine.

15. Test strip as claimed in claim 1 wherein said hydroperoxide is diisopropyl-benzene hydroperoxide or 2,5dimethylhexane-2,S-dihydroperoxide.

16. Test strip as claimed in claim 1 wherein said indicator is of the benzidine series or of the heterocyclic azine series.

17. Test strip as claimed in claim 1 wherein said composition also contains a small amount of a complex forming agent.

18. Test strip as claimed in claim 1 wherein said composition also contains a thickening agent.

19. Test strip as claimed in claim 1 wherein said composition also contains a wetting agent.

20. Test strip as claimed in claim 1 comprising citrate buffer ethylenediaminetetraacetic: acid, disodium salt dodecyl-benzene-sulfonic acid sodium salt 2,S-dimethylhexane-Z.S-dihydroperoxide phosphoric acid trimorpholide o-tolidine o-stilbazole.

21. Test strip as claimed in claim 1 wherein the carrier is an absorbent material impregnated with the reagents.

22. Test strip as claimed in claim 21 wherein the carrier is a water-stable film with the reagents incorporated therein.

23. Method of detecting a peroxidatively active substance in a body fluid which method comprises contacting a sample of said body fluid with a test strip composition as claimed in claim 1 and observing a color change in said test strip composition as an indication of the absence or presence of the peroxidatively active sub stance.

24. Method as claimed in claim 23 wherein said peroxidatively active substance is blood.

25. Method as claimed in claim 23 wherein said body fluid is urine.

Claims (25)

1. TEST STRIP COMPOSITION FOR THE DETECTION OF PEROXIDATIVELY-ACTIVE SUBSTANCES IN BODY FLUIDS, COMPRISING A CARRIER CONTAINING A HYDROPEROXIDE, AT LEAST ONE CHROMOGEN AND, AS AN ACTIVATOR, A COMPOUND OF THE FORMULA:
2. Test strip as claimed in claim 1 and wherein R1 in the formula of said activator compound is pyridyl.
3. Test strip as claimed in claim 1 wherein R1 in the formula of said activator compound is phenyl.
4. Test strip as claimed in claim 1 wherein R1 in the formula of said activator compound is pyridyl substituted by methyl or methoxy.
5. Test strip as claimed in claim 1 wherein R1 in the formula of said activator compound is phenyl substituted by methyl or methoxy.
6. Test strip as claimed in claim 1 wherein R2 in the formula of said activator compound is hydrogen.
7. Test strip as claimed in claim 1 wherein R2 in the formula of said activator compound is methyl.
8. Test strip as claimed in claim 1 wherein said activator compound is 2-(phenylvinyl)-4-methylpyridine.
9. Test strip as claimed in claim 1 wherein said activator compound is pyridyl-2-pyridyl-4-ethylene.
10. Test strip as claimed in claim 1 wherein said activator compound is 2-(4-methylphenylvinyl)-pyridine.
11. Test strip as claimed in claim 1 wherein said activator compound is 2-(4-methoxyphenylvinyl)-pyridine.
12. Test strip as claimed in claim 1 wherein said activator compound is di-(pyridyl-2)-ethylene.
13. Test strip as claimed in claim 1 wherein said activator compound is pyridyl-2-pyridyl-3-ethylene.
14. Test strip as claimed in claim 1 wherein said activator compound is Alpha -styryl-pyridine.
15. Test strip as claimed in claim 1 wherein said hydroperoxide is diisopropyl-benzene hydroperoxide or 2,5-dimethylhexane-2,5-dihydroperoxide.
16. Test strip as claimed in claim 1 wherein said indicator is of the benzidine series or of the heterocyclic azine series.
17. Test strip as claimed in claim 1 wherein said composition also contains a small amount of a complex forming agent.
18. Test strip as claimed in claim 1 wherein said composition also contains a thickening agent.
19. Test strip as claimed in claim 1 wherein said composition also contains a wetting agent.
20. Test strip as claimed in claim 1 comprising citrate buffer ethyLenediamine-tetraacetic acid, disodium salt dodecyl-benzene-sulfonic acid sodium salt 2,5-dimethylhexane-2,5-dihydroperoxide phosphoric acid trimorpholide o-tolidine o-stilbazole.
21. Test strip as claimed in claim 1 wherein the carrier is an absorbent material impregnated with the reagents.
22. Test strip as claimed in claim 21 wherein the carrier is a water-stable film with the reagents incorporated therein.
23. Method of detecting a peroxidatively active substance in a body fluid which method comprises contacting a sample of said body fluid with a test strip composition as claimed in claim 1 and observing a color change in said test strip composition as an indication of the absence or presence of the peroxidatively active substance.
24. Method as claimed in claim 23 wherein said peroxidatively active substance is blood.
25. Method as claimed in claim 23 wherein said body fluid is urine.
US3917452A 1973-12-20 1974-11-25 Diagnostic agent for the detection of peroxidatively active substances Expired - Lifetime US3917452A (en)

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Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4050898A (en) * 1976-04-26 1977-09-27 Eastman Kodak Company Integral analytical element
US4071321A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4071317A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances and process for preparing same
US4071318A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4148611A (en) * 1978-06-28 1979-04-10 Miles Laboratories, Inc. Test composition, device and method for the detection of peroxidatively active substances
US4175923A (en) * 1978-06-26 1979-11-27 Friend William G Method and apparatus for occult blood testing in the home
EP0014929A1 (en) * 1979-02-14 1980-09-03 Boehringer Mannheim Gmbh Diagnostic means, process for its preparation and its use in determining leucocytes in body fluids
US4251222A (en) * 1979-12-17 1981-02-17 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
US4251223A (en) * 1979-12-17 1981-02-17 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
EP0029926A1 (en) * 1979-11-13 1981-06-10 Miles Laboratories, Inc. A composition and a test device based on a benzidine-type indicator for detecting the presence of a constituent in a test sample
US4278439A (en) * 1979-12-17 1981-07-14 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
US4333734A (en) * 1980-01-18 1982-06-08 Sloan-Kettering Institute For Cancer Research Diagnostic device for fecal occult blood and method of use
US4339242A (en) * 1979-11-13 1982-07-13 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4339243A (en) * 1979-11-13 1982-07-13 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340392A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340393A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340395A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340394A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4380585A (en) * 1979-11-13 1983-04-19 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4481295A (en) * 1979-06-29 1984-11-06 Behringwerke Aktiengesellschaft Substituted or condensed pyridines in a process for the detection of substances having a peroxidatic effect and a diagnostic agent containing such pyridines
US4615982A (en) * 1984-12-11 1986-10-07 Lawrence Paul J Fecal occult blood test
US4670402A (en) * 1982-07-26 1987-06-02 Macherey-Nagel & Co.-Chemikalienhandel Use of benzimidazole derivatives for the detection of blood and other peroxidatically active substances in body fluids and excretion products
US4737457A (en) * 1986-02-26 1988-04-12 Eastman Kodak Company Analytical composition, element and method for the determination of hydrogen peroxide
US4818702A (en) * 1986-06-02 1989-04-04 Litmus Concepts, Inc. Fecal occult blood test reagent
US4886760A (en) * 1985-01-31 1989-12-12 Savyon Diagnostics Limited Stable chemical compositions containing chromogenic materials, peroxides, and stabilizing chemicals
US4956300A (en) * 1982-01-05 1990-09-11 Helena Laboratories Corporation Aid for determining the presence of occult blood, method of making the aid, and method of using the aid
US5053342A (en) * 1987-12-24 1991-10-01 Litmus Concepts, Inc. Fecal occult blood test reagents
US5081040A (en) * 1987-06-29 1992-01-14 Helena Laboratories Corporation Composition and kit for testing for occult blood in human and animal excretions, fluids, or tissue matrixes
US5182191A (en) * 1988-10-14 1993-01-26 Pacific Biotech, Inc. Occult blood sampling device and assay
US5196167A (en) * 1989-04-04 1993-03-23 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5217874A (en) * 1989-04-04 1993-06-08 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5273888A (en) * 1984-01-16 1993-12-28 Helena Laboratories Corporation Chemical test kit and method for determining the presence of blood in a specimen and for verifying the effectiveness of the chemicals
US5426032A (en) * 1986-08-13 1995-06-20 Lifescan, Inc. No-wipe whole blood glucose test strip
US5702913A (en) * 1983-12-21 1997-12-30 Helena Laboratories Corporation Chromgen-reagent test system
US5827677A (en) * 1996-02-01 1998-10-27 Universal Lavel Method and device for specifically detecting myoglobin using a non-discriminating peroxidase sensitive assay
US5885789A (en) * 1997-03-20 1999-03-23 Stc Technologies Incorporated Solution-based assay for peroxidatively-active substances in bodily fluids
US6458326B1 (en) 1999-11-24 2002-10-01 Home Diagnostics, Inc. Protective test strip platform
US6525330B2 (en) 2001-02-28 2003-02-25 Home Diagnostics, Inc. Method of strip insertion detection
US6541266B2 (en) 2001-02-28 2003-04-01 Home Diagnostics, Inc. Method for determining concentration of an analyte in a test strip
US6562625B2 (en) 2001-02-28 2003-05-13 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US20050079637A1 (en) * 2003-10-10 2005-04-14 Wilhelm Hoa La Wearable article with multi-level alert system

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5838552Y2 (en) * 1977-11-25 1983-08-31
JPH0827280B2 (en) * 1986-10-30 1996-03-21 テルモ株式会社 Test composition and it carries the test device
CN104341374A (en) * 2014-11-11 2015-02-11 联化科技(德州)有限公司 Preparation method for morpholine carbonyl chloride compound

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3558435A (en) * 1966-09-01 1971-01-26 Boehringer Mannheim Gmbh Diagnostic agents for use in the determination of hydroperoxides and of peroxidate-active substances and methods for manufacturing and using the same
US3630847A (en) * 1967-07-20 1971-12-28 Boehringer Mannheim Gmbh Diagnostic agent for use in the determination of hydroperoxides and of peroxidate-active substances
US3654180A (en) * 1971-03-01 1972-04-04 Miles Lab Indicator for detecting hydrogen peroxide and peroxidative compounds containing alpha naphthoflavone
US3654179A (en) * 1971-03-01 1972-04-04 Miles Lab Indicator for detecting hydrogen peroxide and peroxidative compounds containing bindschedler's green
US3853471A (en) * 1972-07-18 1974-12-10 Boehringer Mannheim Gmbh Diagnostic composition for the detection of peroxidatively active substances in body fluids

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3558435A (en) * 1966-09-01 1971-01-26 Boehringer Mannheim Gmbh Diagnostic agents for use in the determination of hydroperoxides and of peroxidate-active substances and methods for manufacturing and using the same
US3630847A (en) * 1967-07-20 1971-12-28 Boehringer Mannheim Gmbh Diagnostic agent for use in the determination of hydroperoxides and of peroxidate-active substances
US3654180A (en) * 1971-03-01 1972-04-04 Miles Lab Indicator for detecting hydrogen peroxide and peroxidative compounds containing alpha naphthoflavone
US3654179A (en) * 1971-03-01 1972-04-04 Miles Lab Indicator for detecting hydrogen peroxide and peroxidative compounds containing bindschedler's green
US3853471A (en) * 1972-07-18 1974-12-10 Boehringer Mannheim Gmbh Diagnostic composition for the detection of peroxidatively active substances in body fluids

Cited By (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4050898A (en) * 1976-04-26 1977-09-27 Eastman Kodak Company Integral analytical element
US4071321A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4071317A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances and process for preparing same
US4071318A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4175923A (en) * 1978-06-26 1979-11-27 Friend William G Method and apparatus for occult blood testing in the home
US4148611A (en) * 1978-06-28 1979-04-10 Miles Laboratories, Inc. Test composition, device and method for the detection of peroxidatively active substances
US4299917A (en) * 1979-02-14 1981-11-10 Boehringer Manneheim Gmbh Diagnostic agents for the detection of leukocytes in body fluids
EP0014929A1 (en) * 1979-02-14 1980-09-03 Boehringer Mannheim Gmbh Diagnostic means, process for its preparation and its use in determining leucocytes in body fluids
US4481295A (en) * 1979-06-29 1984-11-06 Behringwerke Aktiengesellschaft Substituted or condensed pyridines in a process for the detection of substances having a peroxidatic effect and a diagnostic agent containing such pyridines
US4340393A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340394A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
EP0029926A1 (en) * 1979-11-13 1981-06-10 Miles Laboratories, Inc. A composition and a test device based on a benzidine-type indicator for detecting the presence of a constituent in a test sample
US4340395A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4380585A (en) * 1979-11-13 1983-04-19 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4339243A (en) * 1979-11-13 1982-07-13 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4340392A (en) * 1979-11-13 1982-07-20 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4339242A (en) * 1979-11-13 1982-07-13 Miles Laboratories, Inc. Stabilization of benzidine-type indicators with various enhancers
US4278439A (en) * 1979-12-17 1981-07-14 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
EP0030683B1 (en) * 1979-12-17 1983-04-06 Miles Laboratories, Inc. Test composition for peroxidatively active substances, test device containing the composition, process for preparing same and method for the determination of peroxidatively active substances
US4251223A (en) * 1979-12-17 1981-02-17 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
US4251222A (en) * 1979-12-17 1981-02-17 Miles Laboratories, Inc. Sensitizers for peroxidative activity tests
US4333734A (en) * 1980-01-18 1982-06-08 Sloan-Kettering Institute For Cancer Research Diagnostic device for fecal occult blood and method of use
US4956300A (en) * 1982-01-05 1990-09-11 Helena Laboratories Corporation Aid for determining the presence of occult blood, method of making the aid, and method of using the aid
US4670402A (en) * 1982-07-26 1987-06-02 Macherey-Nagel & Co.-Chemikalienhandel Use of benzimidazole derivatives for the detection of blood and other peroxidatically active substances in body fluids and excretion products
US5702913A (en) * 1983-12-21 1997-12-30 Helena Laboratories Corporation Chromgen-reagent test system
US5273888A (en) * 1984-01-16 1993-12-28 Helena Laboratories Corporation Chemical test kit and method for determining the presence of blood in a specimen and for verifying the effectiveness of the chemicals
US4615982A (en) * 1984-12-11 1986-10-07 Lawrence Paul J Fecal occult blood test
US4886760A (en) * 1985-01-31 1989-12-12 Savyon Diagnostics Limited Stable chemical compositions containing chromogenic materials, peroxides, and stabilizing chemicals
US4737457A (en) * 1986-02-26 1988-04-12 Eastman Kodak Company Analytical composition, element and method for the determination of hydrogen peroxide
US4818702A (en) * 1986-06-02 1989-04-04 Litmus Concepts, Inc. Fecal occult blood test reagent
US6268162B1 (en) 1986-08-13 2001-07-31 Lifescan, Inc. Reflectance measurement of analyte concentration with automatic initiation of timing
US5563042A (en) * 1986-08-13 1996-10-08 Lifescan, Inc. Whole blood glucose test strip
US6881550B2 (en) 1986-08-13 2005-04-19 Roger Phillips Method for the determination of glucose employing an apparatus emplaced matrix
US6858401B2 (en) 1986-08-13 2005-02-22 Lifescan, Inc. Minimum procedure system for the determination of analytes
US5426032A (en) * 1986-08-13 1995-06-20 Lifescan, Inc. No-wipe whole blood glucose test strip
US6887426B2 (en) 1986-08-13 2005-05-03 Roger Phillips Reagents test strip adapted for receiving an unmeasured sample while in use in an apparatus
US6821483B2 (en) 1986-08-13 2004-11-23 Lifescan, Inc. Reagents test strip with alignment notch
US5843692A (en) * 1986-08-13 1998-12-01 Lifescan, Inc. Automatic initiation of a time interval for measuring glucose concentration in a sample of whole blood
US5081040A (en) * 1987-06-29 1992-01-14 Helena Laboratories Corporation Composition and kit for testing for occult blood in human and animal excretions, fluids, or tissue matrixes
US5053342A (en) * 1987-12-24 1991-10-01 Litmus Concepts, Inc. Fecal occult blood test reagents
US5182191A (en) * 1988-10-14 1993-01-26 Pacific Biotech, Inc. Occult blood sampling device and assay
US5196167A (en) * 1989-04-04 1993-03-23 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5217874A (en) * 1989-04-04 1993-06-08 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5827677A (en) * 1996-02-01 1998-10-27 Universal Lavel Method and device for specifically detecting myoglobin using a non-discriminating peroxidase sensitive assay
US5885789A (en) * 1997-03-20 1999-03-23 Stc Technologies Incorporated Solution-based assay for peroxidatively-active substances in bodily fluids
US6458326B1 (en) 1999-11-24 2002-10-01 Home Diagnostics, Inc. Protective test strip platform
US6979571B2 (en) 1999-11-24 2005-12-27 Home Diagnostics, Inc. Method of using a protective test strip platform for optical meter apparatus
US6562625B2 (en) 2001-02-28 2003-05-13 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US6541266B2 (en) 2001-02-28 2003-04-01 Home Diagnostics, Inc. Method for determining concentration of an analyte in a test strip
US6525330B2 (en) 2001-02-28 2003-02-25 Home Diagnostics, Inc. Method of strip insertion detection
US7390665B2 (en) 2001-02-28 2008-06-24 Gilmour Steven B Distinguishing test types through spectral analysis
US20050079637A1 (en) * 2003-10-10 2005-04-14 Wilhelm Hoa La Wearable article with multi-level alert system
US7241627B2 (en) * 2003-10-10 2007-07-10 Kimberly-Clark Worldwide, Inc. Wearable article with multi-level alert system

Also Published As

Publication number Publication date Type
CA1027832A1 (en) grant
DE2363344A1 (en) 1975-06-26 application
FI361074A (en) 1975-06-21 application
NL164965C (en) 1981-02-16 grant
NL7416484A (en) 1975-06-24 application
FI57025B (en) 1980-01-31 application
GB1443133A (en) 1976-07-21 application
JPS5097395A (en) 1975-08-02 application
JPS5412360B2 (en) 1979-05-22 grant
NL164965B (en) 1980-09-15 application
FI57025C (en) 1980-05-12 grant
FR2283441A1 (en) 1976-03-26 application
CA1027832A (en) 1978-03-14 grant
DE2363344B2 (en) 1977-01-27 application
FR2283441B1 (en) 1981-04-10 grant

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