US4299917A
Expired / Lapsed
US
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Diagnostic agents for the detection of leukocytes in body fluids
Assignee: Roche Diagnostics GmbH
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Filing: 1980-01-21
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Granted: 1981-11-10
•
Expires: 2000-01-21
Abstract
Abstract This invention relates to diagnositc agents and methods for the detection of leukocytes in body fluids. In additional aspect, the invention provides a process for the production of such diagnostic agents.
Inventors
- 👤 Dieter Berger
- 👤 Gunter Frey
- 👤 Manfred Kuhr
- 👤 Wolfgang Werner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 06:04
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/34; C12Q1/37; C09; C09B; C09B11/00; C09B11/04; C09B11/06; C09B11/08; C09B43/00; C09B43/18; C09B43/20; C12Q1/02; C12Q1/04; C12Q1/44; C12Q2334/00; C12Q2334/40; C12Q2334/50
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
625 words
Diagnostic agent for the detection of esterolytic and proteolytic enzymes in body fluids, which agent comprises at least one substrate, and adjuvants suitable for said substrate, and at least one activator, and wherein said substrate is a sulphonphthalein ester of the formula ##STR5## wherein R 1 " is a carboxylic acid residue optionally substituted by halogen or a lower alkoxy radical or is an amino acid or peptide residue provided with a nitrogen protective group conventional in peptide chemistry; R 2 " is a halogen atom or a lower alkyl radical; and R 3 " and R 4 ", which can be the same or different are hydrogen or halogen atoms; or an azo dyestuff ester of the formula A'--N═N--B'(OR).sub.n wherein A' is a five- or six-membered, optionally benzo-annellated residue with one or two heteroatoms selected from nitrogen, sulfur and oxygen, which is optionally substituted one or more times by halogen, lower alkyl or lower alkoxy radicals or is a phenyl radical substituted one, two or three times by lower alkyl, lower alkoxy, nitro, sulphonato or acylamino radicals; B' is a benzene, naphthalene or quinoline radical optionally substituted once or twice by sulphonato, lower alkoxy or lower alkoxypolyalkyleneoxy radicals; R is a carboxylic acid residue or an amino acid or peptide residue provided with a nitrogen protective group conventional in peptide chemistry; and n is 1 or 2; or an indoxyl ester of the formula ##STR6## wherein R 1 '", R 2 '", R 3 '" and R 4 '", which can be the same or different, are hydrogen or halogen atoms, lower alkyl, lower alkoxy, aryl, aralkyl, aralkoxy, hydroxyl, carboxy, carboxy lower alkoxy, aralkoxycarbonyl, aralkoxycarbonyl lower alkoxy, nitro or lower acylamino radicals or in which two adjacent substituents represent a benzo-annellated residue optionally substituted by halogen; X is a sulfur atom or an imino group optionally substituted by a lower alkyl, aryl, aralkyl or acyl radical; A" is an amino acid or peptide residue; and B" is a nitrogen protective group conventional in peptide chemistry or derived therefrom. and said activator is selected from the following: (a) pyridine derivatives of the general formula: ##STR7## in which R 1 , R 2 , R 3 , R 4 and R 5 , which can be the same or different, are hydrogen or halogen atoms, lower alkyl or lower alkoxy radicals, vinyl radicals which are substituted by an aryl radical optionally substituted one or more times by lower alkoxy, amino, alkylamino or dialkylamino, or by a heterocyclic radical, whereby two adjacent substituents can represent an indeno- or benzo-annellated residue optionally substituted one or more times by halogen, hydroxyl, lower alkyl or lower alkoxy, which annellated residue can, in turn, carry a benzo- or pyrido-annellated residue optionally substituted by a lower alkyl radical and R 3 can also stand for a vinylquinuclidyl-carbinol radical; (b) imidazole derivatives of the general formula: ##STR8## in which R 1 ' is a hydrogen atom, a lower alkyl radical or an aryl radical optionally substituted by a hydroxyl group or an acyl radical and R 2 ' is a hydrogen atom, an aminoalkyl, N-acylaminoalkyl or a lower aliphatic, optionally unsaturated carboxylic acid residue or a lower aliphatic α-amino acid residue optionally acylated on the nitrogen; (c) alcohols of the general formula: X--A--OH in which X is a hydrogen atom or a hydroxyl group and A is a hydrocarbon radical; (d) metal complexes of the general formula: D.sub.m [B(CN).sub.n (NO).sub.p ] in which D is an alkali metal ion, B is a heavy metal ion, m is 2, 3, 4 or 5, n is 4, 5, 6, 7 or 8 and p is 0 or 1, the number m being given by the valency of the heavy metal ion and the number n.
Claim 2
Dependent Claim
625 words
Diagnostic agent for the detection of esterolytic and proteolytic enzymes in body fluids, which agent comprises at least one substrate, and adjuvants suitable for said substrate, and at least one activator, and wherein said substrate is a sulphonphthalein ester of the formula ##STR5## wherein R 1 " is a carboxylic acid residue optionally substituted by halogen or a lower alkoxy radical or is an amino acid or peptide residue provided with a nitrogen protective group conventional in peptide chemistry; R 2 " is a halogen atom or a lower alkyl radical; and R 3 " and R 4 ", which can be the same or different are hydrogen or halogen atoms; or an azo dyestuff ester of the formula A'--N═N--B'(OR).sub.n wherein A' is a five- or six-membered, optionally benzo-annellated residue with one or two heteroatoms selected from nitrogen, sulfur and oxygen, which is optionally substituted one or more times by halogen, lower alkyl or lower alkoxy radicals or is a phenyl radical substituted one, two or three times by lower alkyl, lower alkoxy, nitro, sulphonato or acylamino radicals; B' is a benzene, naphthalene or quinoline radical optionally substituted once or twice by sulphonato, lower alkoxy or lower alkoxypolyalkyleneoxy radicals; R is a carboxylic acid residue or an amino acid or peptide residue provided with a nitrogen protective group conventional in peptide chemistry; and n is 1 or 2; or an indoxyl ester of the formula ##STR6## wherein R 1 '", R 2 '", R 3 '" and R 4 '", which can be the same or different, are hydrogen or halogen atoms, lower alkyl, lower alkoxy, aryl, aralkyl, aralkoxy, hydroxyl, carboxy, carboxy lower alkoxy, aralkoxycarbonyl, aralkoxycarbonyl lower alkoxy, nitro or lower acylamino radicals or in which two adjacent substituents represent a benzo-annellated residue optionally substituted by halogen; X is a sulfur atom or an imino group optionally substituted by a lower alkyl, aryl, aralkyl or acyl radical; A" is an amino acid or peptide residue; and B" is a nitrogen protective group conventional in peptide chemistry or derived therefrom. and said activator is selected from the following: (a) pyridine derivatives of the general formula: ##STR7## in which R 1 , R 2 , R 3 , R 4 and R 5 , which can be the same or different, are hydrogen or halogen atoms, lower alkyl or lower alkoxy radicals, vinyl radicals which are substituted by an aryl radical optionally substituted one or more times by lower alkoxy, amino, alkylamino or dialkylamino, or by a heterocyclic radical, whereby two adjacent substituents can represent an indeno- or benzo-annellated residue optionally substituted one or more times by halogen, hydroxyl, lower alkyl or lower alkoxy, which annellated residue can, in turn, carry a benzo- or pyrido-annellated residue optionally substituted by a lower alkyl radical and R 3 can also stand for a vinylquinuclidyl-carbinol radical; (b) imidazole derivatives of the general formula: ##STR8## in which R 1 ' is a hydrogen atom, a lower alkyl radical or an aryl radical optionally substituted by a hydroxyl group or an acyl radical and R 2 ' is a hydrogen atom, an aminoalkyl, N-acylaminoalkyl or a lower aliphatic, optionally unsaturated carboxylic acid residue or a lower aliphatic α-amino acid residue optionally acylated on the nitrogen; (c) alcohols of the general formula: X--A--OH in which X is a hydrogen atom or a hydroxyl group and A is a hydrocarbon radical; (d) metal complexes of the general formula: D.sub.m [B(CN).sub.n (NO).sub.p ] in which D is an alkali metal ion, B is a heavy metal ion, m is 2, 3, 4 or 5, n is 4, 5, 6, 7 or 8 and p is 0 or 1, the number m being given by the valency of the heavy metal ion and the number n.
Claim 3
Dependent Claim
29 words
Diagnostic agent as claimed in claim 1 wherein said conventional adjuvants are selected from buffers, complex formers, wetting agents, oxidation agents, film formers, galenical additional materials and structure formers.
Claim 4
Dependent Claim
15 words
Diagnostic agent as claimed in claim 1 wherein said activator is a pyridine derivative (a).
Claim 5
Dependent Claim
15 words
Diagnostic agent as claimed in claim 1 wherein said activator is an imidazole derivative (b).
Claim 6
Dependent Claim
14 words
Diagnostic agent as claimed in claim 1 wherein said activator is an alcohol (c).
Claim 7
Dependent Claim
15 words
Diagnostic agent as claimed in claim 1 wherein said activator is a metal complex (d).
Claim 8
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is benzo-[h]-quinoline.
Claim 9
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is 4-azafluorene.
Claim 10
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is quinine.
Claim 11
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is 2-[phenyl]-vinyl-pyridine-(2').
Claim 12
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is imidazole.
Claim 13
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is histamine.
Claim 14
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is decan-1-ol.
Claim 15
Dependent Claim
12 words
Diagnostic agent as claimed in claim 1 wherein said activator is tetradecan-1-ol.
Claim 16
Dependent Claim
13 words
Diagnostic agent as claimed in claim 1 wherein said activator is tripotassium-hexacyanoferrate III.
Claim 17
Dependent Claim
13 words
Diagnostic agent as claimed in claim 1 wherein said activator is disodium-pentacyano-nitrosylferrate II.
Claim 18
Dependent Claim
22 words
Method of detecting leukocytes in body fluid which method comprises contacting a sample with a diagnostic agent as claimed in claim 1.
Claim 19
Dependent Claim
12 words
Method as claimed in claim 17 wherein said body fluid is urine.
Claim 20
Dependent Claim
25 words
Method as claimed in claim 17 wherein said activator is selected from benzo-[h]-quinoline; 4-azafluorene; quinine; 2-[phenyl]-vinyl-pyridine-(2'); imidazole; histamine; decan-1-ol; tetradecan-1-ol; tripotassium-hexacyanoferrate III; and disodium-pentacyano-nitrosylferrate II.
Claim 21
Dependent Claim
11 words
Method as claimed in claim 17 wherein said activator is quinine.
Claim 22
Dependent Claim
11 words
Method as claimed in claim 17 wherein said activator is decan-1-ol.
Claim 23
Dependent Claim
12 words
Method as claimed in claim 17 wherein said activator is disodium-pentacyano-nitrosylferrate II.
Claim 24
Dependent Claim
42 words
Process for preparing a diagnostic agent as claimed in claim 1 which process comprises impregnating an absorbent carrier with at least one said substrate selected from said esterase and protease substrates, with conventional adjuvants, and additionally with at least one said activator.
Claim 25
Dependent Claim
15 words
Process as claimed in claim 23 wherein said absorbent carrier is impregnated in two stages.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-11-09 | 1985-05-11 | 1985-11-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-11-09 | 1989-05-11 | 1989-11-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-11-09 | 1993-05-11 | 1993-11-10 | $7700.00 | Window Closed / Lapsed |