Analytical element

Claim 2

An analytical element for the detection of a substance which generates hydrogen peroxide upon reaction with an enzyme which comprises a support and a reagent layer comprising a peroxidative substance, a diffusion-resistant phenol compound having been oil-protected, and an aromatic primary amine compound or salt thereof, said aromatic primary amine compound being capable of being oxidized to form an oxidized product, said oxidized product being capable of undergoing a coupling reaction with said diffusion-resistant phenol compound, to thereby produce a diffusion-resistant dyestuff.

Claim 3

The analytical element of claim 1, wherein said aromatic primary amine compound is an o- or p-aminophenol compound or an o- or p-phenylenediamine compound.

Claim 4

The analytical element of claim 1, wherein said diffusion-resistant phenol compound is substituted on its benzene nucleus with a ballast group having a size and a steric configuration which permits the phenol compound to retain its diffusion-resistant state.

Claim 5

The analytical element of claim 3, wherein said diffusion-resistant phenol compound is unsubstituted in at least one of the o-position and p-position relative to the hydroxy group.

Claim 6

The analytical element of claim 4, wherein said diffusion-resistant phenol compound is selected from a compound of the formula: ##STR10## wherein R 1 is a mono-valent organic group or atom; Z' is a hydrogen atom, a split-off group or a split-off atom; R 6 is selected from the group consisting of a hydrogen atom, an aliphatic hydrocarbon residue, an alicyclic compound residue, an aryl group and a heterocyclic residue; R 7 is selected from the group consisting of an aliphatic hydrocarbon residue, an alicyclic compound residue, an aryl group, a heterocyclic residue, an acyl group, --SO 2 R 6 ', and a carbamoyl group, wherein R 6 ' is an alkyl or aryl group; l is an integer of 0 to 3; when l is 2 or 3, each of R 1 ' may be identical or different; and at least one of R 1 ', Z' and ##STR11## is a ballast group.

Claim 7

The analytical element of claim 5, wherein R 1 ' is selected from the group consisting of a halogen atom, an alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 16 carbon atoms, an acyl group having 2 to 36 carbon atoms, ##STR12## and --SO 2 R 9 , wherein R 8 is a hydrogen atom or an alkyl group having 2 to 36 carbon atoms, and R 9 is an alkyl group having 2 to 36 carbon atoms or an aryl group having 6 to 16 carbon atoms; Z' is selected from the group consisting of a hydrogen atom, a halogen atom, --O--R 12 or --O--CO--R 13 , wherein R 12 and R 13 are each an alkyl group having 2 to 36 carbon atoms or an aryl group having 6 to 16 carbon atoms.

Claim 8

The analytical element of claim 5, wherein said aliphatic hydrocarbon residue represented by R 6 or R 7 is an alkyl group having 2 to 36 carbon atoms or an alkenyl group having 2 to 36 carbon atoms; said alicyclic compound residue represented by R 6 or R 7 is a 6- or 6-membered group; said aryl group represented by R 6 or R 7 is a phenyl or naphthyl group; and said heterocyclic residue represented by R 6 or R 7 is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, quinolyl, pyrrolidyl, furalyl, thienyl, piperidyl, pyrolyl, pyrolinyl, tetrazolyl, thiadinyl, imidazolyl, morpholino, furyl, oxazolyl, thiazolyl, benzimidazolyl, benzoxazolyl and benzthiazolyl.

Claim 9

The analytical element of claim 4, wherein said diffusion-resistant phenol compound is selected from a compound having the formula: ##STR13## wherein R 1 is a mono-valent organic group or atom; Z is a hydrogen atom or a group or an atom which is capable of being split off during said coupling reaction; k is an integer of 0 to 4 provided that at least one of R 1 and Z is a ballast group and when k is 2 to 4, each R 1 may be either identical or different; and when two R 1 's are attached at adjacent positions to the benzene ring, said R 1 's may be bonded to each other to form a non-aromatic ring fused to said benzene ring.

Claim 10

The analytical element of claim 8, wherein R 1 is selected from the group consisting of a halogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted heterocyclic residue, a substituted heterocyclic residue, an unsubstituted aryl group, a substituted aryl group, a --SCN group, a --OR 4 group, a --OCOR 4 group, a --OSO 2 R 4 group, a --SR 4 group, a --OCONHR 4 group, a --OSO 2 NHR 4 group, ##STR14## wherein R 4 and R 5 are each selected from the group consisting of a hydrogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heterocyclic residue and a substituted heterocyclic residue; Z is selected from the group consisting of a hydrogen atom, a halogen atom, a --OR 2 group, a --OCOR 2 group, a --OSO 2 R 2 group, a --SR 2 group, a --OCONHR 2 group, a --OSO 2 NHR 2 group, ##STR15## and a --SCN group wherein R 2 and R 3 are each selected from the group consisting of a hydrogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heterocyclic residue, a substituted hetercyclic residue; and said non-aromatic ring fused to the benzene ring which is formed by the bond of the two R 1 groups is selected from a 5- or 6-membered ring.

Claim 11

The analytical element of claim 9, wherein said aliphatic hydrocarbon residue represented by R 1 to R 5 is an alkyl group having 1 to 36 carbon atoms or an alkenyl group having 1 to 36 carbon atoms; said alicyclic compound residue represented by R 1 to R 5 is a 5- or 6-membered group; said heterocyclic residue represented by R 1 to R 5 is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, quinolyl, pyrrolidyl, furalyl, thienyl, piperidyl, pyrolyl, pyrolinyl, tetrazolyl, thiadinyl, imidazolyl, morpholino, furyl, oxazoyl, thiazolyl, benzimidazolyl, benzoxazolyl and benzthiazolyl; and said aryl group represented by R 1 to R 3 is a phenol of naphthyl group.

Claim 12

The analytical element of claim 9, wherein the substituent or substituents on said aliphatic hydrocarbon residue, said alicyclic compound residue, said heterocyclic residue or said aryl group are selected from the group consisting of halogen atoms, nitro groups, cyano groups, hydroxy groups, keto groups, carboxyl groups, sulfo groups, amino groups, alkyl groups, alkenyl groups, aryl groups, heterocyclic residues, alkoxy groups, aryloxy groups, arylthio groups, amide groups, carbamoyl groups, sulfamoyl groups, alkylsulfonyl groups, arylsulfonyl groups, acyl groups, acyloxy groups, acyloxycarbonyl groups, alkoxycarbonyl groups, aryloxycarbonyl groups, and arylthiocarbonyl groups.

Claim 13

An analytical element for the detection of a substance which generates hydrogen peroxide upon reaction with an enzyme which comprises a support and a reagent layer comprising a peroxidative substance, a diffusion-resistant phenol compound having been oil-protected, and an aromatic primary amine compound or salt thereof, said aromatic primary amine compound being capable of being oxidized to form an oxidized product, said oxidized product being capable of undergoing a coupling reaction with said diffusion-resistant phenol compound, to thereby produce a diffusion-resistant dyestuff; said aromatic primary amine being a p-phenylenediamine selected from the compounds having the formula: ##STR16## wherein A and B are each a hydrogen atom, an alkyl group or a substituted alkyl group, or together form a heterocyclic ring together with the nitrogen atom; D, E, G and J are each selected from the group consisting of hydrogen atoms, halogen atoms, hydroxy groups, amino groups, unsubstituted alkoxy groups, substituted alkoxy groups, unsubstituted acylamide groups, substituted acylamide groups, arylsulfonamide groups, unsubstituted alkylsulfonamide groups, substituted alkylsulfonamide groups and alkyl groups.

Claim 14

An analytical element for the detection of a substance which generates hydrogen peroxide upon reaction with an enzyme which comprises a support and a reagent layer comprising a peroxidative substance, a diffusion-resistant phenol compound having been oil-protected, and an aromatic primary amine compound or salt thereof, said aromatic primary amine compound being capable of being oxidized to form an oxidized product, said oxidized product being capable of undergoing a coupling reaction with said diffusion-resistant phenol compound, to thereby produce a diffusion-resistant dyestuff; said aromatic primary amine being a p-phenylenediamine selected from the compounds having the formula: ##STR16## wherein A and B are each a hydrogen atom, an alkyl group or a substituted alkyl group, or together form a heterocyclic ring together with the nitrogen atom; D, E, G and J are each selected from the group consisting of hydrogen atoms, halogen atoms, hydroxy groups, amino groups, unsubstituted alkoxy groups, substituted alkoxy groups, unsubstituted acylamide groups, substituted acylamide groups, arylsulfonamide groups, unsubstituted alkylsulfonamide groups, substituted alkylsulfonamide groups and alkyl groups.

Claim 15

The analytical element of claim 12, wherein at least one of A and B is an alkyl group with is substituted with a substituent selected from the group consisting of a ureido group, a tetrahydrofuryl group, a carboxyl group, a methansulfonamide group, a sulfo group, a methoxy group, an ethoxy group, a methoxyethoxy group, a methoxyethoxyethoxy group and a methoxytetraethoxy group.

Claim 16

The analytical element of claim 12, wherein D, G and J are each selected from the group consisting of hydrogen atoms, alkoxy groups, alkylsulfonamide groups and arylsulfonamide groups.

Claim 17

The analytical element of claim 12, wherein E is a hydrogen atom, an alkyl group or an acylamide group.

Claim 18

The analytical element of claim 12, wherein the diffusion-resistant phenol compound is oil-protected in the presence of a solvent having a boiling point of at least 160° C.

Claim 19

The analyticl element of claim 12, wherein said diffusion-resistant phenol compound is substituted on its benzene nucleus with a ballast group having a side and a steric configuration which permits the phenol compound to retain its diffusion-resistant state.

Claim 20

The analytical element of claim 17, wherein said diffusion resistant phenol compound is substituted as the o-position or p-position relative to the hydroxy group with a substituent which is capable of being split off as a result of said coupling reaction.

Claim 21

The analytical element of claim 17, wherein said diffusion-resistant phenol compound is unsubstituted in at least one of the o-position and p-position relative to the hydroxy group.

Claim 22

The analytical element of claim 19, wherein said diffusion-resistant phenol compound is selected from a compound of the formula: ##STR17## wherein R 1 is a mono-valent organic group or atom; Z' is a hydrogen atom, a split-off group or a split-off atom; R 6 is selected from the group consisting of a hydrogen atom, an aliphatic hydrocarbon residue, an alicyclic compound residue, an aryl group and a heterocyclic residue; R 7 is selected from the group consisting of an aliphatic hydrocarbon residue, an alicyclic compound residue, an aryl group, a heterocyclic residue, an acyl group, --SO 2 R 6 ', and a carbamoyl group, wherein R 6 ' is an alkyl or aryl group; l is an integer of 0 to 3; when l is 2 or 3, each of R 1 ' may be identical or different; and at least one of R 1 ', Z' and ##STR18## is a ballast group.

Claim 23

The analytical element of claim 20, wherein R 1 ' is selected from the group consisting of a halogen atom, an alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 16 carbon atoms, an acyl group having 2 to 36 carbon atoms, ##STR19## and --SO 2 R 9 , wherein R 8 is a hydrogen atom or an alkyl group having 2 to 36 carbon atoms, and R 9 is an alkyl group having 2 to 36 carbon atoms or an aryl group having 6 to 16 carbon atoms; Z' is selected from the group consisting of a hydrogen atom, a halogen atom, --O--R 12 or --O--CO--R 13 , wherein R 12 and R 13 are each an alkyl group having 2 to 36 carbon atoms or an aryl group having 6 to 16 carbon atoms.

Claim 24

The analytical element of claim 20, wherein said aliphatic hydrocarbon residue represented by R 6 or R 7 is an alkyl group having 2 to 36 carbon atoms or an alkenyl group having 2 to 36 carbon atoms; said alicyclic compound residue represented by R 6 or R 7 is a 5- or 6-membered group; said aryl group represented by R 6 or R 7 is a phenyl or naphthyl group; and said heterocyclic residue represented by R 6 or R 7 is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, quinolyl, pyrrolidyl, furalyl, thienyl, piperidyl, pyrolyl, pyrolinyl, tetrazolyl, thiadinyl, imidazolyl, morpholino, furyl, oxazoyl, thiazolyl, benzimidazolyl, benzoxazolyl and benzthiazolyl.

Claim 25

The analytical element of claim 19, wherein said diffusion-resistant phenol compound is selected from a compound having the formula: ##STR20## wherein R 1 is a mono-valent organic group or atom; Z is a hydrogen atom or a group or an atom which is capable of being split off during said coupling reaction; k is an integer of 0 to 4 provided that at least one of R 1 and Z is a ballast group and when k is 2 to 4, each R 1 may be either identical or different; and when two R 1 's are attached at adjacent positions to the benzene ring, said R 1 's may be bonded to each other to form a non-aromatic ring fused to said benzene ring.

Claim 26

The analytical element of claim 23, wherein R 1 is selected from the group consisting of a halogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted heterocyclic residue, a substituted heterocyclic residue, an unsubstituted aryl group, a substituted aryl group, a --SCN group, a --OR 4 group, a --OCOR 4 group, a --OSO 2 R 4 group, a --SR 4 group, a --OCONHR 4 group, a --OSO 2 NHR 4 group, ##STR21## wherein R 4 and R 5 are each selected from the group consisting of a hydrogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heterocyclic residue and a substituted heterocyclic residue; Z is selected from the group consisting of a hydrogen atom, a halogen atom, a --OR 2 group, a --OCOR 2 group, a --OSO 2 R 2 group, a --SR 2 group, a --OCONHR 2 group, a --OSO 2 NHR 2 group, ##STR22## and a --SCN group wherein R 2 and R 3 are each selected from the group consisting of a hydrogen atom, an unsubstituted aliphatic hydrocarbon residue, a substituted aliphatic hydrocarbon residue, an unsubstituted alicyclic compound residue, a substituted alicyclic compound residue, an unsubstituted aryl group, a substituted aryl group, an unsubstituted heterocyclic residue, a substituted hetercyclic residue; and said non-aromatic ring fused to the benzene ring which is formed by the bond of the two R 1 groups is selected from a 5- or 6-membered ring.

Claim 27

The analytical element of claim 24, wherein said aliphatic hydrocarbon residue represented by R 1 to R 5 is an alkyl group having 1 to 36 carbon atoms or an alkenyl group having 2 to 36 carbon atoms; said alicyclic compound residue represented by R 1 to R 5 is a 5- or 6-membered group; said heterocyclic residue represented by R 1 to R 5 is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, quinolyl, pyrrolidyl, furalyl, thienyl, piperidyl, pyrolyl, pyrolinyl, tetrazolyl, thiadinyl, imidazolyl, morpholino, furyl, oxazoyl, thiazolyl, benzimidazolyl, benzoxazolyl and benzthiazolyl; and said aryl group represented by R 1 to R 5 is a phenol or naphthyl group.

Claim 28

The analytical element of claim 24, wherein the substituent or substituents on said aliphatic hydrocarbon residue, said alicyclic compound residue, said heterocyclic residue or said aryl group are selected from the group, hydroxy groups, keto groups, carboxyl groups, sulfo groups, amino groups, alkyl groups, alkenyl groups, aryl groups, heterocyclic residues, alkoxy groups, aryloxy groups, arylthio groups, amide groups, carbamoyl groups, sulfamoyl groups, alkylsulfonyl groups, arylsulfonyl groups, acyl groups, acyloxy groups, acyloxycarbonyl groups, alkoxycarbonyl groups, aryloxycarbonyl groups, and arylthiocarbonyl groups.