Method for increasing shelf-life of a serum bilirubin reference composition and composition produced thereby

Claim 2

An improved blood serum reference composition of the type comprising blood serum having a bilirubin constituent of known value, characterized in that said composition possesses a pH of from about 8.2 to about 9.2 and further comprises: (a) a sulfhydryl compound in an amount sufficient to further enhance the stability of bilirubin and (b) a chelating agent in an amount sufficient to bind the metals present in said blood serum.

Claim 3

The composition of claim 1 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is from about -30 to about -300 millivolts and wherein said composition comprises from about 25 to about 1,000 mg chelating agent per 100 ml serum.

Claim 4

The composition of claim 1 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is from about -100 to about -200 millivolts, wherein said composition comprises from about 50 to about 150 mg chelating agent per 100 ml serum, and wherein said composition possesses a pH of from about 8.4 to about 8.9.

Claim 5

The composition of claim 3 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is about -160 millivolts, wherein said composition comprises about 100 mg chelating agent per 100 ml serum, and wherein said composition possesses a pH of about 8.7.

Claim 6

The composition of claim 4 wherein said sulfhydryl compound is selected from a group consisting of dithioerythreitol, dithiothreitol, mercaptrethanol, cysteine, reduced gluthione, N-acetyl cysteine, mercaptoacetate, and mixtures thereof, and wherein said chelating agent is selected from a group consisting of ethylenediaminetetraacetic acid, nitrilotriacetic acid, ethylenediamino, diethylenetriamine, triethyltetramine, tetraethylenepentamine, pentaethylenehexamine, N-hydroxyethyliminodiacetic acid, N-hydroxyethyl-N,N',N', ethylenediaminitriacetic acid, N,N,N',N",N"-diethylenetriaminepentaacetic acid, citric acid, tartanic acid, gluconic acid, tripolyphosphate ion, polyphosphate anion, N,N'-ethylenebis[2-(o-hydroxyphenyl]glycine, 3,5-disulfopyrocatechol, bis-(orthohydroxybenzyl)ethylenediamine-N,N'-diacetic acid, salts thereof, and mixtures thereof.

Claim 7

The composition of claim 5 wherein said sulfhydryl compound is dithiothreitol and wherein said chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid, salts thereof, and mixtures thereof.

Claim 8

An improved bilirubin reference composition comprising in its non-biological component from about 60 to about 80 weight percent water, from about 20 to about 40 weight percent of at least one alkylene polyol having from 2 to 5 carbon atoms, the remainder being bilirubin and, optionally, other natural biological materials selected from a group consisting of blood serum, enzymes, metabolites, electrolytes, and hormones, characterized in that said composition possesses a pH of from about 8.2 to about 9.2 and further comprises: (a) a sulfhydryl compound in an amount sufficient to further enhance the stability of bilirubin and (b) a chelating agent in an amount sufficient to bind the metals present in said blood serum.

Claim 9

An improved bilirubin reference composition comprising in its non-biological component from about 60 to about 80 weight percent water, from about 20 to about 40 weight percent of at least one alkylene polyol having from 2 to 5 carbon atoms, the remainder being bilirubin and, optionally, other natural biological materials selected from a group consisting of blood serum, enzymes, metabolites, electrolytes, and hormones, characterized in that said composition possesses a pH of from about 8.2 to about 9.2 and further comprises: (a) a sulfhydryl compound in an amount sufficient to further enhance the stability of bilirubin and (b) a chelating agent in an amount sufficient to bind the metals present in said blood serum.

Claim 10

The composition of claim 7 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is from about -30 to about -300 millivolts and wherein said composition comprises from about 25 to about 1,000 mg chelating agent per 100 ml serum.

Claim 11

The composition of claim 7 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is from about -100 to about -200 millivolts, wherein composition comprises from about 50 to about 150 mg chelating agent per 100 ml serum, and wherein said composition possesses a pH of from about 8.4 to about 8.9.

Claim 12

The composition of claim 9 wherein said sulfhydryl compound is present in an amount such that the oxidation-reduction potential of said composition is about -160 millivotls, wherein said composition comprises about 100 mg chelaying agent per 100 ml serum, and wherein said composition possesses a pH of about 8.7.

Claim 13

The composition of claim 10 wherein said sulfhydryl compound is selected from a group consisting of dithioerythreitol, dithiothreitol, mercaptrethanol, cysteine, reduced gluthione, N-acetyl cysteine, mercaptoacetate, and mixtures thereof, and wherein said chelating agent is selected from a group consisting of ethylenediaminetetraacetic acid, nitrilotriacetic acid, ethylenediamino, diethylenetriamine, triethyltetramine, tetraethylenepentamine, pentaethylenehexamine, N-hydroxyethyliminodiacetic acid, N-hydroxyethyl-N,N',N',ethylenediamietriacetic acid, N,N,N',N",N"-diethylenetriaminepentaacetic acid, citric acid, tartanic acid, gluconic acid, tripolyphosphate ion, polyphosphate anion, N,N'-ethylenebis[2-(o-hydroxyphenyl]glycine, 3,5-disulfopyrocatechol, bis-(orthohydroxybenzyl)ethylenediamine-N,N'-diacetic acid, salts thereof, and mixtures thereof.

Claim 14

The composition of claim 7 wherein said sulfhydryl compound is dithiothreitol and wherein said chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid, salts thereof, and mixtures thereof.

Claim 15

An article comprising a gas impervious container having located therein an inert gas and the composition of any one of claims 1-11 or 12.

Claim 16

An article comprising a gas impervious container which is also impervious to visible light and having located therein an inert gas and the composition of any one of claims 1-11 or 12.