Reagents with enhanced performance in clinical diagnostic systems

• US 5,667,983 A
• Filed: 10/24/1994
• Issued: 09/16/1997
• Est. Priority Date: 10/24/1994
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Chiron Diagnostics Corp (Bayer AG)
• Inventors: Abel, Allison L., Uretsky, Laura S., D'Orazio, Paul A., McCaffrey, Robert R., Dalzell, Bonnie C.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): LEARY, LOUISE N
• Application Number:
  US08/327,856
• Time in Patent Office: 1,058 Days
• Field of Search: 435/14, 435/4, 435/25, 435/15, 435/817, 514/372, 514/359, 514/353, 514/351, 514/373, 514/252, 540/546, 548/336.1, 548/336.5
• US Class Current: 435/14
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 43/32 six-membered rings
• CPC Class Codes: A01N 43/50 1,3-Diazoles; Hydrogenated 1,3-diazoles
• CPC Class Codes: A01N 43/80 five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

It has been found that imidazole and related buffers enhance the activity of certain preservatives, for example either (1) a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one or (2) 5-bromo-5-nitro-1,3-dioxane, that are used in clinical diagnostic reagents. It has also been found that these buffers and certain surfactants, such as BRIJ 700 and related hydrophilic surfactants, enhance the precision and accuracy of enzyme biosensors.

Claims

1. A method of enhancing the antimicrobial activity in a clinical diagnostic reagent by including therein a buffer system consisting of imidazole or imidazole derivatives, wherein the antimicrobial products contained in said diagnostic reagents are (1) a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, said mixture being present at a concentration of approximately 1 to 25 ppm and (2) 5-bromo-5-nitro-1,3-dioxane, present at a concentration of approximately 30 to 250 ppm, and wherein said buffer system is present at a concentration of approximately 48 to 58 mmol/L.

2. A method of stabilizing the response of biosensors by utilizing therewith a calibrating reagent comprising imidazole or a related buffer.

3. A method of claim 2 in which the biosensor is for glucose or lactate.

4. A method of claim 2 in which the reagent additionally comprises a hydrophilic surfactant.

5. A method of claim 2 in which the reagent additionally comprises a hydrophilic surfactant having a hydrophilic/lipophilic character or balance (HLB) equal to or greater than 18.

6. A method of claim 5 in which the surfactant is polyoxyethylene(100) stearyl ether.