Reagents with enhanced performance in clinical diagnostic systems

• US 6,150,128 A
• Filed: 05/09/1997
• Issued: 11/21/2000
• Est. Priority Date: 10/24/1994
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Uretsky, Laura S.
• Primary Examiner(s): Leary, Louise N.
• Application Number:
  US08/853,511
• Time in Patent Office: 1,292 Days
• Field of Search: 435/32, 435/29, 435/14, 435/4, 435/25, 435/15, 435/817, 514/372, 514/359, 514/353, 514/351, 514/373, 514/252, 514/235.8, 514/727, 540/546, 548/336.1, 548/336.5, 548/146, 548/161, 548/327.1
• US Class Current: 435/32
• 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 of products comprising isothiazolines or nitrobromo compounds comprising the steps of:

preparing a formulation comprising isothiazoline or a nitrobromo compound; and

including in said formulation a buffer system comprising imidazole or monoalkyl derivatives thereof.

2. The method of claim 1 wherein said products comprise both isothiazolines and nitrobromo compounds.

3. A method of claim 2 wherein the products are clinical diagnostic reagents.

4. A method of claim 3 wherein the isothiazoline is a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one.

5. A method of claim 4 wherein the concentration of said isothiazolines is approximately between 1 and 25 parts per million of solution.

6. The method of claim 5 wherein said concentration is approximately between 10 and 25 ppm.

7. The method of claim 6 wherein said concentration is approximately between 16 and 20 ppm.

8. A method of claim 3 wherein the nitrobromo compound is 5-bromo-5-nitro-1,3-dioxane.

9. A method of claim 8 wherein the 5-bromo-5-nitro-1,3-dioxane is present at a concentration of approximately between 30 and 250 parts per million of solution.

10. The method of claim 9 wherein said 5-bromo-5-nitro-1,3-dioxane is present approximately between 100 and 250 ppm.

11. The method of claim 10 in which said 5-bromo-5-nitro-1,3-dioxane is present approximately between 180 and 220 ppm.

12. The method of claim 1 in which said buffer system is present from approximately 5 to 70 mmol/L of solution.

13. The method of claim 12 in which said buffer is present from approximately 40 to 60 mmol/L solution.

14. The method of claim 13 in which said buffer is present from approximately 48 to 58 mmol/L.

15. An antimicrobial system for clinical diagnostic reagents comprising (1) isothiazolines or nitrobromo compounds and (2) imidazole or monoalkyl derivatives thereof.

16. A method of enhancing the antimicrobial activity of products comprising isothiazolines or nitrobromo compounds by including in said products a buffer system comprising imidazole or 4-methyl imidazole.

17. An antimicrobial system for clinical diagnostic reagents comprising (1) isothiazolines or nitrobromo compounds and (2) imidazole or 4-methyl imidazole.