EP-3727456-B1 - COMPOSITIONS COMPRISING STABILIZED OXYGEN AND METHODS OF FORMING THE SAME

Inventors

• SAMPRONI, JENNIFER
• HORAN, KEVIN
• NARAYAN, Murli

Dates

Publication Date

20260513

Application Date

20181219

Claims (11)

1. An aqueous diagnostic quality control or calibration reagent comprising, in liquid solution: oxygen, a sugar selected from the group consisting of glucose, maltose, lactose, maltulose, iso-maltulose, lactulose and combinations thereof, and an amino acid, wherein the amino acid is selected from the group consisting of ornithine, arginine and combinations thereof and inhibits chemical reaction between the sugar and the oxygen, said amino acid being present in an amount sufficient to stabilize the oxygen (pO 2 ) relative to a control composition which comprises the oxygen and the sugar but not the amino acid.
2. The reagent of claim 1, comprising from about 0.5 mmol/l to about 11 mmol/l of the amino acid and comprising from about 25 mm Hg to about 650 mm Hg of oxygen.
3. The reagent of any one of the previous claims, comprising from about 27 mg/dl to about 750 mg/dl of glucose.
4. The reagent of any one of the previous claims, further comprising from about 4.5 mg/dl to about 200 mg/dl of Blood Urea Nitrogen (BUN).
5. The reagent of any one of the previous claims, further comprising sodium, chloride, potassium, calcium, magnesium, or any combination thereof.
6. The reagent of any one of the previous claims, wherein the composition has a pH of from about 6.6 to about 7.7.
7. The reagent of any one of the previous claims, wherein the composition is disposed in a closed system.
8. The reagent of any of the previous claims, adapted to calibrate oxygen sensors, glucose sensors, or both oxygen sensors and glucose sensors of an analytical instrument.
9. A method of stabilizing oxygen in an aqueous diagnostic quality control or calibration reagent for use with a diagnostic sensor, the method comprising: adding a stabilizing amount of an amino acid to the liquid solution, wherein the liquid solution contains oxygen and a sugar, wherein the sugar is selected from the group consisting of glucose, maltose, lactose, maltulose, iso-maltulose, lactulose and combinations thereof, and the amino acid is selected from the group consisting of ornithine, arginine and combinations thereof, wherein said amino acid inhibits chemical reaction between the sugar and the oxygen.
10. The method of any one of claims 9, wherein the liquid solution contains from about 0.5 mmol/l to about 11 mmol/l of the amino acid and contains from about 25 mm Hg to about 650 mmHg of oxygen.
11. The method of claim 9 or 10, wherein the liquid solution contains from about 27 mg/dl to about 750 mg/dl of glucose.

Description

The subject application claims benefit under 35 USC § 119(e) of US provisional Application No. 62/608,677, filed December 21, 2017. FIELD OF THE INVENTION Disclosed herein are compositions comprising stabilized oxygen and methods of forming the same. BACKGROUND OF THE INVENTION Aqueous diagnostic quality controls and calibration reagents generally must be stored at 2-8 °C due to the instability of oxygen (pO2) at room temperature. Users may require assays to be performed where refrigeration is not available nearby making expansion of the storage temperature range to 2 - 30 °C preferable. Thus, storage at 2-8 °C is often times not sufficient for storing diagnostic quality controls and calibration reagents. Aqueous compositions containing a predetermined and stabilized concentration of oxygen are known. Such, WO 2017/195852 A1 (corresponding to EP 3 456 815 A1) teaches an aqueous solution containing oxygen nanobubbles having a mean particle size of 30 nm or less and a density of 1016 bubbles or more per 1 ml of solution. The solution can be administered to a living body for supplying sufficient oxygen to peripheral cells and thereby to protect these cells under anaerobic stimulation. US 2004/0137633 A1 discloses aqueous solutions for calibrating an oxygen sensor of an electrochemical sensor system. The aqueous solution comprises cholin or a salt thereof and a known concentration of oxygen, wherein the concentration of cholin is sufficient to reduce the rate of oxygen loss. The content of oxygen in the solution is preferably in a range of from about 10 mmHg to 300 mmHg. Glucose may be added to the calibration solution. SUMMARY OF THE INVENTION Disclosed herein is an aqueous diagnostic quality control or calibration reagent comprising, in liquid solution: oxygen, a sugar selected from the group consisting of glucose, maltose, lactose, maltulose, iso-maltulose and combinations thereof, and an amino acid, wherein the amino acid is selected from the group consisting of ornithine, arginine and combinations thereof. The amino acid inhibits chemical reaction between the sugar and the oxygen and is present in an amount sufficient to stabilize the oxygen (pO2) relative to a control control composition which comprises the oxygen and the sugar but not the amino acid. Further provided is a method of stabilizing oxygen in an aqueous diagnostic quality control or calibration reagent for use with a diagnostic sensor, the method comprising: adding a stabilizing amount of an amino acid to the liquid solution, wherein the liquid solution contains oxygen and a sugar selected from the group consisting of glucose, maltose, lactose, maltulose, iso-maltulose, lactulose and combinations thereof, and the amino acid is selected from the group consisting of ornithine, arginine and combinations thereof, wherein said amino acid inhibits chemical reaction between the sugar or sugar alcohol and the oxygen. BRIEF DESCRIPTION OF THE DRAWINGS The summary, as well as the following detailed description, is further understood when read in conjunction with the appended drawings. For the purpose of illustrating the disclosed reagents, and methods there are shown in the drawings exemplary embodiments of the compositions, reagents, and methods; however, the compositions, reagents, and methods are not limited to the specific embodiments disclosed. In the drawings: FIG 1 illustrates the percent (%) pO2 degradation vs. glucose concentration in solutions stored for 2 weeks at 45 °C.FIG. 2 illustrates the percent (%) oxygen recovery in amino acid containing solutions stored at 25 °C for 12 weeks as compared to time zero (baseline). DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS The disclosed reagents and methods may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures, which form a part of this disclosure.. Unless specifically stated otherwise, any description as to a possible mechanism or mode of action or reason for improvement is meant to be illustrative only, and the disclosed compositions, reagents, and methods are not to be constrained by the correctness or incorrectness of any such suggested mechanism or mode of action or reason for improvement. Throughout this text, the descriptions refer to compositions comprising stabilized oxygen and methods of stabilizing oxygen in a liquid solution. Where the disclosure describes or claims a feature or embodiment associated with the compositions, such a feature or embodiment is equally applicable to the disclosed methods. Likewise, where the disclosure describes or claims a feature or embodiment associated with the disclosed methods, such a feature or embodiment is equally applicable to the compositions. Where a range of numerical values is recited or established herein, the range includes the endpoints thereof and all the individual integers and fractions within the range, and also includes each of the narrower ranges therein formed