WO1995013536A1 - Preparation de controle pour bandelettes d'essai pour la detection du glucose - Google Patents

Preparation de controle pour bandelettes d'essai pour la detection du glucose Download PDF

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Publication number
WO1995013536A1
WO1995013536A1 PCT/US1994/013445 US9413445W WO9513536A1 WO 1995013536 A1 WO1995013536 A1 WO 1995013536A1 US 9413445 W US9413445 W US 9413445W WO 9513536 A1 WO9513536 A1 WO 9513536A1
Authority
WO
WIPO (PCT)
Prior art keywords
glucose
control reagent
clay mineral
control
reagent
Prior art date
Application number
PCT/US1994/013445
Other languages
English (en)
Other versions
WO1995013536A9 (fr
Inventor
Myron Rapkin
Diana Storhoff
Walter Jernigan
Original Assignee
Boehringer Mannheim Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Mannheim Corporation filed Critical Boehringer Mannheim Corporation
Priority to EP95902651A priority Critical patent/EP0728306A1/fr
Publication of WO1995013536A1 publication Critical patent/WO1995013536A1/fr
Publication of WO1995013536A9 publication Critical patent/WO1995013536A9/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard

Definitions

  • the present invention relates to control material useful in validating testing devices such as test strips and dipsticks. More particularly, the present invention relates to a non-serum based, aqueous glucose control material and to a method for making said control material.
  • the field of clinical chemistry and clinical analysis is concerned, inter alia , with the determination and quantification of various substances in body fluids. Many examples of the substances which are determined can be given, and these include cholesterol, urea, cations, and glucose. These examples of analytes, as well as others, are assayed in diverse body fluids such as urine and blood.
  • the monitoring of the level of glucose in blood is important to the management of diabetes.
  • the level of glucose in the blood is controlled by the amount of carbohydrate ingested and by insulin. Too much insulin lowers the glucose level, and too little will result in an abnormally high level of glucose. Both circumstances lead to serious health problems for the diabetic.
  • Most of the glucose testing done outside of the hospital laboratory is done in non-laboratory settings such as nurses 1 stations, physicians' offices and at home. Testing is frequently done by measuring the amount of glucose in urine. As the level of glucose rises in the blood, it exceeds the ability of the kidney to reabsorb it, and glucose is excreted into the urine. Although measurement of glucose in urine is useful, measurement of glucose in blood provides a more accurate reflection of the condition of the subject. Urine glucose does not accurately reflect the level of glucose in the blood since the level of glucose in urine is determined by the level of glucose in the blood and the ability of the kidney to reabsorb the glucose. Therefore, the urine sample cannot tell the diabetic how low his glucose level is.
  • Dry reagent test strips sometimes referred to as dipsticks, are widely used for detecting glucose in urine and blood. These devices are characterized by their simplicity of use.
  • test strips comprise plastic strips provided at one end thereof with an absorbent paper portion which has been impregnated with reagents such as an enzyme system and a color indicator compound which produces or changes color to form a detectable signal when the test strip is contacted with the analyte being determined.
  • reagents such as an enzyme system
  • a color indicator compound which produces or changes color to form a detectable signal when the test strip is contacted with the analyte being determined.
  • This change in color can be measured by comparing the color formed on the strip with a standard color chart calibrated to various glucose concentrations.
  • instruments More recently, however, to more accurately control the level of glucose in blood, instruments have been developed which measure the color change in a reflectance photometer and thereby produce quantitative results.
  • oxidative reactions such as the glucose oxidase/peroxidase method
  • reductive reactions such as the glucose oxidase/ferricyanide method.
  • Instruments have also been developed which determine glucose by means of electrochemical methods in which a change in current is measured.
  • control material as "a specimen, or solution, which is analyzed solely for quality control purposes and is not used for calibration purposes.”
  • This standard reference work goes on to describe some of the requisites of control materials as follows: “They need to be stable materials, available in aliquots or vials, that can be analyzed periodically over a long time. There should be little vial-to-vial variation so that differences between repeated measurements can be attributed to the analytical method alone.”
  • the above-cited reference, at page 433 discusses how the matrix of the control material should be the same as the material being analyzed. To that end, modified human serum is discussed as one type of control material.
  • control serum as referring to control material based upon serum.
  • control reagent refers to a control material which is not based upon, and which does not contain, serum of any type.
  • stability one of the criteria which control materials have to satisfy is stability.
  • Control materials based upon serum are inherently unstable due to the various components contained therein. Further, sera will vary from source to source, so uniformity from lot to lot cannot be guaranteed. Thus, it is sometimes desirable to have a control material based upon a non-serum or serum-free medium.
  • control reagent as used herein, is described in U.S.
  • the Ryan '959 patent points to a problem with aqueous control reagents at column 1, lines 50-55. Briefly, erythrocytes impart a degree of viscosity to blood which is absent in water based systems. This problem was also recognized in U.S. Pat. No. 3,920,580 issued to Mast. This patent teaches that aqueous solutions had not been consistent, and that a lack of reproducibility was observed when dry reagent strips were used with such materials. Mast teaches that suitable reagents could be prepared by using an antidiffusing agent in combination with glucose and water. The antidiffusing agents taught by Mast include polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, dextran, and bovine serum albumin.
  • Beneficial amounts are taught to be between about 3 and 35 percent of antidiffusing agent.
  • the control solution may also include adjuvants to obtain a particular color or physical appearance, which include colored latex particles and water-insoluble lake dyes.
  • Terashi a in European Appl. No. 266,216, discloses control or calibration solutions containing a water- insoluble dispersed phase, which can be a solid polymer or copolymer having a molecular weight of 10 5 to 10 6 , a liquid phase, or an emulsion of natural polymers such as sodium alginate.
  • Particle sizes taught are about 0.01 ⁇ m to about 10 ⁇ m, and amounts taught are 1 to 50 percent by weight, preferably 10 to 50 percent by weight.
  • Louderback, in U.S. Pat. No. 3,977,995, teaches a calibrating fluid for automated instruments for blood cell counting and hemoglobin determination comprising a solution of hemoglobin which contains latex particles.
  • the latex particles have a particle size of from about 5 to 20 microns, approximately the size of leukocytes, and are employed in the calibrating fluid at a concentration of 8,000 to 22,000 particles per microliter.
  • Kennamer et al . in U.S. Pat. No. 5,028,542, the content of which is herein incorporated by reference, describe a non-serum based, glucose measurement control reagent in which the viscosity agent polystyrene sulfonate is used.
  • a suitable glucose control reagent can be formed without using any of the organic, polymeric materials referred to in Mast and others in the art as required ingredients. Rather, by combining an inorganic, non-polymeric clay mineral with a predetermined amount of glucose and water, along with additional optional materials, a suitable glucose control reagent can be made.
  • the present invention is a non-serum based glucose control reagent which comprises a predetermined, known amount of glucose, water, and an inorganic clay mineral.
  • Preferred clay minerals are selected from the smectite group of clays, and an especially preferred clay is hectorite.
  • the preferred concentration for the clay mineral is between about 0.1 and 1 percent by weight.
  • composition of the present invention is useful in validating testing devices such as test strips for the measurement of glucose.
  • control reagent of the invention is useful with a variety of types of glucose testing devices, including those devices employing oxidative glucose measurement methods, devices employing reductive glucose measurement methods, and also with devices utilizing electrochemical methods for determining glucose. Additional materials such as a buffer, a preservative, or a surfactant, either alone or in various additive combinations, may be mixed with the three required components.
  • Another aspect of the present invention is a method for making the control reagent by mixing the glucose, water, and the clay mineral together.
  • a preferred clay mineral used in the invention is selected from the smectite, or montmorillonite, group of clays, which includes montmorillonite, beidellite, nontronite, hectorite, saponite and sauconite. Less common smectite clays include volkhonskoite, med onite and pimelite. An especially preferred clay mineral is hectorite. Smectites are crystalline clay minerals that carry a lattice charge and characteristically expand when solvated with water and alcohols.
  • Hectorite is preferably and conveniently used in the form of a rheological additive, a specially processed hectorite clay gellant with a fine particle size which makes it readily dispersible in aqueous systems using conventional high speed dispersers.
  • Wet particles should be fine enough to pass through a No. 200 sieve and thus less than about 75 ⁇ m in size.
  • Clay minerals from other groups such as kaolinite and attapulgite clays are also within the scope and spirit of the present invention. In general, the clay chosen must be in a purified form free from grit, very fine-grained, and dispersible in liquid.
  • Essential to the invention are a predetermined amount of glucose, water, and the recited clay mineral.
  • the water is used, of course, to create a reagent solution in which the clay particles are suspended.
  • predetermined is meant that, prior to formulation of the actual reagent, a concentration of glucose has been selected. This concentration may vary, as those skilled in the art will recognize. As has been mentioned above, the art recognized, e.g., a range of from 40 to 500 mg/dl, but one may envision lower ranges to, e.g., about 20 mg/dl. Some typical ranges would be from about 60 to about 240 mg/dl, or from about 60 to about 300 mg/dl.
  • the essential features of the invention when the reagent is in the form of a dispersion or solution, are the solvent (water) , the predetermined amount of glucose, and the clay mineral.
  • the clay mineral may be present in, e.g., a range of about 0.1 to about 1 percent by weight of the reagent. The weight percent of the clay mineral will be determined by the final reagent viscosity desired and the desired diffusion or permeability characteristics of the control material with the particular testing device with which it is to be used.
  • Such characteristics will vary according to the particular clay chosen and its specific properties, which include the predominant content of the clay mineral, which is typically a hydrated silicate of aluminum, iron, or magnesium, the fineness of individual clay particles, which may be of colloidal size in at least one dimension, rheological properties, and the property of thixotropy in various degrees of complexity.
  • the particular clay selected should also be one whose reactivity does not adversely interfere with the determination of glucose. It is not necessary that the control material have the same viscosity as whole blood; however, it is desirable that the permeability of the material, i.e., the diffusion rate of the analyte, through the reagent matrix of the test strip approximate that of whole blood.
  • control material optionally includes typical additives such as buffers, preservatives, and surfactants.
  • typical additives such as buffers, preservatives, and surfactants.
  • a colored or colorable substance in the reagent mixture. This can be desirable because body fluid -samples frequently possess a particular color as one of their properties. As the control reagent is being used to calibrate per a body fluid sample, it can be useful to calibrate against conditions as similar to the tested fluid as possible, including color.
  • Fig. 1 is a graph showing the percent reflectance of the control material of the present invention at varying levels of glucose.
  • DESCRIPTION OF PREFERRED EMBODIMENTS EXAMPLE 1 Preparation of Control Reagent A preferred formulation of the control reagent of the present invention was prepared as follows: A 1 percent by weight aqueous dispersion of BENTONE ® EW (Rheox, Inc., Hightstown, NJ) hectorite clay particles was prepared. It has been found that best results are obtained if the dispersion is made under high shear (minimum 3000 rpm) for at least 15 minutes using tepid water between pH 7 and 8.
  • EXAMPLE 2 Efficacy of Control Reagent with Reductive Method
  • the control reagent described in Example 1 was then tested for its efficacy.
  • one of the most important features of a control reagent is its consistency, meaning that values obtained using it should be fairly uniform from run to run.
  • Example 1 the control reagent of Example 1 was applied to 5 different lots of test strips containing the glucose determination system described in U.S. Pat. No. 4,929,545. Briefly, this publication describes the determination of glucose using a reagent containing a glucose oxidase/ferricyanide/ferric compound system.
  • the hexokinase-measured glucose level was 23 mg/dl for the 1% Bentone control and 19 mg/dl for the Reference E control material.
  • control reagent comprising a 1 percent aqueous dispersion of VAN GEL ® ES (R.T. Vanderbilt Company, Inc., Norwalk, CT) clay particles was prepared using the following: 2.0 g Van Gel ES, 200.0 g deionized water, and 0.20 g PLURONIC ® L-35 (polyoxyalkylene ether from BASF Corp.). To this was added 0.5 M MES/CAPS buffer to make 50 mM. The mixture was homogenized for 15 minutes. Eleven aliquots of this dispersion then had glucose added to them in predetermined amounts ranging from 26.0 to 429.0 mg/dl as measured using a hexokinase reference method.
  • EXAMPLE 4 Efficacy of Control Reagent with Electrochemical Method A 0.55 percent by weight aqueous dispersion of Bentone EW clay particles was prepared as described in Example 1. Several biocides were also added, 0.30% by weight 2-phenoxyethanol, 0.30% by weight Germall 115, and 0.15% by weight methylparaben. Thirteen aliquots of this dispersion then had glucose added to them in predetermined amounts ranging from 21.0 to 661.0 mg/dl as measured using a hexokinase reference method. One aliquot had no glucose added. Using the electrochemical, amperometric biosensor method described in PCT Application No.

Abstract

On décrit un réactif de contrôle sans sérum qui est utile pour valider des dispositifs tels que des bandelettes d'essai utilisées pour détecter le glucose. Cette composition de réactif contient de l'eau, une quantité prédéterminée de glucose, et une argile minérale. L'argile minérale que l'on préfère tout particulièrement est l'hectorite. On décrit également un procédé pour fabriquer ce réactif de contrôle.
PCT/US1994/013445 1993-11-12 1994-11-14 Preparation de controle pour bandelettes d'essai pour la detection du glucose WO1995013536A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP95902651A EP0728306A1 (fr) 1993-11-12 1994-11-14 Preparation de controle pour bandelettes d'essai pour la detection du glucose

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15384293A 1993-11-12 1993-11-12
US08/153,842 1993-11-12

Publications (2)

Publication Number Publication Date
WO1995013536A1 true WO1995013536A1 (fr) 1995-05-18
WO1995013536A9 WO1995013536A9 (fr) 1995-08-10

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CA (1) CA2175907A1 (fr)
WO (1) WO1995013536A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6900058B2 (en) * 2003-03-11 2005-05-31 Bionostics, Inc. Control solution for photometric analysis
US7504020B2 (en) 2002-10-31 2009-03-17 Panasonic Corporation Determination method for automatically identifying analyte liquid and standard solution for biosensor
EP2267150A1 (fr) 2005-04-08 2010-12-29 Bayer Healthcare LLC Composé oxydable servant de référence interne d'une solution de contrôle pour biocapteurs
US8102517B2 (en) 2004-12-13 2012-01-24 Bayer Healthcare, Llc Method of differentiating between blood and control solutions containing a common analyte
US8337691B2 (en) 2007-12-10 2012-12-25 Bayer Healthcare Llc Control markers for auto-detection of control solution and method of use
US8696880B2 (en) 2004-02-06 2014-04-15 Bayer Healthcare Llc Oxidizable species as an internal reference for biosensors and method of use
WO2017108765A1 (fr) * 2015-12-21 2017-06-29 Cilag Gmbh International Fluide imitant les propriétés électrochimiques du sang
EP3483598A1 (fr) 2005-09-30 2019-05-15 Ascensia Diabetes Care Holdings AG Voltampérométrie commandée

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109470533B (zh) * 2018-10-24 2021-09-21 北京市临床检验中心 一种用于便携式血糖仪的人源全血基质质控品的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3950349A (en) * 1973-04-19 1976-04-13 Imperial Chemical Industries Limited N-(N1 -11 -Benzisothiazolin-31 -31 -onylcarbonylthio)-1,2-benzisothiazolin-3-one
US4237019A (en) * 1977-12-23 1980-12-02 Imperial Chemical Industries Limited 1-Thiocyanato-8-substituted naphthalene compounds and their use as biocides
US4291497A (en) * 1979-02-26 1981-09-29 Manankov Mikhail K Method of introducing chemical agents into plants
US4826535A (en) * 1988-04-12 1989-05-02 Rich Art Color Company, Inc. Stain-free tempera paints
US5028542A (en) * 1990-02-07 1991-07-02 Boehringer Mannheim Corporation Glucose measurement control reagent and method of making the same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3950349A (en) * 1973-04-19 1976-04-13 Imperial Chemical Industries Limited N-(N1 -11 -Benzisothiazolin-31 -31 -onylcarbonylthio)-1,2-benzisothiazolin-3-one
US4237019A (en) * 1977-12-23 1980-12-02 Imperial Chemical Industries Limited 1-Thiocyanato-8-substituted naphthalene compounds and their use as biocides
US4291497A (en) * 1979-02-26 1981-09-29 Manankov Mikhail K Method of introducing chemical agents into plants
US4826535A (en) * 1988-04-12 1989-05-02 Rich Art Color Company, Inc. Stain-free tempera paints
US5028542A (en) * 1990-02-07 1991-07-02 Boehringer Mannheim Corporation Glucose measurement control reagent and method of making the same

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7504020B2 (en) 2002-10-31 2009-03-17 Panasonic Corporation Determination method for automatically identifying analyte liquid and standard solution for biosensor
US6900058B2 (en) * 2003-03-11 2005-05-31 Bionostics, Inc. Control solution for photometric analysis
US10067082B2 (en) 2004-02-06 2018-09-04 Ascensia Diabetes Care Holdings Ag Biosensor for determining an analyte concentration
US8696880B2 (en) 2004-02-06 2014-04-15 Bayer Healthcare Llc Oxidizable species as an internal reference for biosensors and method of use
US8102517B2 (en) 2004-12-13 2012-01-24 Bayer Healthcare, Llc Method of differentiating between blood and control solutions containing a common analyte
US8681324B2 (en) 2004-12-13 2014-03-25 Bayer Healthcare, Llc Method of differentiating between blood and control solutions containing a common analyte
US8416398B2 (en) 2004-12-13 2013-04-09 Bayer Healthcare, Llc Method of differentiating between blood and control solutions containing a common analyte
US9766198B2 (en) 2005-04-08 2017-09-19 Ascensia Diabetes Care Holdings Ag Oxidizable species as an internal reference in control solutions for biosensors
US8002965B2 (en) 2005-04-08 2011-08-23 Bayer Healthcare Llc Oxidizable species as an internal reference in control solutions for biosensors
US8702926B2 (en) 2005-04-08 2014-04-22 Bayer Healthcare Llc Oxidizable species as an internal reference in control solutions for biosensors
US9244078B2 (en) 2005-04-08 2016-01-26 Bayer Healthcare Llc Oxidizable species as an internal reference in control solutions for biosensors
EP2267150A1 (fr) 2005-04-08 2010-12-29 Bayer Healthcare LLC Composé oxydable servant de référence interne d'une solution de contrôle pour biocapteurs
EP3483598A1 (fr) 2005-09-30 2019-05-15 Ascensia Diabetes Care Holdings AG Voltampérométrie commandée
US8716024B2 (en) 2007-12-10 2014-05-06 Bayer Healthcare Llc Control solution for use in testing an electrochemical system
US8871517B2 (en) 2007-12-10 2014-10-28 Bayer Healthcare Llc Method of using a control solution and preparing for testing using the same
US8337691B2 (en) 2007-12-10 2012-12-25 Bayer Healthcare Llc Control markers for auto-detection of control solution and method of use
US9933385B2 (en) 2007-12-10 2018-04-03 Ascensia Diabetes Care Holdings Ag Method of using an electrochemical test sensor
US10690614B2 (en) 2007-12-10 2020-06-23 Ascensia Diabetes Care Holdings Ag Method of using an electrochemical test sensor
WO2017108765A1 (fr) * 2015-12-21 2017-06-29 Cilag Gmbh International Fluide imitant les propriétés électrochimiques du sang

Also Published As

Publication number Publication date
CA2175907A1 (fr) 1995-05-18
EP0728306A1 (fr) 1996-08-28

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