US3880590A - Test strip for ketone bodies - Google Patents

Test strip for ketone bodies Download PDF

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Publication number
US3880590A
US3880590A US481913A US48191374A US3880590A US 3880590 A US3880590 A US 3880590A US 481913 A US481913 A US 481913A US 48191374 A US48191374 A US 48191374A US 3880590 A US3880590 A US 3880590A
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US
United States
Prior art keywords
nitroprusside
salt
chloride
ketone bodies
test strip
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
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US481913A
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English (en)
Inventor
Yasunao Ogawa
Ukio Yonetani
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Shionogi and Co Ltd
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Shionogi and Co Ltd
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Publication date
Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd
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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
    • G01N33/64—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving ketones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/20—Oxygen containing
    • Y10T436/200833—Carbonyl, ether, aldehyde or ketone containing

Definitions

  • test strip for the detection of ketone bodies, comprising an absorbing material, a heavy metal salt and a nitroprusside salt.
  • the test strip is useful in the diagnosis of various diseases such as diabetes, disorders in the digestive organs, renal insufficiency, uremia, selfpoisoning or malignant carcinoma.
  • This invention relates to a test strip for the detection of ketone bodies and a composition therefor. More particularly, the present invention relates to a test strip for the detection'of ketone bodies, comprising an absorbing material, a heavy metal salt and a nitroprusside salt, and to a composition therefor comprising a heavy metal salt and a nitroprusside salt.
  • ketosis takes place owing to insufficient intake of sugars or disorder of sugar availability in the living bodies.
  • ketone bodies such as acetoacetic acid, acetic acid, acetone or B-hydroxybutyric acid increase in the blood, and they are excreted mainly as acetoacetic acid in the urine.
  • the ketosis indicates the presence of various diseases such as diabetes, disorders in the digestive organs, renal insufficiency, uremia, self-poisoning, malignant carcinoma, etc.
  • detection of ketone bodies in the body fluids such as urine, serum or plasma can provide a diagnosis of such diseases.
  • ketone bodies Hitherto, a number of methods for the detection of ketone bodies have been employed in the art.
  • a test strip comprising a nitroprusside salt and an alkali substance is known for the detection of ketone bodies.
  • nitroprusside salts are very unstable to an alkali, such known method which is carried out under alkaline conditions is not a good test method for the detection of ketone bodies.
  • the test strips heretofore employed in the art have drawbacks in that their production is complicated and their sensitivity to ketone bodies is not high.
  • test strips and the compositions for the detection of ketone bodies in accordance with the present invention can be prepared in the following manner.
  • a nitroprusside salt and a heavy metal salt are dissolved or suspended in a suitable solvent to give a solution. Then, an absorbing material is dipped in the solution and dried in the air or at a temperature of from room temperature to about 50C, to give a test strip for the detection of ketone bodies.
  • the solution itself may be used in the detection of ketone bodies, but a test strip prepared as above can be more conveniently used in view of the preservation, stability and handling, rather than the solution itself.
  • the heavy metal salt can be inorganic salts of a heavy metal of which specific gravity is approximately more than 5.
  • the heavy metal are nickel, copper, cobalt, manganese, chromium and zinc
  • typical examples of such heavy metal salt are nickel chloride, ferric chloride, ferrous chloride, ferric ammonium sulfate, ferrous sulfate, euprous chloride, cupric chloride, cobalt dichloride and cobaltic chloride.
  • the most preferred heavy metal salt is nickel chloride.
  • the metal salts can be used usually at a concentration of 1-207c, preferably 5-l57c.
  • nitroprusside salt it is preferred to use a nitroprusside inorganic salt such as alkali metal salts (e.g. sodium salt, potassium salt).
  • alkali metal salts e.g. sodium salt, potassium salt.
  • the nitroprusside salt can be usually used at a concentration of l-207c, especially 5-157z.
  • Examples of the solvent in preparing an impregnating solution containing the heavy metal salt and the nitroprusside salt are water, organic solvents (e.g. dimethylformamide, dimethylsulfoxide, methanol, ethanol) and a mixture thereof.
  • the absorbing material to be dipped in a solution containing the nitroprusside salt and the heavy metal salt can be a sheet of paper, a piece of cloth and a stick of porous wood.
  • Examples of the kind of paper are filter paper, blotting paper, adsorbent paper (e.g. silica gel paper, alumina paper), ion-exchange cellulose paper (e.g.
  • phosphonomethyl cellulose paper phosphonomethyl cellulose paper, sulfoethyl cellulose paper, phospho cellulose paper, carboxymethyl cellulose paper, guanidoethyl cellulose paper, diethylaminoethyl cellulose paper, aminoethyl cellulose paper, Ecteola-cellulose paper which is an epichlorhydrin, triethanolamine reacted cellulose ion exchange paper, as note U.S. Pat. No. 3,598,704, paminobenzyl cellulose paper, polyethyleneimine cellulose paper), ion-exchange Sephadex paper and ionexchange resin paper.
  • the shape of the absorbing material is not particularly limited, though it is usually used in a strip form. Among such absorbing materials, ion-exchange cellulose papers, particularly diethylaminoethyl cellulose paper, can be preferably employed.
  • the solution itself containing the necessary ingredients may be used to detect ketone bodies by adding it to a specimen of body fluids such as urine. plasma or serum, whereby detectable color change results.
  • body fluids such as urine. plasma or serum
  • the composition is advantageously used in the form of a solid prepareation, rather than the im-- pregnating solution itself.
  • Solid preparations such as tablets, granules, pills or powders can be prepared in a conventional manner.
  • suitable additives e.g. excipient, disintegrating agent, dispersing agent. stabilizer, binder
  • the color change is detectable only by dissolving such solid preparation in the body fluids containing the ketone bodies.
  • the color reaction may be effected in such a manner that a tablet containing a heavy metal salt and a tablet containing a nitroprusside salt, normally separately packed, are combined in a specimen of body fluids when used.
  • the test strip of the invention is used by dipping it in a test sample or by impregnating a test sample into the test strip, whereby detectable color change results.
  • plasma or serum is used as a test sample, the same application is possible using the test strip of the invention.
  • the test strip of the invention may be, if desired, used in a more convenient form such as, for example, being held on a plastic sheet.
  • the test strip of the invention is sensitive to ketone bodies, particularly to acetoacetic acid in the urine. Since characteristic color reaction takes place depending on the concentration of the ketone bodies to be detected, semi-quantitative detection for such ketone bodies is possible. It is possible to detect acetoacetic acid in an amount of more than 1 mg/lOO ml in the urine with the test strip of the invention. Other ketone bodies such as acetone or B-hydroxybutyric acid are generally not detectable with the present test strip. In general, color tone of the test strip depends on the kind of the heavy metal salts used.
  • test strip when nickel salts or cobalt salts; iron salts; and copper salts are employed, the test strip turns purple; orange to brown; and blue to purple, respectively, in the presence of acetoacetic acid.
  • This various color tones seem to be due to the formation of specific colored chelate among the nitroprusside salt, acetoacetic acid and heavy metal salt. It is considered that this chelate formation contributes much to the stability of the nitroprusside salt, thus giving a distinct and uniform color with strong intensity.
  • a test strip containing additionally tris- (hydroxymethyl)-aminomethane having a buffer action.
  • EXAMPLE 1 To a aqueous solution ml) of nickel chloride was added a 5% dimethylformamide solution (3 ml) of sodium nitroprusside in water, thus giving a turbid pale yellowish solution. A piece (5 X 6 cm) of diethylaminoethyl cellulose paper DE-8l (Whatman Co.) was dipped in the solution for one minute and then the strip was dried at room temperature in a dark place. Then, the strip was cut into narrower pieces l X 0.8 cm) and the strips were each held on a basic body such as a plastic sheet.
  • a basic body such as a plastic sheet.
  • test strips thus obtained were dipped independently in urine samples containing acetoacetic acid of l, 5, 10, 20, 50, and 100 mg/lOO ml, respectively.
  • the test strip turned reddish purple with strong intensity within one minute, depending on the concentration of acetoacetic acid of more than 1 mg/lOO ml.
  • the strip did not change color and it retained its original color (pale yellow).
  • test strip did not react with ascorbic acid or thiol compounds, but it turned greenish blue in the presence of pyruvic acid and pale brown in the presence of a-ketoglutaric acid.
  • EXAMPLE 2 A 5% dimethylformamide solution (3 ml) of sodium nitroprusside in water was added to a 5% aqueous solution 10 ml) of ferric chloride to give a pale yellowish solution. A piece (5 X 5 mc) of silica gel paper M3F 8860 (Carl Chleicher & Chull Co.) was dipped in this solution for one minute, dried in the air, cut into pieces (1 X 1 cm) and held on a plastic sheet to give the desired strips. The sensitivity of the test strip to acetoacetic acid was the same with that of the test strip obtained in EXAMPLE I.
  • the sensitivity of the test strips obtained above was the same with that of the test strip obtained in EXAM- PLE 1.
  • EXAMPLE 4 Using a filter paper (Toyo filter paper No. 131) or a diethylaminoethyl cellulose paper SG-8l (Whatman Co.), the same procedure as described in EXAMPLE 1 was carried out to give corresponding test strips.
  • EXAMPLE 5 Using a 5% nickel chloride solution 10 ml) prepared with 0.3M tris-(hydroxymethyl)-aminomethane solution (pH 6.8), the same procedure as described in EX- AMPLE l was carried out to give the desired test strip.
  • a test strip for the detection of ketone bodies comprising an absorbing material, a heavy metal salt and a nitroprusside salt.
  • a composition for the detection of ketone bodies comprising a heavy metal salt and a nitroprusside salt.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
US481913A 1973-11-08 1974-06-21 Test strip for ketone bodies Expired - Lifetime US3880590A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP48125667A JPS5143796B2 (enrdf_load_stackoverflow) 1973-11-08 1973-11-08

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US (1) US3880590A (enrdf_load_stackoverflow)
JP (1) JPS5143796B2 (enrdf_load_stackoverflow)
BE (1) BE816926A (enrdf_load_stackoverflow)
CA (1) CA1021237A (enrdf_load_stackoverflow)
CH (1) CH587491A5 (enrdf_load_stackoverflow)
DE (1) DE2432753C3 (enrdf_load_stackoverflow)
DK (1) DK142296B (enrdf_load_stackoverflow)
ES (1) ES427803A1 (enrdf_load_stackoverflow)
FR (1) FR2250999B1 (enrdf_load_stackoverflow)
GB (1) GB1451268A (enrdf_load_stackoverflow)
IT (1) IT1016633B (enrdf_load_stackoverflow)
NL (1) NL162478C (enrdf_load_stackoverflow)
NO (1) NO143826C (enrdf_load_stackoverflow)
SE (1) SE397733B (enrdf_load_stackoverflow)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2390733A1 (fr) * 1977-05-13 1978-12-08 Behringwerke Ag Solution de controle pour la detection, en vue du diagnostic, de substances contenues dans l'urine
US4147514A (en) * 1977-11-21 1979-04-03 Miles Laboratories, Inc. Test means and method for detecting ketone bodies
US4405721A (en) * 1980-03-22 1983-09-20 Behringwerke Aktiengesellschaft Diagnostic agent for the detection of ketone bodies
US4440724A (en) * 1982-11-01 1984-04-03 Helena Laboratories Corporation Composition for detecting ketone bodies and method of preparation
US4970172A (en) * 1986-12-22 1990-11-13 Abbott Laboratories Method and device for ketone measurements
US5071769A (en) * 1986-12-22 1991-12-10 Abbott Laboratories Method and device for ketone measurement
US5922283A (en) * 1997-07-07 1999-07-13 Teco Diagnostics Test strips for the determination of the ionic strength or specific gravity of an aqueous sample
RU2139543C1 (ru) * 1998-06-01 1999-10-10 Пермская государственная медицинская академия Способ диагностики почечной недостаточности у лиц с наружным дренированием брюшной полости
US6149865A (en) * 1997-07-07 2000-11-21 Teco Diagnostics, Inc. Test strips for the determination of the ionic strength or specific gravity of an aqueous sample
US6541216B1 (en) 1999-12-22 2003-04-01 Roche Diagnostics Corporation Amperometric biosensor test strip
US6583722B2 (en) 2000-12-12 2003-06-24 Kimberly-Clark Worldwide, Inc. Wetness signaling device
US6603403B2 (en) 2000-12-12 2003-08-05 Kimberly-Clark Worldwide, Inc. Remote, wetness signaling system
US20100150778A1 (en) * 2005-06-23 2010-06-17 Siemens Healthcare Diagnostics Inc. Detection of Adulterated Samples
US10352940B2 (en) * 2012-05-15 2019-07-16 Invoy Holdings, Llc Method and apparatus for analyzing acetone in breath
EP3757573A4 (en) * 2018-02-23 2021-08-25 Sysmex Corporation SAMPLE FOR DETECTION OF KETONIC BODY IN URINE

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4931404A (en) * 1986-12-22 1990-06-05 Abbott Laboratories Method and device for ketone measurement
KR102509855B1 (ko) 2018-05-04 2023-03-14 에프. 호프만-라 로슈 아게 테스트 스트립용 스틱팩-유형 패키징

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2186902A (en) * 1939-04-07 1940-01-09 Lilly Co Eli Urine acetone test
US2362478A (en) * 1941-12-24 1944-11-14 Denver Chemical Mfg Company Reagent for testing for acetone
US2509140A (en) * 1948-03-02 1950-05-23 Miles Lab Test reagent composition
US2577978A (en) * 1949-02-04 1951-12-11 Miles Lab Diagnostic composition
US2990253A (en) * 1959-05-21 1961-06-27 Miles Lab Diagnostic composition
US3212855A (en) * 1962-08-06 1965-10-19 Miles Lab Diagnostic device
US3598704A (en) * 1966-01-05 1971-08-10 Kabi Ab Diagnostic device for various sugars

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2186902A (en) * 1939-04-07 1940-01-09 Lilly Co Eli Urine acetone test
US2362478A (en) * 1941-12-24 1944-11-14 Denver Chemical Mfg Company Reagent for testing for acetone
US2509140A (en) * 1948-03-02 1950-05-23 Miles Lab Test reagent composition
US2577978A (en) * 1949-02-04 1951-12-11 Miles Lab Diagnostic composition
US2990253A (en) * 1959-05-21 1961-06-27 Miles Lab Diagnostic composition
US3212855A (en) * 1962-08-06 1965-10-19 Miles Lab Diagnostic device
US3598704A (en) * 1966-01-05 1971-08-10 Kabi Ab Diagnostic device for various sugars

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2390733A1 (fr) * 1977-05-13 1978-12-08 Behringwerke Ag Solution de controle pour la detection, en vue du diagnostic, de substances contenues dans l'urine
US4172049A (en) * 1977-05-13 1979-10-23 Behringwerke Aktiengesellschaft Control-solution for diagnostic detection methods for substances contained in the urine
US4147514A (en) * 1977-11-21 1979-04-03 Miles Laboratories, Inc. Test means and method for detecting ketone bodies
DE2838675A1 (de) * 1977-11-21 1979-05-23 Miles Lab Testmittel und verfahren zum nachweis von ketonkoerpern
US4405721A (en) * 1980-03-22 1983-09-20 Behringwerke Aktiengesellschaft Diagnostic agent for the detection of ketone bodies
US4440724A (en) * 1982-11-01 1984-04-03 Helena Laboratories Corporation Composition for detecting ketone bodies and method of preparation
US4970172A (en) * 1986-12-22 1990-11-13 Abbott Laboratories Method and device for ketone measurements
US5071769A (en) * 1986-12-22 1991-12-10 Abbott Laboratories Method and device for ketone measurement
US6149865A (en) * 1997-07-07 2000-11-21 Teco Diagnostics, Inc. Test strips for the determination of the ionic strength or specific gravity of an aqueous sample
US5922283A (en) * 1997-07-07 1999-07-13 Teco Diagnostics Test strips for the determination of the ionic strength or specific gravity of an aqueous sample
RU2139543C1 (ru) * 1998-06-01 1999-10-10 Пермская государственная медицинская академия Способ диагностики почечной недостаточности у лиц с наружным дренированием брюшной полости
US6541216B1 (en) 1999-12-22 2003-04-01 Roche Diagnostics Corporation Amperometric biosensor test strip
US6583722B2 (en) 2000-12-12 2003-06-24 Kimberly-Clark Worldwide, Inc. Wetness signaling device
US6603403B2 (en) 2000-12-12 2003-08-05 Kimberly-Clark Worldwide, Inc. Remote, wetness signaling system
US20100150778A1 (en) * 2005-06-23 2010-06-17 Siemens Healthcare Diagnostics Inc. Detection of Adulterated Samples
US8293188B2 (en) * 2005-06-23 2012-10-23 Siemens Healthcare Diagnostics, Inc. Detection of adulterated samples
US10352940B2 (en) * 2012-05-15 2019-07-16 Invoy Holdings, Llc Method and apparatus for analyzing acetone in breath
US11353462B2 (en) 2012-05-15 2022-06-07 Invoy Holdings Inc. Method and apparatus for analyzing acetone in breath
US11977079B2 (en) 2012-05-15 2024-05-07 Invoy Holdings Inc. Method and apparatus for analyzing acetone in breath
EP3757573A4 (en) * 2018-02-23 2021-08-25 Sysmex Corporation SAMPLE FOR DETECTION OF KETONIC BODY IN URINE

Also Published As

Publication number Publication date
NO143826B (no) 1981-01-05
DE2432753B2 (de) 1981-01-22
FR2250999A1 (enrdf_load_stackoverflow) 1975-06-06
DK336474A (enrdf_load_stackoverflow) 1975-07-14
SE7408488L (enrdf_load_stackoverflow) 1975-05-09
JPS5078394A (enrdf_load_stackoverflow) 1975-06-26
DE2432753A1 (de) 1975-05-15
BE816926A (fr) 1974-10-16
NL162478C (nl) 1980-05-16
JPS5143796B2 (enrdf_load_stackoverflow) 1976-11-24
ES427803A1 (es) 1977-02-01
NL162478B (nl) 1979-12-17
GB1451268A (en) 1976-09-29
NL7410509A (nl) 1975-05-12
IT1016633B (it) 1977-06-20
CA1021237A (en) 1977-11-22
SE397733B (sv) 1977-11-14
FR2250999B1 (enrdf_load_stackoverflow) 1977-10-07
NO742323L (enrdf_load_stackoverflow) 1975-06-02
CH587491A5 (enrdf_load_stackoverflow) 1977-05-13
AU7061474A (en) 1976-01-08
DK142296C (enrdf_load_stackoverflow) 1981-03-02
DK142296B (da) 1980-10-06
DE2432753C3 (de) 1981-09-10
NO143826C (no) 1981-04-15

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