US2970945A - Diagnostic composition - Google Patents
Diagnostic composition Download PDFInfo
- Publication number
- US2970945A US2970945A US765065A US76506558A US2970945A US 2970945 A US2970945 A US 2970945A US 765065 A US765065 A US 765065A US 76506558 A US76506558 A US 76506558A US 2970945 A US2970945 A US 2970945A
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- acid
- effervescent couple
- oxydase
- monohydrochloride
- diagnostic composition
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- 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.)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
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- 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
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/871—Neisseria
Definitions
- This invention relates to diagnostic compositions for the detection of gonococci, and is particularly concerned with such compositions in tablet form afiording accurate and convenient means for preparing a solution of oxydase reagent for use in detecting colonies of Neisseria gonorrheae in accordance with the well known oxydase test.
- the presence of gonococci is determined by incubating genital tract exudate on a Petri plate containing blood agar or some other suitable medium at 37 C. in the presence of increased carbon dioxide tension. At the end of 36 to 48 hours, a freshly prepared solution of p-aminodimethylaniline monohydrochloride is added to the plate and gonococcal colonies quickly assume a characteristic pink color which changes to maroon and finally to black. While the test is fairly simple to perform and provides accurate results when conducted with ordinary care, its popularity has been confined essentially to clinics and other institutional practices where numbers of tests are performed daily, and fresh solutions of the p-arninodimethylaniline monohydrochloride are routinely prepared daily.
- test has been readily adaptable to private practice Where, because the aqueous solution of p-aminodimethylaniline monohydrochloride is unstable, it is necessary to prepare a fresh solution at the time each test is to be made, re quiring the expenditure of valuable time by the physician or his technician.
- a diagnostic composition in accordance with the invention comprises an oxydase reagent, such as p-aminodimethylaniline monohydrochloride or tetramethyl-pphenyleuediamine, and an effervescent couple, the ingredients being intimately mixed in finely divided form, and preferably compressed into tablets of convenient size for use in preparing predetermined quantities of the oxydase solution.
- the oxydase reagent is the active agent for the test, while the effervescent couple hastens disintegration of the tablet and dissolution of the oxydase reagent when the tablet is dissolved in water.
- a further function of the effervescent couple is that it provides components which tend to buffer the solution, thereby promoting the reaction of the oxydase reagent with the oxydasepositive colony.
- the effervescent couple may be formed from any of a number of solid acids and/or acid-reacting salts in combination with any of the alkali metal carbonates and/or bicarbonates.
- the acid component we prefer to use citric acid because it is highly efiicient, stable and Cit 'ice readily available at low cost.
- other acids .or acid reacting substances such as tartaric .acid, alkali metal acid citrates, such as potassium acid citrate, or alkali metal acid sulfates, such as sodium or potassium acid sulfate, may be used instead forthis purpose, if desired.
- the carbonate component of the effervescent couple we prefer to use sodium bicarbonate, but other water-soluble salts of carbonic acid, including the alkali metal normal carbonates, sesquicarbonates and bicarbonates, e.g. sodium carbonate, sodium sesquicarbonate, or potassium bicarbonate may be 'used instead with satisfactory results.
- the acid and carbonate components of the effervescent couple are in substantially stoichiometric proportions. This is the preferred condition, although a slight excess of either the acid or carbonate, to give a pH betWen 6 and 8, is permissible.
- Example I When one of the present diagnostic compositions, as represented by the formulation of Example I, is dropped into 10 m1. of water, it efiervesces vigorously during solution due to the reaction between the citric acid and the sodium bicarbonate. The p-aminodimethylaniline monohydrochloride is thus quickly dissolved and is uniformly distributed throughout the solution, which utilizes the bufiering activity of the effervescent couple. After efiervescence ceases, the solution may be added directly to the petri plate where any colonies of gonococci will be detected by the procedure described above.
- the proportion of the effervescent couple with respect to the oxydase reagent is not closely critical and may be considerably varied. We prefer to prepare our compositions so that the proportion of the effervescent couple is between about and about 98% of the total weight of the composition. Smaller proportions of the eifervescent couple correspondingly delay solubility of the com position, and larger proportions do not afford any significant advantage in increasing the solubility rate.
- tetramethyl-p-phenylenediamine may be used as the oxydase reagent, as shown in the following example.
- Example ll 5 grams tetramethyl-p-phenylenediamine 41 grams citric acid 54 grams sodium bicarbonate The above ingredients, finely divided, are intimately mixed and preferably pressed into 1000 mg. tablets following the procedure described in Example I.
- the p-aminodimethylaniline monohydrochloride is preferred over the tetramethyl-p-phenylenediamine as the oxydase reagent since it is much less expensive and gives tablets of better stability.
- an intimate admixture of dry ingredients consisting essentially of an effervescent couple and a member of the group consisting of p-amino dimethylaniline monohydrochloride and tetramethyl-pr phenylenediamine.
- composition in accordance with claim 1 wherein the effervescent couple consists of a Water-soluble salt of 3 carbonic acid and a member of the group consisting of solid acids and acid-reacting salts.
- composition in accordance with claim 3 wherein the proportion of the effervescent couple is between about 85% and about 98% of the total weight of said composition.
- an intimate admixture of dry ingredients in tablet form consisting essentially of p-aminodimethylaniline monohydrochloride and an of fervescent couple.
- a diagnostic composition comprising an intimate admixture, in tablet form, of a minor proportion of paminodimethylaniline monohydrochlo'ride and a major proportion of an effervescent couple consisting essentially of citric acid and sodium bicarbonate.
- a diagnostic composition comprising an intimate admixture, in tablet form, of a minor proportion of tetramethyl-p-phenylenediamine and a major proportion of an effervescent couple consisting essentially of citric acid and sodium bicarbonate.
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Description
DIAGNGSTIC COMPOSITION Alfred H. Free and'Leonard B. Schweiger, Elkhart, Ind., assignors to Miles Laboratories, Inc, Elkhart, Ind., a corporation of Indiana No Drawing. Filed Oct. 3, 1958, Ser. No. 765,065
-8 Claims. (Cl. 167-845) This invention relates to diagnostic compositions for the detection of gonococci, and is particularly concerned with such compositions in tablet form afiording accurate and convenient means for preparing a solution of oxydase reagent for use in detecting colonies of Neisseria gonorrheae in accordance with the well known oxydase test.
In the oxydase test, the presence of gonococci is determined by incubating genital tract exudate on a Petri plate containing blood agar or some other suitable medium at 37 C. in the presence of increased carbon dioxide tension. At the end of 36 to 48 hours, a freshly prepared solution of p-aminodimethylaniline monohydrochloride is added to the plate and gonococcal colonies quickly assume a characteristic pink color which changes to maroon and finally to black. While the test is fairly simple to perform and provides accurate results when conducted with ordinary care, its popularity has been confined essentially to clinics and other institutional practices where numbers of tests are performed daily, and fresh solutions of the p-arninodimethylaniline monohydrochloride are routinely prepared daily. The test has been readily adaptable to private practice Where, because the aqueous solution of p-aminodimethylaniline monohydrochloride is unstable, it is necessary to prepare a fresh solution at the time each test is to be made, re quiring the expenditure of valuable time by the physician or his technician.
It is an object of the invention to provide a diagnostic composition in tablet form which may be carried conveniently 1n the physicans bag, and which will not deteriorate over long periods of time under ordinary conditions of temperature and humidity, but which may be quickly converted to a solution for use in the oxydase test for gonorrhea simply by dropping a tablet into a measured quantity of water.
Other objects will be apparent from the description of the invention which follows.
A diagnostic composition in accordance with the invention comprises an oxydase reagent, such as p-aminodimethylaniline monohydrochloride or tetramethyl-pphenyleuediamine, and an effervescent couple, the ingredients being intimately mixed in finely divided form, and preferably compressed into tablets of convenient size for use in preparing predetermined quantities of the oxydase solution. The oxydase reagent is the active agent for the test, while the effervescent couple hastens disintegration of the tablet and dissolution of the oxydase reagent when the tablet is dissolved in water. A further function of the effervescent couple is that it provides components which tend to buffer the solution, thereby promoting the reaction of the oxydase reagent with the oxydasepositive colony.
The effervescent couple may be formed from any of a number of solid acids and/or acid-reacting salts in combination with any of the alkali metal carbonates and/or bicarbonates. As the acid component we prefer to use citric acid because it is highly efiicient, stable and Cit 'ice readily available at low cost. However, other acids .or acid reacting substances such as tartaric .acid, alkali metal acid citrates, such as potassium acid citrate, or alkali metal acid sulfates, such as sodium or potassium acid sulfate, may be used instead forthis purpose, if desired.
As the carbonate component of the effervescent couple, we prefer to use sodium bicarbonate, but other water-soluble salts of carbonic acid, including the alkali metal normal carbonates, sesquicarbonates and bicarbonates, e.g. sodium carbonate, sodium sesquicarbonate, or potassium bicarbonate may be 'used instead with satisfactory results.
Example I The following ingredients:
5 grams of p-aminodimethylaniline monohydrochloride 41 grams of citric acid 54 grams of sodium bicarbonate are mixed until a homogeneous mixture of all of the ingredients has been achieved. The mixture is then preferably pressed into tablets of convenient size, e.g., 1000 mg, so that each tablet contains about 50 mg. of paminodimethylaniline monohydrochloride.
In the above example, the acid and carbonate components of the effervescent couple are in substantially stoichiometric proportions. This is the preferred condition, although a slight excess of either the acid or carbonate, to give a pH betWen 6 and 8, is permissible.
When one of the present diagnostic compositions, as represented by the formulation of Example I, is dropped into 10 m1. of water, it efiervesces vigorously during solution due to the reaction between the citric acid and the sodium bicarbonate. The p-aminodimethylaniline monohydrochloride is thus quickly dissolved and is uniformly distributed throughout the solution, which utilizes the bufiering activity of the effervescent couple. After efiervescence ceases, the solution may be added directly to the petri plate where any colonies of gonococci will be detected by the procedure described above.
The proportion of the effervescent couple with respect to the oxydase reagent is not closely critical and may be considerably varied. We prefer to prepare our compositions so that the proportion of the effervescent couple is between about and about 98% of the total weight of the composition. Smaller proportions of the eifervescent couple correspondingly delay solubility of the com position, and larger proportions do not afford any significant advantage in increasing the solubility rate.
Instead of p-aminodimethylaniline monohydrochlo-ride, tetramethyl-p-phenylenediamine may be used as the oxydase reagent, as shown in the following example.
Example ll 5 grams tetramethyl-p-phenylenediamine 41 grams citric acid 54 grams sodium bicarbonate The above ingredients, finely divided, are intimately mixed and preferably pressed into 1000 mg. tablets following the procedure described in Example I.
The p-aminodimethylaniline monohydrochloride is preferred over the tetramethyl-p-phenylenediamine as the oxydase reagent since it is much less expensive and gives tablets of better stability.
What we claim is:
1. As a diagnostic composition, an intimate admixture of dry ingredients consisting essentially of an effervescent couple and a member of the group consisting of p-amino dimethylaniline monohydrochloride and tetramethyl-pr phenylenediamine.
2. A composition in accordance with claim 1 wherein the effervescent couple consists of a Water-soluble salt of 3 carbonic acid and a member of the group consisting of solid acids and acid-reacting salts.
3. A composition in accordance with claim 2 wherein the components of said effervescent couple are present in substantially stoichiomctric quantities.
4. A composition in accordance with claim 3 wherein the proportion of the effervescent couple is between about 85% and about 98% of the total weight of said composition.
5. As a diagnostic composition, an intimate admixture of dry ingredients in tablet form consisting essentially of p-aminodimethylaniline monohydrochloride and an of fervescent couple.
6. A diagnostic composition comprising an intimate admixture, in tablet form, of a minor proportion of paminodimethylaniline monohydrochlo'ride and a major proportion of an effervescent couple consisting essentially of citric acid and sodium bicarbonate.
7. An aqueous solution of the composition claimed in claim 6.
8. A diagnostic composition comprising an intimate admixture, in tablet form, of a minor proportion of tetramethyl-p-phenylenediamine and a major proportion of an effervescent couple consisting essentially of citric acid and sodium bicarbonate.
References Cited in the file of this patent UNITED STATES PATENTS 2,387,244 Compton Oct. 23, 1945 2,799,660 Nicholls July 16, 1957 OTHER REFERENCES Merck Index, Merck and Co., Rahway, N.J., 6th
ed., 1952, pp. 361, 943, 962.
Difco Manual, Difco Lab., Detroit 1, Mich., 9th ed., 1953, pp. 296, 297. r r I y
Claims (1)
1. AS A DIAGNOSTIC COMPOSITION, AN INTIMATE ADMIXTURE OF DRY INGREDIENTS CONSISTING ESSENTIALLY OF AN EFFERVESCENT COUPLE AND A MEMBER OF THE GROUP CONSISTING OF P-AMINODIMETHYLANILINE MONOHYDROCHLORIDE AND TETRAMETYYL-PPHENYLENEDIAMINE.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US765065A US2970945A (en) | 1958-10-03 | 1958-10-03 | Diagnostic composition |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US765065A US2970945A (en) | 1958-10-03 | 1958-10-03 | Diagnostic composition |
Publications (1)
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US2970945A true US2970945A (en) | 1961-02-07 |
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US765065A Expired - Lifetime US2970945A (en) | 1958-10-03 | 1958-10-03 | Diagnostic composition |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3247841A (en) * | 1961-05-29 | 1966-04-26 | Galen B Cook | Diagnostic method |
US3313292A (en) * | 1965-06-24 | 1967-04-11 | Galen B Cook | Diagnostic composition package |
US3979262A (en) * | 1974-02-12 | 1976-09-07 | Hoffmann-La Roche Inc. | Compositions and methods for the determination of oxidizing agents |
US4018653A (en) * | 1971-10-29 | 1977-04-19 | U.S. Packaging Corporation | Instrument for the detection of Neisseria gonorrhoeae without culture |
DE2653821A1 (en) * | 1975-12-22 | 1977-06-30 | Smithkline Corp | STABLE OXIDASE REAGENT SOLUTION |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2387244A (en) * | 1942-06-19 | 1945-10-23 | Miles Lab | Tablet and method of dissolving same |
US2799660A (en) * | 1954-04-15 | 1957-07-16 | Miles Lab | Blood test composition and method |
-
1958
- 1958-10-03 US US765065A patent/US2970945A/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2387244A (en) * | 1942-06-19 | 1945-10-23 | Miles Lab | Tablet and method of dissolving same |
US2799660A (en) * | 1954-04-15 | 1957-07-16 | Miles Lab | Blood test composition and method |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3247841A (en) * | 1961-05-29 | 1966-04-26 | Galen B Cook | Diagnostic method |
US3313292A (en) * | 1965-06-24 | 1967-04-11 | Galen B Cook | Diagnostic composition package |
US4018653A (en) * | 1971-10-29 | 1977-04-19 | U.S. Packaging Corporation | Instrument for the detection of Neisseria gonorrhoeae without culture |
US3979262A (en) * | 1974-02-12 | 1976-09-07 | Hoffmann-La Roche Inc. | Compositions and methods for the determination of oxidizing agents |
DE2653821A1 (en) * | 1975-12-22 | 1977-06-30 | Smithkline Corp | STABLE OXIDASE REAGENT SOLUTION |
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