US2671748A - Composition of matter - Google Patents
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- US2671748A US2671748A US162821A US16282150A US2671748A US 2671748 A US2671748 A US 2671748A US 162821 A US162821 A US 162821A US 16282150 A US16282150 A US 16282150A US 2671748 A US2671748 A US 2671748A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
Definitions
- Chloramphenicol is an antibiotic which can be produced by chemical synthesis or by cultivation of Streptomyces venezuelae on or in a nutrient medium under aerobic conditions. Chemically it is (Z) -1-p-nitrophenyl-2-dichloroacetamidopropane-1,3-dil and has the following structural formula,
- Chloramphenicol and its optical racemate are of great value in the treatment of many infections and diseases which before their advent were fatal and/or resulted in long, lingering illnesses.
- infections and diseases were typhoid fever, Malta fever, Rocky Mountain spotted fever, typhus, yaws, pneumonia, pertussis. brucellosis, urinary infections, gonorrhea, certain types of syphilis, etc.
- the customary dosage is l3 g. of chloroamphenicol orally per day, while slightly larger quantities of the optical racemate are usually used. In many instances oral administration of these products is not possible or feasible due to the age or condition of the patient.
- the preferred mode of administration is the parenteral route and, in particular, the intravenous route.
- the virtual oil and water-insolubility of chloramphenicol and optically racemic chloramphenicol make it impossible to use this alternative method of administration and hence many patients have prior to the instant invention been deprived of the therapeutic efiects of these valuable antibiotics.
- a further object of the invention is to provide solutions containing a high concentration of 2 chloramphenicol or optically racemic chloramphenicol which are chemically stable, that is, do not lose their therapeutic efficacy even on prolonged storage.
- a still further object of the invention is to provide solutions of the above character which upon intravenous administration or upon dilution with water, normal saline, isotonic glucose solution, or plasma remain perfectly clear and do not deposit crystals of chloramphenicol or optically racemic chloramphenicol.
- R and R1 are the same or different and represent hydrogen or alkyl radicals containing 1 to 2 carbon atoms inclusive and R2 is an alkyl radical containing 1 to 2 carbon atoms inclusive.
- the balance of the solvent solution is made up of water which can contain, if desired, such things as sodium chloride, sucrose, glucose and the like.
- the solutions of the invention are chemically stable, that is, upon prolonged storage the solutions retain their titre of chloramphenicol and insofar as can be determined the water-miscible amides undergo no chemical change.
- the solutions are also physically stable and do not deposit crystals upon storage or on dilution with aqueous solvents such as water, normal saline, isotonic glucose solution and plasma even though in the diluted form they contain a greater concentra tion of chloramphenicol or its optical racemate than is obtainable in an otherwise identical solution of water, normal saline, isotonic glucose solution or plasma containing no water-miscible amide.
- This stability upon dilution is of extreme importance in intravenous therapy in that there is no danger of crystals of the antibiotic forming in the blood stream when using the undiluted preparations.
- This latter property is also of importance in that it permits dispensing chloramphenicol or its optical racemate in a concentrated form which can be diluted in case the physician desires to administer the drug by venoclysis.
- the products of the invention like chloramphenicol and its optical racemate are relatively non-toxic.
- a solution containing 25% by weight of chloramphenicol in a solvent composed of equal parts of water and N.N- dimethylacetamide has a maximum tolerated dose upon intravenous administration to albino rats of 0.767 cc./kg. and an LDso of 1.109 cc./kg.
- Another solution having the same composition has been administered intravenously in doses of 4 cc. per day to human patients suffering from yaws. This medication was continued for a p riod of six days at the end of which time-none of the patients showed any toxic manifestations.
- the concentration of the antibiotic obtainable in the compositions of the invention varies with the amide employed and the amount of water present in the preparation. However, even when using the amides having the poorest ability to dissolve chloramphenicol (and its racemate) and a solution containing 65 to 70% water, solutions containing at least by weight of the antibiotic can be prepared.
- the tertiary amides that is, those wherein R1 is an alkyl radical, uniformly make it possible to prepare more concentrated solutions of chloramphenicol (or its racemate) than do the corresponding secondary amides wherein R1 is hydrogen and hence the tertiary amides as a class are preferred for the purposes of this invention.
- solutions containing about 50 to 65% by weight of chloramphenicol can be prepared.
- concentrations of chloramphenicol obtainable using some of the above defined water-miscible amides with varying proportions of water is shown more fully in normal saline, isotonic glucose solution or plasma,
- the solution remains perfectly clear.
- the undiluted preparation is both chemically and physically stable for long periods of time.
- Example 3 26.6 g. of chloramphenicol is added to 20 cc. of N,N-dimethyl acetamide and the mixture shaken until solution is complete.
- the solution thus obtained after sterilization by filtration through a porous stone filter is suitable for intravenous administration or for use as a concentrate to prepare more dilute solutions for this purpose.
- the solution is stable in its undiluted form and also upon dilution with water, normal saline, etc. It contains about 645 mg. of chloramphenicol per cc.
- Example 4 10 g. of chloramphenicol is added to 22 cc. of a solvent mixture composed of 3 volumes of N,N- dimethyl formamide and 1 volume of isotonic saline. The mixture is shaken until solution is complete, sterilized by filtration through a porous stone filter and filled into ampoules. The solution thus obtained contains 33.3% by weight or the following table. 333 mg./cc. of chloramphenicol. It is suitable TABLE Milligrams oi chloramphenicol Which Can be Dissolved in 1 cc.
- Example 1 25 g. of chloramphenicol is added to 80 cc. of a solvent mixture composed of equal volumes of N,N-dimethyl acetamide and distilled water at room temperature and the mixture stirred or shaken until solution is complete.
- the solution is sterilized by filtration through an earthenware or porous stone filter and filled into ampoules. Each cubic centimeter of the solution thus obtained contains 25% by weight or 250 mg. of chloramphenicol.
- This solution is chemically and physically stable for long periods of time. Upon dilution with water, normal saline, isotonic glucose solution or plasma, no cloudiness or crystal formation takes place. It is relatively nontoxic and can besafely administered intravenously to humans for at least six days in dosages of as high as 2 cc. per day.
- Example 5 10 g. of chloramphenicol is added to 35 cc. of a solvent mixture composed of equal volumes of N,N-diethyl acetamide and distilled water. The mixture is shaken until solution is complete and then 1 g. of glucose added. The mixture is shaken until the glucose is dissolved and then made up to a volume of 50 cc. by the addition of the amide solvent mixture. The clear solution is sterilized by filtration through an earthenware filter and filled into ampoules. The solution thus obtained is suitable for intravenous administration. It contains 20% by weight or 200 mg./cc. of chloramphenicol and isboth physically and chemically stable. The solution can be diluted with any amount of water without causing the chloramphenicol to separate from the solution.
- Example 6 g. of chloramphenicol is added to 32 cc. of a solvent mixture composed of equal volumes of N,N-dimethyl propionamide and distilled water and the resulting mixture shaken at room temperature until solution is complete.
- the solution is sterilized by filtration through a porous stone filter and filled into ampoules. This solution is suitable for intravenous administration and contains 25% by weight or 250 mg./cc. of
- chloramphenicol The chloramphenicol present in the solution does not crystallize out on standing or upon dilution of the solution with water, normal saline, plasma or isotonic glucose solution.
- a clear, stable, liquid therapeutic composition comprising an antibiotic of the class consisting of chloramphenicol and optically racemic chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of a water-miscible amide of formula,
- R. and R1 are members of the class consisting of hydrogen and alkyl radicals containing 1 to 2 carbon atoms inclusive and R2 is an alkyl radical containing 1 to 2 carbon atoms inclusive; said composition being suitable for intravenous administration of said antibiotic and yielding upon dilution with an aqueous solvent a clear, stable solution containing the antibiotic in a concentration greater than its solubility in an otherwise identical solution not containing the water-miscible amide.
- a clear, stable, liquid therapeutic composi tion comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-dimethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl acetamide.
- a clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution composed of essentially equal volumes of water and N,N-dimethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl acetamide.
- a clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume or N,N-dimethyl toramide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear,
- a clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-diethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-diethyl acetamide.
- a clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-dimethyl propionamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl propionamide.
- a therapeutic solution for parenteral administration comprising chloramphenicol dissolved in an aqueous solution containing at least 30% by volume of N,N-dimethyl acetamide.
- a clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N-methyl acetamide, said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N- methyl acetamide.
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Description
Patented Mar, 9, 1954 COMPOSITION OF MATTER Harry M. Crooks, In, Detroit, Mich., assignor to lParke, Davis & Company, Detroit, Mich., a corporation of Michigan No Drawing. Application May 18, 1950, Serial No. 162,821
(Cl. l6'l--65) 8 Claims,
Chloramphenicol is an antibiotic which can be produced by chemical synthesis or by cultivation of Streptomyces venezuelae on or in a nutrient medium under aerobic conditions. Chemically it is (Z) -1-p-nitrophenyl-2-dichloroacetamidopropane-1,3-dil and has the following structural formula,
| NO CH-CH-CHrOH Other chemical names for this product are D- threo 2-dichloroacetamido-l-p-nitrophenyl1,3- propanediol and D-threo-N- 1,1 dihydroxy-l-pnitrophenylisopropyl) dichloroacetamide.
Chloramphenicol and its optical racemate, the (dl) form, are of great value in the treatment of many infections and diseases which before their advent were fatal and/or resulted in long, lingering illnesses. Among such infections and diseases were typhoid fever, Malta fever, Rocky Mountain spotted fever, typhus, yaws, pneumonia, pertussis. brucellosis, urinary infections, gonorrhea, certain types of syphilis, etc. In the treatment of these ailments the customary dosage is l3 g. of chloroamphenicol orally per day, while slightly larger quantities of the optical racemate are usually used. In many instances oral administration of these products is not possible or feasible due to the age or condition of the patient. In these and many other cases the preferred mode of administration is the parenteral route and, in particular, the intravenous route. Unfortunately, the virtual oil and water-insolubility of chloramphenicol and optically racemic chloramphenicol make it impossible to use this alternative method of administration and hence many patients have prior to the instant invention been deprived of the therapeutic efiects of these valuable antibiotics.
It is an object of the present invention to produce clear solutions containing a high concentration of chloramphenicol or optically racemic chloramphenicol which are suitable for parenteral administration.
It is also an object of the present invention to provide solutions containing a high concentration of chloramphenicol or optically racemic chloramphenicol which are physically stable and from which the chloramphenicol or optically racemic chloramphenical does not separate even on lon storage.
A further object of the invention is to provide solutions containing a high concentration of 2 chloramphenicol or optically racemic chloramphenicol which are chemically stable, that is, do not lose their therapeutic efficacy even on prolonged storage.
A still further object of the invention is to provide solutions of the above character which upon intravenous administration or upon dilution with water, normal saline, isotonic glucose solution, or plasma remain perfectly clear and do not deposit crystals of chloramphenicol or optically racemic chloramphenicol.
In accordance with the invention these and other objects which will appear hereinafter are realized by dissolving chloramphenicol or optically racemic chloramphenicol in a water-miscible amide solution containing at least 30% by volume of a water-miscible amide of the formula,
where R and R1 are the same or different and represent hydrogen or alkyl radicals containing 1 to 2 carbon atoms inclusive and R2 is an alkyl radical containing 1 to 2 carbon atoms inclusive. In the dilute solutions, that is, those in which the solvent is not composed solely of the water-misclble amide, the balance of the solvent solution is made up of water which can contain, if desired, such things as sodium chloride, sucrose, glucose and the like.
The solutions of the invention are chemically stable, that is, upon prolonged storage the solutions retain their titre of chloramphenicol and insofar as can be determined the water-miscible amides undergo no chemical change. The solutions are also physically stable and do not deposit crystals upon storage or on dilution with aqueous solvents such as water, normal saline, isotonic glucose solution and plasma even though in the diluted form they contain a greater concentra tion of chloramphenicol or its optical racemate than is obtainable in an otherwise identical solution of water, normal saline, isotonic glucose solution or plasma containing no water-miscible amide. This stability upon dilution is of extreme importance in intravenous therapy in that there is no danger of crystals of the antibiotic forming in the blood stream when using the undiluted preparations. This latter property is also of importance in that it permits dispensing chloramphenicol or its optical racemate in a concentrated form which can be diluted in case the physician desires to administer the drug by venoclysis.
The products of the invention like chloramphenicol and its optical racemate are relatively non-toxic. For example, a solution containing 25% by weight of chloramphenicol in a solvent composed of equal parts of water and N.N- dimethylacetamide has a maximum tolerated dose upon intravenous administration to albino rats of 0.767 cc./kg. and an LDso of 1.109 cc./kg. Another solution having the same composition has been administered intravenously in doses of 4 cc. per day to human patients suffering from yaws. This medication was continued for a p riod of six days at the end of which time-none of the patients showed any toxic manifestations.
The concentration of the antibiotic obtainable in the compositions of the invention varies with the amide employed and the amount of water present in the preparation. However, even when using the amides having the poorest ability to dissolve chloramphenicol (and its racemate) and a solution containing 65 to 70% water, solutions containing at least by weight of the antibiotic can be prepared. In this connection it has been found that the tertiary amides, that is, those wherein R1 is an alkyl radical, uniformly make it possible to prepare more concentrated solutions of chloramphenicol (or its racemate) than do the corresponding secondary amides wherein R1 is hydrogen and hence the tertiary amides as a class are preferred for the purposes of this invention. Using this preferred class of amides in the anhydrous form, solutions containing about 50 to 65% by weight of chloramphenicol can be prepared. The relative concentrations of chloramphenicol obtainable using some of the above defined water-miscible amides with varying proportions of water is shown more fully in normal saline, isotonic glucose solution or plasma,
the solution remains perfectly clear. The undiluted preparation is both chemically and physically stable for long periods of time.
Example 3 26.6 g. of chloramphenicol is added to 20 cc. of N,N-dimethyl acetamide and the mixture shaken until solution is complete. The solution thus obtained after sterilization by filtration through a porous stone filter is suitable for intravenous administration or for use as a concentrate to prepare more dilute solutions for this purpose. The solution is stable in its undiluted form and also upon dilution with water, normal saline, etc. It contains about 645 mg. of chloramphenicol per cc.
Example 4 10 g. of chloramphenicol is added to 22 cc. of a solvent mixture composed of 3 volumes of N,N- dimethyl formamide and 1 volume of isotonic saline. The mixture is shaken until solution is complete, sterilized by filtration through a porous stone filter and filled into ampoules. The solution thus obtained contains 33.3% by weight or the following table. 333 mg./cc. of chloramphenicol. It is suitable TABLE Milligrams oi chloramphenicol Which Can be Dissolved in 1 cc. of Amide Solution Percent by Volume of Amide in O 0 0 0 0 0 Solvent 1 I HON(CH:): CHM-NECK; OH ON(OH:)1 OHsO-NH-CsHl CH:C-N(C2Hl)2 OH:CH1 CN(CH|) pure amide 100% 1, 333 l, 000 1,333 800 870 1, 000 070 000 76 1,000 560 1,000 600 7 V 420 so 300 no 330 540 600 500 182 440 500 276 280 260 pure water 0% 3 3 3 3 3 3 1 Balance of 100% made up with distilled water.
The invention is illustrated further by the following examples.
Example 1 25 g. of chloramphenicol is added to 80 cc. of a solvent mixture composed of equal volumes of N,N-dimethyl acetamide and distilled water at room temperature and the mixture stirred or shaken until solution is complete. The solution is sterilized by filtration through an earthenware or porous stone filter and filled into ampoules. Each cubic centimeter of the solution thus obtained contains 25% by weight or 250 mg. of chloramphenicol. This solution is chemically and physically stable for long periods of time. Upon dilution with water, normal saline, isotonic glucose solution or plasma, no cloudiness or crystal formation takes place. It is relatively nontoxic and can besafely administered intravenously to humans for at least six days in dosages of as high as 2 cc. per day.
Example 5 10 g. of chloramphenicol is added to 35 cc. of a solvent mixture composed of equal volumes of N,N-diethyl acetamide and distilled water. The mixture is shaken until solution is complete and then 1 g. of glucose added. The mixture is shaken until the glucose is dissolved and then made up to a volume of 50 cc. by the addition of the amide solvent mixture. The clear solution is sterilized by filtration through an earthenware filter and filled into ampoules. The solution thus obtained is suitable for intravenous administration. It contains 20% by weight or 200 mg./cc. of chloramphenicol and isboth physically and chemically stable. The solution can be diluted with any amount of water without causing the chloramphenicol to separate from the solution.
Example 6 g. of chloramphenicol is added to 32 cc. of a solvent mixture composed of equal volumes of N,N-dimethyl propionamide and distilled water and the resulting mixture shaken at room temperature until solution is complete. The solution is sterilized by filtration through a porous stone filter and filled into ampoules. This solution is suitable for intravenous administration and contains 25% by weight or 250 mg./cc. of
chloramphenicol. The chloramphenicol present in the solution does not crystallize out on standing or upon dilution of the solution with water, normal saline, plasma or isotonic glucose solution.
What I claim is:
l. A clear, stable, liquid therapeutic composition comprising an antibiotic of the class consisting of chloramphenicol and optically racemic chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of a water-miscible amide of formula,
0 R, R N
where R. and R1 are members of the class consisting of hydrogen and alkyl radicals containing 1 to 2 carbon atoms inclusive and R2 is an alkyl radical containing 1 to 2 carbon atoms inclusive; said composition being suitable for intravenous administration of said antibiotic and yielding upon dilution with an aqueous solvent a clear, stable solution containing the antibiotic in a concentration greater than its solubility in an otherwise identical solution not containing the water-miscible amide.
2. A clear, stable, liquid therapeutic composi tion comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-dimethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl acetamide.
3. A clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution composed of essentially equal volumes of water and N,N-dimethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl acetamide.
4. A clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume or N,N-dimethyl toramide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear,
- stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl formamide.
5. A clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-diethyl acetamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-diethyl acetamide.
6. A clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N,N-dimethyl propionamide; said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N,N-dimethyl propionamide.
7. A therapeutic solution for parenteral administration comprising chloramphenicol dissolved in an aqueous solution containing at least 30% by volume of N,N-dimethyl acetamide.
8. A clear, stable, liquid therapeutic composition comprising chloramphenicol dissolved in a water-miscible amide solution containing at least 30% by volume of N-methyl acetamide, said composition being suitable for intravenous administration of chloramphenicol and yielding upon dilution with an aqueous solvent a clear, stable solution containing chloramphenicol in a concentration greater than its solubility in an otherwise identical solution not containing the N- methyl acetamide.
HARRY M. CROOKS. JR.
i References Cited in the file of this patent v UNITED STATES PATENTS Number Name Date 1,921,722 Berendes Aug. 8, 1933 2,027,905 Goth Jan. 14, 1936 2,067,317 Gruber Jan. 12, 1937 2,483,871 Bartz Oct. 4, 1949 FOREIGN PATENTS" Number Country Date 325,847 Great Britain Feb. 28, 1930 485,569 Great Britain May 17, 1938 OTHER REFERENCES The Lancet, Chloromycetin: An Antibiotic Eflective by Mouth. December 27, 1947, page 952.
Science, Supplement, volume 78, No. 2030, November 24, 1933, page 6, Science News, A Versatile Solven
Claims (1)
1. A CLEAR, STABLE, LIQUID THERAPEUTIC COMPOSITION COMPRISING AN ANTIBIOTIC OF THE CLASS CONSISTING OF CHLORAMPHENICOL AND OPTICALLY RACEMIC CHLORAMPHENICOL DISSOLVED IN A WATER-MISCIBLE AMIDE SOLUTION CONTAINING AT LEASTS 30% BY VOLUME OF A WATER-MISCIBLE AMIDE OF FORMULA,
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Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2855342A (en) * | 1955-07-27 | 1958-10-07 | Schenley Ind Inc | Analgesic compositions |
| US2900304A (en) * | 1956-09-21 | 1959-08-18 | Ici Ltd | Griseofulvin uses and compositions |
| US2917431A (en) * | 1957-08-01 | 1959-12-15 | American Cyanamid Co | Aqueous inorganic salt-sulfosuccinate solutions |
| US2980584A (en) * | 1957-10-29 | 1961-04-18 | Pfizer & Co C | Parenteral magnesium oxytetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3008876A (en) * | 1955-06-25 | 1961-11-14 | Glaxo Lab Ltd | Compositions containing griseofulvin |
| US3051616A (en) * | 1956-03-23 | 1962-08-28 | Bayer Ag | Mothproofing agents |
| US3062717A (en) * | 1958-12-11 | 1962-11-06 | Pfizer & Co C | Intramuscular calcium tetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3068145A (en) * | 1958-06-17 | 1962-12-11 | Upjohn Co | Topical pharmaceutical formulations containing n, n-dimethylacetamide as an anti-inflammatory ingredient |
| US3070502A (en) * | 1958-06-17 | 1962-12-25 | Upjohn Co | Parenteral aqueous tetracycline composition containing n, n-dimethylacetamide solvent |
| US3192932A (en) * | 1963-03-06 | 1965-07-06 | Dorothy J Hart | Multipurpose barrette |
| US3238102A (en) * | 1961-07-14 | 1966-03-01 | Taisho Pharmaceutical Co Ltd | Solubilization of hydrocortisone acetate |
| US3265573A (en) * | 1962-07-27 | 1966-08-09 | Squibb & Sons Inc | Benzothiadiazinesulfonamide-1, 1-dioxide composition |
| US20040242546A1 (en) * | 2003-05-29 | 2004-12-02 | Schering-Plough Animal Health Corporation | Compositions and method for treating infection in cattle and swine |
| US20080146640A1 (en) * | 2006-12-13 | 2008-06-19 | Glinka Tomasz W | Water-Soluble Prodrugs of Chloramphenicol, Thiamphenicol, and Analogs Thereof |
| US20110166359A1 (en) * | 2008-07-30 | 2011-07-07 | Paquette Leo A | Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol |
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| GB325847A (en) * | 1928-11-30 | 1930-02-28 | Ig Farbenindustrie Ag | Process for the manufacture of aqueous solutions of barbituric acids |
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Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3008876A (en) * | 1955-06-25 | 1961-11-14 | Glaxo Lab Ltd | Compositions containing griseofulvin |
| US2855342A (en) * | 1955-07-27 | 1958-10-07 | Schenley Ind Inc | Analgesic compositions |
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| US2900304A (en) * | 1956-09-21 | 1959-08-18 | Ici Ltd | Griseofulvin uses and compositions |
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