Showing papers in "Journal of the American Pharmaceutical Association in 1950"
TL;DR: Evidence presented in this report confirms the earlier work indicating that acute oral toxicity, dermal toxicity, and irritating properties of the polyethylene glycols are very low.
Abstract: Information developed during recent years upon the toxicological actions of the fluid and solid polyethylene glycols is summarized. This information has been re-interpreted and supplemented. Evidence presented in this report confirms the earlier work indicating that acute oral toxicity, dermal toxicity, and irritating properties of the polyethylene glycols are very low. The safe rat dose of “Carbowax” 1500 is now known to be substantially greater than originally reported, and of “Carbowax” 4000, slightly greater.
114 citations
57 citations
TL;DR: Results are reported of studies involving the administration of PEG 400 both orally and intravenously to human subjects and subsequently determining the rate and extent of excretion in the urine, indicating, that ethylene glycol is not formed as a metabolite of P EG 400.
Abstract: Additional data have been developed on the absorption and excretion of liquid polyethylene glycols. Results are reported of studies involving the administration of PEG 400 both orally and intravenously to human subjects and subsequently determining the rate and extent of excretion in the urine. Single oral DOSES OF PEG 400 were also administered to rabbits and the percentage recoveries from feces and urine determined. Evidences from these and other studies indicates, that ethylene glycol is not formed as a metabolite of PEG 400.
51 citations
TL;DR: The mucous membrane test for irritation using the rabbit eye has been extended to include a simplified and more practical method for expressing the results in terms of the Threshold Irritant Concentration (T. I. C.), which produces no more than a “mild” irritation.
Abstract: An objective method has been described for determining the irritant properties of substances designed for parenteral administration by means of the trypan blue test. Various concentrations of the substance to be studied are injected intracutaneously into the abdominal skin of the rabbit followed by the intravenous injection of 10 mg./Kg. of trypan blue. Extravasation of the blue dye into the injured areas is interpreted according to a table of weighted numerical scores. The test results are summarized in terms of the Threshold Irritant Concentration (T. I. C.) defined as the concentration expressed in per cent which produces no more than a “mild” irritation. The mucous membrane test for irritation using the rabbit eye (9) has been extended to include a simplified and more practical method for expressing the results in terms of the T. I. C. The trypan blue response of quinine hydrochloride was not abolished by an antihistaminic drug. Histamine diphosphate failed to produce a typical trypan blue response in rabbits whereas histamine wheals in the dog stained a deep blue following the intravenous injection of trypan blue.
38 citations
TL;DR: The results in this paper indicate the reactivity of digitoxin with the Baljet reagent follows Lambert-Beer's law.
Abstract: The color reaction of digitoxin with the Baljet reaction has been used in a quantitative study. Contrary to the statements of the literature, the results in this paper indicate the reactivity of digitoxin with the Baljet reagent follows Lambert-Beer's law.
32 citations
TL;DR: It is shown in the pregnant dog, that each uterine contraction, either spontaneous or induced by drug action, decreases the uterine arterial blood flow.
Abstract: A method for studying the uterine blood flow and myometrial activity of intact experimental animals is described. It is shown, in the pregnant dog, that each uterine contraction, either spontaneous or induced by drug action, decreases the uterine arterial blood flow. The actions of fifteen pharmacological agents on uterine flow and myometrial activity are reported. The results indicate that drugs have an important effect on the uterine flow both by direct vascular and indirect myometrial action.
27 citations
TL;DR: 4,4′-Dihydroxy benzylidene aniline produced an estrogenic response in 12.5 mg.
Abstract: The relation between chemical constitution and estrogenic action has been investigated in a group of azomethine derivatives comprising all 4,4′ substitution combinations of four groups—H, CH3, CH3O, OH. 4,4′-Dihydroxy benzylidene aniline produced an estrogenic response in 12.5 mg. doses subcutaneously and 25 γ doses intravaginally. Absorption spectra were determined for all derivatives.
26 citations
TL;DR: The cumulative urinary excretion and the concentration in the urine at any given time was greater for terramycin than for aureomycin, and a relatively marked increase in blood concentrations occurs with an increase in dose of terramYcin.
Abstract: Terramycin, a recently discovered antibiotic, is compared with aureomycin. These antibiotics are very similar in their antibacterial spectra and in the blood concentrations produced following oral doses in man. A relatively marked increase in blood concentrations occurs with an increase in dose of terramycin. This increase was not as pronounced with aureomycin. The cumulative urinary excretion and the concentration in the urine at any given time was greater for terramycin than for aureomycin.
26 citations
TL;DR: Spectrophotometric experiments indicated that licorice root is a steroid, and other evidence points to its identity with estriol, and an efficient process was devised for its concentration.
Abstract: Licorice root was found to contain an estrogenic hormone in appreciable quantity, and an efficient process was devised for its concentration. Spectrophotometric experiments indicated that it is a steroid, and other evidence points to its identity with estriol. An antihormonal principle may also be present. Asclepias, helonias, and aletris were also found to be estrogenic.
25 citations
TL;DR: It is shown that the over-all reaction is the sum of two reactions involving the free base and the singly charged ion, which means that general equations relating the half life of procaine solutions to their temperature and pH are derived.
Abstract: Procaine solutions are subject to hydrolytic deteriortion. In the present paper results of a chemical kinetical investigation of this reaction together with its theoretical analysis are given. It is shown that the over-all reaction is the sum of two reactions involving the free base and the singly charged ion. The activation energies have been found to be 13.8 and 12 kilocalories per mole, respectively, for the two hydrolytic reactions. From the data obtained general equations relating the half life of procaine solutions to their temperature and pH are derived.
24 citations
TL;DR: Black and mallard ducks have been found to be highly susceptible to phosphorus poisoning and an investigation of the effects of poisoning from the administration of white phosphorus is reported.
Abstract: Black and mallard ducks have been found to be highly susceptible to phosphorus poisoning. The results of an investigation of the effects of poisoning from the administration of white phosphorus are reported.
TL;DR: A buffer system composed of aluminum dihydroxyaminoacetate and magnesium carbonate is described in this article, which when administered with acetylsalicylic acid reduces gastrointestinal distress in man and gastric damage in rats.
Abstract: A buffer system composed of aluminum dihydroxyaminoacetate and magnesium carbonate is described. This buffer system, when administered with acetylsalicylic acid, reduces gastrointestinal distress in man and gastric damage in Shay rats. It also increases at least twofold the rate of absorption of salicylates from the gastrointestinal tract.
TL;DR: The low toxicity of K 5 suggests its use not only for topical treatment of dermatophytic infections but as a preservative for pharmaceuticals, foods, and beverages.
Abstract: Vitamin K 5 (2-methyl-4-amino-1-naphthol hydrochloride) is a strong antimicrobial agent: a number of pathogenic bacteria and fungi, as well as saprophytic bacterial, yeast, and fungal despoilers of foods, beverages, and other products are markedly inhibited or killed by concentrations of K 5 ranging from 10 to 300 parts per million, depending on the organism. The low toxicity of K 5 suggests its use not only for topical treatment of dermatophytic infections but as a preservative for pharmaceuticals, foods, and beverages. Upon oxidation the compound is subject to discoloration and, in aqueous solution, forms a flocculent precipitate, but this can be obviated by use of appropriate solvents and reducing agents. Vitamin K 5 of high purity can be prepared in almost quantitative yields from vitamin K 3 (2-methyl-1,4-naphthoquinone) which, in turn, is obtained by direct oxidation of 2-methyl-naphthalene.
TL;DR: A new compound, Bentyl hydrochloride, has been demonstrated to possess parasympathetic depressant properties and has a marked relaxing action in vivo on normal and barium-stimulated intestine, and it strongly antagonizes the intestinal effects of acetylcholine.
Abstract: A new compound, Bentyl hydrochloride (β-diethylaminoethyl 1-cyclohexylcyclo-hexanecarboxylate hydrochloride), has been demonstrated to possess parasympathetic depressant properties. It has a marked relaxing action in vivo on normal and barium-stimulated intestine, and it strongly antagonizes the intestinal effects of acetylcholine. The bulk of Bentyl administered to animals appears to be destroyed in the body, and the substance has low toxicity following single and repeated administration to animals.
TL;DR: A procedure is described which circumvents the difficulty in the assay of vitamin A by employing a tocopherol-containing blank, and data are presented indicating the effectiveness of the procedure in eliminating the difficulty.
Abstract: The Morton-Stubbs procedure in the assay of vitamin A is subject to considerable over-correction when tocopherols are present. A procedure is described which circumvents the difficulty by employing a tocopherol-containing blank. The blank is prepared by shaking the vitamin A-tocopherol solution in hexane with 60 per cent sulfuric acid, followed by reading the acid-treated solution against the untreated solution. Data are presented indicating the effectiveness of the procedure in eliminating the difficulty.
TL;DR: The preparation of a relatively nontoxic bacterial pyrogen from a Pseudomonas species is described by enzymatic degradation of the cellular substance followed by the removal of all dialyzable material.
Abstract: The preparation of a relatively nontoxic bacterial pyrogen from a Pseudomonas species is described. This has been achieved by enzymatic degradation of the cellular substance followed by the removal of all dialyzable material. Several investigators have used this pyrogen for a study of the physiology of fever.
TL;DR: In this article, the extinction coefficients at λ 2970 A, which is at the maximum of the erythema action spectrum, have been calculated and are given in a table.
Abstract: About 90 compounds which have been suggested by various workers for use in sunburn preventive preparations are tabulated with references to the literature. The structural formulas are given for the nuclei of the major families of compounds and the absorption spectra of 25 compounds are figured. The extinction coefficients at λ 2970 A., which is at the maximum of the erythema action spectrum, have been calculated and are given in a table.
TL;DR: The acute toxicities in mice following intravenous and oral administration are reported and pathological changes in rats are compared after treatment for six months with natural and synthetic glycerin.
Abstract: Acute and prolonged studies have failed to show any differences in the toxicity of natural and synthetic glycerin. The acute toxicities in mice following intravenous and oral administration are reported. Pathological changes in rats are compared after treatment for six months with natural and synthetic glycerin.
TL;DR: A rapid and reliable assay method applicable to both impure and purified preparations of terramycin is described, utilizing Klebsiella pneumoniae P. C. I. 602 as the test organism.
Abstract: A rapid and reliable assay method applicable to both impure and purified preparations of terramycin is described. The method described involves a turbidimetric procedure utilizing Klebsiella pneumoniae P. C. I. 602 as the test organism. An incubation period of only three and one-half hours is required.
TL;DR: The study of many furan derivatives suggests certain necessary structural configurations for in vitro and in vivo antibacterial activity for nitrofurans containing the necessary carbonyl group in the 2 position.
Abstract: The study of many furan derivatives suggests certain necessary structural configurations for in vitro and in vivo antibacterial activity. The specificity of a nitro group in the 5 position of 2-substituted furans in conferring antibacterial activity is well demonstrated. Certain requirements need be met in the nature of the substituent in the 2 position in order to also obtain in vivo activity. Chemotherapeutic activity is displayed by a number of semicarbazone and substituted semicarbazone derivatives of nitrofurans containing the necessary carbonyl group in the 2 position. The substitution of other heterocyclic ring systems such as thiophene and pyrrole does not lead to the antibacterial effectiveness of analogous nitrofuran compounds. Attempts to explain or correlate antibacterial activity with structural configuration by physicochemical methods have not met with success. Certain suggestions as to the mode of antibacterial action of the nitrofurans have been made.
TL;DR: A simplified laboratory procedure for the preparation of this intermediate is reported and a description is given of its use in the synthesis of two antihistamine-type compounds derived from carbazole and diphenylamine.
Abstract: Although β-dimethylaminoethyl chloride hydrochloride is a very important intermediate which has been especially useful in the synthesis of various antihistaminic agents, publications mentioning its use often neglect to refer to a convenient method of preparation. A simplified laboratory procedure for the preparation of this intermediate is reported and a description is given of its use in the synthesis of two antihistamine-type compounds derived from carbazole and diphenylamine.
TL;DR: A procedure for the synthesis of 3,3-dialkylglutarimides is described and three alkylmethylglutarate compounds are reported but no physiological activity of significance can be attributed to any one of the three compounds.
Abstract: A procedure for the synthesis of 3,3-dialkylglutarimides is described and three alkylmethylglutarimides are reported. No physiological activity of significance can be attributed to any one of the three compounds.
TL;DR: It has been found that hydroquinone is responsible for the toxic effects produced by the ingestion of various species of Xanthium.
Abstract: It has been found that hydroquinone is responsible for the toxic effects produced by the ingestion of various species of Xanthium. A method of isolation of the toxic principle is discussed as well as the preliminary report on the toxicology of hydroquinone. A comparative chemical study of the kernel and the bur is also included.
TL;DR: In this article, a new iron-containing phenolsulfonic acid type reagent was developed for the Kober reaction of α- and β-estradiol, which is stable for months and is characterized by much higher sensitivity for α-estrogens and a lower sulfuric acid content than is usual in Kober reagents.
Abstract: Minute quantities of iron markedly affect the development of characteristic colors of estrogens in the Kober reaction. Detailed study of these effects on the yellow and red phases of the Kober colors produced by α- and β-estradiols resulted in development of a new iron-containing phenolsulfonic acid type reagent for these estrogens. The reagent is characterized by much higher sensitivity for α-estradiol and a lower sulfuric acid content than is usual in Kober reagents. It is stable for months. The diluted reagent is highly sensitive for β-estradiol but does not give a color with α-estradiol. Analytical procedures are presented for the determination of α-estradiol and β-estradiol in mixtures containing up to 30 μg. of total estradiols. Results of analysis of such mixtures including laboratory-prepared oil solutions, show very good precision and accuracy. Analyses of typical commercial α-estradiol preparations (oil solution, aqueous suspension, tablets) yield precise results in good agreement with those obtained by the infrared method. The colorimetric method is presented in conjunction with a simple extraction procedure intended primarily for application to those pharmaceutical α-estradiol preparations essentially free of phenolic estrogens other than the estradiols. Its application in combination with partition chromatography to more complex estrogenic pharmaceuticals will be described in a later report.
TL;DR: Filtrates of mold cultures representing 31 species which were propagated on a dextrose-peptone medium were injected intravenosly in rabbits andPyrogen production appeared to be dependent upon the composition of the media.
Abstract: Filtrates of mold cultures representing 31 species which were propagated on a dextrose-peptone medium were injected intravenosly in rabbits. Significant elevations in body temperature varying over a wide range were observed for 16 of the 31 species. Pyrogen production appeared to be dependent upon the composition of the media.
TL;DR: The acid dye method for the estimation of certain alkaloid and other base compounds has been extended to atropine and other tropine alkaloids and applications to tinctures and extracts of belladonna and hyoscyamus will be discussed.
Abstract: The acid dye method for the estimation of certain alkaloids and other base compounds has been extended to atropine and other tropine alkaloids. This procedure is based on the observation that certain acidic dyes combine with many alkaloids to form saltlike compounds which are characterized by their solubility in organic solvents. They can thus be separated and the dye component can be estimated colorimetrically. The procedure has been adapted to the determination of atropine and hyoscyamine with the help of bromocresol purple. The method permits the quantitative estimation of these alkaloids in amounts ranging from 0.1 to 2.0 mg. per sample. Applications of the method to tinctures and extracts of belladonna and hyoscyamus will be discussed.
TL;DR: The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards and to highly toxic to rats with the minimum lethal dose by oral administration.
Abstract: The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst rather than accept water containing 1.0 mg. of actidione per liter. The compound is highly toxic to rats with the minimum lethal dose by oral administration being approximately 1.0 mg./Kg. body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar untreated boards were pierced within thirty to sixty minutes.
TL;DR: Removal of menthofurane by franctional distillation resulted in an increase in the levorotation of pepperment oil and made it possible to produce an oil which conforms to the U. S. P. standards.
Abstract: A study of three types of pappermint oil found in the Pacific NOrthwest was made to determine the cause of the unusual characteristics of peppermeitnt oil produced in eastern Washington. These were fractionally distilled and a strongly dextrorotatory substance was found to be more predominant in the eastern Washingtonoil, wich accounted for its low levo optical rotation. This substance was identified as menthofurance and a quantitative colorimetric procedure was developed for its estimation. Other compounds identified in eact of the three oils were: l-Limonene, cineol, pulegone menthone, menthol, acetic, and isovaleric acids. The acids were separated and estimated by chromatographic technique. Removal of menthofurane by franctional distillation resulted in an increase in the levorotation of pepperment oil and made it possible to produce an oil which conforms to the U. S. P. standards.