Showing papers in "Journal of the American Pharmaceutical Association in 1955"
TL;DR: The chemical examination of the fourth 1,000 accessions in a survey of plants for steroidal sapogenins is a continuation of the reports on the first three reports, with no previously published chemical information on about 50 per cent of the species examined.
Abstract: This is a report of the chemical examination of the fourth 1,000 accessions in a survey of plants for steroidal sapogenins and is thus a continuation of the reports on the first three 1,000 accessions (1-6). Data are given for 950 samples, representing 100 families, 272 genera, and 432 identified species. Of these, 14 families, 151 genera, and 376 species are new in this series. Quantitative data are given for the occurrence of 15 steroidal sapogenins, of which two, gentrogenin and correllogenin, are new. Qualitative data are given for the occurrence of these groups of constituents: saponins, flavonoids, alkaloids, tannins, and unsaturated sterols. There is no previously published chemical information on about 50 per cent of the species examined.
99 citations
TL;DR: Young and adult quail and pheasants were fed diets containing DDT and chemical analysis of tissues indicated that quantities of DDT stored were not proportional to total amounts administered nor to duration of exposure, but were related to the severity of toxic symptoms.
Abstract: Young and adult quail and pheasants were fed diets containing DDT.Chemical analysis of tissues indicated that quantities of DDT stored were not proportional to total amounts administered nor to duration of exposure, but were related to the severity of toxic symptoms.Concentration of the toxicant in breast muscle of birds dying of acute DDT poisoning was approximately 34 jug./ Gm.in adult quail and 22 jug./Gm.in adult pheasants.
90 citations
TL;DR: An improved method has been developed for the measurement of salicylic acid and salicyluric acid in blood plasma and for these two substances and Salicyl glycuronates in urine and a higher value than previously reported has been found.
Abstract: An improved method has been developed for the measurement of salicylic acid and salicyluric acid in blood plasma and for these two substances and salicyl glycuronates in urine. Older methods measured salicyluric acid by the different extraction efficiencies of two solvents and the weaker color formation of salicyluric acid with ferric nitrate. This method measures salicyluric acid more specifically by means of its marked fluorescence at p H 10. A low concentration of a fluorescent substance, probably salicyluric acid, which has not been reported previously was found in dog plasma following large doses of sodium salicylate. The rate of hydrolysis of salicyluric acid by concentrated hydrochloric acid, an important factor in the calculation of the salicyl glycuronate fraction in this and former methods, has been re-examined and a higher value than previously reported has been found. An explanation of this difference is suggested. A synthetic sample of the glycuronate of salicylic acid coupled through the phenolic hydroxyl group, which has not been isolated from urine in pure form, has been tested for reactivity in the method.
87 citations
TL;DR: This work supports the view that the polyethylene glycols may be considered inert when taken by mouth, and is definitely less toxic by mouth than those of lower molecular weights.
Abstract: Polyethylene glycols were fed in the diet to rats for two years and to dogs for one year.Apparently a compound with a mean molecular weight of 6,000 is definitely less toxicby mouth than those of lower molecular weights.This work supports the view that the polyethylene glycols may be considered inert when taken by mouth.
74 citations
TL;DR: A series of pentenyl barbituric acid derivatives has been studied and one of these compounds is shorter acting than two well-knownbarbiturates and with a better therapeutic index.
Abstract: A series of pentenyl barbituric acid derivatives has been studied. In general, the amount required to produce anesthesia is independent of the duration of action. Furthermore, there is no obvious relationship between the pharmacological action and chemical structure of these compounds. Many of these derivatives are isomeric, but show considerable variation in action, dosage, duration of action and therapeutic index. One of these compounds is shorter acting than two well-known barbiturates and with a better therapeutic index.
57 citations
TL;DR: A new procedure for the laboratory determination of drug addiction has been devised and subjected to a preliminary trial using rats as experimental subjects, and preliminary data indicate the method to be worthy of further study.
Abstract: A new procedure for the laboratory determination of drug addiction has been devised and subjected to a preliminary trial using rats as experimental subjects. Automatic equipment has been constructed and utilized to produce permanent records indicating the influence of morphine, codeine, glucose, saline, and insulin administration to pretreated and deprived animals. Preliminary data indicate the method to be worthy of further study.
54 citations
TL;DR: When the energies expended in the processes of tablet ejection, overcoming wall friction and removing the upper punch from the die, were summed for a single punch machine making these tablets at the rate of 100 per minute, it was found that 43 kilocalories would be expended in each hour of operation if the tablets were unlubricated.
Abstract: Energy expended in the tablet compression process was calculated by consideration of the magnitude and relation between the several compression variables. In the compression of about 0.4 Gm. of unlubricated sulfathiazole granulation to a maximum force of 1200 Kg, on the lower punch with flat‐faced 3/8‐inch punches, about 8.6 calories were expended. For about the same weight of lubricated granulation the corresponding value was about 2.0 calories. By considering that only energy expended in the process of eliminating void space to form the tablet caused a temperature rise in the tablet, the temperature rise expected in the lubricated or unlubricated tablets mentioned above would be about 5°. When the energies expended in the processes of tablet ejection, overcoming wall friction and removing the upper punch from the die, were summed for a single punch machine making these tablets at the rate of 100 per minute, it was found that 43 kilocalories would be expended in each hour of operation if the tablets were unlubricated. If lubricated granulation were used the value would be 3 kilocalories. The bulk of these expenditures would probably cause heating of the punches and die and if the granulation was either poorly lubricated or unlubricated the heating might be severe.
49 citations
TL;DR: The method is applied to the prediction of color stability at shelf temperatures in a liquid multisulfa preparation and the color intensity is predicted at the end of several years by a study completed within a month's time.
Abstract: A procedure for prediction of thermal stability of a component in a complex pharmaceutical preparation is outlined. It is based on the reproducibility of the degradation rate function at the various elevated temperatures and extrapolation of the Arrhenius relation to obtain the rate constants that would describe degradation rates at marketing temperatures. The method is applied to the prediction of color stability at shelf temperatures in a liquid multisulfa preparation and the color intensity is predicted at the end of several years by a study completed within a month's time.
39 citations
TL;DR: The velocity constant for the conditons employed in the procedure and the dissolution rate of compressed benzoic acid tablets were determined and it was found that when neutral ionic and nonionic organic compounds were employed as additives the dissolved rate was linearly dependent upon the solubility of benzosic acid in the particular solvent system.
Abstract: A method for determining the dissolution rate and the underlying physical‐chemical theories are presented. The velocity constant for the conditons employed in the procedure and the dissolution rate of compressed benzoic acid tablets were determined. In the density range investigated the dissolution rate was essentially independent of the tablet density. When neutral ionic and nonionic organic compounds were employed as additives the dissolution rate was linearly dependent upon the solubility of benzoic acid in the particular solvent system.
38 citations
TL;DR: The results of pharmacologic studies with a new analgesic compound show analgesic activity in animals with a notable lack of tolerance development and/or respiratory depression.
Abstract: The results of pharmacologic studies with a new analgesic compound are presented. They show analgesic activity in animals with a notable lack of tolerance development and/or respiratory depression.
37 citations
TL;DR: Active chemical and pharmacological interest in R. serpentina has resulted in the discovery of several new alkaloids, and the isolation by Muller, Schlittler, and Bein of reserpine, an alkaloid with pronounced hypotensive and sedative activity, has lent further impetus to the pharmacological and chemical study of the alkal steroids of R. Serpentina.
Abstract: Rauwolfia is an important genus of the plant family Apocynaceae. There are nearly one hundred and twenty‐five species of Rauwolfia which are distributed all over the tropical regions of the world (1‐8). The most important member of the genus is R. serpentina Benth; the crude drug was known to the ancient Indians as a useful febrifuge (8), a remedy for snake bite, and as a cure for dysentery. In more recent times it has been used for insomnia, hypochondria and insanity.
The presence of alkaloidal principles in R. serpentina was first pointed out in 1890 by Greshoff (9). In 1933, Chopra, Gupta, and Mukherjee (10) reported the hypotensive activity of the material extracted from the plant and in 1931 Siddiqui and Siddiqui (11) isolated a series of crystalline alkaloids from R. serpentina. Active chemical and pharmacological interest in R. serpentina has resulted in the discovery of several new alkaloids (Table I). The isolation by Muller, Schlittler, and Bein (12) of reserpine, an alkaloid with pronounced hypotensive and sedative activity, has lent further impetus to the pharmacological and chemical study of the alkaloids of R. serpentha. A brief summary of the chemical aspects of R. serpentina will be presented in this review.
TL;DR: Evidence is presented to show that the off‐taste of saccharin is intrinsic in the saccharIn molecule as tasted by individuals who are sensitive to it, and decomposition products or trace impurities are not essential to the off-taste response.
Abstract: Standard taste panel techniques have been used to study the incidence of the off‐taste of saccharin salt solutions, freshly prepared without heating. Evidence is presented to show that the off‐taste of saccharin is intrinsic in the saccharin molecule as tasted by individuals who are sensitive to it. Decomposition products or trace impurities are not essential to the off‐taste response. Approximately 25 per cent of the population can be expected to detect the off‐taste in saccharin concentrations up to 0.026 per cent, equivalent to about 10 per cent sucrose. It has been shown that the off‐taste response was substantially the same for saccharin sodium, saccharin calcium, and for saccharin sodium prepared by new synthetic methods intended to eliminate trace impurities.
TL;DR: The response angle of a sulfathiazole granulation was studied as a function of average particle size, presence of lubricants, and admixture of fines to find that the repose angle increased with decreasing particle size.
Abstract: In order to study the problem of granulation flow in tableting as it is related to interparticle friction, the response angle of a sulfathiazole granulation was studied as a function of average particle size, presence of lubricants, and admixture of fines.In general, the repose angle increased with decreasing particle size.Talc added to granules in small concentrations decreased the repose angle but tended to increase the angle at higher concentrations.Magnesium stearate had little or no effect on the repose angle of the granulation samples studied.Addition of fines to coarse granules caused a striking increase in repose angle.
TL;DR: A comparison between various emulsions made with carrageenin and acacia as a standard was made and individual emulsion evaluated on the basis of viscosity and particle counts.
Abstract: A comparison between various emulsions made with carrageenin and acacia as a standard was made. Individual emulsions were evaluated on the basis of viscosity and particle counts.
TL;DR: The tube assay employing Escherichia coli 113‐3 with the medium of Davis and Mingioli gave low estimates of potency for vitamin B12 in aqueous extracts of multi‐vitamin preparations when compared with the U. S. P. P.'s method.
Abstract: The tube assay employing Escherichia coli 113‐3 with the medium of Davis and Mingioli gave low estimates of potency for vitamin B12 in aqueous extracts of multi‐vitamin preparations when compared with the U. S. P. method. The presence of thiamine in the multivitamin samples was found to be responsible for these low values which were most evident in the shaken assays. When samples were extracted with sodium meta‐bisulfite to destroy the thiamine, the potency estimates agreed well with those obtained with the U. S. P. procedure. This extraction eliminated the need for cyanide treatment. In view of its stability of response and greater simplicity as compared with the U. S. P. assay, the E. coli method seems particularly applicable to the estimation of vitamin B12 activity in the absence of interfering materials, e. g., pseudo‐forms of vitamin B12 or methionine.
TL;DR: In this article, 17 uracils and five related compounds were tested for their ability to protect mice from electroshock and Metrazol® convulsions, and it was possible to demonstrate a limited structure-activity relationship for the electroshock testing.
Abstract: Seventeen uracils and five related compounds were tested for their ability to protect mice from electroshock and Metrazol® convulsions. It was possible to demonstrate a limited structure‐activity relationship for the electroshock testing. Such a relationship was not apparent from the chemoshock results.
TL;DR: The addition of meparfynol to an anticonvulsant did not cause the protective index to rise above that of the better component in the combination, and the combined drug had no effect on neurotoxicity in mice.
Abstract: Combinations of meparfynol and anticonvulsant drugs were tested for anti-Metrazol® potency and neurotoxicity in mice. The addition of meparfynol to an anticonvulsant did not cause the protective index to rise above that of the better component in the combination.
TL;DR: This paper summarizes these activities and what is known about the relation of structure to such activities of ilavonoids and suggests that this is a fruitful field for further research.
Abstract: There are known at present at least 137 natural ilavonoids, occurring in at least 62 families, 153 genera, and 277 species of plants.About 33 different types of physiological and biochemical activities have been reported for one or another of 30 of these ilavonoids.This paper summarizes these activities and what is known about the relation of structure to such activities.It is suggested that this is a fruitful field for further research.
TL;DR: In this article, a method of analysis is described which is applicable to solutions of epinephrine and norepinephrine, such as Epinephrine injection U.S. P. and levarterenol bitartrate injection N. N. R.
Abstract: A method of analysis is described which is applicable to solutions of epinephrine and norepinephrine, such as epinephrine injection U. S. P. and levarterenol bitartrate injection N. N. R. The method depends on the quantitative conversion of the substances into O3, O4, N‐triacetyl derivatives which may be extracted into chloroform, weighed, identified, and examined polarimetrically for the determination of stereo‐chemical composition. Excellent recoveries of the physiologically potent l‐isomer are obtained, and results of analyses of solutions of epinephrine show very good agreement with potencies determined by the U. S. P. XIV dog bioassay. By supplementing the method with partition chromatography of the acetylation product, the norepinephrine in a solution of U. S. P. epinephrine may be quantitatively isolated as its triacetyl derivative and determined colorimetrically after deacetylation and oxidation to noradrenochrome.
TL;DR: The mixture showed potentiation of sweetness, since it was sweeter than would be expected from the known sweetness of its components and less than for either component in corresponding concentrations.
Abstract: Taste panel techniques were used to study the relative sweetness and the incidence of off-taste in solutions of cyclamate, of saccharin, and of their 10:1 mixture.The mixture showed potentiation of sweetness, since it was sweeter than would be expected from the known sweetness of its components.Off-taste is minimized in the mixture to the extent that it is less than for either component in corresponding concentrations.The decrease in off-taste is more noteworthy when the approximately doubled sweetness of the mixture is considered.
TL;DR: It is shown that the rate of hydrolysis of benzocaine in aqueous solution can be substantially inhibited by addition of caffeine which has previously been shown to complex with this drug.
Abstract: A new approach to possible preservation of drugs undergoing hydrolytic degradation is presented. It is shown that the rate of hydrolysis of benzocaine in aqueous solution can be substantially inhibited by addition of caffeine which has previously been shown to complex with this drug. Presence of two and one‐half per cent of caffeine in the system resulted in reduction of the hydrolytic rate to less than one‐fifth of that in absence of the xanthine. Mathematical analysis of the results obtained indicates that the complexed form of the drug does not undergo, surprisingly, any perceptible cleavage at the ester linkage.
TL;DR: The copper chelate, found to be relatively uncontaminated with metal hydroxide, exhibited more prolonged blood levels in guinea pigs than streptomycin sulfate, but also a greater toxicity.
Abstract: Streptomycin has been found to undergo chelation with several metals in aqueous solution. Evidence for chelate formation is provided by a drop in pH during the formation, production of characteristic colors, decreased solubility in water, and absence of metal ions in the solution. The copper chelate, found to be relatively uncontaminated with metal hydroxide, exhibited more prolonged blood levels in guinea pigs than streptomycin sulfate, but also a greater toxicity.
TL;DR: The anticonvulsant activity of uracil and thymine has been surpassed by several members of this new series of 5‐alkyluracils prepared for evaluation as anti‐convulsants.
Abstract: A convenient laboratory synthesis has been devised by which a series of new 5‐alkyluracils has been prepared for evaluation as anti‐convulsants. Certain other 5‐substituted uracils and their N,N‐dimethyl derivatives, and related compounds, have also been synthesized. The anticonvulsant activity of uracil and thymine has been surpassed by several members of this new series.
TL;DR: In the search for a way of speeding up the pendant drop method of measuring surface tension, a development was made which permitted a reduction of approximately 75 per cent in time required for a determination.
Abstract: In the search for a way of speeding up the pendant drop method of measuring surface tension, a development was made which permitted a reduction of approximately 75 per cent in time required for a determination. This modified method permits a monetary saving in addition to the saving in time, by eliminating a photographic process. This method offers advantages over other surface tension methods for certain uses.
TL;DR: The free‐amino ester of 4-amino‐salicylic acid was obtained in excellent yield for tuberculostatic and toxicity determinations and the protected glucose esters were found to be stable.
Abstract: Glucose esters of 4‐ and 5‐aminosalicylic acid were obtainable by reaction of the benzyloxynitrobenzoic acid chlorides with diacetone glucose, followed by catalytic hydrogenation of the nitro groups. Conversion of the amines to hydrochlorides removed one or both of the acetone groups from the glucose. Complete removal of the acetone groups gave a glucose ester that was unstable on standing, but the protected glucose esters were found to be stable. The free‐amino ester of 4‐amino‐salicylic acid was obtained in excellent yield for tuberculostatic and toxicity determinations.
TL;DR: Several phytochemical componeats have been isolated from Desmodium gangeticum and a preliminary study of their physical and chemical properties is reported.
Abstract: Several phytochemical componeats have been isolated from Desmodium gangeticum. The isolation of these principles has been described and a preliminary study of their physical and chemical properties is reported.
TL;DR: A previously unreported cardioactive glycoside has been isolated from the leaves of D. lanata and found to be closely related to digoxin and gitoxin.
Abstract: A previously unreported cardioactive glycoside has been isolated from the leaves of D. lanata and found to be closely related to digoxin and gitoxin. Both the glycoside and its aglycone are relatively water soluble.
TL;DR: Ascorbic acid was relatively stable in glycerin and propylene glycol and in sugar and sorbitol solutions and in syrups containing conjointly vitamins of the B‐complex is not materially affected.
Abstract: The stability of ascorbic acid at several concentrations in various liquid media including aqueous solutions of cellulose gums, pectin, sucrose, dextrose, corn syrup, and in glycerin and propylene glycol was studied The effect of p H in aqueous solutions of ascorbic acid was also studied Viscosity alone as produced by gums did not prevent decomposition of ascorbic acid Sugar and sorbitol solutions exerted a marked stabilizing effect Ascorbic acid was relatively stable in glycerin and propylene glycol and in sugar and sorbitol solutions Data are presented on the rates of decomposition of ascorbic acid in these media after storage at room temperature and at 40°C The stability of ascorbic acid in syrups containing conjointly vitamins of the B‐complex is not materially affected
TL;DR: An assay procedure has been developed for tablet preparations containing reserpine alkaloid, and the results of the application of this method to a powdered extract of Rauwolfia serpentina is reported.
Abstract: The fluorescence of solutions of reserpine under ultraviolet light is increased by heating with hydrogen peroxide, and is quantitatively related to its concentration. An assay procedure has been developed for tablet preparations containing reserpine alkaloid, and the results of the application of this method to a powdered extract of Rauwolfia serpentina is reported.
TL;DR: Alcoholic solutions of Pentothal® and pentobarbital as well as aqueous solutions of their sodium salts were absorbed sublingually as demonstrated by the increased sleeping time of anesthetized mice, and alcoholic solutions produced the greatest increase.
Abstract: Solutions of drugs were sublingually administered to anesthetized animals whose esophagus had been ligated and trachea cannulated.This method was devised so that there would he no possibility of the drug being swallowed.As determined by the time for convulsions to appear in anesthetized rats or for death to occur in anesthetized mice, strychnine sulfate in alcohol, strychnine sulfate in water, and strychnine in alcohol were found to be well absorbed sublingually, and in that order, while strychnine suspended in water was not absorbed.The use of the base or the salt and the vehicle employed had a more important effect on sublingual absorption than on oral absorption.Aconitine in alcohol was more rapidly absorbed sublingually than aconitine hydrochloride in water although there was no difference in subcutaneous absorption.Alcoholic solutions of Pentothal® and pentobarbital as well as aqueous solutions of their sodium salts were absorbed sublingually as demonstrated by the increased sleeping time of anesthetized mice.Alcoholic solutions produced the greatest increase.The form of a drug and the vehicle used play an important role in sublingual absorption.