Showing papers in "Journal of the American Pharmaceutical Association in 1957"
1,646 citations
TL;DR: A number of esters of hydrocortisone and related steroids have been examined for activity in the granuloma inhibition (subcutaneous cotton pellet) test, both after local application of the steroids and after systemic administration as mentioned in this paper.
Abstract: A number of esters of hydrocortisone and related steroids have been examined for activity in the granuloma inhibition (subcutaneous cotton pellet) test, both after local application of the steroids and after systemic administration. Liver glycogen deposition activity was examined by a one-day oral test in mice, a six-day test in rats, and for duration of action after a single subcutaneous injection. Rates of absorption and activity per mg. of steroid absorbed also were determined. Wide differences in activity were found, depending upon the configuration at C-21. Part of this difference was due to diverse rates of absorption, but there were also differences in activity per mg. of steroid absorbed. It is concluded that ease of hydrolysis of the ester is also a factor in determining potency. The tertiary butyl acetate is particularly effective when locally applied, but systemic activity of this ester is relatively low because of reduced rate of absorption and decreased activity per mg. absorbed. After subcutaneous injection, the free alcohol of hydrocortisone is more rapidly absorbed and gives a more prompt response than any of its esters examined. The 9α-fluoro derivative is more gradually absorbed and gives a more sustained response than does hydrocortisone.
294 citations
TL;DR: In this paper, it was suggested that the fundamental reason for differences found by clinical workers in comparing blood levels from oral administration of the choline and isopropanolamine salts with the ethylenediamine salt was due to differences in solution rate.
Abstract: The solution rate of several theophylline salts was determined in buffer solutions covering a range of hydrogen ion concentrations somewhat greater than those to which the salts would be exposed after oral administration. It was found that marked differences existed in the rate with which the several salts dissolved and the rates were relatively independent of buffer pH. It was suggested that the fundamental reason for differences found by clinical workers in comparing blood levels from oral administration of the choline and isopropanolamine salts with the ethyl-enediamine salt was due to differences in solution rate. The in vitro solution rates determined strongly support this explanation. The effect of solution rate on maximum blood level and rate of build-up of blood level with time was discussed by means of a mathematical model relating blood level with solution rate and elimination rate from the blood stream. The solution rate of theophylline in acidic and basic media was determined and found to vary inversely with the hydrogen ion concentration of the diffusion layer. A relationship was developed between solution rate of theophylline and diffusion layer pH and it was shown to be capable of roughly predicting solution rate of salts from measurement of this pH.
81 citations
TL;DR: The PVP-iodine resulting from this combination retains the germicidal and chemical nature of the iodine yet it provides a more stable form of iodine in solution than iodine alone or some of the more common iodine preparations such as iodine tincture and Lugol's solution.
Abstract: Polyvinylpyrrolidone is a water-soluble, physiologically acceptable polymer which has the ability to tie up iodine. The PVP-iodine resulting from this combination retains the germicidal and chemical nature of the iodine yet it is more water-soluble than iodine alone; it provides a more stable form of iodine in solution than iodine alone or some of the more common iodine preparations such as iodine tincture and Lugol's solution. The iodine present in PVP-iodine is not as irritating to tissue and mucosa as other iodine preparations of the same strength, and the toxicity of the iodine is reduced.
61 citations
TL;DR: Experimental studies involving partitioning between two solvents suggest that caffeine undergoes rather marked association in aqueous solution, existing primarily as monomer, dimer, and tetramer, while 1-ethyltheobromine appears to exist in aQueous solution only in monomeric and dimeric forms.
Abstract: Experimental studies involving partitioning between two solvents suggest that caffeine undergoes rather marked association in aqueous solution, existing primarily as monomer, dimer, and tetramer. A graphical method has been utilized to estimate the association constants for the dimerization and tetramerization equilibria in water. Similar studies with 7-ethyltheophylline and 7-propyltheophylline indicate that they also undergo considerable association in aqueous solution forming dimeric and tetrameric associated species. The degree of association decreases as the length of the side chain increases. In contrast, 1-ethyltheobromine appears to exist in aqueous solution only in monomeric and dimeric forms.
49 citations
TL;DR: Biological utilization and easy availability of the cobalt and iron components was proved by administering the complex to rats under various experimental conditions and the toxicity of the complex is no greater than a mixture of the simple salts.
Abstract: A cobalt, iron, and amino acetic acid complex was prepared and shown to be a true complex rather than a mixture of metallic glycinates. Biological utilization and easy availability of the cobalt and iron components was proved by administering the complex to rats under various experimental conditions. The hematopoietic response was compared to that of equivalent doses of cobalt chloride and ferrous sulfate and was found to be of the same order of magnitude. The toxicity of the complex is no greater than a mixture of the simple salts.
41 citations
TL;DR: This procedure, after the excess polyphosphoric acid was decomposed and neutralized, when applied to glycine, alanine, leucine, isoleucine and phenylalanine, gave good yields of the corresponding diketopiperazines.
Abstract: Conversion of an alpba -amino acid to its corresponding 2,5-diketopiperazine was accomplished by heating the amino acid with a suitable dehydrating agent such as polyphosphoric acid. This procedure, after the excess polyphosphoric acid was decomposed and neutralized, when applied to glycine, alanine, leucine, isoleucine, and phenylalanine, gave good yields of the corresponding diketopiperazines. The temperature of the reaction is the most critical factor in obtaining satisfactory yields. The optimum reaction conditions for each of the five amino acids are reported.
36 citations
TL;DR: The botanical character of the fungus Cordyceps sinensis (Berkeley) Saccardo has been described in this paper, whose structure has been elucidated to be 1,3,4,5-tetrahydroxy-cyclohexanoic acid, an isomer of quinic acid.
Abstract: The botanical character of the fungus Cordyceps sinensis (Berkeley) Saccardo has been described. It has yielded cordycepic acid, C 7 H 12 O 6 , whose structure has been elucidated to be 1,3,4,5-tetrahydroxy-cyclohexanoic acid, an isomer of quinic acid.
32 citations
TL;DR: Tests for arousal of hexobarbitalized mice, respiratory stimulation, running movement, and total movement did not indicate any consistent differences between the two groups, suggesting the possible advantage of some terpenones as convulsants for the screening of petit mal anticonvulsants.
Abstract: Dicyclic and monocyclic terpenones were studied for their central stimulating effects. Differences in the convulsive actions were noted for the two types of terpenones and a structure-activity relationship is postulated to explain variations in toxicity. Tests for arousal of hexobarbitalized mice, respiratory stimulation, running movement, and total movement did not indicate any consistent differences between the two groups. The possible advantage of some terpenones as convulsants for the screening of petit mal anticonvulsants is studied and discussed.
31 citations
TL;DR: A homologous series of twenty basic esters of mono-and dialkylmalonic acid has been pharmacologically investigated as discussed by the authors, and the most active compound of the series is a more active spasmolytic than papaverine hydrochloride, is equal to the local anesthetic activity of cocaine hydrochlorides, and is less active than atropine sulfate in inhibiting unstimulated gastric secretions.
Abstract: A homologous series of twenty basic esters of mono- and dialkylmalonic acid has been pharmacologically investigated. The preliminary testing included antispas-modic testing against spontaneous contractions, barium-induced spasms, and metha-choline-induced spasms of the isolated guinea pig ileum; local anesthetic testing employing the rabbit cornea and the guinea pig wheal; and anti-secretory testing employing pyloric ligation in the rat. The monobasic esters possess greater anti-spasmodic, local anesthetic, and antisecretory activity than the dibasic esters. Activity increased with the length of the side chains. The most active compound of the series is a more active spasmolytic than papaverine hydrochloride, is equal to the local anesthetic activity of cocaine hydrochloride, and is less active than atropine sulfate in inhibiting unstimulated gastric secretions.
30 citations
TL;DR: Propylene glycol has a significant and useful preservative activity in many preparations including those made with sorbitol, and is probably one related to its chemical structure.
Abstract: Glycerin and sorbitol were found to supplement each other in their inhibition of both molds and bacteria. It is believed that this inhibitory action is purely one of osmotic effect. Propylene glycol appears to have a specific inhibitory effect against bacteria and most molds; the addition of 10% w/v propylene glycol was found to inhibit the growth of these organisms. Thirty per cent w/v propylene glycol is required to inhibit Monilia albicans. Studies have indicated that the inhibition produced by the addition of propylene glycol to sorbitol solutions is not purely the result of osmotic effect, as is the case with glycerin, but probably one related to its chemical structure. It may, therefore, be concluded that propylene glycol has a significant and useful preservative activity in many preparations including those made with sorbitol.
TL;DR: Studying on various cosmetic formulations containing nonionic surfactants of the sorbitan partial fatty acid ester and polyoxyethylene ester types indicate that sorbic acid and combinations of sorbIC acid and hexylene glycol are effective preservatives.
Abstract: Forty-eight substances and combinations were studied for their possible effectiveness as preservatives for solutions of nonionic surfactants of the sorbitan partial fatty acid ester and polyoxyethylene ester types. Results indicated that sorbic acid (0.2 per cent w/v); phenylmercuric borate (0.007 per cent w/v); phenylmercuric nitrate (0.01 per cent w/v); phenylmercuric acetate (0.007 per cent w/v); n -trichloromethylmercapto-4-cyclohexene-1,2-dicarboximide (Vancide® 89 RE, 0.04 per cent w/v); diethylene glycol monomethyl ether (methyl Carbitol, 3 per cent w/v); hexylene glycol (3 per cent w/v); and benzalkonium chloride (0.1 per cent w/v) are effective in preserving these solutions. The failure of various phenolic preservatives to preserve these surfactant solutions is attributed to complex formation between phenolic and polyether groups. Studies on various cosmetic formulations containing nonionic surfactants indicate that sorbic acid (0.2 per cent w/w) and combinations of sorbic acid and hexylene glycol are effective preservatives. These preservatives were also found effective in products containing sorbitol as well as nonionic surfactants.
TL;DR: A rationale for the use of ion exchange resins as carriers in ointments has been postulated and formulation tests to develop a hydrophilic base showing maximum stability and acceptable cosmetic properties resulted in the development of an o/w base containing pectin and a Veegum base.
Abstract: A rationale for the use of ion exchange resins as carriers in ointments has been postulated. Tests run to determine the activity of ion exchangers in various types of bases showed that an o/w emulsion base showed the best rate of exchange, the exchange rate being increased with increased water content and decreased ointment consistency. Formulation tests to develop a hydrophilic base showing maximum stability and acceptable cosmetic properties resulted in the development of an o/w base containing pectin and a Veegum base. These bases were shown by ion diffusion studies to be much superior to the U. S. P. hydrophilic base in the length of time over which ion exchange occurred from resins incorporated in the bases.
TL;DR: The constants obtained for this reaction have been combined with those previously reported for the hydroxyl catalyzed reactions and an equation proposed to predict the half life of atropine undergoing hydrolysis at constant pH and temperature is proposed.
Abstract: A kinetic study of the proton catalyzed hydrolysis of atropine has been carried out and the temperature dependency of this reaction established. The constants obtained for this reaction have been combined with those previously reported for the hydroxyl catalyzed reactions and an equation proposed to predict the half life of atropine undergoing hydrolysis at constant pH and temperature. The pH of minimum hydrolysis has been calculated and found to vary with temperature from pH 4.11 at 0° to pH 3.24 at 100°. Calculated half lives of atropine in solution over the region of pH 2 to 7 at temperatures from 20° to 100° are given.
TL;DR: Absorption studies indicate that Tetramine is rapidly absorbed from the mucosa of the pharynx and oral cavity; it appears to be metabolized at a rate approximately one-fourth the LD 50 per day.
Abstract: Pharmacological studies have been made of Tetramine (tetraethylenedisulfotetramine), employing principally a saturated aqueous solution of the compound. Tetramine was found to be stable in aqueous solutions and the LD 50 of this solution for the albino rat has been determined. The compound was shown to have no major activity on peripheral nerves, skeletal muscles, or the neuromuscular junction; investigations of autonomic activity were without significant positive results. Convulsive activity of Tetramine was shown to lie entirely within the brain stem. The coin-pound greatly increased both rate and amplitude of respiration in the deeply anesthetized dog. Absorption studies indicate that Tetramine is rapidly absorbed from the mucosa of the pharynx and oral cavity; it appears to be metabolized at a rate approximately one-fourth the LD 50 per day.
TL;DR: A method for the assay of Rauwolfia root material by paper chromatography is presented in this article, where a number of rau wolfia species are evaluated for reserpine content and for the distribution of other alkaloids.
Abstract: A method for the assay of Rauwolfia root material by paper chromatography is presented. A number of Rauwolfia species are evaluated for reserpine content and for the distribution of other alkaloids.
TL;DR: Bacteriological and chemical tests indicated that the amount of cetylpyridinium chloride inactivated by 1 Gm.
Abstract: A method for determining the adsorptive capacity of talc and kaolin for cetylpyridinium chloride and benzalkonium chloride is described. The adsorption isotherms were determined at 25° ± 0.3° and the results plotted according to the Langmuir and Freundlich equations. The Langmuir constant b was calculated for talccetylpyridinium chloride and kaolincetylpyridinium chloride combinations. Talc and kaolin gave the same type of curves with both compounds. They differed only in adsorptive capacity. Cetylpyridinium chloride was adsorbed to a greater extent than benzalkonium chloride by kaolin and talc. The adsorption patterns of these two quaternaries were found to be different. Bacteriological and chemical tests indicated that the amount of cetylpyridinium chloride inactivated by 1 Gm. of talc is approximately 5 mg.
TL;DR: In this article, it was shown that when mixtures of menthol in propylene glycol and nicotine are administered i.v. to cats and rabbits, the degree of vasoconstriction produced by nicotine is blocked completely when the ratio of menthal to nicotine is 40 to 80.
Abstract: l -Menthol in Propylene glycol produces a fall in blood pressure of cats and rabbits when administered i.v. in dosages of 0.25 mg./Kg. and above. When mixtures of l -menthol in propylene glycol and nicotine are administered i. v. to cats and rabbits the vasoconstriction produced by nicotine is blocked completely when the ratio of menthol to nicotine is 40 to 80. The degree of vasoconstriction is decreased 10 to 60 per cent when the ratio of menthol to nicotine is 6 to 20.
TL;DR: A technique for contaminating and for making quantitative measurements of organisms killed was developed and the adsorbed Ethylene oxide provides an additional safety margin in the sterilization process.
Abstract: Intravenous injection equipment composed entirely of plastic is readily sterilized in the shipping carton by ethylene oxide vapor. Sterility was achieved in four hours but not in two hours with a temperature of about 75°F. and a gas pressure of 0.5 atmosphere. A technique for contaminating and for making quantitative measurements of organisms killed was developed. The basis of this method is a filter paper test strip impregnated with spores of Bacillus globigii A.T.C.C. 9372. The ethylene oxide vapor adsorbed by the plastic and the package had a marked sterilizing effect after the material was removed from the chamber. The experiments carried out in this study were designed to minimize this effect. Under practical conditions, the adsorbed Ethylene oxide provides an additional safety margin in the sterilization process.
TL;DR: The results show that the compounds investigated behave similarly in their interaction with p -hydroxybenzoic acid despite their differences in structure, and the suggestion is made that soluble forms of higher order may be present in solution.
Abstract: The results show that the compounds investigated behave similarly in their interaction with p -hydroxybenzoic acid despite their differences in structure. The solubilities of the complexes formed, however, appear to be markedly dependent on the structure of the parent xanthines. Only one to one species are precipitated in the systems under the conditions employed. The suggestion is made, however, that soluble forms of higher order may be present in solution.
TL;DR: The action of 275 kc.
Abstract: The action of 275 kc. ultrasonic waves on several naturally occuring gums and one natural material, partially modified by synthesis, has been studied. Methods were given for the interpretation of solution viscosities in terms of molecular weight decrease. Possible oxidative influences on the depolymerizations were also investigated and specific rate constants were calculated.
TL;DR: Application of this semiquantitative technique to the study of penetration of protective films by noxious chemicals gives an index to protective capacity.
Abstract: A semiquantitative method has been developed for measuring permeation of semi-solid materials by true diffusion. Adherence to theory has been demonstrated using aniline, nitrobenzene, and isovaleric acid as penetrants and white petrolatum and Jelene 1 as barriers. Application of this technique to the study of penetration of protective films by noxious chemicals gives an index to protective capacity.
TL;DR: Sterilization of a number of pharmaceuticals in the final package was accomplished with, in most cases, no loss in potency or increase in toxicity, and the use of irradiated products clinically has shown no unfavorable reactions.
Abstract: Sterilization of a number of pharmaceuticals in the final package was accomplished with, in most cases, no loss in potency or increase in toxicity. A dose of 2 × 10 6 REP of cathode rays was adequate for the complete destruction of any bacterial contamination. The use of irradiated products clinically has shown no unfavorable reactions. Irradiated dog plasma when reinfused into dogs showed no untoward reactions. Cathode ray irradiations were also used for the selection of high yielding mutants of Penicillium cbrysogenum, Streptomyces fradiae , and Streptomyces erytbreus .
TL;DR: The results indicate that this structural factor is associated with retention of depressor effects on motor activity, and also introduces anti-inflammatory properties as a pharmacological characteristic of the compounds studied.
Abstract: Analogs of chlorpromazine were studied in which the amino moiety was rendered less flexible by incorporation as part of a piperidine ring system The results indicate that this structural factor is associated with retention of depressor effects on motor activity, and also introduces anti-inflammatory properties as a pharmacological characteristic of the compounds studied
TL;DR: In this article, the effects of 5-HT and LSD on mice were studied following intracerebral injection in conscious mice, and the results showed that LSD and its derivatives caused hyperexcitability, piloerection, muscle incoordination, and sensitivity to touch.
Abstract: The centrally induced effects of 5-HT and LSD and three of its derivatives have been studied following intracerebral injection in conscious mice. The symptoms observed after giving 5-HT were scratching and stupor. LSD and its derivatives caused hyperexcitability, piloerection, muscle incoordination, and sensitivity to touch. LSD also produced a sensitivity to sound, a muscle twitch in the lumbar area and a peculiar alternating stamping of the feet. LSD, 1-acetyl-LSD and 1-methyl-LSD were able to block the central effects of 5-HT whereas d -lysergic acid dimethylamide did not antagonize 5-HT.
TL;DR: The antispasmodic activity of N-methyl-3-piperidyl diphenylglycolate methobromide (JB-340) was evaluated against atropine sulfate on various segments of the normal and spastic gastrointestinal tract of cats and dogs under pentobarbital sodium anesthesia as discussed by the authors.
Abstract: The antispasmodic activity of N-methyl-3-piperidyl diphenylglycolate methobromide (JB-340) was evaluated against atropine sulfate on various segments of the normal and spastic gastrointestinal tract of cats and dogs under pentobarbital sodium anesthesia. JB-340, 0.5 mg./Kg. I.V., exhibited a depressant activity equal to or greater than 0.2 mg./Kg. of atropine sulfate on the colon of cats and dogs. The mean duration of action of JB-340 was approximately equal to atropine sulfate (as determined by blockage of vagal stimuli). Atropine sulfate elicited a spasmogenic effect on the colon of the dog in 60 per cent of the experiments. JB-340,0.5 mg./Kg. I.V., did not significantly affect the blood pressure of normotensive dogs and did not block the superior cervical ganglion of cats.