Showing papers by "Novartis published in 1979"

Biotransformation of diclofenac sodium (Voltaren) in animals and in man. I. Isolation and identification of principal metabolites.

Abstract: 1. The anti-inflammatory agent diclofenac sodium (o-[(2,6-dichlorophenyl)amino]phenylacetic acid sodium salt) is extensively metabolized by rat, dog, baboon and man. The main metabolites were isolated from the urine of all species and from the bile of rat and dog and identified by spectroscopy. 2. Metabolism involves direct conjugation of the unchanged drug, or oxidation of the aromatic rings usually followed by conjugation. Sites of oxidation are either position 3' or 4' of the dichlorophenyl ring or, alternatively, position 5 of the phenyl ring attached to the acetic acid moiety. 3. In the urine of rat, baboon and man conjugates of the hydroxylated metabolites predominate, but the major metabolite in dog urine is the taurine conjugate of unchanged diclofenac. 4. In the bile of rat and dog, the main metabolite is the ester glucuroniade of unchanged diclofenac.

Sensitizers for photopolymerization

Abstract: Aromatic-aliphatic ketones of the formulae I, II, III or IV ##STR1## wherein n is 1 or 2, Ar is an aryl radical, R1 and R2 are monovalent aliphatic, cycloaliphatic or araliphatic radicals, R3 is a direct bond or a divalent organic radical, X is a hydroxyl or amino group or the monovalent etherification or silylation products thereof, and X' is a divalent amino, ether or silyloxy group, Y is a direct bond or CH2 and Z is O, S, SO2, CH2 or C(CH3)2, are suitable sensitizers for the photopolymerization of unsaturated compounds and for the photochemical crosslinking of polyolefins. Some of these compounds are novel and can be obtained by methods analogous to those for obtaining the known compounds of this type.

Family (parental) history and prevalence of hypertension. Results of a nationwide screening program

Abstract: In a nationwide screening program, blood pressure measurements, family (parental) histories of hypertension, and self-evaluations of weight class were obtained for more than a half million people. Positive family history was associated with hypertension prevalence double that found in persons with negative history and was independent of weight. When overweight was also present, however, hypertension prevalence was three to four times as high. Hypertension was more likely to have been previously diagnosed in screenees if family history was positive. However, such screenees did not have a higher proportion receiving effective treatment than those with negative family history. When an index case of hypertension is found, other family members should be examined. For persons with positive family history, nutritional-hygienic recommendations to avoid overweight may be important in reducing the risk of becoming hypertensive. ( JAMA 241:43-46, 1979)

Biotransformation of diclofenac sodium (Voltaren) in animals and in man. II. Quantitative determination of the unchanged drug and principal phenolic metabolites, in urine and bile.

Abstract: 1. Quantitative determinations of unchanged diclofenac and two of its major phenolic metabolites were made by reverse isotope dilution analysis on urine of rat, dog, rhesus monkey, baboon and man and on bile of rat, dog and man. Isotope dilution analysis was performed before and after various methods of enzymic and chemical hydrolysis. 2. The same samples were also analysed by two-dimensional t.l.c. and subsequent autoradiography, to estimate the remaining phenolic metabolites. 3. In contrast to rat, rhesus monkey, baboon and man, which excrete mainly hydroxylated metabolites, the dog does not oxidize diclofenac. Dog urine contained a relatively stable taurine conjugate of diclofenac, and in the bile an ester glucuronide was excreted, which decomposed even in weakly alkaline soln. 4. The unstable ester glucuronide found in dog bile was also demonstrable in rat bile. It presumably hydrolyses in the duodenum, releasing diclofenac which undergoes enterohepatic circulation.

Papulacandin B: an inhibitor of glucan synthesis in yeast spheroplasts.

Abstract: Papulacandin B, the main component of a series of antibiotics produced by the deuteromycete Papularia sphaerosperma, inhibits the growth of yeasts. It is a highly amphophilic substance containing residues of glucose, galactose and two long-chain unsaturated fatty acids. It does not cause the release of potassium ions from yeast cells and therefore differs in its mode of action from the polyene antibiotics. Papulacandin B, at concentrations slightly below the minimal inhibitory concentration, partially but selectively inhibited the incorporation of glucose into cells of Saccharomyces cerevisiae and Candida albicans. A much clearer effect was observed on spheroplasts, obtained by digestion of the yeast cell wall with snail digestive enzyme. Incubation of spheroplasts in a minimal medium stabilised by sorbitol led to the incorporation of glucose into alkali-insoluble glucan, mannan and a fraction containing mainly alkali-soluble 1,3-glucan together with some glycogen. Papulacandin B inhibited the synthesis of the alkali-insoluble fraction, while causing a slight stimulation of glucose incorporation into the other two polysaccharide fractions. The 50% inhibitory concentrations of papulacandin B for glucan synthesis in S. cerevisiae spheroplasts and C. albicans spheroplasts were respectively 0.16 μg/ml and 0.03 μg/ml. C. albicans cells were irradiated with ultraviolet light and selected for maximum resistance to papulacandin B. The 50% inhibitory concentration for glucan synthesis in spheroplasts prepared from this mutant was 2.5 μg/ml. Echinocandin B, a polypeptide antibiotic containing a long-chain fatty acid, also inhibited the synthesis of glucan in spheroplasts. It is concluded that papulacandin B and probably also echinocandin B inhibit glucan synthesis during cell-wall synthesis, and thus cause lysis of cells by osmotic rupture.

Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and postsynaptic central noradrenergic receptor selectivity of alpha-adrenolytic drugs.

Abstract: The effects of various α-adrenoceptorblocking drugs on the depression of exploratory activity (ambulation and rearing) induced by 0.1 mg/kg i.p. clonidine were investigated in the rat. In parallel experiments, the effects of the same drugs on pre- and postsynaptic α-receptors were determined in vitro (field-stimulated cortex slices and isolated vas deferens of the rat, respectively). Tolazoline, esproquine, yohimbine and piperoxan distinctly antagonized the inhibition of exploration produced by clonidine. All these drugs were found to possess relatively higher selectivity for the presynaptic α-receptors, as judged by the ratios of the concentrations inducing a 50% increase in field-stimulated 3H-noradrenaline-overflow and the concentrations required to shift the EC50 for the antagonism of noradrenaline-induced contractions of the vas deferens to the right by a factor of 2 (pA2, ratio 1), potentiated rather than antagonized the effects of clonidine. Mianserin, although preferentially blocking the postsynaptic receptors, had no effect on clonidine-induced hypoactivity up to the high dose of 100 mg/kg i.p., probably because of its additional NA-uptake-inhibiting properties. The antagonism of clonidine by the selective presynaptic α-receptor blockers was observed within a limited dose-range. Increasing the doses above an optimal level, which varied from one compound to another, resulted in a decrease in the effect. It is suggested that this phenomenon reflects the counter-balancing postsynaptic α-adrenoceptor blockade occuring at higher concentrations of these drugs. In general, the results show a fairly good correlation between antagonism of clonidine in vivo and preferential blockade of presynaptic α-receptors in vitro. Clonidine-induced suppression of exploration therefore seems to be a valuable model for the investigation of drug interactions with α-adrenergic receptors in the central nervous system.

2-¬2-HYDROXY-3,5-DI-(.alpha.,.alpha.-DI-METHYLBENZYL) PHENYL|- 2H-BENZOTRIAZOLES AND STABILIZED COMPOSITIONS

Abstract: Compounds of the formula I I in which T1 is hydrogen or chlorine and T2 und T3 inde-pendently of one another are the group

Effects of Subminimal Inhibitory Concentrations of Antibiotics on Adhesiveness of Escherichia coli in Vitro

Abstract: The adhesion of radiolabeled Escherichia coli (strain SS142) to monolayers of Intestine 407, a human epithelioid tissue culture cell line, was investigated. In this assay the adhesion of bacteria grown in the presence of subminimal inhibitory concentrations of tetracycline, clindamycin,, or trimethoprim-sulfametrole was reduced in a manner that was dose dependent. In contrast, at such concentrations nalidixic acid enhanced the adhesion of this bacterial strain, and other antibiotics-e.g., penicillin G, ampicillin, mecillinam, cephacetrile, cephalexin, cefotaxime, chloramphenicol, and streptomycin-did not affect its adhesiveness.

Effects of Subminimal Inhibitory Concentrations of Antibiotics in Experimental Infections

Abstract: The antibacterial effects of subminimal inhibitory concentrations (sub-MICs) of antibiotics were studied in two animal models. In mice, the oral cephalosporin CGP 9000 was effective in 11 of 20 different gram-negative infections and cephalexin was effective in one of these infections, both at 50% effective doses (ED(50)) that produced peak concentrations of drug in plasms equal to one-half to one-sixteenth the minimal inhibitory concentration (MIC) for the infecting organism. In gram-positive infections, both antibiotics were effective only at concentrations above the MIC. In rabbits, sub-MICs of cephaloridine, ampicillin, and gantamicin were maintained for 6-10 hr by intravenous infusion. At steady-state concentrations equal to one half to one-eighth the MIC, the beta-lactam antibiotics caused elongation and filamentation, and gentamicin caused enlargement, of Proteus mirabilis, Escherichia coli, and Salmonella typhimurium in peritoneal exudate; the number of viable cells of each of these bacteria was temporarily reduced. In infections with E. coli and P. mirabilis, sub-MIC's of beta-lactam antibiotics and of gentamicin prolonged the survival rates for infected animals beyond those for control animals. Rabbits infected with S. typhimurium and treated with ampicillin at a concentration of one-third the MIC Tended to die sooner than did control animals.

Predictive evaluation in animals of the contact allergenic potential of medically important substances. II. Comparison of different methods of cutaneous sensitization with "weak" allergens.

Abstract: Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives (formalin, ethylenediamine and sorbic acid), drugs (penicillin G, Benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p-phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as 1 in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.

Gas scrubbing tower

Abstract: A gas scrubbing tower is described which has a top region, a sump region and at least two washing stages between these regions. The tower comprises gas entry means between the the sump region and the lowermost of the washing stages; gas exit means in the top region; a first washing stage, in the direction of gas flow through the tower, constituted by a layer of packing elements resting on supporting means in a cross-sectional plane; a first circulating line for wash liquid from the sump region to the layer of packing elements; a second, packing-free washing stage above the first washing stage; a second circulating line for conducting wash liquid through the second washing stage; a sludge separator, and conduit means for introducing water from outside the tower into a washing stage or into the sludge separator of the tower. A process for operating the scrubbing tower is also described.

2-[2-Hydroxy-3,5-di-tert-octylphenyl]-2H-benzotriazole stabilized compositions

Abstract: 2-[2-Hydroxy-3,5-di-tert-octylphenyl]-2H-benzotriazole exhibits outstanding efficacy in protecting organic substrates from light induced deterioration as well as good resistance to loss by volatilization or exudation during the high temperature processing of stabilized compositions.

Effect of diclofenac and naproxen on gastroduodenal mucosa

Abstract: The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.

Whiteness formulas: a selection.

Abstract: Experience in assessing whiteness and industrial requirements is considered in the selection of whiteness formulas. The problems set by the photometry of fluorescent samples and the calorimetric prerequisites delimit the choice. A standard whiteness formula of neutral hue preference is proposed. Two supplementary whiteness formulas of green and red hue preference, respectively, are added. The feasibility of a complete characterization of white samples by whiteness, tint, and luminance factor is discussed.

6-substituted thia-aza-compounds, their preparation and pharmaceutical compositions containing them

Abstract: Neue 2-Penem-3-carbonsaureverbindung der Formel New 2-penem-3-carboxylic acid compound of formula worin R a fur einen uber ein Kohlenstoffatom mit dem Ringkohlenstoffatom verbundenen organischen Rest, eine freie, veratherte oder veresterte Hydroxy- oder Mercaptogruppe oder fur Halogen steht, R, fur Wasserstoff; wherein R a is a connected through a carbon atom to the ring carbon atom organic radical, a free, etherified or esterified hydroxy or mercapto group or halogen, R, is hydrogen; einen uber ein Kohlenstoffatom mit dem Ringkohlenstoffatom verbundenen organischen Rest oder eine veratherte Mercaptogruppe steht, und R 2 Hydroxy oder einen zusammen mit der Carbonyigruppierung -C(=O)- eine geschutzte Carboxylgruppe bildenden Rest R A bedeutet, ihre Salze. a bonded via a carbon atom to the ring carbon atom organic radical or an etherified mercapto group, and R 2 is hydroxy, or together with the Carbonyigruppierung -C (= O) - a protected carboxyl group-forming group R A means a salt thereof. Verfahren zu ihrer Herstellung, pharmazeutische Praparate enthaltend diese Verbindungen und ihre Verwendung als Antibiotika. Processes for their preparation, pharmaceutical compositions containing these compounds and their use as antibiotics. Die Azetidinone und andere Ausgangsverbindungen der Formel The azetidinones and other starting compounds of formula werden auch beschrieben. are also described.

Process for the production of washing powders of stabilized or enhanced appearance which contain fluorescent whitening agents

Abstract: The invention relates to the production of washing powders of stabilized or enhanced appearance which contain a fluorescent whitening agent of the formula ##STR1## or of the formula ##STR2## wherein R 1 is hydrogen or chlorine, and M is hydrogen, an alkali metal or ammonium ion. The stabilizing or enhancement of the appearance is effected by first dissolving or dispersing the fluorescent whitening agent in a mixture of water and a polyvinyl alcohol or polyvinyl pyrrolidone which is soluble or is able to swell in water, adding this solution or dispersion to the washing powder slurry and drying the slurry. The solution or dispersion can also be subsequently sprayed onto the dried residual washing powder. The appearance can be further enhanced by employing a polyethylene glycol, a surfactant containing ethyleneoxy and/or propyleneoxy groups, and/or a cellulose ether, in addition to the polymer in the solution or dispersion. The solution or dispersion comprising fluorescent whitening agent and polymer can also alternatively be dried, preferably by spray drying, to produce a preparation which, after it has been suspended in water, can also be added to the washing powder slurry. The slurry is then dried, preferably by spray drying.

Fluidized granulation of pigments using organic granulating assistant

Abstract: A process for producing a substantially dry, low dusting, free flowing granular pigment composition comprises (a) contacting a fluidized bed of pigment and a granulating assistant, (b) optionally contacting the granules so obtained with a surfactant and (c) removing the dry granules from the bed.

Curable mixtures based on maleimides and 1-propenyl-substituted phenols

Abstract: Curable mixtures of (a) maleimides of the general formula I ##STR1## wherein R is an n-valent aliphatic or aromatic radical, and n is the number 1,2 or 3; and (b) mono- or polyvalent phenols which contain in the molecule at least one 1-propenyl group in the ortho- or para-position with respect to the hydroxyl group, or isomeric mixtures of mono- or polyvalent phenols which are propenyl-substituted in the ortho- or para-position and mono- or polyvalent phenols which are allyl-substituted in the ortho- or para-position, the proportion of propenyl groups in the isomeric mixture having to be at least 5 equivalent-%, relative to the sum of the equivalents of propenyl and allyl groups. The novel mixtures cure at elevated temperatures relatively rapidly, and produce moulded materials having valuable mechanical properties.

Novel androstadiene-17-carboxylic acid esters

Abstract: The invention provides novel esters of androstadiene 17-carboxyclic acids of the formula ##STR1## wherein R' represents a hydroxyl group which is esterified with a carboxyclic acid having not more than 7 carbon atoms, R" represents a methyl group in the α- or β-position or the methylene group, wherein R is H or Cl, each of X and Y represents a hydrogen, chlorine or fluorine atom, with the proviso that at least one of these substituents is one of these halogens, when R is Cl, and that Y is only Cl or F and X only Cl, when R is H and that the androstadiene-17-carboxylic acid ester group does not contain more than 11 carbon atoms. The new esters have pronounced antiinflammatory action coupled with remarkably low systemic side effects on thymus, adrenals and body weight. They are especially suitable to be used in dermatology.

Silanes containing imide groups

Abstract: The compounds according to the invention have the formula XIX ##STR1## in which R1 and R2 are independently methyl, ethyl, phenyl, vinyl, chlorine or alkoxy, R3 is chlorine or alkoxy, A1 is alkylene and Y is substituted ethenylene These products are to be used as adhesion promoters, especially between inorganic solids and organic resins 4 processes of preparation are given

Piperidine containing malonic acid derivatives

Abstract: Malonic acid derivatives of the formula ##STR1## wherein Z contain sterically hindered piperidines as stabilizers against light-induced degradation for organic material.

Photolysis of organophosphorus insecticides on soil surfaces

Abstract: Photolysis on soil surfaces of the organophosphorus insecticides diazinon, methidathion and profenofos was studied under artificial sunlight conditions. All three compounds were readily degraded under the conditions used. The rate of degradation decreased in the order diazinon, profenofos, methidathion and was always greater in moist than in dry soil. The same order of stability was also observed from photolysis studies in aqueous solution. The major photolysis products identified were 2-isopropyl-6-methylpyrimidin-4-ol from diazinon, 5-methoxy-3H-1,3,4-thiadiazol-2-one from methidathion and 4-bromo-2-chlorophenol and 4-bromo-2-chlorophenyl ethyl hydrogen phosphate from profenofos. The same compounds were formed in hydrolysis studies and also upon photodecomposition in aqueous solutions of diazinon and methidathion. Profenofos, however, showed a different photolytic reaction in aqueous systems, forming O-(2-chlorophenyl) O-ethyl S-propyl phosphorothioate. Soil photolysis studies together with hydrolysis experiments could be a useful quick method for obtaining early information on the chemical breakdown products which are to be expected in the soil environment.