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At least 19 recordsLinked to original sources
PubMed1976

Physical characterization and activity in vivo of polymorphic forms of 7-chloro-5, 11-dihydrodibenz[b, e][1, 4]oxazepine-5-carboxamide, a potential tricyclic antidepressant.

The biological availability in dogs and humans of 7-chloro-5, 11-dihydrodibenz[b,e][1,4]oxazepine-5-carboxamide, a potential antidepressant drug, was increased when the compound was administered in capsule formulations as micronized drug coated with 1% sodium lauryl sulfate or as a lyophilate with poloxamer 407. This increase with these two formulations had been predicted by dissolution tests in vitro. The lyophilized combination with poloxamer 407 was more soluble in 0.1 N HCl than was the untreated compound. Characterization of the lyophilate by differential thermal analysis, X-ray diffraction, and IR spectroscopy indicated that the increase in solubility was attributable to the formation of a polymorphic from. a polymorph of the compound designated form 8, was prepared. The solubility and dissolution characteristics of the two polymorphic forms, A and B, as well as of the lyophilized combination with poloxamer 407, were determined.

Adult↗
PubMed1978

Pharmacological alterations in the clotting mechanism: use in microvascular surgery.

At the present time there is confusion as to what pharmacological adjuncts are helpful toward increasing patency rates of microvascular repairs. To select a drug rationally, an understanding of the clotting mechanism in small vessels is essential so that agents may be selected that alone or in combination will react with the elements of the blood and will allow for continued perfusion without risk of hemorrhage or toxicity. Drugs which are Federal Drug Aministration approved and currently available are drugs having nonspecific effects involving more than one aspect of the clotting mechanism; they often in undesirable as well as desirable effects. Further development will result in the use of more selective and sophisticated agents. Presently it would appear desirable to employ agents to (1) increase blood flow and decrease blood viscosity, such as dextran 70; (2) decrease platelet functions, such as aspirin-type drugs; (3) mitigate against the actions of thrombin on platelets and fibrinogen using low-dose heparin; (4) reduce anxiety and vasospasm using chlorpromazine or Thorazine.

Animals↗
PubMedDate not supplied

The use of pluronic polyols in the precipitation of plasma proteins and its application in the preparation of plasma derivatives.

Pluronic F-38 was used a precipitant of plasma proteins under varying conditions of pH and polymer concentration. Results indicated that marked differences in the solubility of the plasma proteins in F-38 solutions can be appled to the separation of plasma components. The feasibility of the industrial application of this fractionation method was tested in several experiments. Conditions were established for the preparation of albumin, human plasma protein fraction (HPPF), and immune serum globulin (ISG) with similar yield and purity as those prepared by the Cohn methods. Current procedures for the preparation of antihemophilic A (Facor VIII) concentrate and prothrombin complex (Factors II, VII, IX, and X) were adapted to the F-38 process by removal of the clotting factors from the starting plasma prior to polymer precipitation. In addition, a plasma protein solution free of lipoproteins, isoagglutinins, and clotting factors was developed which has proven useful as a perfusion medium in organ preservation.

Blood Preservation↗
PubMed1979

Relationships between poloxamer structure and the solubilization of some para-substituted acetanilides.

Saturation solubilities of several para-substituted acetanilides have been measured at 37 degrees C in aqueous solutions of structurally related polyoxyethylene-polyoxypropylene block copolymers-poloxamers L62, L63, L64, P65 and F68. These poloxamers differ only in the amount of ethylene oxide in the hydrophil. Solubilities increased with increasing poloxamer concentration. As the oxyethylene chain length of the poloxamer increased, then the solubilizing capacity per equivalent of oxyethylene decreased. The moles of acetanilide derivative solubilized per mole of poloxamer increased with poloxamer oxyethylene content in the case of the less hydrophobic acetanilides but was invariant in the more hydrophobic ones. The solubilizing capacities have been discussed in terms of the inter-relationships between the hydrophobic nature of the solubilizate and solubilizer and the site of solubilization on the poloxamer molecule.

Acetanilides↗
PubMed1979

Biological effectiveness, in goldfish, of some p-substituted acetanilides alone and in the presence of poloxamers.

The death times of goldfish have been measured in aqueous solutions containing different concentrations of p-substituted acetanilides alone or in the presence of poloxamers. Plots of reciprocal death time versus concentration were linear with a positive concentration intercept, the minimum effective concentration (MEC). The MEC values were directly related to the pi value (hydrophobic-lipophilic constant) of the functional group on the acetanilide indicating that activity is directly related to lipophilicity. Slopes of reciprocal death time versus drug concentration were linearly related to pi values but there was no direct dependence. The presence of poloxamers in aqueous acetanilide solutions reduced the goldfish death time. The effect of the poloxamers is believed to be one of rendering the goldfish membrane more permeable to drugs.

Acetanilides↗
PubMed1978

Improved sodium and PAH transport in the isolated fluorocarbon-perfused rat kidney.

The effect of an artificial O2 carrier (emulsion of the perfluorochemical FC43 with Pluronic-F-108) on the functional capability of the isolated perfused rat kidney was tested. In control series hydroxyethyl starch (HES) instead of fluorocarbon was used. Improving O2 supply in FC 43 experiments raised Na reabsorption to 149 mumol/g x min compared to 84.1 mumol/g x min in HES experiments. In the presence of PAH, however, Na reabsorption in FC 43 experiments was only 115 mumol/g x min. In both series, perfusion flow, calculated on the basis of CPAH, remained below the directly measured flow rate, unless analysis included all metabolites of PAH. N-acetylated metabolites of PAH were released at a 5 times higher rate by kidneys perfused with FC 43 than by HES-perfused organs. These results demonstrate that sufficient O2 supply is critical both for reabsorption of Na+ and for handling of PAH. Increased tubular Na reabsorption in the absence of PAH indicates that even during perfusion with FC 43 O2 supply is marginal.

Acylation↗
PubMedDate not supplied

Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations.

Because of an apparent typographic error in a US patent, there has been some confusion as to the acute oral toxicity of danthron and danthron in combination with dioctyl sodium sulfosuccinate (DSS). Acute oral toxicity studies in mice revealed LD50 values of greater than 7 gm/kg for danthron, 2.64 gm/kg for DSS and 3.42 gm/kg for danthron/DSS mixture (1:2 ratio). These results indicate that the lethality of these compounds is in the gm/kg range and not in the mg/kg range. A one year chronic toxicity study of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations in dogs failed to reveal any toxic effects. In particular, there was no evidence of hepatotoxicity or of any changes in the myenteric plexuses in the chronically treated dogs.

Animals↗
PubMed1979

[Perfluorochemicals as artificial blood. problems and actual development (author's transl)].

Perfluorochemical-type blood substitutes are excellent carriers of gases such as O2, CO2, CO, N2. These chemical compounds are insoluble in water and have an extreme chemical and biological inertness. They can be prepared as pyrogen-free sterilisable emulsions. In the last 10 years improvements in emulsion techniques and the results of experimental research work in several laboratories aroused increasing interest in fluorocarbons in the medical and biological field. Beside the treatment of severe loss of blood, numerous further potential uses of these substitutes have been described. Further improvements and studies are needed, especially concerning the storage-phenomenon in the reticulohistiocytic system and also the problems linked with the absence or reduction of the clotting system. The existing literature on this subject seems to justify an optimistic view of fluorocarbons as promising blood substitutes.

Animals↗
PubMedDate not supplied

Disposition in rats of a polyoxypropylene-polyoxyethylene copolymer used in plasma fractionation.

A polyoxypropylene-polyoxyethylene block copolymer of about 4750 daltons (Poloxamer 108, Pluronic F-38) used in a new protein fractionation procedure may be infused into patients receiving therapeutic plasma fractions. We studied the disposition and pharmacokinetics of Poloxamer 108 in rats as an initial step towards understanding its behavior in man. After iv administration in rats, about 94% of 7 or 100 mg/kg doses of ethylene-14C-labeled polymer was excreted in the urine in 3 days. About 6% of the label appeared in feces. Erythrocyte membranes were not permeable to the polymer, and only the parent compound was demonstrable in urine. Twenty hours after dosing, small residues were detectable only in the kidney, liver, small intestine, and carcass. The third phase of the plasma disappearance pattern was evident only at the larger dose, but plasma disappearance kinetics were independent of the dose in the range used here. Thus, most of poloxamer 108 was eliminated rapidly in rats by renal excretion, and a smaller portion probably was removed by biliary excretion. These results will be applied to continuing studies of Poloxamer 108 disposition in man.

Age Factors↗
PubMed1977

A double-blind comparison of two bulk laxatives on geriatric patients.

Bulk laxatives have been said to have a good effect in normalizing both hard and loose stools in geriatric patients as concluded from some open studies. In a double-blind study Vi-Siblin, Lunelax and placebo were compared in the six weeks treatment of 29 patients (8 patients on Vi-Siblin, 8 patients on Lunelax, 13 patients on placebo). Two weeks prior to the study and the two last weeks of the study defecation frequency, consistency of stools and the use of additional laxatives were registered by the personnel. Results showed no significant differences between groups or between substances. From this controlled double-blind study it is not possible to draw any definite conclusions regarding the efficacy of bulk laxatives on geriatric patients.

Aged↗
PubMed1978

Iodine disinfectants.

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Anti-Infective Agents, Local↗