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Biomedical subjects

T Yotsuyanagi

Publications and source records attributed to T Yotsuyanagi.

At least 91 records · Page 5Linked to original sources

Bile salt-induced disintegration of egg phosphatidylcholine liposomes: a kinetic study based on turbidity changes.

The disintegration kinetics of egg phosphatidylcholine small unilamellar liposomes in various bile salts (nine species) were investigated by monitoring turbidity changes with a stopped-flow apparatus. The pseudo-first-order rate constants obtained as a function of bile salt concentration (up to 25 mM) were analyzed based on a two-step model in which a penetration-saturation step of bile salt into the bilayer and a lamellar-micellar transition step were assumed for the disintegration mechanism of the bilayer. The order of the rate of the penetration-saturation step, which is assumed to be a measure of the disintegration ability, was as follows: SCDOC greater than SDOC greater than STCDOC greater than STDOC greater than STC greater than SC greater than SGCDOC greater than SGDOC greater than SGC. The results indicated that (1) the dihydroxy bile salts have a greater disintegration ability than the corresponding trihydroxy bile salts, (2) the chenodeoxy bile salts have a greater ability than the corresponding deoxy-bile salts regardless of non-conjugated or conjugated form, (3) the taurine conjugates always have a greater ability than the glycine conjugates. The penetration-saturation rate of the bile salts against the lipid bilayer depends considerably on the chemical nature of each bile salt, varying by a factor of about 10(5). In the conjugated bile salts alone, they were in a narrower range of a factor of 10(3). The physical integrity of liposomes can hardly be maintained in the bile salt-rich intestinal tract but the resulting mixed micelles may contribute substantially to solubilization and enhanced delivery of drugs.

Bile Acids and Salts↗

Micelle-mediated transport of vitamin K1 through porous membranes: contribution of phosphatidylcholine-bile salt mixed micelles.

Diffusion of vitamin K1 solubilized by phosphatidylcholine-sodium deoxycholate mixed micelles through porous membranes having various pore characteristics was examined. The membranes include Nuclepore, Duragard and nitrocellulose membranes, which were intended to mimic the narrow channels in the vicinity of absorptive brush border. The diffusion coefficient of the mixed micelles was 4.6-5.5 x 10(-7) cm2/s, from which the hydrodynamic radius was calculated to be about 50 A. The dependence of the diffusivity on pore size showed that the transport of the micelles is hindered by pores having a radius ratio of the diffusate to the pore of about 0.05 or larger.

Bile Acids and Salts↗

Solubilization of vitamin K1 by bile salts and phosphatidylcholine-bile salts mixed micelles.

The solubilization of vitamin K1 by bile salts (sodium deoxycholate, sodium cholate and their corresponding glycine conjugates) and phosphatidylcholine (egg)-bile salt mixed micelles has been investigated. The solubilization curves were not always linear with increasing bile salts, but the vitamin was appreciably solubilized in the region below their CMCs. In the bile salt solutions (20 mM, phosphate buffered saline, pH 7.5, ions strength 0.2), the solubilized vitamin ranged from 0.3 to 0.9 mM. With increasing phosphatidylcholine, the amount of vitamin solubilized was dramatically increased; at the molar ratio of 1:1 (both 20 mM), the amount of vitamin solubilized was about 25-30 times more than by the corresponding bile salts alone. There is a possibility that exogenous phospholipid given orally as liposomal forms assists the solubilization of vitamin K1, in the intestine. This characteristic is suggested as being responsible, in part, for the enhanced recovery of blood coagulation after oral administration of liposomal vitamin K1 to warfarin-treated rabbits.

Bile Acids and Salts↗

High-performance liquid chromatographic assay of antiinflammatory drugs incorporated in gel ointments. Separation and stability testing.

High-performance liquid chromatographic determinations of gabexate mesilate (FOY), prostaglandin E1 (PGE1), PGE1-alpha-cyclodextrin (PGE1-CD), prednisolone (PD) and butyl flufenamate (BF) incorporated in gel ointment were investigated. The gel ointment is composed of a carboxy vinyl polymer (1.3%, w/w) and a large amount of an aqueous organic solvent. A methanol extraction system offered simultaneous advantages of the removal of the polymer and the recovery of active ingredients from the gel phase. The recoveries of the drugs were 100%. The stabilities of PGE1, PGE1-CD, FOY, PD and BF incorporated in gel ointment, stored at 5, 25 and 40 degrees C for up to 90 days, were investigated.

Alprostadil↗

High-performance liquid chromatographic assay for prostaglandin E1 in various ointment vehicles. Separation and stability testing.

A high-performance liquid chromatographic method for the determination of prostaglandin E1 (PGE1) incorporated in white petrolatum, white ointment, hydrophilic petrolatum and Plastibase was investigated. The prostaglandin was separated from the oleaginous vehicles with n-hexane-aqueous acetonitrile. Most of white petrolatum, which is a principal component in the vehicles, remained in the n-hexane layer, and the recovery of the drug from any vehicle attained 100%. The method was applied to stability studies of PGE1 in white petrolatum and macrogol ointment. In which pure PGE1 and PGE1-alpha-cyclodextrin complex (PGE1-CD) were incorporated. The drug remained intact for up to 6 months when stored at 5 degrees C. At 25 and 40 degrees C, pure PGE1 was more stable than PGE1-CD and both PGE1 species were more stable in white petrolatum than in macrogol ointment.

Alprostadil↗

Coagulation recovery after warfarin-induced hypoprothrombinaemia by oral administration of liposomally-associated vitamin K1 to rabbits.

The effect of liposomally-associated vitamin K1, administered orally, was investigated using rabbits with warfarin-induced hypoprothrombinaemia, and evaluated in comparison with other dosage forms of the vitamin, including a vitamin K1 emulsion, the physical mixture of the emulsion with empty liposomes, polyoxyethylene hydrogenated castor oil (HCO-60)-stabilized emulsion and the vitamin solubilized by HCO-60. The effect on blood coagulation recovery of each preparation was estimated as the time required for the prothrombin complex activity to return to 60% (TPCA60). The coagulation recovery time of the liposomal preparation was much faster than that of the other preparations and it was compared with the response to intravenous administration in which the vitamin was considered to be 100% available. The TPCA60 for the intravenous administration was 1.9 h, that for the oral liposomal preparation was 6.2 h, HCO-60 solubilized vitamin 13.6 h, HCO-60 stabilized emulsion 19.6 h, the physical mixture 17.8 h and plain emulsion 18.2 h. The vitamin K1 dose was maintained at 12 mg kg-1 in each instance.

Animals↗

Kinetic aspects and mechanism of liposome disintegration in polyoxyethylene lauryl ether and sodium cholate solutions.

The disintegration behaviour of liposomes in polyoxyethylene lauryl ether (PLE) and sodium cholate solutions was studied by the turbidity disappearance method. In maximally solubilized systems of liposomes, the molar ratios (phosphatidylcholine/surfactant) were 0.43 and 1.8 for PLE and sodium cholate, respectively. The disintegration process of either unilamellar or multilamellar liposomes followed first-order kinetics. Based on a physical model in which liposomes heterogeneous in size were assumed to disintegrate from the outermost shell one by one, a mathematical expression of the turbidity disappearance rate was introduced and applied to explain the data thus obtained. Model calculations suggested that the number of disintegrated shells would not be so large, even if up to 50% reduction of the initial turbidity was observed. From the dependence of the pseudo-first-order rate constant (kobs) on the surfactant concentration for unilamellar liposomes, it was assumed in general that kobs consists of the contributions of the monomer and micellar fractions: for PLE, both fractions shared in the disintegration, but only the micellar fraction with sodium cholate. Furthermore, in the latter case, kobs depended on the initial liposome concentration. These results are likely to be consistent with the proposed modes of surfactant action classified as type A and type B (Helenius, A. and Simons, K. (1975) Biochim. Biophys. Acta 415, 29-79).

Cholic Acid↗

Simultaneous determinations of cefsulodin and cefotiam in serum and bone marrow blood by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the simultaneous determinations of cefsulodin and cefotiam in serum and bone marrow blood samples. After extraction with acetonitrile, the cephalosporins were applied to a reverse-phase column with an internal standard, cefazolin; the mobile phase was a mixture of 0.005 M tetrabutylammonium phosphate and methanol (35:65, v/v). The method yielded satisfactory resolutions for these agents, and the results were compared with those obtained using the microbiological method. The statistical analysis of the relationship between the methods gave a good correlation for all of these agents and samples. The concentrations of cefsulodin and cefotiam, concurrently administered by the intravenous route to patients subjected to artificial total joint prosthesis, in serum and bone marrow blood collected at 0.5 and 1 hr postinjection were almost equivalent.

Biological Assay↗