Toyoshi Katagi

Chiral separation of propranolol and its ester derivatives on an ovomucoid-bonded silica : influence of pH, ionic strength and organic modifier on retention, enantioselectivity and enantiomeric elution order

SummaryThe retention, enantioselectivity and enantiomeric elution order of racemic propranolol (PP) and its ester derivatives (O-acetyl,-propyl,-butyl and-valeryl PP) on an ovomucoid-bonded silica column have been investigated with respect to pH, ionic strength and organic modifier. For these cationic solutes, an increase in the organic modifier content and/or a decrease in the pH result in a decreased retention of both enantiomers. Enantioselectivity of the ester derivatives was higher than of underivated PP. The enantiomeric elution order was (S)/(R) for PP and (R)/(S) for the four ester derivatives, when ethanol or 2-propanol was used as the organic modifier. When methanol or acetonitrile was used as the organic modifier, inversion of the enantiomeric elution order was observed for O-valeryl PP with the use of methanol and for PP and O-propyl PP with acetonitrile. These results suggest that at least two chiral binding- or recognitionsites are present in a protein molecule and/or conformational changes occur in the chiral binding- or recognition-site(s) of the protein molecule bonded to a silica matrix.

Percutaneous Permeation of Basic Compounds Through Shed Snake Skin as a Model Membrane

Abstract— Relationships between the in‐vitro permeability of basic compounds through shed snake skin as a suitable model membrane for human stratum corneum and their physicochemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of non‐ionized forms of the compounds. Steady‐state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady‐state penetration data and relationships between these parameters and the physicochemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the molecular weights and the partition coefficients of basic compounds.

Gas chromatography of flavonoids

Abstract The gas chromatography of some trimethylsilyl ethers of flavonoids and glycosides was carried out using the OV series of silicone polymers as liquid phases, and useful correlations between the Kovats retention indices and the substituents in flavonoids in some crude drugs by temperature-programmed gas chromatography were devised. It was attempted to determine rutin quantitatively in a crude drug by chromatography.

Syntheses of macrocycles from l-amino acid and their selective transport of amino ester salts through an organic liquid membrane

Abstract Syntheses of 18-membered macrocycle 17 , 24-membered macrocycles 18 , 19 , and 30-membered macrocycles 20 , 21 , 22 , 23 , 25 , were achieved by using diglycolic acid and amino acids as constituents. Selective transport of amino ester salts through an organic liquid membrane was mediated by their macrocycles and intermediate compounds. The transfer abilities of these carriers containing amino acid moieties were different from that of 18-crown-6.

Purification and reconstitution of μ-opioid receptors in liposome

Opioid receptors solubilized from rat brain membranes with digitonin were partially purified with a newly prepared affinity resin, AF-Amino Toyopearl, coupled with a mu-antagonist Tyr-Pro-Tyr-Tyr at the C-terminus of the peptide. The purified materials were reconstituted with an inhibitory GTP-binding protein (Gi) in liposome. From displacement analyses, two binding states, with a high and a low affinities for the mu-agonist [D-Ala2,Me-Phe4,Gly-ol5]enkephalin, were observed in the reconstituted system with Gi, only a low-affinity state was observed in the reconstituted system without Gi. The results suggested that the purified materials contained the mu-opioid receptors and could functionally couple with Gi as observed in the cell membranes.

Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum

Abstract— A direct high‐performance liquid chromatographic method was developed for the assays of the enantiomers of O‐acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O‐acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)‐ and (S)‐propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)‐isomer was about three times faster than that of the ester of (S)‐isomer. The interconversion between (R)‐ and (S)‐isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O‐acetyl propranolol occurs stereoselectively in human serum.

Synthesis of a cyclic octapeptide

Synthese de cyclo ((L-Lys(Z)) 2 -Gly-(L-Phe) 2 -(Gly) 3 ). Utilisation de ce ionophore modele pour le transport de L-Phe-OMe•HCl a travers une membrane organique liquide

Effect of pH on the dissolution of drug particle dispersed in solid matrix of hydrogenated soya phospholipid

Abstract Granules of theophylline were prepared with hydrogenated soya phospholipid, without addition of any binder. Despite very slow dissolution of drug from granules in 0.01 N HCl, the dissolution in phosphate buffer (pH 6.8) occurred rapidly with disintegration of granules and was further accelerated by the presence of bile in the medium. The granules prepared in this study behave as enteric granules.